Atovaquone and proguanil hydrochloride compared with chloroquine or pyrimethamine/sulfadoxine for treatment of acute Plasmodium falciparum malaria in Peru

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Llanos-Cuentas A.

2001-01-01

Full Text Available The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15 or 1,500 mg chloroquine (base over a 3 day period (n=14 (phase 1. The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9 or atovaquone/proguanil as before (n=5 (phase 2. In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] versus 8% [1/13], P<0.0001. In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]. There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.

Simultaneous determination of dapsone, monoacetyldapsone and pyrimethamine in whole blood and plasma by high-performance liquid chromatography

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Lemnge, M M; Rønn, A; Flachs, H

1993-01-01

A sensitive, selective and rapid reversed-phase high-performance liquid chromatographic method was developed for the simultaneous analysis of dapsone, monoacetyldapsone and pyrimethamine in human whole blood and plasma. The procedure involved extraction of the compounds and the internal standard...

In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone▿

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Meneceur, Pascale; Bouldouyre, Marie-Anne; Aubert, Dominique; Villena, Isabelle; Menotti, Jean; Sauvage, Virginie; Garin, Jean-François; Derouin, Francis

2008-01-01

Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC50s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC50s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC50s were in a narrow range of concentrations (mean, 0.06 ± 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC50s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC50s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype. PMID:18212105

Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy.

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Valentini, P; Buonsenso, D; Barone, G; Serranti, D; Calzedda, R; Ceccarelli, M; Speziale, D; Ricci, R; Masini, L

2015-02-01

To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infection in pregnancy. Retrospective study of pregnant women evaluated for suspected toxoplasmosis between 1992 and 2011. A total of 120 mothers and their 123 newborns were included. Prenatal treatment consisted of spiramycin in 43 mothers (35%), spiramycin/cotrimoxazole in 70 (56.9%) and pyrimethamine/sulfonamide in 10 (8.1%). A trend toward reduction in toxoplasmosis transmission was found when Sp/C was compared with Pyr/Sul and particularly with Spy alone (P=0.014). In particular, Spy increased the risk of congenital infection when compared with Sp/C (odds ratio (OR) 4.368; 95% CI: 1.253 to 15.219), but there was no significant reduction when Sp/C was compared with Pyr/Sul (OR 1.83; 95% CI: 0.184 to 18.274). The treatment based on Sp/C has significant efficacy in reducing maternal-fetal transmission of Toxoplasma gondii when compared with Pyr/Sul and particularly to Spy. Randomized controlled trials would be required.

Treatment of infants with congenital toxoplasmosis: Tolerability and plasma concentrations of sulfadiazine and pyrimethamine

DEFF Research Database (Denmark)

Schmidt, D.R.; Høgh, B; Andersen, O

2006-01-01

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodi......The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or Ig...... spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5x10(9)/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was ... efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations...

Molecular Evidence of Increased Resistance to Anti-Folate Drugs in Plasmodium falciparum in North-East India: A Signal for Potential Failure of Artemisinin Plus Sulphadoxine-Pyrimethamine Combination Therapy

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Mohapatra, Pradyumna Kishore; Sarma, Devojit Kumar; Prakash, Anil; Bora, Khukumoni; Ahmed, Md. Atique; Sarma, Bibhas; Goswami, Basanta Kumar; Bhattacharyya, Dibya Ranjan; Mahanta, Jagadish

2014-01-01

North-east India, being a corridor to South-east Asia, is believed to play an important role in transmitting drug resistant Plasmodium falciparum malaria to India and South Asia. North-east India was the first place in India to record the emergence of drug resistance to chloroquine as well as sulphadoxine/pyrimethamine. Presently chloroquine resistance is widespread all over the North-east India and resistance to other anti-malarials is increasing. In this study both in vivo therapeutic efficacy and molecular assays were used to screen the spectrum of drug resistance to chloroquine and sulphadoxine/pyrimethamine in the circulating P. falciparum strains. A total of 220 P. falciparum positives subjects were enrolled in the study for therapeutic assessment of chloroquine and sulphadoxine/pyrimethamine and assessment of point mutations conferring resistances to these drugs were carried out by genotyping the isolates following standard methods. Overall clinical failures in sulphadoxine/pyrimethamine and chloroquine were found 12.6 and 69.5% respectively, while overall treatment failures recorded were 13.7 and 81.5% in the two arms. Nearly all (99.0%) the isolates had mutant pfcrt genotype (76T), while 68% had mutant pfmdr-1 genotype (86Y). Mutation in dhps 437 codon was the most prevalent one while dhfr codon 108 showed 100% mutation. A total of 23 unique haplotypes at the dhps locus and 7 at dhfr locus were found while dhps-dhfr combined loci revealed 49 unique haplotypes. Prevalence of double, triple and quadruple mutations were common while 1 haplotype was found with all five mutated codons (F/AGEGS/T) at dhps locus. Detection of quadruple mutants (51I/59R/108N/164L) in the present study, earlier recorded from Car Nicobar Island, India only, indicates the presence of high levels of resistance to sulphadoxine/pyrimethamine in north-east India. Associations between resistant haplotypes and the clinical outcomes and emerging resistance in sulphadoxine/pyrimethamine in

Implementation of intermittent preventive treatment with sulphadoxine-pyrimethamine for control of malaria in pregnancy in Kisumu, western Kenya

NARCIS (Netherlands)

van Eijk, Anna M.; Ayisi, John G.; ter Kuile, Feiko O.; Slutsker, L.; Otieno, Juliana A.; Misore, Ambrose O.; Odondi, J. O.; Rosen, Daniel H.; Kager, Piet A.; Steketee, Rick W.; Nahlen, Bernard L.

2004-01-01

OBJECTIVE In 1998, the Kenyan Ministry of Health introduced intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP), one treatment dose in the second trimester (16-27 weeks) and one treatment dose between 28 and 34 weeks of gestational age, for the control of malaria in

Efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria: revisiting molecular markers in an area of emerging AQ and SP resistance in Mali

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Wele Mamadou

2009-02-01

Full Text Available Abstract Background To update the National Malaria Control Programme of Mali on the efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria. Methods During the malaria transmission seasons of 2002 and 2003, 455 children – between six and 59 months of age, with uncomplicated malaria in Kolle, Mali, were randomly assigned to one of three treatment arms. In vivo outcomes were assessed using WHO standard protocols. Genotyping of msp1, msp2 and CA1 polymorphisms were used to distinguish reinfection from recrudescent parasites (molecular correction. Results Day 28 adequate clinical and parasitological responses (ACPR were 14.1%, 62.3% and 88.9% in 2002 and 18.2%, 60% and 85.2% in 2003 for chloroquine, amodiaquine and sulphadoxine-pyrimethamine, respectively. After molecular correction, ACPRs (cACPR were 63.2%, 88.5% and 98.0% in 2002 and 75.5%, 85.2% and 96.6% in 2003 for CQ, AQ and SP, respectively. Amodiaquine was the most effective on fever. Amodiaquine therapy selected molecular markers for chloroquine resistance, while in the sulphadoxine-pyrimethamine arm the level of dhfr triple mutant and dhfr/dhps quadruple mutant increased from 31.5% and 3.8% in 2002 to 42.9% and 8.9% in 2003, respectively. No infection with dhps 540E was found. Conclusion In this study, treatment with sulphadoxine-pyrimethamine emerged as the most efficacious on uncomplicated falciparum malaria followed by amodiaquine. The study demonstrated that sulphadoxine-pyrimethamine and amodiaquine were appropriate partner drugs that could be associated with artemisinin derivatives in an artemisinin-based combination therapy.

Dihydrofolate reductase and dihydropteroate synthase genotypes associated with in vitro resistance of Plasmodium falciparum to pyrimethamine, trimethoprim, sulfadoxine, and sulfamethoxazole

DEFF Research Database (Denmark)

Khalil, Insaf; Rønn, Anita M; Alifrangis, Michael

2003-01-01

A total of 70 Plasmodium falciparum isolates were tested in vitro against pyrimethamine (PYR), trimethoprim (TRM), sulfadoxine (SDX), and sulfamethoxazole (SMX), and their dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genotypes were determined. dhfr genotypes correlated...

Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by 2 Unreported HEXA Mutations in the Indian Population.

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Udwadia-Hegde, Anaita; Hajirnis, Omkar

2017-01-01

Juvenile Tay-Sachs disease is rarer than other forms of Tay-Sachs disease and is usually seen in children between the age of 2 and 10 years. Pyrimethamine as a pharmacological chaperone was used to increase β-hexosaminidase A activity in this patient. We describe a patient with Tay-Sachs disease from the Indian population, a juvenile case who presented with developmental regression starting at the age of three, initially with motor followed by language regression. She is currently incapacitated with severe behavioral issues. This brief communication gives an insight into the efficacy of pharmacological chaperones. It also describes two unreported mutations in hexosaminidase A gene from the Indian population. After commencing Pyrimethamine, though initial benefits with increase in levels corresponded with briefly halting the motor regression, the observed increase was only transient and not associated with discernible beneficial neurological or psychiatric effects.

Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine

DEFF Research Database (Denmark)

Fogh, S; Schapira, A; Bygbjerg, Ib Christian

1988-01-01

As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared...... with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 male and 351 female; 384 taking chloroquine phosphate with proguanil hydrochloride and 383 taking...... chloroquine with sulfadoxine-pyrimethamine) completed a diary on the breakthrough of malaria and the side effects of treatment while taking the drugs. They were also asked to make thick blood films when symptoms like those of malaria occurred, which were sent to and analysed in Denmark. Four subjects taking...

Sulfadoxine-pyrimethamine monotherapy in Tanzanian children gives rapid parasite clearance but slow fever clearance that is improved by chloroquine in combination therapy

DEFF Research Database (Denmark)

Tarimo, D S; Minjas, J N; Bygbjerg, I C

2002-01-01

Following widespread chloroquine (CQ) resistance, sulfadoxine plus pyrimethamine (SP) is now the first line antimalarial drug in a number of African countries including Tanzania. Unlike CQ, SP has no antipyretic effects, a feature that might delay fever clearance, and by acting on late stage para...... on possible delayed parasitological and clinical responses to SP that could result from its action on late stage parasites. Despite its diminishing antimalarial activity, CQ has beneficial in vivo antipyretic effects in therapeutic combination with SP.......Following widespread chloroquine (CQ) resistance, sulfadoxine plus pyrimethamine (SP) is now the first line antimalarial drug in a number of African countries including Tanzania. Unlike CQ, SP has no antipyretic effects, a feature that might delay fever clearance, and by acting on late stage...

High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children

NARCIS (Netherlands)

Mombo-Ngoma, G.; Oyakhirome, S.; Ord, R.; Gabor, J.J.; Greutélaers, K.C.; Profanter, K.; Greutélaers, B.; Kurth, F.; Lell, B.; Kun, J.F.J.; Issifou, S.; Roper, C.; Kremsner, P.G.; Grobusch, M.P.

2011-01-01

Background: Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). Methods: The study assessed the frequency of SP resistance-conferring

High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children

NARCIS (Netherlands)

Mombo-Ngoma, Ghyslain; Oyakhirome, Sunny; Ord, Rosalynn; Gabor, Julian J.; Greutélaers, Katja C.; Profanter, Katharina; Greutélaers, Benedikt; Kurth, Florian; Lell, Bertrand; Kun, Jürgen F. J.; Issifou, Saadou; Roper, Cally; Kremsner, Peter G.; Grobusch, Martin P.

2011-01-01

Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). The study assessed the frequency of SP resistance-conferring polymorphisms in

The effect of sulphadoxine/pyrimethamine on gametocytes in falciparum malaria.

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Ittiravivongs, A; Vasuvat, C; Kongrod, S

1984-09-01

A study of the effect of sulphadoxine/pyrimethamine (Fansidar) on P. falciparum's gametocytes in peripheral blood was carried out in Western Thailand. One group of 77 patients with asexual form P. falciparum sensitive to Fansidar were followed weekly to detect the appearance and the duration of gametocytes in peripheral blood after Fansidar treatment on the basis of thick blood film examination. Another group of 14 patients with sexual form P. falciparum was not given any antimalarial treatment and also followed up weekly. No significant difference of average duration of detectable gametocytes was observed between the groups. The average number of days that gametocytes appeared after asexual form in patients receiving treatment was the same as in the untreated group. It is unlikely that Fansidar has the stimulating effect on gametocytogenesis as previously reported.

Temporary Efficacy of Pyrimethamine in Juvenile-Onset Tay-Sachs Disease Caused by 2 Unreported HEXA Mutations in the Indian Population

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Anaita Udwadia-Hegde MD, DCH, MRCPCH

2017-01-01

Full Text Available Background: Juvenile Tay-Sachs disease is rarer than other forms of Tay-Sachs disease and is usually seen in children between the age of 2 and 10 years. Pyrimethamine as a pharmacological chaperone was used to increase β-hexosaminidase A activity in this patient. Patient: We describe a patient with Tay-Sachs disease from the Indian population, a juvenile case who presented with developmental regression starting at the age of three, initially with motor followed by language regression. She is currently incapacitated with severe behavioral issues. Conclusion: This brief communication gives an insight into the efficacy of pharmacological chaperones. It also describes two unreported mutations in hexosaminidase A gene from the Indian population. After commencing Pyrimethamine, though initial benefits with increase in levels corresponded with briefly halting the motor regression, the observed increase was only transient and not associated with discernible beneficial neurological or psychiatric effects.

Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine.

Science.gov (United States)

Fogh, S; Schapira, A; Bygbjerg, I C; Jepsen, S; Mordhorst, C H; Kuijlen, K; Ravn, P; Rønn, A; Gøtzsche, P C

1988-03-19

As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 male and 351 female; 384 taking chloroquine phosphate with proguanil hydrochloride and 383 taking chloroquine with sulfadoxine-pyrimethamine) completed a diary on the breakthrough of malaria and the side effects of treatment while taking the drugs. They were also asked to make thick blood films when symptoms like those of malaria occurred, which were sent to and analysed in Denmark. Four subjects taking chloroquine with proguanil hydrochloride and three taking chloroquine with sulfadoxine-pyrimethamine developed falciparum malaria, which was verified microscopically. Side effects were reported by 36 subjects taking chloroquine phosphate with proguanil hydrochloride and 55 taking the other regimen (p = 0.043). The side effects of both regimens were generally mild, but the combination of chloroquine phosphate with proguanil hydrochloride is recommended because it results in fewer side effects. As breakthroughs of malaria occurred at the earliest after seven weeks self treatment should not be recommended for travellers staying only a short time. Thick blood films are useful for diagnosis of suspected cases of malaria, can be prepared by non-specialists in Africa, and can be analysed successfully after long delays.

Efficacies of artesunate plus either sulfadoxine-pyrimethamine or amodiaquine, for the treatment of uncomplicated, Plasmodium falciparum malaria in eastern Sudan

DEFF Research Database (Denmark)

Ibrahium, A M; Kheir, M M; Osman, M E

2007-01-01

Artemisinin-based combination therapy (ACT) is increasingly being adopted as the first-line treatment for malaria in sub-Saharan Africa. In September-November 2005, in New Halfa, eastern Sudan, the efficacy of artesunate-sulfadoxine-pyrimethamine (AS-SP) for the treatment of uncomplicated...... of uncomplicated, P. falciparum malaria in eastern Sudan....

Characterizing the impact of sustained sulfadoxine/pyrimethamine use upon the Plasmodium falciparum population in Malawi

DEFF Research Database (Denmark)

Ravenhall, Matt; Benavente, Ernest Diez; Mipando, Mwapatsa

2016-01-01

BACKGROUND: Malawi experienced prolonged use of sulfadoxine/pyrimethamine (SP) as the front-line anti-malarial drug, with early replacement of chloroquine and delayed introduction of artemisinin-based combination therapy. Extended use of SP, and its continued application in pregnancy is impacting...... the genomic variation of the Plasmodium falciparum population. METHODS: Whole genome sequence data of P. falciparum isolates covering 2 years of transmission within Malawi, alongside global datasets, were used. More than 745,000 SNPs were identified, and differences in allele frequencies between countries...

High rates of parasite recrudescence following intermittent preventive treatment with sulphadoxine-pyrimethamine during pregnancy in Benin

DEFF Research Database (Denmark)

Moussiliou, Azizath; Sissinto-Savi De Tove, Yolande; Doritchamou, Justin

2013-01-01

the second dose. Women with persistent parasitaemia had an increased prevalence of anaemia (P = 0.03). CONCLUSION: The data presented here, highlight the inability of SP to ensure optimal antiplasmodial protection in late pregnancy, and invite urgent consideration of an alternative drug or strategy.......BACKGROUND: Despite widespread parasite resistance to sulphadoxine-pyrimethamine (SP) its use for intermittent preventative treatment during pregnancy remains the policy in Benin and throughout most of sub-Saharan Africa. METHODS: In a prospective study, 982 pregnant women were recruited in Benin...

Continued efficacy of sulfadoxine-pyrimethamine as second line treatment for malaria in children in Guinea-Bissau

DEFF Research Database (Denmark)

Kofoed, Poul-Erik; Rodrigues, Amabelia; Aaby, Peter

2006-01-01

BACKGROUND: Sulfadoxine-pyrimethamine (S/P) is widely used for treatment of failures following the first line treatment for malaria in Africa. In Guinea-Bissau, it has been recommended as second line therapy by the National Malaria Programme since 1996. In order to monitor any change of the in vivo...... sensitivity, the efficacy of S/P was studied immediately before the introduction of the drug and 6-9 years later. METHODS: Children participating in clinical in vivo studies were given S/P if having late clinical treatment failure following the treatment with quinine, chloroquine, or amodiaquine...

Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials

NARCIS (Netherlands)

Aponte, John J.; Schellenberg, David; Egan, Andrea; Breckenridge, Alasdair; Carneiro, Ilona; Critchley, Julia; Danquah, Ina; Dodoo, Alexander; Kobbe, Robin; Lell, Bertrand; May, Jürgen; Premji, Zul; Sanz, Sergi; Sevene, Esperanza; Soulaymani-Becheikh, Rachida; Winstanley, Peter; Adjei, Samuel; Anemana, Sylvester; Chandramohan, Daniel; Issifou, Saadou; Mockenhaupt, Frank; Owusu-Agyei, Seth; Greenwood, Brian; Grobusch, Martin P.; Kremsner, Peter G.; Macete, Eusebio; Mshinda, Hassan; Newman, Robert D.; Slutsker, Laurence; Tanner, Marcel; Alonso, Pedro; Menendez, Clara

2009-01-01

BACKGROUND: Intermittent preventive treatment (IPT) is a promising strategy for malaria control in infants. We undertook a pooled analysis of the safety and efficacy of IPT in infants (IPTi) with sulfadoxine-pyrimethamine in Africa. METHODS: We pooled data from six double-blind, randomised,

Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

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Rogers William O

2010-04-01

Full Text Available Abstract Background Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. Methods In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. Results The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Conclusion Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study

Increase in the prevalence of mutations associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates collected from early to late pregnancy in Nanoro, Burkina Faso

NARCIS (Netherlands)

Ruizendaal, Esmée; Tahita, Marc C.; Geskus, Ronald B.; Versteeg, Inge; Scott, Susana; d'Alessandro, Umberto; Lompo, Palpouguini; Derra, Karim; Traore-Coulibaly, Maminata; de Jong, Menno D.; Schallig, Henk D. F. H.; Tinto, Halidou; Mens, Petra F.

2017-01-01

Pregnant women are a high-risk group for Plasmodium falciparum infections, which may result in maternal anaemia and low birth weight newborns, among other adverse birth outcomes. Intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy (IPTp-SP) is widely implemented to

Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger.

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Grais, Rebecca F; Laminou, Ibrahim M; Woi-Messe, Lynda; Makarimi, Rockyath; Bouriema, Seidou H; Langendorf, Celine; Amambua-Ngwa, Alfred; D'Alessandro, Umberto; Guérin, Philippe J; Fandeur, Thierry; Sibley, Carol H

2018-02-27

In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine-pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011-2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing. Prior to SMC implementation, the samples showed a high proportion of clinical samples that carried the pfdhfr 51I/59R/108N haplotype associated with resistance to pyrimethamine and pfdhps 436A/F/H and 437G mutations associated with reduced susceptibility to sulfadoxine. In contrast mutations in codons 581G, and 613S in the pfdhps gene, and in pfmdr1, 86Y, 184Y, 1042D and 1246Y associated with resistance to amodiaquine, were less frequently observed. Importantly, pfdhfr I164L and pfdhps K540E mutations shown to be the most clinically relevant markers for high level clinical resistance to SP were not detected in Gabi. Although parasites with genotypes associated with the highest levels of resistance to AQ + SP are not yet common in this setting, their importance for deployment of SMC and IPTp dictates that monitoring of these markers of resistance should accompany these interventions. This study also highlights the parasite heterogeneity within a small spatial area and the need to

Pyrimethamine-induced alterations in human lymphocytes in vitro. Mechanisms and reversal of the effect

DEFF Research Database (Denmark)

Bygbjerg, Ib Christian

1985-01-01

It has previously been shown that the antiprotozoal drug pyrimethamine (PYR) in concentrations corresponding to those obtained in clinical practice temporarily suppressed the proliferation of phytohaemagglutinin (PHA-) stimulated human lymphocytes in vitro; 10-fold higher concentrations permanently...... suppressed PHA-stimulated cells, as indicated by decreased numbers of cells and DNA synthesis. In the present study, it was found that the 3H-deoxyuridine incorporation in PHA-stimulated lymphocytes was suppressed by PYR, and that PYR caused defective deoxyuridine suppression of 14C-thymidine incorporation......, reduced thymidylate synthesis cannot be the sole consequence of PYR exposure. It is suggested that an additional folate-dependent factor plays an important role in the antimitotic activity of PYR on lymphocytes....

Molecular epidemiology of malaria in Cameroon. XXX. sequence analysis of Plasmodium falciparum ATPase 6, dihydrofolate reductase, and dihydropteroate synthase resistance markers in clinical isolates from children treated with an artesunate-sulfadoxine-pyrimethamine combination.

Science.gov (United States)

Menemedengue, Virginie; Sahnouni, Khalifa; Basco, Leonardo; Tahar, Rachida

2011-07-01

Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are reliable molecular markers for antifolate resistance. The P. falciparum ATPase 6 (pfatp6) gene has been proposed to be a potential marker for artemisinin resistance. In our previous clinical study, we showed that artesunate-sulfadoxine-pyrimethamine is highly effective against uncomplicated malaria in Yaoundé, Cameroon. In the present study, dhfr, dhps, and pfatp6 mutations in P. falciparum isolates obtained from children treated with artesunate-sulfadoxine-pyrimethamine were determined. All 61 isolates had wild-type Pfatp6 263, 623, and 769 alleles, and 11 (18%) had a single E431K substitution. Three additional mutations, E643Q, E432K, and E641Q, were detected. The results did not indicate any warning signal of serious concern (i.e., no parasites were seen with quintuple dhfr-dhps, DHFR Ile164Leu, or pfatp6 mutations), as confirmed by the high clinical efficacy of artesunate-sulfadoxine-pyrimethamine. Further studies are required to identify a molecular marker that reliably predicts artemisinin resistance.

Effectiveness of Intermittent Preventive Treatment in Pregnancy with Sulphadoxine-Pyrimethamine against Submicroscopic falciparum Malaria in Central Region, Ghana

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Ekene K. Nwaefuna

2015-01-01

Full Text Available Malaria infections undetectable by microscopy but detectable by Polymerase Chain Reaction (PCR (submicroscopic malaria are common in endemic areas like Ghana. Submicroscopic malaria has been linked with severe pregnancy outcomes as well as contributing to malaria transmission. In this cross-sectional study 872 consenting pregnant women (gestation ≥ 20 weeks were recruited from 8 hospitals in Central Region, Ghana, between July and December 2009. Malaria infection was detected by microscopy and PCR. Haemoglobin was measured and anaemia was defined as haemoglobin lower than 11 g/dL. Majority of the women, 555 (63.6%, were Intermittent Preventive Treatment in Pregnancy with Sulphadoxine-Pyrimethamine (IPTp-SP users while 234 (36.4% were nonusers. The prevalence of malaria by microscopy was 20.9% (182/872 and 9.7% (67/688 of microscopy negative women had submicroscopic malaria. IPTp-SP usage significantly (odds ratio = 0.13, 95% confidence interval = 0.07–0.23, p=0.005 reduced the prevalence of submicroscopic malaria as more nonusers (51/234 than users (16/454 were PCR positive. After controlling for other variables the effect of IPTp-SP remained statistically significant (odds ratio = 0.11, 95% confidence interval = 0.02–0.22, p=0.006. These results suggest that Intermittent Preventive Treatment with Sulphadoxine-Pyrimethamine is useful in the reduction of submicroscopic malaria in pregnancy.

High frequency of Plasmodium falciparum CICNI/SGEAA and CVIET haplotypes without association with resistance to sulfadoxine/pyrimethamine and chloroquine combination in the Daraweesh area, in Sudan

DEFF Research Database (Denmark)

A-Elbasit, I E; Khalil, I F; Elbashir, M I

2008-01-01

Estimation of the prevalence of the molecular markers of sulfadoxine/pyrimethamine (SP) and chloroquine (CQ) resistance and validation of the association of mutations with resistance in different settings is needed for local policy guidance and for contributing to a global map for anti-malarial d......Estimation of the prevalence of the molecular markers of sulfadoxine/pyrimethamine (SP) and chloroquine (CQ) resistance and validation of the association of mutations with resistance in different settings is needed for local policy guidance and for contributing to a global map for anti......-malarial drug resistance. In this study, malaria patients treated with SP alone (60) and SP with CQ (194) had a total treatment failure (TF) of 35.4%, with no difference between the two arms. The polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA) method was used to identify polymorphisms...

Efficacy of chloroquine, amodiaquine, sulphadoxine-pyrimethamine and combination therapy with artesunate in Mozambican children with non-complicated malaria

DEFF Research Database (Denmark)

Abacassamo, F; Enosse, S; Aponte, J J

2004-01-01

This paper reports a two-phase study in Manhiça district, Mozambique: first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine (CQ), sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ), then we tested the safety and efficacy in the treatment of......% to AQ. Co-administration of AQ + SP, AR + SP and AQ + AR was safe and had 100% clinical efficacy at 14-day follow-up. The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up....

Intermittent preventive treatment with sulphadoxine-pyrimethamine is effective in preventing maternal and placental malaria in Ibadan, south-western Nigeria

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Mokuolu Olugbenga A

2007-07-01

Full Text Available Abstract Background Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPT-SP is currently the recommended regimen for prevention of malaria in pregnancy in endemic areas. This study sets out to evaluate the effectiveness of IPT-SP in the prevention of maternal and placental malaria in parturient mothers in Ibadan, Nigeria, where the risk of malaria is present all year round. Method During a larger study evaluating the epidemiology of congenital malaria, the effect of malaria prophylaxis was examined in 983 parturient mothers. Five hundred and ninety eight mothers (60.8% received IPT-SP, 214 (21.8% received pyrimethamine (PYR and 171 (17.4% did not take any chemoprophylactic agent (NC. Results The prevalence of maternal parasitaemia in the IPT-SP, PYR and NC groups was 10.4%, 15.9% and 17% respectively (p = 0.021. The prevalence of placental parasitaemia was 10.5% in the IPT-SP, 16.8% PYR and 17% NC groups, respectively (p = 0.015. The prevalence of maternal anaemia (haematocrit Conclusion IPT-SP is effective in preventing maternal and placental malaria as well as improving pregnancy outcomes among parturient women in Ibadan, Nigeria. The implementation of the recently adopted IPT-SP strategy should be pursued with vigour as it holds great promise for reducing the burden of malaria in pregnancy in Nigeria.

Atovaquone and proguanil hydrochloride compared with chloroquine or pyrimethamine/sulfadoxine for treatment of acute Plasmodium falciparum malaria in Peru

OpenAIRE

Llanos-Cuentas, A.; Campos, P.; Clendenes, M.; Canfield, C. J.; Hutchinson, D. B. A.

2001-01-01

The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were sub...

Malaria chemoprophylaxis in travellers to east Africa: a comparative prospective study of chloroquine plus proguanil with chloroquine plus sulfadoxine-pyrimethamine

OpenAIRE

Fogh, S; Schapira, A; Bygbjerg, I C; Jepsen, S; Mordhorst, C H; Kuijlen, K; Ravn, P; Rønn, A; Gøtzsche, P C

1988-01-01

As malaria caused by Plasmodium falciparum has become resistant to chloroquine alternative drug regimens need to be developed. The prophylactic efficacy against malaria and the side effects of chloroquine phosphate 500 mg weekly with proguanil hydrochloride 200 mg daily was compared with the efficacy of chloroquine 500 mg weekly with sulfadoxine 500 mg-pyrimethamine 25 mg weekly in a randomised study of Scandinavian travellers to Kenya and Tanzania during 1984-5. A total of 767 subjects (416 ...

Intermittent Preventive Therapy for Malaria During Pregnancy Using 2 vs 3 or More Doses of Sulfadoxine-Pyrimethamine and Risk of Low Birth Weight in Africa

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Kayentao, Kassoum; Garner, Paul; van Eijk, Anne Maria; Naidoo, Inbarani; Roper, Cally; Mulokozi, Abdunoor; MacArthur, John R.; Luntamo, Mari; Ashorn, Per; Doumbo, Ogobara K.; ter Kuile, Feiko O.

2015-01-01

Importance Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a pivotal period for fetal weight gain. Objective To perform a systematic review and meta-analysis of trials to determine whether regimens containing 3 or more doses of sulfadoxine-pyrimethamine for intermittent preventive therapy during pregnancy are associated with a higher birth weight or lower risk of low birth weight (LBW) (<2500 g) than standard 2-dose regimens. Data Sources and Study Selection ISI Web of Knowledge, EMBASE, SCOPUS, PubMed, LILACS, the Malaria in Pregnancy Library, Cochrane CENTRAL, and trial registries from their inception to December 2012, without language restriction. Eligible studies included randomized and quasi-randomized trials of intermittent preventive therapy during pregnancy with sulfadoxine-pyrimethamine monotherapy. Data Extraction Data were independently abstracted by 2 investigators. Relative risk (RR), mean differences, and 95% CIs were calculated with random-effects models. Results Of 241 screened studies, 7 trials of 6281 pregnancies were included. The median birth weight in the 2-dose group was 2870 g (range, 2722–3239 g) and on average 56 g higher (95% CI, 29–83 g; I2=0%) in the ≥3-dose group. Three or more doses were associated with fewer LBW births (RR,0.80; 95% CI, 0.69–0.94; I2=0%), with a median LBW risk per 1000 women in the 2-dose group (assumed control group risk) of 167 per 1000 vs 134 per 1000 in the ≥3-dose group (absolute risk reduction, 33 per 1000 [95% CI, 10–52]; number needed to treat=31). The association was consistent across a wide range of sulfadoxine-pyrimethamine resistance (0% to 96% dihydropteroate-synthase K540E mutations). There was no evidence of small-study bias. The ≥3-dose group had

Low-grade sulfadoxine-pyrimethamine resistance in Plasmodium falciparum parasites from Lubango, Angola.

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Kaingona-Daniel, Elsa P S; Gomes, Larissa Rodrigues; Gama, Bianca E; Almeida-de-Oliveira, Natália K; Fortes, Filomeno; Ménard, Didier; Daniel-Ribeiro, Cláudio Tadeu; Ferreira-da-Cruz, Maria de Fátima

2016-06-07

Malaria is a major parasitic disease, affecting millions of people in endemic areas. Plasmodium falciparum parasites are responsible for the most severe cases and its resistance to anti-malarial drugs is notorious. This is a possible obstacle to the effectiveness of intermittent preventive treatment (IPT) based on sulfadoxine-pyrimethamine (SP) cures administrated to pregnant women (IPTp) during their pregnancy. As this intervention is recommended in Angola since 2006, it has assessed, in this country, the molecular profiles in P. falciparum dhfr and dhps, two polymorphic genes associated to pyrimethamine and sulfadoxine resistance, respectively. Blood samples from 52 falciparum patients were collected in Lubango, Angola and pfdhfr and pfdhps polymorphisms were analysed using nested-PCR and DNA sequencing. In the pfdhfr gene, the 108N mutation was almost fixed (98 %), followed by 59R (63 %), 51I (46 %), 50R and 164L (2 %, respectively). No 16V/S mutations were found. The most common double mutant genotype was CNRN (59 + 108; 46 %), followed by CICN (51 + 108; 29 %) whereas IRN (51 + 59 + 108; 15 %), CNRNVL (59 + 108 + 164; 2 %) and RICN (50 + 51 + 108; 2 %) triple mutant genotypes were detected. Investigations of the pfdhps gene showed that the 437G mutation was the most prevalent (97 %). Only two and one samples disclosed the 540E (7 %) and the 436A (3 %), respectively. Single mutant SGKAA (437; 86 %) was higher than SGEAA (437 + 540; 7 %) or AGKAA (436 + 437; 3 %) double mutants genotypes. No polymorphism was detected at codons 581G and 613T/S. Combining pfdhfr and pfdhps alleles two triple mutant haplotypes (double mutant in dhfr and single mutant in dhps) were observed: the ACICNVI/SGKAA in 14 (56 %) samples and the ACNRNVI/SGKAA in five (20 %) samples. One quadruple mutant haplotype was detected (ACIRNVI/SGKAA) in six (24 %) P. falciparum samples. No quintuple pfdhfr-pfdhps mutant was noted. pfdhfr and pfdhps gene

Marked reduction in prevalence of malaria parasitemia and anemia in HIV-infected pregnant women taking cotrimoxazole with or without sulfadoxine-pyrimethamine intermittent preventive therapy during pregnancy in Malawi

NARCIS (Netherlands)

Kapito-Tembo, Atupele; Meshnick, Steven R.; van Hensbroek, Michaël Boele; Phiri, Kamija; Fitzgerald, Margaret; Mwapasa, Victor

2011-01-01

Effectiveness of cotrimoxazole (CTX) compared with sulfadoxine-pyrimethamine (SP) intermittent-preventive-therapy (IPTp) for malaria in HIV-infected pregnant women is unknown. We examined effectiveness of CTX with or without SP-IPTp versus SP-IPTp at reducing malaria parasitemia and anemia. From

An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).

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Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

2011-01-01

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were

An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay–Sachs or Sandhoff variants)

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Clarke, Joe T.R.; Mahuran, Don J.; Sathe, Swati; Kolodny, Edwin H.; Rigat, Brigitte A.; Raiman, Julian A.; Tropak, Michael B.

2010-01-01

Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of β-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay–Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period. The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal β-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were

Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

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Mombo-Ngoma Ghyslain

2010-10-01

Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine

DEFF Research Database (Denmark)

Schmidt, Dorte Remmer; Høgh, Birthe; Andersen, O

2006-01-01

Abstract The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or Ig...... detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5×109/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was 0.5×109/l or lower...... of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits....

Efficacy of Artesunate + Sulphadoxine-Pyrimethamine (AS + SP and Amodiaquine + Sulphadoxine-Pyrimethamine (AQ + SP for Uncomplicated falciparum Malaria in Equatorial Guinea (Central Africa

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Pilar Charle

2009-01-01

Full Text Available Objectives. The objectives of the study were (i to evaluate the efficacy of combination drugs, such as artesunate + sulphadoxine-pyrimethamine (AS + SP and amodiaquine + sulphadoxine-pyripethamine (AQ + SP in treatment of uncomplicated falciparum malaria (ii to differentiate recrudescence from reinfection by analysing msp-1 and msp-2 genes of Plasmodium falciparum in treatment failure cases. Methods. We carried out an in vivo study in the year 2005 in 206 children between 6 to 59 months age groups. Of the 206, 120 received AQ + SP, and 86 received AS + SP. A clinical and parasitological followup during 14 days was undertaken. Finger-prick blood sample from each patient was taken on Whatman filter paper (no. 3 on days 0, 7, 14 and also the day when the parasite and symptoms reappeared for PCR analysis. Results. Late treatment failure was observed in 3.5% (4/114 with AQ + SP, and 2.5% (2/79 with AS + SP. The success rate was 96.5% with AQ + SP and 97.5% with AS + SP. No deaths and severe reactions were recorded. Out of the 6 treatment failure cases, one was reinfection as observed by PCR analysis of msp-1 and msp-2 genes on day 14. Discussion. Both the combinations found to be efficacious and safe and could be used as a first-line treatment for uncomplicated falciparum malaria in Equatorial Guinea.

Intermittent preventive therapy for malaria during pregnancy using 2 vs 3 or more doses of sulfadoxine-pyrimethamine and risk of low birth weight in Africa: systematic review and meta-analysis

NARCIS (Netherlands)

Kayentao, Kassoum; Garner, Paul; van Eijk, Anne Maria; Naidoo, Inbarani; Roper, Cally; Mulokozi, Abdunoor; MacArthur, John R.; Luntamo, Mari; Ashorn, Per; Doumbo, Ogobara K.; ter Kuile, Feiko O.

2013-01-01

Intermittent preventive therapy with sulfadoxine-pyrimethamine to control malaria during pregnancy is used in 37 countries in sub-Saharan Africa, and 31 of those countries use the standard 2-dose regimen. However, 2 doses may not provide protection during the last 4 to 10 weeks of pregnancy, a

A fixed-dose 24-hour regimen of artesunate plus sulfamethoxypyrazine-pyrimethamine for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan

DEFF Research Database (Denmark)

Adam, Ishag; Magzoub, Mamoun; Osman, Maha E

2006-01-01

-sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....

Effect of cyclic, low dose pyrimethamine treatment in patients with Late Onset Tay Sachs: an open label, extended pilot study.

Science.gov (United States)

Osher, Etty; Fattal-Valevski, Aviva; Sagie, Liora; Urshanski, Nataly; Sagiv, Nadav; Peleg, Leah; Lerman-Sagie, Tally; Zimran, Ari; Elstein, Deborah; Navon, Ruth; Valevski, Avi; Stern, Naftali

2015-04-17

Late Onset Tay- Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the α subunit (HEXA) of β-hexosaminidase enzyme (HexA). At the present time, no effective treatment exists for LOTS and other neurodegenerative diseases involving the central nerve system (CNS). Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.g., αG269S), but not all LOTS-related mutations. The present study assessed the effect of cyclic, low dose and long term pyrimethamine treatment on HexA in subjects with LOTS. In an open label trial in 4 LOTS patients, PMT was initiated at an average daily dose of ~2.7 mg and administered cyclically guided by blood lymphocyte HexA activity for a mean duration of 82.8 (±22.5; SD) weeks (~1.5 year). HexA activity rose in all subjects, with a mean peak increase of 2.24 folds (±0.52; SD) over baseline activity (range 1.87-3). The mean treatment time required to attain this peak was of 15.7 (±4.8; SD) weeks. Following increase in activity, HexA gradually declined with the continued use of PMT, which was then stopped, resulting in the return of HexA activity to baseline. A second cycle of PMT treatment was then initiated, resulting again in an increase in HexA activity. Three of the patients experienced a measurable neuropsychiatric deterioration whereas one subject remained entirely stable. Cyclic low dose of PMT can increase HexA activity in LOTS patients. However, the observed increase is repeatedly transient and not associated with discernible beneficial neurological or psychiatric effects.

A comparative study on the efficacy of artesunate plus sulphadoxine/pyrimethamine versus artemether-lumefantrine in eastern Sudan

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Mansour Fathi A

2007-07-01

Full Text Available Abstract Background A combination of artesunate (AS plus sulphadoxine/pyrimethamine (SP as first-line and artemether-lumefantrine (AL as second-line treatment are currently recommended against uncomplicated P. falciparum infection in Sudan. However, there is limited information on the efficacy of ACTs in the country and only one report of PCR-corrected results for AS/SP only. Methods The WHO protocol for the assessment of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria was employed. Artesunate plus sulphadoxine/pyrimethamine (AS/SP was compared to artemether-lumefantrine (AL in a 28-day follow up. Samples that were classified as early treatment failure (ETF, late treatment failure (LCF or late parasitological failure (LPF were genotyped for msp-1 and msp-2 genes to differentiate recrudescence from reinfection. Results A total of 178 patients were screened and 160 met the enrolment criteria and were recruited to the study of which 157 (98.1% completed the follow up and had an analysed treatment outcome. On the AS/SP arm, three (0.038% patients were lost during the follow-up, two on day 1 and one on day 7, and 77 (96.3 completed the study, while all 80 (100% patients completed the follow up in the AL arm. In the per protocol analysis for AS/SP the treatment outcome for patients who completed the follow-up were as follows: adequate clinical and parasitological response (ACPR; 84.4% ETF; 1.3%, LCF; 3.9%, (LPF; 10.4%. For the AL arm the out come was as follows, ACPR; 90%, ETF; 0%, LCF; 6.3% and LPF; 3.8%. However, when PCR-corrected, 6.5% (5/77 of patients treated with AS/SP maintained parasites from their primary infection, while (7/80 in the AL group maintained their initial parasite genotype. Therefore, PCR-corrected efficacy was 93.5% in the AS/SP treated group and for AL it was 91.3%. Conclusion Both AS/SP and AL are highly effective for the treatment of uncomplicated falciparum malaria in eastern Sudan. However

Intermittent preventive sulfadoxine-pyrimethamine treatment of primigravidae reduces levels of plasma immunoglobulin G, which protects against pregnancy-associated Plasmodium falciparum malaria

DEFF Research Database (Denmark)

Staalsoe, Trine; Shulman, Caroline E; Dorman, Edgar K

2004-01-01

Pregnancy-associated malaria (PAM) is an important cause of maternal and neonatal suffering. It is caused by Plasmodium falciparum capable of inhabiting the placenta through expression of particular variant surface antigens (VSA) with affinity for proteoglycans such as chondroitin sulfate A....... Protective immunity to PAM develops following exposure to parasites inhabiting the placenta, and primigravidae are therefore particularly susceptible to PAM. The adverse consequences of PAM in primigravidae are preventable by intermittent preventive treatment (IPTp), where women are given antimalarials...... at specified intervals during pregnancy, but this may interfere with acquisition of protective PAM immunity. We found that Kenyan primigravidae receiving sulfadoxine-pyrimethamine IPTp had significantly lower levels of immunoglobulin G (IgG) with specificity for the type of parasite-encoded VSA-called VSA(PAM...

Population Pharmacokinetics of Pyrimethamine and Sulfadoxine in Children Treated for Congenital Toxoplasmosis

Science.gov (United States)

Corvaisier, Stéphane; Charpiat, Bruno; Mounier, Cyril; Wallon, Martine; Leboucher, Gilles; Al Kurdi, Mounzer; Chaulet, Jean-François; Peyron, François

2004-01-01

The population pharmacokinetics of pyrimethamine (PYR) and sulfadoxine (SDX) for a group of 32 children with congenital toxoplasmosis was investigated by nonparametric modeling analysis. A one-compartment model was used as the structural model, and individual pharmacokinetic parameters were estimated by Bayesian modeling. PYR (1.25 mg/kg of body weight) and SDX (25 mg/kg) were administered orally every 10 days for 1 year, with adjustment of the dose to body weight every 3 months. Drug concentrations were measured by high-performance liquid chromatography. A total of 101 measurements in serum were available for both drugs. Mean absorption rate constants, volumes of distribution, elimination rate constants, and half-lives were 0.915 h−1, 4.379 liters/kg, 0.00839 h−1, and 5.5 days for PYR and 1.659 h−1, 0.392 liters/kg, 0.00526 h−1, and 6.6 days for SDX, respectively. Wide interindividual variability was observed. The estimated minimum and maximum concentrations of PYR in serum differed 8- and 25-fold among patients, respectively, and those of SDX differed 4- and 5-fold, respectively. Increases in the concentration of PYR were observed for eight children, and increases in the SDX concentration were observed for seven children. Serum PYR-SDX concentrations are unpredictable even when the dose is standardized for body weight. The concentrations of the PYR-SDX combination that are most efficacious for children have not yet been established. A model such as ours, associated with long-term follow-up, is needed to study the correlation between exposure to these two drugs and clinical outcome in children. PMID:15388436

Prevalence of mutation and phenotypic expression associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum and Plasmodium vivax.

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Zakai, Haytham A; Khan, Wajihullah; Asma, Umme

2013-09-01

Therapeutic efficacy of sulfadoxine-pyrimethamine (SP), which is commonly used to treat falciparum malaria, was assessed in isolates of Plasmodium falciparum (Welch, 1897) and Plasmodium vivax (Grassi et Feletti, 1890) ofAligarh, Uttar Pradesh, North India and Taif, Saudi Arabia during 2011-2012. Both the species showed mutations in dihydrofolate reductase (DHFR) enzyme as they have common biochemical drug targets. Mutation rate for pfdhfr was higher compared to pvdhfr because the drug was mainly given to treat falciparum malaria. Since both the species coexist, P. vivax was also exposed to SP due to faulty species diagnosis or medication without specific diagnosis. Low level of mutations against SP in P. falciparum of Saudi isolates indicates that the SP combination is still effective for the treatment of falciparum malaria. Since SP is used as first-line of treatment because of high level of resistance against chloroquine (CQ), it may result in spread of higher level of mutations resulting in drug resistance and treatment failure in near future. Therefore, to avoid further higher mutations in the parasite, use of better treatment regimens such as artesunate combination therapy must be introduced against SP combination.

Prevalence of Plasmodium falciparum resistance markers to sulfadoxine-pyrimethamine among pregnant women receiving intermittent preventive treatment for malaria in Uganda

DEFF Research Database (Denmark)

Mbonye, Anthony K; Birungi, Josephine; Yanow, Stephanie K

2015-01-01

The aim of this study was to assess the prevalence of mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes among pregnant women using sulfadoxine-pyrimethamine (SP) as an intermittent preventive treatment (IPTp). A molecular epidemiological...... in the Pfdhfr and Pfdhps genes that are associated with SP resistance. The prevalence of the single-nucleotide mutations in Pfdhfr at codons 51I, 59R, and 108N and in Pfdhps at codons 437G and 540E was high (>98%), reaching 100% fixation after one dose of SP, while the prevalence of 581G was 3.3% at baseline...... and anemia. However, women infected with P. falciparum had 1.3-g/dl-lower hemoglobin levels (P = 0.001) and delivered babies with a 400-g-lower birth weight (P = 0.001) compared to nonparasitemic women. Despite this, 44 women who were P. falciparum positive at baseline became negative after one or two doses...

Modelling the impact of antimalarial quality on the transmission of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum

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Aleisha R. Brock

2017-05-01

Full Text Available Background: The use of poor quality antimalarial medicines, including the use of non-recommended medicines for treatment such as sulfadoxine-pyrimethamine (SP monotherapy, undermines malaria control and elimination efforts. Furthermore, the use of subtherapeutic doses of the active ingredient(s can theoretically promote the emergence and transmission of drug resistant parasites. Methods: We developed a deterministic compartmental model to quantify the impact of antimalarial medicine quality on the transmission of SP resistance, and validated it using sensitivity analysis and a comparison with data from Kenya collected in 2006. We modelled human and mosquito population dynamics, incorporating two Plasmodium falciparum subtypes (SP-sensitive and SP-resistant and both poor quality and good quality (artemether-lumefantrine antimalarial use. Findings: The model predicted that an increase in human malaria cases, and among these, an increase in the proportion of SP-resistant infections, resulted from an increase in poor quality SP antimalarial use, whether it was full- or half-dose SP monotherapy. Interpretation: Our findings suggest that an increase in poor quality antimalarial use predicts an increase in the transmission of resistance. This highlights the need for stricter control and regulation on the availability and use of poor quality antimalarial medicines, in order to offer safe and effective treatments, and work towards the eradication of malaria. Keywords: Deterministic compartmental model, Falsified antimalarial medicine, Substandard antimalarial treatments, Antimalarial quality, Plasmodium falciparum malaria, Drug resistance

Quality of Sulfadoxine-Pyrimethamine Given as Antimalarial Prophylaxis in Pregnant Women in Selected Health Facilities in Central Region of Ghana

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Danny F. Yeboah

2016-01-01

Full Text Available The use of sulfadoxine-pyrimethamine (SP as an intermittent preventive treatment (IPT against malaria during pregnancy has become a policy in most sub-Sahara African countries and crucially depends on the efficacy of SP. This study sets out to evaluate the effectiveness of the SP given to the pregnant women in some selected health facilities in the Central Region of Ghana to prevent maternal malaria in pregnant women. A total of 543 pregnant women recruited from 7 selected health centres in Central Region of Ghana participated in the study. Parasite density of Plasmodium falciparum was determined from peripheral blood of the pregnant women using microscopy. High performance liquid chromatography (HPLC and dissolution tester were used to determine the quality of the SP. Malaria infection was recorded in 11.2% of pregnant women who had a history of SP consumption. SP failed the dissolution test. Pregnant women who did not receive IPT-SP were 44%. Low haemoglobin level was recorded in 73.5% of the pregnant women. The results indicated that SP was substandard. IPT-SP is ineffective in preventing malaria infection.

Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique

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Enosse, Sonia; Magnussen, Pascal; Abacassamo, Fatima

2008-01-01

BACKGROUND: In late 2002, the health authorities of Mozambique implemented sulphadoxine-pyrimethamine (SP)/amodiaquine (AQ) as first-line treatment against uncomplicated falciparum malaria. In 2004, this has been altered to SP/artesunate in line with WHO recommendations of using Artemisinin...... Combination Therapies (ACTs), despite the fact that all the neighbouring countries have abandoned SP-drug combinations due to high levels of SP drug resistance. In the study area, one year prior to the change to SP/AQ, SP alone was used to treat uncomplicated malaria cases. The study described here...... haplotype (CIRNI) remained high and only changed marginally from 46% to 53% (P = 0.405) after one year with SP as first-line treatment in the study area. Conversely, the combined Pfdhfr/Pfdhps quintuple mutant haplotype increased from 8% to 26% (P = 0.005). The frequency of the chloroquine resistance...

Appraisal on the prevalence of malaria and anaemia in pregnancy and factors influencing uptake of intermittent preventive therapy with sulfadoxine-pyrimethamine in Kibaha district, Tanzania.

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Tarimo, S Donath

2007-10-01

To appraise the prevalence of malaria and anaemia in antenatal mothers; and explore the factors influencing coverage of intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) under operational conditions in the national programme for malaria control in pregnancy. Descriptive cross-sectional survey. The reproductive and child health clinic in Kibaha district hospital, Tanzania SUBECTS: Pregnant mothers on routine antenatal visits Prevalence of malaria (peripheral parasitaemia) and anaemia, coverage of IPT with SP and the factors influencing coverage. A total of 395 mothers were recruited; 27.3% had malaria. Moderate anaemia i.e. haemoglobin (Hb) level 8. -10.9 g/dl was detected in 56.7% of mothers; 34.2% had severe anaemia (Hb 8.0 g/dl was strongly associated with negative parasitaemia while Hb < 8.0 gidl was strongly associated with positive parasitaemia. About a third (40.0%) of the mothers did not receive SP for IPT

Hitchhiking and Selective Sweeps of Plasmodium falciparum Sulfadoxine and Pyrimethamine Resistance Alleles in a Population from Central Africa▿ †

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McCollum, Andrea M.; Basco, Leonardo K.; Tahar, Rachida; Udhayakumar, Venkatachalam; Escalante, Ananias A.

2008-01-01

Sulfadoxine-pyrimethamine (SP) resistance in Plasmodium falciparum is encoded by a number of mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes. Here, we have characterized point mutations in dhfr and dhps and microsatellite loci around dhfr on chromosome 4 and dhps on chromosome 8 as well as neutral markers on chromosomes 2 and 3 in 332 samples from Yaoundé, Cameroon. The triple mutant dhfr haplotype that originated in Southeast Asia is the most predominant in this sample set, but we also find additional independent haplotypes at low frequency and an incipient process of genetic differentiation among alleles of Southeast Asian origin. As reported for other African populations, we find evidence of a selective sweep for resistant dhfr mutants in this Cameroonian population due to drug selection. Although we find evidence for a selective sweep in dhps mutants associated with SP resistance, the dynamics of dhps mutants appear different than those observed for dhfr mutants. Overall, our results yield support for the use of microsatellite markers to track resistant parasites; however, the detection of resistant dhfr alleles in low frequency, the evidence of divergence among dhfr alleles that share a common evolutionary origin, and the distinct dynamics of resistant dhps alleles emphasize the importance of comprehensive, population-based investigations to evaluate the effects of drug selection on parasite populations. PMID:18765692

High efficacy of two artemisinin-based combinations: artesunate + sulfadoxine-pyrimethamine and artemether-lumefantrine for falciparum malaria in Yemen.

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Adeel, Ahmed A; Saeed, Niaz Abdo; Aljasari, Adel; Almohager, Amar M; Galab, Mohamed H; AlMahdi, Amar; Mahammed, Mansor H; AlDarsi, Mohammed; Salaeah, Yahiya A; Atta, Hoda; Zamani, Ghasem; Warsame, Marian; Barrette, Amy; Mohammady, Hanan El; Nada, Rania A

2015-11-14

Artesunate + sulfadoxine-pyrimethamine (AS + SP) has been the first-line treatment and artemether-lumefantrine (AL) the second-line treatment for uncomplicated falciparum malaria in Yemen since 2005. This paper reports the results of studies conducted to monitor therapeutic efficacy of these two drugs in sentinel sites in Yemen. Eight therapeutic efficacy studies were conducted in six sentinel sites during the period 2009-2013 in Yemen. Five studies were for the evaluation of AS + SP (total of 465 patients) and three studies (total of 268 patients) for the evaluation of AL. The studies were done according to standard WHO protocol 2009 with 28-day follow-up. In the evaluation of AS + SP, the PCR-corrected cure rate was 98 % (95 % CI 92.2-99.5 %) in one site and 100 % in all of the other four sites. In the sites where AL was evaluated, the PCR-corrected cure rate was 100 % in all the sites. All patients were negative for asexual parasitaemia on day 3 in both the AS + SP and the AL groups. There was a higher rate of clearance of gametocytaemia in the AL-treated group when compared with the AS + SP groups from day 7 onwards. AS + SP remains the effective drug for uncomplicated falciparum malaria in Yemen. AL is also highly effective and can be an appropriate alternative to AS + SP for the treatment of falciparum malaria. AL demonstrated a higher efficacy in clearing microscopic gametocytaemia than AS + SP. Trial registration number ACTRN12610000696099.

Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children.

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Badara Cisse

Full Text Available BACKGROUND: The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA or sulfadoxine-pyrimethamine (SP is as effective, and better tolerated, than SP plus amodiaquine (AQ, when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal. METHODS: Treatments were delivered to children 3-59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events. RESULTS: 1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/microL, 29/671 (4.3% in the SP+AQ group, compared with 22/604 (3.6% in the DHA+PQ group (risk difference 0.47%, 95%CI -2.3%,+3.3%, and 17/618 (2.8% in the SP+PQ group (risk difference 1.2%, 95%CI -1.3%,+3.6%. Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season. CONCLUSIONS: Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites. TRIAL REGISTRATION: ClinicalTrials.gov NCT00529620.

A novel prediction approach for antimalarial activities of Trimethoprim, Pyrimethamine, and Cycloguanil analogues using extremely randomized trees.

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Nattee, Cholwich; Khamsemanan, Nirattaya; Lawtrakul, Luckhana; Toochinda, Pisanu; Hannongbua, Supa

2017-01-01

Malaria is still one of the most serious diseases in tropical regions. This is due in part to the high resistance against available drugs for the inhibition of parasites, Plasmodium, the cause of the disease. New potent compounds with high clinical utility are urgently needed. In this work, we created a novel model using a regression tree to study structure-activity relationships and predict the inhibition constant, K i of three different antimalarial analogues (Trimethoprim, Pyrimethamine, and Cycloguanil) based on their molecular descriptors. To the best of our knowledge, this work is the first attempt to study the structure-activity relationships of all three analogues combined. The most relevant descriptors and appropriate parameters of the regression tree are harvested using extremely randomized trees. These descriptors are water accessible surface area, Log of the aqueous solubility, total hydrophobic van der Waals surface area, and molecular refractivity. Out of all possible combinations of these selected parameters and descriptors, the tree with the strongest coefficient of determination is selected to be our prediction model. Predicted K i values from the proposed model show a strong coefficient of determination, R 2 =0.996, to experimental K i values. From the structure of the regression tree, compounds with high accessible surface area of all hydrophobic atoms (ASA_H) and low aqueous solubility of inhibitors (Log S) generally possess low K i values. Our prediction model can also be utilized as a screening test for new antimalarial drug compounds which may reduce the time and expenses for new drug development. New compounds with high predicted K i should be excluded from further drug development. It is also our inference that a threshold of ASA_H greater than 575.80 and Log S less than or equal to -4.36 is a sufficient condition for a new compound to possess a low K i . Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of folate supplementation on the efficacy of sulfadoxine/pyrimethamine in preventing malaria in pregnancy: the potential of 5-methyl-tetrahydrofolate.

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Nzila, Alexis; Okombo, John; Molloy, Anne M

2014-02-01

Malaria remains the leading cause of mortality and morbidity in children under the age of 5 years and pregnant women. To counterbalance the malaria burden in pregnancy, an intermittent preventive treatment strategy has been developed. This is based on the use of the antifolate sulfadoxine/pyrimethamine, taken at specified intervals during pregnancy, and reports show that this approach reduces the malaria burden in pregnancy. Pregnancy is also associated with the risk of neural tube defects (NTDs), especially in women with low folate status, and folic acid supplementation is recommended in pregnancy to lower the risk of NTDs. Thus, in malaria-endemic areas, pregnant women have to take both antifolate medication to prevent malaria and folic acid to lower the risk of NTDs. However, the concomitant use of folate and antifolate is associated with a decrease in antifolate efficacy, exposing pregnant women to malaria. Thus, there is genuine concern that this strategy may not be appropriate. We have reviewed work carried out on malaria folate metabolism and antifolate efficacy in the context of folate supplementation. This review shows that: (i) the folate supplementation effect on antifolate efficacy is dose-dependent, and folic acid doses required to protect pregnant women from NTDs will not decrease antifolate activity; and (ii) 5-methyl-tetrahydrofolate, the predominant form of folate in the blood circulation, could be administered (even at high dose) concomitantly with antifolate without affecting antifolate efficacy. Thus, strategies exist to protect pregnant women from malaria while maintaining adequate folate levels in the body to reduce the occurrence of NTDs.

Prevention of anaemia in pregnancy using insecticide-treated bednets and sulfadoxine-pyrimethamine in a highly malarious area of Kenya: a randomized controlled trial.

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Njagi, Joseph Kiambo; Magnussen, Pascal; Estambale, Benson; Ouma, John; Mugo, Benbolt

2003-01-01

To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine (SP) given during the second and third trimester of pregnancy, the use of insecticide-treated nets (ITN), or the combination of both on haemoglobin (Hb) levels during pregnancy, a randomized, placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999. Primigravidae and secundigravidae were enrolled into the study and randomized into 4 intervention groups: (i) ITNs and SP, (ii) ITNs and placebo SP, (iii) SP alone, and (iv) placebo SP. All groups were offered case management and iron and folic acid supplementation. Seven hundred and fifty-two women were followed until delivery (53.2% were primigravidae and 46.8% secundigravidae). Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery (107.6 g/L) compared with recruitment (101.9 g/L) (P anaemia was 55.8% (95% CI 30.6-71.8), of SP alone 50.9% (95% CI 22.2-69.0), and of ITNs 41.6% (95% CI 9.8-62.3). Among secundigravidae, Hb levels were slightly lower at delivery compared with recruitment (P = 0.03). It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae, and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae.

Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru Eficácia da sulfadoxina-pirimetamina e mefloquina no tratamento de malária não-complicada por Plasmodium falciparum na bacia amazônica peruana

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Alan J. Magill

2004-06-01

Full Text Available In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.Testes in vivo foram realizados para avaliar resistência a drogas antimalária, em pessoas com malária não complicada, causada por Plasmodium falciparum, numa região isolada da Bacia Amazônica, na fronteira com o Brasil e a Colômbia. Os testes mostraram resistência >50% RII/RIII a sulfadoxina-pirimetamina, mas não evidenciaram resistência a mefloquina.

HUBUNGAN SENSISTIVITAS PLASMODIUM FALCIPARUM TERHADAP KOMBINASI PIRIMETAMIN/SULFADOKSIN DAN KLOROKUIN SECARA IN VITRO

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Sahat Ompusunggu

2012-09-01

Full Text Available An in vitro sensitivity test was conducted to study the sensitivity of Plasmodium falciparum against chloroquine and pyrimethamine/sulphadoxine combination. The relationship between sensitivity of the parasite to the two drugs was also studied. A total of 72 patients from five localities were examined during 1984-1985. Test against chloroquine was conduc­ted according to WHO method, while against pyrimethamine/sulphadoxine combination, a modified method of Nguyen Dinh and Payne and Eastham and Rieckmann was used. The results showed that there is no relationship between the sensitivity of P. falciparum against pyrimethamine/ sulphadoxine combination and chloroquine. It can be concluded that in case of chloroquine resistant P. falciparum, pyrimethamine/sulphadoxine combination could be applied as an alternative chemotherapy.

Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal

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Sow Diarietou

2009-06-01

Full Text Available Abstract Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years (ORa = 3.07 [1.49–6.29]; p = 0.004; and the profession of the head of household (retailer/employee versus farmer (ORa = 2.71 [1.34–5.48]; p = 0.006. Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013, and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001 were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

Implementation of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine (IPTp-SP at a district health centre in rural Senegal

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Vaillant Michel

2008-11-01

Full Text Available Abstract Background Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP is recommended for reducing the risk of malaria in pregnancy and its consequences on mothers and babies (IPTp-SP. Indicators of implementation and effects of IPTp-SP were collected in a rural clinic in Southern Senegal. Methods Women seen routinely at the antenatal clinic (ANC of a rural dispensary during 2000–2007. Deployment of IPTp-SP started in January 2004. Inspection of antenatal and outpatient clinic registries of the corresponding period. Results Between 1st January 2000 and 30th April 2007, 1,781 women of all gravitidities and parities attended the ANC with 965 deliveries (606 and 398 respectively since 1st January 2004, when IPTp-SP was started. 69% of women were seen ≥ 3 times; 95% received at least one dose and 70% two doses of SP (from 61% in 2004 to 86% in 2007. The first visit, first and second dose of SP occurred at a median week 20, 22 and 31. The probability of receiving two doses was > 80% with ≥ 3 antenatal visits and a first dose of SP by week 20. The prevalence of maternal malaria was low and similar pre- (0.7% and during IPTp (0.8%. Effects on of low birth weight (LBW, Unfavourable pregnancy outcomes numbered 72 (7.5% of pregnancies with known outcome, including 30 abortions and 42 later deaths (late foetal deaths, stillbirth, peri-natal of which 13 with one or more malformations (1.35% of all recorded deliveries. Conclusion The implementation of IPTp-SP was high. Early attendance to ANC favours completion of IPTp-SP. The record keeping system in place is amenable to data extraction and linkage. A model was developed that predicts optimal compliance to two SP doses, and could be tested in other settings. Maternal malaria was infrequent and unaffected by IPTp-SP. The risk of LBW was lower during IPT implementation but the difference was non-significant and could have other explanations.

A rodent malarial model of Plasmodium berghei for the development ...

African Journals Online (AJOL)

A rodent malarial model of Plasmodium berghei for the development of pyrimethamine and sulphadoxine-pyrimethamine resistant malaria in mice. ... course approach with 125/6.25mg/kg S/P. The stability of resistance phenotypes, parasite pathogenic disposition and host leukocyte response were also investigated.

Oral trimethoprim-sulfamethoxazole in the treatment of cerebral ...

African Journals Online (AJOL)

Toxoplasma encephalitis is the commonest cause of intracranial mass lesions in AIDS patients, Effective therapy includes pyrimethamine plus sulfadiazine, dindamycin with pyrimethamine, and co-trimoxazole. This study examines the efficacy of oral co-trimoxazole in 20 AIDS patients with toxoplasmosis and seeks to ...

Azithromycin prophylaxis and treatment of murine toxoplasmosis.

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Tabbara, Khalid F; Hammouda, Ehab; Tawfik, Abdulkader; Al-Omar, Othman M; Abu El-Asrar, Ahmed M

2005-03-01

To evaluate the azithromycin effects alone and in combination with other agents in the prophylaxis and treatment of murine toxoplasmosis. A total of 280 BALB/c mice were included, and 2 x 103 Toxoplasma organisms of the RH strain Toxoplasma gondii strain ATCC50174 were given intraperitoneally to each mouse. In experiment one, 40 animals were given azithromycin 200 milligram/kilogram/daily for 3 days starting the day of inoculation, 40 mice were control. In experiment 2, the treatment was started 48 hours after inoculation and given daily for 3 days: one group received azithromycin 200 milligram/kilogram/day, the second group received pyrimethamine 25 milligram/kilogram/day, and the sulfadiazine 100 milligram/kilogram/day. The third group was control. In experiment 3, 7 groups of animals received one of the following (1) none, (2) azithromycin 200 milligram/kilogram/day, (3) pyrimethamine 25 milligram/kilogram/day and sulfadiazine 100 milligram/kilogram/day, (4) azithromycin and sulfadiazine, (5) azithromycin and pyrimethamine, (6) azithromycin with sulfadiazine and pyrimethamine, (7) sulfadiazine alone. Treatment was initiated 72 hours after inoculation for 3 days. The study was conducted at the Animal Care Facility of King Saud University, Riyadh, Kingdom of Saudi Arabia. Animals that received azithromycin simultaneously with inoculation survived, and all control animals died. All animals died in groups receiving single drug therapy. Animals treated with azithromycin and sulfadiazine showed a survival rate of 40%, sulfadiazine and pyrimethamine 40%, or azithromycin with sulfadiazine and pyrimethamine 95% (p<0.0001). Azithromycin alone was found to be effective in the prophylaxis of murine toxoplasmosis. Combination therapy was effective in the treatment of murine toxoplasmosis.

Scheduled Intermittent Screening with Rapid Diagnostic Tests and Treatment with Dihydroartemisinin-Piperaquine versus Intermittent Preventive Therapy with Sulfadoxine-Pyrimethamine for Malaria in Pregnancy in Malawi: An Open-Label Randomized Controlled Trial.

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Mwayiwawo Madanitsa

2016-09-01

Full Text Available In Africa, most plasmodium infections during pregnancy remain asymptomatic, yet are associated with maternal anemia and low birthweight. WHO recommends intermittent preventive therapy in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP. However, sulfadoxine-pyrimethamine (SP efficacy is threatened by high-level parasite resistance. We conducted a trial to evaluate the efficacy and safety of scheduled intermittent screening with malaria rapid diagnostic tests (RDTs and treatment of RDT-positive women with dihydroartemisinin-piperaquine (DP as an alternative strategy to IPTp-SP.This was an open-label, two-arm individually randomized superiority trial among HIV-seronegative women at three sites in Malawi with high SP resistance. The intervention consisted of three or four scheduled visits in the second and third trimester, 4 to 6 wk apart. Women in the IPTp-SP arm received SP at each visit. Women in the intermittent screening and treatment in pregnancy with DP (ISTp-DP arm were screened for malaria at every visit and treated with DP if RDT-positive. The primary outcomes were adverse live birth outcome (composite of small for gestational age, low birthweight [<2,500 g], or preterm birth [<37 wk] in paucigravidae (first or second pregnancy and maternal or placental plasmodium infection at delivery in multigravidae (third pregnancy or higher. Analysis was by intention to treat. Between 21 July 2011 and 18 March 2013, 1,873 women were recruited (1,155 paucigravidae and 718 multigravidae. The prevalence of adverse live birth outcome was similar in the ISTp-DP (29.9% and IPTp-SP (28.8% arms (risk difference = 1.08% [95% CI -3.25% to 5.41%]; all women: relative risk [RR] = 1.04 [95% CI 0.90-1.20], p = 0.625; paucigravidae: RR = 1.10 [95% CI 0.92-1.31], p = 0.282; multigravidae: RR = 0.92 [95% CI 0.71-1.20], p = 0.543. The prevalence of malaria at delivery was higher in the ISTp-DP arm (48.7% versus 40.8%; risk difference = 7.85%, [95% CI 3

Efficacy of sulfadoxine-pyrimethamine in Tanzania after two years as first-line drug for uncomplicated malaria: assessment protocol and implication for treatment policy strategies

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Felger Ingrid

2005-11-01

Full Text Available Abstract Background Systematic surveillance for resistant malaria shows high level of resistance of Plasmodium falciparum to sulfadoxine-pyrimethamine (SP across eastern and southern parts of Africa. This study assessed in vivo SP efficacy after two years of use as an interim first-line drug in Tanzania, and determined the rates of treatment failures obtained after 14 and 28 days of follow-up. Methods The study was conducted in the Ipinda, Mlimba and Mkuranga health facilities in Tanzania. Children aged 6–59 months presenting with raised temperature associated exclusively with P. falciparum (1,000–100,000 parasites per μl were treated with standard dose of SP. Treatment responses were classified according to the World Health Organization (WHO definition as Adequate Clinical and Parasitological Response (ACPR, Early Treatment Failure (ETF, Late Clinical Failure (LCF and Late Parasitological Failure (LPF on day 14 and day 28. Results Overall 196 (85.2% of 230 patients had ACPR on day 14 but only 116 (50.9% on day 28 (57.7% after excluding new infections by parasite genotyping. Altogether 21 (9.1% and 13 (5.7% of the 230 patients assessed up to day 14 and 39 (17.1% and 55 (24.1% of the 228 followed up to day 28 had clinical and parasitological failure, respectively. Conclusion These findings indicate that SP has low therapeutic value in Tanzania. The recommendation of changing first line treatment to artemether + lumefantrine combination therapy from early next year is, therefore, highly justified. These findings further stress that, for long half-life drugs such as SP, establishment of cut-off points for policy change in high transmission areas should consider both clinical and parasitological responses beyond day 14.

The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women.

Science.gov (United States)

Gutman, Julie; Kalilani, Linda; Taylor, Steve; Zhou, Zhiyong; Wiegand, Ryan E; Thwai, Kyaw L; Mwandama, Dyson; Khairallah, Carole; Madanitsa, Mwayi; Chaluluka, Ebbie; Dzinjalamala, Fraction; Ali, Doreen; Mathanga, Don P; Skarbinski, Jacek; Shi, Ya Ping; Meshnick, Steve; ter Kuile, Feiko O

2015-06-15

The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy. Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant. Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: . IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Molecular identification of sulfadoxine-pyrimethamine resistance in malaria infected women who received intermittent preventive treatment in the Democratic Republic of Congo.

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Ruh, Emrah; Bateko, Jean Paul; Imir, Turgut; Taylan-Ozkan, Aysegul

2018-01-09

Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes which confer resistance to sulfadoxine-pyrimethamine (SP) occur at increasing rates. The present study aimed to identify Pfdhfr and Pfdhps mutations in P. falciparum isolates recovered from women who received two doses of SP during pregnancy in Bandundu, the Democratic Republic of Congo (DRC). A total of 48 women with confirmed P. falciparum infection were enrolled in the study. Finger-prick blood samples that were collected on filter paper at the time of delivery were used for DNA isolation. Pfdhfr and Pfdhps genes were amplified by a nested PCR protocol. DNA sequencing was performed on both strands, and the point mutations were analysed. All of the 48 (100.0%) P. falciparum isolates carried at least one polymorphism in both genes. The wild-type haplotypes of Pfdhfr (CNCSI [C50, N51, C59, S108, I164]) and Pfdhps (SAKAA [S436, A437, K540, A581, A613]) were not observed in the study. In Pfdhfr, N51I (85.4%), C59R (60.4%), and S108N (100.0%) polymorphisms were detected. Triple mutation (CIRNI) (mutant amino acids are underlined) was the most prevalent (47.9%) Pfdhfr haplotype. In the study, all P. falciparum isolates (100.0%) harboured the A437G allele in Pfdhps gene. Also, K540E and A581G polymorphisms were observed in one (2.1%) isolate. Single mutant haplotype (SGKAA) was detected in 97.9% of the isolates. Mutant Pfdhfr and Pfdhps allele combinations revealed quintuple (CICNI-SGEGA; 2.1%), quadruple (CIRNI-SGKAA; 47.9%), triple (CICNI-SGKAA; 35.4%, CNRNI-SGKAA; 12.5%), and double (CNCNI-SGKAA; 2.1%) haplotypes. In the study, the rate of SGEGA haplotype was low (2.1%). Although K540E and A581G alleles are more common in Eastern Africa, a distinct lineage of SGEGA is also present in the DRC, which is located in Central Africa. This haplotype is associated with decreased efficacy of SP in pregnant women and infants, therefore, it should be carefully

The usefulness of twenty-four molecular markers in predicting treatment outcome with combination therapy of amodiaquine plus sulphadoxine-pyrimethamine against falciparum malaria in Papua New Guinea

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Reeder John C

2008-04-01

Full Text Available Abstract Background In Papua New Guinea (PNG, combination therapy with amodiaquine (AQ or chloroquine (CQ plus sulphadoxine-pyrimethamine (SP was introduced as first-line treatment against uncomplicated malaria in 2000. Methods We assessed in vivo treatment failure rates with AQ+SP in two different areas in PNG and twenty-four molecular drug resistance markers of Plasmodium falciparum were characterized in pre-treatment samples. The aim of the study was to investigate the association between infecting genotype and treatment response in order to identify useful predictors of treatment failure with AQ+SP. Results In 2004, Day-28 treatment failure rates for AQ+SP were 29% in the Karimui and 19% in the South Wosera area, respectively. The strongest independent predictors for treatment failure with AQ+SP were pfmdr1 N86Y (OR = 7.87, p pfdhps A437G (OR = 3.44, p pfcrt K76T, A220S, N326D, and I356L did not help to increase the predictive value, the most likely reason being that these mutations reached almost fixed levels. Though mutations in SP related markers pfdhfr S108N and C59R were not associated with treatment failure, they increased the predictive value of pfdhps A437G. The difference in treatment failure rate in the two sites was reflected in the corresponding genetic profile of the parasite populations, with significant differences seen in the allele frequencies of mutant pfmdr1 N86Y, pfmdr1 Y184F, pfcrt A220S, and pfdhps A437G. Conclusion The study provides evidence for high levels of resistance to the combination regimen of AQ+SP in PNG and indicates which of the many molecular markers analysed are useful for the monitoring of parasite resistance to combinations with AQ+SP.

The effectiveness and perception of the use of sulphadoxine-pyrimethamine in intermittent preventive treatment of malaria in pregnancy programme in Offinso district of ashanti region, Ghana

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Tutu Emmanuel

2011-12-01

Full Text Available Abstract Background Malaria in pregnant women has been shown to be associated with low birth weight, stillbirth and mortality in newborns. The WHO has adopted the use of sulphadoxine-pyrimethamine (SP to control malaria, a disease which worsens the plight of pregnant women leading to low birth weight, stillbirths and increased neonatal mortality. The present study assessed the effectiveness of SP and perception of its use in pregnant women in Offinso district (Ashanti Region, Ghana. Method Pregnant women, gestational age 32 weeks prior to term, were studied from November 2006 to October 2007. Their haemoglobin levels (Hb, parasitaemia and other quantitative determinants were assessed. In-depth interviews (IDIs and focus group discussions (FGDs were used to assess the perception of SP usage and its effectiveness. Results Of the 306 study participants, 92 (30% took one dose, 100 (33% two doses and 114 (37% three doses of SP, respectively. There was significant association between gravidity and SP dosage taken (Pearson χ2 = 18.9, p χ2 = 2.3, p ≥ 0.32. Peripheral parasitaemia was present in 47 (15% of the subjects. There was a poor negative relationship of doses of SP with parasitaemia (r = -0.07, p ≥ 0.24. Mean Hb was 11.3 ± 1.6 g/dl, with 118 (39% of the subjects anaemic (Hb r = 0.15, p Conclusions This study points to the effectiveness of IPTp using SP as an evidence-based measure for control of malaria and malaria-related anaemia in pregnancy. Therefore, the Ghana Health Service should improve current programme strategies to increase the proportion of pregnant women who take three doses of SP, paying attention to improved face-to-face health education, focussed antenatal care and better social mobilization.

In Vivo Efficacy of Artesunate/Sulphadoxine-Pyrimethamine versus Artesunate/Amodiaquine in the Treatment of Uncomplicated P. falciparium Malaria in Children around the Slope of Mount Cameroon: A Randomized Controlled Trial

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Tobias O. Apinjoh

2016-02-01

Full Text Available Background: The development and spread of antimalarial drug resistant parasites contributes to the global impact of the disease. In vivo efficacy assessments of treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. Artemisinin-based combinations have been adopted as the first-line treatment for uncomplicated P. falciparum malaria in Cameroon since 2004. Methods: A total of 177 children aged six-months to 10 years with uncomplicated mono-infected falciparum malaria were randomized (1:1 to receive artesunate/sulphadoxine-pyrimethamine (AS/SP or artesunate/amodiaquine (AS/AQ pediatric tablets and followed up for 28 days according to the standard World Health Organization in vivo drug efficacy monitoring protocol. The primary and secondary endpoints were PCR uncorrected and corrected cure rates, as measured by adequate clinical and parasitological response (ACPR on day 28. Results: The PCR corrected cure rate was high, overall (88.1%, 95% CI 83.1–93.1, 85.9% (95% CI 78.2–93.6, and 90.2% (95% CI 83.8–96.6 for AS/SP and AS/AQ, respectively. Twenty-one treatment failures were observed during follow-up, constituting one (4.6%, 14 (8.2%, and six (3.5% early treatment failure (ETF, late clinical failure (LCF, and late parasitological failure (LPF, respectively. The drugs were well tolerated with no serious adverse events. Conclusions: Both AS/SP and AS/AQ are highly effective and well-tolerated treatments for uncomplicated P. falciparum malaria around the slope of Mount Cameroon.

Within-host selection of drug resistance in a mouse model of repeated interrupted treatment of Plasmodium yoelii infection

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Nuralitha, Suci; Siregar, Josephine E; Syafruddin, Din; Hoepelman, Andy I M; Marzuki, Sangkot

2017-01-01

BACKGROUND: To study within-host selection of resistant parasites, an important factor in the development of resistance to anti-malarial drugs, a mouse model of repeated interrupted malaria treatment (RIT) has been developed. The characteristics of within host selection of resistance to atovaquone and pyrimethamine in Plasmodium yoelii was examined in such a model. METHODS: Treatment of P. yoelii infected mice, with atovaquone or pyrimethamine, was started at parasitaemia level of 3-5%, inter...

A community effectiveness trial of strategies promoting intermittent preventive treatment with sulphadoxine-pyrimethamine in pregnant women in rural Burkina Faso

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Brabin Bernard

2008-09-01

Full Text Available Abstract Background Intermittent preventive treatment with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP is currently being scaled up in many countries in sub-Saharan Africa. Despite high antenatal clinic (ANC attendance, coverage with the required two doses of SP remains low. The study investigated whether a targeted community-based promotion campaign to increase ANC attendance and SP uptake could effectively improve pregnancy outcomes in the community. Methods Between 2004 and 2006 twelve health centres in Boromo Health District, Burkina Faso were involved in this study. Four were strategically assigned to community promotion in addition to IPTp-SP (Intervention A and eight were randomly allocated to either IPTp-SP (Intervention B or weekly chloroquine (Control. Primi- and secundigravidae were enrolled at village level and thick films and packed cell volume (PCV taken at 32 weeks gestation and at delivery. Placental smears were prepared and newborns weighed. Primary outcomes were peripheral parasitaemia during pregnancy and at delivery, placental malaria, maternal anaemia, mean and low birth weight. Secondary outcomes were the proportion of women with ≥ 3 ANC visits and ≥ 2 doses of SP. Intervention groups were compared using logistic and linear regression with linearized variance estimations to correct for the cluster-randomized design. Results SP uptake (≥ 2 doses was higher with (Intervention A: 70% than without promotion (Intervention B: 49% (OR 2.45 95%CI 1.25–4.82 p = 0.014. Peripheral (33.3% and placental (30.3% parasite rates were significantly higher in the control arm compared to Intervention B (peripheral: 20.1% OR 0.50 95%CI 0.37–0.69 p = 0.001; placental: 20.5% OR 0.59 95%CI 0.44–0.78 p = 0.002 but did not differ between Intervention A (17.4%; 18.1% and Intervention B (20.1; 20.5% (peripheral: OR 0.84 95%CI 0.60–1.18 p = 0.280; placental: OR 0.86 95%CI 0.58–1.29 p = 0.430. Mean PCV and birth weight and

Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

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Djimdé Abdoulaye

2009-04-01

Full Text Available Abstract Background The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Methods Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP three-day (once daily for 3 days regimen (N = 476 or AS-SMP 24-hour (0 h, 12 h, 24 h regimen (N = 458 or artemether-lumefantrine (AL, the regular 6 doses regimen (N = 450. The primary objective was to demonstrate non-inferiority (using a margin of -6% of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. Results The PCR corrected 28-day cure rate on the intention to treat (ITT analysis population were: 96.0%(457/476 in the AS-SMP three-day group, 93.7%(429/458 in the AS-SMP 24-hour group and 92.0%(414/450 in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437 in the AS-SMP three-day group, 99.5%(416/419 in the AS-SMP 24-hour group and 99.7(391/394% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea which were slightly higher in the AS-SMP 24-hour group. Conclusion AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. Trial registration NCT00484900 http://www.clinicaltrials.gov.

Intermittent preventive treatment of malaria in pregnancy

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Mbonye, A.K.; Bygbjerg, Ib Christian; Magnussen, Pascal

2008-01-01

OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non-randomized comm......OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors, community reproductive-health workers, or adolescent peer mobilizers could administer intermittent preventive treatment (IPTp) for malaria with sulfadoxine-pyrimethamine to pregnant women. METHODS: A non......-randomized community trial was implemented in 21 community clusters (intervention) and four clusters where health units provided routine IPTp (control). The primary outcome measures were access and adherence to IPTp, number of malaria episodes, prevalence of anaemia, and birth weight. Numbers of live births, abortions......, still births, and maternal and child deaths were secondary endpoints. FINDINGS: 1404 (67.5%) of 2081 with the new delivery system received two doses of sulfadoxine-pyrimethamine versus 281 (39.9%) of 704 with health units (P malaria episodes decreased from 906 (49...

Frequencies distribution of dihydrofolate reductase and dihydropteroate synthetase mutant alleles associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum population from Hadhramout Governorate, Yemen.

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Bamaga, Omar A A; Mahdy, Mohammed A K; Lim, Yvonne A L

2015-12-22

Malaria in Yemen is mainly caused by Plasmodium falciparum and 25% of the population is at high risk. Sulfadoxine-pyrimethamine (SP) had been used as monotherapy against P. falciparum. Emergence of chloroquine resistance led to the shift in anti-malarial treatment policy in Yemen to artemisinin-based combination therapy, that is artesunate (AS) plus SP as first-line therapy for uncomplicated malaria and artemether-lumefantrine as second-line treatment. This study aimed to screen mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes associated with SP resistance among P. falciparum population in Hadhramout governorate, Yemen. Genomic DNA was extracted from dried blood spots of 137 P. falciparum isolates collected from a community-based study. DNA was amplified using nested polymerase chain reaction (PCR) and subsequently sequenced for Pfdhfr and Pfdhps genes. Sequences were analysed for mutations in Pfdhfr gene codons 51, 59, 108, and 164 and in Pfdhps gene codons 436, 437, and 540. A total of 128 and 114 P. falciparum isolates were successfully sequenced for Pfdhfr and Pfdhps genes, respectively. Each Pfdhfr mutant allele (I51 and N108) in P. falciparum population had a frequency of 84%. Pfdhfr R59 mutant allele was detected in one isolate. Mutation at codon 437 (G437) in the Pfdhps gene was detected in 44.7% of falciparum malaria isolates. Frequencies of Pfdhfr double mutant genotype (I51C59N108I164) and Pfdhfr/Pfdhps triple mutant genotype (I51C59N108I164-S436G437K540) were 82.8 and 39.3%, respectively. One isolate harboured Pfdhfr triple mutant genotype (I51, R59, N108, I164) and Pfdhfr/Pfdhps quadruple mutant genotype (I51R59N108I164-S436G437K540). High frequencies of Pfdhfr and Pfdhps mutant alleles and genotypes in P. falciparum population in Hadhramout, Yemen, highlight the risk of developing resistance for SP, the partner drug of AS, which subsequently will expose the parasite to AS monotherapy increasing then the

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemoglobin Drop after Sulphadoxine-Pyrimethamine Use for Intermittent Preventive Treatment of Malaria during Pregnancy in Ghana - A Cohort Study.

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Ruth Owusu

Full Text Available Sulphadoxine-Pyrimethamine (SP is still the only recommended antimalarial for use in intermittent preventive treatment of malaria during pregnancy (IPTp in some malaria endemic countries including Ghana. SP has the potential to cause acute haemolysis in G6PD deficient people resulting in significant haemoglobin (Hb drop but there is limited data on post SP-IPTp Hb drop. This study determined the difference, if any in proportions of women with significant acute haemoglobin drop between G6PD normal, partial deficient and full deficient women after SP-IPTp.Prospectively, 1518 pregnant women who received SP for IPTp as part of their normal antenatal care were enrolled. Their G6PD status were determined at enrollment followed by assessments on days 3, 7,14 and 28 to document any adverse effects and changes in post-IPTp haemoglobin (Hb levels. The three groups were comparable at baseline except for their mean Hb (10.3 g/dL for G6PD normal, 10.8 g/dL for G6PD partial deficient and 10.8 g/dL for G6PD full defect women.The prevalence of G6PD full defect was 2.3% and 17.0% for G6PD partial defect. There was no difference in the proportions with fractional Hb drop ≥ 20% as compared to their baseline value post SP-IPTp among the 3 groups on days 3, 7, 14. The G6PD full defect group had the highest median fractional drop at day 7. There was a weak negative correlation between G6PD activity and fractional Hb drop. There was no statistical difference between the three groups in the proportions of those who started the study with Hb ≥ 8g/dl whose Hb level subsequently fell below 8g/dl post-SP IPTp. No study participant required transfusion or hospitalization for severe anaemia.There was no significant difference between G6PD normal and deficient women in proportions with significant acute haemoglobin drop post SP-IPTp and lower G6PD enzyme activity was not strongly associated with significant acute drug-induced haemoglobin drop post SP-IPTp but a larger

Functional expression of parasite drug targets and their human orthologs in yeast.

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Elizabeth Bilsland

2011-10-01

Full Text Available The exacting nutritional requirements and complicated life cycles of parasites mean that they are not always amenable to high-throughput drug screening using automated procedures. Therefore, we have engineered the yeast Saccharomyces cerevisiae to act as a surrogate for expressing anti-parasitic targets from a range of biomedically important pathogens, to facilitate the rapid identification of new therapeutic agents.Using pyrimethamine/dihydrofolate reductase (DHFR as a model parasite drug/drug target system, we explore the potential of engineered yeast strains (expressing DHFR enzymes from Plasmodium falciparum, P. vivax, Homo sapiens, Schistosoma mansoni, Leishmania major, Trypanosoma brucei and T. cruzi to exhibit appropriate differential sensitivity to pyrimethamine. Here, we demonstrate that yeast strains (lacking the major drug efflux pump, Pdr5p expressing yeast ((ScDFR1, human ((HsDHFR, Schistosoma ((SmDHFR, and Trypanosoma ((TbDHFR and (TcDHFR DHFRs are insensitive to pyrimethamine treatment, whereas yeast strains producing Plasmodium ((PfDHFR and (PvDHFR DHFRs are hypersensitive. Reassuringly, yeast strains expressing field-verified, drug-resistant mutants of P. falciparum DHFR ((Pfdhfr(51I,59R,108N are completely insensitive to pyrimethamine, further validating our approach to drug screening. We further show the versatility of the approach by replacing yeast essential genes with other potential drug targets, namely phosphoglycerate kinases (PGKs and N-myristoyl transferases (NMTs.We have generated a number of yeast strains that can be successfully harnessed for the rapid and selective identification of urgently needed anti-parasitic agents.

Effect of oral proguanil on human lymphocyte proliferation

DEFF Research Database (Denmark)

Bygbjerg, Ib Christian; Flachs, H

1986-01-01

In vitro studies have indicated that the antifolates pyrimethamine [4, 6] and cycloguanil (the active metabolite of proguanil) suppress the proliferation of stimulated human lymphocytes; proguanil has no effect [2]. During the early growth phase of the cells, 14C-thymidine (14C-TdR) incorporation...... is increased by pyrimethamine and cycloguanil, reflecting blockage of endogenous TdR synthesis [3]. Proguanil (Paludrine) is increasingly being used for malaria prophylaxis. It is considered the most innocuous of the antimalarials currently employed. Since nothing is known about the effect of oral proguanil...

Claritromicina associada com pirímetamina na toxoplasmose cerebral - relato de dois casos

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Marcos Olivicr Dalston

1995-12-01

Full Text Available Os autores relatam a resposta terapêutica da claritromicina associada com pirímetamina em dois casos de toxoplasmose cerebral ocorridos em pacientes com Síndrome de Imunodeficiência Adquirida (SIDA. Nos dois casos o diagnóstico foi presuntivo, baseando-se nas manifestações clínicas e na presença de lesões expansivas hipercaptantes detectadas na tomografia computadorizada (TC de crânio. Em ambos os casos, observou-se exantema com o uso da sulfadiazina e da clindamicina, razão pela qual tais medicamentos foram substituídos pela claritromicina (1,5 a 2g/dia associada à pirímetamina (25mg/dia. A resposta terapêutica foi favorável nos dois casos com melhora das manifestações neurológicas e dos achados neurorradiológicos. Os autores sugerem que a associação claritromicina com pirímetamina pode ser útil como opção terapêutica na toxoplasmose cerebral em pacientes com SIDA que apresentam intolerância ou outra contra-indicação ao emprego das sulfonamidas.The authors report the use and tbe outcome of claritromycin associated with pyrimethamine in the treatment of toxoplasma encephalites in two patients with AIDS. Both patients had the diagnosis stablished on clinical grounds, positive sorology (IgG for toxoplasmosis and computed-tomographic (CT scan of the brain showing lesions consistent with T. gondii encephalitis. The two patients were initially treated with pyrimethamine and sulfadiazme, which was changed to clindamycin due to allergic reactions. These reactions (skin rash occurred with clindamycin as well and the patients were treated with claritromycin and pyrimethamine. The scheduled regimens were 1.5 to 2g of clarithromycin plus 25mg of pyrimethamine. The clinical response was very good in both cases with regression of neurologic signs and encephalitic abnormalities observed on CT scan. The authors suggest that clarithromycin associated with pyrimethamine may be an alternative treatment for toxoplasmosis in AIDS

Mortality, Morbidity, and Developmental Outcomes in Infants Born to Women Who Received Either Mefloquine or Sulfadoxine-Pyrimethamine as Intermittent Preventive Treatment of Malaria in Pregnancy: A Cohort Study.

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María Rupérez

2016-02-01

Full Text Available Little is known about the effects of intermittent preventive treatment of malaria in pregnancy (IPTp on the health of sub-Saharan African infants. We have evaluated the safety of IPTp with mefloquine (MQ compared to sulfadoxine-pyrimethamine (SP for important infant health and developmental outcomes.In the context of a multicenter randomized controlled trial evaluating the safety and efficacy of IPTp with MQ compared to SP in pregnancy carried out in four sub-Saharan countries (Mozambique, Benin, Gabon, and Tanzania, 4,247 newborns, 2,815 born to women who received MQ and 1,432 born to women who received SP for IPTp, were followed up until 12 mo of age. Anthropometric parameters and psychomotor development were assessed at 1, 9, and 12 mo of age, and the incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were determined until 12 mo of age. No significant differences were found in the proportion of infants with stunting, underweight, wasting, and severe acute malnutrition at 1, 9, and 12 mo of age between infants born to women who were on IPTp with MQ versus SP. Except for three items evaluated at 9 mo of age, no significant differences were observed in the psychomotor development milestones assessed. Incidence of malaria, anemia, hospital admissions, outpatient visits, and mortality were similar between the two groups. Information on the outcomes at 12 mo of age was unavailable in 26% of the infants, 761 (27% from the MQ group and 377 (26% from the SP group. Reasons for not completing the study were death (4% of total study population, study withdrawal (6%, migration (8%, and loss to follow-up (9%.No significant differences were found between IPTp with MQ and SP administered in pregnancy on infant mortality, morbidity, and nutritional outcomes. The poorer performance on certain psychomotor development milestones at 9 mo of age in children born to women in the MQ group compared to those in the SP group may deserve

Adherence to intermittent preventive treatment for malaria with sulphadoxine-pyrimethamine and outcome of pregnancy among parturients in South East Nigeria

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Onyebuchi AK

2014-04-01

Full Text Available Azubike Kanario Onyebuchi,1 Lucky Osaheni Lawani,2 Chukwuemeka Anthony Iyoke,3 Chukwudi Robinson Onoh,1 Nwabunike Ekene Okeke4 1Department of Obstetrics and Gynecology, Federal Teaching Hospital, Abakaliki, Nigeria; 2School of Postgraduate Studies, Department of Community Medicine, University of Nigeria; 3Department of Obstetrics and Gynecology, University of Nigeria Teaching Hospital, Enugu, Nigeria; 4Department of Obstetrics and Gynecology, Mile Four Catholic Hospital, Abakaliki, Nigeria Background: Intermittent preventive treatment of malaria for pregnant women (IPTp is a very important strategy for the control of malaria in pregnancy in malaria-endemic tropical countries, where mosquito bites easily occur during evening outdoor activities. Issues related to provision, cost, and acceptability may affect the use of IPTp in some developing countries. The aim of the study was to assess the uptake and adherence to sulphadoxine-pyrimethamine-based intermittent preventive treatment of malaria during pregnancy and the relationship of IPTp use to pregnancy outcomes in two major obstetric centers in South East Nigeria. Methods: This was a prospective descriptive study involving women who received antenatal and delivery services. All recruited women were followed-up from booking until delivery, and statistical analysis was done with Epi Info version 7. Results: A total of 516 parturients were studied. The mean gestational age at booking was 21.8±6.9 weeks while the mean number of antenatal visits throughout the pregnancy was 5.5±3.1. The rate of uptake of at least one dose of prescribed IPTp was 72.1% (367/516. Of the 367 who took prescribed IPTp, adherence to second doses of IPTp was 59.7% (219/367, and only 4.9% (18/367 took a third dose. Clinical malaria occurred in 85% (127/149 of women who did not receive IPTp at all compared to 20.5% of those who received at least one dose of IPTp. All those who had clinical malaria despite IPTp had only one

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR

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Montazeri, Mahbobeh; Ebrahimzadeh, Mohammad Ali; Ahmadpour, Ehsan; Sharif, Mehdi; Sarvi, Shahabeddin

2016-01-01

Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine. PMID:27645234

Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi

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Chimpeni Phillips

2009-08-01

Full Text Available Abstract Background Sulphadoxine-pyrimethamine (SP is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL and chlorproguanil-dapsone (CPD, both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD. Methods Children ≥12 months and adults with uncomplicated malaria were randomized to receive AL, CPD or SP. Adherence was measured using a questionnaire and electronic monitoring devices, MEMS™, pill bottles that recorded the date and time of opening. Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response. Results 841 patients were recruited. The day-28 adequate clinical and parasitological response (ACPR rates, using intention to treat analysis (missing data treated as failure, were AL 85.2%, CPD 63.7% and SP 50%. ACPR rates for AL were higher than CPD or SP on days 28 and 42 (p ≤ 0.002 for all comparisons. CPD was more effective than SP on day-28 (p = 0.01, but not day-42. Very high adherence was reported using the questionnaire, 100% for AL treated patients and 99.2% for the CPD group. Only three CPD participants admitted missing any doses. 164/181 (90.6% of CPD treated patients took all their doses out of the MEMS™ container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container, p = 0.024. Only 7/87 (8% AL treated patients did not take all of their doses out of their MEMS™ container and none had treatment failure. Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures, p = 0.012. There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS™ container and those

Safety of Seasonal Malaria Chemoprevention (SMC with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial.

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J L NDiaye

Full Text Available It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age.A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010.After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance.SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation.ClinicalTrials.gov NCT 00712374.

Efficacy of amodiaquine, sulphadoxine-pyrimethamine and their combination for the treatment of uncomplicated Plasmodium falciparum malaria in children in Cameroon at the time of policy change to artemisinin-based combination therapy

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Hallett Rachel

2010-01-01

Full Text Available Abstract Background The efficacy of amodiaquine (AQ, sulphadoxine-pyrimethamine (SP and the combination of SP+AQ in the treatment of Cameroonian children with clinical malaria was investigated. The prevalence of molecular markers for resistance to these drugs was studied to set the baseline for surveillance of their evolution with time. Methods Seven hundred and sixty children aged 6-59 months with uncomplicated falciparum malaria were studied in three ecologically different regions of Cameroon - Mutengene (littoral equatorial forest, Yaoundé (forest-savannah mosaic and Garoua (guinea-savannah. Study children were randomized to receive either AQ, SP or the combination AQ+SP. Clinical outcome was classified according to WHO criteria, as either early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF or adequate clinical and parasitological response (ACPR. The occurrence of mutations in pfcrt, pfmdr1, dhfr and dhps genes was studied by either RFLP or dot blot techniques and the prevalence of these mutations related to parasitological and therapeutic failures. Results After correction for the occurrence of re-infection by PCR, ACPRs on day 28 for AQ, SP and AQ+SP were 71.2%, 70.1% and 80.9%, in Garoua, 79.2%, 62.5%, and 81.9% in Mutengene, and 80.3%, 67.5% and 76.2% in Yaoundé respectively. High levels of Pfcrt 76T (87.11% and Pfmdr1 86Y mutations (73.83% were associated with quinoline resistance in the south compared to the north, 31.67% (76T and 22.08% (86Y. There was a significant variation (p dhps gene was extremely rare (0.3% and occurred only in Mutengene while the pfmdr1 1034K and 1040D mutations were not detected in any of the three sites. Conclusion In this study the prevalence of molecular markers for quinoline and anti-folate resistances showed high levels and differed between the south and north of Cameroon. AQ, SP and AQ+SP treatments were well tolerated but with low levels of efficacy that

Molecular Docking and Molecular Dynamics Simulation studies of DHFR inhibitors in Plasmodium falciparum

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Prachi Bhole

2017-10-01

Full Text Available Malaria, caused by Plasmodium falciparum is a very common disease that causes 2.5 million deaths worldwide. This makes designing of lead molecules for malaria very exigent. DHFR has been known to be one of the major targets of antimalarial drug therapy which functions as a fundamental cofactor in the synthesis of histidine and methionine as well as purine nucleotides. Inhibition of this DHFR blocks the reduction of Dihydrofolate (DHF to Tetrahydrofolate (THF and hence prevents the synthesis of DNA, resulting in death of Plasmodium falciparum. Pyrimethamine is a Diaminopyrimidine that inhibits pfDHFR (Plasmodium falciparum DHFR at a concentration that is 1000 times less than that required to inhibit the mammalian DHFR. Virtual screening is performed to find Pyrimethamine analogs from PubChem database. Docking studies are performed on DHFR (PDB ID: 3QGT with Pyrimethamine and its 193 derivatives and the differences in their binding modes are investigated. The binding score suggests 53 derivatives to be more potent than Pyrimethamine which has a score of -24.7 showing interaction with Ile14, Asp54 and Ile164. The compound with best binding score (-35 showed interaction with Ile14, Cys15, Asp54, Phe58, Ser108, Ser111, Ile164 and Tyr170. The compounds are screened based on hydrogen bonding, π-π interactions, halogen bonding and orientation within the binding site with high binding score using Maestro (v.11.0.014, Schrodinger. The best screened compound is selected for Molecular Dynamic Simulation analysis up to 20ns using Desmond (v.4.8, Schrodinger which represents a good starting point for further in vivo experimentation and can probably serve as an ideal lead compound for the treatment of Malaria.

Enrofloxacin is able to control Toxoplasma gondii infection in both in vitro and in vivo experimental models.

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Barbosa, Bellisa Freitas; Gomes, Angelica Oliveira; Ferro, Eloisa Amália Vieira; Napolitano, Danielle Reis; Mineo, José Roberto; Silva, Neide Maria

2012-06-08

Currently, toxoplasmosis is treated with sulfadiazine and pyrimethamine. However, this treatment presents several adverse side effects; thus, there is a critical need for the development and evaluation of new drugs, which do not present the same problems of the standard therapy. Enrofloxacin is a fluoroquinolone antibiotic known to control infection against several bacteria in veterinary medicine. Recently, this drug has demonstrated protective effects against protozoan parasites such as Neospora caninum. The present study aimed to determine the effect of enrofloxacin in the control of Toxoplasma gondii infection. For this purpose, human foreskin fibroblast (HFF) cells were infected with T. gondii RH strain and treated with sulfadiazine, penicillin/streptomycin, pyrimethamine, or enrofloxacin. Following treatment, we analyzed the infection index, parasite intracellular proliferation and the number of plaques. Additionally, tissue parasitism and histological changes were investigated in the brain of Calomys callosus that were infected with T. gondii (ME49 strain) and treated with either sulfadiazine or enrofloxacin. Enrofloxacin was able to reduce the infection index, intracellular proliferation and the number of plaques in HFF cells infected by T. gondii in comparison with untreated or penicillin/streptomycin-treated ones. Enrofloxacin was more protective against T. gondii in HFF infected cells than sulfadiazine treatment (Penrofloxacin or the associations of sulfadiazine plus pyrimethamine, enrofloxacin plus sulfadiazine or enrofloxacin plus pyrimethamine-treatments were able to reduce the plaque numbers in HFF cells infected by T. gondii when compared to medium, penicillin/streptomycin or sulfadiazine alone. In vivo experiments demonstrated that enrofloxacin diminished significantly the tissue parasitism as well as the inflammatory alterations in the brain of C. callosus infected with T. gondii when compared with untreated animals. Based on our findings, it can

Drug resistance associated genetic polymorphisms in Plasmodium falciparum and Plasmodium vivax collected in Honduras, Central America.

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Jovel, Irina T; Mejía, Rosa E; Banegas, Engels; Piedade, Rita; Alger, Jackeline; Fontecha, Gustavo; Ferreira, Pedro E; Veiga, Maria I; Enamorado, Irma G; Bjorkman, Anders; Ursing, Johan

2011-12-19

In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P

Antimalarial drug prescribing practice in private and public health facilities in South-east Nigeria: a descriptive study

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Okebe Joseph

2007-05-01

Full Text Available Abstract Background Nigeria's national standard has recently moved to artemisinin combination treatments for malaria. As clinicians in the private sector are responsible for attending a large proportion of the population ill with malaria, this study compared prescribing in the private and public sector in one State in Nigeria prior to promoting ACTs. Objective To assess prescribing for uncomplicated malaria in government and private health facilities in Cross River State. Method Audit of 665 patient records at six private and seven government health facilities in 2003. Results Clinicians in the private sector were less likely to record history or physical examination than those in public facilities, but otherwise practice and prescribing were similar. Overall, 45% of patients had a diagnostic blood slides; 77% were prescribed monotherapy, either chloroquine (30.2%, sulphadoxine-pyrimethamine (22.7% or artemisinin derivatives alone (15.8%. Some 20.8% were prescribed combination therapy; the commonest was chloroquine with sulphadoxine-pyrimethamine. A few patients (3.5% were prescribed sulphadoxine-pyrimethamine-mefloquine in the private sector, and only 3.0% patients were prescribed artemisinin combination treatments. Conclusion Malaria treatments were varied, but there were not large differences between the public and private sector. Very few are following current WHO guidelines. Monotherapy with artemisinin derivatives is relatively common.

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine during pregnancy in Burkina Faso: effect of adding a third dose to the standard two-dose regimen on low birth weight, anaemia and pregnancy outcomes

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Roberfroid Dominique

2010-11-01

Full Text Available Abstract Background Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP is being implemented in most malaria endemic countries as a standard two-doses regimen as it reduces the risk of low birth weight (LBW and the prevalence of maternal anaemia. Nevertheless, where the risk of infection close to delivery is high because of intense transmission, a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome. Methods Pregnant women in the 2nd or 3rd trimester were randomized to receive either 2 (SP2 or 3 doses (SP3 of SP. Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule. Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed. The prevalence of LBW ( Results Data from 1274 singleton pregnancies were analysed (641 in the SP3 and 633 in the SP2 group. The uptake of the intervention appeared to be low. Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Ratio, AIRR = 0.92, 95%CI: 0.69-1.24 in the ITT analysis, the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group (AIRR = 0.38, 95%CI: 0.16 - 0.90. The PP analysis showed a trend of reduced risk of LBW, severe anaemia and premature delivery in the SP3 group, albeit the difference between two and three IPTp-SP did not reach statistical significance. Conclusion The risk of LBW and severe anaemia tended to be lower in the SP3 group, though this was not statistically significant, probably due to the low uptake of the intervention which reduced the power of the study. Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in settings where transmission is markedly seasonal.

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine during pregnancy in Burkina Faso: effect of adding a third dose to the standard two-dose regimen on low birth weight, anaemia and pregnancy outcomes.

Science.gov (United States)

Valea, Innocent; Tinto, Halidou; Drabo, Maxime K; Huybregts, Lieven; Henry, Marie-Claire; Roberfroid, Dominique; Guiguemde, Robert T; Kolsteren, Patrick; D'Alessandro, Umberto

2010-11-12

Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) is being implemented in most malaria endemic countries as a standard two-doses regimen as it reduces the risk of low birth weight (LBW) and the prevalence of maternal anaemia. Nevertheless, where the risk of infection close to delivery is high because of intense transmission, a third IPTp-SP dose may further reduce the negative effects of malaria on pregnancy outcome. Pregnant women in the 2nd or 3rd trimester were randomized to receive either 2 (SP2) or 3 doses (SP3) of SP. Trained field workers paid home visits to the women for drug administration according to a predefined drug delivery schedule. Women were encouraged to attend their scheduled ANC visits and to deliver at the health facilities where the new-born was weighed. The prevalence of LBW (anaemia (Hb pregnancies were analysed (641 in the SP3 and 633 in the SP2 group). The uptake of the intervention appeared to be low. Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Ratio, AIRR = 0.92, 95%CI: 0.69-1.24) in the ITT analysis, the risk of severe anaemia was significantly lower in the SP3 group compared to the SP2 group (AIRR = 0.38, 95%CI: 0.16 - 0.90). The PP analysis showed a trend of reduced risk of LBW, severe anaemia and premature delivery in the SP3 group, albeit the difference between two and three IPTp-SP did not reach statistical significance. The risk of LBW and severe anaemia tended to be lower in the SP3 group, though this was not statistically significant, probably due to the low uptake of the intervention which reduced the power of the study. Further studies are needed for establishing whether a third SP dose has a real benefit in preventing the negative effects of malaria in pregnancy in settings where transmission is markedly seasonal.

In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts.

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Olasehinde, Grace I; Ojurongbe, Olusola; Adeyeba, Adegboyega O; Fagade, Obasola E; Valecha, Neena; Ayanda, Isaac O; Ajayi, Adesola A; Egwari, Louis O

2014-02-20

The resistance of human malaria parasites to anti-malarial compounds has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. One way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents. Sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia ('Ejirin') Diospyros monbuttensis ('Egun eja') and Morinda lucida ('Oruwo') was determined using the in vitro microtest (Mark III) technique to determine the IC50 of the drugs. All the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13% to amodiaquine and 5% to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9%) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30%) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine (P0.05). Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis (IC50 = 3.2 nM) while the lowest was obtained from M. lucida (IC50 = 25 nM). Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs.

ORIGINAL ARTICLES

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PYRIMETHAMINE. I UNCOMPLICATED l'LASMODIUM FA LCIPARUM r IALARIA 3 YEARS AFTER. I TRODUCTION IN. T A:PUMALANGA f uon Mabuza, John Govere, David Durrheim, Nicros . ngomezulu, Barry Bredenkamp, Karen Barnes, Brian ...

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(Necrotic index) and the effectiveness of the antibody's delivery time. ... Treatment with pyrimethamine and sulfadiazine could inhibit the synthesis of folic acid which is ... immunological reaction reaction, such as excessive release of cytokines.

Enrofloxacin and Toltrazuril Are Able to Reduce Toxoplasma gondii Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy

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Rafaela J. da Silva

2017-07-01

Full Text Available Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain, whereas villous samples were only infected by the 2F1 clone. Then, infected cells and villous were treated with all antibiotics and the T. gondii intracellular proliferation as well as the cytokine production were analyzed. Finally, we evaluated the direct effect of enrofloxacin and toltrazuril in tachyzoites to verify possible changes in parasite structure. Enrofloxacin and toltrazuril did not decrease the viability of cells and villous in lower concentrations. Both drugs were able to significantly reduce the parasite intracellular proliferation in BeWo cells and villous explants when compared to untreated conditions. Regardless of the T. gondii strain, BeWo cells infected and treated with enrofloxacin or toltrazuril induced high levels of IL-6 and MIF. In villous explants, enrofloxacin induced high MIF production. Finally, the drugs increased the number of unviable parasites and triggered damage to tachyzoite structure. Taken together, it can be concluded that

Enrofloxacin and Toltrazuril Are Able to Reduce Toxoplasma gondii Growth in Human BeWo Trophoblastic Cells and Villous Explants from Human Third Trimester Pregnancy.

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da Silva, Rafaela J; Gomes, Angelica O; Franco, Priscila S; Pereira, Ariane S; Milian, Iliana C B; Ribeiro, Mayara; Fiorenzani, Paolo; Dos Santos, Maria C; Mineo, José R; da Silva, Neide M; Ferro, Eloisa A V; de Freitas Barbosa, Bellisa

2017-01-01

Classical treatment for congenital toxoplasmosis is based on combination of sulfadiazine and pyrimethamine plus folinic acid. Due to teratogenic effects and bone marrow suppression caused by pyrimethamine, the establishment of new therapeutic strategies is indispensable to minimize the side effects and improve the control of infection. Previous studies demonstrated that enrofloxacin and toltrazuril reduced the incidence of Neospora caninum and Toxoplasma gondii infection. The aim of the present study was to evaluate the efficacy of enrofloxacin and toltrazuril in the control of T. gondii infection in human trophoblast cells (BeWo line) and in human villous explants from the third trimester. BeWo cells and villous were treated with several concentrations of enrofloxacin, toltrazuril, sulfadiazine, pyrimethamine, or combination of sulfadiazine+pyrimethamine, and the cellular or tissue viability was verified. Next, BeWo cells were infected by T. gondii (2F1 clone or the ME49 strain), whereas villous samples were only infected by the 2F1 clone. Then, infected cells and villous were treated with all antibiotics and the T. gondii intracellular proliferation as well as the cytokine production were analyzed. Finally, we evaluated the direct effect of enrofloxacin and toltrazuril in tachyzoites to verify possible changes in parasite structure. Enrofloxacin and toltrazuril did not decrease the viability of cells and villous in lower concentrations. Both drugs were able to significantly reduce the parasite intracellular proliferation in BeWo cells and villous explants when compared to untreated conditions. Regardless of the T. gondii strain, BeWo cells infected and treated with enrofloxacin or toltrazuril induced high levels of IL-6 and MIF. In villous explants, enrofloxacin induced high MIF production. Finally, the drugs increased the number of unviable parasites and triggered damage to tachyzoite structure. Taken together, it can be concluded that enrofloxacin and

290 ORIGINAL ARTICLE

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with the use of Intermittent Preventive Treatment with sulphadoxine pyrimethamine (IPTp-SP), Long Lasting ..... This also falls below the WHO ... determination in health studies: A practical manual. WHO Geneva Switzerland, 1991; 30pp ...

Early treatment failure in concurrent dengue and mixed malaria species infection with suspected resistance to artemisinin combination therapy from a tertiary care center in Delhi: a case report.

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Saksena, Rushika; Matlani, Monika; Singh, Vineeta; Kumar, Amit; Anveshi, Anupam; Kumar, Dilip; Gaind, Rajni

2017-01-01

Concurrent dengue and mixed malaria infections in a single patient present with overlapping clinical manifestations which pose a diagnostic challenge and management dilemma in areas of common endemicities. We report a case of a young male who tested positive for both Plasmodium vivax and Plasmodium falciparum along with dengue infection. He showed signs of early treatment failure to artemisinin combination therapy (artesunate with sulfadoxine+pyrimethamine). Molecular analysis for the drug resistance genes viz: chloroquine resistance ( pfcrt ), multidrug resistance ( pfmdr-1 ), sulfadoxine ( pfdhps ), pyrimethamine ( pfdhfr ), and artemisinin resistance ( keltch 13 ) was performed. A rise in parasitemia from treatment. Mutations in pfcrt , pfmdr-1 , pfdhfr , and pfdhps genes were detected as a possible cause of treatment failure. Increased severity, overlapping symptoms, and suspected resistance to treatment warrants a multidimensional diagnostic approach and diligent therapeutic monitoring.

Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants

NARCIS (Netherlands)

Buchholz, Ulrike; Kobbe, Robin; Danquah, Ina; Zanger, Philipp; Reither, Klaus; Abruquah, Harry H.; Grobusch, Martin P.; Ziniel, Peter; May, Jürgen; Mockenhaupt, Frank P.

2010-01-01

Intermittent preventive treatment in infants with sulphadoxine-pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%. Potentially, however, this intervention may compromise the acquisition of immunity, including the tolerance towards multiple infections with Plasmodium falciparum.

Multiplicity of Plasmodium falciparum infection following intermittent preventive treatment in infants

NARCIS (Netherlands)

Buchholz, U.; Kobbe, R.; Danquah, I.; Zanger, P.; Reither, K.; Abruquah, H.H.; Grobusch, M.P.; Ziniel, P.; May, J.; Mockenhaupt, F.P.

2010-01-01

Background: Intermittent preventive treatment in infants with sulphadoxine-pyrimethamine (IPTi-SP) reduces malaria morbidity by 20% to 33%. Potentially, however, this intervention may compromise the acquisition of immunity, including the tolerance towards multiple infections with Plasmodium

Patterns of case management and chemoprevention for malaria-in-pregnancy by public and private sector health providers in Enugu state, Nigeria.

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Onwujekwe, Ogochukwu C; Soremekun, Rebecca O; Uzochukwu, Benjamin; Shu, Elvis; Onwujekwe, Obinna

2012-07-06

Malaria in pregnancy (MIP) is a major disease burden in Nigeria and has adverse consequences on the health of the mother, the foetus and the newborn. Information is required on how to improve its prevention and treatment from both the providers' and consumers' perspectives. The study sites were two public and two private hospitals in Enugu, southeast Nigeria. Data was collected using a pre-tested structured questionnaire. The respondents were healthcare providers (doctors, pharmacists and nurses) providing ante-natal care (ANC) services. They consisted of 32 respondents from the public facilities and 20 from the private facilities. The questionnaire elicited information on their: knowledge about malaria, attitude, chemotherapy and chemoprophylaxis using pyrimethamine, chloroquine proguanil as well as IPTp with sulphadoxine-pyrimethamine (SP). The data was collected from May to June 2010. Not many providers recognized maternal and neonatal deaths as potential consequences of MIP. The public sector providers provided more appropriate treatment for the pregnant women, but the private sector providers found IPTp more acceptable and provided it more rationally than public sector providers (p sector providers and 25 % of public sector providers prescribed chemoprophylaxis using pyrimethamine, chloroquine and proguanil to pregnant women. There is sub-optimal level of knowledge about current best practices for treatment and chemoprophylaxis for MIP especially in the private sector. Also, IPTp was hardly used in the public sector. Interventions are required to improve providers' knowledge and practices with regards to management of MIP.

Selection of drug resistant mutants from random library of Plasmodium falciparum dihydrofolate reductase in Plasmodium berghei model

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Yuthavong Yongyuth

2011-05-01

Full Text Available Abstract Background The prevalence of drug resistance amongst the human malaria Plasmodium species has most commonly been associated with genomic mutation within the parasites. This phenomenon necessitates evolutionary predictive studies of possible resistance mutations, which may occur when a new drug is introduced. Therefore, identification of possible new Plasmodium falciparum dihydrofolate reductase (PfDHFR mutants that confer resistance to antifolate drugs is essential in the process of antifolate anti-malarial drug development. Methods A system to identify mutations in Pfdhfr gene that confer antifolate drug resistance using an animal Plasmodium parasite model was developed. By using error-prone PCR and Plasmodium transfection technologies, libraries of Pfdhfr mutant were generated and then episomally transfected to Plasmodium berghei parasites, from which pyrimethamine-resistant PfDHFR mutants were selected. Results The principal mutation found from this experiment was S108N, coincident with the first pyrimethamine-resistance mutation isolated from the field. A transgenic P. berghei, in which endogenous Pbdhfr allele was replaced with the mutant PfdhfrS108N, was generated and confirmed to have normal growth rate comparing to parental non-transgenic parasite and also confer resistance to pyrimethamine. Conclusion This study demonstrated the power of the transgenic P. berghei system to predict drug-resistant Pfdhfr mutations in an in vivo parasite/host setting. The system could be utilized for identification of possible novel drug-resistant mutants that could arise against new antifolate compounds and for prediction the evolution of resistance mutations.

THERAPY FOR OCULAR TOXOPLASMOSIS

NARCIS (Netherlands)

ROTHOVA, A; MEENKEN, C; BRINKMAN, CJ; BAARSMA, GS; BOENTAN, TN; DEJONG, PTVM; KLAASSENBROEKEMA, N; SCHWEITZER, CMC; TIMMERMAN, Z; DEVRIES, J; ZAAL, MJW; KIJLSTRA, A

1993-01-01

We conducted a prospective multicenter study of the efficacy of current therapeutic strategies for ocular toxoplasmosis in 149 patients. Treatment consisted of the following three triple-drug combinations: group 1, pyrimethamine, sulfadiazine, and corticosteroids; group 2, clindamycin, sulfadiazine,

Coverage of intermittent preventive treatment and insecticide-treated nets for the control of malaria during pregnancy in sub-Saharan Africa: a synthesis and meta-analysis of national survey data, 2009-11

NARCIS (Netherlands)

van Eijk, Anna Maria; Hill, Jenny; Larsen, David A.; Webster, Jayne; Steketee, Richard W.; Eisele, Thomas P.; ter Kuile, Feiko O.

2013-01-01

Pregnant women in malaria-endemic countries in sub-Saharan Africa are especially vulnerable to malaria. Recommended prevention strategies include intermittent preventive treatment with two doses of sulfadoxine-pyrimethamine and the use of insecticide-treated nets. However, progress with

Plasmodium falciparum mutant haplotype infection during pregnancy associated with reduced birthweight, Tanzania

DEFF Research Database (Denmark)

Minja, Daniel T R; Schmiegelow, Christentze; Mmbando, Bruno

2013-01-01

Intermittent preventive treatment during pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) is a key strategy in the control of pregnancy-associated malaria. However, this strategy is compromised by widespread drug resistance from single-nucleotide polymorphisms in the Plasmodium falciparum...

