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Sample records for falciparum malaria assessing

  1. falciparum malaria?

    African Journals Online (AJOL)

    Wassermann reactions and then lupus anticoagu- lant are now known ... ACA levels in the patient group, or between the ... bral malaria could lead to more effective therapy and an improved ... each patient and a physical examination performed. Particular .... a thrombotic subset of SLE: distinct profiles for epitope specificiry.

  2. Plasmodium falciparum malaria associated with ABO blood ...

    African Journals Online (AJOL)

    Plasmodium falciparum malaria associated with ABO blood phenotypes and ... out to investigate the relationship between blood group types and P. falciparum ... of long lasting treated (LLT) mosquito bed nets and the prevalence of infection.

  3. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum.

    Science.gov (United States)

    Herdiana, Herdiana; Cotter, Chris; Coutrier, Farah N; Zarlinda, Iska; Zelman, Brittany W; Tirta, Yusrifar Kharisma; Greenhouse, Bryan; Gosling, Roly D; Baker, Peter; Whittaker, Maxine; Hsiang, Michelle S

    2016-09-13

    As malaria transmission declines, it becomes more geographically focused and more likely due to asymptomatic and non-falciparum infections. To inform malaria elimination planning in the context of this changing epidemiology, local assessments on the risk factors for malaria infection are necessary, yet challenging due to the low number of malaria cases. A population-based, cross-sectional study was performed using passive and active surveillance data collected in Aceh Besar District, Indonesia from 2014 to 2015. Malaria infection was defined as symptomatic polymerase chain reaction (PCR)-confirmed infection in index cases reported from health facilities, and asymptomatic or symptomatic PCR-confirmed infection identified in reactive case detection (RACD). Potential risk factors for any infection, species-specific infection, or secondary-case detection in RACD were assessed through questionnaires and evaluated for associations. Nineteen Plasmodium knowlesi, 12 Plasmodium vivax and six Plasmodium falciparum cases were identified passively, and 1495 community members screened in RACD, of which six secondary cases were detected (one P. knowlesi, three P. vivax, and two P. falciparum, with four being asymptomatic). Compared to non-infected subjects screened in RACD, cases identified through passive or active surveillance were more likely to be male (AOR 12.5, 95 % CI 3.0-52.1), adult (AOR 14.0, 95 % CI 2.2-89.6 for age 16-45 years compared to malaria infection in index and RACD identified cases was associated with forest exposure, particularly overnights in the forest for work. In low-transmission settings, utilization of data available through routine passive and active surveillance can support efforts to target individuals at high risk.

  4. Plasma concentration of parasite DNA as a measure of disease severity in falciparum malaria

    NARCIS (Netherlands)

    Imwong, M.; Woodrow, C.; Hendriksen, I.C.E.; Veenemans, J.; Verhoef, J.C.M.

    2015-01-01

    In endemic areas malaria parasitemia is common in apparently healthy children and severe malaria is commonly misdiagnosed in patients with incidental parasitemia. We assessed the performance of plasma P. falciparum DNA concentration measurement in distinguishing uncomplicated from severe malaria in

  5. 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).

  6. Sero-epidemiological evaluation of Plasmodium falciparum malaria in Senegal.

    Science.gov (United States)

    Sylla, Khadime; Tine, Roger Clément Kouly; Ndiaye, Magatte; Sow, Doudou; Sarr, Aïssatou; Mbuyi, Marie Louise Tshibola; Diouf, Ibrahima; Lô, Amy Colé; Abiola, Annie; Seck, Mame Cheikh; Ndiaye, Mouhamadou; Badiane, Aïda Sadikh; N'Diaye, Jean Louis A; Ndiaye, Daouda; Faye, Oumar; Dieng, Thérèse; Dieng, Yémou; Ndir, Oumar; Gaye, Oumar; Faye, Babacar

    2015-07-16

    In Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal. Cross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage. A total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence. The use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate

  7. Determination of PCT on admission is a useful tool for the assessment of disease severity in travelers with imported Plasmodium falciparum malaria.

    Science.gov (United States)

    Righi, Elda; Merelli, Maria; Arzese, Alessandra; Siega, Paola Della; Scarparo, Claudio; Bassetti, Matteo

    2016-03-01

    Procalcitonin (PCT) and C-reactive protein (CRP) may be useful to predict complicated forms of malaria. A total of 30 consecutive travelers diagnosed with Plasmodium falciparum malaria over a two-year period were included in the study. Patients with complicated Plasmodium falciparum malaria showed higher levels of parasitemia (P = 0.0001), PCT (P = 0.0018), CRP (P = 0.0005), bilirubinemia (P = 0.004), and a lower platelet count (PPlasmodium falciparum malaria.

  8. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  9. Congenital Plasmodium falciparum Malaria in Washington, DC.

    Science.gov (United States)

    Del Castillo, Melissa; Szymanski, Ann Marie; Slovin, Ariella; Wong, Edward C C; DeBiasi, Roberta L

    2017-01-11

    Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery. © The American Society of Tropical Medicine and Hygiene.

  10. Plasmodium falciparum Malaria, Southern Algeria, 2007

    Science.gov (United States)

    Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria. PMID:20113565

  11. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  12. Guillain-Barré syndrome in Plasmodium falciparum malaria.

    OpenAIRE

    Wijesundere, A.

    1992-01-01

    A patient with Plasmodium falciparum malaria developed peripheral neuropathy. Clinical, cerebro-spinal fluid examination and nerve conduction studies confirmed Guillain-Barré syndrome, not previously reported in P. falciparum malaria.

  13. Assessment of efficacy and safety of artesunate plus sulfadoxine pyrimethamine combination for treatment of uncomplicated falciparum malaria

    Directory of Open Access Journals (Sweden)

    Yash N. Goyal

    2014-06-01

    Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance. [Int J Basic Clin Pharmacol 2014; 3(3.000: 465-469

  14. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Vaughan-Williams Charles H

    2012-12-01

    Full Text Available Abstract Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. Methods An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR. Following diagnosis, patients were treated with artemether-lumefantrine (Coartem® and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Results Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1 gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N. Ten of the 16 samples carried the wild type haplotype (CVMNK at codons 72-76 of the chloroquine resistance transporter gene (pfcrt; three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. Conclusions The absence of mdr1 gene copy number variation detected in this study

  15. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

    Science.gov (United States)

    Vaughan-Williams, Charles H; Raman, Jaishree; Raswiswi, Eric; Immelman, Etienne; Reichel, Holger; Gate, Kelly; Knight, Steve

    2012-12-28

    Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in Kwa

  16. Assessment of Therapeutic Response of Plasmodium vivax and Plasmodium falciparum to Chloroquine in a Malaria Transmission Free Area in Colombia

    Directory of Open Access Journals (Sweden)

    Castillo Carmen Manuela

    2002-01-01

    Full Text Available In order to determine the frequency of therapeutic failures to chloroquine (CQ in patients with malaria due to either Plasmodium falciparum or P. vivax, and to explore the usefulness of a malaria-free city as a sentinel site to monitor the emergence of drug resistance, 53 patients (44 infected with P. vivax and 9 with P. falciparum were evaluated at the Laboratory of Parasitology, Universidad del Valle in Cali, Colombia. Patients received 25 mg/kg of CQ divided in three doses over 48 h; they were followed during 28 days according to WHO/PAHO protocols. While therapeutic failures to CQ in the P. vivax group were not detected, the proportion of therapeutic failures in the P. falciparum group was high (78% and consistent with the reports from endemic areas in Colombia. The diverse origin of cases presenting therapeutic failure confirmed that P. falciparum resistant to CQ is widespread in Colombia, and further supports the change in the national antimalarial drug scheme. Monitoring of drug resistance in malaria free areas would be useful to identify sites requiring efficacy evaluation, and in some situations could be the most appropriate alternative to collect information from endemic areas where therapeutic efficacy studies are not feasible.

  17. Plasma glutamine levels and falciparum malaria.

    Science.gov (United States)

    Cowan, G; Planche, T; Agbenyega, T; Bedu-Addo, G; Owusu-Ofori, A; Adebe-Appiah, J; Agranoff, D; Woodrow, C; Castell, L; Elford, B; Krishna, S

    1999-01-01

    Glutamine deficiency is associated with increased rates of sepsis and mortality, which can be prevented by glutamine supplementation. Changes in glutamine concentration were examined in Ghanaian children with acute falciparum malaria and control cases. The mean (SD) plasma glutamine concentration was lower in patients with acute malaria (401 (82) mumol/L, n = 50) than in control patients (623 (67) mumol/L, n = 7; P sepsis and dyserythropoeisis.

  18. Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.

    Science.gov (United States)

    Slater, Hannah C; Ross, Amanda; Ouédraogo, André Lin; White, Lisa J; Nguon, Chea; Walker, Patrick G T; Ngor, Pengby; Aguas, Ricardo; Silal, Sheetal P; Dondorp, Arjen M; La Barre, Paul; Burton, Robert; Sauerwein, Robert W; Drakeley, Chris; Smith, Thomas A; Bousema, Teun; Ghani, Azra C

    2015-12-03

    Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using

  19. Artemisinin-Resistant Plasmodium falciparum Malaria.

    Science.gov (United States)

    Fairhurst, Rick M; Dondorp, Arjen M

    2016-06-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

  20. An epidemiological study to assess Plasmodium falciparum parasite prevalence and malaria control measures in Burkina Faso and Senegal.

    Science.gov (United States)

    Diallo, Aldiouma; Sié, Ali; Sirima, Sodiomon; Sylla, Khadime; Ndiaye, Mahmadou; Bountogo, Mamadou; Ouedraogo, Espérance; Tine, Roger; Ndiaye, Assane; Coulibaly, Boubacar; Ouedraogo, Alphonse; Faye, Babacar; Ba, El Hadji; Compaore, Guillaume; Tiono, Alfred; Sokhna, Cheikh; Yé, Maurice; Diarra, Amidou; Bahmanyar, Edith Roset; De Boer, Melanie; Pirçon, Jean-Yves; Usuf, Effua Abigail

    2017-02-06

    Malariometric information is needed to decide how to introduce malaria vaccines and evaluate their impact in sub-Saharan African countries. This cross-sectional study (NCT01954264) was conducted between October and November, 2013, corresponding to the high malaria transmission season, in four sites with Health and Demographic Surveillance Systems (DSS) [two sites with moderate-to-high malaria endemicity in Burkina Faso (Nouna and Saponé) and two sites with low malaria endemicity in Senegal (Keur Socé and Niakhar)]. Children (N = 2421) were randomly selected from the DSS lists of the study sites and were stratified into two age groups (6 months-4 years and 5-9 years). A blood sample was collected from each child to evaluate parasite prevalence of Plasmodium falciparum and other Plasmodium species and gametocyte density by microscopy, and rapid diagnosis test in the event of fever within 24 h. Case report forms were used to evaluate malaria control measures and other factors. Plasmodium falciparum was identified in 707 (29.2%) children, with a higher prevalence in Burkina Faso than Senegal (57.5 vs 0.9% of children). In Burkina Faso, prevalence was 57.7% in Nouna and 41.9% in Saponé in the 6 months-4 years age group, and 75.4% in Nouna and 70.1% in Saponé in the 5-9 years age group. Infections with other Plasmodium species were rare and only detected in Burkina Faso. While mosquito nets were used by 88.6-97.0 and 64.7-80.2% of children in Burkina Faso and Senegal, other malaria control measures evaluated at individual level were uncommon. In Burkina Faso, exploratory analyses suggested that use of malaria treatment or any other medication within 14 days, and use of insecticide spray within 7 days decreased the prevalence of malaria infection; older age, rural residence, natural floor, grass/palm roof, and unavailability of electricity in the house were factors associated with increased malaria occurrence. Plasmodium falciparum infection prevalence in children

  1. Predictors of Plasmodium falciparum malaria incidence in Chano Mille, South Ethiopia: a longitudinal study.

    Science.gov (United States)

    Loha, Eskindir; Lindtjørn, Bernt

    2012-09-01

    We assessed potential effects of local meteorological and environmental conditions, indoor residual spraying with insecticides, insecticide-treated nets (ITNs) use at individual and community levels, and individual factors on Plasmodium falciparum malaria incidence in a village in south Ethiopia. A cohort of 8,121 people was followed for 101 weeks with active and passive surveillance. Among 317 microscopically confirmed P. falciparum malaria episodes, 29.3% occurred among temporary residents. The incidence density was 3.6/10,000 person-weeks of observation. We observed higher malaria incidence among males, children 5-14 years of age, ITNs non-users, the poor, and people who lived closer to vector breeding places. Rainfall increased and indoor residual spraying with Deltamethrin reduced falciparum incidence. Although ITNs prevented falciparum malaria for the users, we did not find that free mass ITNs distribution reduced falciparum malaria on a village level.

  2. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with His

  3. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with

  4. A simple and fast method to exclude high Plasmodium falciparum parasitaemia in travellers with imported malaria

    NARCIS (Netherlands)

    T. van Gool (Tom); M.E. van Wolfswinkel (Marlies); R. Koelewijn (Rob); P.P.A.M. van Thiel (Pieter); J. Jacobs (Jan); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2011-01-01

    textabstractBackground: Counts of malaria parasites in peripheral blood are important to assess severity of Plasmodium falciparum malaria. Thin and thick smears are routinely used for this purpose. Methods. In this study the Binax NOW® Malaria Test, an easy-to-perform rapid diagnostic test, with His

  5. A high PCT level correlates with disease severity in Plasmodium falciparum malaria in children.

    Science.gov (United States)

    Carannante, Novella; Rossi, Marco; Fraganza, Fiorentino; Coppola, Grazia; Chiesa, Daniela; Attanasio, Vittorio; Sbrana, Francesco; Corcione, Antonio; Tascini, Carlo

    2017-01-01

    Most clinicians in developed countries have limited experience in making clinical assessments of malaria disease severity and/or monitoring high-level parasitemia in febrile patients with imported malaria. Hyperparasitemia is a risk factor for severe P. falciparum malaria, and procalcitonin (PCT) has recently been related to the severity of malaria. In developed countries, where not all hospital have skilled personnel to count parasitemia, a rapid test might be useful for the prompt diagnosis of malaria but unfortunately these tests are not able to count the number of parasites. In this context, PCT might have a prognostic value for the assessment of severe malaria, especially in children with cerebral malaria. We describe two children with severe cerebral malaria, who were directly admitted to the ICU with a high level of PCT and extremely high (>25%) parasitemia. Our conclusion is that PCT may also be a measure of severity of P. falciparum malaria in children.

  6. Premunition in Plasmodium falciparum malaria

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-08

    Mar 8, 2010 ... parasite, premunition is probably caused by antitoxic immunity. These poor and ... immunity to clinical malaria rather than infection may be of long duration ... use of antimalaria drugs and its possible strategic role in vaccine ...

  7. [Treatment of fulminant falciparum malaria with erythrapheresis].

    Science.gov (United States)

    Rouvier, B; Maudan, P; Debue, J F; Joussemet, M; Roué, R

    1988-01-01

    Ten days after his return from Cameroon, a twenty-six year old Frenchman, serving on voluntary service overseas, presented with fulminant falciparum malaria: shock, altered consciousness, haemolytic anaemia, threatening disseminated coagulation (platelets less than 150 X 10(-6).l-1; prothrombin time and Stuart factor less than 50%; fibrinogen less than 1.5 g.l-1). In spite of quinine therapy, parasitaemia increased from 4 to 35% within 24 h. Using an Haemonetics V50, the exchange of one and a half red blood cell masses was carried out with 17 red blood cell packs. Calcium gluconate was used to prevent the hypocalcaemia induced by the anticoagulant solution. The patient's platelets and plasma were completely reinjected. The result was very satisfactory. This kind of exchange, well tolerated clinically and biologically, would seem better than the classical exchange transfusion. When 10% of the red blood cells are infected by Plasmodium falciparum, it is necessary to exchange from one and a half to two blood masses. Lesser exchanges are always associated with important relapses and quinine therapy must be carried on during and after the exchange. Restricting this exchange only to red blood cells enabled the patient to benefit from his own coagulation factors, antibodies and platelets, and consequently to reduce the number of blood donors involved. However, metabolites (especially bilirubin and circulating immune complexes) were not eliminated. Partial plasmapheresis may be associated with erythropheresis using human albumin as plasma substitute. This technique needs to be assessed, in order to optimize immediate efficiency and post-transfusion infectious risk.

  8. Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Diallo Mouctar

    2009-06-01

    Full Text Available Abstract Background The use of artemisinin derivative-based combination therapy (ACT such as artesunate plus amodiaquine is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. Fixed-dose combinations are more adapted to patients than regimens involving multiple tablets and improve treatment compliance. A fixed-dose combination of artesunate + amodiaquine (ASAQ was recently developed. To assess the efficacy and safety of this new combination and to define its optimum dosage regimen (once or twice daily in the treatment of uncomplicated P. falciparum malaria, a multicentre clinical study was conducted. Methods A multicentre, randomized, controlled, investigator-blinded, parallel-group study was conducted in five African centers in Cameroon, Madagascar, Mali and Senegal from March to December 2006. Efficacy and safety of ASAQ were assessed compared to those of artemether + lumefantrine (AL. The WHO protocol with a 28-day follow-up for assessing the drug therapeutic efficacy was used. Patients suffering from uncomplicated P. falciparum malaria were randomized to receive ASAQ orally once daily (ASAQ1, ASAQ twice daily (ASAQ2 or AL twice daily (AL for three days. The primary outcome was PCR-corrected parasitological cure rate and clinical response. Results Of 941 patients initially randomized and stratified into two age groups ( Conclusion The non-inferiority of ASAQ compared with AL was demonstrated. The fixed-dose combination artesunate + amodiaquine (ASAQ is safe and efficacious even in young children under 5 years of age. Whilst administration on a twice-a-day basis does not improve the efficacy of ASAQ significantly, a once-a-day intake of this new combination clearly appears as an effective and safe therapy in the treatment of uncomplicated P. falciparum malaria both in adults and children. Implications of such findings are of primary importance in terms of public health especially in African countries. As

  9. Taxonomy Icon Data: malaria parasite P. falciparum [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available malaria parasite P. falciparum Plasmodium falciparum Plasmodium_falciparum_L.png Plasmodium_falci...parum_NL.png Plasmodium_falciparum_S.png Plasmodium_falciparum_NS.png http://biosciencedbc.jp/...taxonomy_icon/icon.cgi?i=Plasmodium+falciparum&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Plasmodium+falci...parum&t=NL http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Plasmodium+falci...parum&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Plasmodium+falciparum&t=NS http://togodb.biosciencedbc.jp/togodb/view/taxonomy_icon_comment_en?species_id=218 ...

  10. A new world malaria map: Plasmodium falciparum endemicity in 2010

    Directory of Open Access Journals (Sweden)

    Gething Peter W

    2011-12-01

    Full Text Available Abstract Background Transmission intensity affects almost all aspects of malaria epidemiology and the impact of malaria on human populations. Maps of transmission intensity are necessary to identify populations at different levels of risk and to evaluate objectively options for disease control. To remain relevant operationally, such maps must be updated frequently. Following the first global effort to map Plasmodium falciparum malaria endemicity in 2007, this paper describes the generation of a new world map for the year 2010. This analysis is extended to provide the first global estimates of two other metrics of transmission intensity for P. falciparum that underpin contemporary questions in malaria control: the entomological inoculation rate (PfEIR and the basic reproductive number (PfR. Methods Annual parasite incidence data for 13,449 administrative units in 43 endemic countries were sourced to define the spatial limits of P. falciparum transmission in 2010 and 22,212 P. falciparum parasite rate (PfPR surveys were used in a model-based geostatistical (MBG prediction to create a continuous contemporary surface of malaria endemicity within these limits. A suite of transmission models were developed that link PfPR to PfEIR and PfR and these were fitted to field data. These models were combined with the PfPR map to create new global predictions of PfEIR and PfR. All output maps included measured uncertainty. Results An estimated 1.13 and 1.44 billion people worldwide were at risk of unstable and stable P. falciparum malaria, respectively. The majority of the endemic world was predicted with a median PfEIR of less than one and a median PfRc of less than two. Values of either metric exceeding 10 were almost exclusive to Africa. The uncertainty described in both PfEIR and PfR was substantial in regions of intense transmission. Conclusions The year 2010 has a particular significance as an evaluation milestone for malaria global health policy. The

  11. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  12. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans, L.C. (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J. van Genderen (P.)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  13. Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E; Hartl, Daniel L; Barillas-Mury, Carolina

    2016-11-23

    Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits.

  14. Plasmodium falciparum Malaria Endemicity in Indonesia in 2010

    Science.gov (United States)

    Elyazar, Iqbal R. F.; Gething, Peter W.; Patil, Anand P.; Rogayah, Hanifah; Kusriastuti, Rita; Wismarini, Desak M.; Tarmizi, Siti N.; Baird, J. Kevin; Hay, Simon I.

    2011-01-01

    Background Malaria control programs require a detailed understanding of the contemporary spatial distribution of infection risk to efficiently allocate resources. We used model based geostatistics (MBG) techniques to generate a contemporary map of Plasmodium falciparum malaria risk in Indonesia in 2010. Methods Plasmodium falciparum Annual Parasite Incidence (PfAPI) data (2006–2008) were used to map limits of P. falciparum transmission. A total of 2,581 community blood surveys of P. falciparum parasite rate (PfPR) were identified (1985–2009). After quality control, 2,516 were included into a national database of age-standardized 2–10 year old PfPR data (PfPR2–10) for endemicity mapping. A Bayesian MBG procedure was used to create a predicted surface of PfPR2–10 endemicity with uncertainty estimates. Population at risk estimates were derived with reference to a 2010 human population count surface. Results We estimate 132.8 million people in Indonesia, lived at risk of P. falciparum transmission in 2010. Of these, 70.3% inhabited areas of unstable transmission and 29.7% in stable transmission. Among those exposed to stable risk, the vast majority were at low risk (93.39%) with the reminder at intermediate (6.6%) and high risk (0.01%). More people in western Indonesia lived in unstable rather than stable transmission zones. In contrast, fewer people in eastern Indonesia lived in unstable versus stable transmission areas. Conclusion While further feasibility assessments will be required, the immediate prospects for sustained control are good across much of the archipelago and medium term plans to transition to the pre-elimination phase are not unrealistic for P. falciparum. Endemicity in areas of Papua will clearly present the greatest challenge. This P. falciparum endemicity map allows malaria control agencies and their partners to comprehensively assess the region-specific prospects for reaching pre-elimination, monitor and evaluate the effectiveness of

  15. Spatial and temporal distribution of falciparum malaria in China

    Directory of Open Access Journals (Sweden)

    Lin Hualiang

    2009-06-01

    Full Text Available Abstract Background Falciparum malaria is the most deadly among the four main types of human malaria. Although great success has been achieved since the launch of the National Malaria Control Programme in 1955, malaria remains a serious public health problem in China. This paper aimed to analyse the geographic distribution, demographic patterns and time trends of falciparum malaria in China. Methods The annual numbers of falciparum malaria cases during 1992–2003 and the individual case reports of each clinical falciparum malaria during 2004–2005 were extracted from communicable disease information systems in China Center for Diseases Control and Prevention. The annual number of cases and the annual incidence were mapped by matching them to corresponding province- and county-level administrative units in a geographic information system. The distribution of falciparum malaria by age, gender and origin of infection was analysed. Time-series analysis was conducted to investigate the relationship between the falciparum malaria in the endemic provinces and the imported falciparum malaria in non-endemic provinces. Results Falciparum malaria was endemic in two provinces of China during 2004–05. Imported malaria was reported in 26 non-endemic provinces. Annual incidence of falciparum malaria was mapped at county level in the two endemic provinces of China: Yunnan and Hainan. The sex ratio (male vs. female for the number of cases in Yunnan was 1.6 in the children of 0–15 years and it reached 5.7 in the adults over 15 years of age. The number of malaria cases in Yunnan was positively correlated with the imported malaria of concurrent months in the non-endemic provinces. Conclusion The endemic area of falciparum malaria in China has remained restricted to two provinces, Yunnan and Hainan. Stable transmission occurs in the bordering region of Yunnan and the hilly-forested south of Hainan. The age and gender distribution in the endemic area is

  16. Clinical trials of chemotherapy for falciparum malaria.

    Science.gov (United States)

    Winstanley, P; Olliaro, P

    1998-02-01

    Plasmodium falciparum remains one of the World's most prevalent and devastating pathogens. Mainly for economic reasons, the parasite's ability to develop resistance to drugs has not been matched by the rate at which new compounds are developed. Even so, there are new drugs (or new combinations of old drugs) currently under investigation, or in the process of development (at the moment): Pyronaridine, a well-tolerated, synthetic drug that may have utility for multi-resistant falciparum malaria in many parts of the world; however,problems remain over the formulation of this drug (which is a major determinant of its bioavailability) and its eventual cost. Chlorproguanil-dapsone (lap dap) is being studied as a possible low-cost'successor' to pyrimethamine-sulfadoxine; the utility of chlorproguanil-dapsone as 'salvage' therapy for clinical cases of pyrimethamine-sulfadoxine failure has yet to be tested in clinical trials. Atovaquone-proguanil (malarone) has utility against multi-resistant parasites; however, it is likely to be expensive (but is currently being provided free-of-charge in certain areas of Africa). Artemether-benflumetol (coartemether) combines the advantages of artemether (a rapid reduction in parasite load) with a second drug that reduces the risk of recrudescence; the cost of this combination is unclear. Rectal artesunate is being studied as an intervention to reduce the proportion of children with falciparum malaria who deteriorate to severe disease; the formulation is appropriate for use in rural health centres.

  17. Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression

    DEFF Research Database (Denmark)

    Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline

    2008-01-01

    BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances...

  18. Hyperglycemia in Severe Falciparum Malaria: A Case Report

    OpenAIRE

    Leonardo Chianura; Isabella Corinna Errante; Giovanna Travi; Roberto Rossotti; Massimo Puoti

    2012-01-01

    Occasionally, malaria may present with unusual signs and symptoms. We report a case of an uncommon presentation of Plasmodium falciparum infection in a 59-year-old Ethiopian immigrant, which initially presented with hyperglycaemia and multiple organ dysfunction syndrome (MODS). Reports of unusual presentations of malaria are few and cases of severe malaria with hyperglycaemia are rarely described. As hyperglycaemia is associated to most severe malaria and high mortality, our aim is to catch ...

  19. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abu-Zeid, Y A;

    1991-01-01

    Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...

  20. Loss of cellular immune reactivity during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abu-Zeid, Y A

    1991-01-01

    Sixteen patients suffering from acute Plasmodium falciparum malaria were studied. All were residents of an area of unstable malaria-transmission in Eastern Sudan. Blood-samples were drawn at diagnosis, and 7 and 30 days later. Blood-samples from thirteen donors, drawn outside the malaria...... convalescence. Five donors examined by fluorescence-activated cell sorting (FACS) showed no increase in surface expression of IL-2 receptor on peripheral lymphocytes. The data indicate that acute P. falciparum malaria causes a depletion of antigen-reactive T-cells from the peripheral circulation, probably due...

  1. International population movements and regional Plasmodium falciparum malaria elimination strategies

    National Research Council Canada - National Science Library

    Andrew J. Tatem; David L. Smith; Susan Hanson

    2010-01-01

    ... to areas targeted for elimination. Here, census-based migration data were analyzed with network analysis tools, Plasmodium falciparum malaria transmission maps, and global population databases to map globally communities of countries...

  2. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites

    NARCIS (Netherlands)

    Schats, R.; Bijker, E.M.; Gemert, G.J.A. van; Graumans, W.; Vegte-Bolmer, M. van de; Lieshout, L. van; Haks, M.C.; Hermsen, C.C.; Scholzen, A.; Visser, L.G.; Sauerwein, R.W.

    2015-01-01

    BACKGROUND: Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI) model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization),

  3. Automated erythrocytapheresis in severe falciparum malaria : A critical appraisal

    NARCIS (Netherlands)

    Nieuwenhuis, Jellie A.; Meertens, John H. J. M.; Zijlstra, Jan G.; Ligtenberg, Jack J. M.; Tulleken, Jaap E.; van der Werf, Tjip S.

    2006-01-01

    Imported falciparum malaria is increasing in Western countries. In patients with severe disease, exchange transfusion has been added to antimalarial and conventional supportive therapy to increase removal of parasitized erythrocytes, but hemodynamic compromise limits its use; automated erythrocytaph

  4. HUBUNGAN KEPADATAN PARASIT DENGAN MANIFESTASI KLINIS PADA MALARIA Plasmodium FALCIPARUM DAN Plasmodium VIVAX

    Directory of Open Access Journals (Sweden)

    Rossa Avrina

    2012-07-01

    Full Text Available Malaria is still a public health problem in Indonesia. The clinical manifestation of malaria is varied, and many factors may influence its clinical manifestation. Despite the species of malaria, density of parasitemia is known related to the severity or malignancy of malaria. It is worth to analyse the clinical and laboratory data of malaria cases in monitoring dihydroartemisinin-piperaquine (DHP treatment. The extended analysed was done to assess the relationship between density of parasitemia and clinical manifestations. A subset data of monitoring DHP treatment in subjects with uncomplicated falciparum and vivax malaria in Kalimantan and Sulawesi which were consist of clinical and laboratory day-0 data was used in analysing. Clinical data were recorded through anamnesis and physical examination. Parasite density was counted by health centre microscopist and then cross-checked by certified microscopists of the Natiional Institute of Health Reseach and Development. Haemoglobin level was also measured  by health centre analyst using the existing Sahli hemoglobinmeter. For parasite density category, median is used for cut off point. In P.falciparum malaria, the cut off point is 5588/µl  and in P.vivax malaria is 3375/µl.  The relationship between parasite density and clinical manifestation in falciparum and vivax malaria was determined by bivariate and multivariate analysis with logistic regression using SPSS 17 software. The most of subject with P.falciparum and P.vivax malaria are children (<15 yeras old, male, and non indigenous. From analysis bivariate, variabels that can be analyzed by multivariate in P.falciparum malaria (p<0,25 are children under 15 years old (p=0,0 12 and Sulawesi island where subject live(p=0,163 and In P.vivax malaria is children under 15 years old (p=0,218. Because of other variables are considered biologicaly related to parasite density, therefore all variabel are analyzed with multivariate. From multivariate

  5. Assessment of two malaria rapid diagnostic tests in children under five years of age, with follow-up of false-positive pLDH test results, in a hyperendemic falciparum malaria area, Sierra Leone

    Directory of Open Access Journals (Sweden)

    De Smet Martin

    2010-01-01

    Full Text Available Abstract Background Most malaria rapid diagnostic tests (RDTs use HRP2 detection, including Paracheck-Pf®, but their utility is limited by persistent false positivity after treatment. PLDH-based tests become negative more quickly, but sensitivity has been reported below the recommended standard of 90%. A new pLDH test, CareStart™ three-line P.f/PAN-pLDH, claims better sensitivity with continued rapid conversion to negative. The study aims were to 1 compare sensitivity and specificity of CareStart™ to Paracheck-Pf® to diagnose falciparum malaria in children under five years of age, 2 assess how quickly false-positive CareStart™ tests become negative and 3 evaluate ease of use and inter-reader agreement of both tests. Methods Participants were included if they were aged between two and 59 months, presenting to a Médecins Sans Frontières community health centre in eastern Sierra Leone with suspected malaria defined as fever (axillary temperature > 37.5°C and/or history of fever in the previous 72 hours and no signs of severe disease. The same capillary blood was used for the RDTs and the blood slide, the latter used as the gold standard reference. All positive participants were treated with supervised artesunate and amodiaquine treatment for three days. Participants with a persistent false-positive CareStart™, but a negative blood slide on Day 2, were followed with repeated CareStart™ and blood slide tests every seven days until CareStart™ became negative or a maximum of 28 days. Results Sensitivity of CareStart™ was 99.4% (CI 96.8-100.0, 168/169 and of Paracheck-Pf®, 98.8% (95% CI 95.8-99.8, 167/169. Specificity of CareStart™ was 96.0% (CI 91.9-98.4, 167/174 and of Paracheck-Pf®, 74.7% (CI 67.6-81.0, 130/174 (p ® with excellent inter-reader agreement. Conclusions Both RDTs were highly sensitive, met WHO standards for the detection of falciparum malaria monoinfections where parasitaemia was >100 parasites/μl and were easy

  6. Combating multidrug-resistant Plasmodium falciparum malaria.

    Science.gov (United States)

    Thu, Aung Myint; Phyo, Aung Pyae; Landier, Jordi; Parker, Daniel M; Nosten, François H

    2017-08-01

    Over the past 50 years, Plasmodium falciparum has developed resistance against all antimalarial drugs used against it: chloroquine, sulphadoxine-pyrimethamine, quinine, piperaquine and mefloquine. More recently, resistance to the artemisinin derivatives and the resulting failure of artemisinin-based combination therapy (ACT) are threatening all major gains made in malaria control. Each time resistance has developed progressively, with delayed clearance of parasites first emerging only in a few regions, increasing in prevalence and geographic range, and then ultimately resulting in the complete failure of that antimalarial. Drawing from this repeated historical chain of events, this article presents context-specific approaches for combating drug-resistant P. falciparum malaria. The approaches begin with a context of drug-sensitive parasites and focus on the prevention of the emergence of drug resistance. Next, the approaches address a scenario in which resistance has emerged and is increasing in prevalence and geographic extent, with interventions focused on disrupting transmission through vector control, early diagnosis and treatment, and the use of new combination therapies. Elimination is also presented as an approach for addressing the imminent failure of all available antimalarials. The final drug resistance context presented is one in which all available antimalarials have failed; leaving only personal protection and the use of new antimalarials (or new combinations of antimalarials) as a viable strategy for dealing with complete resistance. All effective strategies and contexts require a multipronged, holistic approach. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  7. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites.

    Directory of Open Access Journals (Sweden)

    Remko Schats

    Full Text Available Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization, requiring only 30-45 mosquitoes bites infected with P. falciparum-sporozoites. Given the large diversity of P. falciparum parasites, it is essential to assess protection against heterologous parasite strains.In an open-label follow-up study, 16 volunteers previously CPS-immunized and challenged with P. falciparum NF54 (West-Africa in a dose de-escalation and challenge trial were re-challenged with clone NF135.C10 (Cambodia at 14 months after the last immunization (NCT01660854.Two out of thirteen NF54 protected volunteers previously fully protected against NF54 were also fully protected against NF135.C10, while 11/13 showed a delayed patency (median prepatent period of 10.5 days (range 9.0-15.5 versus 8.5 days in 5 malaria-naïve controls (p = 0.0005. Analysis of patency by qPCR indicated a 91 to >99% estimated reduction of liver parasite load in 7/11 partially protected subjects. Three volunteers previously not protected against NF54, were also not protected against NF135.C10.This study shows that CPS-immunization can induce heterologous protection for a period of more than one year, which is a further impetus for clinical development of whole parasite vaccines.Clinicaltrials.gov NCT01660854.

  8. A Patient with G6PD Deficiency and Falciparum Malaria

    Directory of Open Access Journals (Sweden)

    Y Fagani

    2007-04-01

    Full Text Available A 20 year old male patient from Afghanistan with a history of G6PD deficiency and clinical manifestations of malaria referred to Bou-Ali Hospital in Tehran, capital of Iran. Giemsa stained thick blood films revealed an infection of Plasmodium falciparum with 33700 parasite/μL of blood. The patient was successfully treated according to malaria treatment guideline.