Therapy for ocular toxoplasmosis

NARCIS (Netherlands)

Rothova, A.; Meenken, C.; Buitenhuis, H. J.; Brinkman, C. J.; Baarsma, G. S.; Boen-Tan, T. N.; de Jong, P. T.; Klaassen-Broekema, N.; Schweitzer, C. M.; Timmerman, Z.

1993-01-01

We conducted a prospective multicenter study of the efficacy of current therapeutic strategies for ocular toxoplasmosis in 149 patients. Treatment consisted of the following three triple-drug combinations: group 1, pyrimethamine, sulfadiazine, and corticosteroids; group 2, clindamycin, sulfadiazine,

Antiplasmodial effects of the aqueous extract of phyllantus amarus ...

African Journals Online (AJOL)

0.05) suppression of P berghei parasites via a repository action. This effect was comparable to the effects of pyrimethamine a standard repository agent. In established infection, the extract at all doses administered, was found to significantly ...

Community-Based Promotional Campaign to Improve Uptake of Intermittent Preventive Antimalarial Treatment in Pregnancy in Burkina Faso

NARCIS (Netherlands)

Gies, Sabine; Coulibaly, Sheick O.; Ky, Clotilde; Ouattara, Florence T.; Brabin, Bernard J.; d'Alessandro, Umberto

2009-01-01

Malaria preventive strategies in pregnancy were assessed in a health center randomized trial comparing intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) with and without community based promotional activities in rural Burkina Faso. The study involved 2,240 secundigravidae

Treatment of Plasmodium falciparum malaria with mefloquine alone or in combination with i.v. quinine at the Department of Communicable and Tropical Diseases, Rigshospitalet, Copenhagen 1982-1988

DEFF Research Database (Denmark)

Magnussen, P; Bygbjerg, Ib Christian

1990-01-01

At the Department of Communicable and Tropical Diseases, Rigshospitalet, Denmark, mefloquine has been used since 1982 for the treatment of patients with suspected or verified chloroquine and sulfadoxine-pyrimethamine resistant P. falciparum malaria. Eighty-one patients treated with mefloquine...

Therapeutic efficacy of mefloquine and sulfadoxine/ pyrimethamine ...

African Journals Online (AJOL)

Preferred Customer

Conclusion: These findings show that MQ (15mg base/kg), administered as a single oral dose, was highly effective .... The dosage was adjusted according to the ... Hemoglobin was measured at the day of registration and at day 14 with a colorimetric method using Drabkin's solution. Thick and thin blood films were stained ...

Intermittent preventive treatment of malaria in pregnancy

DEFF Research Database (Denmark)

Mbonye, A.K.; Hansen, Kristian Schultz; Bygbjerg, Ib Christian

2008-01-01

The main objective of this study was to assess whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilisers could administer intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine (SP) to pregnant women. The study w...

Emergence of mutations associated with resistance to Sulfadoxine ...

African Journals Online (AJOL)

Pyrimethamine (SP) after single therapeutic dose: Implications on the useful therapeutic life of SP in malaria holoedemic areas. DS Tarimo. Abstract. No Abstract. East African Journal of Public Health Vol. 2 (2) October 2005: 28-31. Full Text: EMAIL FULL ...

Increased prevalence of malaria in HIV-infected pregnant women and its implications for malaria control

NARCIS (Netherlands)

Verhoeff, F. H.; Brabin, B. J.; Hart, C. A.; Chimsuku, L.; Kazembe, P.; Broadhead, R. L.

1999-01-01

To examine in pregnant women the relationship between HIV infection and malaria prevalence and to determine, in relation to HIV infection, the effectiveness of sulphadoxine-pyrimethamine in clearing P. falciparum infection. Descriptive cross-sectional analysis of P. falciparum prevalence in pregnant

Decline of placental malaria in southern Ghana after the implementation of intermittent preventive treatment in pregnancy

NARCIS (Netherlands)

Hommerich, Lena; von Oertzen, Christa; Bedu-Addo, George; Holmberg, Ville; Acquah, Patrick A.; Eggelte, Teunis A.; Bienzle, Ulrich; Mockenhaupt, Frank P.

2007-01-01

Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) has been adopted as policy by many countries in sub-Saharan Africa. However, data on the post-implementation effectiveness of this measure are scarce. Clinical and parasitological parameters were assessed among

Efficacy and Safety of Azithromycin-Chloroquine versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Plasmodium falciparum Malaria Infection in Pregnant Women in Africa: An Open-Label, Randomized Trial.

Directory of Open Access Journals (Sweden)

Joshua Kimani

Full Text Available The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp with sulfadoxine-pyrimethamine (SP in African regions with moderate to high malaria transmission. However, growing resistance to SP threatens the effectiveness of IPTp-SP, and alternative drugs are needed. This study tested the efficacy, tolerability, and safety of a fixed-dose combination azithromycin-chloroquine (AZCQ; 250 mg AZ/155 mg CQ base for IPTp relative to IPTp-SP.A randomized, Phase 3, open-label, multi-center study was conducted in sub-Saharan Africa (Benin, Kenya, Malawi, Tanzania, and Uganda between October 2010 and November 2013. Pregnant women received 3 IPTp courses with AZCQ (each course: 1,000/620 mg AZCQ QD for 3 days or SP (each course 1,500/75 mg SP QD for 1 day at 4- to 8-week intervals during the second and third trimester. Long-lasting insecticide-treated bednets were also provided at enrollment. Study participants were followed up until day 28 post delivery (time window: day 28-42. The primary endpoint was the proportion of participants with sub-optimal pregnancy outcomes (a composite endpoint comprising live-borne neonates with low birth weight [LBW, 28 weeks], abortion [≤28 weeks], lost to follow-up prior to observation of pregnancy outcome, or missing birth weight. The study was terminated early after recruitment of 2,891 of the planned 5,044 participants, due to futility observed in a pre-specified 35% interim analysis. In the final intent-to-treat dataset, 378/1,445 (26.2% participants in the AZCQ and 342/1,445 (23.7% in the SP group had sub-optimal pregnancy outcomes, with an estimated risk ratio (RR of 1.11 (95% CI: 0.97, 1.25; p = 0.12. There was no significant difference in the incidence of LBW between treatment groups (57/1138 [5.0%] in the AZCQ group, 68/1188 [5.7%] in the SP group, RR 0.87 [95% CI: 0.62, 1.23]; p = 0.44. IPTp-AZCQ was less well-tolerated in mothers than IPTp-SP. Occurrences of congenital anomalies

Effectiveness of antenatal clinics to deliver intermittent preventive treatment and insecticide treated nets for the control of malaria in pregnancy in Kenya

NARCIS (Netherlands)

Hill, Jenny; Dellicour, Stephanie; Bruce, Jane; Ouma, Peter; Smedley, James; Otieno, Peter; Ombock, Maurice; Kariuki, Simon; Desai, Meghna; Hamel, Mary J.; ter Kuile, Feiko O.; Webster, Jayne

2013-01-01

Malaria in pregnancy can have devastating consequences for mother and baby. Coverage with the WHO prevention strategy for sub-Saharan Africa of intermittent-preventive-treatment (IPTp) with two doses of sulphadoxine-pyrimethamine (SP) and insecticide-treated-nets (ITNs) in pregnancy is low. We

Toxoplasma pericarditis mimicking systemic lupus erythematosus. Diagnostic and treatment difficulties in one patient

DEFF Research Database (Denmark)

Lyngberg, K K; Vennervald, B J; Bygbjerg, I C

1992-01-01

with pyrimethamine-sulphadiazine was needed. Interestingly, the patient's SLE symptoms, including high ANA antibodies, declined to an unexpected remission after treatment for toxoplasmosis. This may not be mere coincidence, but may point to a causative role of toxoplasmosis in some cases of SLE....

Antimalarial drugs in pregnancy: a review

NARCIS (Netherlands)

Nosten, François; McGready, Rose; d'Alessandro, Umberto; Bonell, Ana; Verhoeff, Francine; Menendez, Clara; Mutabingwa, Thenonest; Brabin, Bernard

2006-01-01

In this review we examine the available information on the safety of antimalarials in pregnancy, from both animal and human studies. The antimalarials that can be used in pregnancy include (1) chloroquine, (2) amodiaquine, (3) quinine, (4) azithromycin, (5) sulfadoxine-pyrimethamine, (6) mefloquine,

South African Medical Journal - Vol 95, No 5 (2005)

African Journals Online (AJOL)

... of sulfadoxine-pyrimethamine for Plasmodium falciparum malaria · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Aaron Mabuza, John Govere, Kobus laGrange, Nicros Mngomezulu, Elizabeth Allen, Alpheus Zitha, Frans Mbokazi, David Durrheim, Karen Barnes ...

The evolutionary landscape of antifolate resistance in Plasmodium ...

Indian Academy of Sciences (India)

Permanent link: https://www.ias.ac.in/article/fulltext/jgen/090/02/0187-0190. Keywords. malaria; drug resistance; dihydrofolate reductase; pyrimethamine; chlorcycloguanil; antifolates. Author Affiliations. Marna S. Costanzo1 Daniel L. Hartl1. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, ...

[Mutant alleles associated to chloroquine and sulfadoxine-pyrimethanime resistance in Plasmodium falciparum of the Ecuador-Peru and Ecuador-Colombia borders].

Science.gov (United States)

Arróspide, Nancy; Hijar-Guerra, Gisely; de Mora, Doménica; Diaz-Cortéz, César Eduardo; Veloz-Perez, Raúl; Gutierrez, Sonia; Cabezas-Sánchez, César

2014-04-01

The frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda.

In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii.

Science.gov (United States)

Gomes, Thaís Cobellis; de Andrade Júnior, Heitor Franco; Lescano, Susana Angélica Zevallos; Amato-Neto, Vicente

2012-01-01

Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS), or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. Artesunate showed a mean tachyzoite inhibitory concentration (IC50) of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

Science.gov (United States)

Brentlinger, Paula E; Behrens, Christopher B; Micek, Mark A

2006-02-01

Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.

A new strategy and its effect on adherence to intermittent preventive treatment of malaria in pregnancy in Uganda

DEFF Research Database (Denmark)

Mbonye, Anthony K; Yanow, Stephanie; Birungi, Josephine

2013-01-01

Few women in Uganda access intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). Previous studies have shown that high costs, frequent stock-out of drugs, supplies and poor quality of care are the greatest hindrance for women to access health services...

Malaria chemoprophylaxis during pregnancy: a survey of current ...

African Journals Online (AJOL)

Sulphadoxine/pyrimethamine (SP) has been recommended by the World Health Organisation (WHO) for malaria chemoprophylaxis in pregnancy and has been ... The data were entered into a personal computer and analysed using SPSS for windows version 10.0 and presented as frequency tables and percentages.

Synthesis, characterization and antibacterial screening of 2,4 ...

African Journals Online (AJOL)

Air stable silver Ag(I) complexes of pyrimethamine and trimethoprim drugs have been synthesized and characterized by elemental analysis, Fourier transform infrared (FTIR) and ultraviolet visible (UV-Vis) spectroscopy, and conductivity measurement. The metal complexes formed a three and four coordinate geometry with ...

Therapy of ocular toxoplasmosis

NARCIS (Netherlands)

Rothova, A.; Buitenhuis, H. J.; Meenken, C.; Baarsma, G. S.; Boen-Tan, T. N.; de Jong, P. T.; Schweitzer, C. M.; Timmerman, Z.; de Vries, J.; Zaal, M. J.

1989-01-01

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine,

The Malaria Season Is Upon Us

African Journals Online (AJOL)

imported or Odyssean malaria from countries such as Swaziland,. Mozambique ... can be administered.⁵ The only .... Treatment. With the introduction of an effective vaccine for Southern Africa .... Being prepared for a malaria infection by packing ... sulfadoxine-pyrimethamine against Plasmodium falciparum in Yemen and.

Dhfr and dhps mutations in Plasmodium falciparum isolates in ...

African Journals Online (AJOL)

Sulfadoxine-pyrimethamine (SP), the current first line antimalarial drug in Tanzania, is compromised by evolution and spread of mutations in the parasite's dhfr and dhps genes. In the present study we established the baseline frequencies of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate ...

Distinguishing Plasmodium falciparum treatment failures from re-infections by using polymerase chain reaction genotyping in a holoendemic area in northeastern Tanzania

DEFF Research Database (Denmark)

Magesa, S M; Mdira, K Y; Farnert, A

2001-01-01

susceptibility to a combination of sulfadoxine/pyrimethamine (Fansidar; F. Hoffmann La Roche, Basel, Switzerland). Blood samples were collected before treatment and on days 7, 14, or 28 post-treatment in 51 asymptomatic children, of which 26 could not clear parasitemia within seven days post-treatment. Among...

Plasmodium falciparum malaria

African Journals Online (AJOL)

Durrheim, Karen Barnes. Objectives. To assess the therapeutic efficacy of sulfadoxine- pyrimethamine (SP) after 5 years of use as first-line treatment of uncomplicated Plasmodium falciparum malaria, and thus guide the selection of artemisinin-based combination therapy in Mpumalanga, South Africa. Design. An open-label ...

Synthesis, characterization and antibacterial screening of 2,4 ...

African Journals Online (AJOL)

seafood

2012-05-15

May 15, 2012 ... 2Department of Biochemistry and Microbiology, University of Fort Hare, Alice 5700, South Africa. Accepted 23 February, 2012. Air stable silver Ag(I) complexes of pyrimethamine and trimethoprim drugs have been synthesized and characterized by elemental analysis, Fourier transform infrared (FTIR) and ...

Possible Role of Drugs and Herbal Medicines in Stevens-Johnson ...

African Journals Online (AJOL)

This paper has reviewed three cases of erythema multiforme major who presented with ocular complications. In one of the cases, the patient became blind because of mismanagement. The precipitating factors in the three patients were a herbal remedy, Fansidar® (Sulfadoxine 500mg; Pyrimethamine 25mg) and ...

In vitro action of antiparasitic drugs, especially artesunate, against Toxoplasma gondii

Directory of Open Access Journals (Sweden)

Thaís Cobellis Gomes

2012-08-01

Full Text Available INTRODUCTION: Toxoplasmosis is usually a benign infection, except in the event of ocular, central nervous system (CNS, or congenital disease and particularly when the patient is immunocompromised. Treatment consists of drugs that frequently cause adverse effects; thus, newer, more effective drugs are needed. In this study, the possible activity of artesunate, a drug successfully being used for the treatment of malaria, on Toxoplasma gondii growth in cell culture is evaluated and compared with the action of drugs that are already being used against this parasite. METHODS: LLC-MK2 cells were cultivated in RPMI medium, kept in disposable plastic bottles, and incubated at 36ºC with 5% CO2. Tachyzoites of the RH strain were used. The following drugs were tested: artesunate, cotrimoxazole, pentamidine, pyrimethamine, quinine, and trimethoprim. The effects of these drugs on tachyzoites and LLC-MK2 cells were analyzed using nonlinear regression analysis with Prism 3.0 software. RESULTS: Artesunate showed a mean tachyzoite inhibitory concentration (IC50 of 0.075µM and an LLC MK2 toxicity of 2.003µM. Pyrimethamine was effective at an IC50 of 0.482µM and a toxicity of 11.178µM. Trimethoprim alone was effective against the in vitro parasite. Cotrimoxazole also was effective against the parasite but at higher concentrations than those observed for artesunate and pyrimethamine. Pentamidine and quinine had no inhibitory effect over tachyzoites. CONCLUSIONS: Artesunate is proven in vitro to be a useful alternative for the treatment of toxoplasmosis, implying a subsequent in vivo effect and suggesting the mechanism of this drug against the parasite.

CHAPTER 1

African Journals Online (AJOL)

Dr Olaleye

history of IPTp-Sulfadoxine-Pyrimethamine (SP) use in the index pregnancy were recorded. Finger and heel pricks blood samples from mothers and neonates respectively were used to detect malaria parasitaemia and to determine packed cell volume (PCV). Median number of ANC visits made by the enrollees was 4.0 ...

Download this PDF file

African Journals Online (AJOL)

sulfadoxine-pyrimethamine (SP) tablets in two hundred and twenty eight adult malaria patients in Dar es Salaam region was carried out shortly before the drug was introduced as a first line treatment for malaria in Tanzania. Sources and dispensing practices with SP in the private community pharmacies were also assessed.

Suppressors for Human Epidermal Growth Factor Receptor 2/4 (HER2/4): A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells.

Science.gov (United States)

Kim, Yeong Hoon; Bhatt, Lokraj; Ahn, Hye-Jin; Yang, Zhaoshou; Lee, Won-Kyu; Nam, Ho-Woo

2017-10-01

The effects of tyrosine kinase inhibitors (TKIs) were evaluated on growth inhibition of intracellular Toxoplasma gondii in host ARPE-19 cells. The number of tachyzoites per parasitophorous vacuolar membrane (PVM) was counted after treatment with TKIs. T. gondii protein expression was assessed by western blot. Immunofluorescence assay was performed using Programmed Cell Death 4 (PDCD4) and T. gondii GRA3 antibodies. The TKIs were divided into 3 groups; non-epidermal growth factor receptor (non-EGFR), anti-human EGFR 2 (anti-HER2), and anti-HER2/4 TKIs, respectively. Group I TKIs (nintedanib, AZD9291, and sunitinib) were unable to inhibit proliferation without destroying host cells. Group II TKIs (lapatinib, gefitinib, erlotinib, and AG1478) inhibited proliferation up to 98% equivalent to control pyrimethamine (5 μM) at 20 μM and higher, without affecting host cells. Group III TKIs (neratinib, dacomitinib, afatinib, and pelitinib) inhibited proliferation up to 98% equivalent to pyrimethamine at 1-5 μM, but host cells were destroyed at 10-20 μM. In Group I, TgHSP90 and SAG1 inhibitions were weak, and GRA3 expression was moderately inhibited. In Group II, TgHSP90 and SAG1 expressions seemed to be slightly enhanced, while GRA3 showed none to mild inhibition; however, AG1478 inhibited all proteins moderately. Protein expression was blocked in Group III, comparable to pyrimethamine. PDCD4 and GRA3 were well localized inside the nuclei in Group I, mildly disrupted in Group II, and were completely disrupted in Group III. This study suggests the possibility of a vital T. gondii TK having potential HER2/4 properties, thus anti-HER2/4 TKIs may inhibit intracellular parasite proliferation with minimal adverse effects on host cells.

GEIS Surveillance Network Program

Science.gov (United States)

2013-10-01

influenza-like illness in Kenya, determine etiologies of diarrheal illnesses and the antimicrobial resistance patterns of bacterial causes, determine ...of the blood sample. These drugs include Arteether, Pyronaridine, Primaquine, Artesunate, Proguanil, Trimethoprim , Sulfamethoxazole, Pyrimethamine...that are controlled with Trimethoprim /sulfamethoxazole (TMP/SMZ). Use of TMP/SMZ prophylaxis however might put populations at risk of developing

Author Details

African Journals Online (AJOL)

Bla, KB. Vol 9, No 6 (2010) - Articles PFCRT and DHFR-TS Sequences for Monitoring Drug Resistance in Adzopé Area of Côte d'Ivoire After the Withdrawal of Chloroquine and Pyrimethamine Abstract PDF. ISSN: 1596-9827. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

Polymerase Chain Reaction To Determine Frequency Of ...

African Journals Online (AJOL)

PCR amplification of the DHFR-TS could be used to determine frequency of pyrimethamine resistant P. falciparum strains in malaria blood. Plasmodium falciparum résistant dans ... Les mutations étaient identifiées directement dans les prélèvement de sang obtenus de malades qui visitent les hôpitaux pour les services de ...

Chlorproguanil - Dapsone a new drug in the fight against malaria ...

African Journals Online (AJOL)

... mutation than Sulfadoxine/ pyrimethamine. Though the toxicity data is awaited from the field we can deduce from the information available that it is a safe drug and the only adverse event directly attributed to it is aneamia and this occurred in less than 1% of those studied. African Journal of Health Sciences Vol.11(1&2) ...

Estimated impact on birth weight of scaling up intermittent preventive treatment of malaria in pregnancy given sulphadoxine-pyrimethamine resistance in Africa: A mathematical model.

Directory of Open Access Journals (Sweden)

Patrick G T Walker

2017-02-01

Full Text Available Malaria transmission has declined substantially in the 21st century, but pregnant women in areas of sustained transmission still require protection to prevent the adverse pregnancy and birth outcomes associated with malaria in pregnancy (MiP. A recent call to action has been issued to address the continuing low coverage of intermittent preventive treatment of malaria in pregnancy (IPTp. This call has, however, been questioned by some, in part due to concerns about resistance to sulphadoxine-pyrimethamine (SP, the only drug currently recommended for IPTp.Using an existing mathematical model of MiP, we combined estimates of the changing endemicity of malaria across Africa with maps of SP resistance mutations and current coverage of antenatal access and IPTp with SP (IPTp-SP across Africa. Using estimates of the relationship between SP resistance mutations and the parasitological efficacy of SP during pregnancy, we estimated the varying impact of IPTp-SP across Africa and the incremental value of enhancing IPTp-SP uptake to match current antenatal care (ANC coverage. The risks of MiP and malaria-attributable low birthweight (mLBW in unprotected pregnancies (i.e., those not using insecticide-treated nets [ITNs] leading to live births fell by 37% (33%-41% 95% credible interval [crI] and 31% (27%-34% 95% crI, respectively, from 2000 to 2015 across endemic areas in sub-Saharan Africa. However, these gains are fragile, and coverage is far from optimal. In 2015, 9.5 million (8.3 million-10.4 million 95% crI of 30.6 million pregnancies in these areas would still have been infected with Plasmodium falciparum without intervention, leading to 750,000 (390,000-1.1 million 95% crI mLBW deliveries. In all, 6.6 million (5.6 million-7.3 million 95% crI of these 9.5 million (69.3% pregnancies at risk of infection (and 53.4% [16.3 million/30.6 million] of all pregnancies occurred in settings with near-perfect SP curative efficacy (>99% based on the most recent

Impact of Chloroquine on Viral Load in Breast Milk

Science.gov (United States)

Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

2006-01-01

Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

A modified Plasmodium falciparum growth inhibition assay (GIA) to assess activity of plasma from malaria endemic areas.

Science.gov (United States)

Mlambo, Godfree; Kumar, Nirbhay

2007-02-01

Plasma samples from patients undergoing treatment in malaria endemic countries often contain anti-malaria drugs, that may overstate effects of specific antibodies in growth inhibition assays (GIA). We describe a modified assay that uses drug resistant P. falciparum parasites (W2) that circumvents the requirement for dialyzing samples that may likely contain drugs such as chloroquine and sulfadoxine/pyrimethamine (SP).

The effects of pyrimethamine and sulphadoxine mixture on plasma ...

African Journals Online (AJOL)

-vitro to determine the effect of increasing combined concentrations of pyrime- thamine and sulphadoxine (ratio 20:1w/w) solution on plasma levels of hemoglobin (Fe 2+)/methaemoglobin (Fe 3+) ratio. The concentrations used were 0.2, 0.4, ...

Fitness trade-offs in the evolution of dihydrofolate reductase and drug resistance in Plasmodium falciparum.

Directory of Open Access Journals (Sweden)

Marna S Costanzo

Full Text Available Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance. Understanding how evolution proceeds from drug susceptibility to drug resistance is critical if new antifolate treatments are to have sustained usefulness.We use a transgenic yeast expression system to build on previous studies that described the adaptive landscape for the antifolate drug pyrimethamine, and we describe the most likely evolutionary trajectories for the evolution of drug resistance to the antifolate chlorcycloguanil. We find that the adaptive landscape for chlorcycloguanil is multi-peaked, not all highly resistant alleles are equally accessible by evolution, and there are both commonalities and differences in adaptive landscapes for chlorcycloguanil and pyrimethamine.Our findings suggest that cross-resistance between drugs targeting the same enzyme reflect the fitness landscapes associated with each particular drug and the position of the genotype on both landscapes. The possible public health implications of these findings are discussed.

Increased Prevalence of the pfdhfr/phdhps Quintuple Mutant and Rapid Emergence of pfdhps Eesistance Mutations at Codons 581 and 613 in Kisumu, Kenya

Science.gov (United States)

2010-11-24

Bras JL: In vitro Activity of pyrimethamine, cycloguanil, and other antimalarial drugs against African isolates and clones of Plasmodium...fact-sheet] 2. Shretta R, Omumbo J, Rapuoda B, Snow RW: Using evidence to change antimalarial drug policy in Kenya. Trop Med Int Health 2000, 5:755...Marks F, Amoah K, Opoku E, Meyer CG, Adjei O, May J: A randomized controlled trial of extended intermittent preventive antimalarial treatment in infants

Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the P. falciparum dihydropteroate synthase gene

DEFF Research Database (Denmark)

Alifrangis, Michael; Lusingu, John P; Mmbando, Bruno

2009-01-01

.001). In contrast, the chloroquine-sensitive P. falciparum chloroquine resistance transporter (Pfcrt) CVMNK haplotype increased from 6% to 30% (P use of SP for intermittent presumptive treatment of pregnant women......In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two...

Gametocytogenesis Following Drug Treatment of Plasmodium Falciparum in an Area of Seasonal Transmission in Sudan

International Nuclear Information System (INIS)

Mackinnon, M. J.M; Walliker, D.; Babiker, A.; Ahmed, S.; Abdel-Muhsin, A.; Eltayeb, A.

2007-01-01

We monitored post-treatment Plasmodium falciparum among patients treated with chloroquine (CQ) and pyrimethamine-sulfadoxine (PS) in a village in eastern Sudan. Parasites were examined on day zero (pre-treatment), day 7, day 14 and day 21 (post-treatment) during the transmission season. A further sample was taken two months later (Day 80) at the start of the dry season. Asexual forms and gametocytes were detected by microscopy and reverse transcriptase polymerase chain reaction (RT-PCR) to detect expression of a gametocyte-specific protein pfg377. Gametocyte carriage, as revealed by microscopy, increased significantly following CQ and PS treatment reaching a maximum between days 7 and 14. When measured by RT-PCR, however, there was no significant difference in gametocyte rate between day 0 and day 7 or 14. RT-PCR gametocyte rates dropped dramatically by day 80 post-treatment but were still 33% and 8% in the CQ and PS treated group at this time. Alleles associated with drug resistance of P. falciparum to chloroquine (the chloroquine resistance transporter, pfcrt, and multi-drug resistance, pfmdr-1) and pyrimethamine (dihydrofolate reductase, dhfr) were at high frequency at the beginning of treatment and increased further through time under both drug treatments. Infections with drug-resistant parasites tended to have higher gametocyte prevalence than drug-sensitive infections.

Congenital toxoplasmosis.

Science.gov (United States)

Kieffer, François; Wallon, Martine

2013-01-01

Congenital toxoplasmosis results from the transplacental transmission of the parasite Toxoplasma gondii after a maternal infection acquired in pregnancy. Prevalence of congenital infection ranges from 0.1 to 0.3 per 1000 live births. The maternal-fetal transmission rate increases with gestational age at maternal seroconversion, from less than 15% at 13 weeks of gestation to over 70% at 36 weeks. Conversely, the later the maternal infection, the lower the risk of symptomatic congenital infection (infections acquired during the third trimester are most often asymptomatic at birth). Prenatal diagnosis is currently performed by PCR analysis in amniotic fluid. Antenatal management and treatment vary considerably among countries. In some European countries, maternal infections are detected through serological screening allowing a prompt treatment with spiramycin, which is expected to reduce the risk of vertical transmission. If PCR analysis in amniotic fluid is positive or if maternal infection was acquired in the third trimester of pregnancy, a combination with pyrimethamine and sulphonamide is given until delivery. Benefits of antenatal treatments remain controversial. Infected newborns are prescribed pyrimethamine and sulphonamide for 12 months. Despite antenatal and postnatal treatment, chorioretinitis can occur at any age (prevalence>20% at 10 years of age): long-term ophthalmological follow-up remains necessary. Copyright © 2013 Elsevier B.V. All rights reserved.

Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study

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Kevin J. Lee

2014-10-01

Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.

Perception on the Use of Sulfadoxine-Pyrimethamine Tablets in the ...

African Journals Online (AJOL)

Sources and dispensing practices with SP in the private community pharmacies were also assessed. The study revealed that 80.3% of the patients were relieved from malaria symptoms and 19.7% did not feel any relief after using the drug. Further, the results showed that 39.5% of the patients did not experience side effects ...

Development of behaviour change communication strategy for a vaccination-linked malaria control tool in southern Tanzania

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Mshinda Hassan

2008-09-01

Full Text Available Abstract Background Intermittent preventive treatment of malaria in infants (IPTi using sulphadoxine-pyrimethamine and linked to the expanded programme on immunization (EPI is a promising strategy for malaria control in young children. As evidence grows on the efficacy of IPTi as public health strategy, information is needed so that this novel control tool can be put into practice promptly, once a policy recommendation is made to implement it. This paper describes the development of a behaviour change communication strategy to support implementation of IPTi by the routine health services in southern Tanzania, in the context of a five-year research programme evaluating the community effectiveness of IPTi. Methods Mixed methods including a rapid qualitative assessment and quantitative health facility survey were used to investigate communities' and providers' knowledge and practices relating to malaria, EPI, sulphadoxine-pyrimethamine and existing health posters. Results were applied to develop an appropriate behaviour change communication strategy for IPTi involving personal communication between mothers and health staff, supported by a brand name and two posters. Results Malaria in young children was considered to be a nuisance because it causes sleepless nights. Vaccination services were well accepted and their use was considered the mother's responsibility. Babies were generally taken for vaccination despite complaints about fevers and swellings after the injections. Sulphadoxine-pyrimethamine was widely used for malaria treatment and intermittent preventive treatment of malaria in pregnancy, despite widespread rumours of adverse reactions based on hearsay and newspaper reports. Almost all health providers said that they or their spouse were ready to take SP in pregnancy (96%, 223/242. A brand name, key messages and images were developed and pre-tested as behaviour change communication materials. The posters contained public health messages

Cardiac toxoplasmosis after heart transplantation diagnosed by endomyocardial biopsy.

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Petty, L A; Qamar, S; Ananthanarayanan, V; Husain, A N; Murks, C; Potter, L; Kim, G; Pursell, K; Fedson, S

2015-10-01

We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim-sulfamethoxazole (TMP-SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP-SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Submicroscopic gametocytes and the transmission of antifolate-resistant Plasmodium falciparum in Western Kenya

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Oesterholt, Mayke J A M; Alifrangis, Michael; Sutherland, Colin J

2009-01-01

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the dhfr and dhps genes are associated with sulphadoxine-pyrimethamine (SP) treatment failure and gametocyte carriage. This may result in enhanced transmission of mutant malaria parasites, as previously shown for chloroquine resistant parasites...... gametocytemia or enhanced malaria transmission. The absence of wild-type infections is likely to have reduced our power to detect differences. Our data further support the use of ACT to reduce the transmission of drug-resistant malaria parasites....

Early diagnosis and successful treatment of disseminated toxoplasmosis after cord blood transplantation.

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Kurihara, Taro; Sumi, Masahiko; Kaiume, Hiroko; Takeda, Wataru; Kirihara, Takehiko; Sato, Keijiro; Ueki, Toshimitsu; Hiroshima, Yuki; Ueno, Mayumi; Ichikawa, Naoaki; Kaneko, Yumi; Hikosaka, Kenji; Norose, Kazumi; Kobayashi, Hikaru

2016-06-01

A 66-year-old woman with refractory angioimmunoblastic T-cell lymphoma underwent cord blood transplantation. Prior to transplantation, a serological test for Toxoplasma gondii-specific IgG antibodies was positive. On day 96, she exhibited fever and dry cough. Chest CT showed diffuse centrilobular ground glass opacities in both lungs. The reactivation of T. gondii was identified by the presence of parasite DNA in peripheral blood and bronchoalveolar lavage fluid. Moreover, brain MRI revealed a space occupying lesion in the right occipital lobe. Therefore, disseminated toxoplasmosis was diagnosed. She received pyrimethamine and sulfadiazine from day 99. The lung and brain lesions both showed improvement but the PCR assay for T. gondii DNA in peripheral blood was positive on day 133. On day 146, she developed blurred vision and reduced visual acuity, and a tentative diagnosis of toxoplasmic retinochoroiditis was made based on ophthalmic examination results. As agranulocytosis developed on day 158, we decided to discontinue pyrimethamine and sulfadiazine and the treatment was thus switched to atovaquone. Moreover, we added spiramycin to atovaquone therapy from day 174, and her ocular condition gradually improved. In general, the prognosis of disseminated toxoplasmosis after hematopoietic stem cell transplantation (HSCT) is extremely poor. However, early diagnosis and treatment may contribute to improvement of the fundamentally dismal prognosis of disseminated toxoplasmosis after HSCT.

Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model.

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Eraky, Maysa Ahmad; El-Fakahany, Amany Farouk; El-Sayed, Nagwa Mostafa; Abou-Ouf, Eman Abdel-Rahman; Yaseen, Doaa Ibrahim

2016-07-01

The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.

Antiplasmodial effects of the aqueous ethanolic seed extract of Ziziphus mauritiana against Plasmodium berghei in Swiss albino mice

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Tulika Mishra

2014-08-01

Full Text Available Ziziphus mauritiana is a fruit tree used traditionally since long back for wound healing, immunepotentiator, asthma, sedative, stomachic, styptic, as tonic etc. The present study determines the antiplasmodial effect of aqueous ethanolic seed extract against Chloroquine sensitive Plasmodium berghei berghei nk65 infection in Swiss albino mice. Based upon the acute toxicity data three different doses (100, 200, 400 mg/kg body weight of the plant extract was chosen to study the blood schizonticidal activity in early infection and in established infection and was compared with chloroquine. The Prophylactic activity was also assessed and compared with pyrimethamine. No mortality was observed in acute toxicity study however, above the dose of 1000 mg/kg animals showed the lethargic behaviour. In early infection, and in established infection the doses (100-400 mg/kg b.wt was found to cause significant (P<0.001 suppression of infection in a dose dependent manner as compared to control. Although, the activity was lower than standard chloroquine. Similarly, the extract at all the doses caused the suppression in repository activity but was lower than pyrimethamine. The mean survival time was also increased in mice by 14 and 17 days at the doses of 200 and 400 mg/kg respectively, whereas the control group sustained only for 7 days. Thus, the seed extract showed the effectiveness against plasmodium infection.

In vivo testing of the therapeutic efficacy of chloroquine on falciparum malaria infections in Chirundu, Mashonaland West, Zimbabwe.

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Barduagni, P; Schwartz, U; Nyamayaro, W; Chauke, T L

1998-10-01

To detect the level of the in vivo chloroquine efficacy in falciparum malaria infections, in order to assess the need for change in the management and treatment of uncomplicated malaria. Prospective descriptive study. Chirundu Rural Clinic, Mashonaland West Province. 63 patients confirmed by a positive blood slide for P. falciparum who attended Chirundu clinic, who were eligible for the study and, who also agreed to participate. Frequency of treatment success, early treatment failure and late treatment failure in uncomplicated patients treated with chloroquine. Out of 63 cases enrolled and completely followed up, chloroquine treatment was effective in 54 cases (85.7%) and was not effective in nine cases (14.3%). All treatment failures were successfully treated with sulphadoxine + pyrimethamine (Fansidar) or quinine following the approved guidelines. Chloroquine remains highly effective in the treatment of malaria due to P. falciparum in the Zambezi Valley of Hurungwe district and therefore, has to remain the first line drug. Likewise, guidelines for the use of sulphadoxine + pyrimethamine (Fansidar) or quinine as second line drugs, are adequate to the local situation. Health workers directly supervised the patients when they were swallowing the tablets during the whole course, and this without doubt, indirectly increased the efficacy of chloroquine. It is vital to confirm the malaria diagnosis on the spot appointing microscopists or distributing a limited stock of Parasight-F test.

A simple, high-throughput method to detect Plasmodium falciparum single nucleotide polymorphisms in the dihydrofolate reductase, dihydropteroate synthase, and P. falciparum chloroquine resistance transporter genes using polymerase chain reaction- and enzyme-linked immunosorbent

DEFF Research Database (Denmark)

Alifrangis, Michael; Enosse, Sonia; Pearce, Richard

2005-01-01

Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum dihydrofolate reductase (dhfr), and dihydropteroate synthetase (dhps), and chloroquine resistance transporter (Pfcrt) genes are used as molecular markers of P. falciparum resistance to sulfadoxine/pyrimethamine and chloroquine....... However, to be a practical tool in the surveillance of drug resistance, simpler methods for high-throughput haplotyping are warranted. Here we describe a quick and simple technique that detects dhfr, dhps, and Pfcrt SNPs using polymerase chain reaction (PCR)- and enzyme-linked immunosorbent assay (ELISA...

A simple field kit for the determination of drug susceptibility in Plasmodium falciparum.

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Nguyen-Dinh, P; Magloire, R; Chin, W

1983-05-01

A field kit has been developed which greatly simplifies the performance of the 48-hour in vitro test for drug resistance in Plasmodium falciparum. The kit uses an easily reconstituted lyophilized culture medium, and requires only a fingerprick blood sample. In parallel tests with 13 isolates of P. falciparum in Haiti, the new technique had a success rate equal to that of the previously described method, with comparable results in terms of parasite susceptibility in vitro to chloroquine and pyrimethamine.

Malaria prevalence in Nias District, North Sumatra Province, Indonesia

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Laowo Idaman

2007-08-01

Full Text Available Abstract Background The Nias district of the North Sumatra Province of Indonesia has long been known to be endemic for malaria. Following the economic crisis at the end of 1998 and the subsequent tsunami and earthquake, in December 2004 and March 2005, respectively, the malaria control programme in the area deteriorated. The present study aims to provide baseline data for the establishment of a suitable malaria control programme in the area and to analyse the frequency distribution of drug resistance alleles associated with resistance to chloroquine and sulphadoxine-pyrimethamine. Methods Malariometric and entomology surveys were performed in three subdistricts. Thin and thick blood smears were stained with Giemsa and examined under binocular light microscopy. Blood blots on filter paper were also prepared for isolation of parasite and host DNA to be used for molecular analysis of band 3 (SAO, pfcrt, pfmdr1, dhfr, and dhps. In addition, haemoglobin measurement was performed in the second and third surveys for the subjects less than 10 years old. Results Results of the three surveys revealed an average slide positivity rate of 8.13%, with a relatively higher rate in certain foci. Host genetic analysis, to identify the Band 3 deletion associated with Southeast Asian Ovalocytosis (SAO, revealed an overall frequency of 1.0% among the 1,484 samples examined. One hundred six Plasmodium falciparum isolates from three sub-districts were successfully analysed. Alleles of the dhfr and dhps genes associated with resistance to sulphadoxine-pyrimethamine, dhfr C59R and S108N, and dhps A437G and K540E, were present at frequencies of 52.2%, 82.5%, 1.18% and 1.18%, respectively. The pfmdr1 alleles N86Y and N1042D, putatively associated with mefloquine resistance, were present at 31.4% and 2%, respectively. All but one sample carried the pfcrt 76T allele associated with chloroquine resistance. Entomologic surveys identified three potential anopheline vectors in

A nationwide survey of the quality of antimalarials in retail outlets in Tanzania.

Science.gov (United States)

Kaur, Harparkash; Goodman, Catherine; Thompson, Eloise; Thompson, Katy-Anne; Masanja, Irene; Kachur, S Patrick; Abdulla, Salim

2008-01-01

Retail pharmaceutical products are commonly used to treat fever and malaria in sub-Saharan African countries. Small scale studies have suggested that poor quality antimalarials are widespread throughout the region, but nationwide data are not available that could lead to generalizable conclusions about the extent to which poor quality drugs are available in African communities. This study aimed to assess the quality of antimalarials available from retail outlets across mainland Tanzania. We systematically purchased samples of oral antimalarial tablets from retail outlets across 21 districts in mainland Tanzania in 2005. A total of 1080 antimalarial formulations were collected including 679 antifol antimalarial samples (394 sulfadoxine/pyrimethamine and 285 sulfamethoxypyrazine/pyrimethamine), 260 amodiaquine samples, 63 quinine samples, and 51 artemisinin derivative samples. A systematic subsample of 304 products was assessed for quality by laboratory based analysis to determine the amount of the active ingredient and dissolution profile by following the published United States Pharmacopoeia (USP) monogram for the particular tablet being tested. Products for which a published analytical monogram did not exist were assessed on amount of active ingredient alone. Overall 38 or 12.2% of the samples were found to be of poor quality. Of the antifolate antimalarial drugs tested 13.4% were found to be of poor quality by dissolution and content analysis using high-performance liquid chromatography (HPLC). Nearly one quarter (23.8%) of quinine tablets did not comply within the tolerance limits of the dissolution and quantification analysis. Quality of amodiaquine drugs was relatively better but still unacceptable as 7.5% did not comply within the tolerance limits of the dissolution analysis. Formulations of the artemisinin derivatives all contained the stated amount of active ingredient when analysed using HPLC alone. Substandard antimalarial formulations were widely

A nationwide survey of the quality of antimalarials in retail outlets in Tanzania.

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Harparkash Kaur

Full Text Available Retail pharmaceutical products are commonly used to treat fever and malaria in sub-Saharan African countries. Small scale studies have suggested that poor quality antimalarials are widespread throughout the region, but nationwide data are not available that could lead to generalizable conclusions about the extent to which poor quality drugs are available in African communities. This study aimed to assess the quality of antimalarials available from retail outlets across mainland Tanzania.We systematically purchased samples of oral antimalarial tablets from retail outlets across 21 districts in mainland Tanzania in 2005. A total of 1080 antimalarial formulations were collected including 679 antifol antimalarial samples (394 sulfadoxine/pyrimethamine and 285 sulfamethoxypyrazine/pyrimethamine, 260 amodiaquine samples, 63 quinine samples, and 51 artemisinin derivative samples. A systematic subsample of 304 products was assessed for quality by laboratory based analysis to determine the amount of the active ingredient and dissolution profile by following the published United States Pharmacopoeia (USP monogram for the particular tablet being tested. Products for which a published analytical monogram did not exist were assessed on amount of active ingredient alone. Overall 38 or 12.2% of the samples were found to be of poor quality. Of the antifolate antimalarial drugs tested 13.4% were found to be of poor quality by dissolution and content analysis using high-performance liquid chromatography (HPLC. Nearly one quarter (23.8% of quinine tablets did not comply within the tolerance limits of the dissolution and quantification analysis. Quality of amodiaquine drugs was relatively better but still unacceptable as 7.5% did not comply within the tolerance limits of the dissolution analysis. Formulations of the artemisinin derivatives all contained the stated amount of active ingredient when analysed using HPLC alone.Substandard antimalarial formulations were

Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria.

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Chimere Obiora Agomo

Full Text Available The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine-pyrimethamine (SP is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1 and type 1 antifolate antimalarial medicines (Pfdhfr.Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt gene by real time polymerase chain reaction (PCR using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1 gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene.Two haplotypes of Pfcrt (n = 54 were observed: CVMNK 13(24.2% and CVIET 41 (75.9% of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28 haplotypes were NYSND 15(53.6%, YYSND 5(17.9%, NFSND 6(21.4% and YFSND 2(7.1%. The Pfdhfr (n = 15 were ACNCSVI 4(26.7%, and ACICNSVI 1(6.7% and ACIRNVI 10 (66.7%. The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/μl, P = 0.024 while Pfcrt 76T was associated with young maternal age (mean 24.1 ± 4.5 years; P = 0.006. The median parasitaemia were similar (P>0.05 in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt

A REVIEW OF THE MALARIA SITUATION IN IRIAN JAYA

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Suriadi Gunawan

2012-09-01

Full Text Available Karangan ini merupakan tinjauan mengenai situasi malaria di Irian Jaya hingga tahun 1980. Malaria merupakan masalah kesehatan masyarakat yang penting karena menyebabkan 14% dari kematian di rumah sakit dan 20% dari kunjungan ke fasilitas kesehatan. Malaria adalah hiper sampai mesoendemik di daerah pantai dan dataran rendah, sedangkan di dae­rah pegunungan sampai ketinggian 1700 m malaria tidak stabil dan potensial epidemik. Yang menjadi vektor ialah kelompok Anopheles punctulatus yang exo atau endophagik secara fakultatif serta bersifat exofilik. Program pemberantasan malaria yang didasarkan pada penyemprotan rumah dengan DDT melin­dungi sekitar 300.000 penduduk di 15 lokasi. Di semua lokasi penyemprotan angka parasit memang turun, kecuali di daerah Genyem (Nimboran di mana dicurigai adanya resistensi nyamuk terhadap DDT, tetapi transmisi malaria masih berjalan terus. Pembagian obat secara massal (chloroquin dan pyrimethamin juga tidak menghasilkan penurunan penu­laran yang diharapkan. Pemberantasan malaria di Irian Jaya menghadapi berbagai hambatan yang sangat besar. Selain ma­salah operasional, keuangan dan perilaku manusia, terdapat pula masalah teknis seperti berkembangnya resistensi P. falciparum terhadap pyrimethamin dan proguanil (1959, chloroquin (1973 dan sulfadoxin/ fansidar (1979 serta kemungkinan berkembangnya resistensi vektor terhadap DDT. Pemberantasan malaria di Irian Jaya perlu dievaluasi secara menyeluruh dan penelitian yang ber­sifat operasional perlu dilaksanakan untuk menyusun suatu program yang lebih rasional dan sesuai de­ngan kondisi setempat. Meningkatnya malaria akan menghambat pembangunan, maka penanggulangannya mutlak dilak­sanakan untuk menjamin berhasilnya proyek-proyek pembangunan sosial-ekonomi di propinsi tersebut.

Human toxoplasmosis-Searching for novel chemotherapeutics.

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Antczak, Magdalena; Dzitko, Katarzyna; Długońska, Henryka

2016-08-01

The protozoan Toxoplasma gondii, an obligate intracellular parasite, is an etiological agent of human and animal toxoplasmosis. Treatment regimens for T. gondii-infected patients have not essentially changed for years. The most common chemotherapeutics used in the therapy of symptomatic toxoplasmosis are a combination of pyrimethamine and sulfadiazine plus folinic acid or a combination of pyrimethamine with lincosamide or macrolide antibiotics. To protect a fetus from parasite transplacental transmission, therapy of pregnant women is usually based on spiramycin, which is quite safe for the organism, but not efficient in the treatment of infected children. Application of recommended drugs limits replication of T. gondii, however, it may be associated with numerous an severe adverse effects. Moreover, medicines have no impact on the tissue cysts of the parasite located predominantly in a brain and muscles. Thus, there is urgent need to develop new drugs and establish "gold standard" treatment. In this review classical treatment of toxoplasmosis as well as potential compounds active against T. gondii have been discussed. For two last decades studies on the development of new anti-T. gondii medications have been focused on both natural and novel synthetic compounds based on existing chemical scaffolds. They have revealed several promising drug candidates characterized by a high selectivity, the low IC50 (the half maximal inhibitory concentration) and low cytotoxicity towards host cells. These drugs are expected to replace or supplement current anti-T. gondii drug arsenal soon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania

DEFF Research Database (Denmark)

Mohammed, Asia; Ndaro, Arnold; Kalinga, Akili

2013-01-01

Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to the control of malaria. In 2001 Tanzania replaced chloroquine (CQ) with sulphadoxine-pyrimethamine (SP) as first-line drug, which in turn was replaced by artemisinin combination therapy in 2006. SP has however......, continued to be used in intermittent preventive treatment of malaria in pregnancy (IPTp) despite reports of high levels of resistance to SP due to the lack of alternatives to SP for IPTp. Recent reports have indicated recovery of CQ-susceptibility in Malawi, Kenya, Mozambique, and Tanzania based...

Malaria control at the district level in Africa: the case of the muheza district in northeastern Tanzania

DEFF Research Database (Denmark)

Alilio, Martin S; Kitua, Andrew; Njunwa, Kato

2004-01-01

transmission and incidence over time; use of facility-based care services for malaria; patients' access to professional advice; the trend of treatment failure over time of sulfadoxine-pyrimethamine and chloroquine; survival rates of severe cases at the district hospital; a district malaria control strategy......An assessment was done in Tanzania to determine the extent to which the primary health care services have contributed to reducing the burden of malaria since the system was initiated in the 1980s. Seven descriptive processes and outcome indicators of effectiveness were used: changes of malaria...

Monitoring antifolate resistance in intermittent preventive therapy for malaria

DEFF Research Database (Denmark)

Venkatesan, Meera; Alifrangis, Michael; Roper, Cally

2013-01-01

Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps have rendered sulfadoxine-pyrimethamine (SP) ineffective for malaria treatment in most regions of the world. Yet, SP is efficacious as intermittent preventive therapy in pregnant women (IPTp) and infants (IPTi) and as seasonal malaria...... control in children (SMC). SP-IPTp is being widely implemented in sub-Saharan Africa. SP-IPTi is recommended where the prevalence of SP-resistant malaria parasites is low, whereas SMC is recommended for areas of intense seasonal malaria transmission. The continuing success of these interventions depends...

Perception of chloroquine efficacy and alternative treatments for uncomplicated malaria in children in a holoendemic area of Tanzania: implications for the change of treatment policy

DEFF Research Database (Denmark)

Tarimo, D S; Minjas, J N; Bygbjerg, I C

2001-01-01

Prior to policy change from chloroquine (CQ) to sulphadoxine/pyrimethamine (S/P; Fansidar) we assessed the perception of CQ efficacy and the alternative treatment options for malaria in children among parents/guardians (N=527) of under-fives attending first level health facilities on account...... of fever. It was hypothesized that the long experience with CQ and its antipyretic effect (lacking in S/P) might impede acceptance of S/P for wider use as first-line drug. Malarial fevers in children were most commonly treated with CQ (92.8%), followed by quinine (60.7%) and S/P (28.7%). A 63.2% knew...

Pharmacokinetics of mefloquine and its effect on sulfamethoxazole and trimethoprim steady-state blood levels in intermittent preventive treatment (IPTp) of pregnant HIV-infected women in Kenya.

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Green, Michael; Otieno, Kephas; Katana, Abraham; Slutsker, Laurence; Kariuki, Simon; Ouma, Peter; González, Raquel; Menendez, Clara; ter Kuile, Feiko; Desai, Meghna

2016-01-05

Intermittent preventive treatment in pregnancy with sulfadoxine/pyrimethamine is contra-indicated in HIV-positive pregnant women receiving sulfamethoxazole/trimethoprim prophylaxis. Since mefloquine is being considered as a replacement for sulfadoxine/pyrimethamine in this vulnerable population, an investigation on the pharmacokinetic interactions of mefloquine, sulfamethoxazole and trimethoprim in pregnant, HIV-infected women was performed. A double-blinded, placebo-controlled study was conducted with 124 HIV-infected, pregnant women on a standard regimen of sulfamethoxazole/trimethoprim prophylaxis. Seventy-two subjects received three doses of mefloquine (15 mg/kg) at monthly intervals. Dried blood spots were collected from both placebo and mefloquine arms four to 672 h post-administration and on day 7 following a second monthly dose of mefloquine. A novel high-performance liquid chromatographic method was developed to simultaneously measure mefloquine, sulfamethoxazole and trimethoprim from each blood spot. Non-compartmental methods using a naïve-pooled data approach were used to determine mefloquine pharmacokinetic parameters. Sulfamethoxazole/trimethoprim prophylaxis did not noticeably influence mefloquine pharmacokinetics relative to reported values. The mefloquine half-life, observed clearance (CL/f), and area-under-the-curve (AUC0→∞) were 12.0 days, 0.035 l/h/kg and 431 µg-h/ml, respectively. Although trimethoprim steady-state levels were not significantly different between arms, sulfamethoxazole levels showed a significant 53% decrease after mefloquine administration relative to the placebo group and returning to pre-dose levels at 28 days. Although a transient decrease in sulfamethoxazole levels was observed, there was no change in hospital admissions due to secondary bacterial infections, implying that mefloquine may have provided antimicrobial protection.

Anti-Toxoplasma Effects of Methanol Extracts of Feijoa sellowiana, Quercus castaneifolia, and Allium paradoxum

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Mohammad Ali Ebrahimzadeh

2017-09-01

Full Text Available Objectives: The currently available agents for use against toxoplasmosis have serious limitations. Thus, the aim of the present study was to investigate the anti-Toxoplasma gondii (T. gondii activities of methanol extracts of Feijoa sellowiana (F. sellowiana (leaves and fruits, Quercus castaneifolia (Q. castaneifolia (fruits, and Allium paradoxum (A. paradoxum (leaves in vitro and in vivo. Methods: Vero cells were treated with different concentrations (from 0 to 400 μg/mL of the above extracts or with pyrimethamine at a dose of 50 mg/mL (positive control. Then, the viabilities of the T. gondii-infected cells were measured by using colorimetric MTT (3-(4, 5-dimethylthiazol-2-yl 2, 5-diphenyltetrazolium bromide assays. In addition, the survival rates of mice acutely infected with 2 × 104 RH strain tachyzoites of T. gondii were examined in vivo after intraperitoneal injection of the extracts at doses of 100 and 200 mg/kg/day for 5 days. Results: In the in vitro anti- T. gondii assay, the IC50 values were 12.77, 180.2, 74.73, 213.2 and 163.8 μg/mL, and the selectivity indices were 6.05, 1.31, 0.35, 0.69 and 1.30 for the F. sellowiana (leaves and fruits, Q. castaneifolia, and A. paradoxum extracts and pyrimethamine, respectively. Moreover, the mice treated with F. sellowiana (leaves and fruits achieved better results in terms of survival than the others (P < 0.05. Conclusion: The results of the current study indicate that methanol extract of F. sellowiana has significant anti-Toxoplasma activity. Further study should be conducted to investigate the potential bioactivity of this extract through bioactivity-guided fractionation.

Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria.

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Fivelman, Quinton L; Butcher, Geoffrey A; Adagu, Ipemida S; Warhurst, David C; Pasvol, Geoffrey

2002-02-08

We report the first in vitro and genetic confirmation of Malarone (GlaxoSmithKline; atovaquone and proguanil hydrochloride) resistance in Plasmodium falciparum acquired in Africa. On presenting with malaria two weeks after returning from a 4-week visit to Lagos, Nigeria without prophylaxis, a male patient was given a standard 3-day treatment course of Malarone. Twenty-eight days later the parasitaemia recrudesced. Parasites were cultured from the blood and the isolate (NGATV01) was shown to be resistant to atovaquone and the antifolate pyrimethamine. The cytochrome b gene of isolate NGATV01 showed a single mutation, Tyr268Asn which has not been seen previously.

Mathematical model for optimal use of sulfadoxine-pyrimethamine as a temporary malaria vaccine.

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Dembele, Bassidy; Friedman, Avner; Yakubu, Abdul-Aziz

2010-05-01

In this paper, we introduce a deterministic malaria model for determining the drug administration protocol that leads to the smallest first malaria episodes during the wet season. To explore the effects of administering the malaria drug on different days during the wet season while minimizing the potential harmful effects of drug overdose, we define 40 drug administration protocols. Our results fit well with the clinical studies of Coulibaly et al. at a site in Mali. In addition, we provide protocols that lead to smaller number of first malaria episodes during the wet season than the protocol of Coulibaly et al.

Malaria: prevention in travellers.

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Croft, Ashley M

2010-07-12

Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10 to 14 days but can be up to 18 months depending on the strain of parasite. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in non-pregnant adult travellers? What are the effects of drug prophylaxis in non-pregnant adult travellers? What are the effects of antimalaria vaccines in adult and child travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 79 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), dietary supplementation, doxycycline, electronic mosquito repellents, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vapourising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.

Lessons learnt from 20 years surveillance of malaria drug resistance prior to the policy change in Burkina Faso.

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Tinto, Halidou; Valea, Innocent; Ouédraogo, Jean-Bosco; Guiguemdé, Tinga Robert

2016-01-01

The history of drug resistance to the previous antimalarial drugs, and the potential for resistance to evolve to Artemisinin-based combination therapies, demonstrates the necessity to set-up a good surveillance system in order to provide early warning of the development of resistance. Here we report a review summarizing the history of the surveillance of drug resistance that led to the policy change in Burkina Faso. The first Plasmodium falciparum Chloroquine-Resistance strain identified in Burkina Faso was detected by an in vitro test carried out in Koudougou in 1983. Nevertheless, no further cases were reported until 1987, suggesting that resistant strains had been circulating at a low prevalence before the beginning of the systematic surveillance system from 1984. We observed a marked increase of Chloroquine-Resistance in 2002-2003 probably due to the length of follow-up as the follow-up duration was 7 or 14 days before 2002 and 28 days from 2002 onwards. Therefore, pre-2002 studies have probably under-estimated the real prevalence of Chloroquine-Resistance by not detecting the late recrudescence. With a rate of 8.2% treatment failure reported in 2003, Sulfadoxine-Pyrimethamine was still efficacious for the treatment of uncomplicated malaria in Burkina Faso but this rate might rapidly increase as the result of its spreading from neighboring countries and due to its current use for both the Intermittent Preventive Treatment in pregnant women and Seasonal Malaria Chemoprophylaxis. The current strategy for the surveillance of the Artemisinin-based combination treatments resistance should build on lessons learnt under the previous period of 20 years surveillance of Chloroquine and Sulfadoxine-Pyrimethamine resistance (1994-2004). The most important aspect being to extend the number of sentinel sites so that data would be less patchy and could help understanding the dynamic of the resistance.

Decline of placental malaria in southern Ghana after the implementation of intermittent preventive treatment in pregnancy

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Eggelte Teunis A

2007-11-01

Full Text Available Abstract Background Intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP has been adopted as policy by many countries in sub-Saharan Africa. However, data on the post-implementation effectiveness of this measure are scarce. Methods Clinical and parasitological parameters were assessed among women delivering at a district hospital in rural southern Ghana in the year 2000 when pyrimethamine chemoprophylaxis was recommended (n = 839 and in 2006 (n = 226, approximately one year after the implementation of IPTp-SP. Examinations were performed in an identical manner in 2000 and 2006 including the detection of placental Plasmodium falciparum infection by microscopy, histidine-rich protein 2, and PCR. Results In 2006, 77% of the women reported to have taken IPTp-SP at least once (26%, twice; 24%, thrice. In 2006 as compared to 2000, placental P. falciparum infection was reduced by 43–57% (P P = 0.0009, and median birth weight was 130 g higher (P = 0.02. In 2006, likewise, women who had taken ≥ 1 dose of IPTp-SP revealed less infection and anaemia and their children tended to have higher birth weights as compared to women who had not used IPTp-SP. However, placental P. falciparum infection was still observed in 11% (microscopy to 26% (PCR of those women who had taken three doses of IPTp-SP. Conclusion In southern Ghana, placental malaria and maternal anaemia have declined substantially and birth weight has increased after the implementation of IPTp-SP. Likely, these effects can further be increased by improving IPTp-SP coverage and adherence. However, the remnant prevalence of infection in women having taken three doses of IPTp-SP suggests that additional antimalarial measures are needed to prevent malaria in pregnancy in this region.

Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery.

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Dembele, Laurent; Gego, Audrey; Zeeman, Anne-Marie; Franetich, Jean-François; Silvie, Olivier; Rametti, Armelle; Le Grand, Roger; Dereuddre-Bosquet, Nathalie; Sauerwein, Robert; van Gemert, Geert-Jan; Vaillant, Jean-Christophe; Thomas, Alan W; Snounou, Georges; Kocken, Clemens H M; Mazier, Dominique

2011-03-31

Amongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites. P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured. The non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine. Resistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a practical medium

Towards an in vitro model of Plasmodium hypnozoites suitable for drug discovery.

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Laurent Dembele

2011-03-01

Full Text Available Amongst the Plasmodium species in humans, only P. vivax and P. ovale produce latent hepatic stages called hypnozoites, which are responsible for malaria episodes long after a mosquito bite. Relapses contribute to increased morbidity, and complicate malaria elimination programs. A single drug effective against hypnozoites, primaquine, is available, but its deployment is curtailed by its haemolytic potential in glucose-6-phosphate dehydrogenase deficient persons. Novel compounds are thus urgently needed to replace primaquine. Discovery of compounds active against hypnozoites is restricted to the in vivo P. cynomolgi-rhesus monkey model. Slow growing hepatic parasites reminiscent of hypnozoites had been noted in cultured P. vivax-infected hepatoma cells, but similar forms are also observed in vitro by other species including P. falciparum that do not produce hypnozoites.P. falciparum or P. cynomolgi sporozoites were used to infect human or Macaca fascicularis primary hepatocytes, respectively. The susceptibility of the slow and normally growing hepatic forms obtained in vitro to three antimalarial drugs, one active against hepatic forms including hypnozoites and two only against the growing forms, was measured.The non-dividing slow growing P. cynomolgi hepatic forms, observed in vitro in primary hepatocytes from the natural host Macaca fascicularis, can be distinguished from similar forms seen in P. falciparum-infected human primary hepatocytes by the differential action of selected anti-malarial drugs. Whereas atovaquone and pyrimethamine are active on all the dividing hepatic forms observed, the P. cynomolgi slow growing forms are highly resistant to treatment by these drugs, but remain susceptible to primaquine.Resistance of the non-dividing P. cynomolgi forms to atovaquone and pyrimethamine, which do not prevent relapses, strongly suggests that these slow growing forms are hypnozoites. This represents a first step towards the development of a

Malarone treatment failure and in vitro confirmation of resistance of Plasmodium falciparum isolate from Lagos, Nigeria

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Warhurst David C

2002-02-01

Full Text Available Abstract We report the first in vitro and genetic confirmation of Malarone® (GlaxoSmithKline; atovaquone and proguanil hydrochloride resistance in Plasmodium falciparum acquired in Africa. On presenting with malaria two weeks after returning from a 4-week visit to Lagos, Nigeria without prophylaxis, a male patient was given a standard 3-day treatment course of Malarone®. Twenty-eight days later the parasitaemia recrudesced. Parasites were cultured from the blood and the isolate (NGATV01 was shown to be resistant to atovaquone and the antifolate pyrimethamine. The cytochrome b gene of isolate NGATV01 showed a single mutation, Tyr268Asn which has not been seen previously.

Prophylaxis for malaria. Helping world travelers come home healthy.

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Amin, N M

1992-09-01

Malaria is largely preventable, so travelers should be taught general protective measures and given appropriate chemoprophylaxis before they leave on their trip. Chloroquine phosphate (Aralen) is still the drug of choice in locations where malaria remains chloroquine-sensitive. However, chloroquine-resistant areas infested with Plasmodium falciparum are becoming more numerous. In such areas, mefloquine hydrochloride (Lariam), doxycycline, or proguanil (Paludrine) (obtainable outside the United States) may be used. A single dose of pyrimethamine-sulfadoxine (Fansidar) may be used to treat presumptive malarial infection if medical care is not immediately available. For prevention of relapse of Plasmodium vivax and Plasmodium ovale infection, primaquine phosphate is recommended for the final 2 weeks of chemoprophylaxis on return from a malarious area.

Mefloquine for preventing malaria in pregnant women.

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González, Raquel; Pons-Duran, Clara; Piqueras, Mireia; Aponte, John J; Ter Kuile, Feiko O; Menéndez, Clara

2018-03-21

The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine for malaria for all women who live in moderate to high malaria transmission areas in Africa. However, parasite resistance to sulfadoxine-pyrimethamine has been increasing steadily in some areas of the region. Moreover, HIV-infected women on cotrimoxazole prophylaxis cannot receive sulfadoxine-pyrimethamine because of potential drug interactions. Thus, there is an urgent need to identify alternative drugs for prevention of malaria in pregnancy. One such candidate is mefloquine. To assess the effects of mefloquine for preventing malaria in pregnant women, specifically, to evaluate:• the efficacy, safety, and tolerability of mefloquine for preventing malaria in pregnant women; and• the impact of HIV status, gravidity, and use of insecticide-treated nets on the effects of mefloquine. We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), the Malaria in Pregnancy Library, and two trial registers up to 31 January 2018. In addition, we checked references and contacted study authors to identify additional studies, unpublished data, confidential reports, and raw data from published trials. Randomized and quasi-randomized controlled trials comparing mefloquine IPT or mefloquine prophylaxis against placebo, no treatment, or an alternative drug regimen. Two review authors independently screened all records identified by the search strategy, applied inclusion criteria, assessed risk of bias, and extracted data. We contacted trial authors to ask for additional information when required. Dichotomous outcomes were compared using risk ratios (RRs), count outcomes as incidence rate ratios (IRRs), and continuous outcomes using mean differences (MDs). We have presented all

Molecular monitoring of Plasmodium falciparum super-resistance to sulfadoxine-pyrimethamine in Tanzania

DEFF Research Database (Denmark)

Kavishe, Reginald A; Kaaya, Robert D; Nag, Sidsel

2016-01-01

and A581G Pfdhps. Data were analysed using SPSS version 18 while Chi square and/or Fischer Exact tests were used to compare prevalence between regions. RESULTS: A high inter-regional variation of Pfdhps-540E was observed (χ(2) = 76.8, p

Effect of a community-based delivery of intermittent preventive treatment of malaria in pregnancy on treatment seeking for malaria at health units in Uganda

DEFF Research Database (Denmark)

Mbonye, A K; Schultz Hansen, K; Bygbjerg, I C

2008-01-01

whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer IPTp with sulphadoxine-pyrimethamine (SP) to pregnant women, reach those at greatest risk of malaria, and increase access and compliance with IPTp. STUDY DESIGN...... of the intervention on access to malaria treatment, antenatal care, other services and related costs. RESULTS: More women (67.5%) received two doses of SP through the community approach compared with health units (39.9%; P... in the community had sought malaria treatment (70.3%), suggesting the possibility that the novel approach had a positive impact on care seeking for malaria. Similarly, utilization of antenatal care, insecticide-treated nets and delivery care by women in the community was high. The total costs per woman receiving...

Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum

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Garavito G.

2007-06-01

Full Text Available Methylene blue (MB is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy.

Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial

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Massaga, Julius J; Kitua, Andrew Y; Lemnge, Martha M

2003-01-01

: Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants, in an area with high resistance to other antimalarials. Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health.......BACKGROUND: Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa, and is often complicated by severe anaemia. Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy. We investigated the effect...... of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine. METHODS: 291 infants aged 12-16 weeks who attended three clinics...

Implementing intermittent preventive treatment for malaria in pregnancy

DEFF Research Database (Denmark)

Mubyazi, Godfrey Martin; Magnussen, Pascal; Goodman, Catherine

2011-01-01

Introduction Implementing Intermittent Preventive Treatment for malaria in Pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) through antenatal care (ANC) clinics is recommended for malaria endemic countries. The vast biomedical literature on malaria prevention focuses more on the epidemiological...... of the recommended interventions. Objective To review literature on policy advances, achievements, constraints and challenges to malaria IPTp implementation, emphasising its operational feasibility in the context of health-care financing, provision and uptake, resource constraints and psychosocial factors in Africa...... discriminatory socio-cultural values on and attitudes towards SP, malaria, and quality of ANC; supply and cost of SP at health facilities; understaffing and demoralised staff; ambiguity and impracticability of user-fee exemption policy guidelines on essential ANC services; implementing IPTp, bednets, HIV...

Atovaquone/proguanil for the prophylaxis and treatment of malaria.

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Patel, Samir N; Kain, Kevin C

2005-12-01

Increases in international travel and escalating drug resistance have resulted in a growing number of travelers at risk of contracting malaria. Drug resistance and intolerance to standard agents such as chloroquine, sulfadoxine/pyrimethamine and mefloquine has highlighted the need for new antimalarials. The recently licensed fixed combination of atovaquone and proguanil hydrochloride (Malarone) is a promising new agent to prevent and treat Plasmodium falciparum malaria. Randomized controlled trials have shown that atovaquone/proguanil is well tolerated and efficacious for the prevention and treatment of drug-resistant P. falciparum malaria. Atovaquone/proguanil is active against the liver stage of P. falciparum malaria parasites and when used as a prophylactic agent it can be discontinued shortly after leaving malaria-endemic areas, offering a clear advantage for drug adherence.

Chloroquine-resistant falciparum malaria from Irian Jaya (Indonesian New Guinea).

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Clyde, D F; McCarthy, V C; Miller, R M; Hornick, R B

1976-02-01

A strain of Plasmodium falciparum, transmitted in Irian Jaya (Indonesian New Guinea) was isolated in 1974 and sent to the University of Maryland for characterization in nonimmune volunteers. At Maryland the Indonesia (Whit.) strain, as it has been designated, was transmitted to colonized Anopheles stephensi. Prophylactically, it was not suppressed by proguanil hydrochloride 100 mg. daily. Curatively, parasitaemia was not cleared by treatment with 1-5 g. (base) in three days of chloroquine or amodiaquine (RII responses), nor by treatment with 150 mg. of pyrimethamine in three days (RIII), and some resistance was also shown to quinine. A single dose of 1-5 g. of mefloquine (WR 142,490) produced radical cure in the two patients treated with this new 4-quinolinemethanol compound.

Effect of a community-based delivery of intermittent preventive treatment of malaria in pregnancy on treatment seeking for malaria at health units in Uganda

DEFF Research Database (Denmark)

Mbonye, Anthony; Hansen, Kristian Schultz; Bygbjerg, Ib

2008-01-01

whether traditional birth attendants, drug-shop vendors, community reproductive health workers and adolescent peer mobilizers can administer IPTp with sulphadoxine-pyrimethamine (SP) to pregnant women, reach those at greatest risk of malaria, and increase access and compliance with IPTp. Study design...... of the intervention on access to malaria treatment, antenatal care, other services and related costs. Results: More women (67.5%) received two doses of SP through the community approach compared with health units (39.9%; P... in the community had sought malaria treatment (70.3%), suggesting the possibility that the novel approach had a positive impact on care seeking for malaria. Similarly, utilization of antenatal care, insecticide-treated nets and delivery care by women in the community was high. The total costs per woman receiving...

Intermittent preventive treatment of malaria in pregnancy: a community-based delivery system and its effect on parasitemia, anemia and low birth weight in Uganda

DEFF Research Database (Denmark)

Mbonye, Anthony K; Bygbjerg, Ib; Magnussen, Pascal

2008-01-01

OBJECTIVE: The main objective of the study was to assess the impact of a community-based delivery system of intermittent preventive treatment (IPT) for malaria in pregnancy with sulfadoxine-pyrimethamine (SP) on access, parasitemia, anemia and low birth weight as primary outcome measures. METHODS.......0001). At both health units and the community-based approaches, IPT increased mean hemoglobin by 6.7% (panemia from 5.7% to 3.1% (p.... This intervention was acceptable to 89.6% of the women at the community-based approaches intending to use IPT in the future, while 48.1% of them had recommended it to other women. CONCLUSIONS: The community-based approaches increased access and adherence to IPT with an effect on anemia, severe anemia, parasitemia...

Coverage, adherence and costs of intermittent preventive treatment of malaria in children employing different delivery strategies in Jasikan, Ghana.

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Edith Patouillard

Full Text Available Intermittent preventive treatment of malaria in children (IPTc involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost-effective delivery strategy.A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs or facility-based nurses working at health centres' outpatient departments (OPD or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective.The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc.VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana.ClinicalTrials.gov NCT00119132.

High prevalence of asymptomatic malaria in a tribal population in eastern India.

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Ganguly, Swagata; Saha, Pabitra; Guha, Subhasish K; Biswas, Asit; Das, Sonali; Kundu, Pratip K; Maji, Ardhendu K

2013-05-01

Asymptomatic infection by Plasmodium falciparum is an important obstacle to eliminating malaria. Asymptomatic carriers do not seek treatment for infection, and therefore they become a reservoir for the parasite. For this reason, these carriers pose a real public health risk. The systematic identification and treatment of asymptomatic infections should reduce the parasite reservoir. A large reduction in this pool will lower the chance of transmission of the disease. In this study, we screened a tribal population of 1,040 individuals in the Purulia district of West Bengal by using a dual-antigen rapid diagnostic kit (RDK), microscopy, and species-specific PCR. All positive individuals were treated with artemisinin-based combination therapy (ACT) (artesunate plus sulfadoxine-pyrimethamine) and followed for 42 days. Polymorphisms in candidate genes were screened by DNA sequencing. A significant proportion (8.4%) of the study population was infected with P. falciparum but showed no clinical manifestations. The PCR method was more sensitive in detecting infection than the RDK or microscopy. The efficacy of the ACT was 97%. In the pfcrt gene, the mutation K76T (the mutated amino acid is indicated by bold type) was found in 100% of the cases. In the pfmdr1 gene, the mutations N86Y and Y184F were noted in 55.5% and 11% of the cases, respectively. Six different haplotypes were identified in the pfdhfr-pfdhps genes. Most importantly, the quintuple mutant A(16)I(51)R(59)N(108)I(164)-S(436)G(437)E(540)A(581)A(613) was found in 10% of the isolates, which is potentially important for the development of sulfadoxine-pyrimethamine resistance. A significant proportion of the study population harboring P. falciparum does not seek treatment and therefore serves as a reservoir for the parasite, maintaining the natural cycle. If the National Vector Borne Disease Control Programme (NVBDCP) of India is to eliminate malaria, then this hidden parasite burden needs to be addressed properly

Placental malaria among HIV-infected and uninfected women receiving anti-folates in a high transmission area of Uganda

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Dorsey Grant

2009-11-01

Full Text Available Abstract Background HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP. TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women. Methods This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR. Results Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW. Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used. Conclusion Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a

The national neonatal screening programme for congenital toxoplasmosis in Denmark: results from the initial four years, 1999-2002

DEFF Research Database (Denmark)

Schmidt, Dorte Remmer; Høgh, Birthe; Andersen, O

2006-01-01

AIMS: To describe the outcome of four years' nationwide neonatal screening for congenital toxoplasmosis in liveborn newborns. METHODS: Congenital toxoplasmosis was diagnosed if specific Toxoplasma gondii IgM antibodies were detected in eluate from the PKU Guthrie filter paper card from a child....... Infants diagnosed with congenital toxoplasmosis were examined for intracranial and retinal lesions and treated for three months with sulphadiazine, pyrimethamine, and folinic acid continuously. RESULTS: Eluates from PKU-cards from 262 912 newborns were analysed. The birth prevalence of congenital...... toxoplasma infection was 2.1 per 10 000 liveborns. Congenital toxoplasmosis was suspected in 96 infants and confirmed in 55. Forty seven children were examined for intracranial and retinal lesions soon after birth; 12 had clinical signs at this first examination. Of these, 5 had intracranial calcifications...

Challenges in malaria control in sub-Saharan Africa: the vaccine perspective

DEFF Research Database (Denmark)

Lusingu, John P A; Von Seidlein, Lorenz

2008-01-01

of these interventions. The emergence of resistance against drugs and insecticides requires in response a steady stream of new interventions. Up to the beginning of this millennium, most sub-Saharan African countries have been using chloroquine (CQ) as the first-line antimalarial drug, which had to be replaced...... malaria control measures have been applied such as environmental improvements, use of insecticide impregnated nets, residual indoor spraying, early case detection and treatment with effective antimalarial drugs. However, the adaptation of vector and parasite has so far limited the effect...... with sulphadoxine-pyrimethamine (SP) after resistant parasites had rendered CQ ineffective. Currently the first line treatment of malaria consists of combination therapy which includes an artemisinin derivative. The current approach appears robust but history has taught us to be alert and to expect resistance...

Cytogenetic evaluation of Fansidar on human lymphocyte chromosomes in vitro.

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Praveen, Nuzhat; Saifi, Muheet Alam; Shadab, G G H A

2011-01-01

Fansidar is a fixed combination of two antimalarial agents a diaminopyrimidine (Pyrimethamine) and a sulphonamide (Sulphadoxine) in the ratio 1:20- that have been used extensively worldwide for the treatment of Chloroquine resistant Plasmodium falciparum malaria, toxoplasmosis and Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome. This study examined the effect of Fansidar on chromosomes in human lymphocyte culture. Fansidar was added to peripheral blood lymphocyte cultures in vitro at four different concentrations: 5,15, 25 and 50 microl in the ratio 1:20, 3:60, 5:100 and 10:200 microg ml(-1). Result shows that this drug induces moderate increase in the frequency of gaps, breaks and rearrangements. Therefore it can be concluded that Fansidar has moderate clastogenic effect on human chromosomes in vitro.

Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal

DEFF Research Database (Denmark)

Ndiaye, Magatte; Tine, Roger; Faye, Babacar

2013-01-01

Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children...... on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n=352) were collected from children under 5years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two...... on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant...

Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal

DEFF Research Database (Denmark)

Ranjitkar, Samir; Schousboe, Mette L; Thomsen, Thomas

2011-01-01

ABSTRACT: BACKGROUND: Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against Plasmodium falciparum in highly...... endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of P. falciparum and Plasmodium vivax CQ and SP resistance to determine...... and P. vivax for CQ (Pfcrt, Pfmdr1, Pvmdr1) and SP (Pfdhfr, Pfdhps, Pvdhfr), using various PCR-based methods. RESULTS AND DISCUSSION: Positive P. vivax and P. falciparum infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based...

Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal

DEFF Research Database (Denmark)

Ndiaye, Magatte; Faye, Babacar; Tine, Roger

2012-01-01

Abstract. As a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy. In Senegal, the health authorities changed from chloroquine (CQ) to a combination of sulfadoxine-pyrimethamine (SP) plus...... at the molecular level in selected sites in Senegal, because the scientific community is interested in using CQ again. Finger prick blood samples were collected from Plasmodium falciparum-positive children below the age of 10 years (N = 474) during cross-sectional surveys conducted in two study sites in Senegal...... with different malaria transmission levels. One site is in central Senegal, and the other site is in the southern part of the country. All samples were analyzed for single nucleotide polymorphisms (SNPs) in the P. falciparum CQ resistance transporter gene (Pfcrt; codons 72-76) using polymerase chain reaction...

Emerging drug -resistance and guidelines for treatment of malaria

International Nuclear Information System (INIS)

Khan, M.A.; Smego Jr, R.A.; Razi, S.T.; Beg, M.A.

2004-01-01

The increasing prevalence of multi-resistant Plasmodium falciparum malaria worldwide is a serious public health threat to the global control of malaria, especially in poor countries like Pakistan. In many countries chloroquine-resistance is a huge problem, accounting for more than 90% of malaria cases. In Pakistan, resistance to chloroquine is on the rise and reported in up to 16- 62% of Plasmodium falciparum. Four to 25% of Plasmodium falciparum also reported to be resistant to sulfadoxine-pyrimethamine and several cases of delayed parasite clearance have been observed in patients with Plasmodium falciparum malaria treated with quinine. In this article we have introduced the concept of artemisinin- based combination therapy (ACT) and emphasize the use of empiric combination therapy for all patients with Plasmodium falciparum malaria to prevent development of drug resistance and to obtain additive and synergistic killing of parasite. (author)

Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa

DEFF Research Database (Denmark)

Fernandes, Silke; Sicuri, Elisa; Halimatou, Diawara

2016-01-01

$/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp-AL becomes cost-effective depends on assumptions about the contribution of bed nets to malaria control, bed net coverage and the willingness......-to-pay threshold used.  Conclusions: At SP efficacy levels currently observed in the trial settings it would not be cost-effective to switch from IPTp-SP to ISTp-AL, mainly due to the substantially higher costs of ISTp-AL and limited difference in outcomes. The modelling results indicate thresholds below which IPT......Background: Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment...

Different origin and dispersal of sulfadoxine-resistant Plasmodium falciparum haplotypes between Eastern Africa and Democratic Republic of Congo

DEFF Research Database (Denmark)

Baraka, Vito; Delgado-Ratto, Christopher; Nag, Sidsel

2017-01-01

Sulfadoxine/pyrimethamine (SP) is still used for malaria control in sub-Saharan Africa; however, widespread resistance is a major concern. This study aimed to determine the dispersal and origin of sulfadoxine resistance lineages in the Democratic Republic of the Congo compared with East African.......3 and 7.7 kb) flanking the Pfdhps gene were assayed. Evolutionary analysis revealed a shared origin of Pfdhps haplotypes in East Africa, with a distinct population clustering in DR Congo. Furthermore, in Tanzania there was an independent distinct origin of Pfdhps SGEGA resistant haplotype. In Uganda...... and Tanzania, gene flow patterns contribute to the dispersal and shared origin of parasites carrying double- and triple-mutant Pfdhps haplotypes associated with poor outcomes of intermittent preventive treatment during pregnancy using SP (IPTp-SP). However, the origins of the Pfdhps haplotypes in DR Congo...

Microbial hara-kiri: Exploiting lysosomal cell death in malaria parasites

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Jun-Hong Ch’ng

2015-01-01

Full Text Available The antimalarial drug chloroquine (CQ has been sidelined in the fight against falciparum malaria due to wide-spread CQ resistance. Replacement drugs like sulfadoxine, pyrimethamine and mefloquine have also since been surpassed with the evolution of multi-drug resistant parasites. Even the currently recommended artemisinin-based combination therapies show signs of compromise due to the recent spread of artemisinin delayed-clearance parasites. Though there have been promising breakthroughs in the pursuit of new effective antimalarials, the development and strategic deployment of such novel chemical entities takes time. We therefore argue that there is a crucial need to re-examine the usefulness of ‘outdated’ drugs like chloroquine, and explore if they might be effective alternative therapies in the interim. We suggest that a novel parasite cell death (pCD pathway may be exploited through the reformulation of CQ to address this need.

Asymptomatic Malaria Correlates with Anaemia in Pregnant Women at Ouagadougou, Burkina Faso

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Zoenabo Douamba

2012-01-01

Full Text Available Sub-Saharan Africa records each year about thirty-two million pregnant women living in areas of high transmission of Plasmodium falciparum causing malaria. The aim of this study was to carve out the prevalence of asymptomatic malaria among pregnant women and to emphasize its influence on haematological markers. The prevalence of Plasmodium falciparum asymptomatic infection among pregnant women was 30% and 24% with rapid detection test (RDT and microscopy, respectively. The prevalence of P. falciparum asymptomatic malaria was reduced among pregnant women using sulfadoxine-pyrimethamine's intermittent preventive treatment and 61% of them were anaemic. Anaemia was significantly more common in women infected with P. falciparum compared with the uninfected pregnant women. Most of the women had normal levels of homocysteine and low levels of folate, respectively. Therefore, the systematic diagnosis of malaria should be introduced to pregnant women as a part of the antenatal care.

Malaria treatment policy change and implementation: the case of Uganda.

Science.gov (United States)

Nanyunja, Miriam; Nabyonga Orem, Juliet; Kato, Frederick; Kaggwa, Mugagga; Katureebe, Charles; Saweka, Joaquim

2011-01-01

Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

Malaria Treatment Policy Change and Implementation: The Case of Uganda

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Miriam Nanyunja

2011-01-01

Full Text Available Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010–2012

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Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V.; Sánchez, Juan F.; Macedo, Silvia; Conde, Silvia; Tapia, L. Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A.; Udhayakumar, Venkatachalam; Lescano, Andrés G.

2015-01-01

During 2010–2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998–2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events. PMID:25897626

Molecular Epidemiology of Plasmodium falciparum Malaria Outbreak, Tumbes, Peru, 2010-2012.

Science.gov (United States)

Baldeviano, G Christian; Okoth, Sheila Akinyi; Arrospide, Nancy; Gonzalez, Rommell V; Sánchez, Juan F; Macedo, Silvia; Conde, Silvia; Tapia, L Lorena; Salas, Carola; Gamboa, Dionicia; Herrera, Yeni; Edgel, Kimberly A; Udhayakumar, Venkatachalam; Lescano, Andrés G

2015-05-01

During 2010-2012, an outbreak of 210 cases of malaria occurred in Tumbes, in the northern coast of Peru, where no Plasmodium falciparum malaria case had been reported since 2006. To identify the source of the parasite causing this outbreak, we conducted a molecular epidemiology investigation. Microsatellite typing showed an identical genotype in all 54 available isolates. This genotype was also identical to that of parasites isolated in 2010 in the Loreto region of the Peruvian Amazon and closely related to clonet B, a parasite lineage previously reported in the Amazon during 1998-2000. These findings are consistent with travel history of index case-patients. DNA sequencing revealed mutations in the Pfdhfr, Pfdhps, Pfcrt, and Pfmdr1 loci, which are strongly associated with resistance to chloroquine and sulfadoxine/pyrimethamine, and deletion of the Pfhrp2 gene. These results highlight the need for timely molecular epidemiology investigations to trace the parasite source during malaria reintroduction events.

Repeated Artemisinin-Based Combination Therapies in a Malaria Hyperendemic Area of Mali: Efficacy, Safety, and Public Health Impact

Science.gov (United States)

Sagara, Issaka; Fofana, Bakary; Gaudart, Jean; Sidibe, Bakary; Togo, Amadou; Toure, Sekou; Sanogo, Kassim; Dembele, Demba; Dicko, Alassane; Giorgi, Roch; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

2012-01-01

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria. PMID:22764291

Intracranial toxoplasmosis presenting as panhypopituitarism in an immunocompromised patient.

Science.gov (United States)

Hamdeh, Shadi; Abbas, Anum; Fraker, Jessica; Lambrecht, J E

2015-12-01

A 37-year-old man presented with worsening headache, vomiting, and right-sided weakness over the last few weeks. A head computed tomography showed a left hemispheric posterior medial parietal lobe lesion with surrounding edema. Further imaging with magnetic resonance imaging showed multiple enhancing mass lesions. The largest lesion measured 2.4 cm within the left occipital parietal region (Figure A and B). Laboratory data showed reactive HIV antibodies, confirmed by Western blot. An absolute CD4 count was 22 cells/μL. Other laboratory test results showed low sodium, thyrotropin, FT4, FT3, cortisol levels, corticotropin, luteinizing hormone, and testosterone. Based on these findings, the brain lesions were believed to be causing his panhypopituitarism. A brain biopsy confirmed the presence of Toxoplasma gondii by polymerase chain reaction. The patient was started on pyrimethamine and clindamycin for toxoplasmosis treatment, and azithromycin and sulfamethoxazole/trimethoprime for appropriate prophylaxis. He was also started on hormone supplementation. His symptoms were completely resolved at the time of discharge.

Disseminated toxoplasmosis in an immunocompetent patient from Peruvian Amazon Toxoplasmosis diseminada en un paciente inmunocompetente procedente de la Amazonía peruana

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Juan Nunura

2010-04-01

Full Text Available We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.Reportamos un caso de toxoplasmosis severa en un paciente inmunocompetente caracterizado por neumonía, retinocoroiditis, hepatitis y miositis. El diagnóstico fue confirmado por serología, el hallazgo de T. gondii en gota gruesa y la presencia de bradizoitos en biopsia muscular. El tratamiento con pirimetamina mas sulfadoxina fue exitoso pero solo hubo una parcial recuperación de la agudeza visual y de la capacidad de extensión de la cadera. Este es el primer reporte de un caso de toxoplasmosis severa en el Perú.

Perspective for the reproduction of antimalarial drugs in Brazil

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Benjamin Gilbert

1992-01-01

Full Text Available The appears to be no chemical manufacture of antimalarial drugs is Brazil. Technology at laboratory process level has been developed for chloroquine, mefloquine, pyrimethamine and cycloquanil, but not perfected nor scaled-up, largely for economic reasons and market uncertainty. Development of primaquine has been contracted but it will run into the same difficulty. Manufacturing capacity for sulfadoxine was registred in the SDI by Roche. A project to produce artemisinine and its derivates is under way at UNICAMP-CPQBA but is hampered by low content in the plant. Proguanil could be produced easily, but apparently no attempt has been made to do so. Quinine is imported on a large scale mostly for softdrink production. Since malarial treatment falls largely within responsability of the Government health authorities, manufacture of drugs in Brazil will depend on an assured medium-term purchase order made to a potential local manufacturer, since competition in the world market is scarcelyviable at the present moment.

Toxoplasmic encephalitis in an HIV infected pregnant woman: successful outcome for both mother and child

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Susie Andries Nogueira

Full Text Available This report describes a case of Toxoplasma encephalitis during pregnancy of an HIV infected woman who was severely immunosuppressed (CD4: 17 cells/mm3, had a high viral load (RNA PCR:230,000 copies/ml, was treated with sulfadiazine, pyrimethamine and folinic acid for toxoplasmosis and was being treated with highly potent antiretroviral drugs (AZT, 3TC and nelfinavir for HIV infection. The newborn was born through an elective C-section, received six weeks of AZT according to the 076 protocol and was clinically normal at birth. Subsequently he had two RNA PCR negatives for HIV, seroreverted and had no clinical or laboratory evidence of congenital toxoplasmosis. Despite the concerns of the use of these combined therapies on the foetus during pregnancy, their efficacy illustrates that keeping the mother alive and in good health is an important strategy to protect the unborn child from acquiring these two infections.

A non-inferiority, individually randomized trial of intermittent screening and treatment versus intermittent preventive treatment in the control of malaria in pregnancy

DEFF Research Database (Denmark)

Tagbor, Harry; Cairns, Matthew; Bojang, Kalifa

2015-01-01

BACKGROUND: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women...... with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups. CONCLUSIONS: Despite low levels of resistance to SP in the study areas, ISTp......-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women...

Plasmodium falciparum malaria in pregnancy: prevalence of peripheral parasitaemia, anaemia and malaria care-seeking behaviour among pregnant women attending two antenatal clinics in Edo State, Nigeria.

Science.gov (United States)

Enato, E F O; Mens, P F; Okhamafe, A O; Okpere, E E; Pogoson, E; Schallig, H D F H

2009-05-01

This study evaluated malaria care-seeking behaviour, as well as the prevalence of parasitaemia and anaemia among pregnant women attending antenatal clinics of two tertiary healthcare facilities in Edo State, Nigeria. Malaria was highly prevalent in the study group (20% by microscopy and estimated 25% by PCR), but parasitaemia and incidence decreased with increasing number of pregnancies. Although the level of education of the study participants was relatively high, antimalarial control measures during pregnancy were found to be poorly utilised by the women and malaria care-seeking was often delayed. A minority of the interviewed pregnant women said they had received sulphadoxine/pyrimethamine-based intermittent preventive therapy (IPT) during current pregnancy. Moreover, the use of inferior antimalaria treatment (e.g. chloroquine) was frequent. The majority of the pregnant women, mainly primigravidae, were anaemic. Efforts to improve antimalaria healthcare must be intensified, targeting pregnant women, particularly the primigravidae and secundigravidae and the healthcare providers.

The drug sensitivity and transmission dynamics of human malaria on Nias Island, North Sumatra, Indonesia.

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Fryauff, D J; Leksana, B; Masbar, S; Wiady, I; Sismadi, P; Susanti, A I; Nagesha, H S; Syafruddin; Atmosoedjono, S; Bangs, M J; Baird, J K

2002-07-01

Nias Island, off the north-western coast of Sumatra, Indonesia, was one of the first locations in which chloroquine-resistant Plasmodium vivax malaria was reported. This resistance is of particular concern because its ancient megalithic culture and the outstanding surfing conditions make the island a popular tourist destination. International travel to and from the island could rapidly spread chloroquine-resistant strains of P. vivax across the planet. The threat posed by such strains, locally and internationally, has led to the routine and periodic re-assessment of the efficacy of antimalarial drugs and transmission potential on the island. Active case detection identified malaria in 124 (17%) of 710 local residents whereas passive case detection, at the central health clinic, confirmed malaria in 77 (44%) of 173 cases of presumed 'clinical malaria'. Informed consenting volunteers who had malarial parasitaemias were treated, according to the Indonesian Ministry of Health's recommendations, with sulfadoxine-pyrimethamine (SP) on day 0 (for P. falciparum) or with chloroquine (CQ) on days 0, 1 and 2 (for P. vivax). Each volunteer was then monitored for clinical and parasite response until day 28. Recurrent parasitaemia by day 28 treatment was seen in 29 (83%) of the 35 P. falciparum cases given SP (14, 11 and four cases showing RI, RII and RIII resistance, respectively). Recurrent parasitaemia was also observed, between day 11 and day 21, in six (21%) of the 28 P. vivax cases given CQ. Although the results of quantitative analysis confirmed only low prevalences of CQ-resistant P. vivax malaria, the prevalence of SP resistance among the P. falciparum cases was among the highest seen in Indonesia. When the parasites present in the volunteers with P. falciparum infections were genotyped, mutations associated with pyrimethamine resistance were found at high frequency in the dhfr gene but there was no evidence of selection for sulfadoxine resistance in the dhps gene

Cost-effectiveness of two versus three or more doses of intermittent preventive treatment for malaria during pregnancy in sub-Saharan Africa: a modelling study of meta-analysis and cost data.

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Fernandes, Silke; Sicuri, Elisa; Kayentao, Kassoum; van Eijk, Anne Maria; Hill, Jenny; Webster, Jayne; Were, Vincent; Akazili, James; Madanitsa, Mwayi; ter Kuile, Feiko O; Hanson, Kara

2015-03-01

In 2012, WHO changed its recommendation for intermittent preventive treatment of malaria during pregnancy (IPTp) from two doses to monthly doses of sulfadoxine-pyrimethamine during the second and third trimesters, but noted the importance of a cost-effectiveness analysis to lend support to the decision of policy makers. We therefore estimated the incremental cost-effectiveness of IPTp with three or more (IPTp-SP3+) versus two doses of sulfadoxine-pyrimethamine (IPTp-SP2). For this analysis, we used data from a 2013 meta-analysis of seven studies in sub-Saharan Africa. We developed a decision tree model with a lifetime horizon. We analysed the base case from a societal perspective. We did deterministic and probabilistic sensitivity analyses with appropriate parameter ranges and distributions for settings with low, moderate, and high background risk of low birthweight, and did a separate analysis for HIV-negative women. Parameters in the model were obtained for all countries included in the original meta-analysis. We did simulations in hypothetical cohorts of 1000 pregnant women receiving either IPTp-SP3+ or IPTp-SP2. We calculated disability-adjusted life-years (DALYs) for low birthweight, severe to moderate anaemia, and clinical malaria. We calculated cost estimates from data obtained in observational studies, exit surveys, and from public procurement databases. We give financial and economic costs in constant 2012 US$. The main outcome measure was the incremental cost per DALY averted. The delivery of IPTp-SP3+ to 1000 pregnant women averted 113·4 DALYs at an incremental cost of $825·67 producing an incremental cost-effectiveness ratio (ICER) of $7·28 per DALY averted. The results remained robust in the deterministic sensitivity analysis. In the probabilistic sensitivity analyses, the ICER was $7·7 per DALY averted for moderate risk of low birthweight, $19·4 per DALY averted for low risk, and $4·0 per DALY averted for high risk. The ICER for HIV

Selection of antimalarial drug resistance after intermittent preventive treatment of infants and children (IPTi/c) in Senegal.

Science.gov (United States)

Ndiaye, Magatte; Tine, Roger; Faye, Babacar; Ndiaye, Jean L; Diouf, Ibrahima; Lo, Aminata C; Sylla, Khadime; Dieng, Yemou; Hallett, Rachel; Alifrangis, Michael; Gaye, Oumar

2013-01-01

Senegal has since 2003 used sulphadoxine-pyrimethamine (SP) for Intermittent Preventive Treatment (IPT) of malaria in risk groups. However, the large-scale IPT strategy may result in increasing drug resistance. Our study investigated the possible impact of SP-IPT given to infants and children on the prevalence of SP-resistant haplotypes in the Plasmodium falciparum genes Pfdhfr and Pfdhps, comparing sites with and without IPTi/c. P. falciparum positives samples (n=352) were collected from children under 5years of age during two cross-sectional surveys in 2010 and 2011 in three health districts (two on IPTi/c and one without IPTi/c intervention) located in the southern part of Senegal. The prevalence of SP-resistance-related haplotypes in Pfdhfr and Pfdhps was determined by nested PCR followed by sequence-specific oligonucleotide probe (SSOP)-ELISA. The prevalence of the Pfdhfr double mutant haplotypes (CNRN and CICN) was stable between years atSenegal according to WHO recommendations. Copyright © 2013 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Strengthening of national capacity in implementation of antimalarial drug quality assurance in Thailand.

Science.gov (United States)

Vijaykadga, Saowanit; Cholpol, Sawat; Sitthimongkol, Saipin; Pawaphutanan, Anusorn; Pinyoratanachot, Arunya; Rojanawatsirivet, Chaiporn; Kovithvattanapong, Rojana; Thimasarn, Krongthong

2006-01-01

Substandard and counterfeit pharmaceutical products, including antimalarial drugs, appear to be widespread internationally and affect both the developing and developed countries. The aim of the study was to investigate the quality of antimalarial drugs, ie, artesunate (ART), chloroquine (CHL), mefloquine (MEF), quinine (QUI), sulfadoxine/pyrimethamine (S/P) and tetracycline (TT) obtained from the government sector and private pharmacies in 4 Thai provinces: Mae Hong Son, Kanchanaburi, Ranong, and Chanthaburi. Three hundred sixty-nine samples of 6 antimalarial drugs from 27 government hospitals, 27 malaria clinics, and 53 drugstores, were collected. Drug quality was assessed by simple disintegration test and semi-quantitative thin-layer chromatography in each province; 10% passed, 100% failed and doubtful samples were sent to be verified by high performance liquid chromatography (HPLC) at the Thai National Drug Analysis Laboratory, (NL). Fifteen point four percent of ART, 11.1% of CHL and 29.4% of QUI were substandard. Based on the finding, drug regulatory authorities in the country took appropriate action against violators to ensure that antimalarial drugs consumed by malaria patients are of good quality.

Role of advanced magnetic resonance imaging techniques in diagnosis of cerebral toxoplasmosis in immunocompromised patients: A case report

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Inderpreet Singh

2014-01-01

Full Text Available Cerebral toxoplasmosis commonly affects patients with advanced HIV infection. Toxoplasmosis can be severe and debilitating in patients with Central Nervous System (CNS involvement and the condition may be fatal in patients if not suspected and treated early and adequately. Hence, imaging plays an important role in diagnosis and following during treatment in cases of suspected toxoplasmosis. We report a case of a 51-years-old man who was a known sero-positive since 2 years and presented with altered sensorium. Magnetic Resonance Imaging (MRI scan of the brain showed multiple heterogeneously enhancing lesions in bilateral cerebral as well as cerebellar hemispheres and some of them showed "eccentric target sign." MR spectroscopy showed features of reduced NAA, mildly increased choline, and lipid lactate peak. MR perfusion study showed reduced perfusion favoring diagnosis of cerebellar toxoplasmosis. Patient was started on a combination of pyrimethamine plus sulfadiazine for toxoplasmosis. Follow up MRI after 20 days and 45 days from start of treatment showed significant resolution of the lesions supporting our radiological diagnosis.

Inhibition of Plasmodium falciparum proliferation in vitro by double-stranded RNA directed against malaria histone deacetylase

International Nuclear Information System (INIS)

Sriwilaijaroen, N.; Boonma, S.; Attasart, P.; Pothikasikorn, J.; Panyim, S.; Noonpakdee, W.

2009-01-01

Acetylation and deacetylation of histones play important roles in transcription regulation, cell cycle progression and development events. The steady state status of histone acetylation is controlled by a dynamic equilibrium between competing histone acetylase and deacetylase (HDAC). We have used long PfHDAC-1 double-stranded (ds)RNA to interfere with its cognate mRNA expression and determined the effect on malaria parasite growth and development. Chloroquine- and pyrimethamine-resistant Plasmodium falciparum K1 strain was exposed to 1-25 μg of dsRNA/ml of culture for 48 h and growth was determined by [ 3 H]-hypoxanthine incorporation and microscopic examination. Parasite culture treated with 10 μg/ml pfHDAC-1 dsRNA exhibited 47% growth inhibition when compared with either untreated control or culture treated with an unrelated dsRNA. PfHDAC-1 dsRNA specifically blocked maturation of trophozoite to schizont stages and decreased PfHDAC-1 transcript 44% in treated trophozoites. These results indicate the potential of HDAC-1 as a target for development of novel antimalarials.

[Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention].

Science.gov (United States)

Wallon, Martine; Kieffer, François; Binquet, Christine; Thulliez, Philippe; Garcia-Méric, Patricia; Dureau, Pascal; Franck, Jacqueline; Peyron, François; Bonnin, Alain; Villena, Isabelle; Bonithon-Kopp, Claire; Gouyon, Jean-Bernard; Masson, Sandrine; Félin, Alexandrin; Cornu, Catherine

2011-01-01

In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children. © 2011 Société Française de Pharmacologie et de Thérapeutique.

Population Genetics and Drug Resistance Markers: An Essential for Malaria Surveillance in Pakistan

International Nuclear Information System (INIS)

Raza, A.; Beg, M.A.

2013-01-01

Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control. (author)

Formulation, process development and evaluation of artemether and lumefantrine soft gelatin capsule

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A Patel

2012-01-01

Full Text Available Artemether and Lumefantrine capsules are indicated for the treatment of P. falciparum malaria cases resistant to both chloroquine and sulphadoxine, pyrimethamine combination. Both artemether and lumefantrine act as blood schizontocides. Artemether is a sesquiterpene lactone derived from artemisinin. Artemisinin is a compound derived from the sweet wormwood plant and has been used for centuries in traditional Chinese medicine to treat fever. Lumefantrine is a synthetic aryl-amino alcohol antimalarial (quinine, mefloquine and halofantrine are members of the same group. Artemether is absorbed fairly rapidly with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag period of up to 2 hours, with peak plasma concentration about 6-8 hours after dosing. In order to overcome this problem, we have observed that when the drug is given in the soft gelatin dosage form, the bioavailability of the drug is increased. Thus, increasing the absorption of the drug and peak plasma concentration is reached earlier then the conventional dosage form.

Potential Impact of Seasonal Malaria Chemoprevention on the Acquisition of Antibodies Against Glutamate-Rich Protein and Apical Membrane Antigen 1 in Children Living in Southern Senegal

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Ndiaye, Magatte; Sylla, Khadime; Sow, Doudou

2015-01-01

Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine-pyrimetham......Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine......-pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this......, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC...

Azithromycin-chloroquine and the intermittent preventive treatment of malaria in pregnancy

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Greenwood Brian

2008-12-01

Full Text Available Abstract In the high malaria-transmission settings of sub-Saharan Africa, malaria in pregnancy is an important cause of maternal, perinatal and neonatal morbidity. Intermittent preventive treatment of malaria in pregnancy (IPTp with sulphadoxine-pyrimethamine (SP reduces the incidence of low birth-weight, pre-term delivery, intrauterine growth-retardation and maternal anaemia. However, the public health benefits of IPTp are declining due to SP resistance. The combination of azithromycin and chloroquine is a potential alternative to SP for IPTp. This review summarizes key in vitro and in vivo evidence of azithromycin and chloroquine activity against Plasmodium falciparum and Plasmodium vivax, as well as the anticipated secondary benefits that may result from their combined use in IPTp, including the cure and prevention of many sexually transmitted diseases. Drug costs and the necessity for external financing are discussed along with a range of issues related to drug resistance and surveillance. Several scientific and programmatic questions of interest to policymakers and programme managers are also presented that would need to be addressed before azithromycin-chloroquine could be adopted for use in IPTp.

Within-host selection of drug resistance in a mouse model of repeated incomplete malaria treatment : Comparison between atovaquone and pyrimethamine

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Nuralitha, Suci; Siregar, Josephine E.; Syafruddin, Din; Roelands, Jessica; Verhoef, Jan; Hoepelman, Andy I M; Marzuki, Sangkot

2016-01-01

The evolutionary selection of malaria parasites within individual hosts is an important factor in the emergence of drug resistance but is still not well understood. We have examined the selection process for drug resistance in the mouse malaria agent Plasmodium berghei and compared the dynamics of

Effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy: a systematic review

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ter Kuile, Feiko O.; van Eijk, Annemieke M.; Filler, Scott J.

2007-01-01

In malaria-endemic regions, strategies to control malaria during pregnancy rely on case management of malaria illness and anemia, and preventive measures such as insecticide-treated nets and intermittent preventive therapy (IPT). To determine the effect of increasing resistance to

Molecular genetic transfection of the coccidian parasite Sarcocystis neurona.

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Gaji, Rajshekhar Y; Zhang, Deqing; Breathnach, Cormac C; Vaishnava, Shipra; Striepen, Boris; Howe, Daniel K

2006-11-01

Sarcocystis neurona is an apicomplexan parasite that is the major cause of equine protozoal myeloencephalitis (EPM). The biology of this pathogen remains poorly understood in part due to unavailability of molecular genetic tools. Hence, with an objective to develop DNA transfection capabilities for S. neurona, the 5' flanking region of the SnSAG1 gene was isolated from a genomic library and used to construct expression plasmids. In transient assays, the reporter molecules beta-galactosidase (beta-gal) and yellow fluorescent protein (YFP) could be detected in electroporated S. neurona, thereby confirming the feasibility of transgene expression in this organism. Stable transformation of S. neurona was achieved using a mutant dihydrofolate reductase thymidylate synthase (DHFR-TS) gene of Toxoplasma gondii that confers resistance to pyrimethamine. This selection system was used to create transgenic S. neurona that stably express beta-gal and YFP. As shown in this study, these transgenic clones can be useful for analyzing growth rate of parasites in vitro and for assessing drug sensitivities. More importantly, the DNA transfection methods described herein should greatly facilitate studies examining intracellular parasitism by this important coccidian pathogen.

Simultaneous measurement of proguanil and its metabolites in human plasma and urine by reversed-phase high-performance liquid chromatography, and its preliminary application in relation to genetically determined S-mephenytoin 4'-hydroxylation status.

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Kusaka, M; Setiabudy, R; Chiba, K; Ishizaki, T

1996-02-01

A simple high-performance liquid chromatographic (HPLC) assay method was developed for the measurement of proguanil (PG) and its major metabolites, cycloguanil (CG) and 4-chlorophenyl-biguanide (CPB), in human plasma and urine. The assay allowed the simultaneous determination of all analytes in 1 ml of plasma or 0.1 ml of urine. The detection limits of PG, CG, and CPB, defined as the signal-to-noise ratio of 3, were 1 and 5 ng/ml for plasma and urine samples, respectively. Recoveries of the analytes and the internal standard (pyrimethamine) were > 62% from plasma and > 77% from urine. Intra-assay and interassay coefficients of variation for all analytes in plasma and urine were CG and CPB, which ranged from 10% to 15% at one or two concentrations among 4-5 concentrations studied. The clinical applicability of the method was assessed by the preliminary pharmacokinetic study of PG, CG, and CPB in six healthy volunteers with the individually known phenotypes (extensive and poor metabolizers) of S-mephenytoin 4'-hydroxylation, suggesting that individuals with a poor metabolizer phenotype of S-mephenytoin have a much lower capacity to bioactivate PG to CG compared with the extensive metabolizers.

Detection of Malaria parasite species based on 18S rRNA and assessment of its resistance to the drug for DHPS gene to support the development of irradiation Malaria vaccine

International Nuclear Information System (INIS)

Mukh Syaifudin; Darlina; Siti Nurhayati

2016-01-01

Malaria remains a major public health problem because it causes 1-2 million mortality per year. Therefore the development of its vaccine, including vaccine created by ionizing radiation, is urgently needed to control the disease. Aim of this research was to determine the species of malaria parasite infecting the blood of malaria suspected patients and its resistance to sulfadoxine-pyrimethamine (SP). The number of samples used were 10 blood specimens that obtained from Dok II Hospital in Jayapura. Microscopic examination on thin blood smear was done according to standard procedure, followed by Polymerase Chain Reaction (PCR) based diagnosis to further confirm the parasite using 18S rRNA gene on deoxyribonucleic acid extract. The presence of mutation in the dhps (dihydropteroate synthetase) gene related to SP drugs was examined using restriction fragment length polymorphism (RFLP) method. Results showed that 9 samples were infected with Plasmodium falciparum and 1 infected with P. vivax. Allelic mutants of dhps gene at codon K540E were detected in 3 (33.3%) samples. Even though only in very limited number of samples analyzed, the information obtained will be a great value in additional knowledge for vaccine development with irradiation. (author)

Resistance of Plamodium falciparum to Antimalarial Drugs in Zaragoza (Antioquia, Colombia, 1998

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Silvia Blair-Trujillo

2002-04-01

Full Text Available Plasmodium falciparum sensitivity to chloroquine (CHL, amodiaquine (AMO and sulfadoxine/pyrimethamine (SDX/PYR was assessed in vivo and in vitro in a representative sample from the population of Zaragoza in El Bajo Cauca region (Antioquia-Colombia. There were 94 patients with P. falciparum evaluated. For the in vivo test the patients were followed by clinical examination and microscopy, during 7 days. The in vitro test was performed following the recommendations of the World Health Organization. The in vivo prevalence of resistance to CHL was 67%, to AMO 3% and to SDX/PYR 9%. The in vitro test showed sensitivity to all antimalarials evaluated. Concordance for CHL between the in vivo and in vitro tests was 33%. For AMO and SDX/PYR, the concordance was 100%. We conclude that a high percentage of patients are resistant to CHL (in vivo. A high rate of intestinal parasitism might explain in part, the differences observed between the in vivo and the in vitro results. Therefore, new policies and treatment regimens should be proposed for the treatment of the infection in the region. Nationwide studies assessing the degree of resistance are needed.

Recurrent seizures during acute acquired toxoplasmosis in an immunocompetent traveller returning from Africa.

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Beltrame, Anna; Venturini, Sergio; Crichiutti, Giovanni; Meroni, Valeria; Buonfrate, Dora; Bassetti, Matteo

2016-04-01

We report an unusual case of acute acquired toxoplasmosis (AAT) presenting as lymphadenopathy and recurrent seizures in an immunocompetent 15-year-old boy. The patient reported an 18-day vacation to Africa (Ethiopia), 39 days prior to the first seizure. Electroencephalogram (EEG) showed sporadic single-spike or sharp-wave paroxysms and the magnetic resonance imaging (RMI) of the brain was negative. The serology for T. gondii was compatible with an acute infection defined as positive for both toxoplasma-specific IgG and IgM and a low avidity (6 %), confirmed by a reference laboratory. The patient reported other two episodes of seizures, occurring 7 days apart. He was treated with pyrimethamine plus sulfadiazine and leucovorin for 4 weeks, with an improvement of lymphadenitis and normalization of EEG. After 5 months, new seizures were reported and a diagnosis of epilepsy was done. Toxoplasma polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) and blood were negative. A treatment with valproic acid was started, obtaining control of the neurological disease. Awareness of this neurologic manifestation by clinicians is required, also in immunocompetent patients. The relationship between toxoplasmosis and recurrent seizure needs to be investigated by new studies.

High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

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Löscher Thomas

2006-07-01

Full Text Available Abstract Background In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP and chloroquine (CQ is frequent and intense in some areas. Methods In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assessed. Results P. falciparum and P. vivax were observed in 69% and 31% of the patients, respectively. Pfdhfr triple mutations and pfdhfr/pfdhps quintuple mutations occurred in 87% and 86% of P. falciparum isolates, respectively. Pfcrt T76 was seen in all and pfmdr1 Y86 in 81% of P. falciparum. The P. vivax dhfr core mutations N117 and R58 were present in 94% and 74%, respectively. Conclusion These data point to an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia, and strongly support that both SP and CQ are inadequate drugs for this region.

Evaluation of chloroquine as a potent anti-malarial drug: issues of public health policy and healthcare delivery in post-war Liberia.

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Massaquoi, Moses B F; Kennedy, Stephen B

2003-02-01

Chloroquine-resistant plasmodium falciparum malaria is a serious public health threat that is spreading rapidly across Sub-Saharan Africa. It affects over three quarters (80%) of malarial endemic countries. Of the estimated 300-500 million cases of malaria reported annually, the vast majority of malarial-related morbidities occur among young children in Africa, especially those concentrated in the remote rural areas with inadequate access to appropriate health care services. In Liberia, in vivo studies conducted between 1993 and 2000 observed varying degrees of plasmodium falciparum malaria infections that were resistant to chloroquine, including sulfadiazine-pyrimethamine. As the country emerges from a prolonged civil war, the health care delivery system may not be adequately prepared to implement an effective nation-wide malarial control strategy. As a result, the management of uncomplicated malaria in Liberia poses a significant public health challenge for the government-financed health care delivery system. Therefore, based on extensive literature review, we report the failure of chloroquine as an effective first-line drug for the treatment of uncomplicated plasmodium falciparum malaria in Liberia and recommend that national health efforts be directed at identifying alternative drug(s) to replace it.

Knowledge of malaria influences the use of insecticide treated nets but not intermittent presumptive treatment by pregnant women in Tanzania

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Nganda Rhoida Y

2004-11-01

Full Text Available Abstract Background To reduce the intolerable burden of malaria in pregnancy, the Ministry of Health in Tanzania has recently adopted a policy of intermittent presumptive treatment for pregnant women using sulphadoxine-pyrimethamine (IPTp-SP. In addition, there is strong national commitment to increase distribution of insecticide treated nets (ITNs among pregnant women. This study explores the determinants of uptake for both ITNs and IPTp-SP by pregnant women and the role that individual knowledge and socio-economic status has to play for each. Methods 293 women were recruited post-partum at Kibaha District Hospital on the East African coast. The haemoglobin level of each woman was measured and a questionnaire administered. Results Use of both interventions was associated with a reduced risk of severe anaemia (Hb Conclusion Individual knowledge of malaria was an important factor for ITN uptake, but not for IPTp-SP use, which was reliant on delivery of information by MCH systems. When both these interventions were used, severe anaemia postpartum was reduced by 69% compared to use of neither, thus providing evidence of effectiveness of these interventions when used in combination.

The end of a dogma: the safety of doxycycline use in young children for malaria treatment.

Science.gov (United States)

Gaillard, Tiphaine; Briolant, Sébastien; Madamet, Marylin; Pradines, Bruno

2017-04-13

Anti-malarial drug resistance to chloroquine and sulfadoxine-pyrimethamine has spread from Southeast Asia to Africa. Furthermore, the recent emergence of resistance to artemisinin-based combination therapy (ACT) in Southeast Asia highlights the need to identify new anti-malarial drugs. Doxycycline is recommended for malaria chemoprophylaxis for travel in endemic areas, or in combination with the use of quinine for malaria treatment when ACT is unavailable or when the treatment of severe malaria with artesunate fails. However, doxycycline is not used in young children under 8 years of age due to its contraindication due to the risk of yellow tooth discolouration and dental enamel hypoplasia. Doxycycline was developed after tetracycline and was labelled with the same side-effects as the earlier tetracyclines. However, recent studies report little or no effects of doxycycline on tooth staining or dental enamel hypoplasia in children under 8 years of age. In the United States, the Centers for Disease Control and Prevention have recommended the use of doxycycline for the treatment of acute and chronic Q fever and tick-borne rickettsial diseases in young children. It is time to rehabilitate doxycycline and to recommend it for malaria treatment in children under 8 years of age.

Prevalence and clinical manifestations of malaria in Aligarh, India.

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Asma, Umm-e; Taufiq, Farha; Khan, Wajihullah

2014-12-01

Malaria is one of the most widespread infectious diseases of tropical countries with an estimated 207 million cases globally. In India, there are endemic pockets of this disease, including Aligarh. Hundreds of Plasmodium falciparum and P. vivax cases with severe pathological conditions are recorded every year in this district. The aim of this study is to find out changes in liver enzymes and kidney markers. Specific diagnosis for P. falciparum and P. vivax was made by microscopic examination of Giemsa stained slides. Clinical symptoms were observed in both of these infections. Liver enzymes, such as AST, ALT, and ALP, and kidney function markers, such as creatinine and urea, were estimated by standard biochemical techniques. In Aligarh district, P. vivax, P. falciparum, and mixed infections were 64%, 34%, and 2%, respectively. In case of P. falciparum infection, the incidences of anemia, splenomegaly, renal failure, jaundice, and neurological sequelae were higher compared to those in P. vivax infection. Recrudescence and relapse rates were 18% and 20% in P. falciparum and P. vivax infections, respectively. Liver dysfunctions and renal failures were more common in P. falciparum patients, particularly in elderly patients. Artesunate derivatives must, therefore, be introduced for the treatment of P. falciparum as they resist to chloroquine as well as sulfadoxine-pyrimethamine combinations.

Comparison of mosquito nets, proguanil hydrochloride, and placebo to prevent malaria.

Science.gov (United States)

Nevill, C G; Watkins, W M; Carter, J Y; Munafu, C G

1988-08-06

One hundred and ninety students aged 6 to 18 at a boarding school 120 km west of Nairobi in the Rift Valley participated in a comparative trial of malaria prophylaxis. Treatment with a combination of amodiaquine 25 mg/kg over three days plus doxycycline 100 mg twice daily for five days cleared their blood of Plasmodium falciparum. They were then randomly divided into the following three groups matched for age and sex: one group slept under mosquito nets; one group received one or two tablets (100 mg each) of proguanil hydrochloride daily according to weight; one group received one or two placebo tablets daily which were the same size and colour as the proguanil tablets. Malaria was diagnosed when asexual P falciparum were seen on blood films and was treated with pyrimethamine-sulphadoxine. At the end of one school term 188 of the 190 students had completed the study. One new infection was found during 3893 days of follow up in the mosquito net group, eight new infections over 3667 days in the proguanil group, and 35 new infections over 3677 days in the placebo group, representing a reduction of 97.3% and 77.1% in attack rates for the mosquito net method and for treatment with proguanil respectively. Both provide effective protection from malaria.

Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola

Science.gov (United States)

2011-01-01

Background Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola. Methods Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes. Results The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples). Conclusion This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola. PMID:21864379

An evaluation of the use of reported febrile illness in predicting malaria in pregnancy.

Science.gov (United States)

Nnaji, G A; Ikechebelu, J I

2007-11-01

The object of this study was to evaluate the sensitivity and specificity of reported febrile illness in predicting malaria in pregnant women at booking in NAUTH, Nnewi. This was a case control prospective survey using a structured questionnaire to collect data from pregnant women attending antenatal clinic of Nnamdi Azikiwe University Teaching Hospital between April and September 2001. Peripheral blood smears were examined in 420 pregnant women during their first antenatal visit. This study showed that 57.4% of parasitaemic pregnant women and 54% of aparasitaemic pregnant women reported fever before their first antenatal visit. The sensitivity and specificity of reported febrile illness in predicting malaria were 57.4% and 46%, respectively. However, the predictive value of a positive test was as high as 80.25%, while it was only 22% for the predictive value of a negative test. The efficiency of reported febrile illness as a screening device was 55%. Reliance on reported febrile illness will not be adequate to identify parasitaemic pregnant women because many of those with heavy placental parasitisation may not report fever. This justifies the place of the intermittent presumptive therapy using sulphadoxine-pyrimethamine in pregnant women living in malaria endemic areas such as sub-Saharan Africa.