  9. Naturally acquired immunity to Plasmodium falciparum malaria in Africa

    DEFF Research Database (Denmark)

    Hviid, Lars

    2005-01-01

    protective immunity to P. falciparum malaria is acquired following natural exposure to the parasites is beginning to emerge, not least thanks to studies that have combined clinical and epidemiological data with basic immunological research. This framework involves IgG with specificity for clonally variant......Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective...

  10. Assessment of therapeutic efficacy and safety of artemether-lumefantrine (Coartem®) in the treatment of uncomplicated Plasmodium falciparum malaria patients in Bahir Dar district, Northwest Ethiopia: an observational cohort study.

    Science.gov (United States)

    Ebstie, Yehenew A; Zeynudin, Ahmed; Belachew, Tefera; Desalegn, Zelalem; Suleman, Sultan

    2015-06-05

    Malaria is a complex disease, which varies in its epidemiology and clinical manifestation. Although artemether-lumefantrine has been used as first-line drug for uncomplicated Plasmodium falciparum malaria in Bahir Dar district since 2004, its efficacy has not yet been assessed. The main objective of this study was to quantify the proportion of patients with uncomplicated falciparum malaria who were prescribed artemether-lumefantrine and who failed treatment after a 28-day follow-up. The research team attempted to conduct an observational cohort study on the assessment of therapeutic efficacy and safety of artemether-lumefantrine in falciparum malaria patients aged over five years in Bahir Dar district from March to July 2012. Among 130 participants in the study, 60% were males with 1:5 male to female ratio. The mean of asexual parasitaemia load was 8675 parasites/μL and 96.1% participants were free from parasitaemia at day 3. At the end of the study, 98.5% of participants showed adequate clinical and parasitological response of the drug. In the study, only 1.5% of participants were shown late parasitological failure between seventh and 14th day follow-up and 1.3% of participants were free from anaemia at the end of follow-up. According to the research findings, artemether-lumefantrine fulfilled the inclusion criteria of WHO as first-line drug and continues to be the drug of choice for the treatment of uncomplicated falciparum malaria. Outputs from this study should be supported through advanced molecular techniques and blood concentration and pharmaco-vigilance of the drug.

  11. Two cases of Plasmodium falciparum malaria in the Netherlands without recent travel to a malaria-endemic country.

    Science.gov (United States)

    Arends, Joop E; Oosterheert, Jan Jelrik; Kraaij-Dirkzwager, Marleen M; Kaan, Jan A; Fanoy, Ewout B; Haas, Pieter-Jan; Scholte, Ernst-Jan; Kortbeek, Laetitia M; Sankatsing, Sanjay U C

    2013-09-01

    Recently, two patients of African origin were given a diagnosis of Plasmodium falciparum malaria without recent travel to a malaria-endemic country. This observation highlights the importance for clinicians to consider tropical malaria in patients with fever. Possible transmission routes of P. falciparum to these patients will be discussed. From a public health perspective, international collaboration is crucial when potential cases of European autochthonous P. falciparum malaria in Europe re considered.

  12. Malaria in pregnancy in rural Mozambique: the role of parity, submicroscopic and multiple Plasmodium falciparum infections.

    Science.gov (United States)

    Saute, Francisco; Menendez, Clara; Mayor, Alfredo; Aponte, John; Gomez-Olive, Xavier; Dgedge, Martinho; Alonso, Pedro

    2002-01-01

    Falciparum malaria affects pregnant women, especially primigravidae, but before malaria control programmes targeted to them can be designed, a description of the frequency and parity pattern of the infection is needed. There is little information on the frequency and effect of submicroscopic malaria infection, as well as on multiplicity of Plasmodium falciparum genotypes in pregnancy. This study aimed to describe the prevalence of malaria parasitaemia and anaemia and their relation to parity and age in pregnant women, during two malaria transmission seasons in a rural area of southern Mozambique. It also tried to assess the frequency and effect on anaemia of submicroscopic and multiple falciparum infections. A total of 686 pregnant women were enrolled in three cross-sectional community-based surveys during different transmission seasons in rural southern Mozambique. In each survey a questionnaire was administered on previous parity history, the gestational age was assessed, the axillary temperature recorded and both haematocrit and malaria parasitaemia were determined. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis to determine submicroscopic and multiple P. falciparum infections in a subsample of women. A total of 156 women (23%) had microscopic parasitaemia, of which 144 (92%) were asexual forms of P. falciparum. The prevalence of clinical malaria was 18 of 534 (3%), that of anaemia, 382 of 649 (59%). In a multivariate analysis age but not parity was associated with an increased risk of microscopic parasitaemia. Anaemia was associated with microscopic P. falciparum parasitaemia. Both malaria parasitaemia and anaemia were more frequent during the rainy season. Although not statistically significant, submicroscopic infections tended to be more frequent among grand-multiparous pregnant women. Subpatent infections were not associated with increased anaemia. Multiplicity of infection was not associated with either

  13. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Helegbe, Gideon K; Goka, Bamenla Q; Kurtzhals, Jørgen

    2007-01-01

    BACKGROUND: Severe anaemia (SA), intravascular haemolysis (IVH) and respiratory distress (RD) are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism......55)] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb) levels and RD were investigated. RESULTS: Of the 484 samples tested, 131(27%) were positive in DCT, out of which 115/131 (87.8%) were...... falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement...

  14. Parasite virulence and disease severity in Plasmodium falciparum malaria.

    OpenAIRE

    Ribacke, Ulf

    2009-01-01

    Malaria stands out as one of the most important infectious diseases and one of the world s leading causes of death. Plasmodium falciparum is the parasite responsible for the great majority of severe disease syndromes and mortality, and affects mainly children and pregnant women. Despite intensive research efforts, the understanding of P. falciparum virulence is limited. Infections with the parasite cause everything from asymptomatic parasitemia to severe disease and death, a...

  15. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

    Science.gov (United States)

    Taylor, Steve M; Cerami, Carla; Fairhurst, Rick M

    2013-01-01

    Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite

  16. Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis

    Science.gov (United States)

    Taylor, Steve M.; Cerami, Carla; Fairhurst, Rick M.

    2013-01-01

    Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits—including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia—are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a “natural experiment” to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the “Gordian knot” of host and parasite

  17. Hemoglobinopathies: slicing the Gordian knot of Plasmodium falciparum malaria pathogenesis.

    Directory of Open Access Journals (Sweden)

    Steve M Taylor

    Full Text Available Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits--including hemoglobin S (HbS, hemoglobin C (HbC, and α-thalassemia--are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait. Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1 to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and

  18. Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries

    Science.gov (United States)

    Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi

    2014-01-01

    Background In settings where both Plasmodium vivax and Plasmodium falciparum infection cause malaria, rapid diagnostic tests (RDTs) need to distinguish which species is causing the patients' symptoms, as different treatments are required. Older RDTs incorporated two test lines to distinguish malaria due to P. falciparum, from malaria due to any other Plasmodium species (non-falciparum). These RDTs can be classified according to which antibodies they use: Type 2 RDTs use HRP-2 (for P. falciparum) and aldolase (all species); Type 3 RDTs use HRP-2 (for P. falciparum) and pLDH (all species); Type 4 use pLDH (fromP. falciparum) and pLDH (all species). More recently, RDTs have been developed to distinguish P. vivax parasitaemia by utilizing a pLDH antibody specific to P. vivax. Objectives To assess the diagnostic accuracy of RDTs for detecting non-falciparum or P. vivax parasitaemia in people living in malaria-endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria, and to identify which types and brands of commercial test best detect non-falciparum and P. vivax malaria. Search methods We undertook a comprehensive search of the following databases up to 31 December 2013: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; and IndMED. Selection criteria Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction) in blood samples from a random or consecutive series of patients attending ambulatory health facilities with symptoms suggestive of malaria in non-falciparum endemic areas. Data collection and analysis For each study, two review authors independently extracted a standard set of data using a tailored data extraction form. We grouped comparisons by type of RDT (defined by the combinations of antibodies used), and combined in meta-analysis where appropriate. Average sensitivities and

  19. Treatment of falciparum malaria in the age of drug resistance

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    Shanks G

    2006-01-01

    Full Text Available The growing problem of drug resistance has greatly complicated the treatment for falciparum malaria. Whereaschloroquine and sulfadoxine/pyrimethamine could once cure most infections, this is no longer true and requiresexamination of alternative regimens. Not all treatment failures are drug resistant and other issues such asexpired antimalarials and patient compliance need to be considered. Continuation of a failing treatment policyafter drug resistance is established suppresses infections rather than curing them, leading to increasedtransmission of malaria, promotion of epidemics and loss of public confidence in malaria control programs.Antifolate drug resistance (i.e. pyrimethamine means that new combinations are urgently needed particularlybecause addition of a single drug to an already failing regimen is rarely effective for very long. Atovaquone/proguanil and mefloquine have been used against multiple drug resistant falciparum malaria with resistance toeach having been documented soon after drug introduction. Drug combinations delay further transmission ofresistant parasites by increasing cure rates and inhibiting formation of gametocytes. Most currentlyrecommended drug combinations for falciparum malaria are variants of artemisinin combination therapy wherea rapidly acting artemisinin compound is combined with a longer half-life drug of a different class. Artemisininsused include dihydroartemisinin, artesunate, artemether and companion drugs include mefloquine, amodiaquine,sulfadoxine/pyrimethamine, lumefantrine, piperaquine, pyronaridine, chlorproguanil/dapsone. The standard ofcare must be to cure malaria by killing the last parasite. Combination antimalarial treatment is vital not only tothe successful treatment of individual patients but also for public health control of malaria.

  20. A randomised controlled trial to assess the efficacy of dihydroartemisinin-piperaquine for the treatment of uncomplicated falciparum malaria in Peru.

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    Tanilu Grande

    Full Text Available BACKGROUND: Multi-drug resistant falciparum malaria is an important health problem in the Peruvian Amazon region. We carried out a randomised open label clinical trial comparing mefloquine-artesunate, the current first line treatment in this region, with dihydroartemisinin-piperaquine. METHODS AND FINDINGS: Between July 2003 and July 2005, 522 patients with P. falciparum uncomplicated malaria were recruited, randomized (260 with mefloquine-artesunate and 262 with dihydroartemisinin-piperaquine, treated and followed up for 63 days. PCR-adjusted adequate clinical and parasitological response, estimated by Kaplan Meier survival and Per Protocol analysis, was extremely high for both drugs (99.6% for mefloquine-artesunate and 98.4% and for dihydroartemisinin-piperaquine (RR: 0.99, 95%CI [0.97-1.01], Fisher Exact p = 0.21. All recrudescences were late parasitological failures. Overall, gametocytes were cleared faster in the mefloquine-artesunate group (28 vs 35 days and new gametocytes tended to appear more frequently in patients treated with dihydroartemisinin-piperaquine (day 7: 8 (3.6% vs 2 (0.9%, RR: 3.84, 95%CI [0.82-17.87]. Adverse events such as anxiety and insomnia were significantly more frequent in the mefloquine-artesunate group, both in adults and children. CONCLUSION: Dihydroartemisinin-piperaquine is as effective as mefloquine-artesunate in treating uncomplicated P. falciparum malaria but it is better tolerated and more affordable than mefloquine-artesunate (US$1.0 versus US$18.65 on the local market. Therefore, it should be considered as a potential candidate for the first line treatment of P. falciparum malaria in Peru. TRIAL REGISTRATION: ClinicalTrials.gov NCT00373607.

  1. Proteomic identification of host and parasite biomarkers in saliva from patients with uncomplicated Plasmodium falciparum malaria

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    Huang Honglei

    2012-05-01

    Full Text Available Abstract Background Malaria cases attributed to Plasmodium falciparum account for approximately 600,000 deaths yearly, mainly in African children. The gold standard method to diagnose malaria requires the visualization of the parasite in blood. The role of non-invasive diagnostic methods to diagnose malaria remains unclear. Methods A protocol was optimized to deplete highly abundant proteins from saliva to improve the dynamic range of the proteins identified and assess their suitability as candidate biomarkers of malaria infection. A starch-based amylase depletion strategy was used in combination with four different lectins to deplete glycoproteins (Concanavalin A and Aleuria aurantia for N-linked glycoproteins; jacalin and peanut agglutinin for O-linked glycoproteins. A proteomic analysis of depleted saliva samples was performed in 17 children with fever and a positive–malaria slide and compared with that of 17 malaria-negative children with fever. Results The proteomic signature of malaria-positive patients revealed a strong up-regulation of erythrocyte-derived and inflammatory proteins. Three P. falciparum proteins, PFL0480w, PF08_0054 and PFI0875w, were identified in malaria patients and not in controls. Aleuria aurantia and jacalin showed the best results for parasite protein identification. Conclusions This study shows that saliva is a suitable clinical specimen for biomarker discovery. Parasite proteins and several potential biomarkers were identified in patients with malaria but not in patients with other causes of fever. The diagnostic performance of these markers should be addressed prospectively.

  2. [Plasmodium falciparum malaria: epidemiology and clinical features at Tarapoto Hospital].

    Science.gov (United States)

    Calderon, J; Rodriguez, J; Romero, D

    1997-01-01

    A retrospective study was conducted of the clinical records of 41 patients discharged from a hospital in Tarapoto, Peru, between August 1992 and June 1996 following treatment for Plasmodium falciparum malaria. Patients ranged in age from 18 to 65 years; 25 were male. The cases were uniformly distributed throughout the year. The duration of illness averaged 11 days. At admission, 40 patients had fever, 36 had shaking chills, 29 had headache, 21 had nausea and vomiting, 21 had hyporexia, 15 had pallor, and 13 had splenomegaly. 3 of the 16 women were pregnant. 7 patients reported a history of malaria. The admission diagnosis was malaria in 33 cases. 31 patients were treated with chloroquine; 18 were subsequently treated with pyrimethamine-sulfadoxin and 1 received doxycycline. No cases of grave illness or death occurred. The increasing presence of Plasmodium falciparum malaria in the Peruvian lowlands should promote review of the adequacy of control programs.

  3. Surface antigens and virulence in Plasmodium falciparum malaria

    OpenAIRE

    Normark, Johan

    2008-01-01

    Plasmodium falciparum is an intracellular protozoan that may cause severe forms of malaria. It is a major world health hazard and reaps the highest toll among the children and pregnant mothers of the developing world. An Anopheles mosquito vector injects the pathogen when taking a blood meal. After multiplication in cells of the liver, the parasite escapes and infects red blood cells in a cyclic manner and this is when the clinical manifestations of malaria as a disease beco...

  4. Plasmodium falciparum parasitaemia and clinical malaria among school children living in a high transmission setting in western Kenya.

    Science.gov (United States)

    Kepha, Stella; Nikolay, Birgit; Nuwaha, Fred; Mwandawiro, Charles S; Nankabirwa, Joaniter; Ndibazza, Juliet; Cano, Jorge; Matoke-Muhia, Damaris; Pullan, Rachel L; Allen, Elizabeth; Halliday, Katherine E; Brooker, Simon J

    2016-03-11

    Malaria among school children is increasingly receiving attention, yet the burden of malaria in this age group is poorly defined. This study presents data on malaria morbidity among school children in Bungoma county, western Kenya. This study investigated the burden and risk factors of Plasmodium falciparum infection, clinical malaria, and anaemia among 2346 school children aged 5-15 years, who were enrolled in an individually randomized trial evaluating the effect of anthelmintic treatment on the risks of malaria. At baseline, children were assessed for anaemia and nutritional status and information on household characteristics was collected. Children were followed-up for 13 months to assess the incidence of clinical malaria by active detection, and P. falciparum infection and density evaluated using repeated cross-sectional surveys over 15 months. On average prevalence of P. falciparum infection was 42% and ranged between 32 and 48% during the five cross-sectional surveys. Plasmodium falciparum prevalence was significantly higher among boys than girls. The overall incidence of clinical malaria was 0.26 episodes per person year (95% confidence interval, 0.24-0.29) and was significantly higher among girls (0.23 versus 0.31, episodes per person years). Both infection prevalence and clinical disease varied by season. In multivariable analysis, P. falciparum infection was associated with being male, lower socioeconomic status and stunting. The risk of clinical malaria was associated with being female. These findings show that the burden of P. falciparum parasitaemia, clinical malaria and anaemia among school children is not insignificant, and suggest that malaria control programmes should be expanded to include this age group.

  5. Prediction of outcome in adults with severe falciparum malaria: a new scoring system

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    Mishra Rajalaxmi

    2007-02-01

    Full Text Available Abstract Background Mortality of falciparum malaria is related to the presence of severe complications. However, no scoring system is available to predict outcome of these patients. The aim of this paper was to devise a simple and reliable malaria prognosis score (MPS to predict the outcome of adults with severe malaria. Methods All slide-positive severe falciparum malaria patients admitted to Ispat General Hospital were studied. Eight clinical parameters that may potentially differentiate or influence the outcome were identified to predict recovery or death Results Of 248 severe malaria cases, 35 died. There were 212 adults (34 deaths and 36 children (one death. The malaria score for adults was (MSA = 1(severe anaemia + 2 (acute renal failure + 3(Respiratory distress +4 (cerebral malaria. The MSA ranges from 0 to 10. The mortality was 2% for MSA 0 – 2; 10% for MSA 3–4, 40% for MSA 5–6 and 90% for MSA 7 or more. The sensitivity is 89.9% and positive predictive value is 94.1% when 5 is taken as the cut off value. Conclusion MSA is a simple and sensitive predictor. It can be administered rapidly and repeatedly to prognosticate the outcome of severe malaria in adults. It can help the treating doctor to assess the patient as well as to communicate to the relatives of the patients about prognosis. The score needs revalidation in other geographical areas.

  6. Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik

    2015-01-01

    -lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies...

  7. Refractory pancytopenia and megaloblastic anemia due to falciparum malaria.

    Science.gov (United States)

    Aggarwal, Varun; Maheshwari, Anu; Rath, Bimbadhar; Kumar, Praveen; Basu, Srikanta

    2011-08-01

    Anemia is a common complication in malarial infection. Direct destruction and ineffective erythropoesis does not adequately explain the cause of anemia in malaria. We present a case with refractory megaloblastic anemia with asymptomatic falciparum malaria. We hypothesize that promoter variants in the inducible nitric oxide synthase gene might be the cause of severe refractory megaloblastic anemia and pancytopenia in our patient. Malaria should always be kept in mind as a cause of anemia especially in endemic areas even if the child is asymptomatic or there is no demonstrable parasite on routine smear examination.

  8. Association of ABO blood group and Plasmodium falciparum malaria in Dore Bafeno Area, Southern Ethiopia.

    Science.gov (United States)

    Zerihun, Tewodros; Degarege, Abraham; Erko, Berhanu

    2011-08-01

    To assess the distribution of ABO blood group and their relationship with Plasmodium falciparum (P. falciparum) malaria among febrile outpatients who sought medical attention at Dore Bafeno Health Center, Southern Ethiopia. A total of 269 febrile outpatients who visited Dore Bafeno Health Center, Southern Ethiopia, were examined for malaria and also tested for ABO blood groups in January 2010. The blood specimens were collected by finger pricking, stained with Geimsa, and examined microscopically. Positive cases of the parasitemia were counted. CareStart™ Malaria Pf/Pv Combo was also used to test the blood specimens for malaria. ABO blood groups were determined by agglutination test using ERYCLONE(®) antisera. Data on socio-demographic characteristics and treatment status of the participants were also collected. Chi-square and ANOVA tests were used to assess the difference between frequencies and means, respectively. Out of a total of 269 participants, 178 (66.2%) febrile patients were found to be infected with Plasmodium parasites, among which 146 (54.3%), 28 (10.4%), and 4 (1.5%) belonged to P. falciparum, P. vivax, and mixed infections, respectively. All febrile patients were also tested for ABO blood groups and 51.3%, 23.5%, 21.9% and 3.3% were found to be blood types of O, A, B and AB, respectively. Both total malaria infection and P. falciparum infection showed significant association with blood types (Pfalciparum malaria parasitaemia for blood groups A, B, AB, and O were 3 744/µL, 1 805/µL, 5 331/µL, and 1 515/µL, respectively (Pfalciparum malaria.

  9. Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

    Science.gov (United States)

    Wichapoon, Benjamas; Punsawad, Chuchard; Viriyavejakul, Parnpen

    2017-01-01

    In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). In malarial AKI, the process of apoptosis occurs in ATN. © 2016 Asian Pacific Society of Nephrology.

  10. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goel, Suchi; Palmkvist, Mia; Moll, Kirsten

    2015-01-01

    Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs—preferentiall......Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs......—preferentially of blood group A—to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population....

  11. Anti-phospholipid antibodies in patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S D; Hviid, L;

    1993-01-01

    Plasma levels of antibodies against phosphatidylinositol (PI), phosphatidylcholine (PC) and cardiolipin (CL) were measured by enzyme-linked immunosorbent assay (ELISA) in patients from malaria endemic area of Sudan and The Gambia. Some Sudanese adults produced IgM antibodies against all three types...... of phospholipids (PL) during an acute Plasmodium falciparum infection. The anti-PL antibody titre returned to preinfection levels in most of the donors 30 days after the disease episode. IgG titres against PI, PC and CL were low. In Gambian children with malaria, IgM antibody titres against PI and PC were...... significantly higher in those with severe malaria than in those with mild malaria. These results show that a proportion of malaria patients produce anti-PL antibodies during infection and that titres of these antibodies are associated with the severity of disease....

  12. Asthma and atopic dermatitis are associated with increased risk of clinical Plasmodium falciparum malaria

    Science.gov (United States)

    Herrant, Magali; Loucoubar, Cheikh; Bassène, Hubert; Gonçalves, Bronner; Boufkhed, Sabah; Diene Sarr, Fatoumata; Fontanet, Arnaud; Tall, Adama; Baril, Laurence; Mercereau-Puijalon, Odile; Mécheri, Salaheddine; Sakuntabhai, Anavaj; Paul, Richard

    2013-01-01

    Objectives To assess the impact of atopy and allergy on the risk of clinical malaria. Design A clinical and immunological allergy cross-sectional survey in a birth cohort of 175 children from 1 month to 14 years of age followed for up to 15 years in a longitudinal open cohort study of malaria in Senegal. Malaria incidence data were available for 143 of these children (aged 4 months to 14 years of age) for up to 15 years. Mixed-model regression analysis was used to determine the impact of allergy status on malaria incidence, adjusting for age, gender, sickle-cell trait and force of infection. Main outcome measures Asthma, allergic rhinoconjunctivitis and atopic dermatitis status, the number of clinical Plasmodium falciparum malaria episodes since birth and associated parasite density. Results 12% of the children were classified as asthmatic and 10% as having atopic dermatitis. These groups had respectively a twofold (OR 2.12 95%; CI 1.46 to 3.08; p=8×10−5) and threefold (OR 3.15; 1.56 to 6.33; p=1.3×10−3) increase in the risk of clinical P falciparum malaria once older than the age of peak incidence of clinical malaria (3–4 years of age). They also presented with higher P falciparum parasite densities (asthma: mean 105.3 parasites/μL±SE 41.0 vs 51.3±9.7; p=6.2×10−3. Atopic dermatitis: 135.4±70.7 vs 52.3±11.0; p=0.014). There was no effect of allergy on the number of non-malaria clinical presentations. Individuals with allergic rhinoconjunctivitis did not have an increased risk of clinical malaria nor any difference in parasite densities. Conclusions These results demonstrate that asthma and atopic dermatitis delay the development of clinical immunity to P falciparum. Despite the encouraging decrease in malaria incidence rates in Africa, a significant concern is the extent to which the increase in allergy will exacerbate the burden of malaria. Given the demonstrated antiparasitic effect of antihistamines, administration to atopic

  13. A STUDY OF MANIFESTATIONS OF SEVERE FALCIPARUM MALARIA IN BIDAR DISTRICT

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    Vijay Kuma

    2014-07-01

    Full Text Available : OBJECTIVES: Severe falciparum malaria is a critical illness resulting in multi-organ dysfunctions and death severe malaria is defined by the World Health Organization as qualitative variable. The purpose of this study is to devise a scoring system for predicting outcome in severe falciparum malaria. METHODS: 100 cases of sever falciparum malaria diagnosed as per the WHO criteria, were evaluated to determine the parameters which were significantly associated with mortality. Of all the parameters studied, five variables namely cerebral malaria (GCS3mg/dl, respiratory distress (Respiratory rate>24/min, jaundice (bilirubin >10mg/dl and Shock (Systolic BP<90mm of Hg. were all found to be associated with a poor prognosis. RESULTS: The five selected parameters were analyzed using the odds ratio and new scoring system named as GCRBS score was designed with a possible score from 0-10. With ac cut-off score of 5, the GCRBS score predicted mortality with a sensitivity of 85.3% and a specificity of 95.6%. CONCLUSION: The GCRBS score is an easy to calculate and apply. Of the 5 parameters, 3 are clinical which can be determined at beside and only 2 are biochemical which can be done in any laboratory. The most important advantage of this scoring system is that all the 5 parameters are to be assessed quantitatively for allotting a score, which would eliminate the possibility of observer bias.

  14. [From malaria parasite point of view--Plasmodium falciparum evolution].

    Science.gov (United States)

    Zerka, Agata; Kaczmarek, Radosław; Jaśkiewicz, Ewa

    2015-12-31

    Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human-specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies.

  15. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    Science.gov (United States)

    2012-01-01

    Background In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often absent in peripheral blood samples. The appearance of schizonts in peripheral blood smears is thought to be a marker of high sequestered parasite burden and severe disease. In the present study, the value of schizontaemia as an early marker for severe disease in non-immune individuals with imported malaria was evaluated. Methods All patients in the Rotterdam Malaria Cohort diagnosed with P. falciparum malaria between 1 January 1999 and 1 January 2012 were included. Thick and thin blood films were examined for the presence of schizontaemia. The occurrence of WHO defined severe malaria was the primary endpoint. The diagnostic performance of schizontaemia was compared with previously evaluated biomarkers C-reactive protein and lactate. Results Schizonts were present on admission in 49 of 401 (12.2%) patients. Patients with schizontaemia were more likely to present with severe malaria, a more complicated course and had longer duration of admission in hospital. Schizontaemia had a specificity of 0.95, a sensitivity of 0.53, a negative predictive value of 0.92 and a positive predictive value of 0.67 for severe malaria. The presence of schizonts was an independent predictor for severe malaria. Conclusion Absence of schizonts was found to be a specific marker for exclusion of severe malaria. Presence of schizonts on admission was associated with a high positive predictive value for severe malaria. This may be of help to identify patients who are at risk of a more severe course than would be expected when considering peripheral parasitaemia alone. PMID:22929647

  16. Treatment of severe falciparum malaria: quinine versus artesunate

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    Dipesh Patel

    2013-02-01

    Full Text Available Background: Malaria is the most important disease of human being. More than 40% of the world’s population is considered to be at risk of exposure of this disease. Malaria infection has been increasing over recent years due to combination of factors including increasing resistance of malarial parasite. Most of the strains of P. falciparum are now resistance to conventional drugs like chloroquine in many areas. The objective of this study was to compare the efficacy and safety of quinine and artesunate in treatment of P. falciparum malaria. Methods: This is hospital based prospective study, conducted amongst 35 randomly selected patients of severe P. falciparum malaria. Patients with any contraindications of either drug were excluded to avoid bias. Standard statistical tests were applied for qualitative as well as quantitative data. Results: As per the study end point results of difference of mortality in patients receiving either drug was not significant (p > 0.75, but difference in clinical parameters like fever clearance time (p <0.01, parasite clearance time (p < 0.001 and coma resolution time (p < 0.001 were significant among patients receiving artesunate. There were no any significant differences in adverse effects of both the drugs. Mortality was same in both arms taking either drug. Conclusions: Artesunate is as good as quinine in mortality aspect but artesunate is superior in fever clearance time (FCT & parasite clearance time (PCT. Coma resolution time is faster with quinine as compared to artesunate. There are no significant adverse effects of either drug. So artesunate is equivalent or superior for treatment for severe falciparum malaria. [Int J Basic Clin Pharmacol 2013; 2(1.000: 30-36

  17. Neopterin and procalcitonin are suitable biomarkers for exclusion of severe Plasmodium falciparum disease at the initial clinical assessment of travellers with imported malaria

    NARCIS (Netherlands)

    R. te Witt (René); M.E. van Wolfswinkel (Marlies); P.L. Petit (Pieter); J.J. van Hellemond (Jaap); R. Koelewijn (Rob); A.F. van Belkum (Alex); P.J.J. van Genderen (Perry)

    2010-01-01

    textabstractBackground. Most clinicians in developed, non-malaria endemic countries have limited or no experience in making clinical assessments of malaria disease severity and subsequent decisions regarding the need for parenteral therapy or high-level monitoring in febrile patients with imported

  18. Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

    Science.gov (United States)

    Epstein, Judith E.; Paolino, Kristopher M.; Richie, Thomas L.; Sedegah, Martha; Singer, Alexandra; Ruben, Adam J.; Chakravarty, Sumana; Stafford, April; Ruck, Richard C.; Eappen, Abraham G.; Billingsley, Peter F.; Manoj, Anita; Moser, Kara; Nielsen, Robin; Tosh, Donna; Cicatelli, Susan; Ganeshan, Harini; Case, Jessica; Padilla, Debbie; Davidson, Silas; Saverino, Elizabeth; Murshedkar, Tooba; Gunasekera, Anusha; Twomey, Patrick S.; Reyes, Sharina; Moon, James E.; James, Eric R.; KC, Natasha; Li, Minglin; Abot, Esteban; Belmonte, Arnel; Hauns, Kevin; Belmonte, Maria; Huang, Jun; Vasquez, Carlos; Remich, Shon; Carrington, Mary; Abebe, Yonas; Tillman, Amy; Hickey, Bradley; Regules, Jason; Villasante, Eileen; Sim, B. Kim Lee

    2017-01-01

    BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT02215707. FUNDING: Support was provided through the US Army Medical Research and Development Command, Military Infectious Diseases Research Program, and the Naval Medical Research

  19. A World Malaria Map: Plasmodium falciparum Endemicity in 2007

    Science.gov (United States)

    Hay, Simon I; Guerra, Carlos A; Gething, Peter W; Patil, Anand P; Tatem, Andrew J; Noor, Abdisalan M; Kabaria, Caroline W; Manh, Bui H; Elyazar, Iqbal R. F; Brooker, Simon; Smith, David L; Moyeed, Rana A; Snow, Robert W

    2009-01-01

    Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the

  20. Reduced erythrocyte deformability associated with hypoargininemia during Plasmodium falciparum malaria.

    Science.gov (United States)

    Rey, Juliana; Buffet, Pierre A; Ciceron, Liliane; Milon, Geneviève; Mercereau-Puijalon, Odile; Safeukui, Innocent

    2014-01-20

    The mechanisms underlying reduced red blood cell (RBC) deformability during Plasmodium falciparum (Pf) malaria remain poorly understood. Here, we explore the possible involvement of the L-arginine and nitric oxide (NO) pathway on RBC deformability in Pf-infected patients and parasite cultures. RBC deformability was reduced during the acute attack (day0) and returned to normal values upon convalescence (day28). Day0 values correlated with plasma L-arginine levels (r = 0.69; p = 0.01) and weakly with parasitemia (r = -0.38; p = 0.006). In vitro, day0 patient's plasma incubated with ring-stage cultures at 41°C reduced RBC deformability, and this effect correlated strongly with plasma L-arginine levels (r = 0.89; p falciparum malaria may altogether impair NO production and reduce RBC deformability, particularly at febrile temperature.

  1. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

    NARCIS (Netherlands)

    Tran, T.M.; Jones, M.B.; Ongoiba, A.; Bijker, E.M.; Schats, R.; Venepally, P.; Skinner, J.; Doumbo, S.; Quinten, E.; Visser, L.G.; Whalen, E.; Presnell, S.; O'Connell, E.M.; Kayentao, K.; Doumbo, O.K.; Chaussabel, D.; Lorenzi, H.; Nutman, T.B.; Ottenhoff, T.H.; Haks, M.C.; Traore, B.; Kirkness, E.F.; Sauerwein, R.W.; Crompton, P.D.

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective,

  2. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria

    Science.gov (United States)

    Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

    2014-01-01

    Background The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. Objectives To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE; EMBASE; LILACS; ClinicalTrials.gov; the metaRegister of Controlled Trials (mRCT); and the WHO International Clinical Trials Search Portal up to 16 January 2014. We searched reference lists and conference abstracts, and contacted experts for information about ongoing and unpublished trials. Selection criteria Randomized controlled trials of artesunate-pyronaridine versus other ACTs in adults and children with uncomplicated P. falciparum malaria. For the safety analysis, we also included adverse events data from trials comparing any treatment regimen containing pyronaridine with regimens not containing pyronaridine. Data collection and analysis Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RR) and continuous data using mean differences (MD), and presented all results with a 95% confidence interval (CI). We used the GRADE approach to assess the quality of evidence. Main results We included six randomized controlled trials enrolling 3718 children and adults. Artesunate-pyronaridine versus artemether-lumefantrine In two multicentre trials, enrolling

  3. Non-falciparum malaria infections in pregnant women in West Africa

    DEFF Research Database (Denmark)

    Williams, John; Njie, Fanta; Cairns, Matthew

    2016-01-01

    BACKGROUND: Non-Plasmodium falciparum malaria infections are found in many parts of sub-Saharan Africa but little is known about their importance in pregnancy. METHODS: Blood samples were collected at first antenatal clinic attendance from 2526 women enrolled in a trial of intermittent screening...... for a non-falciparum malaria infection were investigated and the influence of these infections on the outcome of pregnancy was determined. RESULTS: P. falciparum infection was detected frequently (overall prevalence by PCR: 38.8 %, [95 % CI 37.0, 40.8]), with a prevalence ranging from 10.8 % in The Gambia...... to 56.1 % in Ghana. Non-falciparum malaria infections were found only rarely (overall prevalence 1.39 % [95 % CI 1.00, 1.92]), ranging from 0.17 % in the Gambia to 3.81 % in Mali. Ten non-falciparum mono-infections and 25 mixed falciparum and non-falciparum infections were found. P. malariae...

  4. Correlation of interleukin-4 levels with Plasmodium falciparum malaria parasitaemia in Sudanese children.

    Science.gov (United States)

    Elhussein, A B; Huneif, M A; Naeem, A; Fadlelseed, O E; Babiker, W G; Rahma, N E A A; Ahmed, S A M; Ayed, I A M; Shalayel, M H F

    2015-12-01

    This study aimed to measure the level of interleukin-4 (IL-4) in the serum of children patients with falciparum malaria and to correlate the production of this cytokine with the severity of malaria parasitaemia. One hundred ten patients with malaria participated in this study (53 males and 57 females) and their results were compared with that of 60 healthy control subjects. Their ages ranged between 6 months and 15 years. For the detection of parasitaemia, a calibrated thick-smear technique was used with standard Giemsa staining. For designation of the relative parasite count, a simple code from one to four crosses is used according to the criteria mentioned by Gilles and Warrell. The blood samples were assessed for IL-4 using enzyme-linked immunosorbent assay (ELISA) technique. Thirty-three malaria patients (30.27%) had one cross (+) parasitaemia, 13 patients (11.93%) had (++) parasitaemia, 24 patients (22.02%) had (+++) parasitaemia and 39 patients (35.78%) had (++++) parasitaemia. There was a significant difference (P0.0001). It was concluded that elevation of serum IL-4 in Sudanese children suffering from Plasmodium falciparum malaria is correlated with the severity of malaria hyperparasitaemia rather than with the severity of the disease.