Coinfection with Schistosoma haematobium and Plasmodium falciparum and Anaemia Severity among Pregnant Women in Munyenge, Mount Cameroon Area: A Cross-Sectional Study

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Judith K. Anchang-Kimbi

2017-01-01

Full Text Available Background. Malaria and urogenital schistosomiasis are coendemic in Mount Cameroon Area. This study investigated the prevalence of S. haematobium, P. falciparum, and coinfections and their effect on anaemia in pregnancy. Methods. Pregnant women reporting for antenatal care (ANC clinic visit in Munyenge were enrolled. S. haematobium and P. falciparum infections were determined by urine filtration and microscopy, respectively. Haemoglobin (Hb levels were measured using haemoglobinometer. Of 250 women, 46.8%, 39.2%, and 15.2% had S. haematobium, P. falciparum, and coinfections, respectively. Schistosomes infection was higher in younger women (≤25 years and those who bathe in and had domestic contact with stream compared with older age (>25 years women and those who had only domestic contact with stream. Lower infection rate was associated with less water contact (≤2 times/day compared with more water contact (>2 times/day. Compared with no sulphadoxine-pyrimethamine (SP usage, malaria parasitaemia was less among women who used SP. Stream usage increased risk of coinfection while less water contact and SP usage decreased its risk. All coinfected cases were anaemic and coinfection accounted for 93.8% of severe anaemia. Conclusion. Coinfection contributes to anaemia severity. Less water contact and SP usage will reduce coinfection in pregnancy in Munyenge.

Decrease of microscopic Plasmodium falciparum infection prevalence during pregnancy following IPTp-SP implementation in urban cities of Gabon.

Science.gov (United States)

Bouyou-Akotet, M K; Mawili-Mboumba, D P; Kendjo, E; Moutandou Chiesa, S; Tshibola Mbuyi, M L; Tsoumbou-Bakana, G; Zong, J; Ambounda, N; Kombila, M

2016-06-01

Six years after the implementation of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) in Gabon, its impact on placental malaria and pregnancy outcomes remains unknown. Age, gestational data, use of IPTp-SP and birth weight were recorded during a hospital-based cross-sectional survey performed in 2011 in 387 women at the end of pregnancy. Malaria prevalence was 6.7 and 5.3% in peripheral and placental blood respectively. Overall, 59.0% women took at least two IPTp-SP doses which was associated with 50% reduction of Plasmodium; (P.) falciparum infection in primigravidae. Previous malaria treatment was a risk factor for peripheral P. falciparum infection, while uptake of IPTp-SP was associated with reduced parasitaemia. Anaemia prevalence was 38.0%, low birth weight and prematurity rates were 6.0 and 12.0% respectively. Young age was associated with a higher frequency of malaria, anaemia, low birth weight and preterm delivery (pprevalence during pregnancy significantly declined between 2005 and 2011, following IPTp-SP implementation in Gabon. Young women and paucigravidae remain the most susceptible to malaria and associated outcomes. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

DEFF Research Database (Denmark)

Diarra, Amidou; Nebie, Issa; Tiono, Alfred

2012-01-01

ABSTRACT: BACKGROUND: Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment...... of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. METHODS: Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child...... to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. RESULTS: IgG levels to MSP3 were always higher in the successfully treated...

Community-based distribution of sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria during pregnancy improved coverage but reduced antenatal attendance in southern Malawi

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Msyamboza, K. P.; Savage, E. J.; Kazembe, P. N.; Gies, S.; Kalanda, G.; D'Alessandro, U.; Brabin, B. J.

2009-01-01

To evaluate the impact of a 2-year programme for community-based delivery of sulfadoxine-pyremethamine (SP) on intermittent preventive treatment during pregnancy coverage, antenatal clinic attendance and pregnancy outcome. Fourteen intervention and 12 control villages in the catchment areas of

Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

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Diarra Amidou

2012-03-01

Full Text Available Abstract Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

Impact of Sulfadoxine-Pyrimethamine resistance on effectiveness of intermittent preventive therapy for malaria in pregnancy at clearing infections and preventing low birth weight

DEFF Research Database (Denmark)

Desai, Meghna; Gutman, Julie; Taylor, Steve M.

2016-01-01

, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control...... malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance...

Quinine Treatment Selects the pfnhe–1 ms4760–1 Polymorphism in Malian Patients with Falciparum Malaria

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Kone, Aminatou; Mu, Jianbing; Maiga, Hamma; Beavogui, Abdoul H.; Yattara, Omar; Sagara, Issaka; Tekete, Mamadou M.; Traore, Oumar B.; Dara, Antoine; Dama, Souleymane; Diallo, Nouhoum; Kodio, Aly; Traoré, Aliou; Björkman, Anders; Gil, Jose P.; Doumbo, Ogobara K.; Wellems, Thomas E.; Djimde, Abdoulaye A.

2013-01-01

Background. The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium–hydrogen exchanger (pfnhe–1) on chromosome 13. Methods. We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe–1 ms4760–1 among parasites before versus after quinine treatment was determined by direct sequencing. Results. Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760–1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine–pyrimethamine study, the prevalence of ms4760–1 was similar before and after treatment. Conclusions. This study supports a role for pfnhe–1 in decreased susceptibility of P. falciparum to quinine in the field. PMID:23162138

In silico analyses of essential interactions of iminosugars with the Hex A active site and evaluation of their pharmacological chaperone effects for Tay-Sachs disease.

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Kato, Atsushi; Nakagome, Izumi; Nakagawa, Shinpei; Kinami, Kyoko; Adachi, Isao; Jenkinson, Sarah F; Désiré, Jérôme; Blériot, Yves; Nash, Robert J; Fleet, George W J; Hirono, Shuichi

2017-11-15

The affinity of a series of iminosugar-based inhibitors exhibiting various ring sizes toward Hex A and their essential interactions with the enzyme active site were investigated. All the Hex A-inhibiting iminosugars tested formed hydrogen bonds with Arg178, Asp322, Tyr421 and Glu462 and had the favorable cation-π interaction with Trp460. Among them, DMDP amide (6) proved to be the most potent competitive inhibitor with a K i value of 0.041 μM. We analyzed the dynamic properties of both DMDP amide (6) and DNJNAc (1) in aqueous solution using molecular dynamics (MD) calculations; the distance of the interaction between Asp322 and 3-OH and Glu323 and 6-OH was important for stable interactions with Hex A, reducing fluctuations in the plasticity of the active site. DMDP amide (6) dose-dependently increased intracellular Hex A activity in the G269S mutant cells and restored Hex A activity up to approximately 43% of the wild type level; this effect clearly exceeded the border line treatment for Tay-Sachs disease, which is regarded as 10-15% of the wild type level. This is a significantly greater effect than that of pyrimethamine, which is currently in Phase 2 clinical trials. DMDP amide (6), therefore, represents a new promising pharmacological chaperone candidate for the treatment of Tay-Sachs disease.

Clinical and hematological presentation of children and adolescents with polycythemia vera

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McMullin, Mary Frances; Pahl, Heike L.

2014-01-01

Polycythemia vera (PV) in children and adolescents is very rare. Data on clinical and laboratory evaluations as well as on treatment modalities are sparse. Here, we report the long-term clinical course of a PV patient first diagnosed more than 40 years ago at age 12. In addition, after a systematic review of the scientific medical literature, clinical and hematological data of 35 patients (19 female and 17 male) from 25 previous reports are summarized. Three patients developed PV following antecedent hematological malignancies. Budd–Chiari syndrome was diagnosed in seven patients indicating a particular risk of young patients of developing this disorder. One patient presented with ischemic stroke, one patient with gangrene, and three patients with severe hemorrhage. Three patients died from disease-related complications. Hematocrit levels and platelet counts were not correlated with disease severity. Leukocytosis >15×109/L was present in 9/35 patients and associated with a thromboembolic or hemorrhagic complication in seven patients. The few available data on molecular genetics and endogenous erythroid colony growth indicate changes comparable to those detectable in adult patients. Treatment varied enormously. It included aspirin, phlebotomy, hydroxycarbamide, busulfan, melphalan, pyrimethamine, and interferon-alpha. Two patients successfully underwent stem cell transplantation. Currently, it is impossible to treat an individual pediatric PV patient with an evidence-based regimen. PMID:19468728

Ocular toxoplasmosis II: clinical features, pathology and management

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Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

2014-01-01

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. PMID:22712598

[Retrospective study of the implementation of the qualitative PCR technique in biological samples for monitoring toxoplasmosis in pediatric patients receiving hematopoietic stem cell transplantation].

Science.gov (United States)

Nigro, Mónica G; Figueroa, Carlos; Ledesma, Bibiana A

2014-01-01

Toxoplasmosis is an opportunistic infection caused by the parasite Toxoplasma gondii. The infection is severe and difficult to diagnose in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twelve patients receiving HSCT were monitored post-transplant, by qualitative PCR at the Children's Hospital S.A.M.I.C. "Prof. Dr. Juan P. Garrahan". The monitoring of these patients was defined by a history of positive serology for toxoplasmosis in the donor or recipient and because their hematologic condition did not allow the use of trimethoprim-sulfamethoxazole for prophylaxis. During the patients' monitoring, two of them with positive PCR results showed signs of illness by T. gondii and were treated with pyrimethamine-clindamycin. In two other patients, toxoplasmosis was the cause of death and an autopsy finding, showing negative PCR results. Four patients without clinical manifestations received treatment for toxoplasmosis because of positive PCR detection. In four patients there were no signs of toxoplasmosis disease and negative PCR results during follow-up. The qualitative PCR technique proved useful for the detection of toxoplasmosis reactivation in HSCT recipients, but has limitations in monitoring and making clinical decisions due to the persistence of positive PCR over time and manifestations of toxicity caused by the treatment. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España. All rights reserved.

Factors influencing dropout rate of intermittent preventive treatment of malaria during pregnancy.

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Doku, David Teye; Zankawah, Mumuni Mukaila; Adu-Gyamfi, Addae Boateng

2016-10-10

The burden of malaria in terms of morbidity and mortality is huge is Sub-Saharan Africa, particularly among pregnant women. Among the measures to curb down this burden include intermittent preventive treatment (IPT) and effective case management. These strategies were adopted by Ghana and implemented since 2003; however, there is still high dropout rate in IPT coverage. This study sought to investigate factors contributing to high dropout rate between IPT1 and IPT3 in the Tamale Metropolis, one of the health facilities with the highest IPT dropout rates in Ghana. Survey, in-depth interviews and short ethnographic techniques were conducted among pregnant women, antenatal care (ANC) health workers and heads of health facilities to investigate factors which account for dropout rate of intermittent treatment of malaria. Shortage of sulphadoxine pyrimethamine (SP), inadequate supply of portable water for administration of SP, unavailability of IPT during outreach services, lack of knowledge by ANC staff about the dropout rate in their area of jurisdiction and poor attitude of some health workers were identified as barriers to achieving high IPT3 coverage. Late ANC visit, provider and logistical barriers account for the women's missed opportunities to prevent malaria in pregnancy through IPT. Addressing the above barriers will contribute to saving lives and ensuring progress towards the goal of combating malaria as well as reducing maternal, neonatal and child mortalities.

A country on the verge of malaria elimination--the Kingdom of Saudi Arabia.

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Michael Coleman

Full Text Available Significant headway has been made in the global fight against malaria in the past decade and as more countries enter the elimination phase, attention is now focused on identifying effective strategies to shrink the malaria map. Saudi Arabia experienced an outbreak of malaria in 1998, but is now on the brink of malaria elimination, with just 82 autochthonous cases reported in 2012. A review of published and grey literature was performed to identify the control strategies that have contributed to this achievement. The number of autochthonous malaria cases in Saudi Arabia decreased by 99.8% between 1998 and 2012. The initial steep decline in malaria cases coincided with a rapid scaling up of vector control measures. Incidence continued to be reported at low levels (between 0.01 and 0.1 per 1,000 of the population until the adoption of artesunate plus sulfadoxine-pyrimethamine as first line treatment and the establishment of a regional partnership for a malaria-free Arabian Peninsula, both of which occurred in 2007. Since 2007, incidence has decreased by nearly an order of magnitude. Malaria incidence is now very low, but a high proportion of imported cases, continued potential for autochthonous transmission, and an increased proportion of cases attributable to Plasmodium vivax all present challenges to Saudi Arabia as they work toward elimination by 2015.

Prevalence of Low Birth Weight before and after Policy Change to IPTp-SP in Two Selected Hospitals in Southern Nigeria: Eleven-Year Retrospective Analyses

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Nneka U. Igboeli

2018-01-01

Full Text Available Background. In 2005, Nigeria changed its policy on prevention of malaria in pregnancy to intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP. Indicators of impact of effective prevention and control of malaria on pregnancy (MIP are low birth weight (LBW and maternal anaemia by parity. This study determined the prevalence of LBW for different gravidity groups during periods of pre- and postpolicy change to IPTp-SP. Methods. Eleven-year data were abstracted from the delivery registers of two hospitals. Study outcomes calculated for both pre- (2000–2004 and post-IPTp-SP-policy (2005–2010 years were prevalence of LBW for different gravidity groups and risk of LBW in primigravidae compared to multigravidae. Results. Out of the 11,496 singleton deliveries recorded within the 11-year period, the prevalence of LBW was significantly higher in primigravidae than in multigravidae for both prepolicy (6.3% versus 4% and postpolicy (8.6% versus 5.1% years. The risk of LBW in primigravidae compared to multigravidae increased from 1.62 (1.17–2.23 in the prepolicy years to 1.74 (1.436–2.13 during the postpolicy years. Conclusion. The study demonstrated that both the prevalence and risk of LBW remained significantly higher in primigravidae even after the change in policy to IPTp-SP.

Burden of Placental Malaria among Pregnant Women Who Use or Do Not Use Intermittent Preventive Treatment at Mulago Hospital, Kampala

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Charles Okot Odongo

2016-01-01

Full Text Available Intermittent preventive treatment of malaria in pregnancy with sulphadoxine-pyrimethamine (SP-IPTp is widely used to reduce the incidence of adverse pregnancy outcomes. As a monitor for continued effectiveness of this intervention amidst SP resistance, we aimed to assess malaria burden among pregnant women who use or do not use SP-IPTp. In a descriptive cohort study at Mulago Hospital, Kampala, 87 women who received two supervised doses of SP-IPTp were followed up until delivery. Controls were pregnant women presenting in early labour without history of SP-IPTp. Histopathological investigation for placental malaria (PM was performed using the Bulmer classification criterion. Thirty-eight of the 87 women returned for delivery and 33 placentas were successfully collected and processed along with 33 placentas from SP nonusers. Overall, 12% (4/33 of the users had evidence of PM compared to 48% (16/33 of nonusers. Among nonusers, 17/33, 8/33, 2/33, and 6/33 had no placental infection, active infection, active-chronic infection, and past-chronic infection, respectively. Among users, respective proportions were 29/33, 2/33, 0/33, and 2/33. No difference in birth weights was apparent between the two groups, probably due to a higher proportion of infections occurring later in pregnancy. Histological evidence here suggests that SP continues to offer substantial benefit as IPTp.

Morphologic and molecular study of hemoparasites in wild corvids and evidence of sequence identity with Plasmodium DNA detected in captive black-footed penguins (Spheniscus demersus).

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Leclerc, Antoine; Chavatte, Jean-Marc; Landau, Irène; Snounou, Georges; Petit, Thierry

2014-09-01

A morphologic and molecular epidemiologic investigation was conducted on a captive African black-footed penguin (Spheniscus demersus) colony with a history of Plasmodium infections at La Palmyre Zoo (France). Each penguin received 12.5 mg of pyrimethamine twice a week as a prophylaxis every year from April to November. Although Plasmodium parasites were not detected in blood smears and tissues collected from the penguins, various blood parasites were recorded in blood smears from wild Eurasian magpies (Pica pica) and carrion crows (Corvus corone) sampled at the same time in the study area. These parasites consisted of several Plasmodium spp. (P. lenoblei, P. dorsti, P bioccai, P. relictum, P. dherteae, P. beaucournui, P. maior, P. tranieri, and P. snounoui), Parahaemoproteus spp., Trypanosoma spp., and Leucocytozoon spp. On the other hand, nested polymerase chain reaction enabled detection of Plasmodium DNA in 28/44 (64%) penguins, 15/25 (60%) magpies, and 4/9 (44%) crows. Sequencing and phylogenetic analyses indicated that the parasite DNA amplified from the penguins, magpies, and crows were similar. Magpies and crows could therefore act as a reservoir for penguin Plasmodium infections, which may be more prevalent than previously thought. Morphologic characterization of the Plasmodium spp. detected in the penguins, as well as further biological and epidemiologic studies, are needed to fully understand the transmission of Plasmodium parasites to captive penguins.

Effects of Extracts from Thai Piperaceae Plants against Infection with Toxoplasma gondii.

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Arpron Leesombun

Full Text Available Herbal medicines and natural herb extracts are widely used as alternative treatments for various parasitic diseases, and such extracts may also have potential to decrease the side effects of the standard regimen drugs used to treat toxoplasmosis (sulfadiazine-pyrimethamine combination. We evaluated how effective the Thai piperaceae plants Piper betle, P. nigrum and P. sarmentosum are against Toxoplasma gondii infection in vitro and in vivo. Individually, we extracted the piperaceae plants with ethanol, passed them through a rotary evaporator and then lyophilized them to obtain crude extracts for each one. The in vitro study indicated that the P. betle extract was the most effective extract at inhibiting parasite growth in HFF cells (IC50 on RH-GFP: 23.2 μg/mL, IC50 on PLK-GFP: 21.4 μg/mL. Furthermore, treatment of experimental mice with the P. betle extract for 7 days after infection with 1,000 tachyzoites of the T. gondii PLK strain increased their survival (survival rates: 100% in 400 mg/kg-treated, 83.3% in 100 mg/kg-treated, 33.3% in 25 mg/kg-treated, 33.3% in untreated mice. Furthermore, treatment with 400 mg/kg of the P. betle extract resulted in 100% mouse survival following infection with 100,000 tachyzoites. The present study shows that P. betle extract has the potential to act as a medical plant for the treatment of toxoplasmosis.

Effects of Extracts from Thai Piperaceae Plants against Infection with Toxoplasma gondii

Science.gov (United States)

Leesombun, Arpron; Boonmasawai, Sookruetai; Shimoda, Naomi; Nishikawa, Yoshifumi

2016-01-01

Herbal medicines and natural herb extracts are widely used as alternative treatments for various parasitic diseases, and such extracts may also have potential to decrease the side effects of the standard regimen drugs used to treat toxoplasmosis (sulfadiazine-pyrimethamine combination). We evaluated how effective the Thai piperaceae plants Piper betle, P. nigrum and P. sarmentosum are against Toxoplasma gondii infection in vitro and in vivo. Individually, we extracted the piperaceae plants with ethanol, passed them through a rotary evaporator and then lyophilized them to obtain crude extracts for each one. The in vitro study indicated that the P. betle extract was the most effective extract at inhibiting parasite growth in HFF cells (IC50 on RH-GFP: 23.2 μg/mL, IC50 on PLK-GFP: 21.4 μg/mL). Furthermore, treatment of experimental mice with the P. betle extract for 7 days after infection with 1,000 tachyzoites of the T. gondii PLK strain increased their survival (survival rates: 100% in 400 mg/kg-treated, 83.3% in 100 mg/kg-treated, 33.3% in 25 mg/kg-treated, 33.3% in untreated mice). Furthermore, treatment with 400 mg/kg of the P. betle extract resulted in 100% mouse survival following infection with 100,000 tachyzoites. The present study shows that P. betle extract has the potential to act as a medical plant for the treatment of toxoplasmosis. PMID:27213575

[Access to intermittent preventive treatment (IPt) in a situation of abolition of user's fee: role of economic welfare].

Science.gov (United States)

Faye, A; Manga, N M; Seck, I; Niang, K; Leye, M M; Diagne-Camara, M; Diongue, M; Ba, M; Ndiaye, P; Tal-Dia, A

2012-08-01

In Senegal, the free distribution of sulfadoxine pyrimethamine during antenatal care is recommended to remove the disparity in the context of intermittent preventive treatment against malaria. The objective of this study was thus to identify factors influencing access to treatment in a situation of abolition of user fees. It was a cross-sectional and analytical study. It covered a sample of 1906 women aged 15-49 years randomly selected during the national survey on malaria in Senegal. Data were collected during a personal interview. The economic well-being was measured from the characteristics of housing and durable goods. The multivariate analysis was performed using logistic regression. The average age was 27.94 ± 5.34, 64.27% resided in rural area and 71.8% had received no schooling. Among the surveyed women, 23% were in the poorest quintile, while 16.3% were in the richest. Intermittent preventive treatment was performed in 49.3%. IPt were made more in urban areas (OR 1.45 95% [1.17 to 1.72]). It increased with the level of education with an OR of 1.5 and 1.68 in primary and secondary. The completion of the IPt increased with economic welfare. The OR ranged from 1.44 to 2.95 in the second quintile to the richest. Free medication does not necessarily benefit poor people. Other accompanying measures must be developed to facilitate the distribution of drugs particularly at community level with the involvement of people.

PS-15: a potent, orally active antimalarial from a new class of folic acid antagonists.

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Canfield, C J; Milhous, W K; Ager, A L; Rossan, R N; Sweeney, T R; Lewis, N J; Jacobus, D P

1993-07-01

A new, orally-active inhibitor of dihydrofolic acid reductase (DHFR), PS-15 (N-(3-(2,4,5-trichlorophenoxy)propyloxy)-N'-(1-methylethyl)- imidocarbonimidic diamide hydrochloride), has significant activity against drug-resistant Plasmodium falciparum. It is not cross-resistant with other inhibitors of DHFR (e.g., pyrimethamine and cycloguanil). Although it bears similarities to proguanil, PS-15 represents a new antifolate class of drugs that we have named oxyguanils or hydroxylamine-derived biguanides. This compound displays intrinsic antimalarial activity and also is metabolized in vivo to WR99210, an extremely active triazine inhibitor of DHFR. When tested in vitro against drug-resistant clones of P. falciparum, PS-15 was more active than proguanil, and the putative metabolite, WR99210, was more active than the proguanil metabolite cycloguanil. The drug is also more active as well as less toxic than proguanil when administered orally to mice infected with P. berghei. When administered orally to Aotus monkeys infected with multidrug-resistant P. falciparum, PS-15 was more active than either proguanil or WR99210. In 1973, WR99210 underwent clinical trials for safety and tolerance in volunteers. The trials showed gastrointestinal intolerance and limited bioavailability; further development of the drug was abandoned. Because PS-15 has intrinsic antimalarial activity, is not cross-resistant with other DHFR inhibitors, and can be metabolized to WR99210 in vivo, oral administration of this new drug should circumvent the shortcomings and retain the advantages found with both proguanil and WR99210.

[Clinical and developmental aspects of care-related tetanus in the reference service of the teaching hospital of Abidjan].

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Aba, T; Kra, O; Ehui, E; Tanon, K A; Kacou, A R; Ouatara, B; Bissagnéné, E; Kadio, A

2011-02-01

A cross-sectional descriptive study was conducted from medical data of inpatients with tetanus in the Department of Infectious and Tropical Diseases of the University Hospital of Treichville in Abidjan from January 2003 to December 2007. In five years, 221 cases of tetanus have been hospitalized. The tetanus gateway was found in 188 patients (85%). Tetanus gateway linked to care was found in 22 patients (11.7%). Acts of care in question were intramuscular injections (10 cases) and operative procedures (12 cases). Concerning medical care by intramuscular injection, quinine (four cases), sulfadoxine-pyrimethamine (one case), and long-acting penicillin (one case) were the identified drugs. The operative procedures mainly involved were skin sutures (nine cases), cures of hernia (two cases), and flattening of Fournier's gangrene (one case). The average incubation period was 9.5 days. The invasion lasted for an average of 1.8 days. On admission, tetanus was immediately generalized for all patients with the presence of paroxysms in 20 patients (90.9%). The lethality of tetanus related care was 54.5%. The death rate in the first 48 hours of hospitalization was estimated at 83.3%. The average length of hospital stay was 14.6 days. Health workers should be involved in the prevention of tetanus in improving the quality of care and especially in reducing intramuscular injections. Also, any patient not immunized against tetanus should receive anti-tetanus serum and an update of its tetanus vaccine before any invasive procedures.

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

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Newton Paul N

2011-12-01

Full Text Available Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA containing paracetamol (acetaminophen, counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

Management of uncomplicated malaria in children under 13 years of age at a district hospital in Senegal: from official guidelines to usual practices.

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Sarrassat, Sophie; Lalou, Richard; Cissé, Moustapha; Le Hesran, Jean-Yves

2011-09-29

To be effective, national malaria guidelines must be properly followed. This study evaluated nurses' practices in the management of uncomplicated malaria cases at a District Hospital. Its objective was to identify the reasons for discrepancies between official guidelines and usual practices. This study took place at Oussouye hospital, south-western Senegal. Blood smears were available for biological diagnosis in patients aged more than five years while the Integrated Management of Childhood Illness recommended treating fevers presumptively in children under five. First line anti-malarial was Amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP) bi-therapy. Hospital records of children under 13 years of age seen between 2004 and 2005 were reviewed. Among children treated with anti-malarials, 74% (2, 063/2, 789) received AQ+SP. However, only 22% (406/1, 879) of febrile children and 19% (429/2, 198) of children diagnosed with malaria got a blood smear. Moreover, an anti-malarial was prescribed for 80% (377/474) of children with a negative blood smear. The transition from chloroquine to AQ+SP was well followed. Nonetheless, blood smear use was very low and many over-prescriptions were reported. Reasons for discrepancies between guidelines and practices can be classified in three main categories: ambiguous guidelines, health system's dysfunctions and nurses' own considerations. Aside from the strengthening of the public health system, in order to guarantee practices complying with guidelines, training content should be more adapted to nurses' own considerations.

Management of uncomplicated malaria in children under 13 years of age at a district hospital in senegal: from official guidelines to usual practices

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Le Hesran Jean-Yves

2011-09-01

Full Text Available Abstract Background To be effective, national malaria guidelines must be properly followed. This study evaluated nurses' practices in the management of uncomplicated malaria cases at a District Hospital. Its objective was to identify the reasons for discrepancies between official guidelines and usual practices. Methods This study took place at Oussouye hospital, south-western Senegal. Blood smears were available for biological diagnosis in patients aged more than five years while the Integrated Management of Childhood Illness recommended treating fevers presumptively in children under five. First line anti-malarial was Amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP bi-therapy. Hospital records of children under 13 years of age seen between 2004 and 2005 were reviewed. Results Among children treated with anti-malarials, 74% (2, 063/2, 789 received AQ+SP. However, only 22% (406/1, 879 of febrile children and 19% (429/2, 198 of children diagnosed with malaria got a blood smear. Moreover, an anti-malarial was prescribed for 80% (377/474 of children with a negative blood smear. Conclusions The transition from chloroquine to AQ+SP was well followed. Nonetheless, blood smear use was very low and many over-prescriptions were reported. Reasons for discrepancies between guidelines and practices can be classified in three main categories: ambiguous guidelines, health system's dysfunctions and nurses' own considerations. Aside from the strengthening of the public health system, in order to guarantee practices complying with guidelines, training content should be more adapted to nurses' own considerations.

The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women

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Gutman, Julie; Kalilani, Linda; Taylor, Steve; Zhou, Zhiyong; Wiegand, Ryan E.; Thwai, Kyaw L.; Mwandama, Dyson; Khairallah, Carole; Madanitsa, Mwayi; Chaluluka, Ebbie; Dzinjalamala, Fraction; Ali, Doreen; Mathanga, Don P.; Skarbinski, Jacek; Shi, Ya Ping; Meshnick, Steve; ter Kuile, Feiko O.

2015-01-01

Background. The A581G mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased

The efficacy of sulfadoxine-pyrimethamine alone and in combination with chloroquine for malaria treatment in rural Eastern Sudan: the interrelation between resistance, age and gametocytogenesis

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A-Elbasit, Ishraga E; Elbashir, Mustafa I; Khalil, Insaf F

2006-01-01

OBJECTIVE: To compare the efficacy of sulfadoxine-pyremethamine (SP)+chloroquine (CQ) combination treatment against falciparum malaria with SP treatment alone. METHOD: In-vivo study of 254 patients with uncomplicated Plasmodium falciparum malaria in rural eastern Sudan, where the population is semi...

Selection of Parasites with Diminished Drug Sensitivity by Amodiaquine-Containing Antimalarial Regimens in Uganda

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Nawaz, Fatima; Nsobya, Samuel L.; Kiggundu, Moses; Joloba, Moses; Rosenthal, Philip J.

2009-01-01

Background Amodiaquine (AQ) is paired with artesunate (AS) or sulfadoxine-pyrimethamine (SP) in recommended antimalarial regimens. It is unclear how readily AQ resistance will be selected with combination chemotherapy. Methods We collected 61 Plasmodium falciparum samples from a cohort of Ugandan children randomized to treatment with AQ/SP, AS/AQ, or artemether-lumefantrine (AL) for uncomplicated malaria. In vitro sensitivity to monodesethylamodiaquine (MDAQ) was measured with a histidine rich protein-2-based ELISA, and potential resistance-mediating polymorphisms pfmdr-1were evaluated. Results Parasites from subjects previously treated with AQ/SP or AS/AQ within 12 weeks were less sensitive to MDAQ (n=18; mean IC50 62.9 nM; range 12.7–158.3 nM) than parasites from those not treated within 12 weeks (n=43; mean IC50 37.5 nM; range 6.3–184.7 nM; p=0.0085) or only those in the treatment arm that did not contain AQ (n=20; mean IC50 28.8 nM; range 6.3–121.8 nM; p=0.0042). The proportion of strains with polymorphisms expected to mediate diminished response to AQ (pfmdr-1 86Y and 1246Y) increased after prior AQ therapy, although differences were not significant. Conclusions Prior therapy selected for diminished response to MDAQ, suggesting that AQ-containing regimens may rapidly lose efficacy in Africa. The mechanism of diminished MDAQ response is not fully explained by known mutations in pfmdr-1. PMID:19905933

Artemether-lumefantrine versus artesunate plus amodiaquine for treating uncomplicated childhood malaria in Nigeria: randomized controlled trial

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Nwachukwu Chukwuemeka

2006-05-01

Full Text Available Abstract Background The therapeutic efficacy of artesunate plus amodiaquine and artemether/lumefantrine were assessed in an area of Nigeria with high levels of Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine. Participants Children aged 6 to 59 months with uncomplicated P. falciparum infection and parasite density 1,000 to 200,000 parasites/μL enrolled following informed consent by parents. Methods Eligible children were randomly assigned to receive either a 3-day course of artesunate (4 mg/kg plus amodiaquine (10 mg/kg or 6-dose course of artemether/lumefantrine (20/120 mg tablets over three days. Patients were followed up with clinical and laboratory assessments until day 14 using standard WHO in-vivo antimalarial drug test protocol. Results A total 119 eligible children were enrolled but 111 completed the study. Adequate clinical and parasitological response (ACPR was 47 (87.0% and 47 (82.5% for artemether-lumefantrine (AL and artesunate+amodiaquine (AAMQ respectively (OR 0.7, 95% confidence interval 0.22 to 2.22. Early treatment failure (ETF occurred in one participant (1.8% treated with AAQ but in none of those with AL. Two (3.7% patients in the AL group and none in the AAQ group had late clinical failure. Late parasitological failure was observed in 9 (15.8 and 5 (9.3% of patients treated with AAQ and AL respectively. None of participants had a serious adverse event. Conclusion Artemether-lumenfantrine and artesunate plus amodiaquine have high and comparable cure rates and tolerability among under-five children in Calabar, Nigeria.

Severe cutaneous drug reactions in Guinean children: a monocentric retrospective study of 35 cases

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Thierno Mamadou Tounkara

2018-04-01

Full Text Available Background: Data on Severe cutaneous drug reactions (CADRs are not common among in sub-Saharan Africa children. The purpose of this study was to document the clinical, etiological and evolutionary aspects of Severe CDRs in children hospitalized at the dermatology department of university hospitals of Conakry. Material and Methods: Retrospective study, conducted from 1 January 2000 to 31 December 2014. Were included all children aged 0-17 years hospitalized for severe CARDs. The data collected were Socio-demographic, clinical, para-clinical and evolution variables. The data was entered and analyzed using the Excel 8.0 software. Results: During a study period, 4437 patients of all ages was hospitalized in dermatology department. 35 patients were included with an average age of 11.3 years and a sex ratio of 1.5. The main clinical patterns were: Stevens Johnson syndrome 37.14% (13/35 Lyell syndrome 25.71 % and generalized bullous fixed eruption 22.85%. The drug was identified as 32 patients (91.42%: Sulfadoxine–Pyriméthamine 40.62%, cotrimoxazole 21.85%, nevirapin 12.5%, ampicillin 6.25%, traditional Pharmacopoeia 6.25% and griseofulin 3.12%. It was taken following self-medication in 14 patients, including a parental initiative in 9 patients. 7 patients had a history of drug allergy and 4 were HIV positive. We recorded 5 deaths. Conclusion: Our study confirms the rarity of severe CADRs in children. The importance of the sulfadoxine-pyrimethamine in the occurrence of severe CADRs in children is the particularity of our series.

In vitro antimalarial activity of novel semisynthetic nocathiacin I antibiotics.

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Sharma, Indu; Sullivan, Margery; McCutchan, Thomas F

2015-01-01

Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in vitro growth inhibition assay was done using three laboratory strains of P. falciparum displaying various levels of chloroquine (CQ) susceptibility. Our results indicate that BMS461996 has potent antimalarial activity and inhibits parasite growth with mean 50% inhibitory concentrations (IC50s) of 51.55 nM for P. falciparum 3D7 (CQ susceptible), 85.67 nM for P. falciparum Dd2 (accelerated resistance to multiple drugs [ARMD]), and 99.44 nM for P. falciparum K1 (resistant to CQ, pyrimethamine, and sulfadoxine). Similar results at approximately 7-fold higher IC50s were obtained with BMS411886 than with BMS461996. We also tested the effect of BMS491996 on gametocytes; our results show that at a 20-fold excess of the mean IC50, gametocytes were deformed with a pyknotic nucleus and growth of stage I to IV gametocytes was arrested. This preliminary study shows a significant potential for nocathiacin analogues to be developed as antimalarial drug candidates and to warrant further investigation. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Anticancer Properties of Distinct Antimalarial Drug Classes

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Hooft van Huijsduijnen, Rob; Guy, R. Kiplin; Chibale, Kelly; Haynes, Richard K.; Peitz, Ingmar; Kelter, Gerhard; Phillips, Margaret A.; Vennerstrom, Jonathan L.; Yuthavong, Yongyuth; Wells, Timothy N. C.

2013-01-01

We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase) inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase) and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor), emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings. PMID:24391728

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries

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O'Connell Kathryn A

2011-10-01

Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets as compared to first-line quality-assured ACT ( Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

Anticancer properties of distinct antimalarial drug classes.

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Rob Hooft van Huijsduijnen

Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure.

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Mishra, Neelima; Srivastava, Bina; Bharti, Ram Suresh; Rana, Roma; Kaitholia, Kamlesh; Anvikar, Anupkumar R; Das, Manoj Kumar; Ghosh, Susanta K; Bhatt, Rajendra M; Tyagi, Prajesh K; Dev, Vas; Phookan, Sobhan; Wattal, Suman Lata; Sonal, Gagan Singh; Dhariwal, Akshay Chand; Valecha, Neena

2016-01-01

To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas. A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations. Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections. Till 2012, India's national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.

A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

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Jason P Wendler

Full Text Available Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs.Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set.Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

Monitoring and evaluation of malaria in pregnancy – developing a rational basis for control

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Dellicour Stephanie

2008-12-01

Full Text Available Abstract Monitoring and evaluation of malaria control in pregnancy is essential for assessing the efficacy and effectiveness of health interventions aimed at reducing the major burden of this disease on women living in endemic areas. Yet there is no currently integrated strategic approach on how this should be achieved. Malaria control in pregnancy is formulated in relation to epidemiological patterns of exposure. Current emphasis is on intermittent preventive treatment (IPTp during pregnancy with sulphadoxine-pyrimethamine in higher transmission areas, combined with insecticide treated bed nets (ITNs and case management. Emphasis in lower transmission areas is primarily on case management. This paper discusses a rational basis for monitoring and evaluation based on: assessments of therapeutic and prophylactic drug efficacy; proportional reductions in parasite prevalence; seasonal effects; rapid assessment methodologies; birthweight and/or anaemia nomograms; case-coverage methods; maternal mortality indices; operational and programmatic indicators; and safety and pharmacovigilance of antimalarials in pregnancy. These approaches should be incorporated more effectively within National Programmes in order to facilitate surveillance and improve identification of high-risk women. Systems for utilizing routinely collected data should be strengthened, with greater attention to safety and pharmacovigilance with the advent of artemisinin combination therapies, and prospects of inadvertent exposures to artemisinins in the first trimester. Integrating monitoring activities within malaria control, reproductive health and adolescent-friendly services will be critical for implementation. Large-scale operational research is required to further evaluate the validity of currently proposed indicators, and in order to clarify the breadth and scale of implementation to be deployed.

Distribution of Mutations Associated with Antifolate and Chloroquine Resistance among Imported Plasmodium vivax in the State of Qatar.

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Bansal, Devendra; Acharya, Anushree; Bharti, Praveen K; Abdelraheem, Mohamed H; Elmalik, Ashraf; Abosalah, Salem; Khan, Fahmi Y; ElKhalifa, Mohamed; Kaur, Hargobinder; Mohapatra, Pradyumna K; Sehgal, Rakesh; Idris, Mohammed A; Mahanta, Jagadish; Singh, Neeru; Babiker, Hamza A; Sultan, Ali A

2017-12-01

Plasmodium vivax is the most prevalent parasite worldwide, escalating by spread of drug resistance. Currently, in Qatar, chloroquine (CQ) plus primaquine are recommended for the treatment of P. vivax malaria. The present study examined the prevalence of mutations in dihydrofolate reductase ( dhfr ), dihydropteroate synthase ( dhps ) genes and CQ resistance transporter ( crt-o ) genes, associated with sulphadoxine-pyrimethamine (SP) and chloroquine resistance, among imported P. vivax cases in Qatar. Blood samples were collected from patients positive for P. vivax and seeking medical treatment at Hamad General Hospital, Doha, during 2013-2016. The Sanger sequencing method was performed to examine the single nucleotide polymorphisms in Pvdhfr , Pvdhps , and Pvcrt-o genes. Of 314 examined P. vivax isolates, 247 (78.7%), 294 (93.6%) and 261 (83.1%) were successfully amplified and sequenced for Pvdhfr , Pvdhps , and Pvcrt-o , respectively. Overall, 53.8% ( N = 133) carried mutant alleles (58R/117N) in Pvdhfr , whereas 77.2% ( N = 227) and 90% ( N = 235) isolates possessed wild type allele in Pvdhps and Pvcrt-o genes, respectively. In addition, a total of eleven distinct haplotypes were detected in Pvdhfr / Pvdhps genes. Interestingly, K10 insertion in the Pvcrt-o gene was observed only in patients originating from the Indian subcontinent. The results suggested that CQ remains an acceptable treatment regimen but further clinical data are required to assess the effectiveness of CQ and SP in Qatar to support the current national treatment guidelines. In addition, limited distribution of genetic polymorphisms associated with CQ and SP resistance observed in imported P. vivax infections, necessitates regular monitoring of drug resistant P. vivax malaria in Qatar.

Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model

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Wargo, A.R.; Huijben, S.; De Roode, J. C.; Shepherd, J.; Read, A.F.

2007-01-01

Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance. ?? 2007 by The National Academy of Sciences of the USA.

Fixed drug eruption at a dermatology clinic in Lagos, Nigeria

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Olusola Olabisi Ayanlowo

2015-01-01

Full Text Available Background: Fixed drug eruption (FDE is common cutaneous drug eruption characterized by the development of one or more annular, oval, erythematous, and hyperpigmented patches as a result of systemic exposure to a drug. Drugs causing FDE vary with prevailing diseases and prescription pattern in different parts of the world. This study is aimed at reviewing cases of FDE seen at the dermatology outpatient clinic of Lagos University Teaching Hospital (LUTH over a 9-year period, highlighting the spectrum of drugs implicated and the clinical characteristics. Materials and Methods: Data were obtained from the clinic records and patients' case notes. These included the demographic details, duration of presentation, drugs implicated, and clinical characteristics. Results: FDE was diagnosed in 1.8% (295/16,160 of patients seen. There was a slight female preponderance. Antimalarials were the commonest group of medications implicated (51.0% followed by antibiotics (27.9%; analgesics (10.2%, herbal toothpaste (6.1%, and oral hypoglycemic agents (4.1%. Sulfonamides were the commonest group of drugs found in 78 patients (53.1% predominantly as sulfadoxine/pyrimethamine antimalarials and trimethoprim/sulfamethoxazole antibiotics (co-trimoxazole. Conclusion: Concerted efforts are needed to discourage over-the-counter sales and purchase of nonprescription sulfonamide-based medications. A change in prescription pattern from sulfonamides to other classes of antimalarials and antibiotics is desirable and/or recommended. Patients should inform their caregivers at any point of care about their reaction to drugs. It is advised that they have a list of common implicating drugs and they wear a medic alert or carry an ID card bearing this information.

Incidence of malaria and efficacy of combination antimalarial therapies over 4 years in an urban cohort of Ugandan children.

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Tamara D Clark

2010-07-01

Full Text Available Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Children aged 1-10 years were enrolled from randomly selected households in 2004-05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP, artesunate/amodiaquine (AS/AQ, or artemether/lumefantrine (AL. Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria and no deaths were seen.With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.isrctn.org ISRCTN37517549.

Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia

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Manyando Christine

2010-09-01

Full Text Available Abstract Background Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited. This prospective cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine (AL in pregnant women with malaria. Methods Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode (AL vs. sulphadoxine-pyrimethamine, SP. Safety was assessed using standard and pregnancy-specific parameters. Post-delivery follow-up was six weeks for mothers and 12 months for live births. Primary outcome was perinatal mortality (stillbirth or neonatal death within seven days after birth. Results Data from 1,001 pregnant women (AL n = 495; SP n = 506 and 933 newborns (AL n = 466; SP n = 467 showed: perinatal mortality (AL 4.2%; SP 5.0%, comprised of early neonatal mortality (each group 2.3%, stillbirths (AL 1.9%; SP 2.7%; preterm deliveries (AL 14.1%; SP 17.4% of foetuses; and gestational age-adjusted low birth weight (AL 9.0%; SP 7.7%. Infant birth defect incidence was 1.8% AL and 1.6% SP, excluding umbilical hernia. Abortions prior to antenatal care could not be determined: abortion occurred in 4.5% of women treated with AL during their first trimester; none were reported in the 133 women exposed to SP and/or quinine during their first trimester. Overall development (including neurological assessment was similar in both groups. Conclusions These data suggest that exposure to AL in pregnancy, including first trimester, is not associated with particular safety risks in terms of perinatal mortality, malformations, or developmental impairment. However, more data are required on AL use during the first trimester.

In Vivo Antiplasmodial Potentials of the Combinations of Four Nigerian Antimalarial Plants

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Adeleke Clement Adebajo

2014-08-01

Full Text Available Various combinations of Nauclea latifolia root, Artocarpus altilis stem bark, Murraya koenigii leaf and Enantia chlorantha stem bark used in African ethnomedicine as decoctions for malaria and fevers, and combinations with standard drugs, were investigated for antiplasmodial activities using Plasmodium berghei berghei-infected mice. The respective prophylactic and curative ED50 values of 189.4 and 174.5 mg/kg for N. latifolia and chemosuppressive ED50 value of 227.2 mg/kg for A. altilis showed that they were the best antimalarial herbal drugs. A 1.6-fold increase of the survival time given by the negative control was elicited by M. koenigii, thereby confirming its curative activity. Pyrimethamine with an ED50 of 0.5 ± 0.1 mg/kg for the prophylactic, and chloroquine with ED50 = 2.2 ± 0.1 and 2.2 ± 0.0 mg/kg for the chemosuppressive and curative tests, respectively, were significantly (p < 0.05 more active. Co-administrations of N. latifolia with the standard drugs significantly reduced their prophylactic, chemosuppressive and curative actions, possibly increasing the parasites’ resistance. Binary combinations of N. latifolia or M. koenigii with any of the other plants significantly increased the prophylactic and suppressive activities of their individual plants, respectively. Also, E. chlorantha with A. altilis or N. latifolia enhanced their respective prophylactic or curative activities, making these combinations most beneficial against malaria infections. Combinations of three and four extracts gave varied activities. Hence, the results justified the combinations of ethnomedicinal plants in antimalarial herbal remedies and showed the importance of the three in vivo models in establishing antimalarial activity.

PENURUNAN EFIKASI KLOROKUIN DAN SULFADOKSIN/PIRIMETAMIN UNTUK PENGOBATAN MALARIA FALSIPARUM RINGAN DI PULAU BINTAN, PROVINSI KEPUALAUAN RIAU, TAHUN 2003

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Sekar Tuti

2012-11-01

Full Text Available To support Malaria Control Program, on July 2002 to December 2003 monitoring the efficacy of chloroquine (CQ and sulphadoxine/pyrimethamine (S/P as a first and second line drugs for uncomplicated falciparum malaria treatment had been conducted using WHO's method version 2001 guideline. The study was conducted in Bintan Island -Kepulauan Riau Province, which is bordering with Singapore and Malaysia. The activities conducted in two Health Centers (Tanjung Uban and Kijang. It was found that CQ in treated patients as many as 26.67% cases showed ACPR (Adequate Clinical and Parasitological Responses, 33.33% with ETF (Early Treatment Failure and 40% considered as LTF (Late Treatment Failure. The overall treatment failure was 73.33%. For S/P treated patients, as many as 87.5% cases showed ACPR and 12.5% cases considered as LTF. The fever clearance time (FCT in ACPR patients mostly 88.89% occurred on day-1. As many as 7 patients had no temperature increasing since day-0 (below 37.5°C. While the parasite clearance time (PCT on day-2 was 43.75% and on day-3 was 50%. It was concluded that there was a significant decreased of chloroquine efficacy for uncomplicated falciparum malaria in Bintan Island area, Kepulauan Riau Province compared to the efficacy status in the year of 2000. As a preliminary result, the efficacy of S/P in this area is 87.5% Considering the result of the study, the people movement and local malaria situation, this area is not suitable to be one of national sentinel sites for and malaria drug monitoring in Indonesia. Keywords: Falciparum, malaria treatment, drug efficacy.

Treatment of infectious complications of acquired immunodeficiency syndrome.

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Furio, M M; Wordell, C J

1985-01-01

The infectious complications of the acquired immunodeficiency syndrome (AIDS) are discussed, and the conventional and nonconventional therapies used for these infections are reviewed. The infections most commonly encountered in patients with AIDS are Pneumocystis carinii pneumonia (58%), Candida esophagitis (31%), toxoplasmosis (21%), cytomegalovirus infections (15%), and herpes-simplex virus infections (12%). Pneumocystis carinii pneumonia is the most common life-threatening process in these patients. Trimethoprim-sulfamethoxazole (TMP-SMZ) is considered the drug of choice for its treatment. Oral candidiasis often indicates the progression to AIDS in the high-risk populations of homosexual or bisexual men, intravenous drug abusers, and individuals with hemophilia. Nystatin suspension is commonly used to treat oral candidiasis, while Candida esophagitis demands systemic therapy with ketoconazole. Toxoplasmosis most commonly manifests itself in patients with AIDS as a cerebral mass lesion. The recommended therapy includes sulfadiazine and pyrimethamine. AIDS patients frequently experience protozoal invasion of the intestinal tract with Giardia lamblia, Isospora belli, and Cryptosporidium muris. Various drugs have been tried for these infections, including quinacrine hydrochloride, metronidazole, TMP-SMZ, and spiramycin. Cytomegalovirus (CMV) infections commonly involve the lungs, gastrointestinal tract, eyes, brain, and nervous system. Attempts to treat these disseminated CMV infections with antiviral agents, including acyclovir, have not been successful. However, acyclovir has been found beneficial in the treatment of herpes-simplex virus infections. Multiple infectious complications may occur in patients with AIDS as a result of the cellular-immune deficiency associated with this disease. Until more research is done with AIDS patients, therapy must be based on the data available from the treatment of these infections in immunosuppressed patients without AIDS.

Antimalarial Activity of Small-Molecule Benzothiazole Hydrazones.

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Sarkar, Souvik; Siddiqui, Asim A; Saha, Shubhra J; De, Rudranil; Mazumder, Somnath; Banerjee, Chinmoy; Iqbal, Mohd S; Nag, Shiladitya; Adhikari, Susanta; Bandyopadhyay, Uday

2016-07-01

We synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. These hydrazones concentration-dependently chelated free iron and offered antimalarial activity. Upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. Compound 5f also interacted with free heme (KD [equilibrium dissociation constant] = 1.17 ± 0.8 μM), an iron-containing tetrapyrrole released after hemoglobin digestion by the parasite, and inhibited heme polymerization by parasite lysate. Structure-activity relationship studies indicated that a nitrogen- and sulfur-substituted five-membered aromatic ring present within the benzothiazole hydrazones might be responsible for their antimalarial activity. The dose-dependent antimalarial and heme polymerization inhibitory activities of the lead compound 5f were further validated by following [(3)H]hypoxanthine incorporation and hemozoin formation in parasite, respectively. It is worth mentioning that compound 5f exhibited antiplasmodial activity in vitro against a chloroquine/pyrimethamine-resistant strain of Plasmodium falciparum (K1). We also evaluated in vivo antimalarial activity of compound 5f in a murine model where a lethal multiple-drug-resistant strain of Plasmodium yoelii was used to infect Swiss albino mice. Compound 5f significantly suppressed the growth of parasite, and the infected mice experienced longer life spans upon treatment with this compound. During in vitro and in vivo toxicity assays, compound 5f showed minimal alteration in biochemical and hematological parameters compared to control. In conclusion, we identified a new class of hydrazone with therapeutic potential against malaria. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cerebral toxoplasmosis in a diffuse large B cell lymphoma patient

International Nuclear Information System (INIS)

Savsek, Lina; Opaskar, Tanja Ros

2016-01-01

Toxoplasmosis is an opportunistic protozoal infection that has, until now, probably been an underestimated cause of encephalitis in patients with hematological malignancies, independent of stem cell or bone marrow transplant. T and B cell depleting regimens are probably an important risk factor for reactivation of a latent toxoplasma infection in these patients. We describe a 62-year-old HIV-negative right-handed Caucasian female with systemic diffuse large B cell lymphoma who presented with sudden onset of high fever, headache, altered mental status, ataxia and findings of pancytopenia, a few days after receiving her final, 8 th cycle of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone (R-CHOP) chemotherapy regimen. A progression of lymphoma to the central nervous system was suspected. MRI of the head revealed multiple on T2 and fluid attenuated inversion recovery (FLAIR) hyperintense parenchymal lesions with mild surrounding edema, located in both cerebral and cerebellar hemispheres that demonstrated moderate gadolinium enhancement. The polymerase chain reaction on cerebrospinal fluid (CSF PCR) was positive for Toxoplasma gondii. The patient was diagnosed with toxoplasmic encephalitis and successfully treated with sulfadiazine, pyrimethamine and folic acid. Due to the need for maintenance therapy with rituximab for lymphoma remission, the patient now continues with secondary prophylaxis of toxoplasmosis. With this case report, we wish to emphasize the need to consider cerebral toxoplasmosis in patients with hematological malignancies on immunosuppressive therapy when presenting with new neurologic deficits. In such patients, there are numerous differential diagnoses for cerebral toxoplasmosis, and the CNS lymphoma is the most difficult among all to distinguish it from. If left untreated, cerebral toxoplasmosis has a high mortality rate; therefore early recognition and treatment are of essential importance

Comparison of artemisinin suppositories, intramuscular artesunate and intravenous quinine for the treatment of severe childhood malaria.

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Cao, X T; Bethell, D B; Pham, T P; Ta, T T; Tran, T N; Nguyen, T T; Pham, T T; Nguyen, T T; Day, N P; White, N J

1997-01-01

Severe malaria remains a major cause of mortality and morbidity for children living in many tropical regions. With the emergence of strains of Plasmodium falciparum resistant to both chloroquine and quinine, alternative antimalarial agents are required. The artemisinin group of compounds are rapidly effective in severe disease when given by intramuscular or intravenous injection. However, these routes of administration are not always available in rural areas. In an open, randomized comparison 109 Vietnamese children, aged between 3 months and 14 years, with severe P.falciparum malaria, were allocated at random to receive artemisinin suppositories followed by mefloquine (n = 37), intramuscular artesunate followed by mefloquine (n = 37), or intravenous quinine followed by pyrimethamine/sulfadoxine (n = 35). There were 9 deaths: 2 artemisinin, 4 artesunate and 5 quinine-treated children. There was no difference in fever clearance time, coma recovery, or length of hospital stay among the 3 groups. However, parasite clearance times were significantly faster in artemisinin and artesunate-treated patients than in those who received quinine (P children receiving these drugs had lower peripheral reticulocyte counts by day 5 of treatment than those in the quinine group (P = 0.011). No other adverse effect or toxicity was found. There was no treatment failure in these 2 groups, but 4 patients in the quinine group failed to clear their parasites within 7 d of starting treatment and required alternative antimalarial therapy. Artemisinin suppositories are easy to administer, cheap, and very effective for treating children with severe malaria. In rural areas where medical facilities are lacking these drugs will allow antimalarial therapy to be instituted earlier in the course of the disease and may therefore save lives.

Malarone (atovaquone and proguanil hydrochloride): a review of its clinical development for treatment of malaria. Malarone Clinical Trials Study Group.

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Looareesuwan, S; Chulay, J D; Canfield, C J; Hutchinson, D B

1999-04-01

The continuing spread of drug-resistant malaria emphasizes the need for new antimalarial drugs. Atovaquone is a broad-spectrum antiprotozoal drug with a novel mechanism of action, via inhibition of parasite mitochondrial electron transport, and a favorable safety profile. Early studies with atovaquone alone for treatment of malaria demonstrated good initial control of parasitemia but an unacceptable rate of recrudescent parasitemia. Parasites isolated during recrudescence after treatment with atovaquone alone were resistant to atovaquone in vitro. The combination of atovaquone and proguanil is synergistic in vitro, and clinical studies demonstrated enhanced efficacy of the combination compared to either drug alone for treatment of malaria. Malarone, a fixed-dose combination of 250 mg of atovaquone and 100 mg of proguanil hydrochloride, is available in many countries for treatment of acute, uncomplicated malaria caused by Plasmodium falciparum. At the recommended dose (in adults, four tablets once a day for three days), the overall cure rate was > 98% in more than 500 patients with falciparum malaria. In four randomized, controlled clinical trials, treatment with atovaquone and proguanil hydrochloride was significantly more effective than mefloquine (Thailand), amodiaquine (Gabon), chloroquine (Peru and the Philippines) or chloroquine plus pyrimethamine/sulfadoxine (Philippines). In clinical trials where the comparator drug was highly effective, treatment with atovaquone and proguanil hydrochloride was equally effective. Parasites isolated during recrudescence after treatment with the combination of atovaquone and proguanil were not resistant to atovaquone in vitro. The most commonly reported adverse events in clinical trials (abdominal pain, anorexia, nausea, vomiting, diarrhea and coughing) occurred with similar frequency in patients treated with a comparator drug. Malarone is a safe and effective new agent for treatment of malaria.

Do health workers’ preferences influence their practices? Assessment of providers’ attitude and personal use of new treatment recommendations for management of uncomplicated malaria, Tanzania

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Masanja Irene M

2012-11-01

Full Text Available Abstract Background Due to growing antimalarial drug resistance, Tanzania changed malaria treatment policies twice within a decade. First in 2001 chloroquine (CQ was replaced by sulfadoxine-pyrimethamine (SP for management of uncomplicated malaria and by late 2006, SP was replaced by artemether-lumefantrine (AL. We assessed health workers’ attitudes and personal practices following the first treatment policy change, at six months post-change and two years later. Methods Two cross-sectional surveys were conducted in 2002 and 2004 among healthcare workers in three districts in South-East Tanzania using semi-structured questionnaires. Attitudes were assessed by enquiring which antimalarial was considered most suitable for the management of uncomplicated malaria for the three patient categories: i children below 5; ii older children and adults; and iii pregnant women. Practice was ascertained by asking which antimalarial was used in the last malaria episode by the health worker him/herself and/or dependants. Univariate and multivariate logistic regression was used to identify factors associated with reported attitudes and practices towards the new treatment recommendations. Results A total of 400 health workers were interviewed; 254 and 146 in the first and second surveys, respectively. SP was less preferred antimalarial in hospitals and private health facilities (p Conclusion Following changes in malaria treatment recommendations, most health workers did not prefer the new antimalarial drug, and their preferences worsened over time. However, many of them still used the newly recommended drug for management of their own or family members’ malaria episode. This indicates that, other factors than providers’ attitude may have more influence in their personal treatment practices.

Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs

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Sawa Patrick

2010-05-01

Full Text Available Abstract Background There is renewed acknowledgement that targeting gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean gametocyte circulation time and duration of gametocyte carriage in treated malaria patients. Methods Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP plus amodiaquine and artemisinin-based combination therapy (ACT: SP plus artesunate (AS or artemether-lumefantrine. The second trial compared ACT (SP+AS with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ. Mature gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to gametocyte densities to estimate the circulation time per gametocyte; a similar model was fitted to gametocyte prevalences to estimate the duration of gametocyte carriage after efficacious treatment. Results The mean circulation time of gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry gametocytes for an average of 55 days (95% CI 28.7 - 107.7. ACT reduced the duration of gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5. Addition of PQ to ACT resulted in a further fourfold reduction of the duration of gametocyte carriage. Conclusions These findings confirm previous estimates of the circulation time of gametocytes, but indicate a much longer duration of (low density gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of gametocyte carriage considerably, and had the most pronounced effect on mature gametocytes when combined with PQ.

Reduction of malaria transmission to Anopheles mosquitoes with a six-dose regimen of co-artemether.

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Colin J Sutherland

2005-04-01

Full Text Available Resistance of malaria parasites to chloroquine (CQ and sulphadoxine-pyrimethamine (SP is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs.In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91, or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet] (n = 406. Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001. Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001 and were less infectious to mosquitoes at day 7 (p < 0.001 than carriers who had received CQ/SP.Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.

Intermittent Preventive Treatment for Malaria in Pregnancy: Optimization of Target Concentrations of Dihydroartemisinin-Piperaquine.

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Savic, Rada M; Jagannathan, Prasanna; Kajubi, Richard; Huang, Liusheng; Zhang, Nan; Were, Moses; Kakuru, Abel; Muhindo, Mary K; Mwebaza, Norah; Wallender, Erika; Clark, Tamara D; Opira, Bishop; Kamya, Moses; Havlir, Diane V; Rosenthal, Philip J; Dorsey, Grant; Aweeka, Francesca T

2018-03-14

Dihydroartemsinin-piperaquine is highly efficacious as intermittent preventive therapy for malaria during pregnancy (IPTp). Determining associations between piperaquine exposure, malaria risk, and adverse birth outcomes informs optimal dosing strategies. HIV-uninfected pregnant women were enrolled in a placebo-controlled trial of IPTp at 12-20 weeks gestation and randomized to: sulfadoxine-pyrimethamine every 8 weeks (n=106), dihydroartemsinin-piperaquine every 8 weeks (n=94), or dihydroartemsinin-piperaquine every 4 weeks (n=100) during pregnancy. Pharmacokinetic sampling for piperaquine was performed every 4 weeks, and an intensive pharmacokinetic sub-study was performed in 30 women at 28 weeks gestation. Concentration-effect relationships were assessed between exposure to piperaquine; the prevalence of P. falciparum infection during pregnancy; outcomes at delivery including placental malaria, low birthweight, and preterm birth; and risks for toxicity. Simulations of new dosing scenarios were performed. Model-defined piperaquine target venous plasma concentrations of 13.9 ng/ml provided 99% protection from P. falciparum infection during pregnancy. Each 10 day increase in time>target piperaquine concentrations was associated with reduced odds of placental parasitemia (0∙67, P<0.0001), preterm birth (0.74, P<0.01), and low birthweight (0.74, P<0.05), though increases in piperaquine concentrations were associated with QTc prolongation (5 msec increase per 100 ng/ml). Modeling suggests that daily or weekly administration of lower dosages of piperaquine, compared to standard dosing, will maintain piperaquine trough levels above target concentrations with reduced piperaquine peak levels, potentially limiting toxicity. The protective efficacy of IPTp with dihydroartemsinin-piperaquine was strongly associated with higher drug exposure. Studies of the efficacy and safety of alternative dihydroartemsinin-piperaquine IPTp dosing strategies are warranted. NCT02163447.