  5. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites.

    Science.gov (United States)

    Lee, Marcus Cs; Fidock, David A

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  6. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites

    OpenAIRE

    Lee, Marcus CS; David A Fidock

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  7. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria

    OpenAIRE

    Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

    2014-01-01

    Background The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. Objective...

  8. Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria

    KAUST Repository

    Huang, Honglei

    2014-02-10

    Background: Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria. Methods: We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes. Findings: We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor. Conclusion: IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection. 2014 Huang et al.

  9. [Drug sensitivity of falciparum malaria imported into France in 1995].

    Science.gov (United States)

    Longuet, C; Ramiliarisoa, O; Thor, R; Bouchaud, O; Basco, L K; Doury, J C; Le Bras, J

    1997-01-01

    The National Reference Centre for Malaria Chemosusceptibility (CNRCP) and the Tropical Medicine Institute of the Health Department for the Army (IMTSSA) monitor the chemosusceptibility of falciparum malaria introduced in France. In 1995, 353 isolates of P. falciparum are sent to the CNRCP and IMTSSA from malaria cases presenting in 49 civil and military hospitals distributed all over the french country. The patients are mostly Africans living in France and have mainly stayed in West Africa. Half of them did not take any chemoprophylaxis and a quarter took only chloroquine more or less regularly. The curative treatment, when known, is halofantrine alone in 52% of cases and quinine alone in 28% of cases. Three halofantrine failures are reported including 1 incorrect regimen and 4 quinine failures including 3 incorrect regimens. In 1995, in vitro resistance of P. falciparum isolates imported in France to the chemoprophylactic and therapeutic drugs is not worsening. In vitro quinine resistance is rare (1/108), mefloquine resistance (2/20) and halofantrine resistance (12/211) are limited, cycloguanil resistance (42/185) is stable and chloroquine resistance (84/230) is even decreasing (less selective pressure in Africa?).

  10. A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in Hainan Province, 2002-2012.

    Science.gov (United States)

    Sun, Ding-Wei; Du, Jian-Wei; Wang, Guang-Ze; Li, Yu-Chun; He, Chang-Hua; Xue, Rui-De; Wang, Shan-Qing; Hu, Xi-Min

    2015-12-01

    In Hainan Province, China, great achievements in elimination of falciparum malaria have been made since 2010. There have been no locally acquired falciparum malaria cases since that time. The cost-effectiveness of elimination of falciparum malaria has been analyzed in Hainan Province. There were 4,422 falciparum malaria cases reported from 2002 to 2012, more cases occurred in males than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life years (DALYs) were reported because of falciparum malaria. Populations in the age ranges of 15-25 and 30-44 years had higher incidences and DALYs than other age groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds from the provincial government, national government, and the GFATM were US$3.02, US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504 falciparum malaria cases were averted during the period 2003-2012. The estimated cost per falciparum malaria case averted was US$116.5. The falciparum malaria elimination program in Hainan was highly effective and successful. However, funding for maintenance is still needed because of imported cases. © The American Society of Tropical Medicine and Hygiene.

  11. A Cost-Effectiveness Analysis of Plasmodium falciparum Malaria Elimination in Hainan Province, 2002–2012

    Science.gov (United States)

    Sun, Ding-Wei; Du, Jian-Wei; Wang, Guang-Ze; Li, Yu-Chun; He, Chang-Hua; Xue, Rui-De; Wang, Shan-Qing; Hu, Xi-Min

    2015-01-01

    In Hainan Province, China, great achievements in elimination of falciparum malaria have been made since 2010. There have been no locally acquired falciparum malaria cases since that time. The cost-effectiveness of elimination of falciparum malaria has been analyzed in Hainan Province. There were 4,422 falciparum malaria cases reported from 2002 to 2012, more cases occurred in males than in females. From 2002 to 2012, a total of 98.5 disability-adjusted life years (DALYs) were reported because of falciparum malaria. Populations in the age ranges of 15–25 and 30–44 years had higher incidences and DALYs than other age groups. From 2002 to 2012, malaria-related costs for salaries of staff, funds from the provincial government, national government, and the GFATM were US$3.02, US$2.24, US$1.44, and US$5.08 million, respectively. An estimated 9,504 falciparum malaria cases were averted during the period 2003–2012. The estimated cost per falciparum malaria case averted was US$116.5. The falciparum malaria elimination program in Hainan was highly effective and successful. However, funding for maintenance is still needed because of imported cases. PMID:26438030

  12. Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Adam Mayyada B

    2012-08-01

    Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p  Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

  13. Complement activation in Ghanaian children with severe Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Ofori Michael F

    2007-12-01

    Full Text Available Abstract Background Severe anaemia (SA, intravascular haemolysis (IVH and respiratory distress (RD are severe forms of Plasmodium falciparum malaria, with RD reported to be of prognostic importance in African children with malarial anaemia. Complement factors have been implicated in the mechanism leading to excess anaemia in acute P. falciparum infection. Methods The direct Coombs test (DCT and flow cytometry were used to investigate the mean levels of RBC-bound complement fragments (C3d and C3bαβ and the regulatory proteins [complement receptor 1 (CD35 and decay accelerating factor (CD55] in children with discrete clinical forms of P. falciparum malaria. The relationship between the findings and clinical parameters including coma, haemoglobin (Hb levels and RD were investigated. Results Of the 484 samples tested, 131(27% were positive in DCT, out of which 115/131 (87.8% were positive for C3d alone while 16/131 (12.2% were positive for either IgG alone or both. 67.4% of the study population were below 5 years of age and DCT positivity was more common in this age group relative to children who were 5 years or older (Odds ratio, OR = 3.8; 95%CI, 2.2–6.7, p Conclusion These results suggest that complement activation contributed to anaemia in acute childhood P. falciparum malaria, possibly through induction of erythrophagocytosis and haemolysis. In contrast to other studies, this study did not find association between levels of the complement regulatory proteins, CD35 and CD55 and malarial anaemia. These findings suggest that complement activation could also be involved in the pathogenesis of RD but larger studies are needed to confirm this finding.

  14. Lack of Evidence for Chloroquine-Resistant Plasmodium falciparum Malaria, Leogane, Haiti

    Science.gov (United States)

    Neuberger, Ami; Zhong, Kathleen; Kain, Kevin C

    2012-01-01

    Plasmodium falciparum malaria in Haiti is considered chloroquine susceptible, although resistance transporter alleles associated with chloroquine resistance were recently detected. Among 49 patients with falciparum malaria, we found neither parasites carrying haplotypes associated with chloroquine resistance nor instances of chloroquine treatment failure. Continued vigilance to detect emergence of chloroquine resistance is needed. PMID:22932030

  15. Lymphocyte response to purified Plasmodium falciparum antigens during and after malaria

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Jepsen, S; Theander, T G

    1986-01-01

    The peripheral blood lymphocyte response to affinity purified soluble Plasmodium falciparum antigens from in vitro cultures was studied in seven patients with acute falciparum malaria, on eight occasions, and in 15 persons having had malaria, at various times post infection, on 24 occasions. During...

  16. Lack of evidence for chloroquine-resistant Plasmodium falciparum malaria, Leogane, Haiti.

    Science.gov (United States)

    Neuberger, Ami; Zhong, Kathleen; Kain, Kevin C; Schwartz, Eli

    2012-09-01

    Plasmodium falciparum malaria in Haiti is considered chloroquine susceptible, although resistance transporter alleles associated with chloroquine resistance were recently detected. Among 49 patients with falciparum malaria, we found neither parasites carrying haplotypes associated with chloroquine resistance nor instances of chloroquine treatment failure. Continued vigilance to detect emergence of chloroquine resistance is needed.

  17. Possible treatment failure of artemether-lumefantrine in an Italian traveler with uncomplicated falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Ernestina Carla Repetto

    2011-10-01

    Full Text Available Artemisinin-combination therapies (ACTs are recommended for the treatment of uncomplicated malaria in endemic areas with multidrug resistant Plasmodium falciparum. We report a case of possible artemether-lumefantrine failure in an Italian traveler with uncomplicated P. falciparum malaria imported from Democratic Republic of Congo.

  18. Possible clinical failure of artemether-lumefantrine in an italian traveler with uncomplicated falciparum malaria.

    Science.gov (United States)

    Repetto, Ernestina C; Traverso, Antonio; Giacomazzi, Claudio G

    2011-01-01

    Artemisinin-combination therapies (ACTs) are recommended for the treatment of uncomplicated malaria in endemic areas with multidrug resistant Plasmodium falciparum. We report a case of possible artemether-lumefantrine clinical failure in an Italian traveler with uncomplicated P. falciparum malaria imported from Democratic Republic of Congo.

  19. Possible Clinical Failure of Artemether-Lumefantrine in an Italian Traveler with Uncomplicated Falciparum Malaria.

    Science.gov (United States)

    Repetto, Ernestina C.; Traverso, Antonio; Giacomazzi, Claudio G.

    2011-01-01

    Artemisinin-combination therapies (ACTs) are recommended for the treatment of uncomplicated malaria in endemic areas with multidrug resistant Plasmodium falciparum. We report a case of possible artemether-lumefantrine clinical failure in an Italian traveler with uncomplicated P. falciparum malaria imported from Democratic Republic of Congo. PMID:22084655

  20. Transportproteiner som drug-targets hos Plasmodium falciparum. Nye perspektiver i behandlingen af malaria

    DEFF Research Database (Denmark)

    Ellekvist, Peter; Colding, Hanne

    2006-01-01

    The malaria parasite, Plasmodium falciparum, infects and replicates in human erythrocytes. Through the use of substrate-specific transport proteins, P. falciparum takes up nutrients from the erythrocyte's cytoplasm. The sequencing and publishing of the P. falciparum genome have made it possible...

  1. Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children

    Directory of Open Access Journals (Sweden)

    Zongo Issaka

    2008-08-01

    Full Text Available Abstract Background Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs will result in different estimates being reported, with implications for changes in treatment policy. Methods Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a reinfections excluded from the analysis (standard WHO per-protocol analysis or (1b reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a WHO (2001 definitions of failure, or (2b failure defined using parasitological criteria only. Results Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702, artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706 and artemether-lumefantrine (AL, N = 518. Using method (1a, the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference and the others were: (i method 1b = 1.3% [0 to24.8], (ii method 2a = 1.1% [0 to21.5], and (iii method 2b = 0% [-38 to19.3]. The standard per-protocol method (1a tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a. It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size

  2. Epidemiologia de la malaria falciparum complicada: estudio de casos y controles en Tumaco y Turbo, Colombia, 2003 The epidemiology of complicated falciparum malaria: case and controls study in Tumaco and Turbo, Colombia, 2003

    Directory of Open Access Journals (Sweden)

    Alberto Tobón C.

    2006-09-01

    Full Text Available OBJETIVOS: Identificar aspectos del hospedero, del parásito y del ambiente asociados con ocurrencia de malaria por Plasmodium falciparum complicada. MÉTODOS: Estudio de casos y controles en pacientes de Tumaco y Turbo (Colombia aplicando los criterios de complicación de la Organización Mundial de la Salud. RESULTADOS: Entre noviembre 2002 y julio 2003 se captaron 64 casos (malaria complicada y 135 controles (malaria no complicada. Las complicaciones fueron: hiperparasitemia (40%, falla hepática (36%, síndrome dificultad respiratoria aguda (7%, falla renal (4%, trombocitopenia grave (3%, anemia grave (2%, malaria cerebral (2% e hipoglicemia grave (1%. Se encontraron como factores de riesgo para malaria falciparum complicada: a Los antecedentes de malaria falciparum durante el último año fueron menores en los casos (OR= 7.0 (1.2-43.6 P=0.019; b Mayor uso previo de antimaláricos en los casos (OR=2.2 (1.1-4.4 P=0.031 y c mayor uso de cloroquina en los casos (OR=7.4 (1.1-7.8 P=0.017. Se hallaron los alelos MAD-20 y K1 del gen msp1 y FC-27 e IC-1 del gen msp2, cuya distribución de frecuencias fue similar entre casos y controles, aunque el alelo K1 mostró una variación importante entre grupos (casos: 9.4%, controles: 3.5%. La frecuencia de "signos de peligro" fue significativamente mayor en los casos (OR= 3.3, (1.5-7.4 P=0.001. Los criterios de complicación malárica de la Organización Mundial de la Salud se comparan con otros y se discuten algunas implicaciones. CONCLUSIÓN: Se identificaron como factores de riesgo para malaria falciparum complicada, la ausencia de antecedentes de malaria falciparum en el último año y el uso de antimaláricos antes de llegar al hospital.OBJECTIVES: Aimed at identifying host and parasite aspects associated to the presence of Plasmodium falciparum complicated malaria. METHODS: Case and controls study in patients from Tumaco and Turbo (Colombia. We used the World Health Organization criteria to assess the

  3. Cytoadhesion to gC1qR through Plasmodium falciparum erythrocyte membrane protein 1 in severe malaria

    DEFF Research Database (Denmark)

    Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau

    2016-01-01

    Cytoadhesion of Plasmodium falciparum infected erythrocytes to gC1qR has been associated with severe malaria, but the parasite ligand involved is currently unknown. To assess if binding to gC1qR is mediated through the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, we analyzed by s...

  4. In vivo efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in Central Ethiopia

    Directory of Open Access Journals (Sweden)

    Jima Daddi

    2011-07-01

    Full Text Available Abstract Background In vivo efficacy assessments of the first-line treatments for Plasmodium falciparum malaria are essential for ensuring effective case management. In Ethiopia, artemether-lumefantrine (AL has been the first-line treatment for uncomplicated P. falciparum malaria since 2004. Methods Between October and November 2009, we conducted a 42-day, single arm, open label study of AL for P. falciparum in individuals >6 months of age at two sites in Oromia State, Ethiopia. Eligible patients who had documented P. falciparum mono-infection were enrolled and followed according to the standard 2009 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 on days 28 and 42, respectively. Results Of 4426 patients tested, 120 with confirmed falciparum malaria were enrolled and treated with AL. Follow-up was completed for 112 patients at day 28 and 104 patients at day 42. There was one late parasitological failure, which was classified as undetermined after genotyping. Uncorrected cure rates at both day 28 and 42 for the per protocol analysis were 99.1% (95% CI 95.1-100.0; corrected cure rates at both day 28 and 42 were 100.0%. Uncorrected cure rates at day 28 and 42 for the intention to treat analysis were 93.3% (95% CI 87.2-97.1 and 86.6% (95% CI 79.1-92.1, respectively, while the corrected cure rates at day 28 and 42 were 94.1% (95% CI 88.2-97.6 and 87.3% (95% CI 79.9-92.7, respectively. Using survival analysis, the unadjusted cure rate was 99.1% and 100.0% adjusted by genotyping for day 28 and 42, respectively. Eight P. falciparum patients (6.7% presented with Plasmodium vivax infection during follow-up and were excluded from the per protocol analysis. Only one patient had persistent parasitaemia at day 3. No serious adverse events were reported, with cough and nausea/vomiting being the

  5. Standardization of the antibody-dependent respiratory burst assay with human neutrophils and Plasmodium falciparum malaria.

    Science.gov (United States)

    Llewellyn, David; Miura, Kazutoyo; Fay, Michael P; Williams, Andrew R; Murungi, Linda M; Shi, Jianguo; Hodgson, Susanne H; Douglas, Alexander D; Osier, Faith H; Fairhurst, Rick M; Diakite, Mahamadou; Pleass, Richard J; Long, Carole A; Draper, Simon J

    2015-09-16

    The assessment of naturally-acquired and vaccine-induced immunity to blood-stage Plasmodium falciparum malaria is of long-standing interest. However, the field has suffered from a paucity of in vitro assays that reproducibly measure the anti-parasitic activity induced by antibodies in conjunction with immune cells. Here we optimize the antibody-dependent respiratory burst (ADRB) assay, which assesses the ability of antibodies to activate the release of reactive oxygen species from human neutrophils in response to P. falciparum blood-stage parasites. We focus particularly on assay parameters affecting serum preparation and concentration, and importantly assess reproducibility. Our standardized protocol involves testing each serum sample in singlicate with three independent neutrophil donors, and indexing responses against a standard positive control of pooled hyper-immune Kenyan sera. The protocol can be used to quickly screen large cohorts of samples from individuals enrolled in immuno-epidemiological studies or clinical vaccine trials, and requires only 6 μL of serum per sample. Using a cohort of 86 samples, we show that malaria-exposed individuals induce higher ADRB activity than malaria-naïve individuals. The development of the ADRB assay complements the use of cell-independent assays in blood-stage malaria, such as the assay of growth inhibitory activity, and provides an important standardized cell-based assay in the field.

  6. Modelling the potential of focal screening and treatment as elimination strategy for Plasmodium falciparum malaria in the Peruvian Amazon Region.

    Science.gov (United States)

    Rosas-Aguirre, Angel; Erhart, Annette; Llanos-Cuentas, Alejandro; Branch, Oralee; Berkvens, Dirk; Abatih, Emmanuel; Lambert, Philippe; Frasso, Gianluca; Rodriguez, Hugo; Gamboa, Dionicia; Sihuincha, Moisés; Rosanas-Urgell, Anna; D'Alessandro, Umberto; Speybroeck, Niko

    2015-05-07

    Focal screening and treatment (FSAT) of malaria infections has recently been introduced in Peru to overcome the inherent limitations of passive case detection (PCD) and further decrease the malaria burden. Here, we used a relatively straightforward mathematical model to assess the potential of FSAT as elimination strategy for Plasmodium falciparum malaria in the Peruvian Amazon Region. A baseline model was developed to simulate a scenario with seasonal malaria transmission and the effect of PCD and treatment of symptomatic infections on the P. falciparum malaria transmission in a low endemic area of the Peruvian Amazon. The model was then adjusted to simulate intervention scenarios for predicting the long term additional impact of FSAT on P. falciparum malaria prevalence and incidence. Model parameterization was done using data from a cohort study in a rural Amazonian community as well as published transmission parameters from previous studies in similar areas. The effect of FSAT timing and frequency, using either microscopy or a supposed field PCR, was assessed on both predicted incidence and prevalence rates. The intervention model indicated that the addition of FSAT to PCD significantly reduced the predicted P. falciparum incidence and prevalence. The strongest reduction was observed when three consecutive FSAT were implemented at the beginning of the low transmission season, and if malaria diagnosis was done with PCR. Repeated interventions for consecutive years (10 years with microscopy or 5 years with PCR), would allow reaching near to zero incidence and prevalence rates. The addition of FSAT interventions to PCD may enable to reach P. falciparum elimination levels in low endemic areas of the Amazon Region, yet the progression rates to those levels may vary substantially according to the operational criteria used for the intervention.

  7. Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum.

    Science.gov (United States)

    Yamagishi, Junya; Natori, Anna; Tolba, Mohammed E M; Mongan, Arthur E; Sugimoto, Chihiro; Katayama, Toshiaki; Kawashima, Shuichi; Makalowski, Wojciech; Maeda, Ryuichiro; Eshita, Yuki; Tuda, Josef; Suzuki, Yutaka

    2014-09-01

    To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes including TLR2 and TICAM2 that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors, JUND, for example, and signaling molecules, TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions.

  8. Complement binding to erythrocytes is associated with macrophage activation and reduced haemoglobin in Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goka, B Q; Kwarko, H; Kurtzhals, J A

    2001-01-01

    We have examined IgG and complement factor C3d deposition on erythrocytes by means of the direct Coombs' test (DAT) and looked for an association with the anaemia seen in falciparum malaria in children living in an area of hyperendemic malaria transmission (in Ghana). In one study (in 1997), 53 out....... The studies support the role of complement activation and erythrophagocytosis in the pathogenesis of anaemia in falciparum malaria in African children....

  9. Case report of Plasmodium falciparum malaria presenting as wide complex tachycardia

    Institute of Scientific and Technical Information of China (English)

    Sunil Kumar; Diwan SK; Mahajan SN; Shilpa Bawankule; Chetan Mahure

    2011-01-01

    Malaria caused by Plasmodium falciparum is a multisystem disorder and may have diversity of clinical presentations. We are presenting a case report of patients of falciparum malaria who presented to us with palpitation and fever. On electrocardiogram he had wide complex tachycardia. This case reiterates the need to think of malaria in any case with symptoms of fever with chills, even with various unusual presentations like palpitation due to wide complex tachycardia, especially in endemic country like India.

  10. Dihydroartemisinin-piperaquine for treating uncomplicated Plasmodium falciparum malaria

    Science.gov (United States)

    Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David

    2014-01-01

    Background The World Health Organization (WHO) recommends Artemisinin-based Combination Therapy (ACT) for treating uncomplicated Plasmodium falciparum malaria. This review aims to assist the decision-making of malaria control programmes by providing an overview of the relative effects of dihydroartemisinin-piperaquine (DHA-P) versus other recommended ACTs. Objectives To evaluate the effectiveness and safety of DHA-P compared to other ACTs for treating uncomplicated P. falciparum malaria in adults and children. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE; LILACS, and the metaRegister of Controlled Trials (mRCT) up to July 2013. Selection criteria Randomized controlled trials comparing a three-day course of DHA-P to a three-day course of an alternative WHO recommended ACT in uncomplicated P. falciparum malaria. Data collection and analysis Two authors independently assessed trials for eligibility and risk of bias, and extracted data. We analysed primary outcomes in line with the WHO 'Protocol for assessing and monitoring antimalarial drug efficacy’ and compared drugs using risk ratios (RR) and 95% confidence intervals (CI). Secondary outcomes were effects on gametocytes, haemoglobin, and adverse events. We assessed the quality of evidence using the GRADE approach. Main results We included 27 trials, enrolling 16,382 adults and children, and conducted between 2002 and 2010. Most trials excluded infants aged less than six months and pregnant women. DHA-P versus artemether-lumefantrine In Africa, over 28 days follow-up, DHA-P is superior to artemether-lumefantrine at preventing further parasitaemia (PCR-unadjusted treatment failure: RR 0.34, 95% CI 0.30 to 0.39, nine trials, 6200 participants, high quality evidence), and although PCR-adjusted treatment failure was below 5% for both ACTs, it was consistently lower

  11. Malaria

    Science.gov (United States)

    Quartan malaria; Falciparum malaria; Biduoterian fever; Blackwater fever; Tertian malaria; Plasmodium ... now only suggested for use in areas where Plasmodium vivax , P. ... is becoming increasingly resistant to anti-malarial medications ...

  12. Artesunate-induced hemoglobinuria in falciparum malaria

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    Avik Karak

    2016-01-01

    Full Text Available A 26-year-old male got admitted with fever of 103°F with chills and rigor for 6 days. He was diagnosed with Plasmodium falciparum infection by peripheral blood smear examination, later confirmed by polymerase chain reaction analysis. Blood smear showed 2% parasitemia. As the patient was hypotensive, intravenous artesunate was started. Two days later, he reported passing "Coca-Cola"-colored urine. Examination revealed tachycardia, anemia, and mild icterus. Serum free hemoglobin and lactate dehydrogenase was elevated whereas haptoglobin was very low. Urine showed the presence of hemoglobin without red blood cells. Glucose-6-phosphate dehydrogenase assay was normal. Chloroquine, primaquine, and quinine levels in blood were undetectable. There was no evidence of any coinfection. Artesunate was stopped suspecting a causal relationship. Intravenous quinine was started. The urine showed progressive clearance over 3 days, and the patient recovered. The strong temporal association of initiating artesunate and occurrence of hemoglobinuria suggested the possible etiological implication which is not documented before.

  13. Oral clindamycin in the treatment of acute uncomplicated falciparum malaria.

    Science.gov (United States)

    Salazar, N P; Saniel, M C; Estoque, M H; Talao, F A; Bustos, D G; Palogan, L P; Gabriel, A I

    1990-09-01

    Clinical trials on oral clindamycin as an antimalarial in hospitalized patients and residents of endemic communities were conducted in the Philippines between May 1984 and December 1985. Seven and 9 qualified subjects in hospital were treated with 300 mg (regimen A) and 600 mg (regimen B) respectively, twice daily for 5 days. Eighteen patients seen at a rural health unit were given the lower dosage. On the basis of the 28-day extended in vivo test of WHO, P. falciparum in all but one patient showed susceptibility to the drug as a blood schizontocide hence, the clinical cure of malaria. Side effects were few and self-limiting. Ten other patients on regimen A were cured within the 7- and/or 28-day extended test period. Clindamycin per se is currently one of the few alternatives in the treatment of clinically moderate drug-resistant malaria.

  14. The ¿/d T-cell response to Plasmodium falciparum malaria in a population in which malaria is endemic

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Dodoo, D

    1996-01-01

    Frequencies and absolute numbers of peripheral gamma/delta T cells have been reported to increase after episodes of Plasmodium falciparum malaria in adults with limited or no previous malaria exposure. In contrast, little is known about the gamma/delta T-cell response to malaria in children from......, Denmark, all with uncomplicated, primary P. falciparum malaria, showed increased gamma/delta T-cell frequencies similar to those previously reported. All patients had lowered absolute numbers of peripheral gamma/delta T cells at admission, changing to increased numbers by days 7 to 14 and then returning...

  15. Efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in Honduras.

    Science.gov (United States)

    Mejia Torres, Rosa Elena; Banegas, Engels Ilich; Mendoza, Meisy; Diaz, Cesar; Bucheli, Sandra Tamara Mancero; Fontecha, Gustavo A; Alam, Md Tauqeer; Goldman, Ira; Udhayakumar, Venkatachalam; Zambrano, Jose Orlinder Nicolas

    2013-05-01

    Chloroquine (CQ) is officially used for the primary treatment of Plasmodium falciparum malaria in Honduras. In this study, the therapeutic efficacy of CQ for the treatment of uncomplicated P. falciparum malaria in the municipality of Puerto Lempira, Gracias a Dios, Honduras was evaluated using the Pan American Health Organization-World Health Organization protocol with a follow-up of 28 days. Sixty-eight patients from 6 months to 60 years of age microscopically diagnosed with uncomplicated P. falciparum malaria were included in the final analysis. All patients who were treated with CQ (25 mg/kg over 3 days) cleared parasitemia by day 3 and acquired no new P. falciparum infection within 28 days of follow-up. All the parasite samples sequenced for CQ resistance mutations (pfcrt) showed only the CQ-sensitive genotype (CVMNK). This finding shows that CQ remains highly efficacious for the treatment of uncomplicated P. falciparum malaria in Gracias a Dios, Honduras.

  16. Chronic Plasmodium falciparum infections in an area of low intensity malaria transmission in the Sudan

    DEFF Research Database (Denmark)

    Hamad, A A; El Hassan, I M; El Khalifa, A A

    2000-01-01

    Chronic Plasmodium falciparum malaria infections in a Sudanese village, in an area of seasonal and unstable malaria transmission, were monitored and genetically characterized to study the influence of persistent infection on the immunology and epidemiology of low endemicity malaria. During...... the October-December malaria season of 1996, 51 individuals out of a population of 420 had confirmed and treated P. falciparum malaria in the village of Daraweesh in eastern Sudan. In a cross-sectional survey carried out in December 1996, an additional 6 individuals were found to harbour a microscopically...

  17. Therapy of uncomplicated falciparum malaria in Europe: MALTHER – a prospective observational multicentre study

    Directory of Open Access Journals (Sweden)

    Bouchaud Olivier

    2012-06-01

    Full Text Available Abstract Background Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe. Methods A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine. Results Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005 and adverse events (p = 0.001, parasite and fever clearance times (p  Conclusions This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

  18. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia

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    Álvarez Tania

    2006-02-01

    Full Text Available Abstract Objective Evaluate the frequency of failure of eight treatments for non-complicated malaria caused by Plasmodium falciparum in patients from Turbo (Urabá region, El Bagre and Zaragoza (Bajo Cauca region, applying the 1998 protocol of the World Health Organization (WHO. Monotherapies using chloroquine (CQ, amodiaquine (AQ, mefloquine (MQ and sulphadoxine-pyrimethamine (SP, and combinations using chloroquine-sulphadoxine-pyrimethamine (CQ-SP, amodiaquine-sulphadoxine-pyrimethamine (AQ-SP, mefloquine-sulphadoxine-pyrimethamine (MQ-SP and artesunate-sulphadoxine-pyrimethamine (AS-SP, were examined. Methodology A balanced experimental design with eight groups. Samples were selected based on statistical and epidemiological criteria. Patients were followed for 21 to 28 days, including seven or eight parasitological and clinical evaluations, with an active search for defaulting patients. A non-blinded evaluation of the antimalarial treatment response (early failure, late failure, adequate response was performed. Results Initially, the loss of patients to follow-up was higher than 40%, but the immediate active search for the cases and the monetary help for transportation expenses of patients, reduced the loss to 6%. The treatment failure was: CQ 82%, AQ 30%, MQ 4%, SP 24%, CQ-SP 17%, AQ-SP 2%, MQ-S-P 0%, AS-SP 3%. Conclusion The characteristics of an optimal epidemiological monitoring system of antimalarial treatment response in Colombia are discussed. It is proposed to focus this on early failure detection, by applying a screening test every two to three years, based on a seven to 14-day follow-up. Clinical and parasitological assessment would be carried out by a general physician and a field microscopist from the local hospital, with active measures to search for defaulter patients at follow-up.

  19. Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

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    Villasis Elizabeth

    2012-10-01

    Full Text Available Abstract Background Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL and the Reticulocyte Binding-Like (PfRh proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally acquired immunity and immunity generated by parasite blood stage vaccine candidates. The hypotheses tested in this study were 1 that antibody responses against specific P. falciparum invasion ligands (EBL and PfRh differ between symptomatic and asymptomatic individuals living in the low-transmission region of the Peruvian Amazon and 2, such antibody responses might have an association, either direct or indirect, with clinical immunity observed in asymptomatically parasitaemic individuals. Methods ELISA was used to assess antibody responses (IgG, IgG1 and IgG3 against recombinant P. falciparum invasion ligands of the EBL (EBA-175, EBA-181, EBA-140 and PfRh families (PfRh1, PfRh2a, PfRh2b, PfRh4 and PfRh5 in 45 individuals infected with P. falciparum from Peruvian Amazon. Individuals were classified as having symptomatic malaria (N=37 or asymptomatic infection (N=8. Results Antibody responses against both EBL and PfRh family proteins were significantly higher in asymptomatic compared to symptomatic individuals, demonstrating an association with clinical immunity. Significant differences in the total IgG responses were observed with EBA-175, EBA-181, PfRh2b, and MSP119 (as a control. IgG1 responses against EBA-181, PfRh2a and PfRh2b were significantly higher in the asymptomatic individuals. Total IgG antibody responses against PfRh1, PfRh2a, PfRh2b, PfRh5, EBA-175, EBA-181 and MSP119 proteins were negatively correlated with level of parasitaemia. IgG1 responses against EBA-181, PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions These data suggest that falciparum malaria patients who develop

  20. Artesunate-amodiaquine fixed dose combination for the treatment of Plasmodium falciparum malaria in India

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    Anvikar Anupkumar R

    2012-03-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been recommended for the treatment of falciparum malaria by the World Health Organization. Though India has already switched to ACT for treating falciparum malaria, there is need to have multiple options of alternative forms of ACT. A randomized trial was conducted to assess the safety and efficacy of the fixed dose combination of artesunate-amodiaquine (ASAQ and amodiaquine (AQ for the treatment of uncomplicated falciparum malaria for the first time in India. The study sites are located in malaria-endemic, chloroquine-resistant areas. Methods This was an open label, randomized trial conducted at two sites in India from January 2007 to January 2008. Patients between six months and 60 years of age having Plasmodium falciparum mono-infection were randomly allocated to ASAQ and AQ arms. The primary endpoint was 28-day PCR-corrected parasitological cure rate. Results Three hundred patients were enrolled at two participating centres, Ranchi, Jharkhand and Rourkela, Odisha. Two patients in AQ arm had early treatment failure while there was no early treatment failure in ASAQ arm. Late treatment failures were seen in 13 and 12 patients in ASAQ and AQ arms, respectively. The PCR-corrected cure rates in intent-to-treat population were 97.51% (94.6-99.1% in ASAQ and 88.65% (81.3-93.9% in AQ arms. In per-protocol population, they were 97.47% (94.2-99.2% and 88.30% (80-94% in ASAQ and AQ arms respectively. Seven serious adverse events (SAEs were reported in five patients, of which two were reported as related to the treatment. All SAEs resolved without sequel. Conclusion The fixed dose combination of ASAQ was found to be efficacious and safe treatment for P. falciparum malaria. Amodiaquine also showed acceptable efficacy, making it a suitable partner of artesunate. The combination could prove to be a viable option in case India opts for fixed dose combination ACT. Clinical trial registry

  1. Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum.

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    Jessica K O'Hara

    Full Text Available Nicotinamide adenine dinucleotide (NAD+ is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT, is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.

  2. Changes in antigen-specific cytokine and chemokine responses to Plasmodium falciparum antigens in a highland area of Kenya after a prolonged absence of malaria exposure.

    Science.gov (United States)

    Ochola, Lyticia A; Ayieko, Cyrus; Kisia, Lily; Magak, Ng'wena G; Shabani, Estela; Ouma, Collins; John, Chandy C

    2014-09-01

    Individuals naturally exposed to Plasmodium falciparum lose clinical immunity after a prolonged lack of exposure. P. falciparum antigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity of P. falciparum antigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinical P. falciparum malaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document that P. falciparum antigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence of P. falciparum exposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack of P. falciparum exposure. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. [Is Plasmodium falciparum, the parasite responsible for tropical malaria, resistant to fansidar?].

    Science.gov (United States)

    Holzer, B; Keller, H; Frossard, E; Stürchler, D

    1980-03-01

    A world-wide increase of malaria infections is observed. Malaria is imported into Switzerland mainly by tourists and recently by refugees from South East Asia. The strains of P. falciparum resistant to treatment are of increasing importance. A patient with P. falciparum infection from Cambodia is reported, who suffered from three episodes of malaria recrudescence within ten weeks, in spite of adequate therapy with quinine and Fansidar. The definition, the significance and the geographical distribution of resistances and the possible cause for a P. falciparum recrudescence are discussed. For the treatment of repeating recrudescence quinine and Fansidar are recommended, followed by a suppressive Fansidar prophylaxy for 4--8 weeks.

  4. Spleen volume and clinical disease manifestations of severe Plasmodium falciparum malaria in African children.

    Science.gov (United States)

    Kotlyar, Simon; Nteziyaremye, Julius; Olupot-Olupot, Peter; Akech, Samuel O; Moore, Christopher L; Maitland, Kathryn

    2014-05-01

    Plasmodium falciparum malaria is common in African children. Severe disease manifestations include severe malarial anemia (SMA) and cerebral malaria (CM). In vitro studies suggest that splenic sequestration is associated with SMA and protective against CM. We sought to characterize the relationship between ultrasonographically derived spleen volume (SV), clinical manifestations and outcome. We conducted a prospective observational study of severe malaria and SV in children aged 3 months to 12 years in Eastern Uganda. An SV normogram was generated from 186 healthy controls and adjusted for total body surface area (TBSA). Children with severe P. falciparum malaria were classified according to disease phenotype, and SV z-scores were compared for cases and controls to assess the degree of spleen enlargement. One hundred and four children with severe malaria, median age 19.2 months, were enrolled; 54 were classified as having SMA and 15 with CM. Mortality was 27% in the CM group vs 1.9% in the SMA group. TBSA-adjusted SV z-scores were lower in children with CM compared to SMA (1.98 [95% CI 1.38-2.57] vs 2.73 [95% CI 2.41-3.04]; p=0.028). Mean SV z-scores were lower in children who died (1.20 [95% CI 0.14-2.25]) compared to survivors (2.58 [95% CI 2.35-2.81]); p=0.004. SV is lower in CM compared to SMA. Severe malaria with no increase in SV z-score may be associated with mortality.

  5. RELATIONSHIP OF HEPATIC AND RENAL DYSFUNCTION WITH HAEMORRHEOLOGICAL PARAMETERS IN PLASMODIUM FALCIPARUM MALARIA

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    Valluri Satya

    2015-04-01

    Full Text Available The clinical pattern of malaria has changed worldwide including India in last decade. Earlier cerebral malaria was the predominant manifestation of severe malaria, whereas now the combination of jaundice and renal failure are more common. Severe haemorrhage is seen in upto 5% of patients with severe malaria. Studies on renal and hepatic dys function in Plasmodium falciparum malaria are a plenty, but there is a paucity of studies correlating haemorrheological abnormalities with hepatic and renal dysfunction in Plasmodium falciparum malaria. METHODS : 100 patients of malaria with positive periph eral blood smear for plasmodium falciparum , out of which 50 cases with AKI and Hepatic failure during the period January 2012 - June 2013. I n department of general medicine, Government General Hospital, Kakinada. GROUP A : Comprising 50 consecutive adult pat ients of all age groups and both genders who had jaundice or renal failure or both at the time of admission. GROUP B: comprising 50 consecutive cases of plasmodium falciparum malaria and had no complications. RESULTS: In group A patients all parameters are significantly raised as compared to group B patients. CONCLUSION: 10% of patients had clinically overt bleeding manifestations, this indicates subclinical haemorrheological dysfunction in patients suffering from falciparum malaria with hepatic and renal d ysfunction, high incidence of subclinical DIC, evidenced by prolonged aPTT (56%, low total platelet count (58%, and PT (20%. An observational, screening, analytical prospective study. 100 cases of PF positive complicated and uncomplicated cases during t he period - January 2012 - June 2013

  6. Liver changes in severe Plasmodium falciparum malaria: histopathology, apoptosis and nuclear factor kappa B expression

    Science.gov (United States)

    2014-01-01

    Background Liver involvement in severe Plasmodium falciparum infection is commonly a significant cause of morbidity and mortality among humans. The clinical presentation of jaundice often reflects a certain degree of liver damage. This study investigated the liver pathology of severe P. falciparum malaria as well as the regulation and occurrence of apoptosis in cellular components of formalin-fixed, paraffin-embedded liver tissues. Methods The liver tissues used in the study came from patients who died from P. falciparum malaria with hyperbilirubinaemia (total bilirubin (TB) ≥ 51.3 μmol/L or 3 mg/dl) (12 cases), P. falciparum malaria without hyperbilirubinaemia (TB falciparum malaria were associated with higher TB level. Significant correlations were found between NF-κB p65 expression and apoptosis in Kupffer cells and lymphocytes in the portal tracts. Conclusions Hyperplastic Kupffer cells and portal tract inflammation are two main features found in the liver tissues of severe P. falciparum malaria cases. In addition, NF-κB is associated with Kupffer cells and lymphocyte apoptosis in severe P. falciparum malaria. PMID:24636003

  7. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria.

    Science.gov (United States)

    Mbengue, Alassane; Bhattacharjee, Souvik; Pandharkar, Trupti; Liu, Haining; Estiu, Guillermina; Stahelin, Robert V; Rizk, Shahir S; Njimoh, Dieudonne L; Ryan, Yana; Chotivanich, Kesinee; Nguon, Chea; Ghorbal, Mehdi; Lopez-Rubio, Jose-Juan; Pfrender, Michael; Emrich, Scott; Mohandas, Narla; Dondorp, Arjen M; Wiest, Olaf; Haldar, Kasturi

    2015-04-30

    Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination.

  8. Defining childhood severe falciparum malaria for intervention studies.

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    Philip Bejon

    2007-08-01

    Full Text Available Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no "gold standard" individual test for severe malaria, malaria-attributable fractions (MAFs can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints.A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor, lower respiratory tract infection (clinician's final diagnosis, meningitis (on cerebrospinal fluid [CSF] examination, and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%-86.1% without excluding these conditions, 89% (95% CI 88.4%-90.2% after exclusions, and 95% (95% CI 94.0%-95.5% when a threshold of 2,500 parasites/mul was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%-83%.The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician's diagnosis, bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition.

  9. The immuno-epidemiology of pregnancy-associated Plasmodium falciparum malaria: a variant surface antigen-specific perspective

    DEFF Research Database (Denmark)

    Hviid, L

    2004-01-01

    Women living in areas of intense P. falciparum transmission have acquired substantial protective immunity to malaria when they reach childbearing age. Nevertheless, pregnancies in such areas are associated with substantial malaria-related morbidity and mortality, particularly among women of low p...... understanding of how protective immunity to P. falciparum malaria operates and is acquired, have provided important insights into this enigma....

  10. Plasmodium falciparum malaria in infants under 5 kg: retrospective surveillance of hospital records in five sub-saharan African countries.

    Science.gov (United States)

    Alao, Maroufou J; Gbadoé, Adama D; Meremikwu, Martin; Tshefu, Antoinette; Tiono, Alfred B; Cousin, Marc; Hamed, Kamal

    2013-04-01

    To investigate the disease burden, clinical features, treatment and outcomes of Plasmodium falciparum malaria in neonates and infants weighing Plasmodium falciparum malaria exists in this subpopulation. Further epidemiological data are needed to estimate malaria morbidity and mortality in young infants. Moreover, clinical evidence on the efficacy and safety of artemisinin-based combination therapies in this subpopulation is warranted.

  11. Haptoglobin 1-1 is associated with susceptibility to severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Quaye, I K; Ekuban, F A; Goka, B Q

    2000-01-01

    The haptoglobin (Hp) phenotypes were determined by polyacrylamide-gel electrophoresis in plasma samples obtained in 1997 from 113 Plasmodium falciparum malaria patients (aged 1-12 years) with strictly defined cerebral malaria, severe malarial anaemia, or uncomplicated malaria and 42 age...... the reverse was seen with respect to Hp2-1 and Hp2-2. Our data suggest that the Hp1-1 phenotype is associated with susceptibility to P. falciparum malaria in general, and to the development of severe disease in particular....

  12. Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

    NARCIS (Netherlands)

    Teirlinck, A.C.; McCall, M.B.B.; Roestenberg, M.; Scholzen, A.; Woestenenk, R.M.; Mast, Q. de; Ven, A.J.A.M. van der; Hermsen, C.C.; Luty, A.J.F.; Sauerwein, R.W.

    2011-01-01

    Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNgamma) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation

  13. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

    NARCIS (Netherlands)

    Mbugi, E.V.; Mutayoba, B.M.; Malisa, A.L.; Balthazary, S.T.; Nyambo, T.B.; Mshinda, H.

    2006-01-01

    Background - Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods - The genes for

  14. Cortisol and uncomplicatedPlasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

    Institute of Scientific and Technical Information of China (English)

    Ibrahim EA; Kheir MM; Elhardello OA; Almahi WA; Ali NI; Elbashir MI; Ishag Adam

    2011-01-01

    Objective:To investigate the levels of serum cortisol in patients with uncomplicatedPlasmodium falciparum (P. falciparum) malaria in an area of unstable malaria transmission in eastern Sudan. Methods: The concentrations of cortisol were measured in sera of 25 patients with uncomplicated P. falciparum malaria (at presentation, 24 h and7 d later) and25 healthy volunteers using radioimmunoassay gamma counter.Results:There was no significant difference in mean(SD) of total cortisol levels in patients with malaria in comparison with the control group;602.2 (369.6)vs. 449.2(311.7)ng/mL,P=0.12. In patients with uncomplicatedP. falciparum malaria, the mean (SD) presenting cortisol levels were significantly higher in comparison to the levels on day7; 602.2 (369.6)vs.373.6(139.1)ng/mL,P=0.009. In the patients with uncomplicatedP. falciparum malaria (on presentation) cortisol levels were not correlated with initial temperature or the presenting parasitaemia.Conclusions: Thus, cortisol levels were not significantly different between the patients and the controls.

  15. A Comparative Study of Dihydroartemisinin Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

    Institute of Scientific and Technical Information of China (English)

    SONG Jian-ping(宋建平); Duong Socheat; Suou Seila

    2003-01-01

    Objective: To compare the safety and efficacy of two compounds of dihydroartemisinin (DHA) Artekin and Artekin (T) in the treatment of uncomplicated falciparum malaria. Methods: The regimen of 8-tablet for 2 days of Artekin and Artekin (T) were applied to 100 patients with uncomplicated falciparum malaria, who were randomly divided into two groups. Each group contained 50 cases. The cure rate, the mean parasites clearance time, the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compounds used. Results: The mean parasites clearance time was 31.7±9.0 hours in the Artekin group and 32.8±8.8 hours in Artekin (T) group respectively;the mean fever clearance time was 12.7±7.2 hours in Artekin group and 16.5±7.9 hours in Artekin (T) group; there were no recrudescence case in both groups within the 28 days of follow-up,the cure rates in Artekin group and Artekin (T) groups were 100%. It indicated that the tolerability of both compounds were very good, the side-effects such as nausea, abdominal pain were mild and self-limited. Conclusion: The study preliminarily indicated that the DHA and PQ compounds were of high efficacy, rapid acting and low toxicity. Artekin is very promising as a cheap, simple, effective treatment for multi-resistance malaria in Cambodia.

  16. Artesunate – amodiaquine combination therapy for falciparum malaria in young Gabonese children

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    Lell Bertrand

    2007-03-01

    Full Text Available Abstract Background Artesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce. Methods The effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32, compared with the efficacy when given under full supervision (n = 29 to children with falciparum malaria were assessed in an unrandomized study. Results 61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69 – 95 % in the supervised group and 63 % (20 of 32 patients; CI 45 – 77 % in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04. No severe adverse events were reported. Conclusion The effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation.

  17. Field performance of malaria rapid diagnostic test for the detection of Plasmodium falciparum infection in Odisha State, India

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    S S Sahu

    2015-01-01

    Full Text Available Background & objectives: Rapid diagnostic tests (RDTs have become an essential surveillance tool in the malaria control programme in India. The current study aimed to assess the performance of ParaHIT-f, a rapid test in diagnosis of Plasmodium falciparum infection through detecting its specific antigen, histidine rich protein 2 (PfHRP-2, in Odisha State, India. Methods: The study was undertaken in eight falciparum malaria endemic southern districts of Odisha State. Febrile patients included through active case detection, were diagnosed by Accredited Social Health Activists (ASHAs for P. falciparum infection using the RDT, ParaHIT-f. The performance of ParaHIT-f was evaluated using microscopy as the gold standard. Results: A total of 1030 febrile patients were screened by both microscopy and the RDT for P. falciparum infection. The sensitivity of ParaHIT-f was 63.6% (95% CI: 56.0-70.6 and specificity was 98.9% (95% CI: 97.9-99.5, with positive and negative predictive values (PPV and NPV of 92.6% (95% CI: 86.0-96.3 and 93.0% (95% CI: 91.0-94.5, respectively. When related to parasitaemia, the RDT sensitivity was 47.8% at the low parasitaemia of 4 to 40 parasites/µl of blood. Interpretation & conclusions: The results showed that the performance of the RDT, ParaHIT-f, was not as sensitive as microscopy in detecting true falciparum infections; a high specificity presented a low frequency of false-positive RDT results. t0 he sensitivity of ParaHIT-f was around 60 per cent. It is, therefore, essential to improve the efficiency (sensitivity of the kit so that the true falciparum infections will not be missed especially in areas where P. falciparum has been the predominant species causing cerebral malaria.

  18. Chloroquine- and sulfadoxine-pyrimethamine-resistant falciparum malaria in vivo - a pilot study in rural Zambia

    NARCIS (Netherlands)

    Bijl, HM; Kager, J; Koetsier, DW; van der Werf, TS

    2000-01-01

    BACKGROUND Chloroquine (CQ) and Sulfadoxine-Pyrimethamine (SP) are the predominantly used antimalarials in Zambia and other parts of East Africa, but increasing resistance of P. falciparum is a major concern. METHODS Seventy consecutive patients with uncomplicated falciparum malaria were enrolled.

  19. Falciparum malaria: sticking up, standing out and out-standing.

    Science.gov (United States)

    Cooke, B; Coppel, R; Wahlgren, M

    2000-10-01

    Cytoadherence is believed to be fundamental for the survival of Plasmodium falciparum in vivo and, uniquely, is a major determinant of the virulence of this parasite. Despite the widely professed importance of cytoadhesion in the development of severe disease, there are a number of aspects of this highly complex process that remain poorly understood. Recent progress in the understanding of cytoadhesive phenomena was discussed extensively at the Molecular Approaches to Malaria conference, Lorne, Australia, 2-5 February 2000. Here, Brian Cooke, Mats Wahlgren and Ross Coppel consider just how far we have progressed during the past 30 years and highlight what is still missing in our understanding of the mechanisms and clinical relevance of this apparently vital process.

  20. Mitosis in the Human Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Gerald, Noel; Mahajan, Babita; Kumar, Sanjai

    2011-01-01

    Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. PMID:21317311

  1. Distinct patterns of cytokine regulation in discrete clinical forms of Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Akanmori, B D; Kurtzhals, J A; Goka, B Q;

    2000-01-01

    The pathogenesis of two of the most severe complications of Plasmodium falciparum malaria, cerebral malaria (CM) and severe malarial anaemia (SA) both appear to involve dysregulation of the immune system. We have measured plasma levels of TNF and its two receptors in Ghanaian children with strictly...... defined cerebral malaria (CM), severe malarial anaemia (SA), or uncomplicated malaria (UM) in two independent studies in an area of seasonal, hyperendemic transmission of P. falciparum. Levels of TNF, soluble TNF receptor 1 (sTNF-R1) and 2 (sTNF-R2) were found to be significantly higher in CM than...... in the other clinical categories of P. falciparum malaria patients. Levels of both receptors depended on clinical category, whereas only sTNF-R1 levels were significantly dependent on parasitemia. Detailed analysis of the interrelationship between these variables resolved this pattern further, and identified...

  2. Targeting glycolysis in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    van Niekerk, David D; Penkler, Gerald P; du Toit, Francois; Snoep, Jacky L

    2016-02-01

    Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand. The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.bio.vu.nl/database/vanniekerk1. The SEEK-study including the experimental data set is available at DOI 10.15490/seek.1. 56 (http://dx.doi.org/10.15490/seek.1. 56). © 2015 FEBS.

  3. Imputation-based population genetics analysis of Plasmodium falciparum malaria parasites.

    Science.gov (United States)

    Samad, Hanif; Coll, Francesc; Preston, Mark D; Ocholla, Harold; Fairhurst, Rick M; Clark, Taane G

    2015-04-01

    Whole-genome sequencing technologies are being increasingly applied to Plasmodium falciparum clinical isolates to identify genetic determinants of malaria pathogenesis. However, genome-wide discovery methods, such as haplotype scans for signatures of natural selection, are hindered by missing genotypes in sequence data. Poor correlation between single nucleotide polymorphisms (SNPs) in the P. falciparum genome complicates efforts to apply established missing-genotype imputation methods that leverage off patterns of linkage disequilibrium (LD). The accuracy of state-of-the-art, LD-based imputation methods (IMPUTE, Beagle) was assessed by measuring allelic r2 for 459 P. falciparum samples from malaria patients in 4 countries: Thailand, Cambodia, Gambia, and Malawi. In restricting our analysis to 86 k high-quality SNPs across the populations, we found that the complete-case analysis was restricted to 21k SNPs (24.5%), despite no single SNP having more than 10% missing genotypes. The accuracy of Beagle in filling in missing genotypes was consistently high across all populations (allelic r2, 0.87-0.96), but the performance of IMPUTE was mixed (allelic r2, 0.34-0.99) depending on reference haplotypes and population. Positive selection analysis using Beagle-imputed haplotypes identified loci involved in resistance to chloroquine (crt) in Thailand, Cambodia, and Gambia, sulfadoxine-pyrimethamine (dhfr, dhps) in Cambodia, and artemisinin (kelch13) in Cambodia. Tajima's D-based analysis identified genes under balancing selection that encode well-characterized vaccine candidates: apical merozoite antigen 1 (ama1) and merozoite surface protein 1 (msp1). In contrast, the complete-case analysis failed to identify any well-validated drug resistance or candidate vaccine loci, except kelch13. In a setting of low LD and modest levels of missing genotypes, using Beagle to impute P. falciparum genotypes is a viable strategy for conducting accurate large-scale population genetics and

  4. Longevity and composition of cellular immune responses following experimental Plasmodium falciparum malaria infection in humans.

    Directory of Open Access Journals (Sweden)

    Anne C Teirlinck

    2011-12-01

    Full Text Available Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz and asexual blood-stage (PfRBC malaria parasites in naïve human volunteers undergoing single (n = 5 or multiple (n = 10 experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2 responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only 'adaptive' but also 'innate' lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO(+ CD62L(- effector memory (EM phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ(+IL-2(+ EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P

  5. Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

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    Tyagi Prajesh K

    2008-12-01

    Full Text Available Abstract Background Host adhesion molecules play a significant role in the pathogenesis of Plasmodium falciparum malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, ICAM1, PECAM1 and CD36, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India. Methods The frequency distribution of seven selected SNPs of ICAM1, PECAM1 and CD36 was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR for risk assessment was estimated using EpiInfo™ version 3.4. Results Association of the ICAM1 rs5498 (exon 6 G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively. The CD36 rs1334512 (-53 T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004. Interestingly, a SNP of the PECAM1 gene (rs668, exon 3, C/G with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region. Conclusion The data highlights the significance of variations in the ICAM1, PECAM1 and CD36 genes in the manifestation of falciparum malaria in India. The PECAM1 exon 3 SNP exhibits altered association with disease in the

  6. Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum

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    Theander Thor G

    2007-11-01

    Full Text Available Abstract Background In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant Plasmodium falciparum. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of P. falciparum in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP or amodiaquine (AQ. Methods One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA, and IgG antibody responses to a panel of P. falciparum antigens were assessed and related to treatment outcome. Results Parasitological or clinical treatment failure (TF was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP-specific IgG antibodies were significantly higher (P Conclusion These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity.

  7. Protease-associated cellular networks in malaria parasite Plasmodium falciparum

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    Lilburn Timothy G

    2011-12-01

    Full Text Available Abstract Background Malaria continues to be one of the most severe global infectious diseases, responsible for 1-2 million deaths yearly. The rapid evolution and spread of drug resistance in parasites has led to an urgent need for the development of novel antimalarial targets. Proteases are a group of enzymes that play essential roles in parasite growth and invasion. The possibility of designing specific inhibitors for proteases makes them promising drug targets. Previously, combining a comparative genomics approach and a machine learning approach, we identified the complement of proteases (degradome in the malaria parasite Plasmodium falciparum and its sibling species 123, providing a catalog of targets for functional characterization and rational inhibitor design. Network analysis represents another route to revealing the role of proteins in the biology of parasites and we use this approach here to expand our understanding of the systems involving the proteases of P. falciparum. Results We investigated the roles of proteases in the parasite life cycle by constructing a network using protein-protein association data from the STRING database 4, and analyzing these data, in conjunction with the data from protein-protein interaction assays using the yeast 2-hybrid (Y2H system 5, blood stage microarray experiments 678, proteomics 9101112, literature text mining, and sequence homology analysis. Seventy-seven (77 out of 124 predicted proteases were associated with at least one other protein, constituting 2,431 protein-protein interactions (PPIs. These proteases appear to play diverse roles in metabolism, cell cycle regulation, invasion and infection. Their degrees of connectivity (i.e., connections to other proteins, range from one to 143. The largest protease-associated sub-network is the ubiquitin-proteasome system which is crucial for protein recycling and stress response. Proteases are also implicated in heat shock response, signal peptide

  8. The use of activated protein C in severe Plasmodium falciparum malaria.

    Science.gov (United States)

    Rankin, L G; Austin, D L H

    2007-06-01

    A 56-year-old man presented to a peripheral hospital in New Zealand with severe Plasmodium falciparum malaria with cerebral involvement and subsequently developed multi-system organ failure. Activated protein C was used in an attempt to stop the cascade of events into multi-organ failure. Severe infection with P. falciparum is life-threatening and appears to activate a hypercoagulable state similar to that of severe sepsis. Activated protein C is currently used in the treatment of severe sepsis and may provide a new adjuvant therapy for severe P. falciparum malaria.

  9. The relationship between the haemoglobin concentration and the haematocrit in Plasmodium falciparum malaria

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    Newton Paul

    2008-08-01

    Full Text Available Abstract Background Malaria is a very important cause of anaemia in tropical countries. Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration. For comparisons across studies, it is often necessary to derive one measure from the other. Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries, to assess the haemoglobin/haematocrit relationship at different time points in malaria. Using a linear random effects model, a conversion equation for haematocrit was derived based on 3,254 measurements from various time points (ranging from day 0 to day 63 from 1,810 patients with simultaneous measurements of both parameters. Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion. Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin. On average, haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference (± SD of -0.69 (± 1.3 for children under the age of 5 (n = 1,440 measurements from 449 patients. Conclusion Based on this large data set, an accurate and robust conversion factor both in acute malaria and in convalescence was obtained. The commonly used threefold conversion is also valid.

  10. Non-falciparum malaria infections in pregnant women in West Africa

    DEFF Research Database (Denmark)

    Williams, John; Njie, Fanta; Cairns, Matthew;

    2016-01-01

    and treatment of malaria in pregnancy (ISTp) versus intermittent preventive treatment (IPTp) conducted in Burkina Faso, The Gambia, Ghana and Mali. DNA was extracted from blood spots and tested for P. falciparum, Plasmodium vivax, Plasmodium malariae and Plasmodium ovale using a nested PCR test. Risk factors...

  11. Recrudescence of Plasmodium falciparum malaria contracted in Lombok, Indonesia after quinine/doxycycline and mefloquine: case report.

    Science.gov (United States)

    Tish, K N; Pillans, P I

    1997-07-11

    A patient is reported who contracted Plasmodium falciparum malaria in Lombok, Indonesia. The infection recrudesced after quinine/doxycycline and mefloquine. Treatment with halofantrine was successful after he developed cerebral malaria with recovery.

  12. Association of CD40L gene polymorphism with severe Plasmodium falciparum malaria in Indian population.

    Science.gov (United States)

    Purohit, Prasanta; Mohanty, Pradeep Kumar; Patel, Siris; Das, Padmalaya; Das, Kishalaya; Panigrahi, Jogeswar

    2017-01-01

    Many host genetic factors are associated with the disease severity and fatal outcome of falciparum malaria. CD40L gene has been found to be one of the most important factors associated with malaria in African countries. This study was aimed to investigate the possible association of CD40L gene polymorphism in severe falciparum malaria in Indian adults. One hundred fifteen adult cases with severe falciparum malaria were included in the study. Two single- nucleotide polymorphisms (SNPs) of CD40L gene, CD40L-726(C/T) and CD40L+220(C/T) were investigated, and the possible association with different clinical sub-phenotypes of severe falciparum malaria were analyzed. Statistically no significant difference was observed in the incidence of CD40L-726C between the patients and control group. The incidence of CD40L+220C allele was found to be significantly higher (OR, 2.25; p = 0.03) in male patients compared to controls but no significant difference was observed in females. Haplotype data showed the susceptibility of -726T/+220C haplotype to severe malaria whereas -726C/+220T was associated with protection against severe malaria. CD40L+220C allele was associated with severe malarial anaemia in males (χ2 = 6.60; p = 0.01). CD40L gene polymorphism was found to be associated with severe falciparum malaria in Indian population especially in severe malarial anaemia. CD40L may be considered as a factor of immunity in understanding the pathophysiology of falciparum malaria.

  13. Natural antibody responses to Plasmodium falciparum MSP3 and GLURP(R0) antigens are associated with low parasite densities in malaria patients living in the Central Region of Ghana

    DEFF Research Database (Denmark)

    Amoah, L. E.; Nuvor, S. V.; Obboh, E. K.

    2017-01-01

    and adults diagnosed with uncomplicated P. falciparum malaria. Microscopy was used to estimate P. falciparum parasite density and polymerase chain reaction (PCR) amplification of the polymorphic regions of msp1 (PF3D7-0930300) and msp2 (PF3D7-0206800) was used for parasite genotyping and MOI determination......Background: Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are parasite features that have been suggested to influence the acquisition of protective immunity against malaria. This study sought to assess the relationship between MOI and parasite density (PD) in malaria...

  14. Deployment of early diagnosis and mefloquine-artesunate treatment of falciparum malaria in Thailand: the Tak Malaria Initiative.

    Directory of Open Access Journals (Sweden)

    Verena Ilona Carrara

    2006-06-01

    Full Text Available BACKGROUND: Early diagnosis and treatment with artesunate-mefloquine combination therapy (MAS have reduced the transmission of falciparum malaria dramatically and halted the progression of mefloquine resistance in camps for displaced persons along the Thai-Burmese border, an area of low and seasonal transmission of multidrug-resistant Plasmodium falciparum. We extended the same combination drug strategy to all other communities (estimated population 450,000 living in five border districts of Tak province in northwestern Thailand. METHODS AND FINDINGS: Existing health structures were reinforced. Village volunteers were trained to use rapid diagnostic tests and to treat positive cases with MAS. Cases of malaria, hospitalizations, and malaria-related deaths were recorded in the 6 y before, during, and after the Tak Malaria Initiative (TMI intervention. Cross-sectional surveys were conducted before and during the TMI period. P. falciparum malaria cases fell by 34% (95% confidence interval [CI], 33.5-34.4 and hospitalisations for falciparum malaria fell by 39% (95% CI, 37.0-39.9 during the TMI period, while hospitalisations for P. vivax malaria remained constant. There were 32 deaths attributed to malaria during, and 22 after the TMI, a 51.5% (95% CI, 39.0-63.9 reduction compared to the average of the previous 3 y. Cross-sectional surveys indicated that P. vivax had become the predominant species in Thai villages, but not in populations living on the Myanmar side of the border. In the displaced persons population, where the original deployment took place 7 y before the TMI, the transmission of P. falciparum continued to be suppressed, the incidence of falciparum malaria remained low, and the in vivo efficacy of the 3-d MAS remained high. CONCLUSIONS: In the remote malarious north western border area of Thailand, the early detection of malaria by trained village volunteers, using rapid diagnostic tests and treatment with mefloquine-artesunate was

  15. Schistosoma haematobium and Plasmodium falciparum co-infection with protection against Plasmodium falciparum ma-laria in Nigerian children

    Institute of Scientific and Technical Information of China (English)

    Nmorsi OPG; Isaac C; Ukwandu NCD; Ekundayo AO; Ekozien MI

    2009-01-01

    Objective:Malaria remains the single leading killer of children in sub -Sahara Africa and Schistosomiasis is considered to be second to malaria in global importance.Co -infection of malaria and urinary schistosomiasis has been reported to exacerbate disease morbidity such as anaemia.In different part of the globe,the co -in-fection between malaria and schistosomiasis provides some protections on the infected persons.The protective effect of this co -infection elucidated immunologically using cytokines is lacking in our locality.Methods:U-rine and blood samples obtained from the 160 volunteers were subjected to standard parasitological techniques for diagnosis of urinary schistosomiasis and malaria respectively.Blood samples collected from these volunteers comprising 80 children with schistosomiasis and malaria and the 80 children who had malaria only were subjec-ted to cytokines concentration determination using commercial standard enzyme linked immunosorbent assay kits (Abcam,UK).Results:Eighty participants with co -infection had a mean malarial parasitaemia of 662 ±201.1 μL while the 80 participants with only P.falciparum malaria had a mean malarial parasiteamia of 5943 ±3270.7μL.Also the volunteers had mean haemoglobin of 11.2 g/dL for co -infected individuals and 5.7 g/dL for participants with single infection of malaria.The serum cytokine levels of the children with S. haematobium and P.falciparum and only P.falciparum infection are as follows;interleukin -4 (16.6 pg/mL versus 5.2 pg/mL),IL -5 (501.3 pg/mL versus 357.5 pg/mL);IL -8 (2 550 pg/mL versus 309 pg/mL),IL -10 (273 pg/mL versus 290 pg/mL),TNF -α(25 pg/mL versus 290 pg/mL)and IFN -γ(21.9 pg/mL versus 2.5 pg/mL).The TNF -α/IL -10 ratio is 7 for the children with co -infection while those with only P.falciparum malaria infection had a TNF -α/IL -10 ratio of 0.9.Conclusion:We con-clude that the elevated IL -4,IL -5,IL -8 and IFN -γconcentration induced by schistosomiasis altered the Th1 /Th 2

  16. A clinical trial with halofantrine on patients with falciparum malaria in Colombia.

    OpenAIRE

    Restrepo, M.; Botero, D.; Marquez, R. E.; Boudreau, E. F.; Navaratnam, V.

    1996-01-01

    A total of 120 semi-immune adult male malaria patients from an area of multidrug-resistant Plasmodium falciparum malaria were hospitalized for 42 days in Medellin, Colombia (an area of no malaria transmission), and treated with halofantrine in a double-blind, randomized, prospective clinical trial according to five different treatment schedules. Each patient was assigned to one of the following halofantrine schedules: I, one dose of 1000 mg; II, three doses of 500 mg; III, two doses of 500 mg...

  17. Increased plasma levels of soluble IL-2R are associated with severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Jakobsen, P H; Morris-Jones, S; Theander, T G;

    1994-01-01

    Plasma samples from children with mild and severe Plasmodium falciparum malaria and from children with unrelated diseases were collected to investigate whether the clinical outcome of infection was associated with plasma factors which reflected the activity of different cells of the immune system....... Children with severe P. falciparum malaria had significantly higher plasma levels of soluble IL-2R than children with mild malaria. Plasma levels of IL-2R and levels of parasitaemia were significantly correlated. Neither parasitaemia nor plasma levels of tumour necrosis factor-alpha (TNF-alpha), IL-6......, lymphotoxin (LT), interferon-gamma (IFN-gamma), IL-4, soluble IL-4R or soluble CD8 differed significantly between the two groups of children with malaria. High plasma levels of soluble CD8 were associated with failure of lymphocytes to produce IFN-gamma in vitro following stimulation with P. falciparum...

  18. Evidence of endothelial inflammation, T cell activation, and T cell reallocation in uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Elhassan, I M; Hviid, L; Satti, G

    1994-01-01

    To explain the observation that acute Plasmodium falciparum malaria is associated with a transient inability of peripheral blood cells to respond to antigenic stimulation in vitro, we have postulated the disease-induced reallocation of peripheral lymphocytes, possibly by adhesion to inflamed...... endothelium. We measured plasma levels of soluble markers of endothelial inflammation and T cell activation in 32 patients suffering from acute, uncomplication P. falciparum malaria, as well as in 10 healthy, aparasitemic control donors. All donors were residents of a malaria-endemic area of Eastern State...... with the control donors. In addition, we found a disease-induced depletion of T cells with high expression of the LFA-1 antigen, particularly in the CD4+ subset. The results obtained provide further support for the hypothesis of T cell reallocation to inflamed endothelium in acute P. falciparum malaria....

  19. Falciparum malaria as an emerging cause of fever in adults living in Gabon, Central Africa.

    Science.gov (United States)

    Bouyou-Akotet, Marielle K; Offouga, Christelle L; Mawili-Mboumba, Denise P; Essola, Laurence; Madoungou, Blondel; Kombila, Maryvonne

    2014-01-01

    Following the observed increase of malaria prevalence among older children in Gabon, a descriptive observational study was carried out in 2012 to determine the prevalence of malaria in adults presenting with fever in two health centres of Libreville, the capital city of Gabon. Thick- and thin-blood smears for malaria diagnosis were performed in febrile individuals aged more than 15 years old. Age, use of bed nets, previous antimalarial drug treatment, clinical symptoms, chest radiography results, and available haemoglobin data were also recorded. Among the 304 patients screened, the global malaria frequency was of 42.1% (n = 128/34). Plasmodium (P). falciparum was the only species identified. The proportion of patients with a clinical malaria requiring parenteral treatment was 38.5%, whereas 47.5% of outpatients had uncomplicated malaria. According to WHO classification, 14 (19.7%) infected patients had severe malaria; neurological and respiratory symptoms tended to be more frequent in case of P. falciparum infection. Anaemia was found in 51.5% adults and none had severe anaemia. Almost half of adults consulting for fever in two health centres of the urban city of Libreville have malaria. The use of insecticide-treated bed nets, the screening, and the treatment of individuals with P. falciparum microscopic and submicroscopic asymptomatic infection or clinical malaria should be emphasized to reduce the transmission.

  20. Comparative population structure of Plasmodium malariae and Plasmodium falciparum under different transmission settings in Malawi

    Directory of Open Access Journals (Sweden)

    Molyneux Malcolm E

    2011-02-01

    Full Text Available Abstract Background Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. Methods Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI, population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. Results Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008 and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11 and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission

  1. Differential induction of functional IgG using the Plasmodium falciparum placental malaria vaccine candidate VAR2CSA

    DEFF Research Database (Denmark)

    Pinto, Vera V; Ditlev, Sisse B; Jensen, Kamilla E

    2011-01-01

    In Plasmodium falciparum malaria endemic areas placental malaria (PM) is an important complication of malaria. The recurrence of malaria in primigravidae women irrespective of acquired protection during childhood is caused by the interaction between the parasite-expressed VAR2CSA antigen...

  2. Optimising strategies for Plasmodium falciparum malaria elimination in Cambodia: primaquine, mass drug administration and artemisinin resistance.

    Directory of Open Access Journals (Sweden)

    Richard J Maude

    Full Text Available BACKGROUND: Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria. METHOD AND FINDINGS: A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity. CONCLUSIONS: The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite

  3. MÉTODOS PROTEÓMICOS APLICADOS AL ESTUDIO DE LA MALARIA: Plasmodium falciparum Proteomics Methods Applied to Malaria: Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    YESID CUESTA ASTROZ

    2012-12-01

    vertebrate host and mosquito vector. It has proven difficult to characterize the protein expression during each stage throughout the infection process in order to determine the proteome that mediates several metabolic, physiological and energetic processes. Two dimensional electrophoresis, liquid chromatography and mass spectrometry have been useful to assess the effects of antimalarials on parasite protein expression and to characterize the proteomic profile of differentt P. falciparum stages and organelles. The purpose of this review is to present state of the art tools and advances in proteomics applied to the study of malaria, and to present different experimental strategies used to study the parasite's proteome in order to show the advantages and disadvantages of each one.

  4. Immunoglobulin G antibody reactivity to a group A Plasmodium falciparum erythrocyte membrane protein 1 and protection from em>P. falciparum malaria

    DEFF Research Database (Denmark)

    Magistrado, Pamela A; Lusingu, John; Vestergaard, Lasse S;

    2007-01-01

    Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas...... where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP...