Prevalence of malaria and anaemia among HIV infected pregnant women receiving co-trimoxazole prophylaxis in Tanzania: a cross sectional study in Kinondoni Municipality.

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Manyanga, Vicent P; Minzi, Omary; Ngasala, Billy

2014-04-24

HIV-infected pregnant women are particularly more susceptible to the deleterious effects of malaria infection particularly anaemia. In order to prevent opportunistic infections and malaria, a policy of daily co-trimoxazole prophylaxis without the standard Suphadoxine-Pyrimethamine intermittent preventive treatment (SP-IPT) was introduced to all HIV infected pregnant women in the year 2011. However, there is limited information about the effectiveness of this policy. This was a cross sectional study conducted among HIV-infected pregnant women receiving co-trimoxazole prophylaxis in eight public health facilities in Kinondoni Municipality from February to April 2013. Blood was tested for malaria infection and anaemia (haemoglobin anaemia. Pearson chi-square test, Fischer's exact test and multivariate logistic regression were used in the statistical analysis. This study enrolled 420 HIV infected pregnant women. The prevalence of malaria infection was 4.5%, while that of anaemia was 54%. The proportion of subjects with poor adherence to co-trimoxazole was 50.5%. As compared to HIV infected pregnant women with good adherence to co-trimoxazole prophylaxis, the poor adherents were more likely to have a malaria infection (Adjusted Odds Ratio, AOR = 6.81, 95% CI = 1.35-34.43, P = 0.02) or anaemia (AOR = 1.75, 95% CI = 1.03-2.98, P = 0.039). Other risk factors associated with anaemia were advanced WHO clinical stages, current malaria infection and history of episodes of malaria illness during the index pregnancy. The prevalence of malaria was low; however, a significant proportion of subjects had anaemia. Good adherence to co-trimoxazole prophylaxis was associated with reduction of both malaria infection and anaemia among HIV infected pregnant women.

An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso.

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Valea, Innocent; Tinto, Halidou; Drabo, Maxime K; Huybregts, Lieven; Sorgho, Hermann; Ouedraogo, Jean-Bosco; Guiguemde, Robert T; van Geertruyden, Jean Pierre; Kolsteren, Patrick; D'Alessandro, Umberto

2012-03-16

A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP) to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. Study participants were enrolled at antenatal care (ANC) visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C) or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002). The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy.

Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

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Domingos Alves Meira

1988-09-01

Full Text Available A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7th, 24th, 21st, 28th and 35th day both clinically and parasitologically (blood test. Eighty three (40.1% had moderate or severe malaria, and 97 (46.8% had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%, two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.

Increasing prevalence of wildtypes in the dihydrofolate reductase gene of Plasmodium falciparum in an area with high levels of sulfadoxine/pyrimethamine resistance after introduction of treated bed nets

DEFF Research Database (Denmark)

Alifrangis, Michael; Lemnge, Martha M; Rønn, Anita M

2003-01-01

years old living in the villages from 1998 to 2000. In 2000, after two years of bed net use, the prevalence of wild types in codon 51, 59, and 108 of dhfr increased significantly in Magoda compared with previous years. Furthermore, the prevalence of dhfr wild types was significantly higher in Magoda...

Effectiveness of intermittent preventive treatment with sulfadoxine-pyrimethamine during pregnancy on placental malaria, maternal anaemia and birthweight in areas with high and low malaria transmission intensity in Tanzania.

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Mosha, Dominic; Chilongola, Jaffu; Ndeserua, Rabi; Mwingira, Felista; Genton, Blaise

2014-09-01

To assess the effectiveness of IPTp in two areas with different malaria transmission intensities. Prospective observational study recruiting pregnant women in two health facilities in areas with high and low malaria transmission intensities. A structured questionnaire was used for interview. Maternal clinic cards and medical logs were assessed to determine drug intake. Placental parasitaemia was screened using both light microscopy and real-time quantitative PCR. Of 350 pregnant women were recruited and screened for placental parasitaemia, 175 from each area. Prevalence of placental parasitaemia was 16.6% (CI 11.4-22.9) in the high transmission area and 2.3% (CI 0.6-5.7) in the low transmission area. Being primigravida and residing in a high transmission area were significant risk factors for placental malaria (OR 2.4; CI 1.1-5.0; P = 0.025) and (OR 9.4; CI 3.2-27.7; P anaemia or low birthweight, regardless of transmission intensity. The number needed to treat (NNT) was four (CI 2-6) women in the high transmission area and 33 (20-50) in the low transmission area to prevent one case of placental malaria. IPTp may have an effect on lowering the risk of placental malaria in areas of high transmission, but this effect did not translate into a benefit on risks of maternal anaemia or low birthweight. The NNT needs to be considered, and weighted against that of other protective measures, eventually targeting areas which are above a certain threshold of malaria transmission to maximise the benefit. © 2014 John Wiley & Sons Ltd.

In vitro antiplasmodial activity and prophylactic potentials of extract and fractions of Trema orientalis (Linn.) stem bark.

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Olanlokun, John Oludele; David, Oluwole Moses; Afolayan, Anthony Jide

2017-08-15

Trema orientalis (T. orientalis Linn) has been used in the management of malaria in the western part of Nigeria and despite its application in ethnomedicine, there is dearth of scientific evidence to justify the acclaimed prophylactic antimalarial usage of the plant. The aim of this study is to assess the in vitro antiplasmodial cell-free assay and chemopreventive efficacy of the methanol extract of the stem bark of T. orientalis and its fractions as a prophylactic regimen for malaria prevention. Also, the antimicrobial activities of the extract and the fractions were investigated. Vacuum liquid chromatography was used to obtain dichloromethane, ethylacetate and methanol fractions from the methanol extract of T. orientalis. The fractions were tested for their prophylactic and cell-free antimalarial activity using murine models and β-hematin formation assay respectively. Disc diffusion method was used to determine the antibacterial activity of the extract and its fractions against both Gram-positive and Gram-negative bacteria. In the prophylactic experiment, dichloromethane (DCMF), methanol fraction (MF) and extract (ME) (in this order) showed significant chemopreventive effects against P. berghei invasion of the red blood cells when compared with both Sulfadoxine-Pyrimethamine (SP) and untreated controls. Results of the in vitro study showed that the DCMF had the highest effect in preventing the formation of β-hematin when compared with other fractions. The DCMF also had the highest percentage inhibition of β-hematin formation when compared with chloroquine. The extract and fractions showed a concentration dependent antibacterial activity. Methanol extract had a pronounced inhibitory effect on Enterobacter cloaca ATCC 13047 and Enterococcus faecalis ATCC 29212. Serratia mercescens ATCC 9986 and Pseudomonas aeruginosa ATCC 19582 were the most susceptible bacteria. The results obtained showed that both extract and fractions of T. orientalis possessed

Cluster-randomized study of intermittent preventive treatment for malaria in infants (IPTi in southern Tanzania: evaluation of impact on survival

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Schellenberg Joanna

2011-12-01

Full Text Available Abstract Background Intermittent Preventive Treatment for malaria control in infants (IPTi consists of the administration of a treatment dose of an anti-malarial drug, usually sulphadoxine-pyrimethamine, at scheduled intervals, regardless of the presence of Plasmodium falciparum infection. A pooled analysis of individually randomized trials reported that IPTi reduced clinical episodes by 30%. This study evaluated the effect of IPTi on child survival in the context of a five-district implementation project in southern Tanzania. [Trial registration: clinical trials.gov NCT00152204]. Methods After baseline household and health facility surveys in 2004, five districts comprising 24 divisions were randomly assigned either to receive IPTi (n = 12 or not (n = 12. Implementation started in March 2005, led by routine health services with support from the research team. In 2007, a large household survey was undertaken to assess the impact of IPTi on survival in infants aged two-11 months through birth history interviews with all women aged 13-49 years. The analysis is based on an "intention-to-treat" ecological design, with survival outcomes analysed according to the cluster in which the mothers lived. Results Survival in infants aged two-11 months was comparable in IPTi and comparison areas at baseline. In intervention areas in 2007, 48% of children aged 12-23 months had documented evidence of receiving three doses of IPTi, compared to 2% in comparison areas (P P = 0.31. Conclusion The lack of evidence of an effect of IPTi on survival could be a false negative result due to a lack of power or imbalance of unmeasured confounders. Alternatively, there could be no mortality impact of IPTi due to low coverage, late administration, drug resistance, decreased malaria transmission or improvements in vector control and case management. This study raises important questions for programme evaluation design.

Factors Associated with Four or More Antenatal Care Visits and Its Decline among Pregnant Women in Tanzania between 1999 and 2010

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Gupta, Shivam; Yamada, Goro; Mpembeni, Rose; Frumence, Gasto; Callaghan-Koru, Jennifer A.; Stevenson, Raz; Brandes, Neal; Baqui, Abdullah H.

2014-01-01

In Tanzania, the coverage of four or more antenatal care (ANC 4) visits among pregnant women has declined over time. We conducted an exploratory analysis to identify factors associated with utilization of ANC 4 and ANC 4 decline among pregnant women over time. We used data from 8035 women who delivered within two years preceding Tanzania Demographic and Health Surveys conducted in 1999, 2004/05 and 2010. Multivariate logistic regression models were used to examine the association between all potential factors and utilization of ANC 4; and decline in ANC 4 over time. Factors positively associated with ANC 4 utilization were higher quality of services, testing and counseling for HIV during ANC, receiving two or more doses of SP (Sulphadoxine Pyrimethamine)/Fansidar for preventing malaria during ANC and higher educational status of the woman. Negatively associated factors were residing in a zone other than Eastern zone, never married woman, reported long distance to health facility, first ANC visit after four months of pregnancy and woman's desire to avoid pregnancy. The factors significantly associated with decline in utilization of ANC 4 were: geographic zone and age of the woman at delivery. Strategies to increase ANC 4 utilization should focus on improvement in quality of care, geographic accessibility, early ANC initiation, and services that allow women to avoid pregnancy. The interconnected nature of the Tanzanian Health System is reflected in ANC 4 decline over time where introduction of new programs might have had unintended effects on existing programs. An in-depth assessment of the recent policy change towards Focused Antenatal Care and its implementation across different geographic zones, including its effect on the perception and understanding among women and performance and counseling by health providers can help explain the decline in ANC 4. PMID:25036291

Incidence of Malaria and Efficacy of Combination Antimalarial Therapies over 4 Years in an Urban Cohort of Ugandan Children

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Clark, Tamara D.; Njama-Meya, Denise; Nzarubara, Bridget; Maiteki-Sebuguzi, Catherine; Greenhouse, Bryan; Staedke, Sarah G.; Kamya, Moses R.; Dorsey, Grant; Rosenthal, Philip J.

2010-01-01

Background Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda. Methodology/Principal Findings Children aged 1–10 years were enrolled from randomly selected households in 2004–05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen. Conclusions/Significance With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time. Trial Registration isrctn.org ISRCTN37517549 PMID:20689585

Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi from Ghana and Gabon

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Kreuels Benno

2008-10-01

Full Text Available Abstract Background Intermittent preventive treatment in infants (IPTi with sulphadoxine-pyrimethamine (SP reduces the incidence of malaria episodes in young children. The exact mechanism by which the protective effect is mediated needs to be defined. This study aimed to investigate therapeutic, prophylactic, and possible exceeding effects of SP-based IPTi in two clinical trials. Methods Protective efficacies from two IPTi trials performed in Kumasi, Ghana, and Lambaréné, Gabon, were assessed for overlapping time series of 61 days. For six-months periods after each of three IPTi doses a multivariate Poisson regression model with the respective cohort as co-variate was generated and effect modification of protective efficacy with time strata was evaluated by log-likelihood tests. Results Protective efficacies were not significantly different between the two study cohorts. Study-cohort corrected protective efficacy was highest for the first 61 days after each IPTi application and decreased continuously. For the first 61 days after IPTi-1, IPTi-2, and IPTi-3 the protective efficacy was 71%, 44%, and 43%, respectively. A reduction of the malaria incidence rate was detectable for the first 60, 30 and 40 days after IPTi-1, IPTi-2 and IPTi-3 drug application, respectively. After IPTi-3 a higher risk for malaria could be seen after day 60. This effect was mainly based on the overwhelming influence of the Kumasi cohort. Conclusion The results suggest that SP-based IPTi mainly works through a therapeutic and prophylactic effect over 30 to 60 days after drug application and that a sustained effect beyond post-treatment prophylaxis might be very low. Trial registration Data analysis from clinical trials NCT ID # 00206739 (Kumasi Trial and NCT ID # 00167843 (Lambaréné Trial, http://www.clinicaltrials.gov.

Determinants of timely uptake of ITN and SP (IPT) and pregnancy time protected against malaria in Bukoba, Tanzania.

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Protas, Joyce; Tarimo, D; Moshiro, C

2016-06-21

Insecticides treated nets (ITNs) and intermittent preventive therapy with two doses of sulfadoxine-pyrimethamine (SP IPTp) are the cornerstone for malaria control in pregnancy. Despite the coverage of these interventions being high, it is not known whether they confer optimal protection time against malaria in pregnancy. This study investigated the timing and determinants of timely uptake of SP(IPTp) and ITNs and the pregnancy time protected. A health facility based cross-sectional study was carried out in Bukoba urban district from 16th April to 29 May 2013. Involving pregnant women and post natal mothers attending Reproductive and Child Health (RCH) clinics. Data on their socio-economic background, pregnancy history and attendance to RCH, receipt of a voucher and acquisition of an ITN as well as SP for IPTp were collected. Their responses were validated from the records of antenatal cards. Data was analysed using SPSS computer program version 20. A total of 530 mothers were recruited. The overall uptake of SP IPTp was 96 % and the uptake of two SP (IPTp) doses was 86 %. Timely uptake of 1st dose was predicted by early antenatal booking, [AOR 2.59; 95 % CI 1.51-4.46; P = 0.001], and the availability of SP at the facility [AOR 4.63; 95 % CI 2.51-8.54; P discount vouchers at different gestational age and of these, less than a quarter (21.4 %) received timely. Timely receipt of discount voucher was highly predicted by early antenatal booking [AOR 200; 95 % CI 80.38-498; P discount vouchers for ITNs, timely uptake and therefore optimal protection time depended on early antenatal booking, the availability of (SP IPTp) and discount voucher at the health facility.

Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting

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Kabanywanyi Abdunoor M

2010-07-01

Full Text Available Abstract Objectives To identify and implement strategies that help meet safety monitoring requirements in the context of an observational study for artemether-lumefantrine (AL administered as first-line treatment for uncomplicated malaria in rural Tanzania. Methods Pharmacovigilance procedures were developed through collaboration between the investigating bodies, the relevant regulatory authority and the manufacturer of AL. Training and refresher sessions on the pharmacovigilance system were provided for healthcare workers from local health facilities and field recorders of the Ifakara Health Demographic Surveillance System (IHDSS. Three distinct channels for identification of adverse events (AEs and serious adverse events (SAEs were identified and implemented. Passive reporting took place through IHDSS and health care facilities, starting in October 2007. The third channel was through solicited reporting that was included in the context of a survey on AL as part of the ALIVE (Artemether-Lumefantrine In Vulnerable patients: Exploring health impact study (conducted only in March-April 2008. Results Training was provided for 40 healthcare providers (with refresher training 18 months later and for six field recorders. During the period 1st September 2007 to 31st March 2010, 67 AEs were reported including 52 under AL, five under sulphadoxine-pyrimethamine, one under metakelfin, two after antibiotics; the remaining seven were due to anti-pyretic or anti-parasite medications. Twenty patients experienced SAEs; in 16 cases, a relation to AL was suspected. Six of the 20 cases were reported within 24 hours of occurrence. Discussion Safety monitoring and reporting is possible even in settings with weak health infrastructure. Reporting can be enhanced by regular and appropriate training of healthcare providers. SMS text alerts provide a practical solution to communication challenges. Conclusion Experience gained in this setting could help to improve

Substandard anti-malarial drugs in Burkina Faso

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Sie Ali

2008-05-01

Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

Malaria in pregnant women in an area with sustained high coverage of insecticide-treated bed nets

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Mshinda Hassan

2008-07-01

Full Text Available Abstract Background Since 2000, the World Health Organization has recommended a package of interventions to prevent malaria during pregnancy and its sequelae that includes the promotion of insecticide-treated bed nets (ITNs, intermittent preventive treatment in pregnancy (IPTp, and effective case management of malarial illness. It is recommended that pregnant women in malaria-endemic areas receive at least two doses of sulphadoxine-pyrimethamine in the second and third trimesters of pregnancy. This study assessed the prevalence of placental malaria at delivery in women during 1st or 2nd pregnancy, who did not receive intermittent preventive treatment for malaria (IPTp in a malaria-endemic area with high bed net coverage. Methods A hospital-based cross-sectional study was done in Ifakara, Tanzania, where bed net coverage is high. Primi- and secundigravid women, who presented to the labour ward and who reported not using IPTp were included in the study. Self-report data were collected by questionnaire; whereas neonatal birth weight and placenta parasitaemia were measured directly at the time of delivery. Results Overall, 413 pregnant women were enrolled of which 91% reported to have slept under a bed net at home the previous night, 43% reported history of fever and 62% were primigravid. Malaria parasites were detected in 8% of the placenta samples; the geometric mean (95%CI placental parasite density was 3,457 (1,060–11,271 parasites/μl in primigravid women and 2,178 (881–5,383 parasites/μl in secundigravid women. Fifteen percent of newborns weighed Conclusion The observed incidence of LBW and prevalence of placental parasitaemia at delivery suggests that malaria remains a problem in pregnancy in this area with high bed net coverage when eligible women do not receive IPTp. Delivery of IPTp should be emphasized at all levels of implementation to achieve maximum community coverage.

Use of antenatal care, maternity services, intermittent presumptive treatment and insecticide treated bed nets by pregnant women in Luwero district, Uganda

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Mufubenga Patrobas

2008-03-01

Full Text Available Abstract Background To reduce the intolerable burden of malaria in pregnancy, the Ministry of Health in Uganda improved the antenatal care package by including a strong commitment to increase distribution of insecticide-treated nets (ITNs and introduction of intermittent preventive treatment with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP as a national policy in 2000. This study assessed uptake of both ITNs and IPTp-SP by pregnant women as well as antenatal and maternity care use with the aim of optimizing their delivery. Methods 769 post-partum women were recruited from a rural area of central Uganda with perennial malaria transmission through a cross-sectional, community-based household survey in May 2005. Results Of the 769 women interviewed, antenatal clinic (ANC attendance was high (94.4%; 417 (57.7% visiting initially during the 2nd trimester, 242 (33.5% during the 3rd trimester and 266 (37.1% reporting ≥ 4 ANC visits. About 537 (71% and 272 (35.8% received one or ≥ 2 IPTp-SP doses respectively. Only 85 (15.8% received the first dose of IPTp-SP in the 3rd trimester. ITNs were used by 239 (31.3% of women during pregnancy and 314 (40.8% delivered their most recent pregnancy outside a health facility. Post-partum women who lacked post-primary education were more likely not to have attended four or more ANC visits (odds ratio [OR] 3.3, 95% confidence interval [CI] 1.2–9.3. Conclusion These findings illustrate the need to strengthen capacity of the district to further improve antenatal care and maternity services utilization and IPTp-SP uptake. More specific and effective community health strategies to improve effective ANC, maternity services utilization and IPTp-SP uptake in rural communities should be undertaken.

Lending a helping hand, screening chemical libraries for compounds that enhance β-hexosaminidase A activity in GM2 gangliosidosis cells

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Tropak, Michael B.; Mahuran, Don

2010-01-01

Enzyme enhancement therapy is an emerging therapeutic approach that has the potential to treat many genetic diseases. Candidate diseases are those associated with a mutant protein that has difficulty folding and/or assembling into active oligomers in the endoplasmic reticulum. Many lysosomal storage diseases are candidates for enzyme enhancement therapy and have the additional advantage of requiring only 5–10% of normal enzyme levels to reduce and/or prevent substrate accumulation. Our long experience in working with the β-hexosaminidase (EC 3.2.1.52) isozymes system and its associated deficiencies (Tay-Sachs and Sandhoff disease) lead us to search for possible enzyme enhancement therapy-agents that could treat the chronic forms of these diseases which express 2–5% residual activity. Pharmacological chaperones are enzyme enhancement therapy-agents that are competitive inhibitors of the target enzyme. Each of the known β-hexosaminidase inhibitors (low μM IC50) increased mutant enzyme levels to ≥ 10% in chronic Tay-Sachs fibroblasts and also attenuated the thermo-denaturation of β-hexosaminidase. To expand the repertoire of pharmacological chaperones to more ‘drug-like’ compounds, we screened the Maybridge library of 50 000 compounds using a real-time assay for non-carbohydrate-based β-hexosaminidase inhibitors and identified several that functioned as pharmacological chaperones in patient cells. Two of these inhibitors had derivatives that had been tested in humans for other purposes. These observations lead us to screen the NINDS library of 1040 Food and Drug Administration approved compounds for pharmacological chaperones. Pyrimethamine, an antimalarial drug with well documented pharmacokinetics, was confirmed as a β-hexosaminidase pharmacological chaperone and compared favorably with our best carbohydrate-based pharmacological chaperone in patient cells with various mutant genotypes. PMID:17894780

Tracing the origins and signatures of selection of antifolate resistance in island populations of Plasmodium falciparum

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Pinto João

2010-06-01

Full Text Available Abstract Background Resistance of the malaria parasite Plasmodium falciparum to sulfadoxine-pyrimethamine (SP has evolved worldwide. In the archipelago of São Tomé and Principe (STP, West Africa, although SP resistance is highly prevalent the drug is still in use in particular circumstances. To address the evolutionary origins of SP resistance in these islands, we genotyped point mutations at P. falciparum dhfr and dhps genes and analysed microsatellites flanking those genes. Methods Blood samples were collected in July and December 2004 in three localities of São Tomé Island and one in Principe Island. Species-specific nested-PCR was used to identify P. falciparum infected samples. Subsequently, SNPs at the dhfr and dhps genes were identified through PCR-RFLP. Isolates were also analysed for three microsatellite loci flanking the dhfr gene, three loci flanking dhps and four loci located at putative neutral genomic regions. Results An increase of resistance-associated mutations at dhfr and dhps was observed, in particular for the dhfr/dhps quintuple mutant, associated with clinical SP failure. Analysis of flanking microsatellites suggests multiple independent introductions for dhfr and dhps mutant haplotypes, possibly from West Africa. A reduced genetic diversity and increased differentiation at flanking microsatellites when compared to neutral loci is consistent with a selective sweep for resistant alleles at both loci. Conclusions This study provides additional evidence for the crucial role of gene flow and drug selective pressures in the rapid spread of SP resistance in P. falciparum populations, from only a few mutation events giving rise to resistance-associated mutants. It also highlights the importance of human migration in the spread of drug resistant malaria parasites, as the distance between the islands and mainland is not consistent with mosquito-mediated parasite dispersal.

Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents.

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Kumar, Parvin; Kadyan, Kulbir; Duhan, Meenakshi; Sindhu, Jayant; Singh, Vineeta; Saharan, Baljeet Singh

2017-11-14

Acyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively. The present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (5a-g). These molecular hybrids were synthesised by condensation of 1,4-dihydropyridin-4-yl-phenoxyacetohydrazides with differently substituted pyrazole carbaldehyde. The final compound (5) showed two conformations (the major, E, s-cis and the minor, E, s-trans) as revealed by NMR spectral data and further supported by the energy calculations (MOPAC2016 using PM7 method). All the synthesised compounds were screened for their in vitro antimalarial activities against chloroquine-sensitive malaria parasite Plasmodium falciparum (3D7) and antimicrobial activity against Gram positive bacteria i.e. Bacillus cereus, Gram negative bacteria i.e. Escherichia coli and antifungal activity against one yeast i.e. Aspergillus niger. All these compounds were found more potent than chloroquine and clotrimazole, the standard drugs. In vitro antiplasmodial IC 50 value of the most potent compound 5d was found to be 4.40 nM which is even less than all the three reference drugs chloroquine (18.7 nM), pyrimethamine (11 nM) and artimisinin (6 nM). In silico binding study of compound 5d with plasmodial cysteine protease falcipain-2 indicated the inhibition of falcipain-2 as the probable reason for the antimalarial potency of compound 5d. All the compounds had shown good to excellent antimicrobial and antifungal activities.

Prenatal treatment for serious neurological sequelae of congenital toxoplasmosis: an observational prospective cohort study.

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Mario Cortina-Borja

2010-10-01

Full Text Available The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD of congenital toxoplasmosis is not known.Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%. 23/293 (8% fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71. This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15 after maternal seroconversion at 10 weeks, and 18 (9-75 at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95. The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%.The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors' Summary.

Public health facility resource availability and provider adherence to first antenatal guidelines in a low resource setting in Accra, Ghana.

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Amoakoh-Coleman, Mary; Agyepong, Irene Akua; Kayode, Gbenga A; Grobbee, Diederick E; Klipstein-Grobusch, Kerstin; Ansah, Evelyn K

2016-09-21

Lack of resources has been identified as a reason for non-adherence to clinical guidelines. Our aim was to describe public health facility resource availability in relation to provider adherence to first antenatal visit guidelines. A cross-sectional analysis of the baseline data of a prospective cohort study on adherence to first antenatal care visit guidelines was carried out in 11 facilities in the Greater Accra Region of Ghana. Provider adherence was studied in relation to health facility resource availability such as antenatal workload for clinical staffs, routine antenatal drugs, laboratory testing, protocols, ambulance and equipment. Eleven facilities comprising 6 hospitals (54.5 %), 4 polyclinics (36.4 %) and 1 health center were randomly sampled. Complete provider adherence to first antenatal guidelines for all the 946 participants was 48.1 % (95 % CI: 41.8-54.2 %), varying significantly amongst the types of facilities, with highest rate in the polyclinics. Average antenatal workload per month per clinical staff member was higher in polyclinics compared to the hospitals. All facility laboratories were able to conduct routine antenatal tests. Most routine antenatal drugs were available in all facilities except magnesium sulphate and sulphadoxine-pyrimethamine which were lacking in some. Antenatal service protocols and equipment were also available in all facilities. Although antenatal workload varies across different facility types in the Greater Accra region, other health facility resources that support implementation of first antenatal care guidelines are equally available in all the facilities. These factors therefore do not adequately account for the low and varying proportions of complete adherence to guidelines across facility types. Providers should be continually engaged for a better understanding of the barriers to their adherence to these guidelines.

Prenatal treatment for serious neurological sequelae of congenital toxoplasmosis: an observational prospective cohort study.

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Cortina-Borja, Mario; Tan, Hooi Kuan; Wallon, Martine; Paul, Malgorzata; Prusa, Andrea; Buffolano, Wilma; Malm, Gunilla; Salt, Alison; Freeman, Katherine; Petersen, Eskild; Gilbert, Ruth E

2010-10-12

The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known. Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%). The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection. Please see later in the article for the Editors' Summary.

Long-term ocular prognosis in 327 children with congenital toxoplasmosis.

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Wallon, Martine; Kodjikian, Laurent; Binquet, Christine; Garweg, Justus; Fleury, Jacques; Quantin, Catherine; Peyron, François

2004-06-01

Retinochoroiditis is the most frequent consequence of congenital toxoplasmosis. Early diagnosis and treatment are believed to reduce the risk of visual impairment. We report on the clinical evolution of ocular lesions and final visual function in a prospective cohort of congenitally infected children who were identified during monthly maternal prenatal screening. The study included 327 congenitally infected children who were monitored for up to 14 years at the Croix Rousse Hospital in Lyon, France. Data on date of maternal infection; time and type of therapy; antenatal, neonatal, and postnatal work-ups; and ocular status were analyzed. All mothers but 52 had been treated. Pyrimethamine and sulfadiazine was given in utero to 38% of children and after birth to 72% of newborns. Fansidar was given for an average duration of 337 days in all but 2 children. After a median follow-up of 6 years, 79 (24%) children had at least 1 retinochoroidal lesion. In 23 (29%) of them, at least 1 new event had been diagnosed up to 10 years after detection of the first lesions: reactivation of an existing lesion (1 case), new lesion in a previously healthy location (19 cases), or both (3 cases). Fifty-five children had lesions in 1 eye; of the 45 children for whom final visual acuity data were available, 31 (69%) had normal vision. Twenty-four children had lesions in both eyes; of the 21 for whom final visual acuity data were available, 11 had normal vision in both eyes. None had bilateral visual impairment. Clinicians, parents, and elder children with congenital infection should be informed that late-onset retinal lesions and relapse can occur many years after birth but that the overall ocular prognosis of congenital toxoplasmosis is satisfactory when infection is identified early and treated accordingly.

Nonlinear mixed effects modeling of gametocyte carriage in patients with uncomplicated malaria

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Little Francesca

2010-02-01

Full Text Available Abstract Background Gametocytes are the sexual form of the malaria parasite and the main agents of transmission. While there are several factors that influence host infectivity, the density of gametocytes appears to be the best single measure that is related to the human host's infectivity to mosquitoes. Despite the obviously important role that gametocytes play in the transmission of malaria and spread of anti-malarial resistance, it is common to estimate gametocyte carriage indirectly based on asexual parasite measurements. The objective of this research was to directly model observed gametocyte densities over time, during the primary infection. Methods Of 447 patients enrolled in sulphadoxine-pyrimethamine therapeutic efficacy studies in South Africa and Mozambique, a subset of 103 patients who had no gametocytes pre-treatment and who had at least three non-zero gametocyte densities over the 42-day follow up period were included in this analysis. Results A variety of different functions were examined. A modified version of the critical exponential function was selected for the final model given its robustness across different datasets and its flexibility in assuming a variety of different shapes. Age, site, initial asexual parasite density (logged to the base 10, and an empirical patient category were the co-variates that were found to improve the model. Conclusions A population nonlinear modeling approach seems promising and produced a flexible function whose estimates were stable across various different datasets. Surprisingly, dihydrofolate reductase and dihydropteroate synthetase mutation prevalence did not enter the model. This is probably related to a lack of power (quintuple mutations n = 12, and informative censoring; treatment failures were withdrawn from the study and given rescue treatment, usually prior to completion of follow up.

Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

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Olliaro P

2004-01-01

Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction.

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Müller, Fabian; Pontones, Constanza A; Renner, Bertold; Mieth, Maren; Hoier, Eva; Auge, Daniel; Maas, Renke; Zolk, Oliver; Fromm, Martin F

2015-01-01

N(1)-methylnicotinamide (NMN) was proposed as an in vivo probe for drug interactions involving renal cation transporters, which, for example, transport the oral antidiabetic drug metformin, based on a study with the inhibitor pyrimethamine. The role of NMN for predicting other interactions with involvement of renal cation transporters (organic cation transporter 2, OCT2; multidrug and toxin extrusion proteins 1 and 2-K, MATE1 and MATE2-K) is unclear. We determined inhibition of metformin or NMN transport by trimethoprim using cell lines expressing OCT2, MATE1, or MATE2-K. Moreover, a randomized, open-label, two-phase crossover study was performed in 12 healthy volunteers. In each phase, 850 mg metformin hydrochloride was administered p.o. in the evening of day 4 and in the morning of day 5. In phase B, 200 mg trimethoprim was administered additionally p.o. twice daily for 5 days. Metformin pharmacokinetics and effects (measured by OGTT) and NMN pharmacokinetics were determined. Trimethoprim inhibited metformin transport with K i values of 27.2, 6.3, and 28.9 μM and NMN transport with IC50 values of 133.9, 29.1, and 0.61 μM for OCT2, MATE1, and MATE2-K, respectively. In the clinical study, trimethoprim increased metformin area under the plasma concentration-time curve (AUC) by 29.5 % and decreased metformin and NMN renal clearances by 26.4 and 19.9 %, respectively (p ≤ 0.01). Moreover, decreases of NMN and metformin renal clearances due to trimethoprim correlated significantly (r S=0.727, p=0.010). These data on the metformin-trimethoprim interaction support the potential utility of N(1)-methylnicotinamide as an endogenous probe for renal drug-drug interactions with involvement of renal cation transporters.

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

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Mbeye, Nyanyiwe M; ter Kuile, Feiko O; Davies, Mary-Ann; Phiri, Kamija S; Egger, Matthias; Wandeler, Gilles

2014-09-01

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children. © 2014 John Wiley & Sons Ltd.

Factors associated with four or more antenatal care visits and its decline among pregnant women in Tanzania between 1999 and 2010.

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Shivam Gupta

Full Text Available In Tanzania, the coverage of four or more antenatal care (ANC 4 visits among pregnant women has declined over time. We conducted an exploratory analysis to identify factors associated with utilization of ANC 4 and ANC 4 decline among pregnant women over time. We used data from 8035 women who delivered within two years preceding Tanzania Demographic and Health Surveys conducted in 1999, 2004/05 and 2010. Multivariate logistic regression models were used to examine the association between all potential factors and utilization of ANC 4; and decline in ANC 4 over time. Factors positively associated with ANC 4 utilization were higher quality of services, testing and counseling for HIV during ANC, receiving two or more doses of SP (Sulphadoxine Pyrimethamine/Fansidar for preventing malaria during ANC and higher educational status of the woman. Negatively associated factors were residing in a zone other than Eastern zone, never married woman, reported long distance to health facility, first ANC visit after four months of pregnancy and woman's desire to avoid pregnancy. The factors significantly associated with decline in utilization of ANC 4 were: geographic zone and age of the woman at delivery. Strategies to increase ANC 4 utilization should focus on improvement in quality of care, geographic accessibility, early ANC initiation, and services that allow women to avoid pregnancy. The interconnected nature of the Tanzanian Health System is reflected in ANC 4 decline over time where introduction of new programs might have had unintended effects on existing programs. An in-depth assessment of the recent policy change towards Focused Antenatal Care and its implementation across different geographic zones, including its effect on the perception and understanding among women and performance and counseling by health providers can help explain the decline in ANC 4.

Factors associated with four or more antenatal care visits and its decline among pregnant women in Tanzania between 1999 and 2010.

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Gupta, Shivam; Yamada, Goro; Mpembeni, Rose; Frumence, Gasto; Callaghan-Koru, Jennifer A; Stevenson, Raz; Brandes, Neal; Baqui, Abdullah H

2014-01-01

In Tanzania, the coverage of four or more antenatal care (ANC 4) visits among pregnant women has declined over time. We conducted an exploratory analysis to identify factors associated with utilization of ANC 4 and ANC 4 decline among pregnant women over time. We used data from 8035 women who delivered within two years preceding Tanzania Demographic and Health Surveys conducted in 1999, 2004/05 and 2010. Multivariate logistic regression models were used to examine the association between all potential factors and utilization of ANC 4; and decline in ANC 4 over time. Factors positively associated with ANC 4 utilization were higher quality of services, testing and counseling for HIV during ANC, receiving two or more doses of SP (Sulphadoxine Pyrimethamine)/Fansidar for preventing malaria during ANC and higher educational status of the woman. Negatively associated factors were residing in a zone other than Eastern zone, never married woman, reported long distance to health facility, first ANC visit after four months of pregnancy and woman's desire to avoid pregnancy. The factors significantly associated with decline in utilization of ANC 4 were: geographic zone and age of the woman at delivery. Strategies to increase ANC 4 utilization should focus on improvement in quality of care, geographic accessibility, early ANC initiation, and services that allow women to avoid pregnancy. The interconnected nature of the Tanzanian Health System is reflected in ANC 4 decline over time where introduction of new programs might have had unintended effects on existing programs. An in-depth assessment of the recent policy change towards Focused Antenatal Care and its implementation across different geographic zones, including its effect on the perception and understanding among women and performance and counseling by health providers can help explain the decline in ANC 4.

The association between price, competition, and demand factors on private sector anti-malarial stocking and sales in western Kenya: considerations for the AMFm subsidy

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2013-01-01

Background Households in sub-Saharan Africa are highly reliant on the retail sector for obtaining treatment for malaria fevers and other illnesses. As donors and governments seek to promote the use of artemisinin combination therapy in malaria-endemic areas through subsidized anti-malarials offered in the retail sector, understanding the stocking and pricing decisions of retail outlets is vital. Methods A survey of all medicine retailers serving Bungoma East District in western Kenya was conducted three months after the launch of the AMFm subsidy in Kenya. The survey obtained information on each anti-malarial in stock: brand name, price, sales volume, outlet characteristics and GPS co-ordinates. These data were matched to household-level data from the Webuye Health and Demographic Surveillance System, from which population density and fever prevalence near each shop were determined. Regression analysis was used to identify the factors associated with retailers’ likelihood of stocking subsidized artemether lumefantrine (AL) and the association between price and sales for AL, quinine and sulphadoxine-pyrimethamine (SP). Results Ninety-seven retail outlets in the study area were surveyed; 11% of outlets stocked subsidized AL. Size of the outlet and having a pharmacist on staff were associated with greater likelihood of stocking subsidized AL. In the multivariable model, total volume of anti-malarial sales was associated with greater likelihood of stocking subsidized AL and competition was important; likelihood of stocking subsidized AL was considerably higher if the nearest neighbour stocked subsidized AL. Price was a significant predictor of sales volume for all three types of anti-malarials but the relationship varied, with the largest price sensitivity found for SP drugs. Conclusion The results suggest that helping small outlets overcome the constraints to stocking subsidized AL should be a priority. Competition between retailers and prices can play an important

Evaluation of prevalence's of pfdhfr and pfdhps mutations in Angola

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2011-01-01

Background Malaria is the major cause of morbidity and mortality in Angola. The most vulnerable groups to Plasmodium falciparum infection are pregnant women and children under five years of age. The use of an intermittent preventive treatment (IPT) with sulphadoxine/pyrimethamine (SP) in pregnant women was introduced in Angola in 2006 by the National Malaria Control Programme, and currently this strategy has been considered to be used for children malaria control. Considering the previous wide use of SP combination in Angola, together to the reported cases of SP treatment failure it is crucial the evaluation of the prevalence of five mutations in pfdhfr and pfdhps genes associated to P. falciparum resistance to SP before the introduction of S/P IPT in children. Methods The study was conducted in five provinces, with different transmission intensities: Huambo, Cabinda, Uíge, Kwanza Norte, and Malanje. The detection of the mutations in pfdhfr and pfdhps genes was carried out in 452 P. falciparum blood samples by PCR RFLP. Results For pfdhfr gene, 90,3% of the samples carried the mutation 51I, with 7.5% of mixed infections; 51% carried wild type allele 59C, with 29.2% mixed infections and; 99.1% of isolates harboured the mutant allele 108N. Concerning, pfdhps gene, 83,1% were mutant type 437G with 11% mixed infections , while 87% of the studied isolates were wild type for codon 540. Discussion This is the first representative epidemiological study of the whole Angola country on the prevalence of the genotypes associated with SP chemoresistance. A high frequency of individual mutations in both genes (51I and 108N in pfdhfr, and 437G in pfdhps) was found, besides a low prevalence of the quintuple mutation. Conclusion The data showed that the implementation IPT using SP in children needs to be reviewed. PMID:21288345

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic.

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Clara Menéndez

2008-04-01

Full Text Available Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs and intermittent preventive treatment (IPTp. However, there is no information on the safety and efficacy of their combined use.1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP. The main outcome was the reduction in low birth weight.Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79-1.08], low birth weight (RR, 0.99 [95% CI, 0.70-1.39], or overall placental infection (p = 0.964. However, the SP group showed a 40% reduction (95% CI, 7.40-61.20]; p = 0.020 in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15% (p<0.001, and of actively infected placentas (7.04% vs 13.60% (p = 0.002. There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055. These effects were not modified by gravidity or HIV status. Reported ITN's use was more than 90% in both groups.Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.ClinicalTrials.gov NCT00209781.

Asymptomatic Plasmodium falciparum infection is associated with anaemia in pregnancy and can be more cost-effectively detected by rapid diagnostic test than by microscopy in Kinshasa, Democratic Republic of the Congo.

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Matangila, Junior R; Lufuluabo, Jean; Ibalanky, Axel L; Inocêncio da Luz, Raquel A; Lutumba, Pascal; Van Geertruyden, Jean-Pierre

2014-04-02

In areas of high malaria transmission, Plasmodium falciparum infection during pregnancy is characterized by malaria-related anaemia, placental malaria and does not always result in clinical symptoms. This situation is associated with poor pregnancy outcomes. The aim of this study was to determine the extent of asymptomatic P. falciparum infection, its relation with anaemia as well as the most cost-effective technique for its diagnosis in healthy pregnant women living in Kinshasa, Democratic Republic of the Congo. In a cross-sectional study design, information on socio-demographic characteristics and cost data were collected in healthy pregnant women attending antenatal care consultations. Plasmodium falciparum infection was diagnosed using rapid diagnostic test (RDT), microscopy and polymerase chain reaction (PCR). Haemoglobin concentration was also determined. In total, 332 pregnant women were enrolled. RDT and microscopy data were available for all the blood samples and 166 samples were analysed by PCR. The prevalence of asymptomatic P. falciparum infection using microscopy, RDTs and PCR, were respectively 21.6%, 27.4% and 29.5%. Taking PCR as a reference, RDTs had a sensitivity of 81.6% and a specificity of 94.9% to diagnose asymptomatic P. falciparum infection. The corresponding values for microscopy were 67.3% and 97.4%. The prevalence of anaemia was 61.1% and asymptomatic malaria increased five times the odds (p anaemia. RDTs were more cost-effective compared to microscopy. Incremental cost-effectiveness ratio was US$ 63.47 per microscopy adequately diagnosed case. These alarming results emphasize the need to actively diagnose and treat asymptomatic malaria infection during all antenatal care visits. Moreover, in DRC, malaria and anaemia control efforts should be strengthened by promoting the use of insecticide-treated nets, intermittent preventive treatment with sulphadoxine-pyrimethamine and iron and folic acid supplements.

An analysis of timing and frequency of malaria infection during pregnancy in relation to the risk of low birth weight, anaemia and perinatal mortality in Burkina Faso

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Valea Innocent

2012-03-01

Full Text Available Abstract Background A prospective study aiming at assessing the effect of adding a third dose sulphadoxine-pyrimethamine (SP to the standard two-dose intermittent preventive treatment for pregnant women was carried out in Hounde, Burkina Faso, between March 2006 and July 2008. Pregnant women were identified as earlier as possible during pregnancy through a network of home visitors, referred to the health facilities for inclusion and followed up until delivery. Methods Study participants were enrolled at antenatal care (ANC visits and randomized to receive either two or three doses of SP at the appropriate time. Women were visited daily and a blood slide was collected when there was fever (body temperature > 37.5°C or history of fever. Women were encouraged to attend ANC and deliver in the health centre, where the new-born was examined and weighed. The timing and frequency of malaria infection was analysed in relation to the risk of low birth weight, maternal anaemia and perinatal mortality. Results Data on birth weight and haemoglobin were available for 1,034 women. The incidence of malaria infections was significantly lower in women having received three instead of two doses of SP. Occurrence of first malaria infection during the first or second trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p p = 0.034, respectively. After adjusting for possible confounding factors, the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.07, p = 0.002. The risk of maternal anaemia and perinatal mortality was not associated with the timing of first malaria infection. Conclusion Malaria infection during first trimester of pregnancy is associated to a higher risk of low birth weight. Women should be encouraged to use long-lasting insecticidal nets before and throughout their pregnancy.

Sulfadoxine-Pyrimethamine-Based Intermittent Preventive Treatment, Bed Net Use, and Antenatal Care during Pregnancy: Demographic Trends and Impact on the Health of Newborns in the Kassena Nankana District, Northeastern Ghana

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2010-01-01

all children less than five years of age and for pregnant and nursing women. Design. This study was a prospective cohort study in which pregnant...during 2003.7 Similarly, bed net use during pregnancy, which was reported by 29% of 102 nursing and pregnant women sur- veyed in 2000, increased...malarious area of Malawi. Ann Trap Paediatr 24: 311-321. 27. Uneke CJ, I yare FE, Sunday-Adeoye H. Ajayi JA, 2008. Evalua- tion of maternal malaria at

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment

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Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul

2014-01-01

Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We

Isolation and identification of an antiparasitic triterpenoid estersaponin from the stem bark of Pittosporum mannii (Pittosporaceae

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Kennedy D Nyongbela

2013-10-01

Full Text Available Objective: To screen for antiparasitic properties of Pittosporum mannii Hook (Pittosporaceae through in vitro bioassay tests and to identify the bioactive compound(s. Methods: The stem bark of Pittosporum mannii was harvested in Bali Nyonga in January 2007. The CH 2Cl2 and MeOH extracts were tested in vitro for antiparasitic activity. NF54 (an airport strain of unknown origin and sensitive to all known drugs and K1 (a clone originating from Thailand and resistant to chloroquine/pyrimethamine strains were used for the antiplasmodial screening while Leishmania donovani MHOM-ET-67/L82 was used for antileishmanial testing. 1H and 13C NMR spectra were recorded on a Bruker AMX-500 spectrometer using CDCl3 as solvent. EIMS were recorded on a double-focusing mass spectrometer (Varian MAT 311A while HREIMS were recorded on a JEOL HX 110 mass spectrometer. Results: The MeOH extract was active on both the chloroquine-resistant (K1 strain (IC50=4.3 μg/ mL and on the macrophages of Leishmania donovani (IC50=8.6 μg/mL. The CH2Cl2 extract was considered inactive on both parasites (IC50>5.0 μg/mL and 21.7 μg/mL respectively. Compound 1, a constituent that precipitated from the MeOH extract, showed pronounced activity on both Plasmodium falciparum and Leishmania donovani parasites (IC 50=1.02 and 1.80 μg/mL respectively with artemisinin and miltefosine included as reference drugs. Its structure was identified as 1-O-[apha-L-(Rhamnopyranosyl]-23-acetoxyimberbic acid 29-methyl ester, a pentacyclic triterpenoid estersaponin. Conclusions: The present study constitutes the first report on the antiparasitic activity of this plant and provides some support for the traditional use of the plant in the treatment of malaria. The plant has therefore been identified as a potential source for the discovery of antiparasitic lead compounds.

Impact of Malaria Control on Mortality and Anemia among Tanzanian Children Less than Five Years of Age, 1999-2010.

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Paul Smithson

Full Text Available Mainland Tanzania scaled up multiple malaria control interventions between 1999 and 2010. We evaluated whether, and to what extent, reductions in all-cause under-five child mortality (U5CM tracked with malaria control intensification during this period.Four nationally representative household surveys permitted trend analysis for malaria intervention coverage, severe anemia (hemoglobin <8 g/dL prevalence (SAP among children 6-59 months, and U5CM rates stratified by background characteristics, age, and malaria endemicity. Prevalence of contextual factors (e.g., vaccination, nutrition likely to influence U5CM were also assessed. Population attributable risk percentage (PAR% estimates for malaria interventions and contextual factors that changed over time were used to estimate magnitude of impact on U5CM.Household ownership of insecticide-treated nets (ITNs rose from near zero in 1999 to 64% (95% CI, 61.7-65.2 in 2010. Intermittent preventive treatment of malaria in pregnancy reached 26% (95% CI, 23.6-28.0 by 2010. Sulfadoxine-pyrimethamine replaced chloroquine in 2002 and artemisinin-based combination therapy was introduced in 2007. SAP among children 6-59 months declined 50% between 2005 (11.1%; 95% CI, 10.0-12.3% and 2010 (5.5%; 95% CI, 4.7-6.4% and U5CM declined by 45% between baseline (1995-9 and endpoint (2005-9, from 148 to 81 deaths/1000 live births, respectively. Mortality declined 55% among children 1-23 months of age in higher malaria endemicity areas. A large reduction in U5CM was attributable to ITNs (PAR% = 11 with other malaria interventions adding further gains. Multiple contextual factors also contributed to survival gains.Marked declines in U5CM occurred in Tanzania between 1999 and 2010 with high impact from ITNs and ACTs. High-risk children (1-24 months of age in high malaria endemicity experienced the greatest declines in mortality and SAP. Malaria control should remain a policy priority to sustain and further accelerate

Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda.

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Adoke Yeka

2005-07-01

Full Text Available BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ + sulfadoxine-pyrimethamine (SP; amodiaquine (AQ + SP; or AQ + artesunate (AS. Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84% were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01 after AQ + SP or AQ + AS (7%-18% and 4%-12%, respectively. Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003. CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN

Artemisinin versus Nonartemisinin Combination Therapy for Uncomplicated Malaria: Randomized Clinical Trials from Four Sites in Uganda

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Yeka, Adoke; Banek, Kristin; Bakyaita, Nathan; Staedke, Sarah G; Kamya, Moses R; Talisuna, Ambrose; Kironde, Fred; Nsobya, Samuel L; Kilian, Albert; Slater, Madeline; Reingold, Arthur; Rosenthal, Philip J; Wabwire-Mangen, Fred; Dorsey, Grant

2005-01-01

Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. Methods and Findings We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p AQ + SP or AQ + AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, pAQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http

Are patent medicine vendors effective agents in malaria control? Using lot quality assurance sampling to assess quality of practice in Jigawa, Nigeria.

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Sima Berendes

Full Text Available BACKGROUND: Patent medicine vendors (PMV provide antimalarial treatment and care throughout Sub-Saharan Africa, and can play an important role in the fight against malaria. Their close-to-client infrastructure could enable lifesaving artemisinin-based combination therapy (ACT to reach patients in time. However, systematic assessments of drug sellers' performance quality are crucial if their role is to be managed within the health system. Lot quality assurance sampling (LQAS could be an efficient method to monitor and evaluate PMV practice, but has so far never been used for this purpose. METHODS: In support of the Nigeria Malaria Booster Program we assessed PMV practices in three Senatorial Districts (SDs of Jigawa, Nigeria. A two-stage LQAS assessed whether at least 80% of PMV stores in SDs used national treatment guidelines. Acceptable sampling errors were set in consultation with government officials (alpha and beta <0.10. The hypergeometric formula determined sample sizes and cut-off values for SDs. A structured assessment tool identified high and low performing SDs for quality of care indicators. FINDINGS: Drug vendors performed poorly in all SDs of Jigawa for all indicators. For example, all SDs failed for stocking and selling first-line antimalarials. PMV sold no longer recommended antimalarials, such as Chloroquine, Sulfadoxine-Pyrimethamine and oral Artesunate monotherapy. Most PMV were ignorant of and lacked training about new treatment guidelines that had endorsed ACTs as first-line treatment for uncomplicated malaria. CONCLUSION: There is urgent need to regularly monitor and improve the availability and quality of malaria treatment provided by medicine sellers in Nigeria; the irrational use of antimalarials in the ACT era revealed in this study bears a high risk of economic loss, death and development of drug resistance. LQAS has been shown to be a suitable method for monitoring malaria-related indicators among PMV, and should be

Effect of transmission reduction by insecticide-treated bednets (ITNs on antimalarial drug resistance in western Kenya.

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Monica Shah

Full Text Available Despite the clear public health benefit of insecticide-treated bednets (ITNs, the impact of malaria transmission-reduction by vector control on the spread of drug resistance is not well understood. In the present study, the effect of sustained transmission reduction by ITNs on the prevalence of Plasmodium falciparum gene mutations associated with resistance to the antimalarial drugs sulfadoxine-pyrimethamine (SP and chloroquine (CQ in children under the age of five years was investigated during an ITN trial in Asembo area, western Kenya. During the ITN trial, the national first line antimalarial treatment changed from CQ to SP. Smear-positive samples collected from cross sectional surveys prior to ITN introduction (baseline, n = 250 and five years post-ITN intervention (year 5 survey, n = 242 were genotyped for single nucleotide polymorphisms (SNPs at dhfr-51, 59, 108, 164 and dhps-437, 540 (SP resistance, and pfcrt-76 and pfmdr1-86 (CQ resistance. The association between the drug resistance mutations and epidemiological variables was evaluated. There were significant increases in the prevalence of SP dhps mutations and the dhfr/dhps quintuple mutant, and a significant reduction in the proportion of mixed infections detected at dhfr-51, 59 and dhps-437, 540 SNPs from baseline to the year 5 survey. There was no change in the high prevalence of pfcrt-76 and pfmdr1-86 mutations. Multivariable regression analysis further showed that current antifolate use and year of survey were significantly associated with more SP drug resistance mutations. These results suggest that increased antifolate drug use due to drug policy change likely led to the high prevalence of SP mutations 5 years post-ITN intervention and reduced transmission had no apparent effect on the existing high prevalence of CQ mutations. There is no evidence from the current study that sustained transmission reduction by ITNs reduces the prevalence of genes associated with malaria

Exposure to anti-malarial drugs and monitoring of adverse drug reactions using toll-free mobile phone calls in private retail sector in Sagamu, Nigeria: implications for pharmacovigilance

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Ogunwande Isiaka A

2011-08-01

Full Text Available Abstract Background Adverse drug reactions (ADRs contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu - a peri-urban community in Southwest Nigeria. Methods Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP and four Patent and Proprietary Medicine Stores (PPMS in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. Results and Discussion A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases; of this number, purchases of sulphadoxine-pyrimethamine (SP and chloroquine (CQ were highest (39.3 and 25.2% respectiuvely. Other anti-malarials purchased were artesunate monotherapy (AS - 16.1%, artemether-lumefantrine (AL 10.0%, amodiaquine (AQ - 6.6%, quinine (QNN - 1.9%, halofantrine (HF - 0.2% and proguanil (PR - 0.2%. CQ was the cheapest (USD 0.3 and halofantrine the most expensive (USD 7.7. AL was 15.6 times ($4.68 more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1 after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%. Conclusion The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource

Prevalence of antifolate resistance mutations in Plasmodium falciparum isolates in Afghanistan

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2013-01-01

Background Artesunate plus sulphadoxine-pyrimethamine (AS+SP) is now first-line treatment for Plasmodium falciparum infection in several south Asian countries, including Afghanistan. Molecular studies provide a sensitive means to investigate the current state of drug susceptibility to the SP component, and can also provide information on the likely efficacy of other potential forms of artemisinin-combination therapy. Methods During the years 2007 to 2010, 120 blood spots from patients with P. falciparum malaria were obtained in four provinces of Afghanistan. PCR-based methods were used to detect drug-resistance mutations in dhfr, dhps, pfcrt and pfmdr1, as well as to determine copy number of pfmdr1. Results The majority (95.5%) of infections had a double mutation in the dhfr gene (C59R, S108N); no mutations at dhfr positions 16, 51 or 164 were seen. Most isolates were wild type across the dhps gene, but five isolates from the provinces of Kunar and Nangarhar in eastern Afghanistan had the triple mutation A437G / K540E / A581G; all five cases were successfully treated with three receiving AS+SP and two receiving dihydroartemisinin-piperaquine. All isolates showed the pfcrt SVNMT chloroquine resistance haplotype. Five of 79 isolates had the pfmdr1 N86Y mutation, while 52 had pfmdr1 Y184F; positions 1034, 1042 and 1246 were wild type in all isolates. The pfmdr1 gene was not amplified in any sample. Conclusions This study indicates that shortly after the adoption of AS+SP as first-line treatment in Afghanistan, most parasites had a double mutation haplotype in dhfr, and a small number of isolates from eastern Afghanistan harboured a triple mutation haplotype in dhps. The impact of these mutations on the efficacy of AS+SP remains to be assessed in significant numbers of patients, but these results are clearly concerning since they suggest a higher degree of SP resistance than previously detected. Further focused molecular and clinical studies in this region are urgently

Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 1; referees: 2 approved

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Linh Nguyen

2016-12-01

Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than K-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: We now know that this type of models can predict in vitro tumour response to these drugs. These models can thus be further investigated on in vivo tumour models.

Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

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Bertocchi Paola

2007-02-01

Full Text Available Abstract Background The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. Methods In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. Results The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiry date; low content of active substance (in one sample; different, non-declared, active substance (in one sample; sub-standard technological properties and very low dissolution profiles (in about 50% of samples. This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. Conclusion This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution

Polymorphisms in pfdhfr and pfdhps genes after five years of artemisinin combination therapy (ACT) implementation from urban Kolkata, India.

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Chatterjee, Moytrey; Ganguly, Swagata; Saha, Pabitra; Guha, Subhasish K; Maji, Ardhendu Kumar

2017-09-01

In India, sulphadoxine-pyrimethamine (SP) is now in use as a partner drug of ACT (AS+SP) to treat uncomplicated falciparum malaria since 2010. Declined trend of AS+SP efficacy has been reported from north-eastern states of the country. It is not possible to determine the efficacy of SP alone from any study with ACT. So, this work was designed to study the pattern of polymorphisms in pfdhfr and pfdhps genes to predict the SP resistance status among parasite population of urban Kolkata after five years of ACT implementation. A total of 125 P. falciparum positive patients were enrolled in the study during December 2014 to July 2016 and treated with AS+SP. Parasitic DNA was isolated and subjected to sequencing of pfdhfr and pfdhps genes directly from purified PCR products. Genotyping of both the genes was successfully done in 113 isolates. In pfdhfr, 94.69% (107/113) isolates showed mutations at codon 59 and 108. A double mutant genotype ANRNI was mostly prevalent (107/113, 94.69%), while wild-type genotype ANCSI was found only in 5.3% (6/113) isolates. In pfdhps, mutations were recorded at codon 436 and 437 in 65.49% (74/113) and 23.01% (26/113) isolates, respectively. In combined pfdhfr-pfdhps genes, triple mutant ANRNI-FAKAA was most prevalent (45/113, 39.82%) followed by double mutant ANRNI-SAKAA (37/113, 32.74%) and quadruple mutant ANRNI-FGKAA (24/113, 21.24%). SP resistance hallmark mutations i.e., quadruple (AIRNI-SAEAA) or quintuple (AIRNI-SGEAA) genotype in pfdhfr and pfdhps was absent which indicates that SP components of used ACT is still effective in the study area. It is also evident by the clinical response of AS+SP. Monitoring the efficacy of this combination (both by therapeutic and molecular marker study) at a regular interval is highly suggested to record any development of SP resistance in near future. Copyright © 2017 Elsevier B.V. All rights reserved.