  5. Antibodies in falciparum malaria: what matters most, quantity or quality?

    Directory of Open Access Journals (Sweden)

    Hasnaa Bouharoun-Tayoun

    1992-01-01

    Full Text Available In view of the recent demonstration that antibodies that are protective agains Plasmodium falciparum malaria may act in collaboration with blood monocytes, we have investigated the isotype content of sera from individuals with defined clinical states of resistance or susceptibility to malaria. Profound differences in the distribution of each Ig subclass and particulary in the ratio of cytophilic versus noncytophilic antibodies were found. In protected subjects, two cytophilic isotypes, IgG1 and IgG3 were found to predominate. In non-protected subjects, i.e. children and primary attack adults, three different situations were encountered: a an imbalance in which IgG2, a non-cytophilic class, predominated (mostly seen in primary attacks; b imbalance in which mostly IgM antibodies predominated (a frequent event in children or c less frequently, an overall low level of antimalarial antibodies. Of 33 non immune subjects studied all, except one, had one of the above defects. The function of total Ig presenting such an isotype imbalance was studied in vitro in Antibody-Dependent -Cellular-Inhibition assays. Not only did IgG from protected subjects cooperate efficiently with blood monocytes, whilst IgG from non-protected groups did not, but moreover the latter inhibit the in vitro effect of the former: in competition assays whole IgG from primary attack cases with increased IgG2 content, competed with IgG from immune adults, thus suggesting that non-protected subjects had antibodies to epitopes critical for protection, but that these antibodies are non functional.

  6. Dihydroartemisinin-piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study.

    Science.gov (United States)

    Amaratunga, Chanaki; Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Mao, Sivanna; Sopha, Chantha; Sam, Baramey; Dek, Dalin; Try, Vorleak; Amato, Roberto; Blessborn, Daniel; Song, Lijiang; Tullo, Gregory S; Fay, Michael P; Anderson, Jennifer M; Tarning, Joel; Fairhurst, Rick M

    2016-03-01

    Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin-piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia. In this prospective cohort study, we enrolled patients aged 2-65 years with uncomplicated P falciparum malaria in three Cambodian provinces: Pursat, Preah Vihear, and Ratanakiri. Participants were given standard 3-day courses of dihydroartemisinin-piperaquine. Peripheral blood parasite densities were measured until parasites cleared and then weekly to 63 days. The primary outcome was recrudescent P falciparum parasitaemia within 63 days. We measured piperaquine plasma concentrations at baseline, 7 days, and day of recrudescence. We assessed phenotypic and genotypic markers of drug resistance in parasite isolates. The study is registered with ClinicalTrials.gov, number NCT01736319. Between Sept 4, 2012, and Dec 31, 2013, we enrolled 241 participants. In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did. Patients with recrudescent P falciparum infections were more likely to have detectable piperaquine plasma concentrations at baseline compared with non-recrudescent patients, but did not differ significantly in age, initial parasite density, or piperaquine plasma concentrations at 7 days. Recrudescent parasites had a higher prevalence of kelch13 mutations, higher piperaquine 50% inhibitory

  7. Dihydroartemisinin–piperaquine resistance in Plasmodium falciparum malaria in Cambodia: a multisite prospective cohort study

    Science.gov (United States)

    Amaratunga, Chanaki; Lim, Pharath; Suon, Seila; Sreng, Sokunthea; Mao, Sivanna; Sopha, Chantha; Sam, Baramey; Dek, Dalin; Try, Vorleak; Amato, Roberto; Blessborn, Daniel; Song, Lijiang; Tullo, Gregory S; Fay, Michael P; Anderson, Jennifer M; Tarning, Joel; Fairhurst, Rick M

    2016-01-01

    Background Artemisinin resistance in Plasmodium falciparum threatens to reduce the efficacy of artemisinin combination therapies (ACTs), thus compromising global efforts to eliminate malaria. Recent treatment failures with dihydroartemisinin-piperaquine, the current first-line ACT in Cambodia, suggest that piperaquine resistance may be emerging in this country. We explored the relation between artemisinin resistance and dihydroartemisinin–piperaquine failures, and sought to confirm the presence of piperaquine-resistant P falciparum infections in Cambodia. Methods In this prospective cohort study, we enrolled patients aged 2–65 years with uncomplicated P falciparum malaria in three Cambodian provinces: Pursat, Preah Vihear, and Ratanakiri. Participants were given standard 3-day courses of dihydroartemisinin–piperaquine. Peripheral blood parasite densities were measured until parasites cleared and then weekly to 63 days. The primary outcome was recrudescent P falciparum parasitaemia within 63 days. We measured piperaquine plasma concentrations at baseline, 7 days, and day of recrudescence. We assessed phenotypic and genotypic markers of drug resistance in parasite isolates. The study is registered with ClinicalTrials.gov, number NCT01736319. Findings Between Sept 4, 2012, and Dec 31, 2013, we enrolled 241 participants. In Pursat, where artemisinin resistance is entrenched, 37 (46%) of 81 patients had parasite recrudescence. In Preah Vihear, where artemisinin resistance is emerging, ten (16%) of 63 patients had recrudescence and in Ratanakiri, where artemisinin resistance is rare, one (2%) of 60 patients did. Patients with recrudescent P falciparum infections were more likely to have detectable piperaquine plasma concentrations at baseline compared with non-recrudescent patients, but did not differ significantly in age, initial parasite density, or piperaquine plasma concentrations at 7 days. Recrudescent parasites had a higher prevalence of kelch13 mutations

  8. Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria.

    Science.gov (United States)

    Berg, Aase; Otterdal, Kari; Patel, Sam; Gonca, Miguel; David, Catarina; Dalen, Ingvild; Nymo, Stig; Nilsson, Margareta; Nordling, Sofia; Magnusson, Peetra U; Ueland, Thor; Prato, Mauro; Giribaldi, Giuliana; Mollnes, Tom Eirik; Aukrust, Pål; Langeland, Nina; Nilsson, Per H

    2015-12-01

    The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Clinical factors for severity of Plasmodium falciparum malaria in hospitalized adults in Thailand.

    Directory of Open Access Journals (Sweden)

    Patrick Sagaki

    Full Text Available Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases and 151 patients with non-severe malaria (controls. Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1 referrals, (2 no prior history of malaria, (3 body temperature of >38.5°C, (4 white blood cell counts >10×10(9/µL, (5 presence of schizonts in peripheral blood smears, and (6 albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05. Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1 ethnicity of Thai [odds ratio (OR = 3.601, 95% confidence interval (CI = 1.011-12.822] or Myanmar [OR = 3.610, 95% CI = 1.138-11.445]; (2 referrals [OR = 3.571, 95% CI = 1.306-9.762]; (3 no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4 albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop

  10. Clinical Factors for Severity of Plasmodium falciparum Malaria in Hospitalized Adults in Thailand

    Science.gov (United States)

    Sagaki, Patrick; Thanachartwet, Vipa; Desakorn, Varunee; Sahassananda, Duangjai; Chamnanchanunt, Supat; Chierakul, Wirongrong; Pitisuttithum, Punnee; Ruangkanchanasetr, Prajej

    2013-01-01

    Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×109/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011–12.822] or Myanmar [OR = 3.610, 95% CI = 1.138–11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306–9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354–25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802–28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could

  11. Incidence, management, and reporting of severe and fatal Plasmodium falciparum malaria in secondary and tertiary health facilities of Alipurduar, India in 2009.

    Science.gov (United States)

    Sarkar, Jagannath; Shah, Naman K; Murhekar, Manoj V

    2012-09-01

    The proportion of malaria cases that are complicated and fatal are not well described in India. Alipurduar sub-division of Jalpaiguri district in West Bengal is highly endemic for malaria. We constructed a retrospective cohort of severe malaria patients admitted in the secondary and tertiary care facilities in Alipurduar to determine the incidence, assess the management, and evaluate the reporting of severe and fatal malaria. We reviewed routine surveillance data and the case records of all the malaria patients admitted in all secondary and tertiary care facilities, both public and private. We defined severe malaria cases as Plasmodium falciparum infection with clinical signs and symptoms of organ involvement in a resident of Alipurduar admitted during January to December 2009. We compared clinical and demographic characteristics of severe malaria cases that died with those who survived. We also reviewed human resources and laboratory facilities available for the treatment of severe malaria in these health facilities. During 2009, 6191 cases of P. falciparum in Alipurduar were reported to the malaria surveillance system. We identified 336 (5.4%) cases of severe malaria among which 33 (9.8%) patients died. Four malaria deaths were also recorded from primary health centres. Only 17 of the 37 (46%) total deaths recorded were reported to the routine surveillance system. Most severe cases were males (65%), aged >15 years (72%), and nearly half were admitted to secondary care hospitals (48%). In multivariate analysis, the risk factors associated with death included increased delay fever onset and hospitalization, treatment in a secondary level hospital, younger age, and multi-organ involvement. The secondary level public hospital had too few physicians and nurses for supporting severe malaria patients as well as inadequate laboratory facilities for monitoring such patients. Severe and fatal malaria continue to burden Alipurduar and record keeping in health facilities was

  12. Nuclear factor kappa B in urine sediment: a useful indicator to detect acute kidney injury in Plasmodium falciparum malaria.

    Science.gov (United States)

    Punsawad, Chuchard; Viriyavejakul, Parnpen

    2014-03-07

    Acute kidney injury (AKI) is one of the major complications of Plasmodium falciparum malaria, especially among non-immune adults. It has recently been revealed that activation of transcription factor nuclear factor kappa B (NF-κB) induces pro-inflammatory gene expression involved in the development of progressive renal inflammatory diseases. The aim of this study was to determine whether urinary sediment NF-κB p65 can act as a biomarker for AKI in patients with P. falciparum malaria. Urinary sediments from malaria patients, including Plasmodium vivax malaria, uncomplicated P. falciparum malaria, complicated P. falciparum malaria without AKI (serum creatinine-Cr falciparum malaria with AKI (Cr ≥3 mg/dl) were used to determine NF-κB p65 level by sandwich enzyme-linked immunosorbent assay (ELISA). Urinary sediments obtained from healthy controls were used as a normal baseline. Correlations between levels of urinary sediment NF-κB p65 and pertinent clinical data were analysed. Urinary sediment NF-κB p65 levels were significantly increased on the day of admission (day 0) and on day 7 post-treatment in complicated P. falciparum malaria patients with AKI, compared with those without AKI (p=0.001, p falciparum malaria.

  13. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria

    Science.gov (United States)

    Ariey, Frédéric; Witkowski, Benoit; Amaratunga, Chanaki; Beghain, Johann; Langlois, Anne-Claire; Khim, Nimol; Kim, Saorin; Duru, Valentine; Bouchier, Christiane; Ma, Laurence; Lim, Pharath; Leang, Rithea; Duong, Socheat; Sreng, Sokunthea; Suon, Seila; Chuor, Char Meng; Bout, Denis Mey; Ménard, Sandie; Rogers, William O.; Genton, Blaise; Fandeur, Thierry; Miotto, Olivo; Ringwald, Pascal; Le Bras, Jacques; Berry, Antoine; Barale, Jean-Christophe; Fairhurst, Rick M.; Benoit-Vical, Françoise; Mercereau-Puijalon, Odile; Ménard, Didier

    2014-01-01

    Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain (`K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

  14. Sickle Cell Trait and the Risk of Plasmodium falciparum Malaria and Other Childhood Diseases

    Science.gov (United States)

    Williams, Thomas N.; Mwangi, Tabitha W.; Wambua, Sammy; Alexander, Neal D.; Kortok, Moses; Snow, Robert W.; Marsh, Kevin

    2012-01-01

    Background The gene for sickle hemoglobin (HbS) is a prime example of natural selection. It is generally believed that its current prevalence in many tropical populations reflects selection for the carrier form (sickle cell trait [HbAS]) through a survival advantage against death from malaria. Nevertheless, >50 years after this hypothesis was first proposed, the epidemiological description of the relationships between HbAS, malaria, and other common causes of child mortality remains incomplete. Methods We studied the incidence of falciparum malaria and other childhood diseases in 2 cohorts of children living on the coast of Kenya. Results The protective effect of HbAS was remarkably specific for falciparum malaria, having no significant impact on any other disease. HbAS had no effect on the prevalence of symptomless parasitemia but was 50% protective against mild clinical malaria, 75% protective against admission to the hospital for malaria, and almost 90% protective against severe or complicated malaria. The effect of HbAS on episodes of clinical malaria was mirrored in its effect on parasite densities during such episodes. Conclusions The present data are useful in that they confirm the mechanisms by which HbAS confers protection against malaria and shed light on the relationships between HbAS, malaria, and other childhood diseases. PMID:15942909

  15. Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Theander, T G; Abdulhadi, N H

    1991-01-01

    Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area......-bound IL 2R (CD25) and ICAM-1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria....

  16. A Comparative Study of Dihydroartemisinin Compounds in Treatment of Uncomplicated Falciparum Malaria in Kampong of Cambodia

    Institute of Scientific and Technical Information of China (English)

    SONGJian-ping; DuongSocheattffu

    2003-01-01

    Objective:To compare the safety and efficacy of two compounds of dihydroartemisinin (DHA)-Artekin and Artekin(T)in the treatement of uncomplicated falciparum malaria.Methods:The regiment of 8-tablet for 2 days of Artekin and Artekin(T) were applied to 100 patients with uncompli-cated falciparum malaria,who were radomly divided into two groups.Each group contained 50 cases.The cure rate ,the mean parasites clearance time,the mean fever clearance and side-effects were observed to assess the safety and efficacy of the compunds used.Results:The mean parasites clearance time was 31.7±9.0 hours in the Artekin group and 32.8±8.8 hours in Artekin(T) group respectively; the mean fever clearance time was 12.7±7.2 hours in Artekin group and 16.5±7.9 hours in Artekin(T) group; there were no recrudescence case in both groups within the 28 days of follow-up ,the cure rates in Artekin group and Artekin(T)groups were 100%.It indicated that the tolerability of both compunds were very good,the side-effects such as nausea,abdominal pain were mild and self-limited.Conclusion:The study preliminarily indicated that the DHA and PQ compounds were of high efficacy,rapid acting and low toxici-ty.Artekin is very promising as a cheap,simple,effective treatment for multi-resistance malaria in Cam-bodia.

  17. Malaria-induced acquisition of antibodies to Plasmodium falciparum variant surface antigens

    DEFF Research Database (Denmark)

    Ofori, Michael F; Dodoo, Daniel; Staalsoe, Trine

    2002-01-01

    antibody responses to other parasite isolates are relatively unaffected. However, the detailed kinetics of this VSA antibody acquisition are unknown and hence were the aim of this study. We show that P. falciparum malaria in Ghanaian children generally caused a rapid and sustained increase in variant...... donors (the malaria patient). The data from this first detailed longitudinal study of acquisition of VSA antibodies support the hypothesis that naturally acquired protective immunity to P. falciparum malaria is mediated, at least in part, by VSA-specific antibodies.......In areas of intense Plasmodium falciparum transmission, protective immunity is acquired during childhood in parallel with acquisition of agglutinating antibodies to parasite-encoded variant surface antigens (VSA) expressed on parasitized red blood cells. In a semi-immune child in such an area...

  18. Plasmodium falciparum malaria importation from Africa to China and its mortality: an analysis of driving factors

    Science.gov (United States)

    Lai, Shengjie; Wardrop, Nicola A.; Huang, Zhuojie; Bosco, Claudio; Sun, Junling; Bird, Tomas; Wesolowski, Amy; Zhou, Sheng; Zhang, Qian; Zheng, Canjun; Li, Zhongjie; Tatem, Andrew J.; Yu, Hongjie

    2016-12-01

    Plasmodium falciparum malaria importation from Africa to China is rising with increasing Chinese overseas investment and international travel. Identifying networks and drivers of this phenomenon as well as the contributors to high case-fatality rate is a growing public health concern to enable efficient response. From 2011-2015, 8653 P. falciparum cases leading to 98 deaths (11.3 per 1000 cases) were imported from 41 sub-Saharan countries into China, with most cases (91.3%) occurring in labour-related Chinese travellers. Four strongly connected groupings of origin African countries with destination Chinese provinces were identified, and the number of imported cases was significantly associated with the volume of air passengers to China (P = 0.006), parasite prevalence in Africa (P falciparum malaria importation to China can serve to refine malaria elimination strategies and the management of cases, and high risk groups and regions should be targeted.

  19. Analysis of malaria parasite phenotypes using experimental genetic crosses of Plasmodium falciparum

    OpenAIRE

    Ranford-Cartwright, Lisa C; Mwangi, Jonathan M.

    2012-01-01

    We review the principles of linkage analysis of experimental genetic crosses and their application to Plasmodium falciparum. Three experimental genetic crosses have been performed using the human malaria parasite P. falciparum. Linkage analysis of the progeny of these crosses has been used to identify parasite genes important in phenotypes such as drug resistance, parasite growth and virulence, and transmission to mosquitoes. The construction and analysis of genetic maps has been used to char...

  20. Antioxidant vitamin levels among preschool children with uncomplicated Plasmodium falciparum malaria in Sokoto, Nigeria

    Directory of Open Access Journals (Sweden)

    Aghedo FI

    2013-07-01

    Full Text Available Festus I Aghedo,1 Resqua A Shehu,2 Rabiu A Umar,2 Mohammed N Jiya,3 Osaro Erhabor4 1Department of Haematology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria; 2Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria; 3Department of Paediatrics, College of Health Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria; 4Department of Haematology, Faculty of Medical Laboratory Science, Usmanu Danfodiyo University, Sokoto, Nigeria Objective: To assess antioxidant vitamin levels among preschool children with plasmodium malarial infection. Methods: We assessed antioxidant vitamin levels by using a standard procedure in 130 malaria-parasitized preschool children. Packed cell volume and parasite density were also evaluated. Forty healthy age- and gender-matched nonparasitized children were included as controls. Results: Plasmodium falciparum was the causative species in all subjects. The mean malaria parasitemia was 4529.45 ± 1237.5/µL. The mean antioxidant concentrations for vitamins A, C, and E among plasmodium-parasitized subjects were 33.15 ± 1.79 µg/dL, 0.51 ± 0.02 mg/dL, and 0.61 ± 0.02 mg/dL, respectively. The mean concentrations of vitamins A, C, and E among the non-malaria-parasitized controls were 69.72 ± 1.71 µg/dL, 1.25 ± 0.04 mg/dL, and 1.31 ± 0.04 mg/dL respectively. We observed that the mean antioxidant concentrations of vitamins A, C, and E were significantly lower among plasmodium-parasitized subjects compared with non-parasitized controls (P = 0.01. Malaria parasitemia correlated negatively with antioxidant concentrations and packed cell volume (r = -0.736 and -0.723, P = 0.001. We observed that the higher the level of parasitemia, the lower the antioxidant concentration. Conclusion: Our study has shown that the antioxidant levels in plasmodium-parasitized children in the North-West of Nigeria are low and that the more severe the malarial infection, the lower the antioxidant level and the

  1. Temporal association of acute hepatitis A and Plasmodium falciparum malaria in children.

    Directory of Open Access Journals (Sweden)

    Peter Klein Klouwenberg

    Full Text Available BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum and hepatitis A (HAV infections are common, especially in children. Co-infections with these two pathogens may therefore occur, but it is unknown if temporal clustering exists. MATERIALS AND METHODS: We studied the pattern of co-infection of P. falciparum malaria and acute HAV in Kenyan children under the age of 5 years in a cohort of children presenting with uncomplicated P. falciparum malaria. HAV status was determined during a 3-month follow-up period. DISCUSSION: Among 222 cases of uncomplicated malaria, 10 patients were anti-HAV IgM positive. The incidence of HAV infections during P. falciparum malaria was 1.7 (95% CI 0.81-3.1 infections/person-year while the cumulative incidence of HAV over the 3-month follow-up period was 0.27 (95% CI 0.14-0.50 infections/person-year. Children with or without HAV co-infections had similar mean P. falciparum asexual parasite densities at presentation (31,000/µL vs. 34,000/µL, respectively, largely exceeding the pyrogenic threshold of 2,500 parasites/µL in this population and minimizing risk of over-diagnosis of malaria as an explanation. CONCLUSION: The observed temporal association between acute HAV and P. falciparum malaria suggests that co-infections of these two hepatotrophic human pathogens may result from changes in host susceptibility. Testing this hypothesis will require larger prospective studies.

  2. Procalcitonin as a biomarker for severe Plasmodium falciparum disease: a critical appraisal of a semi-quantitative point-of-care test in a cohort of travellers with imported malaria

    Directory of Open Access Journals (Sweden)

    Petit Pieter

    2009-09-01

    Full Text Available Abstract Background Imported malaria occurs as a relatively rare event in developed countries. As a consequence, most clinicians have little experience in making clinical assessments of disease severity and decisions regarding the need for parenteral therapy or high-level monitoring. In this study, the diagnostic accuracy of procalcitonin (PCT for severe Plasmodium falciparum disease was assessed in a cohort of 100 consecutive travellers with various species of imported malaria. Methods and results In all patients, PCT was measured on admission with a semi-quantitative 'point-of-care' test. Patients with severe P. falciparum malaria had significantly higher median PCT levels on admission as compared with patients with uncomplicated P. falciparum disease. In addition, PCT levels in patients with non-falciparum malaria were also higher compared with patients with non-severe falciparum malaria but lower compared with severe P. falciparum malaria. At a cut-off point of 10 ng/mL, PCT had a sensitivity of 0,67 and a specificity of 0,94 for severe falciparum disease. However, at lower cut-off points the specificity and positive predictive value were rather poor although the sensitivity and negative predictive value remained high. Discussion Potential drawbacks in the interpretation of elevated PCT levels on admission may be caused by infections with non-falciparum species and by concomitant bacterial infections. Conclusion Semi-quantitative determination of PCT on admission is of limited use in the initial clinical assessment of disease severity in travellers with imported malaria, especially in settings with limited experience with the treatment of malaria.

  3. Trend and manifestations of falciparum malaria in a tertiary care hospital of India.

    Science.gov (United States)

    Saya, Rama Prakasha; Saya, Ganesh Kumar; Debabrata, Goswami

    2016-01-01

    The recent focus is on the increase in the burden of falciparum cases with a varied spectrum of presentation and outcome, especially in developing countries like India. This study was undertaken to analyze the trend and manifestations of falciparum malaria in a tertiary care hospital. This descriptive study was carried out at the Gauhati Government Medical College and Hospital from June 2006 to May 2007. The data were collected on demographic and time characteristics, clinical and laboratory findings, the outcome of disease and expressed in proportion or percentages. Out of the 100 cases, around 2(nd)/3(rd) (63%) of cases were in the age group of 15-30 years and the mean age was found to be 29.51 years. About 66% of them were males. Clinical presentations included pain abdomen (42, 42%), nausea and vomiting (35, 35%), jaundice (34, 34%), oliguria (24, 24%), altered sensorium (24, 24%), breathing difficulty (10, 10%), and seizures (5, 5%). Number of cases and mortality were more with a peak in the month of May and September. Manifestations of severe falciparum malaria included hepatopathy (38%), renal failure (28%), shock (9%), acute respiratory distress syndrome (7%), hypoglycemia (3%), and severe anemia (1%). Eighty-two cases (82%) recovered and 18 cases (18%) expired. Falciparum malaria is more among younger adult age group and males. Complications and mortality are also more due to falciparum malaria.

  4. Malária por Plasmodium falciparum: estudos proteômicos Plasmodium falciparum malaria: proteomic studies

    Directory of Open Access Journals (Sweden)

    Rodrigo Siqueira-Batista

    2012-12-01

    Full Text Available A despeito dos avanços no tratamento e das campanhas de prevenção e de controle da malária nos distintos continentes nos quais a moléstia grassa, a entidade mórbida permanece com significativa relevância no mundo contemporâneo. O Plasmodium falciparum é o grande responsável pela malária grave, caracterizada por distúrbios em diferentes órgãos e sistemas, com possibilidade de evolução ao óbito. Embora incipientes, os estudos proteômicos na malária têm trazido boas perspectivas para melhor compreensão dos aspectos biológicos do Plasmodium, assim como dos mecanismos fisiopatológicos, diagnósticos, terapêuticos e profiláticos da enfermidade. Desse modo, o objetivo do presente artigo é apresentar uma breve revisão das aplicações da análise proteômica na malária por P. falciparum.Despite advances in treatment and campaigns for prevention and control of malaria on the various continents where it is still rampant, this disease remains significantly relevant to the contemporary world. Plasmodium falciparum is the organism that is mainly responsible for severe malaria, which is characterized by disturbances in different organs and systems, with possibly fatal outcomes. Although incipient, proteomic studies of malaria have yielded favorable prospects for elucidating the biological aspects of Plasmodium as well as the pathophysiological, diagnostic, prophylactic, and therapeutic mechanisms of the disease. Thus, the aim of the present article is to present a brief review of the applications of proteomic analysis in P. falciparum malaria.

  5. K13 mutations and pfmdr1 copy number variation in Plasmodium falciparum malaria in Myanmar.

    Science.gov (United States)

    Win, Aye A; Imwong, Mallika; Kyaw, Myat P; Woodrow, Charles J; Chotivanich, Kesinee; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon

    2016-02-24

    Artemisinin-based combination therapy has been first-line treatment for falciparum malaria in Myanmar since 2005. The wide extent of artemisinin resistance in the Greater Mekong sub-region and the presence of mefloquine resistance at the Myanmar-Thailand border raise concerns over resistance patterns in Myanmar. The availability of molecular markers for resistance to both drugs enables assessment even in remote malaria-endemic areas. A total of 250 dried blood spot samples collected from patients with Plasmodium falciparum malarial infection in five malaria-endemic areas across Myanmar were analysed for kelch 13 sequence (k13) and pfmdr1 copy number variation. K13 mutations in the region corresponding to amino acids 210-726 (including the propeller region of the protein) were detected by nested PCR amplification and sequencing, and pfmdr1 copy number variation by real-time PCR. In two sites, a sub-set of patients were prospectively followed up for assessment of day-3 parasite clearance rates after a standard course of artemether-lumefantrine. K13 mutations and pfmdr1 amplification were successfully analysed in 206 and 218 samples, respectively. Sixty-nine isolates (33.5 %) had mutations within the k13 propeller region with 53 of these (76.8 %) having mutations already known to be associated with artemisinin resistance. F446I (32 isolates) and P574L (15 isolates) were the most common examples. K13 mutation was less common in sites in western border regions (29 of 155 isolates) compared to samples from the east and north (40 of 51 isolates; p < 0.0001). The overall proportion of parasites with multiple pfmdr1 copies (greater than 1.5) was 5.5 %. Seven samples showed both k13 mutation and multiple copies of pfmdr1. Only one of 36 patients followed up after artemether-lumefantrine treatment still had parasites at day 3; molecular analysis indicated wild-type k13 and single copy pfmdr1. The proportion of P. falciparum isolates with mutations in the propeller region of k

  6. Cord blood IgG and the risk of severe Plasmodium falciparum malaria in the first year of life.

    Science.gov (United States)

    Murungi, Linda M; Sondén, Klara; Odera, Dennis; Oduor, Loureen B; Guleid, Fatuma; Nkumama, Irene N; Otiende, Mark; Kangoye, David T; Fegan, Greg; Färnert, Anna; Marsh, Kevin; Osier, Faith H A

    2017-02-01

    Young infants are less susceptible to severe episodes of malaria but the targets and mechanisms of protection are not clear. Cord blood antibodies may play an important role in mediating protection but many studies have examined their association with the outcome of infection or non-severe malaria. Here, we investigated whether cord blood IgG to Plasmodium falciparum merozoite antigens and antibody-mediated effector functions were associated with reduced odds of developing severe malaria at different time points during the first year of life. We conducted a case-control study of well-defined severe falciparum malaria nested within a longitudinal birth cohort of Kenyan children. We measured cord blood total IgG levels against five recombinant merozoite antigens and antibody function in the growth inhibition activity and neutrophil antibody-dependent respiratory burst assays. We also assessed the decay of maternal antibodies during the first 6months of life. The mean antibody half-life range was 2.51months (95% confidence interval (CI): 2.19-2.92) to 4.91months (95% CI: 4.47-6.07). The rate of decline of maternal antibodies was inversely proportional to the starting concentration. The functional assay of antibody-dependent respiratory burst activity predicted significantly reduced odds of developing severe malaria during the first 6months of life (Odds ratio (OR) 0.07, 95% CI: 0.007-0.74, P=0.007). Identification of the targets of antibodies mediating antibody-dependent respiratory burst activity could contribute to the development of malaria vaccines that protect against severe episodes of malaria in early infancy. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Immunoglobulin G isotype responses to variant surface antigens of Plasmodium falciparum in healthy Gabonese adults and children during and after successive malaria attacks.

    NARCIS (Netherlands)

    Cabrera, G.; Yone, C.L.; Tebo, A.E.; Aaken, J. van; Lell, B.; Kremsner, P.G.; Luty, J.F.

    2004-01-01

    We assessed immunoglobulin G (IgG) isotype responses with specificity for the variant surface antigens (VSA) of heterologous Plasmodium falciparum isolates by using flow cytometry and plasma from healthy Gabonese adults and from children during and after two consecutive malaria episodes. The individ

  8. Efficacy of two artemisinin combination therapies for uncomplicated falciparum malaria in children under 5 years, Malakal, Upper Nile, Sudan

    Directory of Open Access Journals (Sweden)

    Alemu Engudaye

    2005-02-01

    Full Text Available Abstract Background The treatment for Plasmodium falciparum malaria in Sudan has been in process of change since 2003. Preceding the change, this study aimed to determine which artemisinin-based combination therapies is more effective to treat uncomplicated malaria in Malakal, Upper Nile, Sudan. Methods Clinical trial to assess the efficacy of 2 antimalarial therapies to treat P. falciparum infections in children aged 6–59 months, in a period of 42 days after treatment. Results A total of 269 children were followed up to 42 days. Artesunate plus Sulfadoxine/Pyrimethamine (AS+SP and Artesunate plus Amodiaquine (AS+AQ were both found to be efficacious in curing malaria infections by rapid elimination of parasites and clearance of fever, in preventing recrudescence and suppressing gametocytaemia. The combination of AS+SP appeared slightly more efficacious than AS+AQ, with 4.4% (4/116 versus 15% (17/113 of patients returning with malaria during the 6-week period after treatment (RR = 0.9, 95% CI 0.81–0.96. PCR analysis identified only one recrudescence which, together with one other early treatment failure, gave efficacy rates of 99.0% for AS+AQ (96/97 and 99.1% for AS+SP (112/113. However, PCR results were incomplete and assuming part of the indeterminate samples were recrudescent infections leads to an estimated efficacy ranging 97–98% for AS+SP and 88–95% for AS+AQ. Conclusion These results lead to the recommendation of ACT, and specifically AS+SP, for the treatment of uncomplicated falciparum malaria in this area of Sudan. When implemented, ACT efficacy should be monitored in sentinel sites representing different areas of the country.

  9. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.;

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human...... endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full......-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support...

  10. Clindamycin plus quinine for treating uncomplicated falciparum malaria: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Obonyo Charles O

    2012-01-01

    Full Text Available Abstract Background Artemisinin-based combinations are recommended for treatment of uncomplicated falciparum malaria, but are costly and in limited supply. Clindamycin plus quinine is an alternative non-artemisinin-based combination recommended by World Health Organization. The efficacy and safety of clindamycin plus quinine is not known. This systematic review aims to assess the efficacy of clindamycin plus quinine versus other anti-malarial drugs in the treatment of uncomplicated falciparum malaria. Methods All randomized controlled trials comparing clindamycin plus quinine with other anti-malarial drugs in treating uncomplicated malaria were included in this systematic review. Databases searched included: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS. Two authors independently assessed study eligibility, extracted data and assessed methodological quality. The primary outcome measure was treatment failure by day 28. Dichotomous data was compared using risk ratio (RR, in a fixed effects model. Results Seven trials with 929 participants were included. Clindamycin plus quinine significantly reduced the risk of day 28 treatment failure compared with quinine (RR 0.14 [95% CI 0.07 to 0.29], quinine plus sulphadoxine-pyrimethamine (RR 0.17 [95% CI 0.06 to 0.44], amodiaquine (RR 0.11 [95% CI 0.04 to 0.27], or chloroquine (RR 0.11 [95% CI 0.04 to 0.29], but had similar efficacy compared with quinine plus tetracycline (RR 0.33 [95% CI 0.01 to 8.04], quinine plus doxycycline (RR 1.00 [95% CI 0.21 to 4.66], artesunate plus clindamycin (RR 0.57 [95% CI 0.26 to 1.24], or chloroquine plus clindamycin (RR 0.38 [95% CI 0.13 to 1.10]. Adverse events were similar across treatment groups but were poorly reported. Conclusion The evidence on the efficacy of clindamycin plus quinine as an alternative treatment for uncomplicated malaria is inconclusive. Adequately powered trials are urgently required to compare this combination with

  11. International funding for malaria control in relation to populations at risk of stable Plasmodium falciparum transmission.

    OpenAIRE

    Snow, Robert W; Guerra, Carlos A; Mutheu, Juliette J; Simon I Hay

    2008-01-01

    Editors' Summary Background. Malaria is one of the most common infectious diseases in the world and one of the greatest global public health problems. The Plasmodium falciparum parasite causes approximately 500 million cases each year and over one million deaths. More than 40% of the world's population is at risk of malaria. The Millennium Development Goals (MDGs), established by the United Nations in 2000, include a target in Goal 6: ?to have halted by 2015 and begun to reverse the incidence...

  12. Rapid reemergence of T cells into peripheral circulation following treatment of severe and uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Goka, B Q

    1997-01-01

    Frequencies and absolute numbers of peripheral T-cell subsets were monitored closely following acute Plasmodium falciparum malaria in 22 Ghanaian children from an area of hyperendemicity for seasonal malaria transmission. The children presented with cerebral or uncomplicated malaria (CM or UM...

  13. Modelling the incidence of Plasmodium vivax and Plasmodium falciparum malaria in Afghanistan 2006-2009.

    Science.gov (United States)

    Alegana, Victor A; Wright, Jim A; Nahzat, Sami M; Butt, Waqar; Sediqi, Amad W; Habib, Naeem; Snow, Robert W; Atkinson, Peter M; Noor, Abdisalan M

    2014-01-01

    Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. From the analysis of healthcare utilisation, over 80% of the population was within 2 hours' travel of the nearest public health facility, while 64.4% were within 30 minutes' travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2-9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4-2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan.

  14. Cytokine balance in human malaria: does Plasmodium vivax elicit more inflammatory responses than Plasmodium falciparum?

    Directory of Open Access Journals (Sweden)

    Raquel M Gonçalves

    Full Text Available BACKGROUND: The mechanisms by which humans regulate pro- and anti-inflammatory responses on exposure to different malaria parasites remains unclear. Although Plasmodium vivax usually causes a relatively benign disease, this parasite has been suggested to elicit more host inflammation per parasitized red blood cell than P. falciparum. METHODOLOGY/PRINCIPAL FINDINGS: We measured plasma concentrations of seven cytokines and two soluble tumor necrosis factor (TNF-α receptors, and evaluated clinical and laboratory outcomes, in Brazilians with acute uncomplicated infections with P. vivax (n = 85, P. falciparum (n = 30, or both species (n = 12, and in 45 asymptomatic carriers of low-density P. vivax infection. Symptomatic vivax malaria patients, compared to those infected with P. falciparum or both species, had more intense paroxysms, but they had no clear association with a pro-inflammatory imbalance. To the contrary, these patients had higher levels of the regulatory cytokine interleukin (IL-10, which correlated positively with parasite density, and elevated IL-10/TNF-α, IL-10/interferon (IFN-γ, IL-10/IL-6 and sTNFRII/TNF-α ratios, compared to falciparum or mixed-species malaria patient groups. Vivax malaria patients had the highest levels of circulating soluble TNF-α receptor sTNFRII. Levels of regulatory cytokines returned to normal values 28 days after P. vivax clearance following chemotherapy. Finally, asymptomatic carriers of low P. vivax parasitemias had substantially lower levels of both inflammatory and regulatory cytokines than did patients with clinical malaria due to either species. CONCLUSIONS: Controlling fast-multiplying P. falciparum blood stages requires a strong inflammatory response to prevent fulminant infections, while reducing inflammation-related tissue damage with early regulatory cytokine responses may be a more cost-effective strategy in infections with the less virulent P. vivax parasite. The early induction

  15. Geographical patterns of malaria transmission based on serological markers for falciparum and vivax malaria in Ratanakiri, Cambodia

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    Karen Kerkhof

    2016-10-01

    Full Text Available Abstract Background Malaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure. Methods Blood samples collected in a community-based randomized trial performed in 98 high endemic communities in Ratanakiri province, north-eastern Cambodia, were screened with a multiplex serological assay for five serological markers (three Plasmodium falciparum and two Plasmodium vivax. The antibody half-lives range from approximately six months until more than two years. Geographical heterogeneity in malaria transmission was examined using a spatial scan statistic on serology, PCR prevalence and malaria incidence rate data. Furthermore, to identify behavioural patterns or intrinsic factors associated with malaria exposure (antibody levels, risk factor analyses were performed by using multivariable random effect logistic regression models. The serological outcomes were then compared to PCR prevalence and malaria incidence data. Results A total of 6502 samples from two surveys were screened in an area where the average parasite prevalence estimated by PCR among the selected villages is 3.4 %. High-risk malaria pockets were observed adjacent to the ‘Tonle San River’ and neighbouring Vietnam for all three sets of data (serology, PCR prevalence and malaria incidence rates. The main risk factors for all P. falciparum antigens and P. vivax MSP1.19 are age, ethnicity and staying overnight at the plot hut. Conclusion It is possible to identify similar malaria pockets of higher malaria

  16. Geographical patterns of malaria transmission based on serological markers for falciparum and vivax malaria in Ratanakiri, Cambodia.

    Science.gov (United States)

    Kerkhof, Karen; Sluydts, Vincent; Heng, Somony; Kim, Saorin; Pareyn, Myrthe; Willen, Laura; Canier, Lydie; Sovannaroth, Siv; Ménard, Didier; Sochantha, Tho; Coosemans, Marc; Durnez, Lies

    2016-10-19

    Malaria transmission is highly heterogeneous, especially in low endemic countries, such as Cambodia. This results in geographical clusters of residual transmission in the dry, low transmission season, which can fuel the transmission to wider areas or populations during the wet season. A better understanding of spatial clustering of malaria can lead to a more efficient, targeted strategy to reduce malaria transmission. This study aims to evaluate the potential of the use of serological markers to define spatial patterns in malaria exposure. Blood samples collected in a community-based randomized trial performed in 98 high endemic communities in Ratanakiri province, north-eastern Cambodia, were screened with a multiplex serological assay for five serological markers (three Plasmodium falciparum and two Plasmodium vivax). The antibody half-lives range from approximately six months until more than two years. Geographical heterogeneity in malaria transmission was examined using a spatial scan statistic on serology, PCR prevalence and malaria incidence rate data. Furthermore, to identify behavioural patterns or intrinsic factors associated with malaria exposure (antibody levels), risk factor analyses were performed by using multivariable random effect logistic regression models. The serological outcomes were then compared to PCR prevalence and malaria incidence data. A total of 6502 samples from two surveys were screened in an area where the average parasite prevalence estimated by PCR among the selected villages is 3.4 %. High-risk malaria pockets were observed adjacent to the 'Tonle San River' and neighbouring Vietnam for all three sets of data (serology, PCR prevalence and malaria incidence rates). The main risk factors for all P. falciparum antigens and P. vivax MSP1.19 are age, ethnicity and staying overnight at the plot hut. It is possible to identify similar malaria pockets of higher malaria transmission together with the potential risk factors by using serology

  17. Falciparum malaria and climate change in the northwest frontier province of Pakistan.

    Science.gov (United States)

    Bouma, M J; Dye, C; van der Kaay, H J

    1996-08-01

    Following a striking increase in the severity of autumnal outbreaks of Plasmodium falciparum during the last decade in the Northwest Frontier Province (NWFP) of Pakistan, the role of climatologic variables was investigated. A multivariate analysis showed that during the transmission season of P. falciparum, the amount of rainfall in September and October, the temperature in November and December, and the humidity in December were all correlated (r2 = 0.82) with two measures of P. falciparum, the falciparum rate (percent of slides examined positive for P. falciparum) since 1981 and the annual P. falciparum proportion (percent of all malaria infections diagnosed as P. falciparum) since 1978. Climatologic records since 1876 show an increase in mean November and December temperatures by 2 degrees C and 1.5 degrees C, respectively, and in October rainfall. Mean humidity in December has also been increasing since 1950. These climatologic changes in the area appear to have made conditions for transmission of P. falciparum more favorable, and may account for the increase in incidence observed in the NWFP in recent years.

  18. Kinetics of B Cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F

    2014-01-01

    Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why...... confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against...

  19. Chloroquine resistant Plasmodium falciparum malaria in Osogbo Nigeria: efficacy of amodiaquine + sulfadoxine-pyrimethamine and chloroquine + chlorpheniramine for treatment

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    TO Ogungbamigbe

    2008-02-01

    Full Text Available Chloroquine (CQ resistance in Plasmodium falciparum contributes to increasing malaria-attributable morbidity and mortality in Sub-Saharan Africa. Despite a change in drug policy, continued prescription of CQ did not abate. Therefore the therapeutic efficacy of CQ in uncomplicated falciparum malaria patients was assessed in a standard 28-day protocol in 116 children aged between six and 120 months in Osogbo, Southwest Nigeria. Parasitological and clinical assessments of response to treatment showed that 72 (62.1% of the patients were cured and 44 (37.9% failed the CQ treatment. High initial parasite density and young age were independent predictors for early treatment failure. Out of the 44 patients that failed CQ, 24 received amodiaquine + sulphadoxine/pyrimethamine (AQ+SP and 20 received chlorpheniramine + chloroquine (CH+CQ combinations. Mean fever clearance time in those treated with AQ+SP was not significantly different from those treated with CH+CQ (p = 0.05. There was no significant difference in the mean parasite density of the two groups. The cure rate for AQ+SP group was 92% while those of CH+CQ was 85%. There was a significant difference in parasite clearance time (p = 0.01 between the two groups. The 38% treatment failure for CQ reported in this study is higher than the 10% recommended by World Health Organization in other to effect change in antimalarial treatment policy. Hence we conclude that CQ can no more be solely relied upon for the treatment of falciparum malaria in Osogbo, Nigeria. AQ+SP and CH+CQ are effective in the treatment of acute uncomplicated malaria and may be considered as useful alternative drugs in the absence of artemisinin-based combination therapies.

  20. Influences of intermittent preventive treatment and persistent multiclonal Plasmodium falciparum infections on clinical malaria risk.

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    Anne Liljander

    Full Text Available BACKGROUND: Intermittent preventive treatment (IPT of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria. MATERIAL AND METHODS: The study included 2227 Ghanaian children (3-59 months who were given sulphadoxine-pyrimethamine (SP bimonthly, artesunate plus amodiaquine (AS+AQ monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up. RESULTS: Monthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment. CONCLUSION: Molecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that

  1. Blood monocyte oxidative burst activity in acute P. falciparum malaria

    DEFF Research Database (Denmark)

    Nielsen, H; Theander, T G

    1989-01-01

    The release of superoxide anion from blood monocytes was studied in eight patients with acute primary attack P. falciparum malaria. Before treatment a significant enhancement of the oxidative burst prevailed, which contrasts with previous findings of a depressed monocyte chemotactic responsiveness....... During treatment and after clinical recovery the activity of superoxide anion release normalized in all patients....

  2. Development of vaccines against Plasmodium falciparum malaria: taking lessons from naturally acquired protective immunity

    DEFF Research Database (Denmark)

    Hviid, Lars

    2007-01-01

    The acquisition of substantial anti-malarial protection in people naturally exposed to P. falciparum is often cited as evidence that malaria vaccines can be developed, but is rarely used to guide the development. We are pursuing the development of vaccines based on antigens and immune responses...

  3. The efficacy of artemether in the treatment of Plasmodium falciparum malaria in Sudan

    DEFF Research Database (Denmark)

    Elhassan, I M; Satti, G H; Ali, A E

    1994-01-01

    The efficacy of artemether (a qinghaosu derivative) administered intramuscularly for the treatment of Plasmodium falciparum malaria was compared to quinine in an open randomized trial including 54 patients in eastern Sudan, where chloroquine resistance is common. The artemether treatment (5 d...

  4. Cytokine production and apoptosis among T cells from patients under treatment for Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kemp, K; Akanmori, B D; Adabayeri, V

    2002-01-01

    Available evidence suggests that Plasmodium falciparum malaria causes activation and reallocation of T cells, and that these in vivo primed cells re-emerge into the periphery following drug therapy. Here we have examined the cytokine production capacity and susceptibility to programmed cell death...

  5. Increased levels of soluble CD30 in plasma of patients with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kemp, Kåre; Kurtzhals, Jørgen; Akanmori, Bartholomew D

    2002-01-01

    Levels of soluble CD30 (sCD30) in serum were elevated in patients with Plasmodium falciparum malaria but showed decline following treatment. The levels of sCD30 in serum were correlated significantly with the expression of gamma interferon by peripheral T cells. These data suggest that CD30...

  6. High-Dose Chloroquine for Treatment of Chloroquine-Resistant Plasmodium falciparum Malaria

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Bergqvist, Yngve;

    2016-01-01

    to determine the in vivo efficacy of higher chloroquine concentrations against P. falciparum with resistance-conferring genotypes. METHODS:  Standard or double-dose chloroquine was given to 892 children aged malaria during 3 clinical trials (2001-2008) with ≥35 days follow...

  7. Opsoclonus myoclonus ataxia syndrome due to falciparum malaria in two Indian children

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    Kallol Bose

    2016-01-01

    Full Text Available Opsoclonus-myoclonus ataxia (OMA syndrome is rare in children, mostly caused by neuroblastoma. Here, we present two very rare cases presenting with OMA due to falciparum malaria. Both of them responded to a high dose of adrenocorticotrophin hormone and intravenous immunoglobulin without recurrence and complication.

  8. Opsoclonus myoclonus ataxia syndrome due to falciparum malaria in two Indian children.

    Science.gov (United States)

    Bose, Kallol; Saha, Sudip; Islam, Md Rahiul; Chakraborty, Chayan; Laskar, Mustakim

    2016-11-01

    Opsoclonus-myoclonus ataxia (OMA) syndrome is rare in children, mostly caused by neuroblastoma. Here, we present two very rare cases presenting with OMA due to falciparum malaria. Both of them responded to a high dose of adrenocorticotrophin hormone and intravenous immunoglobulin without recurrence and complication.

  9. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

    NARCIS (Netherlands)

    Mbugi, E.V.; Mutayoba, B.M.; Malisa, A.L.; Balthazary, S.T.; Nyambo, T.B.; Mshinda, H.

    2006-01-01

    Background - Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods - The genes for dih

  10. Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.

    Science.gov (United States)

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2016-06-01

    Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.

  11. Asymptomatic falciparum malaria and intestinal helminths co-infection among school children in Osogbo, Nigeria

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    Olusola Ojurongbe

    2011-01-01

    Full Text Available Background: Malaria and intestinal helminths are parasitic diseases causing high morbidity and mortality in most tropical parts of the world, where climatic conditions and sanitation practices favor their prevalence. The aim of this study was to determine the prevalence and possible impact of falciparum malaria and intestinal helminths co-infection among school children in Kajola, Osun state, Nigeria. Methods: Fresh stool and blood samples were collected from 117 primary school children age range 4-15 years. The stool samples were processed using both Kato-Katz and formol-ether concentration techniques and microscopically examined for intestinal parasitic infections. Blood was collected by finger prick to determine malaria parasitemia using thick film method; and packed cell volume (PCV was determined by hematocrit. Univariate analysis and chi-square statistical tests were used to analyze the data. Results: The prevalence of Plasmodium falciparum, intestinal helminth infections, and co-infection of malaria and helminth in the study were 25.6%, 40.2% and 4.3%, respectively. Five species of intestinal helminths were recovered from the stool samples and these were Ascaris lumbricoides (34.2%, hookworm (5.1%, Trichuris trichiura (2.6%, Diphyllobothrium latum (0.9% and Trichostrongylus species (0.9%. For the co-infection of both malaria and intestinal helminths, females (5.9% were more infected than males (2.0% but the difference was not statistically significant (p = 0.3978. Children who were infected with helminths were equally likely to be infected with malaria as children without intestinal helminths [Risk Ratio (RR = 0.7295]. Children with A. lumbricoides (RR = 1.359 were also likely to be infected with P. falciparum as compared with uninfected children. Conclusions: Asymptomatic falciparum malaria and intestinal helminth infections do co-exist without clinical symp-toms in school children in Nigeria.

  12. Efficience of human Plasmodium falciparum malaria vaccine candidates in Aotus lemurinus monkeys

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    Socrates Herrera

    1992-01-01

    Full Text Available The protective efficacy of several recombinat and a synthetic Plasmodium falciparum protein was assessed in Aoutus monkeys. The rp41 aldolase, the 190L fragment of the MSA-1 protein and fusion 190L-CS. T3 protein containg the CS. T3 helper "universal epitope were emulsified in Freund's adjuvants and injected 3 times in groups of 4-5 monkeys each one. The synthetic polymer Spf (6630 also emulsified in Freund's adjuvants was injected 6 times. Control groups for both experiments were immunized with saline solution in the same adjuvant following the same schedules. Serology for malaria specific antibodies showed seroconversion in monkeys immunized with the recombinant proteins but not in those immunized with the polymer nor in the controls. Challenge was performed with the 10 (elevado a quinta potência parasites from the P. falciparum FVO isolate. Neither rp41 nor SPf (6630 induced protection, whereas 190L induced significant delay of parasitemia. The fusion of the CS. T3 epitope to 190L significantly increased is protective capacity.

  13. Combined measurement of soluble and cellular ICAM-1 among children with Plasmodium falciparum malaria in Uganda

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    Cserti-Gazdewich Christine M

    2010-08-01

    Full Text Available Abstract Background Intercellular adhesion molecule-1 (ICAM-1 is a cytoadhesion molecule implicated in the pathogenesis of Plasmodium falciparum malaria. Elevated levels of soluble ICAM-1 (sICAM-1 have previously been reported with increased malaria disease severity. However, studies have not yet examined both sICAM-1 concentrations and monocyte ICAM-1 expression in the same cohort of patients. To better understand the relationship of soluble and cellular ICAM-1 measurements in malaria, both monocyte ICAM-1 expression and sICAM-1 concentration were measured in children with P. falciparum infection exhibiting a spectrum of clinical severity. Methods Samples were analysed from 160 children, aged 0.5 to 10.8 years, with documented P. falciparum malaria in Kampala, Uganda. The patients belonged to one of three pre-study defined groups: uncomplicated malaria (UM, severe non-fatal malaria (SM-s, and fatal malaria (SM-f. Subset analysis was done on those with cerebral malaria (CM or severe malaria anaemia (SMA. Monocyte ICAM-1 was measured by flow cytometry. sICAM-1 was measured by enzyme immunoassay. Results Both sICAM-1 and monocyte cell-surface ICAM-1 followed a log-normal distribution. Median sICAM-1 concentrations increased with greater severity-of-illness: 279 ng/mL (UM, 462 ng/mL (SM-s, and 586 ng/mL (SM-f, p Conclusion In this cohort of children with P. falciparum malaria, sICAM-1 levels were associated with severity-of-illness. Patients with UM had higher monocyte ICAM-1 expression consistent with a role for monocyte ICAM-1 in immune clearance during non-severe malaria. Among the subsets of patients with either SMA or CM, monocyte ICAM-1 levels were higher in CM, consistent with the role of ICAM-1 as a marker of cytoadhesion. Categories of disease in pediatric malaria may exhibit specific combinations of soluble and cellular ICAM-1 expression.

  14. Spatial and space-time distribution of Plasmodium vivax and Plasmodium falciparum malaria in China, 2005-2014.

    Science.gov (United States)

    Hundessa, Samuel H; Williams, Gail; Li, Shanshan; Guo, Jinpeng; Chen, Linping; Zhang, Wenyi; Guo, Yuming

    2016-12-19

    Despite the declining burden of malaria in China, the disease remains a significant public health problem with periodic outbreaks and spatial variation across the country. A better understanding of the spatial and temporal characteristics of malaria is essential for consolidating the disease control and elimination programme. This study aims to understand the spatial and spatiotemporal distribution of Plasmodium vivax and Plasmodium falciparum malaria in China during 2005-2009. Global Moran's I statistics was used to detect a spatial distribution of local P. falciparum and P. vivax malaria at the county level. Spatial and space-time scan statistics were applied to detect spatial and spatiotemporal clusters, respectively. Both P. vivax and P. falciparum malaria showed spatial autocorrelation. The most likely spatial cluster of P. vivax was detected in northern Anhui province between 2005 and 2009, and western Yunnan province between 2010 and 2014. For P. falciparum, the clusters included several counties of western Yunnan province from 2005 to 2011, Guangxi from 2012 to 2013, and Anhui in 2014. The most likely space-time clusters of P. vivax malaria and P. falciparum malaria were detected in northern Anhui province and western Yunnan province, respectively, during 2005-2009. The spatial and space-time cluster analysis identified high-risk areas and periods for both P. vivax and P. falciparum malaria. Both malaria types showed significant spatial and spatiotemporal variations. Contrary to P. vivax, the high-risk areas for P. falciparum malaria shifted from the west to the east of China. Further studies are required to examine the spatial changes in risk of malaria transmission and identify the underlying causes of elevated risk in the high-risk areas.

  15. A systematic review of the safety and efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria during pregnancy

    Directory of Open Access Journals (Sweden)

    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

  16. STUDY OF CLINICAL, HAEMATOLOGICAL AND HEPATIC MANIFESTATIONS IN PATIENTS WITH FALCIPARUM MALARIA

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    Balaraj

    2014-05-01

    Full Text Available OBJECTIVE: Malarial infection is a major health problem in many parts of India. Several factors have been attributed to increased morbidity and mortality in malaria with altered hematological and hepatic parameters playing an important role. Our aim is to study the clinical, hematological and hepatic manifestations in patients with falciparum malaria. METHODS: This observational study was conducted from November 2012 to October 2013 at Kempegowda Institute of Medical Science and Research Hospital Bangalore. 75 patients of falciparum malaria confirmed by PS, MPQBC positive for Plasmodium falciparum or both falciparum and vivax were included in the study. All patients underwent detailed clinical history, thorough physical examination and investigated with hematological and hepatic parameters. This was followed by monitoring the outcome of the patients with respect to morbidity and mortality. Data was analyzed with descriptive statistical tools. RESULT: Of the 75 patients fever was present in all cases. Pallor (62% was the most common sign followed by splenomegaly (58% and icterus (48%. Anemia (60% was the most common complication, followed by jaundice (44%, cerebral malaria (40%, ARF (25%, ARDS (12%. 12 patients had severe anemia (Hb% <6 gm %. Severe thrombocytopenia (<50, 000 mm3 was seen in 5% of the patients. PT and APTT were increased in 23% and 12% of the cases respectively. 2 patients in the study expired. CONCLUSION: Clinical manifestations of plasmodium falciparum infection ranged from only fever to severe complications including cerebral malaria, acute renal failure, acute hemolytic crisis and hepatic dysfunction. Acute onset fever and splenomegaly were most common clinical manifestations found. Severe Anemia and jaundice are poor prognostic factor and has adverse outcome. Thrombocytopenia increased PT; aPTT does not have any correlation to mortality

  17. Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome.

    Science.gov (United States)

    Ladhani, Shamez; Lowe, Brett; Cole, Andrew O; Kowuondo, Ken; Newton, Charles R J C

    2002-12-01

    Little is known about the changes in white blood cells and platelets in children with falciparum malaria in endemic areas. We measured the white cell count (WCC) and platelets of 230 healthy children from the community, 1369 children admitted to hospital with symptomatic malaria, and 1461 children with other medical conditions. Children with malaria had a higher WCC compared with community controls, and leucocytosis was strongly associated with younger age, deep breathing, severe anaemia, thrombocytopenia and death. The WCC was not associated with a positive blood culture. In children with malaria, high lymphocyte and low monocyte counts were independently associated with mortality. A platelet count of less than 150 x 109/l was found in 56.7% of children with malaria, and was associated with age, prostration and parasite density, but not with bleeding problems or mortality. The mean platelet volume was also higher in children with malaria compared with other medical conditions. This may reflect early release from the bone marrow in response to peripheral platelet destruction. Thus, leucocytosis was associated with both severity and mortality in children with falciparum malaria, irrespective of bacteraemia, whereas thrombocytopenia, although very common, was not associated with adverse outcome.

  18. Transcriptomic evidence for modulation of host inflammatory responses during febrile Plasmodium falciparum malaria

    Science.gov (United States)

    Tran, Tuan M.; Jones, Marcus B.; Ongoiba, Aissata; Bijker, Else M.; Schats, Remko; Venepally, Pratap; Skinner, Jeff; Doumbo, Safiatou; Quinten, Edwin; Visser, Leo G.; Whalen, Elizabeth; Presnell, Scott; O’Connell, Elise M.; Kayentao, Kassoum; Doumbo, Ogobara K.; Chaussabel, Damien; Lorenzi, Hernan; Nutman, Thomas B.; Ottenhoff, Tom H. M.; Haks, Mariëlle C.; Traore, Boubacar; Kirkness, Ewen F.; Sauerwein, Robert W.; Crompton, Peter D.

    2016-01-01

    Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum malaria is controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis of blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points from Malian adults who were either asymptomatic (n = 5) or febrile (n = 3) during their first seasonal PCR-positive P. falciparum infection with those from malaria-naïve Dutch adults after a single controlled human malaria infection (n = 5). Our data show a graded activation of pathways downstream of pro-inflammatory cytokines, with the highest activation in malaria-naïve Dutch individuals and significantly reduced activation in malaria-experienced Malians. Newly febrile and asymptomatic infections in Malians were statistically indistinguishable except for genes activated by pro-inflammatory cytokines. The combined data provide a molecular basis for the development of a pyrogenic threshold as individuals acquire immunity to clinical malaria. PMID:27506615

  19. Acute Renal Failure in Patients with Severe Falciparum Malaria: Using the WHO 2006 and RIFLE Criteria

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    Vipa Thanachartwet

    2013-01-01

    Full Text Available There are limited data on the application of the RIFLE criteria among patients with severe malaria. This retrospective study was conducted by reviewing 257 medical records of adult hospitalized patients with severe falciparum malaria at the Mae Sot General Hospital, Tak province in the northern part of Thailand. The aims of this study were to determine the incidence of acute renal failure (ARF in patients with severe falciparum malaria and its association with RRT as well as in-hospital mortality. Using the WHO 2006 criteria, ARF was the second most common complication with incidence of 44.7% (115 patients. The requirement for RRT was 45.2% (52 patients and the in-hospital mortality was 31.9% (36 patients. Using the RIFLE criteria, 73.9% (190 patients had acute kidney injury (AKI. The requirement for RRT was 11.6% (5 patients in patients with RIFLE-I and 44.9% (48 patients in patients with RIFLE-F. The in-hospital mortality gradually increased with the severity of AKI. The requirement for RRT (P<0.05 and the in-hospital mortality (P<0.05 were significantly higher in ARF patients with severe falciparum malaria using both criteria. In conclusion, the RIFLE criteria could be used for diagnosing AKI and predicting outcomes in patients with severe malaria similar to the WHO 2006 criteria.

  20. Haemoglobin variants and Plasmodium falciparum malaria in children under five years of age living in a high and seasonal malaria transmission area of Burkina Faso

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    Bougouma Edith C

    2012-05-01

    Full Text Available Abstract Background Genetic factors play a key role in determining resistance/susceptibility to infectious disease. Susceptibility of the human host to malaria infection has been reported to be influenced by genetic factors, which could be confounders if not taken into account in the assessment of the efficacy of interventions against malaria. This study aimed to assess the relationship between haemoglobin genotypes and malaria in children under five years in a site being characterized for future malaria vaccine trials. Methods The study population consisted of 452 children living in four rural villages. Hb genotype was determined at enrolment. Clinical malaria incidence was evaluated over a one-year period using combined active and passive surveillance. Prevalence of infection was evaluated via bi-annual cross-sectional surveys. At each follow-up visit, children received a brief clinical examination and thick and thin blood films were prepared for malaria diagnosis. A clinical malaria was defined as Plasmodium falciparum parasitaemia >2,500 parasites/μl and axillary temperature ≥37.5°C or reported fever over the previous 24 hours. Results Frequencies of Hb genotypes were 73.2% AA; 15.0% AC; 8.2% AS; 2.2% CC; 1.1% CS and 0.2% SS. Prevalence of infection at enrolment ranged from 61.9%-54.1% among AA, AC and AS children. After one year follow-up, clinical malaria incidence (95% CI (episodes per person-year was 1.9 (1.7-2.0 in AA, 1.6 (1.4-2.1 in AC, and 1.7 (1.4-2.0 in AS children. AC genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 1–2 years [rate ratio (95% CI 0.66 (0.42-1.05] and 2–3 years [rate ratio (95% CI 0.37 (0.18-0.75]; an association of opposite direction was however apparent among children aged 3–4 years. AS genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 2–3 years [rate ratio (95% CI 0.63 (0

  1. Investigation of Hydrogen Sulfide Gas as a Treatment against P. falciparum, Murine Cerebral Malaria, and the Importance of Thiolation State in the Development of Cerebral Malaria

    DEFF Research Database (Denmark)

    Dellavalle, Brian; Staalsoe, Trine; Kurtzhals, Jørgen Anders;

    2013-01-01

    Cerebral malaria (CM) is a potentially fatal cerebrovascular disease of complex pathogenesis caused by Plasmodium falciparum. Hydrogen sulfide (HS) is a physiological gas, similar to nitric oxide and carbon monoxide, involved in cellular metabolism, vascular tension, inflammation, and cell death...

  2. The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Barillas-Mury, Carolina

    2014-08-01

    Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

  3. The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes

    Directory of Open Access Journals (Sweden)

    Alvaro Molina-Cruz

    2014-08-01

    Full Text Available Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

  4. Distribution of two species of malaria, Plasmodium falciparum and Plasmodium vivax, on Lombok Island, Indonesia.

    Science.gov (United States)

    Nagao, Yoshiro; Dachlan, Yoes Prijatna; Soedarto; Hidajati, Sri; Yotopranoto, Subagyo; Kusmartisnawati; Subekti, Sri; Ideham, Bariah; Tsuda, Yoshio; Kawabata, Masato; Takagi, Masahiro; Looareesuwan, Somchai

    2003-09-01

    Medical and entomological surveys were conducted to determine the risk factors of Plasmodium falciparum and P. vivax infections on Lombok Island, Indonesia, to find the risk factors and the main mosquito vectors for each malaria. Multivariate longitudinal analysis demonstrated two significant risk factors for infection with P. falciparum: disappearance of P. vivax parasitemia (p<0.001) and a specific study site (p<0.001). In contrast, younger age (p=0.024) and the interpolated virtual density of An. subpictus (p=0.041) were significantly associated with increased risk of infection with P. vivax. Thus, it seems that the distribution of P. vivax was determined largely by the presence of An. subpictus, whilst that of P. falciparum was influenced by antagonism with P. vivax. This result shows the importance of following-up treated P. vivax patients to identify recrudescence of P. falciparum in this area.

  5. TRALI Syndrome During the Treatment of a Plasmodium falciparum Malaria Case.

    Science.gov (United States)

    Çaşkurlu, Hülya; Nurmuhammedov, Rahman; Htway, Zarni

    2016-12-01

    Malaria, which is one of the three most important infectious diseases globally, is endemic in many areas of the world. Plasmodium falciparum is not endemic to Turkey but can be seen after travel to epidemic countries. Transfusion-related acute lung injury (TRALI) syndrome is a rare disease, which may develop following the transfusion of all types of blood products, including plasma. Here we describe a case of TRALI syndrome in a 29-year-old male, who presented with fever after 15 days of returning from a business trip to Burkina Faso. It developed immediately after the infusion of fresh frozen plasma during the treatment of P. falciparum malaria. The patient's condition improved on respiratory support treatment in the intensive care unit for 48 hours without the need of mechanical ventilation. This case indicated that TRALI syndrome has to be considered in the differential diagnosis as an emerging acute lung disease during the treatment of malaria.

  6. Defining childhood severe falciparum malaria for intervention studies.

    OpenAIRE

    Bejon, P.; Berkley, JA; MWANGI, T; Ogada, E; Mwangi, I; Maitland, K; Williams, T; Scott, JA; English, M; Lowe, BS; Peshu, N; Newton, CR; Marsh, K.

    2007-01-01

    Editors' Summary Background. Malaria is responsible for over a million deaths every year, and most of those who die are children in Africa. Until a few years ago, not enough research was being done on malaria, but now many researchers are active in this field. Doctors describe some cases of malaria as being “severe.” Severe malaria in children is very hard to diagnose precisely. Current protocols for diagnosing severe malaria are very sensitive: that is, virtually all children who do have sev...

  7. A Phase III, Randomized, Non-Inferiority Trial to Assess the Efficacy and Safety of Dihydroartemisinin-Piperaquine in Comparison with Artesunate-Mefloquine in Patients with Uncomplicated Plasmodium falciparum Malaria in Southern Laos

    Science.gov (United States)

    Mayxay, Mayfong; Keomany, Sommay; Khanthavong, Maniphone; Souvannasing, Phoutthalavanh; Stepniewska, Kasia; Khomthilath, Tiengthong; Keola, Siamphay; Pongvongsa, Tiengkham; Phompida, Samlane; Ubben, David; Valecha, Neena; White, Nicholas J.; Newton, Paul N.

    2010-01-01

    We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4–99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was −0.5% (−5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4–0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study. PMID:21118925

  8. IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria

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    Kalambaheti Thareerat

    2009-12-01

    Full Text Available Abstract Background The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences. Methods Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test. Results The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P = 0.031, but not with uncomplicated malaria (P = 0.622. Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P = 0.0156, while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P = 0.0206 compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P = 0.075. In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P = 0.004, P = 0.002, respectively. Conclusion The results suggest that IL4-590C or T alleles participated differently in the

  9. Analysis of the Clinical Profile in Patients with Plasmodium falciparum Malaria and Its Association with Parasite Density.

    Science.gov (United States)

    Mangal, Praveen; Mittal, Shilpa; Kachhawa, Kamal; Agrawal, Divya; Rath, Bhabagrahi; Kumar, Sanjay

    2017-01-01

    Malaria remains a major health hazard in the modern world, particularly in developing countries. In Plasmodium falciparum malaria, there is a direct correlation between asexual erythrocytic stage parasite density and disease severity. Accordingly, the correlations between parasite density and various clinical presentations, severity, and outcome were examined in falciparum malaria in India. The study was conducted in a tertiary health-care center in North India. Of 100 cases of falciparum malaria, 65 patients were male and 35 were female. A total of 54 patients were in the uncomplicated group and 46 patients were in the complicated malaria group. Fever, anemia, icterus, splenomegaly, hepatomegaly, and hepatosplenomegaly were common clinical findings. All clinical findings were significantly more common in the complicated malaria group and patients with a high parasite density than in the uncomplicated group and those with a low parasite density. All patients in the uncomplicated malaria group had a parasite density of 5%, and the difference between groups was statistically significant. The incidence of cerebral malaria was significantly higher in cases with a high parasite density; 58.33% mortality was observed in these cases. Cerebral malaria and hyperbilirubinemia was the most frequently encountered combination of complications. In P. falciparum malaria, parasite density was associated with complications and poor clinical outcomes. These results may inform treatment decisions and suggest that a threshold parasite density of 5% is informative.

  10. Cytokine profiling in immigrants with clinical malaria after extended periods of interrupted exposure to Plasmodium falciparum.

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    Gemma Moncunill

    Full Text Available Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200. Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495 and IFN-γ (rho=0.3044P=0.0282. However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001. Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100 than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500. Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies.

  11. Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia

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    Wongsrichanalai Chansuda

    2009-01-01

    Full Text Available Abstract Background The combination of artesunate and mefloquine was introduced as the national first-line treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy. Methods Blood samples were collected from P. falciparum-infected patients enrolled in two in vivo efficacy studies in north-western Cambodia: 135 patients were treated with artemether-lumefantrine (AL group in Sampovloun in 2002 and 2003, and 140 patients with artesunate-mefloquine (AM group in Sampovloun and Veal Veng in 2003 and 2004. At enrollment, the in vitro IC50 was tested and the strains were genotyped for pfmdr1 copy number by real-time PCR. Results The pfmdr1 copy number was analysed for 115 isolates in the AM group, and for 109 isolates in the AL group. Parasites with increased pfmdr1 copy number had significantly reduced in vitro susceptibility to mefloquine, lumefantrine and artesunate. There was no association between pfmdr1 polymorphisms and in vitro susceptibilities. In the patients treated with AM, the mean pfmdr1copy number was lower in subjects with adequate clinical and parasitological response compared to those who experienced late treatment failure (n = 112, p p = 0.364. The presence of three or more copies of pfmdr1 were associated with recrudescence in artesunate-mefloquine treated patients (hazard ratio (HR = 7.80 [95%CI: 2.09–29.10], N = 115, p = 0.002 but not with recrudescence in artemether-lumefantrine treated patients (HR = 1.03 [95%CI: 0.24–4.44], N = 109, p = 0.969. Conclusion This study shows that pfmdr1 copy number is a molecular

  12. Kinetics of B cell responses to Plasmodium falciparum erythrocyte membrane protein 1 in Ghanaian women naturally exposed to malaria parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F;

    2014-01-01

    Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why...... acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute....... In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed...