Utilization of intermittent preventive treatment for malaria among pregnant women attending antenatal clinics in health facilities of Cross River State, Nigeria

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Esu E

2013-09-01

Full Text Available Ekpereonne Esu,1,2 Emmanuel Effa,1,2 Ekong Udoh,1,2 Olabisi Oduwole,1,2 Friday Odey,1,2 Moriam Chibuzor,1 Angela Oyo-Ita,1,2 Martin Meremikwu1,2 1Calabar Institute of Tropical Diseases Research and Prevention, University of Calabar Teaching Hospital, Calabar, Nigeria; 2College of Medical Sciences, University of Calabar, Calabar, Nigeria Objective: This study assessed the utilization of intermittent preventive treatment with sulfadoxine–pyrimethamine for the prevention of malaria in pregnancy against the national treatment policy among women attending health care facilities in Cross River State, Nigeria. Methods: A clinical audit was carried out between January 2012 and March 2012 using case records of pregnant women who received antenatal care in health facilities in the state. Facilities were selected by simple random sampling. Information on the frequency of antenatal clinic (ANC visits by the women, as well as parity, age, and adherence to intermittent preventive treatment (IPTp doses was obtained using an audit checklist. Results: A total of 322 pregnant women were assessed across 36 health care facilities. In addition, 246 (76% of them attended the ANC in public health facilities. Age, parity, and gestational age at booking were recorded in more than 95% of the cases evaluated. The audit showed that 13.7% of the women did not utilize IPTp, 53.1% had one dose of IPTp (IPTp1, 24.2% had two doses of IPTp (IPTp2, while 3.1% had three doses of IPTp (IPTp3. The overall utilization of two doses or more of IPTp (IPTp2+ was 30.7%. Conclusion: There was good documentation of the basic obstetric information of pregnant women in the health care facilities examined in this study, but the overall utilization of IPTp was very low. Efforts at ensuring early ANC booking and regular visits may be a potential means of increasing IPTp utilization in health care facilities in the state. Keywords: intermittent preventive treatment, malaria, pregnancy, clinical

Access to artemisinin-combination therapy (ACT) and other anti-malarials: national policy and markets in Sierra Leone.

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Amuasi, John H; Diap, Graciela; Nguah, Samuel Blay; Karikari, Patrick; Boakye, Isaac; Jambai, Amara; Lahai, Wani Kumba; Louie, Karly S; Kiechel, Jean-Rene

2012-01-01

Malaria remains the leading burden of disease in post-conflict Sierra Leone. To overcome the challenge of anti-malarial drug resistance and improve effective treatment, Sierra Leone adopted artemisinin-combination therapy artesunate-amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum malaria. Other national policy anti-malarials include artemether-lumefantrine (AL) as an alternative to AS+AQ, quinine and artemether for treatment of complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp). This study was conducted to evaluate access to national policy recommended anti-malarials. A cross-sectional survey of 127 medicine outlets (public, private and NGO) was conducted in urban and rural areas. The availability on the day of the survey, median prices, and affordability policy and available non-policy anti-malarials were calculated. Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely available in public medicine outlets; AL was only available in the private and NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets and over one-third of private outlets. SP was widely available in all outlets. Non-policy anti-malarials were predominantly available in the private outlets. AS+AQ in the public sector was widely offered for free. Among the anti-malarials sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine tablets (US$0.63), were found in both the public and private sectors. Quinine injection had a median cost of US$0.31 in the public sector and US$0.47 in the private sector, while SP had a median cost of US$0.31 in the public sector compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable at nearly two days' worth of wages in both the public and private sectors.

Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

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Jie Feng

2015-09-01

Full Text Available Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS. While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV, thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin, and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy

Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data

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2011-01-01

Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine (SP) resistance, 90% of sub-Saharan African countries had adopted policies of artemisinin-based combination therapy (ACT) for treatment of uncomplicated malaria by 2007. In Malawi, cessation of chloroquine use was followed by the re-emergence of chloroquine-susceptible malaria. It was expected that introduction of ACT would lead to a return in chloroquine susceptibility throughout Africa, but this has not yet widely occurred. This observation suggests that there is continuing use of ineffective anti-malarials in Africa and that persistent chloroquine-resistant malaria is due to ongoing drug pressure despite national policy changes. Methods To estimate drug use on a national level, 2006-2007 Demographic Health Survey and Multiple Indicator Cluster Survey data from 21 African countries were analysed. Resistance data were compiled by systematic review of the published literature on the prevalence of the Plasmodium falciparum chloroquine resistance transporter polymorphism at codon 76, which causes chloroquine resistance. Results Chloroquine was the most common anti-malarial used according to surveys from 14 of 21 countries analysed, predominantly in West Africa. SP was most commonly reported in two of 21 countries. Among eight countries with longitudinal molecular resistance data, the four countries where the highest proportion of children treated for fever received chloroquine (Uganda, Burkina Faso, Guinea Bissau, and Mali) also showed no significant declines in the prevalence of chloroquine-resistant infections. The three countries with low or decreasing chloroquine use among children who reported fever treatment (Malawi, Kenya, and Tanzania) had statistically significant declines in the prevalence of chloroquine resistance. Conclusions This study demonstrates that in 2006-2007, chloroquine and SP continued to be used at high rates in many African countries. In countries reporting

Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs).

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Kindermans, Jean-Marie; Vandenbergh, Daniel; Vreeke, Ed; Olliaro, Piero; D'Altilia, Jean-Pierre

2007-07-10

Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs), the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe). From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1-1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum). There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania). Additional studies are required to build a more robust methodology, and to assess current consumptions more accurately in order to better quantify volumes and finances for

Malaria treatment in the retail sector: Knowledge and practices of drug sellers in rural Tanzania

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Makemba Ahmed M

2008-05-01

Full Text Available Abstract Background Throughout Africa, the private retail sector has been recognised as an important source of antimalarial treatment, complementing formal health services. However, the quality of advice and treatment at private outlets is a widespread concern, especially with the introduction of artemisinin-based combination therapies (ACTs. As a result, ACTs are often deployed exclusively through public health facilities, potentially leading to poorer access among parts of the population. This research aimed at assessing the performance of the retail sector in rural Tanzania. Such information is urgently required to improve and broaden delivery channels for life-saving drugs. Methods During a comprehensive shop census in the districts of Kilombero and Ulanga, Tanzania, we interviewed 489 shopkeepers about their knowledge of malaria and malaria treatment. A complementary mystery shoppers study was conducted in 118 retail outlets in order to assess the vendors' drug selling practices. Both studies included drug stores as well as general shops. Results Shopkeepers in drug stores were able to name more malaria symptoms and were more knowledgeable about malaria treatment than their peers in general shops. In drug stores, 52% mentioned the correct child-dosage of sulphadoxine-pyrimethamine (SP compared to only 3% in general shops. In drug stores, mystery shoppers were more likely to receive an appropriate treatment (OR = 9.6, but at an approximately seven times higher price. Overall, adults were more often sold an antimalarial than children (OR = 11.3. On the other hand, general shopkeepers were often ready to refer especially children to a higher level if they felt unable to manage the case. Conclusion The quality of malaria case-management in the retail sector is not satisfactory. Drug stores should be supported and empowered to provide correct malaria-treatment with drugs they are allowed to dispense. At the same time, the role of general shops

Genetic diversity of Plasmodium falciparum and distribution of drug resistance haplotypes in Yemen.

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Al-Hamidhi, Salama; Mahdy, Mohammed A K; Al-Hashami, Zainab; Al-Farsi, Hissa; Al-mekhlafi, Abdulsalam M; Idris, Mohamed A; Beja-Pereira, Albano; Babiker, Hamza A

2013-07-15

Despite evident success of malaria control in many sites in the Arabian Peninsula, malaria remains endemic in a few spots, in Yemen and south-west of Saudi Arabia. In addition to local transmission, imported malaria sustains an extra source of parasites that can challenge the strengths of local control strategies. This study examined the genetic diversity of Plasmodium falciparum in Yemen and mutations of drug resistant genes, to elucidate parasite structure and distribution of drug resistance genotypes in the region. Five polymorphic loci (MSP-2, Pfg377 and three microsatellites on chromosome 8) not involved in anti-malarial drug resistance, and four drug resistant genes (pfcrt, pfmdr1, dhfr and dhps) were genotyped in 108 P. falciparum isolates collected in three sites in Yemen: Dhamar, Hodeidah and Taiz. High diversity was seen in non-drug genes, pfg377 (He = 0.66), msp-2 (He = 0.80) and three microsatellites on chr 8, 7.7 kb (He = 0.88), 4.3 kb (He = 0.77) and 0.8 kb (He = 0.71). There was a high level of mixed-genotype infections (57%), with an average 1.8 genotypes per patient. No linkage disequilibrium was seen between drug resistant genes and the non-drug markers (p Yemen is indicative of a large parasite reservoir, which represents a challenge to control efforts. The presence of two distinct pfcrt genotype, CVIET and SVMNT, suggests that chloroquine resistance can possibly be related to a migratory path from Africa and Asia. The absence of the triple mutant dhfr genotype (IRN) and dhps mutations supports the use of artesunate + sulphadoxine-pyrimethamine as first-line therapy. However, the prevalent pfmdr1 genotype NFSND [21%] has previously been associated with tolerance/resistance response to artemisinin combination therapy (ACT). Regular surveys are, therefore, important to monitor spread of pfmdr1 and dhfr mutations and response to ACT.

Modelling the epidemiological impact of intermittent preventive treatment against malaria in infants.

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Amanda Ross

Full Text Available BACKGROUND: Trials of intermittent preventive treatment against malaria in infants (IPTi using sulphadoxine-pyrimethamine (SP have shown a positive, albeit variable, protective efficacy against clinical malaria episodes. The impact of IPTi in different epidemiological settings and over time is unknown and predictions are hampered by the lack of knowledge about how IPTi works. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality. METHODS/PRINCIPAL FINDINGS: We used a comprehensive, individual-based, stochastic model of malaria epidemiology to simulate recently published trials of IPTi using SP with site-specific characteristics as inputs. This baseline model was then modified to represent hypotheses concerning the duration of action of SP, the temporal pattern of fevers caused by individual infections, potential benefits of avoiding fevers on immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The baseline model reproduced the pattern of results reasonably well. None of the models based on alternative hypotheses improved the fit between the model predictions and observed data. Predictions suggest that IPTi would have a beneficial effect across a range of transmission intensities. IPTi was predicted to avert a greater number of episodes where IPTi coverage was higher, the health system treatment coverage lower, and for drugs which were more efficacious and had longer prophylactic periods. The predicted cumulative benefits were proportionately slightly greater for severe malaria episodes and malaria-attributable mortality than for acute episodes in the settings modelled. Modest increased susceptibility was predicted between doses and following the last dose, but these were outweighed by the cumulative benefits. The impact on transmission intensity was negligible. CONCLUSIONS: The pattern of trial results can be accounted for by differences between

Ensuring sustained ACT production and reliable artemisinin supply

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Olliaro Piero

2007-09-01

Full Text Available Abstract Introduction This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal. Stability data are derived from a development project on rectal artesunate. Discussion The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than $1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar. A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250–300 per kg. Conclusion Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of A. annua and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened. While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would

Ensuring sustained ACT production and reliable artemisinin supply.

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Kindermans, Jean-Marie; Pilloy, Jacques; Olliaro, Piero; Gomes, Melba

2007-09-15

This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal). Stability data are derived from a development project on rectal artesunate. The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than $1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar.A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250-300 per kg. Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of A. annua and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened.While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would permanently discredit it and impede any progress in rolling malaria back.

Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

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Khatib Rashid A

2012-04-01

Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS co-administered with SP (AS + SP, was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at

Costs and cost-effectiveness of delivering intermittent preventive treatment through schools in western Kenya

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Jukes Matthew CH

2008-09-01

Full Text Available Abstract Background Awareness of the potential impact of malaria among school-age children has stimulated investigation into malaria interventions that can be delivered through schools. However, little evidence is available on the costs and cost-effectiveness of intervention options. This paper evaluates the costs and cost-effectiveness of intermittent preventive treatment (IPT as delivered by teachers in schools in western Kenya. Methods Information on actual drug and non-drug associated costs were collected from expenditure and salary records, government budgets and interviews with key district and national officials. Effectiveness data were derived from a cluster-randomised-controlled trial of IPT where a single dose of sulphadoxine-pyrimethamine and three daily doses of amodiaquine were provided three times in year (once termly. Both financial and economic costs were estimated from a provider perspective, and effectiveness was estimated in terms of anaemia cases averted. A sensitivity analysis was conducted to assess the impact of key assumptions on estimated cost-effectiveness. Results The delivery of IPT by teachers was estimated to cost US$ 1.88 per child treated per year, with drug and teacher training costs constituting the largest cost components. Set-up costs accounted for 13.2% of overall costs (equivalent to US$ 0.25 per child whilst recurrent costs accounted for 86.8% (US$ 1.63 per child per year. The estimated cost per anaemia case averted was US$ 29.84 and the cost per case of Plasmodium falciparum parasitaemia averted was US$ 5.36, respectively. The cost per case of anaemia averted ranged between US$ 24.60 and 40.32 when the prices of antimalarial drugs and delivery costs were varied. Cost-effectiveness was most influenced by effectiveness of IPT and the background prevalence of anaemia. In settings where 30% and 50% of schoolchildren were anaemic, cost-effectiveness ratios were US$ 12.53 and 7.52, respectively. Conclusion This

Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya.

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Ye, Yazoume; Madise, Nyovani; Ndugwa, Robert; Ochola, Sam; Snow, Robert W

2009-07-15

In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT) and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Of the 1,069 participants visited, 983 (92%) consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%-20.5%) and higher among children below five years (20.1%, 95%CI:13.8%-27.8%). Of the fever episodes with treatment information 54.3% (95%CI:46.3%-62.2%) were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies, including testing for malaria parasites to reduce the inappropriate

Fever treatment in the absence of malaria transmission in an urban informal settlement in Nairobi, Kenya

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Ochola Sam

2009-07-01

Full Text Available Abstract Background In sub-Saharan Africa, knowledge of malaria transmission across rapidly proliferating urban centres and recommendations for its prevention or management remain poorly defined. This paper presents the results of an investigation into infection prevalence and treatment of recent febrile events among a slum population in Nairobi, Kenya. Methods In July 2008, a community-based malaria parasite prevalence survey was conducted in Korogocho slum, which forms part of the Nairobi Urban Health and Demographic Surveillance system. Interviewers visited 1,069 participants at home and collected data on reported fevers experienced over the preceding 14 days and details on the treatment of these episodes. Each participant was tested for malaria parasite presence with Rapid Diagnostic Test (RDT and microscopy. Descriptive analyses were performed to assess the period prevalence of reported fever episodes and treatment behaviour. Results Of the 1,069 participants visited, 983 (92% consented to be tested. Three were positive for Plasmodium falciparum using RDT; however, all were confirmed negative on microscopy. Microscopic examination of all 953 readable slides showed zero prevalence. Overall, from the 1,004 participants who have data on fever, 170 fever episodes were reported giving a relatively high period prevalence (16.9%, 95% CI:13.9%–20.5% and higher among children below five years (20.1%, 95%CI:13.8%–27.8%. Of the fever episodes with treatment information 54.3% (95%CI:46.3%–62.2% were treated as malaria using mainly sulphadoxine-pyrimethamine or amodiaquine, including those managed at a formal health facility. Only four episodes were managed using the nationally recommended first-line treatment, artemether-lumefantrine. Conclusion The study could not demonstrate any evidence of malaria in Korogocho, a slum in the centre of Nairobi. Fever was a common complaint and often treated as malaria with anti-malarial drugs. Strategies

Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs

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Vreeke Ed

2007-07-01

Full Text Available Abstract Background Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs, the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. Methods The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe. From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Results Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1–1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum. There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania. Conclusion Additional studies are required to build a more robust methodology, and to assess current consumptions

Quality of antimalarial drugs and antibiotics in Papua New Guinea: a survey of the health facility supply chain.

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Hetzel, Manuel W; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M E; Lavu, Evelyn K

2014-01-01

Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of

A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy

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Manyando Christine

2012-05-01

Full Text Available Abstract Malaria during pregnancy, particularly Plasmodium falciparum malaria, has been linked to increased morbidity and mortality, which must be reduced by both preventive measures and effective case management. The World Health Organization (WHO recommends artemisinin-based combination therapy (ACT to treat uncomplicated falciparum malaria during the second and third trimesters of pregnancy, and quinine plus clindamycin during the first trimester. However, the national policies of many African countries currently recommend quinine throughout pregnancy. Therefore, the aim of this article is to provide a summary of the available data on the safety and efficacy of artemether-lumefantrine (AL in pregnancy. An English-language search identified 16 publications from 1989 to October 2011 with reports of artemether or AL exposure in pregnancy, including randomized clinical trials, observational studies and systematic reviews. Overall, there were 1,103 reports of AL use in pregnant women: 890 second/third trimester exposures; 212 first trimester exposures; and one case where the trimester of exposure was not reported. In the second and third trimesters, AL was not associated with increased adverse pregnancy outcomes as compared with quinine or sulphadoxine-pyrimethamine, showed improved tolerability relative to quinine, and its efficacy was non-inferior to quinine. There is evidence to suggest that the pharmacokinetics of anti-malarial drugs may change in pregnancy, although the impact on efficacy and safety needs to be studied further, especially since the majority of studies report high cure rates and adequate tolerability. As there are fewer reports of AL safety in the first trimester, additional data are required to assess the potential to use AL in the first trimester. Though the available safety and efficacy data support the use of AL in the second and third trimesters, there is still a need for further information. These findings reinforce the

Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.

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Choi, Sung Eun; Brandeau, Margaret L; Bendavid, Eran

2017-10-06

Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to

Cost-effectiveness of intermittent preventive treatment of malaria in pregnancy in southern Mozambique.

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Elisa Sicuri

2010-10-01

Full Text Available Malaria in pregnancy is a public health problem for endemic countries. Economic evaluations of malaria preventive strategies in pregnancy are needed to guide health policies.This analysis was carried out in the context of a trial of malaria intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP, where both intervention groups received an insecticide treated net through the antenatal clinic (ANC in Mozambique. The cost-effectiveness of IPTp-SP on maternal clinical malaria and neonatal survival was estimated. Correlation and threshold analyses were undertaken to assess the main factors affecting the economic outcomes and the cut-off values beyond which the intervention is no longer cost-effective. In 2007 US$, the incremental cost-effectiveness ratio (ICER for maternal malaria was 41.46 US$ (95% CI 20.5, 96.7 per disability-adjusted life-year (DALY averted. The ICER per DALY averted due to the reduction in neonatal mortality was 1.08 US$ (95% CI 0.43, 3.48. The ICER including both the effect on the mother and on the newborn was 1.02 US$ (95% CI 0.42, 3.21 per DALY averted. Efficacy was the main factor affecting the economic evaluation of IPTp-SP. The intervention remained cost-effective with an increase in drug cost per dose up to 11 times in the case of maternal malaria and 183 times in the case of neonatal mortality.IPTp-SP was highly cost-effective for both prevention of maternal malaria and reduction of neonatal mortality in Mozambique. These findings are likely to hold for other settings where IPTp-SP is implemented through ANC visits. The intervention remained cost-effective even with a significant increase in drug and other intervention costs. Improvements in the protective efficacy of the intervention would increase its cost-effectiveness. Provision of IPTp with a more effective, although more expensive drug than SP may still remain a cost-effective public health measure to prevent malaria in pregnancy

Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library.

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Feng, Jie; Weitner, Megan; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Zhang, Ying

2015-09-16

Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2-4 week antibiotic treatment, 10%-20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity against Borrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive

Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women

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Anchang-Kimbi Judith K

2009-06-01

Full Text Available Abstract Background In sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated. Method In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for P. falciparum in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded. Results Among these women, P. falciparum infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4% than placental blood film (41.5% and peripheral blood (8.0% microscopy. In multivariate analysis, age (≤ 20 years old (OR = 4.61, 95% CI = 1.47 – 14.70, history of fever attack (OR = 2.98, 95% CI = 1.58 – 5.73 were significant risk factors associated with microscopically detected parasitaemia. The use of ≥ 2 SP doses (OR = 0.18, 95% CI = 0.06 – 0.52 was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years (OR = 0.34, 95% CI = 0.15 – 0.75 was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33–5.62 was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia. Conclusion Placenta histological examination was the most sensitive indicator of malaria infection at

Antimalarial drug quality in Africa.

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Amin, A A; Kokwaro, G O

2007-10-01

There are several reports of sub-standard and counterfeit antimalarial drugs circulating in the markets of developing countries; we aimed to review the literature for the African continent. A search was conducted in PubMed in English using the medical subject headings (MeSH) terms: 'Antimalarials/analysis'[MeSH] OR 'Antimalarials/standards'[MeSH] AND 'Africa'[MeSH]' to include articles published up to and including 26 February 2007. Data were augmented with reports on the quality of antimalarial drugs in Africa obtained from colleagues in the World Health Organization. We summarized the data under the following themes: content and dissolution; relative bioavailability of antimalarial products; antimalarial stability and shelf life; general tests on pharmaceutical dosage forms; and the presence of degradation or unidentifiable impurities in formulations. The search yielded 21 relevant peer-reviewed articles and three reports on the quality of antimalarial drugs in Africa. The literature was varied in the quality and breadth of data presented, with most bioavailability studies poorly designed and executed. The review highlights the common finding in drug quality studies that (i) most antimalarial products pass the basic tests for pharmaceutical dosage forms, such as the uniformity of weight for tablets, (ii) most antimalarial drugs pass the content test and (iii) in vitro product dissolution is the main problem area where most drugs fail to meet required pharmacopoeial specifications, especially with regard to sulfadoxine-pyrimethamine products. In addition, there are worryingly high quality failure rates for artemisinin monotherapies such as dihydroartemisinin (DHA); for instance all five DHA sampled products in one study in Nairobi, Kenya, were reported to have failed the requisite tests. There is an urgent need to strengthen pharmaceutical management systems such as post-marketing surveillance and the broader health systems in Africa to ensure populations in the

Effect of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali.

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Mahamar, Almahamoudou; Issiaka, Djibrilla; Barry, Amadou; Attaher, Oumar; Dembele, Adama B; Traore, Tiangoua; Sissoko, Adama; Keita, Sekouba; Diarra, Bacary Soumana; Narum, David L; Duffy, Patrick E; Dicko, Alassane; Fried, Michal

2017-07-18

Seasonal malaria chemoprevention (SMC) is a new strategy to reduce malaria burden in young children in Sahelian countries. It consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. However, it is not clear if there is a cumulative effect of SMC over time on acquisition of antibodies to malaria antigens. A cross-sectional serosurvey was carried out 1 month after the last dose of SMC in 2016. Children aged 3-4 years were randomly selected from areas where SMC was given for 1, 2 or 3 years during the malaria season. Children in the areas where SMC had been implemented for 1 year but who failed to receive SMC were used as comparison group. Antibody extracted from dry blood spots was used to measure IgG levels to CSP, MSP-1 42 and AMA1. The prevalence of antibodies to AMA-1 were high and similar in children who received SMC for 1, 2 or 3 years and also when compared to those who never received SMC (96.3 vs 97.5%, adjusted OR = 0.99, 95% CI 0.33-2.97, p = 0.99). The prevalence of antibodies to MSP-1 42 and to CSP were similar in children that received SMC for 1, 2 or 3 years, but were lower in these children compared to those who did not receive SMC (87.1 vs 91.2%, adjusted OR = 0.55, 95% CI 0.29-1.01, p = 0.05 for MSP-1 42 ; 79.8 vs 89.2%, adjusted OR = 0.52, 95% CI 0.30-0.90, p = 0.019 for CSP). SMC reduced seropositivity to MSP-1 42 and CSP, but the duration of SMC did not further reduce seropositivity. Exposure to SMC did not reduce the seropositivity to AMA1.

The malaria testing and treatment landscape in Kenya: results from a nationally representative survey among the public and private sector in 2016.

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Musuva, Anne; Ejersa, Waqo; Kiptui, Rebecca; Memusi, Dorothy; Abwao, Edward

2017-12-21

Since 2004, Kenya's national malaria treatment guidelines have stipulated artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria, and since 2014, confirmatory diagnosis of malaria in all cases before treatment has been recommended. A number of strategies to support national guidelines have been implemented in the public and private sectors in recent years. A nationally-representative malaria outlet survey, implemented across four epidemiological zones, was conducted between June and August 2016 to provide practical evidence to inform strategies and policies in Kenya towards achieving national malaria control goals. A total of 17,852 outlets were screened and 2271 outlets were eligible and interviewed. 78.3% of all screened public health facilities stocked both malaria diagnostic testing and quality-assured ACT (QAACT). Sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment in pregnancy was available in 70% of public health facilities in endemic areas where it is recommended for treatment. SP was rarely found in the public sector outside of the endemic areas (private sector had lower levels of QAACT (46.7%) and malaria blood testing (20.8%) availability but accounted for majority of anti-malarial distribution (70.6% of the national market share). More than 40% of anti-malarials were distributed by unregistered pharmacies (37.3%) and general retailers (7.1%). QAACT accounted for 58.2% of the total anti-malarial market share, while market share for non-QAACT was 15.8% and for SP, 24.8%. In endemic areas, 74.9% of anti-malarials distributed were QAACT. Elsewhere, QAACT market share was 49.4% in the endemic-prone areas, 33.2% in seasonal-transmission areas and 37.9% in low-risk areas. Although public sector availability of QAACT and malaria diagnosis is relatively high, there is a gap in availability of both testing and treatment that must be addressed. The private sector in Kenya, where the majority of anti

Feasibility and coverage of implementing intermittent preventive treatment of malaria in pregnant women contacting private or public clinics in Tanzania: experience-based viewpoints of health managers in Mkuranga and Mufindi districts.

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Mubyazi, Godfrey M; Magnussen, Pascal; Byskov, Jens; Bloch, Paul

2013-10-01

Evidence on healthcare managers' experience on operational feasibility of malaria intermittent preventive treatment for malaria during pregnancy (IPTp) using sulphadoxine-pyrimethamine (SP) in Africa is systematically inadequate. This paper elucidates the perspectives of District Council Health Management Team (CHMT)s regarding the feasibility of IPTp with SP strategy, including its acceptability and ability of district health care systems to cope with the contemporary and potential challenges. The study was conducted in Mkuranga and Mufindi districts. Data were collected between November 2005 and December 2007, involving focus group discussion (FGD) with Mufindi CHMT and in-depth interviews were conducted with few CHMT members in Mkuranga where it was difficult to summon all members for FGD. Participants in both districts acknowledged the IPTp strategy, considering the seriousness of malaria in pregnancy problem; government allocation of funds to support healthcare staff training programmes in focused antenatal care (fANC) issues, procuring essential drugs distributed to districts, staff remuneration, distribution of fANC guidelines, and administrative activities performed by CHMTs. The identified weaknesses include late arrival of funds from central level weakening CHMT's performance in health supervision, organising outreach clinics, distributing essential supplies, and delivery of IPTp services. Participants anticipated the public losing confidence in SP for IPTp after government announced artemither-lumefantrine (ALu) as the new first-line drug for uncomplicated malaria replacing SP. Role of private healthcare staff in IPTp services was acknowledged cautiously because CHMTs rarely supplied private clinics with SP for free delivery in fear that clients would be required to pay for the SP contrary to government policy. In Mufindi, the District Council showed a strong political support by supplementing ANC clinics with bottled water; in Mkuranga such support was

Assessing supply-side barriers to uptake of intermittent preventive treatment for malaria in pregnancy: a qualitative study and document and record review in two regions of Uganda.

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Rassi, Christian; Graham, Kirstie; Mufubenga, Patrobas; King, Rebecca; Meier, Joslyn; Gudoi, Sam Siduda

2016-07-04

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), provided as part of routine antenatal care (ANC), is one of three malaria-in-pregnancy prevention and control mechanisms recommended by the World Health Organization (WHO). However, despite high ANC attendance and increased efforts to address known obstacles, IPTp uptake figures have remained low. This study aimed to identify and assess barriers that continue to impede IPTp uptake in Uganda, in particular for women who attend ANC. The paper focuses on supply-side barriers, i.e., challenges relating to the health service provider. In-depth interviews were conducted in two regions of Uganda in November 2013 and April/May 2014 with four different target audiences: seven district health officials, 15 health workers, 19 women who had attended ANC, and five opinion leaders. In addition, a document and record review was carried out at four health facilities. Guidelines with regard to IPTp provision in Uganda have been shown to be inconsistent and, at the time of the research, did not reflect the most recent WHO policy recommendation. There is a lack of training and supervision opportunities for health workers, resulting in poor knowledge of IPTp guidelines and uncertainty about the safety and efficacy of SP. ANC is not consistently offered in health facilities, leading to some women being denied services. While strengthening of the supply chain appears to have reduced the occurrence of stock-outs of SP in public facilities, stock-outs reportedly continue to occur in the private sector. There are also sources of data inaccuracy along the data recording and reporting chain, limiting policy makers' ability to react adequately to trends and challenges. Given the high ANC attendance rates in Uganda, supply-side barriers are likely to account for many missed opportunities for the provision of IPTp in Uganda. Improvements will require consistent provision of ANC, implementation of current

Malaria: Antimalarial resistance and policy ramificationsand challenges

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Kshirsagar N

2006-01-01

Full Text Available ′The National health Policy 2002" of India and the "Roll Back Malaria" policy makers have set up an ambitious goal of reducing malaria mortality and morbidity by 25% by 2007, and by 50% by 2010. To achieve these goals, problems should be identified, available evidence analyzed and policy should be changed early. Infection with drug resistant malarial parasites has a tremendous impact on health (prolonged recurrent illness, increased hospital admissions and death, health system (higher cost of treatment and socioeconomics of the region. In view of the evidence of the economic burden of malaria, it has been suggested that second line treatment could be considered at 10% failure instead of 25%. Effective schizonticidal drugs will not only reduce morbidity and mortality but will also reduce transmission. Studies have shown that prevalence of viable (as tested by exflagellation test gametocytes is considerably more after the Chloroquine or Chloroquine + Sulphadoxine-Pyrimethamine treatment compared to Quinine. Unfortunately, the only gametocytocidal drug for Plasmodium falciparum, primaquine, is also loosing its efficacy. 45 mg Primaquine reduces gametocyte prevalence by 50% while a new drug, 75 mg bulaquine or 60 mg primaquine reduces it by 90%. Plasmodium vivax forms 60-70% of malaria cases in India. Relapses which occur in 10-20% of cases adds to the burden. Efficacy, as confirmed by Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCRSSCP to differentiate relapse and re-infection, of standard dose of primaquine (15 mg/day for 5 days, even 15 mg/day for 14 days for vivax malaria is reducing. Fourteen day treatment is also impractical as compliance is poor. Newer drugs, newer drug delivery systems are thus needed. Slow release formulations with blood levels maintained for one week may be useful. Rationale of giving primaquine in higher doses and different timing need to be considered. The genome of Plasmodium falciparum and

Systematic assessment of multi-gene predictors of pan-cancer cell line sensitivity to drugs exploiting gene expression data [version 2; referees: 2 approved

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Linh Nguyen

2017-03-01

Full Text Available Background: Selected gene mutations are routinely used to guide the selection of cancer drugs for a given patient tumour. Large pharmacogenomic data sets, such as those by Genomics of Drug Sensitivity in Cancer (GDSC consortium, were introduced to discover more of these single-gene markers of drug sensitivity. Very recently, machine learning regression has been used to investigate how well cancer cell line sensitivity to drugs is predicted depending on the type of molecular profile. The latter has revealed that gene expression data is the most predictive profile in the pan-cancer setting. However, no study to date has exploited GDSC data to systematically compare the performance of machine learning models based on multi-gene expression data against that of widely-used single-gene markers based on genomics data. Methods: Here we present this systematic comparison using Random Forest (RF classifiers exploiting the expression levels of 13,321 genes and an average of 501 tested cell lines per drug. To account for time-dependent batch effects in IC50 measurements, we employ independent test sets generated with more recent GDSC data than that used to train the predictors and show that this is a more realistic validation than standard k-fold cross-validation. Results and Discussion: Across 127 GDSC drugs, our results show that the single-gene markers unveiled by the MANOVA analysis tend to achieve higher precision than these RF-based multi-gene models, at the cost of generally having a poor recall (i.e. correctly detecting only a small part of the cell lines sensitive to the drug. Regarding overall classification performance, about two thirds of the drugs are better predicted by the multi-gene RF classifiers. Among the drugs with the most predictive of these models, we found pyrimethamine, sunitinib and 17-AAG. Conclusions: Thanks to this unbiased validation, we now know that this type of models can predict in vitro tumour response to some of these

Assessment of coverage of preventive treatment and insecticide-treated mosquito nets in pregnant women attending antenatal care services in 11 districts in Mozambique in 2011: the critical role of supply chain.

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Salomão, Cristolde; Sacarlal, Jahit; Gudo, Eduardo Samo

2017-05-25

Malaria during pregnancy is associated with poor maternal and pregnancy outcome and the World Health Organization recommends the administration of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) and distribution of insecticide-treated mosquito nets (ITNs) to all pregnant women attending antenatal care (ANC) services. This study was conducted with the aim to assess the uptake of IPTp and ITNs in pregnant women attending ANC services and correlate with ANC attendance and frequency of stock-outs in 22 health facilities Mozambique. A cross-sectional study was conducted between July and December 2011 in 22 health units in 11 districts situated in 11 provinces in Mozambique. Two health facilities were selected per district (one urban and one rural). Data were collected by reviewing logbooks of antenatal consultations as well as from monthly district reports. During the period under investigation, a total of 23,524 pregnant women attended their 1st antenatal care visits, of which 12,775 (54.3%) and 7581 (32.2%) received one and two doses of IPTp, respectively. In regard to ITNs, a total of 16,436 (69.9%) pregnant women received ITNs. Uptake of IPTp and ITNs by pregnant women at ANC services was higher in southern Mozambique and lower in districts situated in the northern part of the country. Stock-outs of SP and ITNs were reported in 50.0% (11/22) and 54.5% (12/22) of the health facilities, respectively. Coverage of IPTp and ITN in health facilities with stock-outs of SP and ITNs was much lower as compared to health facilities with no stock-outs. Altogether, data from this study shows that coverage of the 2nd dose of IPTp, as well as ITNs, was low in pregnant women attending ANC services in Mozambique. In addition, this data also shows that stock-outs of SP and ITNs were frequent and led to lower coverage of IPTp and ITN, representing a serious barrier for the accomplishment of targets. In conclusion, this study recommends that

“…still waiting for chloroquine”: the challenge of communicating changes in first-line treatment policy for uncomplicated malaria in a remote Kenyan district

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2014-01-01

Background Widespread parasite resistance to first-line treatment for uncomplicated malaria leads to introduction of new drug interventions. Introducing such interventions is complex and sensitive because of stakeholder interests and public resistance. To enhance take up of such interventions, health policy communication strategies need to deliver accurate and accessible information to empower communities with necessary information and address problems of cultural acceptance of new interventions. Objectives To explore community understanding of policy changes in first-line treatment for uncomplicated malaria in Kenya; to evaluate the potential role of policy communication in influencing responses to changes in first-line treatment policy. Methods Data collection involved qualitative strategies in a remote district in the Kenyan Coast: in-depth interviews (n = 29), focus group discussions (n = 14), informal conversations (n = 11) and patient narratives (n = 8). Constant comparative method was used in the analysis. Being malaria-prone and remotely located, the district offered an ideal area to investigate whether or not and how policy communication about a matter as critical as change of treatment policy reaches vulnerable populations. Results Three years after initial implementation (2009), there was limited knowledge or understanding regarding change of first-line treatment from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (AL) for treatment of uncomplicated malaria in the study district. The print and electronic media used to create awareness about the drug change appeared to have had little impact. Although respondents were aware of the existence of AL, the drug was known neither by name nor as the official first-line treatment. Depending on individuals or groups, AL was largely viewed negatively. The weaknesses in communication strategy surrounding the change to AL included poor choice of communication tools, confusing

Sub-optimal delivery of intermittent preventive treatment for malaria in pregnancy in Nigeria: influence of provider factors

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Onoka Chima A

2012-09-01

Full Text Available Abstract Background The level of access to intermittent preventive treatment for malaria in pregnancy (IPTp in Nigeria is still low despite relatively high antenatal care coverage in the study area. This paper presents information on provider factors that affect the delivery of IPTp in Nigeria. Methods Data were collected from heads of maternal health units of 28 public and six private health facilities offering antenatal care (ANC services in two districts in Enugu State, south-east Nigeria. Provider knowledge of guidelines for IPTp was assessed with regard to four components: the drug used for IPTp, time of first dose administration, of second dose administration, and the strategy for sulphadoxine-pyrimethamine (SP administration (directly observed treatment, DOT. Provider practices regarding IPTp and facility-related factors that may explain observations such as availability of SP and water were also examined. Results Only five (14.7% of all 34 providers had correct knowledge of all four recommendations for provision of IPTp. None of them was a private provider. DOT strategy was practiced in only one and six private and public providers respectively. Overall, 22 providers supplied women with SP in the facility and women were allowed to take it at home. The most common reason for doing so amongst public providers was that women were required to come for antenatal care on empty stomachs to enhance the validity of manual fundal height estimation. Two private providers did not think it was necessary to use the DOT strategy because they assumed that women would take their drugs at home. Availability of SP and water in the facility, and concerns about side effects were not considered impediments to delivery of IPTp. Conclusion There was low level of knowledge of the guidelines for implementation of IPTp by all providers, especially those in the private sector. This had negative effects such as non-practice of DOT strategy by most of the providers

Population genetics analysis during the elimination process of Plasmodium falciparum in Djibouti.

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Khaireh, Bouh Abdi; Assefa, Ashenafi; Guessod, Hawa Hassan; Basco, Leonardo K; Khaireh, Mohamed Abdi; Pascual, Aurélie; Briolant, Sébastien; Bouh, Samatar Mohamed; Farah, Ismaïl Hassan; Ali, Habib Moussa; Abdi, Abdoul-Ilah Ahmed; Aden, Mouna Osman; Abdillahi, Zamzam; Ayeh, Souleiman Nour; Darar, Houssein Youssouf; Koeck, Jean-Louis; Rogier, Christophe; Pradines, Bruno; Bogreau, Hervé

2013-06-13

Case management of imported malaria within the context of malaria pre-elimination is increasingly considered to be relevant because of the risk of resurgence. The assessment of malaria importation would provide key data i) to select countries with propitious conditions for pre-elimination phase and ii) to predict its feasibility. Recently, a sero-prevalence study in Djibouti indicated low malaria prevalence, which is propitious for the implementation of pre-elimination, but data on the extent of malaria importation remain unknown. Djiboutian plasmodial populations were analysed over an eleven-year period (1998, 1999, 2002 and 2009). The risk of malaria importation was indirectly assessed by using plasmodial population parameters. Based on 5 microsatellite markers, expected heterozygosity (H.e.), multiplicity of infection, pairwise Fst index, multiple correspondence analysis and individual genetic relationship were determined. The prevalence of single nucleotide polymorphisms associated with pyrimethamine resistance was also determined. Data indicated a significant decline in genetic diversity (0.51, 0.59, 0.51 and 0 in 1998, 1999, 2002 and 2009, respectively) over the study period, which is inconsistent with the level of malaria importation described in a previous study. This suggested that Djiboutian malaria situation may have benefited from the decline of malaria prevalence that occurred in neighbouring countries, in particular in Ethiopia. The high Fst indices derived from plasmodial populations from one study period to another (0.12 between 1999 and 2002, and 0.43 between 2002 and 2009) suggested a random sampling of parasites, probably imported from neighbouring countries, leading to oligo-clonal expansion of few different strains during each transmission season. Nevertheless, similar genotypes observed during the study period suggested recurrent migrations and imported malaria. In the present study, the extent of genetic diversity was used to assess the risk

Improvements in access to malaria treatment in Tanzania following community, retail sector and health facility interventions -- a user perspective

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Obrist Brigit

2010-06-01

Full Text Available Abstract Background The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment. Methods Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days. Results Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%; an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%; higher treatment coverage with anti-malarials (86% to 96% and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs. Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%. The availability of outlets (health facilities or drug shops is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent. Conclusions An

Knowledge and utilization of intermittent preventive treatment for malaria among pregnant women attending antenatal clinics in primary health care centers in rural southwest, Nigeria: a cross-sectional study.

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Akinleye, Stella O; Falade, Catherine O; Ajayi, Ikeoluwapo O

2009-07-09

Intermittent preventive treatment for prevention of malaria in pregnancy (IPTp) is a key component of malaria control strategy in Nigeria and sulfadoxine-pyrimethamine (SP) is the drug of choice. Despite the evidence of the effectiveness of IPTp strategy using SP in reducing the adverse effects of malaria during pregnancy the uptake and coverage in Nigeria is low. This study set out to assess the use of IPTp among pregnant women attending primary health centres in the rural area and determine factors that influence the uptake. A cross-sectional study was carried out between July and August 2007 among 209 pregnant women selected by systematic random sampling from antenatal care attendees at primary health care in a rural Local Government Area of Ekiti State, Nigeria. Information on knowledge of IPT, delivery, adherence and acceptability was obtained using an interviewer administered questionnaire. Descriptive statistics such as means, range, proportions were used. Chi-square test was used to examine association between categorical variables. All analyses were performed at 5% level of significance. One hundred and nine of 209 (52.2%) respondents have heard about IPTp but only 26 (23.9%) were able to define it. Fifty seven (27.3%) reported to have received at least one dose of IPTp during the index pregnancy and all were among those who have heard of IPTp (52.3%). Twenty one of the 57 (36.8%) took the SP in the clinic. Only three of the twenty-one (14.3%) were supervised by a health worker. Twenty two of the 36 women (61.1%) who did not take their drugs in the clinic would have liked to do so if allowed to bring their own drinking cups. Almost half (43.9%) of those who had used IPTp during the index pregnancy expressed concern about possible adverse effect of SP on their pregnancies. Periodic shortages of SP in the clinics were also reported. In this study, IPTp use among pregnant women was very low and there was poor adherence to the Directly Observed Therapy (DOT

Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas

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Massougbodji Achille

2007-12-01

Full Text Available Abstract Malaria in pregnancy is one of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp. IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP is the drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy, there are many issues still to be explored to optimize it. This paper reviewed data on IPTp efficacy and discussed how to improve it. In particular, the determination of both the optimal number of doses and time of administration of the drug is essential, and this has not yet been done. As both foetal growth and deleterious effects of malaria are maximum in late pregnancy women should particularly be protected during this period. Monitoring of IPTp efficacy should be applied to all women, and not only to primi- and secondigravidae, as it has not been definitively established that multigravidae are not at risk for malaria morbidity and mortality. In HIV-positive women, there is an urgent need for specific information on drug administration patterns (need for higher doses, possible interference with sulpha-based prophylaxis of opportunistic infections. Because of the growing level of resistance of parasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently one of the most attractive options because of its long half life, high efficacy in sub-Saharan Africa and safety during pregnancy. Also, efforts should be made to increase IPTp coverage by improving the practices of health care workers, the motivation of women and their perception of malaria complications in pregnancy. Because IPTp

Implementation of co-trimoxazole preventive therapy policy for malaria in HIV-infected pregnant women in the public health facilities in Tanzania.

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Kamuhabwa, Appolinary Ar; Gordian, Richard; Mutagonda, Ritah F

2016-01-01

In 2011, Tanzania adopted a policy for provision of daily co-trimoxazole prophylaxis to HIV-infected pregnant women for prevention of malaria and other opportunistic infections. As per the policy, HIV-infected pregnant women should not be given sulfadoxine-pyrimethamine (SP) for intermittent preventive therapy. The challenges associated with this policy change and the extent to which the new policy for prevention of malaria in pregnant women coinfected with HIV was implemented need to be assessed. To assess the implementation of malaria-preventive therapy policy among HIV-infected pregnant women in the public health facilities in Dar es Salaam, Tanzania. The study was conducted in Kinondoni Municipality, Dar es Salaam, Tanzania, from January 2015 to July 2015. Three hundred and fifty-three HIV-infected pregnant women who were attending antenatal clinics (ANCs) and using co-trimoxazole for prevention of malaria were interviewed. Twenty-six health care workers working at the ANCs were also interviewed regarding provision of co-trimoxazole prophylaxis to pregnant women. A knowledge scale was used to grade the level of knowledge of health care providers. Focus group discussions were also conducted with 18 health care workers to assess the level of implementation of the policy and the challenges encountered. Twenty-three (6.5%) pregnant women with known HIV serostatus were using co-trimoxazole for prevention of opportunistic infections even before they became pregnant. Out of the 353 HIV-infected pregnant women, eight (2.5%) were coadministered with both SP and co-trimoxazole. Sixty (16.7%) pregnant women had poor adherence to co-trimoxazole prophylaxis. Out of the 26 interviewed health care providers, 20 had high level of knowledge regarding malaria-preventive therapy in HIV-infected pregnant women. Lack of adequate supply of co-trimoxazole in health facilities and inadequate training of health care providers were among the factors causing poor implementation of co

Pooled-DNA sequencing identifies genomic regions of selection in Nigerian isolates of Plasmodium falciparum.

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Oyebola, Kolapo M; Idowu, Emmanuel T; Olukosi, Yetunde A; Awolola, Taiwo S; Amambua-Ngwa, Alfred

2017-06-29

The burden of falciparum malaria is especially high in sub-Saharan Africa. Differences in pressure from host immunity and antimalarial drugs lead to adaptive changes responsible for high level of genetic variations within and between the parasite populations. Population-specific genetic studies to survey for genes under positive or balancing selection resulting from drug pressure or host immunity will allow for refinement of interventions. We performed a pooled sequencing (pool-seq) of the genomes of 100 Plasmodium falciparum isolates from Nigeria. We explored allele-frequency based neutrality test (Tajima's D) and integrated haplotype score (iHS) to identify genes under selection. Fourteen shared iHS regions that had at least 2 SNPs with a score > 2.5 were identified. These regions code for genes that were likely to have been under strong directional selection. Two of these genes were the chloroquine resistance transporter (CRT) on chromosome 7 and the multidrug resistance 1 (MDR1) on chromosome 5. There was a weak signature of selection in the dihydrofolate reductase (DHFR) gene on chromosome 4 and MDR5 genes on chromosome 13, with only 2 and 3 SNPs respectively identified within the iHS window. We observed strong selection pressure attributable to continued chloroquine and sulfadoxine-pyrimethamine use despite their official proscription for the treatment of uncomplicated malaria. There was also a major selective sweep on chromosome 6 which had 32 SNPs within the shared iHS region. Tajima's D of circumsporozoite protein (CSP), erythrocyte-binding antigen (EBA-175), merozoite surface proteins - MSP3 and MSP7, merozoite surface protein duffy binding-like (MSPDBL2) and serine repeat antigen (SERA-5) were 1.38, 1.29, 0.73, 0.84 and 0.21, respectively. We have demonstrated the use of pool-seq to understand genomic patterns of selection and variability in P. falciparum from Nigeria, which bears the highest burden of infections. This investigation identified known

User and Provider Acceptability of Intermittent Screening and Treatment and Intermittent Preventive Treatment with Dihydroartemisinin-Piperaquine to Prevent Malaria in Pregnancy in Western Kenya.

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Jenny Hill

Full Text Available The World Health Organization recommends intermittent preventive treatment in pregnancy (IPTp with sulphadoxine-pyrimethamine (SP alongside long-lasting insecticide-treated nets (LLIN and case management for reducing the risks associated with malaria in pregnancy in areas of moderate-to-high transmission in sub-Saharan Africa. Due to increasing Plasmodium falciparum resistance to SP, the search for alternative drugs or strategies to control malaria in pregnancy is a priority. We assessed the acceptability among pregnant women and health providers of intermittent screening and treatment (ISTp and IPTp with dihydroartemisinin-piperaquine (DP as alternative strategies in the context of an un-blinded clinical trial.Qualitative data were collected through ten focus group discussions with women participating in a randomized controlled trial to evaluate ISTp or IPTp with DP (multi-day regimen versus IPTp with SP (single dose in western Kenya. Individual in-depth interviews were conducted with 26 health providers working in the trial facilities and trial staff.Women appreciated the advantages of being tested with a rapid diagnostic test (RDT at every ANC visit (although a few women disliked finger pricks and accepted that they would not receive any antimalarial when tested RDT-negative. There were differences in women's experiences of the efficacy of antimalarials between the trial arms, with more women in the IPTp-SP arm reporting they had experienced malaria episodes. Side effects were experienced among women taking DP and SP. Although women and trial staff reported adherence to the full DP regimen within the trial, health providers were not confident that women would adhere to multi-day regimens in non-trial settings. Health providers recognized the advantages of ISTp in reducing unnecessary exposure to drugs, but lacked confidence in the reliability of RDTs compared to microscopy.Our findings indicate that, within a trial context, ISTp-DP and IPTp

Pharmacokinetics and pharmacodynamics of artesunate and dihydroartemisinin following oral treatment in pregnant women with asymptomatic Plasmodium falciparum infections in Kinshasa DRC

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Wesche David

2011-02-01

Full Text Available Abstract Background In many malaria-endemic countries, increasing resistance may soon compromise the efficacy of sulphadoxine-pyrimethamine (SP for intermittent preventative treatment (IPT of malaria in pregnancy. Artemisinin-based IPT regimens represent a promising potential alternative to SP. Pharmacokinetic and safety data supporting the use of artemisinin derivatives in pregnancy are urgently needed. Methods Subjects included pregnant women with asymptomatic falciparum parasitaemia between 22-26 weeks (n = 13 or 32-36 weeks gestation (n = 13, the same women at three months postpartum, and 25 non-pregnant parasitaemic controls. All subjects received 200 mg orally administered AS. Plasma total and free levels of AS and its active metabolite DHA were determined using a validated LC-MS method. Non-compartmental pharmacokinetic analysis was performed using standard methods. Results All pregnant women delivered live babies. The median birth weight was 3025 grams [range 2130, 3620]; 2 of 26 babies had birth weights less than 2500 grams. Rates of parasite clearance by 12 hours post-dose were high and comparable among the groups. Rapid elimination of AS was observed in all three groups. The 90% CI for the pregnancy:postpartum ratio of geometric means for total and free AUC fell within the pre-specified 0.66 - 1.50 therapeutic equivalence interval. However, more pronounced pharmacokinetic differences were observed between the pregnancy and control subjects, with the 90% CI for the pregnancy:control ratio of geometric means for both total 0.68 (90% CI 0.57-0.81 and free AUC 0.78 (90% CI 0.63-0.95 not fully contained within the 0.66 - 1.50 interval. All subjects cleared parasites rapidly, and there was no difference in the percentage of women who were parasitaemic 12 hours after dosing. Conclusions A single dose of orally administered AS was found to be both effective and without adverse effects in this study of second and third trimester pregnant women

Molecular epidemiology of drug-resistant Plasmodium falciparum in Benguela province, Angola.

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Foumane Ngane, Vincent; Allico Djaman, Joseph; Culeux, Cécile; Piette, Nathalie; Carnevale, Pierre; Besnard, Patrick; Fortes, Filomeno; Basco, Leonardo K; Tahar, Rachida

2015-03-14

with antifolate resistance in Benguela province. The hallmark of clinical resistance observed in East Africa, i.e. triple pfdhfr mutant haplotype (AIRNI) and double pfdhps mutant haplotype (SGEAA), was absent. These molecular findings need to be further evaluated in parallel with clinical studies, in particular with the efficacy of intermittent preventive treatment using sulphadoxine-pyrimethamine in pregnant women and artesunate-amodiaquine for uncomplicated malaria.

Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase

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O'Neil Michael T

2008-04-01

Full Text Available Abstract Background In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions. Methods The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network. Results Synonymous and non-synonymous single nucleotide polymorphisms (SNPs within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel. SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu. Conclusion It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts

Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells.

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Sanfelice, Raquel Arruda; da Silva, Suelen Santos; Bosqui, Larissa Rodrigues; Miranda-Sapla, Milena Menegazzo; Barbosa, Bellisa Freitas; Silva, Rafaela José; Ferro, Eloísa A Vieira; Panagio, Luciano Aparecido; Navarro, Italmar Teodorico; Bordignon, Juliano; Conchon-Costa, Ivete; Pavanelli, Wander Rogerio; Almeida, Ricardo Sergio; Costa, Idessania Nazareth

2017-03-01

The conventional treatment for toxoplasmosis with pyrimethamine and sulfadiazine shows toxic effects to the host, and it is therefore necessary to search for new drugs. Some studies suggest the use of statins, which inhibit cholesterol synthesis in humans and also the initial processes of isoprenoid biosynthesis in the parasite. Thus, the objective of this study was to evaluate the activity of the statins pravastatin and simvastatin in HeLa cells infected in vitro with the RH strain of T. gondii. HeLa cells (1×10 5 ) were infected with T. gondii tachyzoites (5×10 5 ) following two different treatment protocols. In the first protocol, T. gondii tachyzoites were pretreated with pravastatin (50 and 100μg/mL) and simvastatin (1.56 and 3.125μg/mL) for 30min prior to infection. In the second, HeLa cells were first infected (5×10 5 ) with tachyzoites and subsequently treated with pravastatin and simvastatin for 24h at the concentrations noted above. Initially, we evaluated the cytotoxicity of drugs by the MTT assay, number of tachyzoites adhered to cells, number of infected cells, and viability of tachyzoites by trypan blue exclusion. The supernatant of the cell cultures was collected post-treatment for determination of the pattern of Th1/Th2/Th17 cytokines by cytometric bead array. There was no cytotoxicity to HeLa cells with 50 and 100μg/mL pravastatin and 1.56 and 3.125μg/mL simvastatin. There was no change in the viability of tachyzoites that received pretreatment. Regarding the pre- and post-treatment of the cells with pravastatin and simvastatin alone, there was a reduction in adhesion, invasion and proliferation of cells to T. gondii. As for the production of cytokines, we found that IL-6 and IL-17 were significantly reduced in cells infected with T. gondii and treated with pravastatin and simvastatin, when compared to control. Based on these results, we can infer that pravastatin and simvastatin alone possess antiproliferative effects on tachyzoites forms

Malaria prevention practices and delivery outcome: a cross sectional study of pregnant women attending a tertiary hospital in northeastern Nigeria.

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Muhammad, Hamzat U; Giwa, Fatima J; Olayinka, Adebola T; Balogun, Shakir M; Ajayi, IkeOluwapo; Ajumobi, Olufemi; Nguku, Patrick

2016-06-18

Malaria in pregnancy remains a public health problem in Nigeria. It causes maternal anaemia and adversely affects birth outcome leading to low birth weight, abortions and still births. Nigeria has made great strides in addressing the prevention and control of malaria in pregnancy. However, recent demographic survey shows wide disparities in malaria control activities across the geopolitical zones. This situation has been compounded by the political unrest and population displacement especially in the Northeastern zone leaving a significant proportion of pregnant women at risk of diseases, including malaria. The use of malaria preventive measures during pregnancy and the risk of malaria parasitaemia, anaemia and low birth weight babies were assessed among parturient women in an insurgent area. A cross-sectional survey was conducted among 184 parturient women at Federal Medical Centre, Nguru in Yobe state, between July and November 2014. Information on demographics, antenatal care and prevention practices was collected using an interviewer-administered questionnaire. Maternal peripheral and the cord blood samples were screened for malaria parasitaemia by microscopy of Giemsa-stained blood films. The presence of anaemia was also determined by microhaemocrit method using the peripheral blood samples. Data was analysed using descriptive and analytical statistics. Prevalence of malaria parasitaemia, anaemia and low birth weight babies was 40.0, 41.0 and 37.0 %, respectively, and mothers aged younger than 25 years were mostly affected. Eighty (43.0 %) of the women received up to two doses of sulfadoxine-pyrimethamine for intermittent preventive treatment (IPTp-SP) during pregnancy and most, 63 (83.0 %) of those tested malaria positive received less than these. Presence of malaria infection at antenatal clinic enrollment (OR: 6.6; 95 % CI: 3.4-13.0), non-adherence to direct observation therapy for administration of IPTp-SP (OR: 4.6; 95 % CI: 2.2-9.5) and receiving

Risk of malaria in British residents returning from malarious areas.

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Phillips-Howard, P A; Radalowicz, A; Mitchell, J; Bradley, D J

1990-01-01

infection was 73% and 54% in west and east Africa respectively. Lower values were obtained for chloroquine alone and proguanil alone. The efficacy of Maloprim (pyrimethamine-dapsone) was 61% in west Africa, but only 9% in east Africa. Visitors to west Africa who did not comply with their chemoprophylactic regimen were at a 2.5-fold higher risk of infection than fully compliant users. Non-compliant visitors to east Africa had similar rates of infection as non-drug users. CONCLUSIONS--In 1987 chloroquine plus proguanil was the preferred chemoprophylactic regimen for P falciparum infection in Africa; antimalarial drugs must be taken regularly to be effective. PMID:2107927

Assessment of the molecular marker of Plasmodium falciparum chloroquine resistance (Pfcrt) in Senegal after several years of chloroquine withdrawal.

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Ndiaye, Magatte; Faye, Babacar; Tine, Roger; Ndiaye, Jean Louis; Lo, Aminata; Abiola, Annie; Dieng, Yemou; Ndiaye, Daouda; Hallett, Rachel; Alifrangis, Michael; Gaye, Oumar

2012-10-01

As a result of widespread antimalarial drug resistance, all African countries with endemic malaria have, in recent years, changed their malaria treatment policy. In Senegal, the health authorities changed from chloroquine (CQ) to a combination of sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) in 2003. Since 2006, the artemisinin combination therapies (ACTs) artemether-lumefantrine (AL) and artesunate plus amodiaquine (AS/AQ) were adopted for uncomplicated malaria treatment. After several years of CQ withdrawal, the current study wished to determine the level of CQ resistance at the molecular level in selected sites in Senegal, because the scientific community is interested in using CQ again. Finger prick blood samples were collected from Plasmodium falciparum-positive children below the age of 10 years (N = 474) during cross-sectional surveys conducted in two study sites in Senegal with different malaria transmission levels. One site is in central Senegal, and the other site is in the southern part of the country. All samples were analyzed for single nucleotide polymorphisms (SNPs) in the P. falciparum CQ resistance transporter gene (Pfcrt; codons 72-76) using polymerase chain reaction (PCR) sequence-specific oligonucleotide probe (SSOP) enzyme-linked immunosorbent assay (ELISA) and real-time PCR methods. In total, the 72- to 76-codon region of Pfcrt was amplified in 449 blood samples (94.7%; 285 and 164 samples from the central and southern sites of Senegal, respectively). In both study areas, the prevalence of the Pfcrt wild-type single CVMNK haplotype was very high; in central Senegal, the prevalence was 70.5% in 2009 and 74.8% in 2010, and in southern Senegal, the prevalence was 65.4% in 2010 and 71.0% in 2011. Comparing data with older studies in Senegal, a sharp decline in the mutant type Pfcrt prevalence is evident: from 65%, 64%, and 59.5% in samples collected from various sites in 2000, 2001, and 2004 to approximately 30% in our study. A similar

Lectins from Synadenium carinatum (ScLL) and Artocarpus heterophyllus (ArtinM) Are Able to Induce Beneficial Immunomodulatory Effects in a Murine Model for Treatment of Toxoplasma gondii Infection.

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Ramos, Eliézer L P; Santana, Silas S; Silva, Murilo V; Santiago, Fernanda M; Mineo, Tiago W P; Mineo, José R

2016-01-01

Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine, and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of T. gondii infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs) were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from T. gondii . The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL, or sulfadiazine, and the following parameters analyzed: Cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus ArtinM treatment induced

Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

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Maiteki-Sebuguzi, Catherine; Jagannathan, Prasanna; Yau, Vincent M; Clark, Tamara D; Njama-Meya, Denise; Nzarubara, Bridget; Talisuna, Ambrose O; Kamya, Moses R; Rosenthal, Philip J; Dorsey, Grant; Staedke, Sarah G

2008-01-01

Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP), artesunate + amodiaquine (AS+AQ), or artemether-lumefantrine (AL). Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years). At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7), or AS+AQ (anorexia: RR 2.10, 95% CI 1

Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

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Kamya Moses R

2008-06-01

Full Text Available Abstract Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP, artesunate + amodiaquine (AS+AQ, or artemether-lumefantrine (AL. Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years. At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7, or AS

A threshold analysis of the cost-effectiveness of artemisinin-based combination therapies in sub-saharan Africa.