  13. Safety profile of L-arginine infusion in moderately severe falciparum malaria.

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    Tsin W Yeo

    Full Text Available BACKGROUND: L-arginine infusion improves endothelial function in malaria but its safety profile has not been described in detail. We assessed clinical symptoms, hemodynamic status and biochemical parameters before and after a single L-arginine infusion in adults with moderately severe malaria. METHODOLOGY AND FINDINGS: In an ascending dose study, adjunctive intravenous L-arginine hydrochloride was infused over 30 minutes in doses of 3 g, 6 g and 12 g to three separate groups of 10 adults hospitalized with moderately severe Plasmodium falciparum malaria in addition to standard quinine therapy. Symptoms, vital signs and selected biochemical measurements were assessed before, during, and for 24 hours after infusion. No new or worsening symptoms developed apart from mild discomfort at the intravenous cannula site in two patients. There was a dose-response relationship between increasing mg/kg dose and the maximum decrease in systolic (rho = 0.463; Spearman's, p = 0.02 and diastolic blood pressure (r = 0.42; Pearson's, p = 0.02, and with the maximum increment in blood potassium (r = 0.70, p<0.001 and maximum decrement in bicarbonate concentrations (r = 0.53, p = 0.003 and pH (r = 0.48, p = 0.007. At the highest dose (12 g, changes in blood pressure and electrolytes were not clinically significant, with a mean maximum decrease in mean arterial blood pressure of 6 mmHg (range: 0-11; p<0.001, mean maximal increase in potassium of 0.5 mmol/L (range 0.2-0.7 mmol/L; p<0.001, and mean maximal decrease in bicarbonate of 3 mEq/L (range 1-7; p<0.01 without a significant change in pH. There was no significant dose-response relationship with blood phosphate, lactate, anion gap and glucose concentrations. All patients had an uncomplicated clinical recovery. CONCLUSIONS/SIGNIFICANCE: Infusion of up to 12 g of intravenous L-arginine hydrochloride over 30 minutes is well tolerated in adults with moderately severe malaria, with no clinically important changes in

  14. Contrasting Transmission Dynamics of Co-endemic Plasmodium vivax and P. falciparum: Implications for Malaria Control and Elimination

    OpenAIRE

    Rintis Noviyanti; Farah Coutrier; Utami, Retno A. S.; Hidayat Trimarsanto; Yusrifar K Tirta; Leily Trianty; Andreas Kusuma; Inge Sutanto; Ayleen Kosasih; Rita Kusriastuti; Hawley, William A; Ferdinand Laihad; Neil Lobo; Jutta Marfurt; Clark, Taane G.

    2015-01-01

    Background Outside of Africa, P. falciparum and P. vivax usually coexist. In such co-endemic regions, successful malaria control programs have a greater impact on reducing falciparum malaria, resulting in P. vivax becoming the predominant species of infection. Adding to the challenges of elimination, the dormant liver stage complicates efforts to monitor the impact of ongoing interventions against P. vivax. We investigated molecular approaches to inform the respective transmission dynamics of...

  15. Perturbation and proinflammatory type activation of Vd1+ gamma delta T cells in African children with Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Kurtzhals, J A; Adabayeri, V

    2001-01-01

    of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta 1 and had a highly activated phenotype. Analysis of the T...... of the expanded V delta 1(+) T-cell population in this group of semi-immune P. falciparum malaria patients....

  16. Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.

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    Ilse C E Hendriksen

    Full Text Available In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2 is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria.Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054. In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209, acidosis (p<0.0001, and severe anaemia (p<0.0001. Admission geometric mean (95%CI plasma PfHRP2 was 1,611 (1,350-1,922 ng/mL in fatal cases (n = 381 versus 1,046 (991-1,104 ng/mL in survivors (n = 3,445, p<0.0001, without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10 plasma PfHRP2 and risk of death. Mortality increased 20% per log(10 increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009. A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018 in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82. A limitation of the study is that some

  17. Diagnosing severe falciparum malaria in parasitaemic African children: a prospective evaluation of plasma PfHRP2 measurement.

    Directory of Open Access Journals (Sweden)

    Ilse C E Hendriksen

    Full Text Available BACKGROUND: In African children, distinguishing severe falciparum malaria from other severe febrile illnesses with coincidental Plasmodium falciparum parasitaemia is a major challenge. P. falciparum histidine-rich protein 2 (PfHRP2 is released by mature sequestered parasites and can be used to estimate the total parasite burden. We investigated the prognostic significance of plasma PfHRP2 and used it to estimate the malaria-attributable fraction in African children diagnosed with severe malaria. METHODS AND FINDINGS: Admission plasma PfHRP2 was measured prospectively in African children (from Mozambique, The Gambia, Kenya, Tanzania, Uganda, Rwanda, and the Democratic Republic of the Congo aged 1 month to 15 years with severe febrile illness and a positive P. falciparum lactate dehydrogenase (pLDH-based rapid test in a clinical trial comparing parenteral artesunate versus quinine (the AQUAMAT trial, ISRCTN 50258054. In 3,826 severely ill children, Plasmadium falciparum PfHRP2 was higher in patients with coma (p = 0.0209, acidosis (p<0.0001, and severe anaemia (p<0.0001. Admission geometric mean (95%CI plasma PfHRP2 was 1,611 (1,350-1,922 ng/mL in fatal cases (n = 381 versus 1,046 (991-1,104 ng/mL in survivors (n = 3,445, p<0.0001, without differences in parasitaemia as assessed by microscopy. There was a U-shaped association between log(10 plasma PfHRP2 and risk of death. Mortality increased 20% per log(10 increase in PfHRP2 above 174 ng/mL (adjusted odds ratio [AOR] 1.21, 95%CI 1.05-1.39, p = 0.009. A mechanistic model assuming a PfHRP2-independent risk of death in non-malaria illness closely fitted the observed data and showed malaria-attributable mortality less than 50% with plasma PfHRP2≤174 ng/mL. The odds ratio (OR for death in artesunate versus quinine-treated patients was 0.61 (95%CI 0.44-0.83, p = 0.0018 in the highest PfHRP2 tertile, whereas there was no difference in the lowest tertile (OR 1.05; 95%CI 0.69-1.61; p = 0.82. A

  18. Proteomic Investigation of Falciparum and Vivax Malaria for Identification of Surrogate Protein Markers

    Science.gov (United States)

    Ray, Sandipan; Renu, Durairaj; Srivastava, Rajneesh; Gollapalli, Kishore; Taur, Santosh; Jhaveri, Tulip; Dhali, Snigdha; Chennareddy, Srinivasarao; Potla, Ankit; Dikshit, Jyoti Bajpai; Srikanth, Rapole; Gogtay, Nithya; Thatte, Urmila; Patankar, Swati; Srivastava, Sanjeeva

    2012-01-01

    This study was conducted to analyze alterations in the human serum proteome as a consequence of infection by malaria parasites Plasmodium falciparum and P. vivax to obtain mechanistic insights about disease pathogenesis, host immune response, and identification of potential protein markers. Serum samples from patients diagnosed with falciparum malaria (FM) (n = 20), vivax malaria (VM) (n = 17) and healthy controls (HC) (n = 20) were investigated using multiple proteomic techniques and results were validated by employing immunoassay-based approaches. Specificity of the identified malaria related serum markers was evaluated by means of analysis of leptospirosis as a febrile control (FC). Compared to HC, 30 and 31 differentially expressed and statistically significant (pphenotypic classes (FM, VM, FC and HC) were predicted with over 95% prediction accuracy. Individual performance of three classifier proteins; haptoglobin, apolipoprotein A-I and retinol-binding protein in diagnosis of malaria was analyzed using receiver operating characteristic (ROC) curves. The discrimination of FM, VM, FC and HC groups on the basis of differentially expressed serum proteins demonstrates the potential of this analytical approach for the detection of malaria as well as other human diseases. PMID:22912677

  19. Influence of host factors and parasite biomass on the severity of imported Plasmodium falciparum malaria.

    Science.gov (United States)

    Argy, Nicolas; Kendjo, Eric; Augé-Courtoi, Claire; Cojean, Sandrine; Clain, Jérôme; Houzé, Pascal; Thellier, Marc; Hubert, Veronique; Deloron, Philippe; Houzé, Sandrine

    2017-01-01

    Imported malaria in France is characterized by various clinical manifestations observed in a heterogeneous population of patients such as travelers/expatriates and African migrants. In this population, host factors and parasite biomass associated with severe imported malaria are poorly known. From data collected by the Centre National de Référence du Paludisme, we identified epidemiological, demographic and biological features including parasite biomass and anti-plasmodial antibody levels (negative, positive and strongly positive serology) associated with different disease severity groups (very severe, moderately severe, and uncomplicated malaria) in 3 epidemiological groups (travelers/expatriates, first- and second-generation migrants). Age, ethnicity, absence of prior infection with P. falciparum, antibody levels, plasma PfHRP2 levels, total and circulating parasite biomass were related to severe malaria onset. Sequestered parasite biomass tended to be increased in very severe malaria, and was strongly correlated to the antibody level of the host. Prior exposure to P. falciparum is associated with high anti-plasmodial antibody levels which influence clinical presentation of imported malaria and its correlated circulating and sequestered parasite burden.

  20. The return of chloroquine-susceptible Plasmodium falciparum malaria in Zambia.

    Science.gov (United States)

    Mwanza, Sydney; Joshi, Sudhaunshu; Nambozi, Michael; Chileshe, Justin; Malunga, Phidelis; Kabuya, Jean-Bertin Bukasa; Hachizovu, Sebastian; Manyando, Christine; Mulenga, Modest; Laufer, Miriam

    2016-12-05

    Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy. Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use. In Zambia, chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003. Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued. Parasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial. The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter, the gene that is associated with CQ resistance. Three-hundred and two specimens were successfully analysed. No chloroquine-resistant genotypes were detected. The study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure. Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future.

  1. Plasmodium falciparum Protein Microarray Antibody Profiles Correlate With Protection From Symptomatic Malaria in Kenya.

    Science.gov (United States)

    Dent, Arlene E; Nakajima, Rie; Liang, Li; Baum, Elisabeth; Moormann, Ann M; Sumba, Peter Odada; Vulule, John; Babineau, Denise; Randall, Arlo; Davies, D Huw; Felgner, Philip L; Kazura, James W

    2015-11-01

    Immunoglobulin G antibodies (Abs) to Plasmodium falciparum antigens have been associated with naturally acquired immunity to symptomatic malaria. We probed protein microarrays covering 824 unique P. falciparum protein features with plasma from residents of a community in Kenya monitored for 12 weeks for (re)infection and symptomatic malaria after administration of antimalarial drugs. P. falciparum proteins recognized by Abs from 88 children (aged 1-14 years) and 86 adults (aged ≥ 18 years), measured at the beginning of the observation period, were ranked by Ab signal intensity. Abs from immune adults reacted with a total 163 of 824 P. falciparum proteins. Children gradually acquired Abs to the full repertoire of antigens recognized by adults. Abs to some antigens showed high seroconversion rates, reaching maximal levels early in childhood, whereas others did not reach adult levels until adolescence. No correlation between Ab signal intensity and time to (re)infection was observed. In contrast, Ab levels to 106 antigens were significantly higher in children who were protected from symptomatic malaria compared with those who were not. Abs to antigens predictive of protection included P. falciparum erythrocyte membrane protein 1, merozoite surface protein (MSP) 10, MSP2, liver-stage antigen 3, PF70, MSP7, and Plasmodium helical interspersed subtelomeric domain protein. Protein microarrays may be useful in the search for malaria antigens associated with protective immunity. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Naturally acquired antibodies to the glutamate-rich protein are associated with protection against Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Dodoo, D; Theisen, M; Kurtzhals, J A

    2000-01-01

    of the Plasmodium falciparum glutamate-rich protein (GLURP). The data show that levels of the GLURP-specific IgG that occurs in the nonrepeat region of the antigen are significantly correlated with clinical protection from P. falciparum malaria, after correction for the confounding effect of age. Furthermore...

  3. Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria With High Parasitemia

    Science.gov (United States)

    Maude, Richard J.; Silamut, Kamolrat; Plewes, Katherine; Charunwatthana, Prakaykaew; Ho, May; Abul Faiz, M.; Rahman, Ridwanur; Hossain, Md Amir; Hassan, Mahtab U.; Bin Yunus, Emran; Hoque, Gofranul; Islam, Faridul; Ghose, Aniruddha; Hanson, Josh; Schlatter, Joel; Lacey, Rachel; Eastaugh, Alison; Tarning, Joel; Lee, Sue J.; White, Nicholas J.; Chotivanich, Kesinee; Day, Nicholas P. J.; Dondorp, Arjen M.

    2014-01-01

    Background. Cytoadherence and sequestration of erythrocytes containing mature stages of Plasmodium falciparum are central to the pathogenesis of severe malaria. The oral anthelminthic drug levamisole inhibits cytoadherence in vitro and reduces sequestration of late-stage parasites in uncomplicated falciparum malaria treated with quinine. Methods. Fifty-six adult patients with severe malaria and high parasitemia admitted to a referral hospital in Bangladesh were randomized to receive a single dose of levamisole hydrochloride (150 mg) or no adjuvant to antimalarial treatment with intravenous artesunate. Results. Circulating late-stage parasites measured as the median area under the parasite clearance curves were 2150 (interquartile range [IQR], 0–28 025) parasites/µL × hour in patients treated with levamisole and 5489 (IQR, 192–25 848) parasites/µL × hour in controls (P = .25). The “sequestration ratios” at 6 and 12 hours for all parasite stages and changes in microvascular blood flow did not differ between treatment groups (all P > .40). The median time to normalization of plasma lactate (<2 mmol/L) was 24 (IQR, 12–30) hours with levamisole vs 28 (IQR, 12–36) hours without levamisole (P = .15). Conclusions. There was no benefit of a single-dose of levamisole hydrochloride as adjuvant to intravenous artesunate in the treatment of adults with severe falciparum malaria. Rapid parasite killing by intravenous artesunate might obscure the effects of levamisole. PMID:23943850

  4. The pathogenesis of Plasmodium falciparum malaria in humans: insights from splenic physiology

    Science.gov (United States)

    Safeukui, Innocent; Deplaine, Guillaume; Brousse, Valentine; Prendki, Virginie; Thellier, Marc; Turner, Gareth D.; Mercereau-Puijalon, Odile

    2011-01-01

    Clinical manifestations of Plasmodium falciparum infection are induced by the asexual stages of the parasite that develop inside red blood cells (RBCs). Because splenic microcirculatory beds filter out altered RBCs, the spleen can innately clear subpopulations of infected or uninfected RBC modified during falciparum malaria. The spleen appears more protective against severe manifestations of malaria in naïve than in immune subjects. The spleen-specific pitting function accounts for a large fraction of parasite clearance in artemisinin-treated patients. RBC loss contributes to malarial anemia, a clinical form associated with subacute progression, frequent splenomegaly, and relatively low parasitemia. Stringent splenic clearance of ring-infected RBCs and uninfected, but parasite-altered, RBCs, may altogether exacerbate anemia and reduce the risks of severe complications associated with high parasite loads, such as cerebral malaria. The age of the patient directly influences the risk of severe manifestations. We hypothesize that coevolution resulting in increased splenic clearance of P. falciparum–altered RBCs in children favors the survival of the host and, ultimately, sustained parasite transmission. This analysis of the RBC–spleen dynamic interactions during P falciparum infection reflects both data and hypotheses, and provides a framework on which a more complete immunologic understanding of malaria pathogenesis may be elaborated. PMID:20852127

  5. [Erythrocyte polymorphism in Mali: epidemiology and resistance mechanisms against severe Plasmodium falciparum malaria].

    Science.gov (United States)

    Doumbo, Ogobara

    2007-01-01

    Homo sapiens and Plasmodium falciparum have co-evolved since the beginning of agriculture, 10,000 to 20,000 years ago. By domesticating plants and animals, humans linked their destiny to one of the main vectors of malaria, Anopheles gambiae sl complex. The biological interaction between these three species led to exchanges of genes and biochemical processes with significant mutual influence. Humans acquired mutations with selective protective advantages against serious and fatal forms of this hemosporidiosis. This is the case of hemoglobin S, hemoglobin C, hemoglobin E, thalassemias, ovalocytosis and G6PD deficiency, among others. Many epidemiological studies published since 1949 have shown a geographic link between malaria and certain erythrocyte polymorphisms. The link with hemoglobin C was discovered only recently, in 2000, initially in Mali in the Dogon population, then in Burkina Faso. Epidemiological and molecular and cellular biology studies done in Mali and elsewhere showed that the C and S alleles, and G6PD deficiency [A-], conferred significant protection against lethal forms of Plasmodium falciparum malaria. Molecular genetic studies, based on functional genomics, transcriptomics and proteomics, provided possible explanations. Advances in molecular biology and a better understanding of the immune mechanisms underlying this protection will hopefully lead to the development of effective second- and third-generation malaria vaccines. Epidemiological and fundamental research efforts have identified some of the mechanisms by which these erythrocyte polymorphisms protect against the most lethal hematozoan parasite, Plasmodium falciparum.

  6. Epidemiological and clinical features of Plasmodium falciparum malaria in united nations personnel in Western Bahr el Ghazal State, South Sudan.

    Science.gov (United States)

    He, Dengming; Zhang, Yuqi; Liu, Xiaofeng; Guo, Shimin; Zhao, Donghong; Zhu, Yunjie; Li, Huaidong; Kong, Li

    2013-01-01

    Western Bahr el Ghazal State is located in northwestern South Sudan, which is a tropical area subject to Plasmodium falciparum malaria epidemics. The aim of this study is to explore the epidemiological and clinical features of Plasmodium falciparum malaria in United Nations personnel stationed in this area. From July 2006 to June 2009, epidemiological data and medical records of 678 patients with Plasmodium falciparum malaria at the U.N. level 2 hospital were analyzed. The U.N. personnel were divided into individuals not immune to Plasmodium falciparum and individuals semi-immune to Plasmodium falciparum. The patients were divided into a chemoprophylaxis group (non-immune individuals who complied with the chemoprophylaxis regimen, 582 cases) and a no/incomplete chemoprophylaxis group (non-immune individuals who either did not fully comply with chemoprophylaxis or did not use it at all and semi-immune individuals who did not use chemoprophylaxis, 96 cases). Overall morbidity was about 11.3%. There was a significant difference in the morbidity of semi-immune and non-immune individuals (1.3% vs. 15.1%, PPlasmodium falciparum malaria mainly occurred in rainy season. Gastrointestinal symptoms are an important precursor of malaria. Blood smears and rapid diagnostic tests should be performed after the onset of gastrointestinal symptoms. Appropriate chemoprophylaxis is necessary for reducing the severity of malaria.

  7. Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru

    DEFF Research Database (Denmark)

    Villasis, Elizabeth; Lopez-Perez, Mary; Torres, Katherine

    2012-01-01

    , PfRh2a and PfRh2b and IgG3 response for PfRh2a were also negatively correlated with parasitaemia. Conclusions: These data suggest that falciparum malaria patients who develop clinical immunity (asymptomatic parasitaemia) in a low transmission setting such as the Peruvian Amazon have antibody......Background: Erythrocyte invasion by Plasmodium falciparum is a complex process that involves two families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins. Antibodies that inhibit merozoite attachment and invasion are believed to be important in mediating naturally...

  8. Plasmodium falciparum malaria occurring four years after leaving an endemic area.

    Science.gov (United States)

    Vantomme, B; Van Acker, J; Rogge, S; Ommeslag, D; Donck, J; Callens, S

    2016-04-01

    We present a case of a 52-year-old woman of Ghanaian origin who developed Plasmodium falciparum malaria 4 years after leaving Africa. She had not returned to an endemic area since. We hypothesize several possible scenarios to explain this infection, of which we believe recrudescence of P. falciparum is the most plausible. This occurred most likely as a consequence of waning immunity several years after leaving a high-transmission area. She recovered after a 3-day treatment with atovaquone/proguanil.

  9. Effect of acute Plasmodium falciparum malaria on reactivation and shedding of the eight human herpes viruses.

    Directory of Open Access Journals (Sweden)

    Arnaud Chêne

    Full Text Available Human herpes viruses (HHVs are widely distributed pathogens. In immuno-competent individuals their clinical outcomes are generally benign but in immuno-compromised hosts, primary infection or extensive viral reactivation can lead to critical diseases. Plasmodium falciparum malaria profoundly affects the host immune system. In this retrospective study, we evaluated the direct effect of acute P. falciparum infection on reactivation and shedding of all known human herpes viruses (HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8. We monitored their presence by real time PCR in plasma and saliva of Ugandan children with malaria at the day of admission to the hospital (day-0 and 14 days later (after treatment, or in children with mild infections unrelated to malaria. For each child screened in this study, at least one type of HHV was detected in the saliva. HHV-7 and HHV-6 were detected in more than 70% of the samples and CMV in approximately half. HSV-1, HSV-2, VZV and HHV-8 were detected at lower frequency. During salivary shedding the highest mean viral load was observed for HSV-1 followed by EBV, HHV-7, HHV-6, CMV and HHV-8. After anti-malarial treatment the salivary HSV-1 levels were profoundly diminished or totally cleared. Similarly, four children with malaria had high levels of circulating EBV at day-0, levels that were cleared after anti-malarial treatment confirming the association between P. falciparum infection and EBV reactivation. This study shows that acute P. falciparum infection can contribute to EBV reactivation in the blood and HSV-1 reactivation in the oral cavity. Taken together our results call for further studies investigating the potential clinical implications of HHVs reactivation in children suffering from malaria.

  10. Screening the Medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.

    Directory of Open Access Journals (Sweden)

    Alessandro Paiardini

    Full Text Available Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.

  11. Optimizing the HRP-2 In Vitro Malaria Drug Susceptibility Assay Using a Reference Clone to Improve Comparisons of Plasmodium falciparum Field Isolates

    Science.gov (United States)

    2012-09-13

    available soon. Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum...Optimizing the HRP-2 in vitro malaria drug susceptibility assay using a reference clone to improve comparisons of Plasmodium falciparum field isolates 5a...Date: 13 September 2012 14. ABSTRACT Apparent emerging artemisinin-resistant Plasmodium falciparum malaria in Southeast Asia requires development

  12. Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

    DEFF Research Database (Denmark)

    Jensen, Anja T R; Magistrado, Pamela; Sharp, Sarah;

    2004-01-01

    Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria...... genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria....

  13. Molecular epidemiology of Plasmodium vivax and Plasmodium falciparum malaria among Duffy-positive and Duffy-negative populations in Ethiopia.

    Science.gov (United States)

    Lo, Eugenia; Yewhalaw, Delenasaw; Zhong, Daibin; Zemene, Endalew; Degefa, Teshome; Tushune, Kora; Ha, Margaret; Lee, Ming-Chieh; James, Anthony A; Yan, Guiyun

    2015-02-19

    Malaria is the most prevalent communicable disease in Ethiopia, with 75% of the country's landmass classified as endemic for malaria. Accurate information on the distribution and clinical prevalence of Plasmodium vivax and Plasmodium falciparum malaria in endemic areas, as well as in Duffy-negative populations, is essential to develop integrated control strategies. A total of 390 and 416 community and clinical samples, respectively, representing different localities and age groups across Ethiopia were examined. Malaria prevalence was estimated using nested PCR of the 18S rRNA region. Parasite gene copy number was measured by quantitative real-time PCR and compared between symptomatic and asymptomatic samples, as well as between children/adolescents and adults from the local community. An approximately 500-bp segment of the human DARC gene was amplified and sequenced to identify Duffy genotype at the -33rd nucleotide position for all the clinical and community samples. Plasmodium vivax prevalence was higher in the south while P. falciparum was higher in the north. The prevalence of P. vivax and P. falciparum malaria is the highest in children compared to adolescents and adults. Four P. vivax infections were detected among the Duffy-negative samples. Samples from asymptomatic individuals show a significantly lower parasite gene copy number than those from symptomatic infections for P. vivax and P. falciparum. Geographical and age differences influence the distribution of P. vivax and P. falciparum malaria in Ethiopia. These findings offer evidence-based guidelines in targeting malaria control efforts in the country.

  14. Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso.

    Science.gov (United States)

    Somé, Anyirékun Fabrice; Zongo, Issaka; Compaoré, Yves-Daniel; Sakandé, Souleymane; Nosten, François; Ouédraogo, Jean-Bosco; Rosenthal, Philip J

    2014-07-01

    Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT00941785.).

  15. Novel Plasmodium falciparum malaria vaccines: evidence-based searching for variant surface antigens as candidates for vaccination against pregnancy-associated malaria

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Jensen, Anja T R; Theander, Thor G

    2002-01-01

    to statistically significant co-variation with protection rather than on demonstration of causal relationships. We have studied the relationship between variant surface antigen-specific antibodies and clinical protection from Plasmodium falciparum malaria in general, and from pregnancy-associated malaria (PAM...

  16. Evaluation of the NOW Malaria Immunochromatographic Test for Quantitative Diagnosis of Falciparum and Vivax Malaria Parasite Density.

    Science.gov (United States)

    Katakai, Yuko; Komaki-Yasuda, Kanako; Tangpukdee, Noppadon; Wilairatana, Polrat; Krudsood, Srivicha; Kano, Shigeyuki

    2011-12-01

    The NOW® Malaria Test, an immunochromatographic test (ICT), was evaluated to determine its ability to quantitatively detect malaria parasites using 100 blood samples from Thailand, including 50 Plasmodium falciparum (Pf) infections and 50 P. vivax (Pv) infections. Intensities of the thickness of the visible bands of the positive ICT were compared with the parasite densities. In cases of Pf infection, the intensities of both HRP-2 bands (T1 bands: Pf specific bands) and aldolase bands (T2 bands: pan-Plasmodium bands) correlated with the parasite densities. The intensities of T2 bands in Pf positive samples showed better correlation with the parasite densities than the T1 bands. In the cases of Pv infection, the intensities of T2 bands were also well correlated with parasite density. These results suggest that the ICT is useful not only for rapid detection of malaria parasites but also for estimating parasite density.

  17. Transplacental Transmission of Plasmodium falciparum in a Highly Malaria Endemic Area of Burkina Faso

    Directory of Open Access Journals (Sweden)

    Alphonse Ouédraogo

    2012-01-01

    Full Text Available Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4% contained malaria parasites (Plasmodium falciparum. Out of the 369 (28.2% women with peripheral positive parasitemia, 211 (57.2% had placental malaria and 14 (3.8% had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR=9.24, ≪0.001, placental parasitemia (OR=10.74, ≪0.001, high-density peripheral parasitemia (OR=9.62, ≪0.001, and high-density placental parasitemia (OR=4.91, =0.03. In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low.

  18. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

    Directory of Open Access Journals (Sweden)

    Alberto Tobón-Castaño

    2015-01-01

    Full Text Available Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%, 313 with P. vivax infection (35.2%, and 19 with mixed infection by these species (2.1%. Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54% followed by monocytosis (11%; the differential granulocyte count in 298 patients revealed eosinophilia (15% and high basophil counts (8%. Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response.

  19. Therapeutic efficacy of artemether-lumefantrine against uncomplicated Plasmodium falciparum malaria in a high-transmission area in northwest Ethiopia.

    Science.gov (United States)

    Teklemariam, Michael; Assefa, Ashenafi; Kassa, Moges; Mohammed, Hussien; Mamo, Hassen

    2017-01-01

    Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia. The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study of a 28-day follow-up was conducted from October 2014 to January 2015 according to the revised WHO 2009 drug efficacy study protocol. Study end-points were classified into primary end-point and secondary end-point. While the primary end-point was the day-28 adequate clinical and parasitological response the secondary end-points were clinical and parasitological evaluations (parasite, fever and gametocyte clearance rate, incidence of drug adverse events) and the relative increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total of 92 patients were enrolled and 79 had completed the 28-day follow-up period. The overall cure rate was 98.8% with 95% confidence interval of 0.915-0.998 without polymerase chain reaction correction. The parasite clearance rate was high with fast resolution of clinical symptoms; 100% of the study participants cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration significantly increased on D28 compared to that on D14. There was no serious adverse event. AL was efficacious and safe in a high-transmission setting for treatment of uncomplicated falciparum malaria.

  20. Defining the protein interaction network of human malaria parasite Plasmodium falciparum

    KAUST Repository

    Ramaprasad, Abhinay

    2012-02-01

    Malaria, caused by the protozoan parasite Plasmodium falciparum, affects around 225. million people yearly and a huge international effort is directed towards combating this grave threat to world health and economic development. Considerable advances have been made in malaria research triggered by the sequencing of its genome in 2002, followed by several high-throughput studies defining the malaria transcriptome and proteome. A protein-protein interaction (PPI) network seeks to trace the dynamic interactions between proteins, thereby elucidating their local and global functional relationships. Experimentally derived PPI network from high-throughput methods such as yeast two hybrid (Y2H) screens are inherently noisy, but combining these independent datasets by computational methods tends to give a greater accuracy and coverage. This review aims to discuss the computational approaches used till date to construct a malaria protein interaction network and to catalog the functional predictions and biological inferences made from analysis of the PPI network. © 2011 Elsevier Inc.

  1. Identification of a Platelet Membrane Glycoprotein as a Falciparum Malaria Sequestration Receptor

    Science.gov (United States)

    Ockenhouse, Christian F.; Tandon, Narendra N.; Magowan, Cathleen; Jamieson, G. A.; Chulay, Jeffrey D.

    1989-03-01

    Infections with the human malaria parasite Plasmodium falciparum are characterized by sequestration of erythrocytes infected with mature forms of the parasite. Sequestration of infected erythrocytes appears to be critical for survival of the parasite and to mediate immunopathological abnormalities in severe malaria. A leukocyte differentiation antigen (CD36) was previously suggested to have a role in sequestration of malaria-infected erythrocytes. CD36 was purified from platelets, where it is known as GPIV, and was shown to be a receptor for binding of infected erythrocytes. Infected erythrocytes adhered to CD36 immobilized on plastic; purified CD36 exhibited saturable, specific binding to infected erythrocytes; and purified CD36 or antibodies to CD36 inhibited and reversed binding of infected erythrocytes to cultured endothelial cells and melanoma cells in vitro. The portion of the CD36 molecule that reverses cytoadherence may be useful therapeutically for rapid reversal of sequestration in cerebral malaria.

  2. Plasmodium vivax and Plasmodium falciparum are Common Malaria Species in Pakistan

    Directory of Open Access Journals (Sweden)

    Tauseef Ahmad

    2016-06-01

    Full Text Available The microbes have a diverse nature, it makes human laugh and cry. Some microbes are fruitful for humans while others are harmful. Infectious diseases are a key problem in the modern world. In the last few decades, million of peoples have died from different diseases, including bacterial, viral, fungal, parasitic, etc. Among these diseases, malaria is one of the major health problems for developing countries including Pakistan. This study was undertaken to provide baseline information about the prevalence of malaria, species distribution and to contribute to the data regarding epidemiology in Pakistan. For a collection of literature, the electronic search engine was used, using different key words i.e. prevalence, species distribution, epidemiology of malaria in Pakistan, etc. The time frame of the obtained articles was from 2000 to 2014. The two species of malaria Plasmodium vivax and Plasmodium falciparum are common in Pakistan. [Biomed Res Ther 2016; 3(6.000: 666-672

  3. Artesunate: investigational drug for the treatment of severe falciparum malaria in Hawai'i.

    Science.gov (United States)

    Callender, David M; Hsue, Gunther

    2011-04-01

    There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai'i. A 49-year-old man presented to Tripler Army Medical Center, Hawai'i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria.

  4. Artesunate: Investigational Drug for the Treatment of Severe Falciparum Malaria in Hawai‘i

    Science.gov (United States)

    Hsue, Gunther

    2011-01-01

    Introduction There are hundreds of millions of cases of malaria each year worldwide resulting in a million deaths. These deaths are mostly due to Plasmodium falciparum. The only Federal Drug Administration approved treatment for severe malaria is intravenous quinidine gluconate. Intravenous quinidine is increasingly unavailable in the United States. In 2007, the Center for Disease Control and Prevention implemented an investigational new drug protocol to allow the use of intravenous artesunate for cases of severe malaria in the United States. The authors present such a case treated under this protocol at Tripler Army Medical Center, Hawai‘i. Case Report A 49-year-old man presented to Tripler Army Medical Center, Hawai‘i in February 2009 with a one-month history of fever, chills, and weight loss. He recently travelled to multiple malaria endemic areas. Physical examination was significant for fever and prostration. Laboratory studies revealed anemia, thrombocytopenia, and a high parasite load of Plasmodium falciparum. A strategic network was activated to obtain and administer intravenous artesunate. His condition rapidly improved as his parasitemia cleared. He was discharged after six days with no adverse medication effects and full recovery upon six-month follow-up. Discussion Our patient met the criteria for severe Plasmodium falciparum malaria. He was immediately treated with intravenous artesunate and manifested a quick and durable response to therapy. At present, intravenous artesunate is awaiting Federal Drug Administration approval but available via a strategic network controlled by the Centers for Disease Control and Prevention. This case highlights a common delay in diagnosis, importance of optimal prophylaxis, and attention to travel history as they relate to the development of severe malaria. PMID:21785506

  5. Aotus infulatus monkey is susceptible to Plasmodium falciparum infection and may constitute an alternative experimental model for malaria

    Directory of Open Access Journals (Sweden)

    Carvalho Leonardo JM

    2000-01-01

    Full Text Available Aotus is one of the WHO-recommended primate models for studies in malaria, and several species can be infected with Plasmodium falciparum or P. vivax. Here we describe the successful infection of the species A. infulatus from eastern Amazon with blood stages of P. falciparum. Both intact and splenectomized animals were susceptible to infection; the intact ones were able to keep parasitemias at lower levels for several days, but developed complications such as severe anemia; splenectomized monkeys developed higher parasitemias but no major complications. We conclude that A. infulatus is susceptible to P. falciparum infection and may represent an alternative model for studies in malaria.

  6. Risk factors for Plasmodium falciparum and Plasmodium vivax gametocyte carriage in Papua New Guinean children with uncomplicated malaria.

    Science.gov (United States)

    Karl, Stephan; Laman, Moses; Moore, Brioni R; Benjamin, John M; Salib, Mary; Lorry, Lina; Maripal, Samuel; Siba, Peter; Robinson, Leanne J; Mueller, Ivo; Davis, Timothy M E

    2016-08-01

    There are limited data on gametocytaemia risk factors before/after treatment with artemisinin combination therapy in children from areas with transmission of multiple Plasmodium species. We utilised data from a randomised trial comparing artemether-lumefantrine (AL) and artemisinin-naphthoquine (AN) in 230 Papua New Guinean children aged 0.5-5 years with uncomplicated malaria in whom determinants of gametocytaemia by light microscopy were assessed at baseline using logistic regression and during follow-up using multilevel mixed effects modelling. Seventy-four (32%) and 18 (8%) children presented with P. falciparum and P. vivax gametocytaemia, respectively. Baseline P. falciparum gametocytaemia was associated with Hackett spleen grade 1 (odds ratio (95% CI) 4.01 (1.60-10.05) vs grade 0; P<0.001) and haemoglobin (0.95 (0.92-0.97) per 1g/L increase; P<0.001), and P. falciparum asexual parasitaemia in slide-positive cases (0.36 (0.19-0.68) for a 10-fold increase; P=0.002). Baseline P. vivax gametocytaemia was associated with Hackett grade 2 (12.66 (1.31-122.56); P=0.028), mixed P. falciparum/vivax infection (0.16 (0.03-1.00); P=0.050), P. vivax asexual parasitaemia (5.68 (0.98-33.04); P=0.053) and haemoglobin (0.94 (0.88-1.00); P=0.056). For post-treatment P. falciparum gametocytaemia, independent predictors were AN vs AL treatment (4.09 (1.43-11.65)), haemoglobin (0.95 (0.93-0.97)), presence/absence of P. falciparum asexual forms (3.40 (1.66-0.68)) and day post-treatment (0.086 (0.82-0.90)) (P<0.001). Post-treatment P. vivax gametocytaemia was predicted by presence of P. vivax asexual forms (596 (12-28,433); P<0.001). Consistent with slow P. falciparum gametocyte maturation, low haemoglobin, low asexual parasite density and higher spleen grading, markers of increased prior infection exposure/immunity, were strong associates of pre-treatment gametocyte positivity. The persistent inverse association between P. falciparum gametocytaemia and haemoglobin during follow

  7. Multiple clinical episodes of Plasmodium falciparum malaria in a low transmission intensity setting: exposure versus immunity.