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Coleman, Paul G; Morel, Chantal; Shillcutt, Sam; Goodman, Catherine; Mills, Anne J

2004-08-01

-effective under most conditions, other than very low levels of initial resistance to sulfadoxine/pyrimethamine and a five-year time frame. These predictions are conservative in that 95% certainty is a stringent decision rule favoring the rejection of new policies. The importance of other variables not included in the analysis for the robustness of the findings are discussed (e.g., consideration of the entire population at risk for malaria, the affordability of ACTs in specific settings, and the growth of resistance modeled according to population genetic parameters). Copyright 2004 The American Society of Tropical Medicine and Hygiene

Health service providers in Somalia: their readiness to provide malaria case-management.

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Noor, Abdisalan M; Rage, Ismail A; Moonen, Bruno; Snow, Robert W

2009-05-13

Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT) or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53.1% prescribed chloroquine as first-line therapy. 31.4% of

Toxoplasmose congênita em filho de mãe cronicamente infectada com reativação de retinocoroidite na gestação Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy an underestimated event?

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Gláucia M. Q. Andrade

2010-02-01

Full Text Available OBJETIVO: Apresentar um caso raro de toxoplasmose congênita de uma mãe imunocompetente com infecção crônica que teve reativação da doença ocular durante a gestação. DESCRIÇÃO: O recém-nascido estava assintomático no nascimento e foi identificado através de triagem neonatal (IgM anti-Toxoplasma gondii em sangue seco entre outros 190 bebês com toxoplasmose congênita durante um período de 7 meses. Sua mãe tinha tido um episódio não tratado de reativação de retinocoroidite toxoplásmica durante a gestação, com títulos de IgG estáveis e resultados negativos para IgM. Os resultados de IgM e IgG no soro do recém-nascido e o teste de immunoblotting para IgG foram positivos, e detectou-se lesões retinocoroideanas ativas na periferia da retina. O recém-nascido foi tratado com sulfadiazina, pirimetamina e ácido folínico. Aos 14 meses de vida, a criança permanecia assintomática, com regressão das lesões retinocoroideanas e persistência de IgG. COMENTÁRIOS: É possível que a triagem neonatal sistemática em áreas com alta prevalência de infecção possa identificar esses casos.OBJECTIVES: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTIONS:The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn’s serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of

Community response to artemisinin-based combination therapy for childhood malaria: a case study from Dar es Salaam, Tanzania

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Nyato Daniel J

2010-02-01

Full Text Available Abstract Background New malaria treatment guidelines in Tanzania have led to the large-scale deployment of artemether-lumefantrine (Coartem®, popularly known as ALu or dawa mseto. Very little is known about how people in malaria endemic areas interpret policy makers' decision to replace existing anti-malarials, such as sulphadoxine-pyrimethamine (SP with "new" treatment regimens, such as ALu or other formulations of ACT. This study was conducted to examine community level understandings and interpretations of ALu's efficacy and side-effects. The paper specifically examines the perceived efficacy of ALu as articulated by the mothers of young children diagnosed with malaria and prescribed ALu. Methods Participant observation, six focus group discussions in two large villages, followed by interviews with a random sample of 110 mothers of children less than five years of age, who were diagnosed with malaria and prescribed ALu. Additionally, observations were conducted in two village dispensaries involving interactions between mothers/caretakers and health care providers. Results While more than two-thirds of the mothers had an overall negative disposition toward SP, 97.5% of them spoke favourably about ALu, emphasizing it's ability to help their children to rapidly recover from malaria, without undesirable side-effects. 62.5% of the mothers reported that they were spending less money dealing with malaria than previously when their child was treated with SP. 88% of the mothers had waited for 48 hours or more after the onset of fever before taking their child to the dispensary. Mothers' knowledge and reporting of ALu's dosage was, in many cases, inconsistent with the recommended dosage schedule for children. Conclusion Deployment of ALu has significantly changed community level perceptions of anti-malarial treatment. However, mothers continue to delay seeking care before accessing ALu, limiting the impact of highly subsidized rollout of the drug

Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications

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Chance Michael L

2011-08-01

Full Text Available Abstract Background This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP. Methods Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr-C59R and dihydropteroate synthase (dhps-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Results Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9. The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. Conclusion This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum

Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications.

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Mubjer, Reem A; Adeel, Ahmed A; Chance, Michael L; Hassan, Amir A

2011-08-21

This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ) against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP). Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt)-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr)-C59R and dihydropteroate synthase (dhps)-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9). The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African) CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum parasites from Yemen. Mutant pfcrtT76 is highly prevalent but it

Epidemiology of malaria in the forest-savanna transitional zone of Ghana

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Newton Sam

2009-09-01

Full Text Available Abstract Background Information on the epidemiology of malaria is essential for designing and interpreting results of clinical trials of drugs, vaccines and other interventions. As a background to the establishment of a site for anti-malarial drugs and vaccine trials, the epidemiology of malaria in a rural site in central Ghana was investigated. Methods Active surveillance of clinical malaria was carried out in a cohort of children below five years of age (n = 335 and the prevalence of malaria was estimated in a cohort of subjects of all ages (n = 1484 over a 12-month period. Participants were sampled from clusters drawn around sixteen index houses randomly selected from a total of about 22,000 houses within the study area. The child cohort was visited thrice weekly to screen for any illness and a blood slide was taken if a child had a history of fever or a temperature greater than or equal to 37.5 degree Celsius. The all-age cohort was screened for malaria once every eight weeks over a 12-month period. Estimation of Entomological Inoculation Rate (EIR and characterization of Anopheline malaria vectors in the study area were also carried out. Results The average parasite prevalence in the all age cohort was 58% (95% CI: 56.9, 59.4. In children below five years of age, the average prevalence was 64% (95% CI: 61.9, 66.0. Geometric mean parasite densities decreased significantly with increasing age. More than 50% of all children less than 10 years of age were anaemic. Children less than 5 years of age had as many as seven malaria attacks per child per year. The attack rates decreased significantly with increasing cut-offs of parasite density. The average Multiplicity of Infection (MOI was of 6.1. All three pyrimethamine resistance mutant alleles of the Plasmodium falciparum dhfr gene were prevalent in this population and 25% of infections had a fourth mutant of pfdhps-A437G. The main vectors were Anopheles funestus and Anopheles gambiae and the EIR

Plasmodium falciparum resistance to anti-malarial drugs in Papua New Guinea: evaluation of a community-based approach for the molecular monitoring of resistance

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Reeder John C

2010-01-01

Full Text Available Abstract Background Molecular monitoring of parasite resistance has become an important complementary tool in establishing rational anti-malarial drug policies. Community surveys provide a representative sample of the parasite population and can be carried out more rapidly than accrual of samples from clinical cases, but it is not known whether the frequencies of genetic resistance markers in clinical cases differ from those in the overall population, or whether such community surveys can provide good predictions of treatment failure rates. Methods Between 2003 and 2005, in vivo drug efficacy of amodiaquine or chloroquine plus sulphadoxine-pyrimethamine was determined at three sites in Papua New Guinea. The genetic drug resistance profile (i.e., 33 single nucleotide polymorphisms in Plasmodium falciparum crt, mdr1, dhfr, dhps, and ATPase6 was concurrently assessed in 639 community samples collected in the catchment areas of the respective health facilities by using a DNA microarray-based method. Mutant allele and haplotype frequencies were determined and their relationship with treatment failure rates at each site in each year was investigated. Results PCR-corrected in vivo treatment failure rates were between 12% and 28% and varied by site and year with variable longitudinal trends. In the community samples, the frequencies of mutations in pfcrt and pfmdr1 were high and did not show significant changes over time. Mutant allele frequencies in pfdhfr were moderate and those in pfdhps were low. No mutations were detected in pfATPase6. There was much more variation between sites than temporal, within-site, variation in allele and haplotype frequencies. This variation did not correlate well with treatment failure rates. Allele and haplotype frequencies were very similar in clinical and community samples from the same site. Conclusions The relationship between parasite genetics and in vivo treatment failure rate is not straightforward. The

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.

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Raquel González

2014-09-01

Full Text Available BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp with sulfadoxine-pyrimethamine (SP is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ in women receiving CTXp and long-lasting insecticide treated nets (LLITNs. METHODS AND FINDINGS: A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008, placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021, and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031 in the intention to treat (ITT analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration. HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048 in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015. The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. CONCLUSIONS: An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with

Health service providers in Somalia: their readiness to provide malaria case-management

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Moonen Bruno

2009-05-01

Full Text Available Abstract Background Studies have highlighted the inadequacies of the public health sector in sub-Saharan African countries in providing appropriate malaria case management. The readiness of the public health sector to provide malaria case-management in Somalia, a country where there has been no functioning central government for almost two decades, was investigated. Methods Three districts were purposively sampled in each of the two self-declared states of Puntland and Somaliland and the south-central region of Somalia, in April-November 2007. A survey and mapping of all public and private health service providers was undertaken. Information was recorded on services provided, types of anti-malarial drugs used and stock, numbers and qualifications of staff, sources of financial support and presence of malaria diagnostic services, new treatment guidelines and job aides for malaria case-management. All settlements were mapped and a semi-quantitative approach was used to estimate their population size. Distances from settlements to public health services were computed. Results There were 45 public health facilities, 227 public health professionals, and 194 private pharmacies for approximately 0.6 million people in the three districts. The median distance to public health facilities was 6 km. 62.3% of public health facilities prescribed the nationally recommended anti-malarial drug and 37.7% prescribed chloroquine as first-line therapy. 66.7% of public facilities did not have in stock the recommended first-line malaria therapy. Diagnosis of malaria using rapid diagnostic tests (RDT or microscopy was performed routinely in over 90% of the recommended public facilities but only 50% of these had RDT in stock at the time of survey. National treatment guidelines were available in 31.3% of public health facilities recommended by the national strategy. Only 8.8% of the private pharmacies prescribed artesunate plus sulphadoxine/pyrimethamine, while 53

Intermittent screening and treatment versus intermittent preventive treatment of malaria in pregnancy: a randomised controlled non-inferiority trial.

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Harry Tagbor

2010-12-01

Full Text Available The effectiveness of intermittent preventive treatment of malaria in pregnancy (IPTp may be compromised by the spread of resistance to sulphadoxine/pyrimethamine (SP across Africa. But little information exists on alternative drugs for IPTp or alternative strategies for the prevention of malaria in pregnancy. Therefore, we have investigated whether screening with a rapid diagnostic test and treatment of those who are positive (IST at routine antenatal clinic attendances is as effective and as safe as SP-IPTp in pregnant women.During antenatal clinic sessions in six health facilities in Ghana held between March 2007 and September 2007, 3333 pregnant women who satisfied inclusion criteria were randomised into three intervention arms (1 standard SP-IPTp, (2 IST and treatment with SP or (3 IST and treatment with amodiaquine+artesunate (AQ+AS. All women received a long-lasting insecticide treated net. Study women had a maximum of three scheduled follow-up visits following enrollment. Haemoglobin concentration and peripheral parasitaemia were assessed between 36 and 40 weeks of gestation. Birth weight was measured at delivery or within 72 hours for babies delivered at home. Parasite prevalence at enrollment in primigravidae and in multigravidae was 29.6% and 10.2% respectively. At 36-40 weeks of gestation the prevalence of asymptomatic parasitaemia was 12.1% in study women overall and was very similar in all treatment groups. The risk of third trimester severe anaemia or low birth weight did not differ significantly between the three treatment groups regardless of gravidity. IST with AQ+AS or SP was not inferior to SP-IPTp in reducing the risk of low birth weight (RD  =  -1.17[95%CI; -4.39-1.02] for IST-SP vs. SP-IPTp and RD = 0.78[95%CI; -2.11-3.68] for IST-AQAS vs. SP-IPTp; third trimester severe anaemia (RD = 0.29[95%CI; -0.69-1.30] for IST-SP vs. SP-IPTp and RD  =  -0.36[95%CI;-1.12-0.44] for IST-AQAS vs. SP-IPTp.The results of this study

Lectins from Synadenium carinatum (ScLL and Artocarpus heterophyllus (ArtinM are able to induce beneficial immunomodulatory effects in a murine model for treatment of Toxoplasma gondii infection

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Leandro Peixoto Ferreira Souza

2016-11-01

Full Text Available Infection by Toxoplasma gondii affects around one-third of world population and the treatment for patients presenting toxoplasmosis clinically manifested disease is mainly based by a combination of sulfadiazine, pyrimethamine and folinic acid. However, this therapeutic protocol is significantly toxic, causing relevant dose-related bone marrow damage. Thus, it is necessary to improve new approaches to investigate the usefulness of more effective and non-toxic agents for treatment of patients with toxoplasmosis. It has been described that lectins from plants can control parasite infections, when used as immunological adjuvants in vaccination procedures. This type of lectins, such as ArtinM and ScLL is able to induce immunostimulatory activities, including efficient immune response against parasites. The present study aimed to evaluate the potential immunostimulatory effect of ScLL and ArtinM for treatment of T. gondii infection during acute phase, considering that there is no study in the literature accomplishing this issue. For this purpose, bone marrow-derived macrophages (BMDMs were treated with different concentrations from each lectin to determine the maximum concentration without or with lowest cytotoxic effect. After, it was also measured the cytokine levels produced by these cells when stimulated by the selected concentrations of lectins. We found that ScLL showed high capacity to induce of pro-inflammatory cytokine production, while ArtinM was able to induce especially an anti-inflammatory cytokines production. Furthermore, both lectins were able to increase NO levels. Next, we evaluated the treatment effect of ScLL and ArtinM in C57BL/6 mice infected by ME49 strain from T. gondii. The animals were infected and treated with ScLL, ArtinM, ArtinM plus ScLL or sulfadiazine, and the following parameters analyzed: cytokines production, brain parasite burden and survival rates. Our results demonstrated that the ScLL or ScLL plus Artin

The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya

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Otieno Dorothy N

2007-05-01

Full Text Available Abstract Backgound Sulphadoxine/sulphalene-pyrimethamine (SP was adopted in Kenya as first line therapeutic for uncomplicated malaria in 1998. By the second half of 2003, there was convincing evidence that SP was failing and had to be replaced. Despite several descriptive investigations of policy change and implementation when countries moved from chloroquine to SP, the different constraints of moving to artemisinin-based combination therapy (ACT in Africa are less well documented. Methods A narrative description of the process of anti-malarial drug policy change, financing and implementation in Kenya is assembled from discussions with stakeholders, reports, newspaper articles, minutes of meetings and email correspondence between actors in the policy change process. The narrative has been structured to capture the timing of events, the difficulties and hurdles faced and the resolutions reached to the final implementation of a new treatment policy. Results Following a recognition that SP was failing there was a rapid technical appraisal of available data and replacement options resulting in a decision to adopt artemether-lumefantrine (AL as the recommended first-line therapy in Kenya, announced in April 2004. Funding requirements were approved by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM and over 60 million US$ were agreed in principle in July 2004 to procure AL and implement the policy change. AL arrived in Kenya in May 2006, distribution to health facilities began in July 2006 coincidental with cascade in-service training in the revised national guidelines. Both training and drug distribution were almost complete by the end of 2006. The article examines why it took over 32 months from announcing a drug policy change to completing early implementation. Reasons included: lack of clarity on sustainable financing of an expensive therapeutic for a common disease, a delay in release of funding, a lack of comparative efficacy data

A trial of intermittent preventive treatment and home-based management of malaria in a rural area of The Gambia

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Webb Emily L

2011-01-01

Full Text Available Abstract Background Individual malaria interventions provide only partial protection in most epidemiological situations. Thus, there is a need to investigate whether combining interventions provides added benefit in reducing mortality and morbidity from malaria. The potential benefits of combining IPT in children (IPTc with home management of malaria (HMM was investigated. Methods During the 2008 malaria transmission season, 1,277 children under five years of age resident in villages within the rural Farafenni demographic surveillance system (DSS in North Bank Region, The Gambia were randomized to receive monthly IPTc with a single dose of sulphadoxine/pyrimethamine (SP plus three doses of amodiaquine (AQ or SP and AQ placebos given by village health workers (VHWs on three occasions during the months of September, October and November, in a double-blind trial. Children in all study villages who developed an acute febrile illness suggestive of malaria were treated by VHWs who had been taught how to manage malaria with artemether-lumefantrine (Coartem™. The primary aims of the project were to determine whether IPTc added significant benefit to HMM and whether VHWs could effectively combine the delivery of both interventions. Results The incidence of clinical attacks of malaria was very low in both study groups. The incidence rate of malaria in children who received IPTc was 0.44 clinical attacks per 1,000 child months at risk while that for control children was 1.32 per 1,000 child months at risk, a protective efficacy of 66% (95% CI -23% to 96%; p = 0.35. The mean (standard deviation haemoglobin concentration at the end of the malaria transmission season was similar in the two treatment groups: 10.2 (1.6 g/dL in the IPTc group compared to 10.3 (1.5 g/dL in the placebo group. Coverage with IPTc was high, with 94% of children receiving all three treatments during the study period. Conclusion Due to the very low incidence of malaria, no firm

Vaccines for preventing malaria (blood-stage).

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Graves, P; Gelband, H

2006-10-18

A malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials. To assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death. In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Randomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Both authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI). Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to

A single LC-tandem mass spectrometry method for the simultaneous determination of 14 antimalarial drugs and their metabolites in human plasma.

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Hodel, E M; Zanolari, B; Mercier, T; Biollaz, J; Keiser, J; Olliaro, P; Genton, B; Decosterd, L A

2009-04-01

Among the various determinants of treatment response, the achievement of sufficient blood levels is essential for curing malaria. For helping us at improving our current understanding of antimalarial drugs pharmacokinetics, efficacy and toxicity, we have developed a liquid chromatography-tandem mass spectrometry method (LC-MS/MS) requiring 200mul of plasma for the simultaneous determination of 14 antimalarial drugs and their metabolites which are the components of the current first-line combination treatments for malaria (artemether, artesunate, dihydroartemisinin, amodiaquine, N-desethyl-amodiaquine, lumefantrine, desbutyl-lumefantrine, piperaquine, pyronaridine, mefloquine, chloroquine, quinine, pyrimethamine and sulfadoxine). Plasma is purified by a combination of protein precipitation, evaporation and reconstitution in methanol/ammonium formate 20mM (pH 4.0) 1:1. Reverse-phase chromatographic separation of antimalarial drugs is obtained using a gradient elution of 20mM ammonium formate and acetonitrile both containing 0.5% formic acid, followed by rinsing and re-equilibration to the initial solvent composition up to 21min. Analyte quantification, using matrix-matched calibration samples, is performed by electro-spray ionization-triple quadrupole mass spectrometry by selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effect variability, overall process efficiency, standard addition experiments as well as antimalarials short- and long-term stability in plasma. The reactivity of endoperoxide-containing antimalarials in the presence of hemolysis was tested both in vitro and on malaria patients samples. With this method, signal intensity of artemisinin decreased by about 20% in the presence of 0.2% hemolysed red-blood cells in plasma, whereas its derivatives were essentially not affected. The method is precise (inter-day CV%: 3.1-12.6%) and sensitive

Implementation of co-trimoxazole preventive therapy policy for malaria in HIV-infected pregnant women in the public health facilities in Tanzania

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Kamuhabwa AAR

2016-12-01

Full Text Available Appolinary AR Kamuhabwa, Richard Gordian, Ritah F Mutagonda Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania Background: In 2011, Tanzania adopted a policy for provision of daily co-trimoxazole prophylaxis to HIV-infected pregnant women for prevention of malaria and other opportunistic infections. As per the policy, HIV-infected pregnant women should not be given sulfadoxine-pyrimethamine (SP for intermittent preventive therapy. The challenges associated with this policy change and the extent to which the new policy for prevention of malaria in pregnant women coinfected with HIV was implemented need to be assessed. Aim: To assess the implementation of malaria-preventive therapy policy among HIV-infected pregnant women in the public health facilities in Dar es Salaam, Tanzania. Methodology: The study was conducted in Kinondoni Municipality, Dar es Salaam, Tanzania, from January 2015 to July 2015. Three hundred and fifty-three HIV-infected pregnant women who were attending antenatal clinics (ANCs and using co-trimoxazole for prevention of malaria were interviewed. Twenty-six health care workers working at the ANCs were also interviewed regarding provision of co-trimoxazole prophylaxis to pregnant women. A knowledge scale was used to grade the level of knowledge of health care providers. Focus group discussions were also conducted with 18 health care workers to assess the level of implementation of the policy and the challenges encountered. Results: Twenty-three (6.5% pregnant women with known HIV serostatus were using co-trimoxazole for prevention of opportunistic infections even before they became pregnant. Out of the 353 HIV-infected pregnant women, eight (2.5% were coadministered with both SP and co-trimoxazole. Sixty (16.7% pregnant women had poor adherence to co-trimoxazole prophylaxis. Out of the 26 interviewed health care providers, 20 had high

Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

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Sevene, Esperança; Mariano, Alda; Mehta, Ushma; Machai, Maria; Dodoo, Alexander; Vilardell, David; Patel, Sam; Barnes, Karen; Carné, Xavier

2008-01-01

the first training, 67 ADR reports involving 74 adverse events were received by the NPU involving 25 separate drugs, 16 of which were causally (certainly, probably or possibly) linked to the reaction. Most reported ADRs were dermatological reactions (83.1%). Antimalarial drugs (chloroquine, amodiaquine, quinine, artesunate and sulfadoxine/pyrimethamine) were mentioned in 33 (50.8%) of the reports. There were 14 reactions classified as serious and no fatal reactions were reported. There were differences in telecommunications and transport facilities between the districts that might have contributed to the different number of reports. Health professionals of all levels of education (including basic training) from rural areas could contribute to ADR spontaneous reporting systems. Training, quality-assurance visits and the ongoing presence of focal persons can promote reporting and improve the quality of reports submitted.

Travel and the emergence of high-level drug resistance in Plasmodium falciparum in southwest Uganda: results from a population-based study.

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Lynch, Caroline A; Pearce, Richard; Pota, Hirva; Egwang, Connie; Egwang, Thomas; Bhasin, Amit; Cox, Jonathan; Abeku, Tarekegn A; Roper, Cally

2017-04-17

The I164L mutation on the dhfr gene confers high level resistance to sulfadoxine-pyrimethamine (SP) but it is rare in Africa except in a cluster of reports where prevalence >10% in highland areas of southwest Uganda and eastern Rwanda. The occurrence of the dhfr I164L mutation was investigated in community surveys in this area and examined the relationship to migration. A cross-sectional prevalence survey was undertaken in among villages within the catchment areas of two health facilities in a highland site (Kabale) and a highland fringe site (Rukungiri) in 2007. Sociodemographic details, including recent migration, were collected for each person included in the study. A total of 206 Plasmodium falciparum positive subjects were detected by rapid diagnostic test; 203 in Rukungiri and 3 in Kabale. Bloodspot samples were taken and were screened for dhfr I164L. Sequence analysis confirmed the presence of the I164L mutations in twelve P. falciparum positive samples giving an estimated prevalence of 8.6% in Rukungiri. Of the three parasite positive samples in Kabale, none had I164L mutations. Among the twelve I164L positives three were male, ages ranged from 5 to 90 years of age. None of those with the I164L mutation had travelled in the 8 weeks prior to the survey, although three were from households from which at least one household member had travelled during that period. Haplotypes were determined in non-mixed infections and showed the dhfr I164L mutation occurs in both as a N51I + S108N + I164L haplotype (n = 2) and N51I + C59R + S108N + I164L haplotype (n = 5). Genotyping of flanking microsatellite markers showed that the I164L occurred independently on the triple mutant (N51I, C59R + S108N) and double mutant (N51I + S108N) background. There is sustained local transmission of parasites with the dhfr I164L mutation in Rukungiri and no evidence to indicate its occurrence is associated with recent travel to highly resistant neighbouring areas. The

Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries.

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O'Connell, Kathryn A; Gatakaa, Hellen; Poyer, Stephen; Njogu, Julius; Evance, Illah; Munroe, Erik; Solomon, Tsione; Goodman, Catherine; Hanson, Kara; Zinsou, Cyprien; Akulayi, Louis; Raharinjatovo, Jacky; Arogundade, Ekundayo; Buyungo, Peter; Mpasela, Felton; Adjibabi, Chérifatou Bello; Agbango, Jean Angbalu; Ramarosandratana, Benjamin Fanomezana; Coker, Babajide; Rubahika, Denis; Hamainza, Busiku; Chapman, Steven; Shewchuk, Tanya; Chavasse, Desmond

2011-10-31

Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (sector, first-line quality-assured ACT was available for free in all countries except Benin and the DRC (US$1.29 [Inter Quartile Range (IQR): $1.29-$1.29] and $0.52[IQR: $0.00-$1.29] per adult equivalent dose respectively). In the private sector, first-line quality-assured ACT was 5-24 times more expensive than non-artemisinin therapies. The exception was Madagascar where, due to national social marketing of subsidized ACT, the price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

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Glinz, Dominik; Hurrell, Richard F; Ouattara, Mamadou; Zimmermann, Michael B; Brittenham, Gary M; Adiossan, Lukas G; Righetti, Aurélie A; Seifert, Burkhardt; Diakité, Victorine G; Utzinger, Jürg; N'Goran, Eliézer K; Wegmüller, Rita

2015-09-17

Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb

Progress towards malaria elimination in Zimbabwe with special reference to the period 2003-2015.

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Sande, Shadreck; Zimba, Moses; Mberikunashe, Joseph; Tangwena, Andrew; Chimusoro, Anderson

2017-07-24

An intensive effort to control malaria in Zimbabwe has produced dramatic reductions in the burden of the disease over the past 13 years. The successes have prompted the Zimbabwe's National Malaria Control Programme to commit to elimination of malaria. It is critical to analyse the changes in the morbidity trends based on surveillance data, and scrutinize reorientation to strategies for elimination. This is a retrospective study of available Ministry of Health surveillance data and programme reports, mostly from 2003 to 2015. Malaria epidemiological data were drawn from the National Health Information System database. Data on available resources, malaria control strategies, morbidity and mortality trends were analysed, and opportunities for Zimbabwe malaria elimination agenda was perused. With strong government commitment and partner support, the financial gap for malaria programming shrank by 91.4% from about US$13 million in 2012 to US$1 million in 2015. Vector control comprises indoor residual house spraying (IRS) and long-lasting insecticidal nets, and spray coverage increased from 28% in 2003 to 95% in 2015. Population protected by IRS increased also from 20 to 96% for the same period. In 2009, diagnostics improved from clinical to parasitological confirmation either by rapid diagnostic tests or microscopy. Artemisinin-based combination therapy was used to treat malaria following chloroquine resistance in 2000, and sulfadoxine-pyrimethamine in 2004. In 2003, there were 155 malaria cases per 1000 populations reported from all health facilities throughout the country. The following decade witnessed a substantial decline in cases to only 22 per 1000 populations in 2012. A resurgence was reported in 2013 (29/1000) and 2014 (39/1000), thereafter morbidity declined to 29 cases per 1000 populations, only to the same level as in 2013. Overall, morbidity declined by 81% from 2003 to 2015. Inpatient malaria deaths per 100,000 populations doubled in 4 years, from 2

The Cost-Effectiveness of Intermittent Preventive Treatment for Malaria in Infants in Sub-Saharan Africa

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Conteh, Lesong; Sicuri, Elisa; Manzi, Fatuma; Hutton, Guy; Obonyo, Benson; Tediosi, Fabrizio; Biao, Prosper; Masika, Paul; Matovu, Fred; Otieno, Peter; Gosling, Roly D.; Hamel, Mary; Odhiambo, Frank O.; Grobusch, Martin P.; Kremsner, Peter G.; Chandramohan, Daniel; Aponte, John J.; Egan, Andrea; Schellenberg, David; Macete, Eusebio; Slutsker, Laurence; Newman, Robert D.; Alonso, Pedro; Menéndez, Clara; Tanner, Marcel

2010-01-01

Background Intermittent preventive treatment in infants (IPTi) has been shown to decrease clinical malaria by approximately 30% in the first year of life and is a promising malaria control strategy for Sub-Saharan Africa which can be delivered alongside the Expanded Programme on Immunisation (EPI). To date, there have been limited data on the cost-effectiveness of this strategy using sulfadoxine pyrimethamine (SP) and no published data on cost-effectiveness using other antimalarials. Methods We analysed data from 5 countries in sub-Saharan Africa using a total of 5 different IPTi drug regimens; SP, mefloquine (MQ), 3 days of chlorproguanil-dapsone (CD), SP plus 3 days of artesunate (SP-AS3) and 3 days of amodiaquine-artesunate (AQ3-AS3).The cost per malaria episode averted and cost per Disability-Adjusted Life-Year (DALY) averted were modeled using both trial specific protective efficacy (PE) for all IPTi drugs and a pooled PE for IPTi with SP, malaria incidence, an estimated malaria case fatality rate of 1.57%, IPTi delivery costs and country specific provider and household malaria treatment costs. Findings In sites where IPTi had a significant effect on reducing malaria, the cost per episode averted for IPTi-SP was very low, USD 1.36–4.03 based on trial specific data and USD 0.68–2.27 based on the pooled analysis. For IPTi using alternative antimalarials, the lowest cost per case averted was for AQ3-AS3 in western Kenya (USD 4.62) and the highest was for MQ in Korowge, Tanzania (USD 18.56). Where efficacious, based only on intervention costs, IPTi was shown to be cost effective in all the sites and highly cost-effective in all but one of the sites, ranging from USD 2.90 (Ifakara, Tanzania with SP) to USD 39.63 (Korogwe, Tanzania with MQ) per DALY averted. In addition, IPTi reduced health system costs and showed significant savings to households from malaria cases averted. A threshold analysis showed that there is room for the IPTi-efficacy to fall and still

Use of Intermittent Preventive Treatment among Pregnant Women in Sub-Saharan Africa: Evidence from Malaria Indicator Surveys

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Sanni Yaya

2018-02-01

Full Text Available Uptake of intermittent preventive therapy in pregnancy (IPTp with sulfadoxine-pyrimethamine (IPTp-SP is a clinically-proven method to prevent the adverse outcomes of malaria in pregnancy (MiP for the mother, her foetus, and the neonates. The majority of countries in sub-Saharan Africa have introduced IPTp policies for pregnant women during the past decade. Nonetheless, progress towards improving IPTp coverage remains dismal, with widespread regional and socioeconomic disparities in the utilisation of this highly cost-effective service. In the present study, our main objective was to measure the prevalence of IPTp uptake in selected malaria-endemic countries in sub-Saharan Africa, and to investigate the patterns of IPTp uptake among different educational and wealth categories adjusted for relevant sociodemographic factors. For this study, cross-sectional data on 18,603 women aged between 15 and 49 years were collected from the Malaria Indicator Surveys (MIS conducted in Burkina Faso, Ghana, Mali, Malawi, Kenya, Nigeria, Sierra Leone, and Uganda. The outcome variable was taking three doses of IPTp-SP in the last pregnancy, defined as adequate by the WHO. According to the analysis, the overall prevalence of taking three doses of IPTp-SP in the latest pregnancy was 29.5% (95% CI = 28.2–30.5, with the prevalence being highest for Ghana (60%, 95% CI = 57.1–62.8, followed by Kenya (37%, 95% CI = 35.3–39.2 and Sierra Leone (31%, 95% CI = 29.2–33.4. Women from non-poor households (richer—20.7%, middle—21.2%, richest—18.1% had a slightly higher proportion of taking three doses of IPTp-SP compared with those from poorest (19.0% and poorer (21.1% households. Regression analysis revealed an inverse association between uptake of IPTp-SP and educational level. With regard to wealth status, compared with women living in the richest households, those in the poorest, poorer, middle, and richer households had significantly higher odds of not taking

Open-label trial on efficacy of artemether/lumefantrine against the uncomplicated Plasmodium falciparum malaria in Metema district, Northwestern Ethiopia

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Wudneh F

2016-08-01

Full Text Available Feven Wudneh,1,2 Ashenafi Assefa,3 Desalegn Nega,3 Hussien Mohammed,3 Hiwot Solomon,4 Tadesse Kebede,2 Adugna Woyessa,3 Yibeltal Assefa,3 Amha Kebede,3 Moges Kassa3 1Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, 2Biomedical Department, College of Health Sciences and Medicine, Dilla University, Dilla, 3Malaria and Other Parasitological and Entomological Research Team, Bacterial, Parasitic and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, 4Malaria Research Team, Disease Prevention and Control Directorate, Federal Ministry of Health, Addis Ababa, Ethiopia Purpose: Following the increased Plasmodium falciparum resistance to chloroquine and sulfadoxine/pyrimethamine, Ethiopia adopted artemether/lumefantrine (AL as the first-line treatment for uncomplicated P. falciparum in 2004. According to the recommendation of the World Health Organization, this study was carried out for regular monitoring of the efficacy of AL in treating the uncomplicated P. falciparum malaria in Metema district, Gondar Zone, Northwest Ethiopia.Patients and methods: This is a one-arm prospective 28-day in vivo therapeutic efficacy study among the uncomplicated P. falciparum malaria patients aged 6 months and older. The study was conducted from October 2014 to January 2015, based on the revised World Health Organization protocol of 2009 for surveillance of antimalarial drug therapeutic efficacy study. Standard six-dose regimen of AL was given twice daily for 3 days, and then the treatment outcomes were assessed on days 0, 1, 2, 3, 7, 14, 21, 28, and any other unscheduled day for emergency cases.Results: There were 91 study subjects enrolled in this study, of whom 80 study subjects completed the full follow-up schedules and showed adequate clinical and parasitological responses on day 28, with no major adverse event. Per protocol analysis, the unadjusted

Determinants of maternal health services utilization in urban settings of the Democratic Republic of Congo – A Case study of Lubumbashi City

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2012-01-01

Background The use of maternal health services, known as an indirect indicator of perinatal death, is still unknown in Lubumbashi. The present study was therefore undertaken in order to determine the factors that influence the use of mother and child healthcare services in Lubumbashi, Democratic Republic of the Congo. Methods This was transversal study of women residing in Lubumbashi who had delivered between January and December 2009. In total, 1762 women were sampled from households using indicator cluster surveys in all health zones. Antenatal consultations (ANC), delivery assisted by qualified healthcare personnel (and delivery in a healthcare facility) as well as postnatal consultations (PNC) were dependent variables of study. The factors determining non-use of maternal healthcare services were researched via logistic regression with a 5% materiality threshold. Results The use of maternal healthcare services was variable; 92.6% of women had attended ANC at least once, 93.8% of women had delivered at a healthcare facility, 97.2% had delivered in the presence of qualified healthcare personnel, while the rate of caesarean section was 4.5%. Only 34.6% postnatal women had attended PNC by 42 days after delivery. During these ANC visits, only 60.6% received at least one dose of vaccine, while 38.1% received Mebendazole, 35.6% iron, 32.7% at least one dose of SulfadoxinePyrimethamine, 29.2% folic acid, 15.5% screening for HIV and 12.8% an insecticide treated net. In comparison to women that had had two or three deliveries before, primiparous and grand multiparous women were twice as likely not to use ANC during their pregnancy. Women who had unplanned pregnancies were also more likely not to use ANC or PNC than those who had planned pregnancies alone or with their partner. The women who had not used ANC were also more likely not to use PNC. The women who had had a trouble-free delivery were more likely not to use PNC than those who had complications when delivering

Determinants of maternal health services utilization in urban settings of the Democratic Republic of Congo--a case study of Lubumbashi City.

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Abel Ntambue, M L; Françoise Malonga, K; Dramaix-Wilmet, Michèle; Donnen, Philippe

2012-07-10

The use of maternal health services, known as an indirect indicator of perinatal death, is still unknown in Lubumbashi. The present study was therefore undertaken in order to determine the factors that influence the use of mother and child healthcare services in Lubumbashi, Democratic Republic of the Congo. This was transversal study of women residing in Lubumbashi who had delivered between January and December 2009. In total, 1762 women were sampled from households using indicator cluster surveys in all health zones. Antenatal consultations (ANC), delivery assisted by qualified healthcare personnel (and delivery in a healthcare facility) as well as postnatal consultations (PNC) were dependent variables of study. The factors determining non-use of maternal healthcare services were researched via logistic regression with a 5% materiality threshold. The use of maternal healthcare services was variable; 92.6% of women had attended ANC at least once, 93.8% of women had delivered at a healthcare facility, 97.2% had delivered in the presence of qualified healthcare personnel, while the rate of caesarean section was 4.5%. Only 34.6% postnatal women had attended PNC by 42 days after delivery. During these ANC visits, only 60.6% received at least one dose of vaccine, while 38.1% received Mebendazole, 35.6% iron, 32.7% at least one dose of SulfadoxinePyrimethamine, 29.2% folic acid, 15.5% screening for HIV and 12.8% an insecticide treated net.In comparison to women that had had two or three deliveries before, primiparous and grand multiparous women were twice as likely not to use ANC during their pregnancy. Women who had unplanned pregnancies were also more likely not to use ANC or PNC than those who had planned pregnancies alone or with their partner. The women who had not used ANC were also more likely not to use PNC. The women who had had a trouble-free delivery were more likely not to use PNC than those who had complications when delivering. In Lubumbashi, a significant

Determinants of maternal health services utilization in urban settings of the Democratic Republic of Congo – A Case study of Lubumbashi City

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ML Abel

2012-07-01

Full Text Available Abstract Background The use of maternal health services, known as an indirect indicator of perinatal death, is still unknown in Lubumbashi. The present study was therefore undertaken in order to determine the factors that influence the use of mother and child healthcare services in Lubumbashi, Democratic Republic of the Congo. Methods This was transversal study of women residing in Lubumbashi who had delivered between January and December 2009. In total, 1762 women were sampled from households using indicator cluster surveys in all health zones. Antenatal consultations (ANC, delivery assisted by qualified healthcare personnel (and delivery in a healthcare facility as well as postnatal consultations (PNC were dependent variables of study. The factors determining non-use of maternal healthcare services were researched via logistic regression with a 5% materiality threshold. Results The use of maternal healthcare services was variable; 92.6% of women had attended ANC at least once, 93.8% of women had delivered at a healthcare facility, 97.2% had delivered in the presence of qualified healthcare personnel, while the rate of caesarean section was 4.5%. Only 34.6% postnatal women had attended PNC by 42 days after delivery. During these ANC visits, only 60.6% received at least one dose of vaccine, while 38.1% received Mebendazole, 35.6% iron, 32.7% at least one dose of SulfadoxinePyrimethamine, 29.2% folic acid, 15.5% screening for HIV and 12.8% an insecticide treated net. In comparison to women that had had two or three deliveries before, primiparous and grand multiparous women were twice as likely not to use ANC during their pregnancy. Women who had unplanned pregnancies were also more likely not to use ANC or PNC than those who had planned pregnancies alone or with their partner. The women who had not used ANC were also more likely not to use PNC. The women who had had a trouble-free delivery were more likely not to use PNC than those who had

Private sector role, readiness and performance for malaria case management in Uganda, 2015.

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Kaula, Henry; Buyungo, Peter; Opigo, Jimmy

2017-05-25

survey illustrate that the majority of anti-malarials were distributed through the private sector (54.3%), with 31.4% of all anti-malarials distributed through drug stores and 14.4% through private for-profit health facilities. Availability of different anti-malarials and diagnostic testing in the private sector was: ACT (80.7%), quality-assured (QA) ACT (72.0%), sulfadoxine-pyrimethamine (SP) (47.1%), quinine (73.2%) and any malaria blood testing (32.9%). Adult QAACT ($1.62) was three times more expensive than SP ($0.48). The results from the fever case management study found 44.4% of respondents received a malaria test, and among those who tested positive for malaria, 60.0% received an ACT, 48.5% received QAACT; 14.4% a non-artemisinin therapy; 14.9% artemether injection, and 42.5% received an antibiotic. The private sector plays an important role in malaria case management in Uganda. While several private sector initiatives have improved availability of QAACT, there are gaps in malaria diagnosis and distribution of non-artemisinin monotherapies persists. Further private sector strategies, including those focusing on drug stores, are needed to increase coverage of parasitological testing and removal of non-artemisinin therapies from the marketplace.

A new strategy and its effect on adherence to intermittent preventive treatment of malaria in pregnancy in Uganda.

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Mbonye, Anthony K; Yanow, Stephanie; Birungi, Josephine; Magnussen, Pascal

2013-09-21

Few women in Uganda access intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP). Previous studies have shown that high costs, frequent stock-out of drugs, supplies and poor quality of care are the greatest hindrance for women to access health services. In order to increase adherence to IPTp, we conceptualised an intervention that offset delivery care costs through providing a mama kit, created awareness on health benefits of IPTp and built trust between the provider and the client. The new strategy was conceived along four constructs namely: 1) creating awareness by training midwives to explain the benefits of SP and the importance of adhering to the two doses of SP as IPTp to all pregnant women who attended ANC and consented to the study. Midwives were trained for two days in customer care and to provide a friendly environment. The pregnant women were also informed of the benefits of attending ANC and delivering at health facilities. 2) Each woman was promised a mama kit during ANC; 3) trust was built by showing the mama kit to each woman and branding it with her name; 4) keeping the promise by providing the mama kit when women came to deliver. The strategy to increase adherence to two doses of SP and encourage women to deliver at health facilities was implemented at two health facilities in Mukono district (Kawolo hospital and Mukono health centre IV). The inclusion criteria were women who: i) consented to the study and ii) were in the second trimester of pregnancy. All pregnant women in the second trimester (4-6 months gestation) who attended ANC and consented to participate in the study were informed of the benefits of SP, the importance of delivering at health facilities, were advised to attend the scheduled visits, promised a mama kit and ensured the kit was available at delivery. The primary outcome was the proportion of pregnant women adhering to a two dose SP regimen. A total of 2,276 women received the first

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-negative women: a multicentre randomized controlled trial.

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Raquel González

2014-09-01

Full Text Available Intermittent preventive treatment in pregnancy (IPTp with sulfadoxine-pyrimethamine (SP is recommended by WHO to prevent malaria in African pregnant women. The spread of SP parasite resistance has raised concerns regarding long-term use for IPT. Mefloquine (MQ is the most promising of available alternatives to SP based on safety profile, long half-life, and high efficacy in Africa. We evaluated the safety and efficacy of MQ for IPTp compared to those of SP in HIV-negative women.A total of 4,749 pregnant women were enrolled in an open-label randomized clinical trial conducted in Benin, Gabon, Mozambique, and Tanzania comparing two-dose MQ or SP for IPTp and MQ tolerability of two different regimens. The study arms were: (1 SP, (2 single dose MQ (15 mg/kg, and (3 split-dose MQ in the context of long lasting insecticide treated nets. There was no difference on low birth weight prevalence (primary study outcome between groups (360/2,778 [13.0%] for MQ group and 177/1,398 (12.7% for SP group; risk ratio [RR], 1.02 (95% CI 0.86-1.22; p=0.80 in the ITT analysis. Women receiving MQ had reduced risks of parasitemia (63/1,372 [4.6%] in the SP group and 88/2,737 [3.2%] in the MQ group; RR, 0.70 [95% CI 0.51-0.96]; p=0.03 and anemia at delivery (609/1,380 [44.1%] in the SP group and 1,110/2743 [40.5%] in the MQ group; RR, 0.92 [95% CI 0.85-0.99]; p=0.03, and reduced incidence of clinical malaria (96/551.8 malaria episodes person/year [PYAR] in the SP group and 130/1,103.2 episodes PYAR in the MQ group; RR, 0.67 [95% CI 0.52-0.88]; p=0.004 and all-cause outpatient attendances during pregnancy (850/557.8 outpatients visits PYAR in the SP group and 1,480/1,110.1 visits PYAR in the MQ group; RR, 0.86 [0.78-0.95]; p=0.003. There were no differences in the prevalence of placental infection and adverse pregnancy outcomes between groups. Tolerability was poorer in the two MQ groups compared to SP. The most frequently reported related adverse events were dizziness

Comportamiento de la toxoplasmosis ocular activa en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer" Behavior of the active ocular toxoplasmosis in patients of the "Ramón Pando Ferrer" Cuban Institute of Ophthalmology

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Eddy Mesa Hernández

2011-06-01

total laboratory and ophthalmologic examination. RESULTS: The commonest presentation way was as a retinitis and the more involved age-group was that of 20-29 years, with a slight predominance of female sex. The vision decrease and the floaters were the main symptoms of presentation, the clinical diagnosis was made in 106 patients. Inflammation predominated in the 1 retinal zone and involved mainly in a moderate way the vision of patients in the involved eye at diagnosis. In 122 of the 128 treatment was applied consisted in most of the standard scheme of pyrimethamine, sulfadiazine and prednisone. The 43.1 % of involved eyes recovered it normal vision, whereas 34 eyes remained with a severe decrease, most caused by complications including macular scars, which were the more registered. CONCLUSIONS: It is possible to achieve good visual results with an appropriate therapy although it will depend on the involved retinal area, the level of intraocular inflammation and the length of the disease.

Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

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Domingos Alves Meira

1988-09-01

Full Text Available A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7th, 24th, 21st, 28th and 35th day both clinically and parasitologically (blood test. Eighty three (40.1% had moderate or severe malaria, and 97 (46.8% had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%, two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.De 1981 a 1984, 207 doentes com malária, causada pelo Plasmodium falciparum, foram tratados com 5 esquemas de clindamicina: A - 89 doente tratados com 20 mg/kg/dia, pelas vias endovenosa e oral, ou intramuscular e oral, em duas aplicações diárias, durante 5 a 7 dias; B - 40 doentes tratados com 20 mg/kg/dia, por via oral, em duas tomadas diárias, durante 5 a 7 dias; C - 27 doentes tratados com 20 mg/kg/dia, por via oral ou endovenosa, em

Malaria Surveillance - United States, 2014.

Science.gov (United States)

Mace, Kimberly E; Arguin, Paul M

2017-05-26

. Less than 1.0% of patients were infected with two species. The infecting species was unreported or undetermined in 11.7% of cases. CDC provided diagnostic assistance for 14.2% of confirmed cases and tested 12.0% of P. falciparum specimens for antimalarial resistance markers. Of patients who reported purpose of travel, 57.5% were visiting friends and relatives (VFR). Among U.S. residents for whom information on chemoprophylaxis use and travel region was known, 7.8% reported that they initiated and adhered to a chemoprophylaxis drug regimen recommended by CDC for the regions to which they had traveled. Thirty-two cases were among pregnant women, none of whom had adhered to chemoprophylaxis. Among all reported cases, 17.0% were classified as severe illness, and five persons with malaria died. CDC received 137 P. falciparum-positive samples for the detection of antimalarial resistance markers (although some loci for chloroquine and mefloquine were untestable for up to nine samples). Of the 137 samples tested, 131 (95.6%) had genetic polymorphisms associated with pyrimethamine drug resistance, 96 (70.0%) with sulfadoxine resistance, 77 (57.5%) with chloroquine resistance, three (2.3%) with mefloquine drug resistance, one (html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Recent molecular laboratory advances have enabled CDC to identify and conduct molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) and improve the ability of CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and globally. For this effort to be successful, specimens should be submitted for all cases diagnosed in the United States. Clinicians should consult CDC Guidelines for Treatment of Malaria in the

Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

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Badara Cissé

2016-11-01

Full Text Available Seasonal Malaria Chemoprevention (SMC with sulfadoxine-pyrimethamine (SP plus amodiaquine (AQ, given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age.SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC

Toxoplasmosis in pregnancy: prevention, screening, and treatment.

Science.gov (United States)

Paquet, Caroline; Yudin, Mark H

2013-01-01

given to starting therapy with spiramycin immediately, without waiting for the repeat test results. (II-2B) 4. Amniocentesis should be offered to identify Toxoplasma gondii in the amniotic fluid by polymerase chain reaction (a) if maternal primary infection is diagnosed, (b) if serologic testing cannot confirm or exclude acute infection, or (c) in the presence of abnormal ultrasound findings (intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction). (II-2B) 5. Amniocentesis should not be offered for the identification of Toxoplasma gondii infection at less than 18 weeks' gestation and should be offered no less than 4 weeks after suspected acute maternal infection to lower the occurrence of false-negative results. (II-2D) 6. Toxoplasma gondii infection should be suspected and screening should be offered to pregnant women with ultrasound findings consistent with possible TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes, and other) infection, including but not limited to intracranial calcification, microcephaly, hydrocephalus, ascites, hepatosplenomegaly, or severe intrauterine growth restriction. (II-2B) 7. Each case involving a pregnant woman suspected of having an acute Toxoplasma gondii infection acquired during gestation should be discussed with an expert in the management of toxoplasmosis. (III-B) 8. If maternal infection has been confirmed but the fetus is not yet known to be infected, spiramycin should be offered for fetal prophylaxis (to prevent spread of organisms across the placenta from mother to fetus). (I-B) 9. A combination of pyrimethamine, sulfadiazine, and folinic acid should be offered as treatment for women in whom fetal infection has been confirmed or is highly suspected (usually by a positive amniotic fluid polymerase chain reaction). (I-B) 10. Anti-toxoplasma treatment in immunocompetent pregnant women with previous infection with Toxoplasma gondii should not be necessary

Conquering the intolerable burden of malaria: what's new, what's needed: a summary.

Science.gov (United States)

Breman, Joel G; Alilio, Martin S; Mills, Anne

2004-08-01

approach for countering the spread and intensity of Plasmodium falciparum resistance to chloroquine, sulfadoxine/pyrimethamine, and other antimalarial drugs. Although costly, ACT ($1.20-2.50 per adult treatment) becomes more cost-effective as resistance to alternative drugs increases; early use of ACT may delay development of resistance to these drugs and prevent the medical toll associated with use of ineffective drugs. The burden of malaria in one district in Tanzania has not decreased since the primary health care approach replaced the vertical malaria control efforts of the 1960s. Despite decentralization, this situation resulted, in part, from weak district management capacity, poor coordination, inadequate monitoring, and lack of training of key staff. Experience in the Solomon Islands showed that spraying with DDT, use of insecticide-treated bed nets (ITNs), and health education were all associated with disease reduction. The use of nets permitted a reduction in DDT spraying, but could not replace it without an increased malaria incidence. Baseline data and reliable monitoring of key outcome indicators are needed to measure whether the ambitious goals for the control of malaria and other diseases has occurred. Such systems are being used for evidence-based decision making in Tanzania and several other countries. Baseline cluster sampling surveys in several countries across Africa indicate that only 53% of the children with febrile illness in malarious areas are being treated; chloroquine (CQ) is used 84% of the time, even where the drug may be ineffective. Insecticide-treated bed nets were used only 2% of the time by children less than five years of age. Progress in malaria vaccine research has been substantial over the past five years; 35 candidate malaria vaccines are in development, many of which are in clinical trials. Development of new vaccines and drugs has been the result of increased investments and formation of public-private partnerships. Before malaria

Antimalarial activity of selected Sudanese medicinal plants with emphasis to Maytenus senegalensis

Energy Technology Data Exchange (ETDEWEB)

Idris, Ahmed El Tahir Mohamed [Department of Biochemistry, Faculty of Medicine, University of Khartoum, Khartoum (Sudan)

1998-03-01

The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity against 3D7 with IC{sub 50} values {<=} 50 {mu} g/ml. While 21 extracts (57%) showed antimalrial activities with IC{sub 50} values {<=} 50 {mu} g/ml on Dd2. 13 extracts (22%) and ten extracts (18%) only showed an activity with IC{sub 50} values {<=} 5 {mu} g/ml on 3 D7 and Dd2, respectively. The activities of some plant extracts, which affected 3D7 strain, were measured using the radiolabelled ({sup 3}H) hypoxanthine method and microscopical count. 15 plant extracts (48%) from 32 showed IC{sub 50} values {<=} 50 {mu} g/ml against 3D7 strain using the radiolabelled hypoxanthine methods and only 5 extracts (16%) showed IC{sub 50} values {<=} 5 {mu} g/ml against 3D7. Most of the extracts screened had a low effect on lymphocyte proliferation (IC{sub 50} values >100 {mu} g/ml), where as Sonochous cornatus, Balanites aegyptiaca, Tamarindus indica, Acacia nilotica, Annona squamosa, Eucalyptus globulus and Cassia tora enhanced lymphocyte proliferation. liquid-liquid partition of methanolic preparation of Acacia nilotica seeds and husk showed that the ethylacetate phase

Antimalarial activity of selected Sudanese medicinal plants with emphasis to Maytenus senegalensis

International Nuclear Information System (INIS)

Idris, Ahmed El Tahir Mohamed

1998-03-01

The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity against 3D7 with IC 50 values ≤ 50 μ g/ml. While 21 extracts (57%) showed antimalrial activities with IC 50 values ≤ 50 μ g/ml on Dd2. 13 extracts (22%) and ten extracts (18%) only showed an activity with IC 50 values ≤ 5 μ g/ml on 3 D7 and Dd2, respectively. The activities of some plant extracts, which affected 3D7 strain, were measured using the radiolabelled ( 3 H) hypoxanthine method and microscopical count. 15 plant extracts (48%) from 32 showed IC 50 values ≤ 50 μ g/ml against 3D7 strain using the radiolabelled hypoxanthine methods and only 5 extracts (16%) showed IC 50 values ≤ 5 μ g/ml against 3D7. Most of the extracts screened had a low effect on lymphocyte proliferation (IC 50 values >100 μ g/ml), where as Sonochous cornatus, Balanites aegyptiaca, Tamarindus indica, Acacia nilotica, Annona squamosa, Eucalyptus globulus and Cassia tora enhanced lymphocyte proliferation. liquid-liquid partition of methanolic preparation of Acacia nilotica seeds and husk showed that the ethylacetate phase possessed the highest activity against both 3D7 and Dd2

Subsidising artemisinin-based combination therapy in the private retail sector.

Science.gov (United States)

Opiyo, Newton; Yamey, Gavin; Garner, Paul

2016-03-09

years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence).The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence).The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence).None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria.Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health.

Malaria Surveillance - United States, 2015.

Science.gov (United States)

Mace, Kimberly E; Arguin, Paul M; Tan, Kathrine R

2018-05-04

polymorphisms associated with resistance to pyrimethamine were identified in 132 (86.3%), to sulfadoxine in 112 (73.7%), to chloroquine in 48 (31.4%), to mefloquine in six (4.3%), and to artemisinin in one (https://www.cdc.gov/malaria/travelers/drugs.html). Malaria infections can be fatal if not diagnosed and treated promptly with antimalarial medications appropriate for the patient's age and medical history, the likely country of malaria acquisition, and previous use of antimalarial chemoprophylaxis. Health care providers should consult the CDC Guidelines for Treatment of Malaria in the United States and contact the CDC's Malaria Hotline for case management advice when needed. Malaria treatment recommendations are available online (https://www.cdc.gov/malaria/diagnosis_treatment) and from the Malaria Hotline (770-488-7788 or toll-free at 855-856-4713). Persons submitting malaria case reports (care providers, laboratories, and state and local public health officials) should provide complete information because incomplete reporting compromises case investigations and efforts to prevent infections and examine trends in malaria cases. Compliance with recommended malaria prevention strategies is low among U.S. travelers visiting friends and relatives. Evidence-based prevention strategies that effectively target travelers who are visiting friends and relatives need to be developed and implemented to reduce the numbers of imported malaria cases in the United States. Molecular surveillance of antimalarial drug resistance markers (https://www.cdc.gov/malaria/features/ars.html) has enabled CDC to track, guide treatment, and manage drug resistance in malaria parasites both domestically and internationally. More samples are needed to improve the completeness of antimalarial drug resistance marker analysis; therefore, CDC requests that blood specimens be submitted for all cases diagnosed in the United States.

Primaquine for reducing Plasmodium falciparum transmission.

Science.gov (United States)

Graves, Patricia M; Gelband, Hellen; Garner, Paul

2012-09-12

this may modify any PQ effect. We calculated the area under the curve (AUC) for gametocyte density over time for comparisons for which data were available, and also sought data on haematologic and other adverse effects. We used GRADE guidelines to assess evidence quality, and this is reflected in the wording of the results: high quality ("PQ reduces ...."); moderate quality ("PQ probably reduces ..."); low quality ("PQ may reduce...."); and very low quality ("we don't know if PQ reduces...."). We included 11 individually randomized trials, with a total of 1776 individuals. The 11 trials included 20 comparisons with partner drugs, which included chloroquine (CQ), sulfadoxine-pyrimethamine (SP), mefloquine (MQ), quinine (QN), artesunate (AS), and a variety of artemisinin combination therapies (ACTs). For G6PD deficiency, studies either did not test (one study), tested and included all (one study), included only G6PD deficient (one study), excluded G6PD deficient (two studies), or made no comment (six studies).None of the trials we included assessed effects on malaria transmission (incidence, prevalence, or entomological inoculation rate (EIR)) in the trial area.With non-artemisinin drug regimens, PQ may reduce the infectiousness to mosquitoes of individuals treated, based on one small study with large effects (Risk Ratio (RR) 0.06 on day 8 after treatment, 95% confidence interval (CI) 0 to 0.89; low quality evidence). Participants who received PQ had fewer circulating gametocytes up to day 43 (log(10) AUC relative decrease from 24.3 to 27.1%, one study (two comparisons), moderate quality evidence); and there were 38% fewer people with gametocytes on day 8 (RR 0.62, 95% CI 0.51 to 0.76, four studies (five comparisons), moderate quality evidence). We did not identify any study that looked for effects of the drug on haemolytic anaemia.With artemisinin-based drug regimens, we do not know if PQ influences infectiousness to mosquitoes, as no study has examined this directly

Subsidising artemisinin-based combination therapy in the private retail sector

Science.gov (United States)

Opiyo, Newton; Yamey, Gavin; Garner, Paul

2016-01-01

very low. The ACT subsidy programmes decreased the median cost of ACTs for children under five years of age by US$ 0.84 (median cost per ACT course without subsidy: US$ 1.08 versus with subsidy: US$ 0.24; 1 study, high certainty evidence). The ACT subsidy programmes increased the market share of ACTs for children under five years of age by between 23.6 and 63.0 percentage points (1 study, high certainty evidence). The ACT subsidy programmes decreased the use of older antimalarial drugs (such as amodiaquine and sulphadoxine-pyrimethamine) among children under five years of age by 10.4 percentage points (95% CI 3.9 to 16.9 percentage points; 1 study, high certainty evidence). None of the three studies of ACT subsidies reported the number of patients treated who had confirmed malaria. Vouchers increased the likelihood that an illness is treated with an ACT by 16 to 23 percentage points; however, vouchers were associated with a high rate of over-treatment of malaria (only 56% of patients taking ACTs from the drug shop tested positive for malaria under the 92% subsidy; 1 study, high certainty evidence). Authors' conclusions Programmes that include substantive subsidies for private sector retailers combined with training of providers and social marketing improved use and availability of ACTs for children under five years of age with suspected malaria in research studies from three countries in East Africa. These programmes also reduced prices of ACTs, improved market share of ACTs and reduced the use of older antimalarial drugs among febrile children under five years of age. The research evaluates drug delivery but does not assess whether the patients had confirmed (parasite-diagnosed) malaria. None of the included studies assessed patient outcomes; it is therefore not known whether the effects seen in the studies would translate to an impact on health. PLAIN LANGUAGE SUMMARY Subsidising artemisinin-based combination therapy in drug shops and pharmacies We conducted a review