    Science.gov (United States)

    Rono, Josea; Färnert, Anna; Murungi, Linda; Ojal, John; Kamuyu, Gathoni; Guleid, Fatuma; Nyangweso, George; Wambua, Juliana; Kitsao, Barnes; Olotu, Ally; Marsh, Kevin; Osier, Faith Ha

    2015-05-13

    Epidemiological studies indicate that some children experience many more episodes of clinical malaria than their age mates in a given location. Whether this is as a result of the micro-heterogeneity of malaria transmission with some children effectively getting more exposure to infectious mosquitoes than others, or reflects a failure in the acquisition of immunity needs to be elucidated. Here, we investigated the determinants of increased susceptibility to clinical malaria by comparing the intensity of exposure to Plasmodium falciparum and the acquisition of immunity in children at the extreme ends of the over-dispersed distribution of the incidence of clinical malaria. The study was nested within a larger cohort in an area where the intensity of malaria transmission was low. We identified children who over a five-year period experienced 5 to 16 clinical malaria episodes (children at the tail-end of the over-dispersed distribution, n = 35), remained malaria-free (n = 12) or had a single episode (n = 26). We quantified antibodies against seven Plasmodium falciparum merozoite antigens in plasma obtained at six cross-sectional surveys spanning these five years. We analyzed the antibody responses to identify temporal dynamics that associate with disease susceptibility. Children experiencing multiple episodes of malaria were more likely to be parasite positive by microscopy at cross-sectional surveys (X (2) test for trend 14.72 P = 0.001) and had a significantly higher malaria exposure index, than those in the malaria-free or single episode groups (Kruskal-Wallis test P = 0.009). In contrast, the five-year temporal dynamics of anti-merozoite antibodies were similar in the three groups. Importantly in all groups, antibody levels were below the threshold concentrations previously observed to be correlated with protective immunity. We conclude that in the context of a low malaria transmission setting, susceptibility to clinical malaria is not accounted

  8. Genetic diversity and gene flow of humans, Plasmodium falciparum, and Anopheles farauti s.s. of Vanuatu: inferred malaria dispersal and implications for malaria control.

    Science.gov (United States)

    Lum, J K; Kaneko, A; Taleo, G; Amos, M; Reiff, D M

    2007-08-01

    A comparison of the patterns of gene flow within and between islands and the genetic diversities of the three species required for malaria transmission (humans, Plasmodium falciparum, and Anopheles farauti s.s.) within the model island system of Vanuatu, shows that the active dispersal of An. farauti s.s. is responsible for within island movement of parasites. In contrast, since both P. falciparum and An. farauti s.s. populations are largely restricted to islands, movement of parasites between islands is likely due to human transport. Thus, control of vectors is crucial for controlling malaria within islands, while control of human movement is essential to control malaria transmission across the archipelago.

  9. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  10. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  11. Non-falciparum malaria in Dakar: a confirmed case of Plasmodium ovale wallikeri infection.

    Science.gov (United States)

    Diallo, Mamadou A; Badiane, Aida S; Diongue, Khadim; Deme, Awa; Lucchi, Naomi W; Gaye, Marie; Ndiaye, Tolla; Ndiaye, Mouhamadou; Sene, Louise K; Diop, Abdoulaye; Gaye, Amy; Ndiaye, Yaye D; Samb, Diama; Yade, Mamadou S; Ndir, Omar; Udhayakumar, Venkatachalam; Ndiaye, Daouda

    2016-08-24

    Plasmodium ovale is rarely described in Senegal. A case of clinical malaria due to P. ovale wallikeri in West Central of Senegal is reported. A 34-year-old male baker in Dakar, with no significant previous medical history, was admitted to a health clinic with fever and vomiting. Fever had been lasting for 4 days with peaks every 48 h. As monospecific Plasmodium falciparum HRP-2 RDT was negative, he was treated with antibiotics. However, owing to persisting symptoms, he was referred to the emergency unit of the Youssou Mbargane Diop Hospital, Dakar, Senegal. Clinical examination found impaired general condition. All other physical examinations were normal. Laboratory tests showed anaemia (haemoglobin 11.4 g/dl), severe thrombocytopaenia (platelets 30 × 10(9)/mm(3)), leukopenia (3650/mm(3)), lymphocytopenia (650/mm(3)). Renal function was normal as indicated by creatininaemia and uraemia (11 mg/l and 0.25 g/l, respectively) and liver enzymes were slightly elevated (aspartate aminotransferase 77 UI/l and alanine aminotransferase 82 UI/l). Blood smear evaluations in Parasitology Laboratory of Aristide Le Dantec Hospital showed malaria parasites of the species P. ovale with a 0.08 % parasitaemia. Molecular confirmation was done by real time PCR targeting the 18S rRNA gene. The P. ovale infection was further analysed to species level targeting the potra gene and was identified as P. ovale wallikeri. According to the hospital's malaria treatment guidelines for severe malaria, treatment consisted of intravenous quinine at hour 0 (start of treatment) and 24 h after initial treatment, followed by artemether-lumefantrine 24 h later. A negative microscopy was noted on day 3 post-treatment and the patient reported no further symptoms. Malaria due to non-falciparum species is probably underestimated in Senegal. RDTs specific to non-falciparum species and/or pan specific RDTs should be included as tools of diagnosis to fight against malaria in Senegal. In addition

  12. Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

    Science.gov (United States)

    Mita, Toshihiro; Tachibana, Shin-Ichiro; Hashimoto, Muneaki; Hirai, Makoto

    2016-01-01

    Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.

  13. Gibberellin biosynthetic inhibitors make human malaria parasite Plasmodium falciparum cells swell and rupture to death.

    Directory of Open Access Journals (Sweden)

    Tomoko Toyama

    Full Text Available Malaria remains as one of the most devastating infectious disease, and continues to exact an enormous toll in medical cost and days of labor lost especially in the tropics. Effective malaria control and eventual eradication remain a huge challenge, with efficacious antimalarials as important intervention/management tool. Clearly new alternative drugs that are more affordable and with fewer side effects are desirable. After preliminary in vitro assays with plant growth regulators and inhibitors, here, we focus on biosynthetic inhibitors of gibberellin, a plant hormone with many important roles in plant growth, and show their inhibitory effect on the growth of both apicomplexa, Plasmodium falciparum and Toxoplasma gondii. Treatment of P. falciparum cultures with the gibberellin biosynthetic inhibitors resulted in marked morphological changes that can be reversed to a certain degree under hyperosmotic environment. These unique observations suggest that changes in the parasite membrane permeability may explain the pleiotropic effects observed within the intracellular parasites.

  14. VAR2CSA and protective immunity against pregnancy-associated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Hviid, L; Salanti, A

    2007-01-01

    People living in areas with stable transmission of P. falciparum parasites acquire protective immunity to malaria over a number of years and following multiple disease episodes. Immunity acquired this way is mediated by IgG with specificity for parasite-encoded, clonally variant surface antigens...... (VSA) on the surface of infected erythrocytes (IEs). However, women in endemic areas become susceptible to P. falciparum infection when they become pregnant, particularly for the first time, regardless of previously acquired protective immunity. This conundrum was resolved when it was observed...... that the selective placental accumulation of IEs that characterizes pregnancy-associated malaria (PAM) is caused by an immunologically and functionally unique subset of VSA (VSAPAM) that is only expressed by parasites infecting pregnant women, and that protective immunity to PAM is mediated by IgG with specificity...

  15. Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Ekström, Mattias

    2010-01-01

    The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Su...... to uncomplicated Plasmodium falciparum malaria....

  16. Morbidity from malaria and immune responses to defined Plasmodium falciparum antigens in children with sickle cell trait in The Gambia

    DEFF Research Database (Denmark)

    Allen, S J; Bennett, S; Riley, E M

    1993-01-01

    Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbA...

  17. Cellulose filtration of blood from malaria patients for improving ex vivo growth of Plasmodium falciparum parasites

    DEFF Research Database (Denmark)

    Mkumbaye, Sixbert I; Minja, Daniel T R; Jespersen, Jakob S;

    2017-01-01

    BACKGROUND: Establishing in vitro Plasmodium falciparum culture lines from patient parasite isolates can offer deeper understanding of geographic variations of drug sensitivity and mechanisms of malaria pathogenesis and immunity. Cellulose column filtration of blood is an inexpensive, rapid...... and effective method for the removal of host factors, such as leucocytes and platelets, significantly improving the purification of parasite DNA in a blood sample. METHODS: In this study, the effect of cellulose column filtration of venous blood on the initial in vitro growth of P. falciparum parasite isolates....... falciparum merozoite surface protein 2 genotyping was performed using nested PCR on extracted genomic DNA, and the var gene transcript levels were investigated, using quantitative PCR on extracted RNA, at admission and 4 days of culture. RESULTS: The cellulose-filtered parasites grew to higher parasitaemia...

  18. Serine Proteases of Malaria Parasite Plasmodium falciparum: Potential as Antimalarial Drug Targets

    Directory of Open Access Journals (Sweden)

    Asrar Alam

    2014-01-01

    Full Text Available Malaria is a major global parasitic disease and a cause of enormous mortality and morbidity. Widespread drug resistance against currently available antimalarials warrants the identification of novel drug targets and development of new drugs. Malarial proteases are a group of molecules that serve as potential drug targets because of their essentiality for parasite life cycle stages and feasibility of designing specific inhibitors against them. Proteases belonging to various mechanistic classes are found in P. falciparum, of which serine proteases are of particular interest due to their involvement in parasite-specific processes of egress and invasion. In P. falciparum, a number of serine proteases belonging to chymotrypsin, subtilisin, and rhomboid clans are found. This review focuses on the potential of P. falciparum serine proteases as antimalarial drug targets.

  19. Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Enfranze, north-west Ethiopia.

    Science.gov (United States)

    Getnet, Gebeyaw; Fola, Abebe Alemu; Alemu, Agersew; Getie, Sisay; Fuehrer, Hans-Peter; Noedl, Harald

    2015-06-24

    Plasmodium falciparum accounts for approximately 60% of malaria cases in Ethiopia and artemether-lumefantrine has been used as a first-line treatment for uncomplicated P. falciparum malaria since 2004. The aim of this study was to assess the therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of uncomplicated P. falciparum malaria in north-western Ethiopia. A 28-day one-arm, prospective evaluation of the clinical and parasitological response to the first-line treatment for uncomplicated P. falciparum malaria was conducted in Enfranze Health Centre in accordance with the 2009 WHO efficacy study guidelines. Patients were treated with a 3-day course of AL and clinical and parasitological parameters were monitored over a 28-day follow-up. All data from recruited patients were imported into an electronic data base and Kaplan-Meier survival analysis was used for analysing primary [early treatment failures (ETF), late clinical failure (LCF), late parasitological failures (LPF), and adequate clinical and parasitological response (ACPR)] and secondary (PCT, GCT and FCT) outcomes. Eighty patients were enrolled and all of them completed the 28-day follow-up period. The PCR-corrected cure rate was 95.0% (95% CI 87.0-98.4%) and there were two ETF, one LCF and three LPF. Two of the LPF were classified as re infections by PCR. Seventy three point seven five percent, 91.25 and 95% of patients had cleared their parasitaemia by days 1, 2, and 3, respectively, and 75, 91.25 and 96.25% of patients had cleared their fever by days 1, 2, and 3. All patients completely cleared their gametocytes by day 7. The relatively high cure rate, low proportion of patients still positive on day 3 as well as parasite clearance times in this study would indicate no imminent threat of artemisinin resistance development in the region. However, the threat of spreading or de novo development of artemisinin resistance warrants regular monitoring of drug efficacy throughout the region.

  20. Characterization of Plasmodium falciparum genes associated with drug resistance in Hodh Elgharbi, a malaria hotspot near Malian-Mauritanian border.

    Science.gov (United States)

    Ould Ahmedou Salem, Mohamed Salem; Mint Lekweiry, Khadijetou; Bouchiba, Houssem; Pascual, Aurelie; Pradines, Bruno; Ould Mohamed Salem Boukhary, Ali; Briolant, Sébastien; Basco, Leonardo K; Bogreau, Hervé

    2017-04-05

    A malaria hotspot in the southeastern region of Mauritania, near the Malian border, may hamper malaria control strategies. The objectives were to estimate the prevalence of genetic polymorphisms associated with drug resistance in Plasmodium falciparum isolates and establish baseline data. The study was conducted in two malaria-endemic areas in Hodh Elgharbi, situated in the Malian-Mauritanian border area. Blood samples were collected from symptomatic patients. Single nucleotide polymorphisms in Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps were genotyped using PCR-restriction fragment length polymorphism, DNA sequencing and primer extension. The Pfmdr1 gene copy number was determined by real-time PCR. Of 280 P. falciparum-infected patients, 193 (68.9%) carried the Pfcrt 76T mutant allele. The Pfmdr1 86Y and 184F mutations were found in 61 (23.1%) of 264 isolates and 167 (67.6%) of 247 samples that were successfully genotyped, respectively. Pfmdr1 mutant alleles 1034C, 1042D and 1246Y were rarely observed. Of 102 P. falciparum isolates analysed, ten (9.8%) had more than one copy of Pfmdr1 gene. The prevalence of isolates harbouring at least triple mutant Pfdhfr 51I, 59R, 108 N/T was 42% (112/268), of which 42 (37.5%) had an additional Pfdhps 437G mutation. The Pfdhps 540E mutation was observed in four isolates (1.5%), including three associated with Pfdhfr triple mutant. Only two quintuple mutants (Pfdhfr-51I-59R-108N Pfdhps-437G-540E) were observed. The observed mutations in Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt may jeopardize the future of seasonal malaria chemoprevention based on amodiaquine-sulfadoxine-pyrimethamine, intermittent preventive treatment for pregnant women using sulfadoxine-pyrimethamine, and treatment with artesunate-amodiaquine. Complementary studies should be carried out to document the distribution, origin and circulation of P. falciparum populations in this region and more widely in the country to assess the risk of the spread of resistance.

  1. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  2. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  3. Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

    DEFF Research Database (Denmark)

    Lundquist, Rasmus; Nielsen, Leif Kofoed; Jafarshad, Ali

    2006-01-01

    Immunoglobulins from individuals with immunity to malaria have a strong antiparasitic effect when transferred to Plasmodium falciparum malaria infected patients. One prominent target of antiparasitic antibodies is the merozoite surface antigen 3 (MSP-3). We have investigated the antibody response...

  4. Nanovaccines for Malaria Using Plasmodium falciparum Antigen Pfs25 Attached Gold Nanoparticles

    OpenAIRE

    Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti; Bansal, Geetha P.; Angov, Evelina; Kumar, Nirbhay

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinet...

  5. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

    OpenAIRE

    Fry, Andrew E.; Griffiths, Michael J.; Auburn, Sarah; Diakite, Mahamadou; Forton, Julian T.; Green, Angela; Richardson, Anna; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin; Malcolm E Molyneux

    2007-01-01

    There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across 3 African pop...

  6. Nanovaccines for Malaria Using Plasmodium falciparum Antigen Pfs25 Attached Gold Nanoparticles

    OpenAIRE

    kumar, Rajesh; Ray, Paresh C.; Datta, Dibyadyuti; Bansal, Geetha P.; Angov, Evelina; Kumar, Nirbhay

    2015-01-01

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinet...

  7. Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia.

    Directory of Open Access Journals (Sweden)

    Mohd Ridzuan Mohd Abd Razak

    Full Text Available Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1, merozoite surface protein-2 (MSP-2, glutamate rich protein (GLURP and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI, mean number of alleles (Na, expected heterozygosity (He, linkage disequilibrium (LD and genetic differentiation (FST were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01 and Kota Marudu P. falciparum populations (0.601, p<0.01. High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0

  8. Artesunate-amodiaquine versus artesunate-sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in children

    Directory of Open Access Journals (Sweden)

    Novie H. Rampengan

    2014-01-01

    Full Text Available Background Malaria is a major cause of morbidity and mortality in children, especially in developing countries. Artemisinin combination therapy (ACT has higher rates of parasite clearance and inhibition of anti-malarial drugs resistance than non-ACT. Hence, we compared the efficacies of artesunate-amodiaquine (AS-AQ versus artesunate-sulfadoxine pyrimethamine (AS-SP combination therapies in children with uncomplicated falciparum malaria. Objective To compare the fever clearance time, parasite clearance time, and length of hospital stay in uncomplicated falciparum malaria patients treated with AS-AQ and AS-SP. Methods We reviewed the medical records of children aged 1-14 years with uncomplicated falciparum malaria admitted to Prof. Dr. R. D. Kandou Hospital between January 2002 – June 2010. Treatment efficacy was evaluated by fever clearance time, parasite clearance time, and length of hospital stay. The differences of treatment efficacy between the two groups of therapy were analyzed by independent T-test. Results We identified 185 children with uncomplicated falciparum malaria, 104 cases were treated with AS-AQ while the other 81 received AS-SP. Parasite clearance time was shorter in AS-AQ group than in AS-SP group at 1.38 (SD 0.69 versus 1.91 (SD 0.93 days, respectively (95%CI of differences 0.30 to 0.76, P<0.05. The length of hospital stay was shorter in AS-AQ group than in the AS-SP group, at 5.01 (SD 1.22 versus 6.04 (SD 0.98 days, respectively (95%CI of differences 0.71 to 1.35, P<0.05. However, there was no statistically significant difference in fever clearance time between the groups. Conclusion AS-AQ combination therapy reduces parasite clearance time and length of hospital stay compared to AS-SP combination therapy in children with uncomplicated falciparum malaria. [Paediatr Indones. 2014;54:46-51.].

  9. [Establishment of early warning system of malaria in Jiangsu Province V Es- tablishment of prevention and control system of imported falciparum malaria].

    Science.gov (United States)

    Wang, Wei-ming; Zhou, Hua-yun; Liu, Yao-bao; Cao, Yuan-yuan; Cao, Jun; Gao, Qi

    2015-08-01

    To establish a system of the prevention and control of imported falciparum malaria in Jiangsu Prov- ince and provide the new scientific basis for the prevention and control of imported falciparum malaria. The data- bases for overseas labor companies and labors in Jiangsu Province were built and the health education was conducted to the overseas labors. The "1-3-7" elimination strategy was established. A weekly reporting system for malaria case details was es- tablished. A system for screening accompanies of imported malaria patients was established. At the end of 2013, the database of companies engaged in labor export was built and1 405 companies were incorporated into the database. The time interval between the symptom onset and the first health facility visit was reduced to 3.07 days in 2013. The time interval be- tween the first health facility visit to malaria diagnosis was reduced to 1.57 days in 2013. The rate of laboratory confirmation was increased to 100% in 2013, and there was a statistically significant difference among the rates of laboratory confirmation from 2009 to 2013 (χ2 = 36.35, P system of the prevention and control of imported falciparum malaria, which plays an important role in the prevention and control of overseas imported falciparum malaria.

  10. Acute Kidney Injury in Children with Plasmodium falciparum Malaria: Determinants for Mortality.

    Science.gov (United States)

    Prasad, Rajniti; Mishra, Om P

    2016-01-01

    ♦ Acute kidney injury (AKI) in P. falciparum malaria infection is an important morbidity in children. The purpose of the present study was done to observe the renal involvement, associated morbidities and outcome. ♦ Out of 156 patients with severe P. falciparum malaria, diagnosed on the basis of compatible clinical presentations and positive malarial parasites in the peripheral blood smear and/or histidine rich protein 2 antigen, 31 had AKI at presentation and were analyzed. ♦ Of 31 (19.9%) patients with AKI, 4 were classified at risk, 11 injury, and 16 failure stage, as per pRIFLE criteria (pediatric version of RIFLE [R = risk, I = injury, F = failure, L = loss E = end-stage kidney disease]). Mean age of children with AKI was 7.7 ± 3.2 years. A significantly higher proportion of patients with AKI had hypoglycemia (41.9%), pulmonary edema (32.2%), and disseminated intravascular coagulation (DIC) (29.0%) compared to those without AKI (18.4%, 4.8%, and 3.2%, respectively). Twelve patients (38.7%) required peritoneal dialysis (PD), 8 (25.8%) died, and all were in failure stage. The non-survivors had significantly higher blood urea (p = 0.005) and serum creatinine levels (p = 0.042), lower glomerular filtration rate (p falciparum malaria is one of the severe systemic complications. Duration of illness and presence of comorbidities adversely affected the outcome. Copyright © 2016 International Society for Peritoneal Dialysis.

  11. Antigenic variation and the genetics and epigenetics of the PfEMP1 erythrocyte surface antigens in Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Arnot, David E; Jensen, Anja T R

    2011-01-01

    do become immune to P. falciparum malaria, but this is a slow process requiring multiple disease episodes which many, particularly young children, do not survive. Adult survivors are immune to the symptoms of malaria, and unless pregnant, can control the growth of most or all new inoculations....... Sterile immunity is not achieved and chronic parasitization of apparently healthy adults is the norm. In this article, we analyse the best understood malaria "antigenic variation" system, that based on Plasmodium falciparum's PfEMP1-type cytoadhesion antigens, and critically review recent literature...

  12. Evidence of non-Plasmodium falciparum malaria infection in Kédougou, Sénégal.

    Science.gov (United States)

    Daniels, Rachel F; Deme, Awa Bineta; Gomis, Jules F; Dieye, Baba; Durfee, Katelyn; Thwing, Julie I; Fall, Fatou B; Ba, Mady; Ndiop, Medoune; Badiane, Aida S; Ndiaye, Yaye Die; Wirth, Dyann F; Volkman, Sarah K; Ndiaye, Daouda

    2017-01-03

    Expanded malaria control efforts in Sénégal have resulted in increased use of rapid diagnostic tests (RDT) to identify the primary disease-causing Plasmodium species, Plasmodium falciparum. However, the type of RDT utilized in Sénégal does not detect other malaria-causing species such as Plasmodium ovale spp., Plasmodium malariae, or Plasmodium vivax. Consequently, there is a lack of information about the frequency and types of malaria infections occurring in Sénégal. This study set out to better determine whether species other than P. falciparum were evident among patients evaluated for possible malaria infection in Kédougou, Sénégal. Real-time polymerase chain reaction speciation assays for P. vivax, P. ovale spp., and P. malariae were developed and validated by sequencing and DNA extracted from 475 Plasmodium falciparum-specific HRP2-based RDT collected between 2013 and 2014 from a facility-based sample of symptomatic patients from two health clinics in Kédougou, a hyper-endemic region in southeastern Sénégal, were analysed. Plasmodium malariae (n = 3) and P. ovale wallikeri (n = 2) were observed as co-infections with P. falciparum among patients with positive RDT results (n = 187), including one patient positive for all three species. Among 288 negative RDT samples, samples positive for P. falciparum (n = 24), P. ovale curtisi (n = 3), P. ovale wallikeri (n = 1), and P. malariae (n = 3) were identified, corresponding to a non-falciparum positivity rate of 2.5%. These findings emphasize the limitations of the RDT used for malaria diagnosis and demonstrate that non-P. falciparum malaria infections occur in Sénégal. Current RDT used for routine clinical diagnosis do not necessarily provide an accurate reflection of malaria transmission in Kédougou, Sénégal, and more sensitive and specific methods are required for diagnosis and patient care, as well as surveillance and elimination activities. These findings have implications for other

  13. Effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria in outbreak prone districts of Rajasthan, India.

    Science.gov (United States)

    Lingala, Mercy A L

    2017-03-09

    Malaria is a public health problem caused by Plasmodium parasite and transmitted by anopheline mosquitoes. Arid and semi-arid regions of western India are prone to malaria outbreaks. Malaria outbreak prone districts viz. Bikaner, Barmer and Jodhpur were selected to study the effect of meteorological variables on Plasmodium vivax and Plasmodium falciparum malaria outbreaks for the period of 2009-2012. The data of monthly malaria cases and meteorological variables was analysed using SPSS 20v. Spearman correlation analysis was conducted to examine the strength of the relationship between meteorological variables, P. vivax and P. falciparum malaria cases. Pearson's correlation analysis was carried out among the meteorological variables to observe the independent effect of each independent variable on the outcome. Results indicate that malaria outbreaks have occurred in Bikaner and Barmer due to continuous rains for more than two months. Rainfall has shown to be an important predictor of malaria outbreaks in Rajasthan. P. vivax is more significantly correlated with rainfall, minimum temperature (P<0.01) and less significantly with relative humidity (P<0.05); whereas P. falciparum is significantly correlated with rainfall, relative humidity (P<0.01) and less significantly with temperature (P<0.05). The determination of the lag period for P. vivax is relative humidity and for P. falciparum is temperature. The lag period between malaria cases and rainfall is shorter for P. vivax than P. falciparum. In conclusion, the knowledge generated is not only useful to take prompt malaria control interventions but also helpful to develop better forecasting model in outbreak prone regions. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  14. Randomized clinical trial of artemisinin versus non-artemisinin combination therapy for uncomplicated falciparum malaria in Madagascar

    Directory of Open Access Journals (Sweden)

    Ratsimbasoa Arsène

    2007-05-01

    Full Text Available Abstract Background Data concerning antimalarial combination treatment for uncomplicated malaria in Madagascar are largely lacking. Randomized clinical trial was designed to assess therapeutic efficacies of chloroquine (CQ, amodiaquine (AQ, sulphadoxine-pyrimethamine (SP, amodiaquine plus sulphadoxine-pyrimethamine combination (AQ+SP and artesunate plus amodiaquine combination (AQ+AS. Methods 287 children between 6 months and 15 years of age, with uncomplicated falciparum malaria, were enrolled in the study. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Results All treatment regimens, except for CQ treatment, gave clinical cure rates above 97% by day-14 and 92% by day-28 (PCR-corrected. AQ+SP was as effective as AQ+AS. The risk of new infection within the month after therapy was generally higher for AQ+AS than AQ+SP. Conclusion These findings show that the inexpensive and widely available combination AQ+SP may be valuable in for the treatment of uncomplicated malaria in Madagascar and could have an important role in this country, where much of the drugs administered go to patients who do not have malaria.

  15. Mefloquine pharmacokinetics and mefloquine-artesunate effectiveness in Peruvian patients with uncomplicated Plasmodium falciparum malaria

    Directory of Open Access Journals (Sweden)

    Quezada Wilmer

    2009-04-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is recommended as a means of prolonging the effectiveness of first-line malaria treatment regimens. Different brands of mefloquine (MQ have been reported to be non-bioequivalent; this could result in sub-therapeutic levels of mefloquine with decreased efficacy. In 2002, mefloquine-artesunate (MQ-AS combination therapy was adopted as the first-line treatment for uncomplicated Plasmodium falciparum malaria in the Amazon region of Peru. Although MQ resistance has yet to be reported from the Peruvian Amazon, it has been reported from other countries in the Amazon Region. Therefore, continuous monitoring is warranted to ensure that the first-line therapy remains efficacious. This study examines the in vivo efficacy and pharmacokinetic parameters through Day 56 of three commercial formulations of MQ (Lariam®, Mephaquin®, and Mefloquina-AC® Farma given in combination with artesunate. Methods Thirty-nine non-pregnant adults with P. falciparum mono-infection were randomly assigned to receive artesunate in combination with either (1 Lariam, (2 Mephaquin, or (3 Mefloquina AC. Patients were assessed on Day 0 (with blood samples for pharmacokinetics at 0, 2, 4, and 8 hours, 1, 2, 3, 7, and then weekly until day 56. Clinical and parasitological outcomes were based on the standardized WHO protocol. Whole blood mefloquine concentrations were determined by high-performance liquid chromatography and pharmacokinetic parameters were determined using non-compartmental analysis of concentration versus time data. Results By day 3, all patients had cleared parasitaemia except for one patient in the AC Farma arm; this patient cleared by day 4. No recurrences of parasitaemia were seen in any of the 34 patients. All three MQ formulations had a terminal half-life of 14–15 days and time to maximum plasma concentration of 45–52 hours. The maximal concentration (Cmax and interquartile range was 2,820 ng

  16. High antibody responses against Plasmodium falciparum in immigrants after extended periods of interrupted exposure to malaria.

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    Gemma Moncunill

    Full Text Available BACKGROUND: Malaria immunity is commonly believed to wane in the absence of Plasmodium falciparum exposure, based on limited epidemiological data and short-lived antibody responses in some longitudinal studies in endemic areas. METHODS: A cross-sectional study was conducted among sub-Saharan African adults residing in Spain for 1 up to 38 years (immigrants with clinical malaria (n=55 or without malaria (n=37, naïve adults (travelers with a first clinical malaria episode (n=20 and life-long malaria exposed adults from Mozambique (semi-immune adults without malaria (n=27 or with clinical malaria (n=50. Blood samples were collected and IgG levels against the erythrocytic antigens AMA-1 and MSP-1₄₂ (3D7 and FVO strains, EBA-175 and DBL-α were determined by Luminex. IgG levels against antigens on the surface of infected erythrocytes (IEs were measured by flow cytometry. RESULTS: Immigrants without malaria had lower IgG levels than healthy semi-immune adults regardless of the antigen tested (P≤0.026, but no correlation was found between IgG levels and time since migration. Upon reinfection, immigrants with malaria had higher levels of IgG against all antigens than immigrants without malaria. However, the magnitude of the response compared to semi-immune adults with malaria depended on the antigen tested. Thus, immigrants had higher IgG levels against AMA-1 and MSP-1₄₂ (P≤0.015, similar levels against EBA-175 and DBL-α, and lower levels against IEs (P≤0.016. Immigrants had higher IgG levels against all antigens tested compared to travelers (P≤0.001, both with malaria. CONCLUSIONS: Upon cessation of malaria exposure, IgG responses to malaria-specific antigens were maintained to a large extent, although the conservation and the magnitude of the recall response depended on the nature of the antigen. Studies on immigrant populations can shed light on the factors that determine the duration of malaria specific antibody responses and its

  17. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

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    Neida K Mita-Mendoza

    Full Text Available BACKGROUND: Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. METHODOLOGY/PRINCIPAL FINDINGS: We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1, vascular cell adhesion molecule-1 (sVCAM-1, E-selectin (sE-Selectin, thrombomodulin (sTM, tissue factor (sTF and vascular endothelial growth factor (VEGF in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487 and non-cerebral severe malaria (NCSM, n = 68. In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season. We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001. Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043, sICAM-1 (r = 0.255, p<0.0001 and sTM (r = 0.175, p = 0.0001 levels. After adjusting for parasite density, UA levels predict sTM levels. CONCLUSIONS/SIGNIFICANCE: Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of

  18. A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

    Science.gov (United States)

    Mita-Mendoza, Neida K; van de Hoef, Diana L; Lopera-Mesa, Tatiana M; Doumbia, Saibou; Konate, Drissa; Doumbouya, Mory; Gu, Wenjuan; Anderson, Jennifer M; Santos-Argumedo, Leopoldo; Rodriguez, Ana; Fay, Michael P; Diakite, Mahamadou; Long, Carole A; Fairhurst, Rick M

    2013-01-01

    Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria. We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels. Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in

  19. Model variations in predicting incidence of Plasmodium falciparum malaria using 1998-2007 morbidity and meteorological data from south Ethiopia

    Science.gov (United States)

    2010-01-01

    Background Malaria transmission is complex and is believed to be associated with local climate changes. However, simple attempts to extrapolate malaria incidence rates from averaged regional meteorological conditions have proven unsuccessful. Therefore, the objective of this study was to determine if variations in specific meteorological factors are able to consistently predict P. falciparum malaria incidence at different locations in south Ethiopia. Methods Retrospective data from 42 locations were collected including P. falciparum malaria incidence for the period of 1998-2007 and meteorological variables such as monthly rainfall (all locations), temperature (17 locations), and relative humidity (three locations). Thirty-five data sets qualified for the analysis. Ljung-Box Q statistics was used for model diagnosis, and R squared or stationary R squared was taken as goodness of fit measure. Time series modelling was carried out using Transfer Function (TF) models and univariate auto-regressive integrated moving average (ARIMA) when there was no significant predictor meteorological variable. Results Of 35 models, five were discarded because of the significant value of Ljung-Box Q statistics. Past P. falciparum malaria incidence alone (17 locations) or when coupled with meteorological variables (four locations) was able to predict P. falciparum malaria incidence within statistical significance. All seasonal AIRMA orders were from locations at altitudes above 1742 m. Monthly rainfall, minimum and maximum temperature was able to predict incidence at four, five and two locations, respectively. In contrast, relative humidity was not able to predict P. falciparum malaria incidence. The R squared values for the models ranged from 16% to 97%, with the exception of one model which had a negative value. Models with seasonal ARIMA orders were found to perform better. However, the models for predicting P. falciparum malaria incidence varied from location to location, and among

  20. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe.

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    Susanne H Sheehy

    Full Text Available Controlled human malaria infection (CHMI studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18. Six participants received 2,500 sporozoites intradermally (ID, six received 2,500 sporozoites intramuscularly (IM and six received 25,000 sporozoites IM.Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test.2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.ClinicalTrials.gov NCT01465048.

  1. Artemether-Lumefantrine versus Dihydroartemisinin-Piperaquine for Treatment of Uncomplicated Plasmodium falciparum Malaria in Children Aged Less than 15 Years in Guinea-Bissau - An Open-Label Non-Inferiority Randomised Clinical Trial

    DEFF Research Database (Denmark)

    Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia

    2016-01-01

    BACKGROUND: Artemether-lumefantrine (AL) was introduced for treatment of uncomplicated malaria in Guinea-Bissau in 2008. Malaria then resurged and recurrent malaria after treatment with AL and stock-outs of AL were common. This study therefore aimed to assess the efficacy of AL and identify an al...... treatments. CONCLUSIONS: Both treatments achieved the WHO recommended efficacy for antimalarials about to be adopted as policy. DP was not inferior to AL for treatment of uncomplicated P. falciparum malaria in Guinea-Bissau. TRIAL REGISTRATION: ClinicalTrials.gov NTC01704508....

  2. 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.

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

    Science.gov (United States)

    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

  4. In vivo drug resistance of falciparum malaria in mining areas of Venezuela.

    Science.gov (United States)

    Aché, A; Escorihuela, M; Vivas, E; Páez, E; Miranda, L; Matos, A; Pérez, W; Díaz, O; Izarra, E

    2002-09-01

    The Lot Quality Assurance Double-Sampling Plan (LQADSP) technique was used in three areas, Maripa, Kilómetro 88 and Ikabaru, to assess the efficacy of antimalarials used routinely by the Venezuelan Malaria Programme. The use of chloroquine (25 mg/kg), chloroquine (40 mg/kg) and the combination of sulfadoxine (500 mg) and pyrimethamine (25 mg) registered treatment failures above the threshold level of 25% in Maripa and Kilómertro 88. In Ikabaru the use of chloroquine (40 mg/kg) did not surpass that quality level and could possibly be less than 10%. Quinine (30 mg/kg) was totally effective in curing patients in all three areas. The use of this technique seems adequate for rapid field evaluations and in this case for providing appropriate information to assist this health programme. However, whilst being an ideal technique for surveying areas in which considerable variation may exist among lots and particularly for Plasmodium falciparum infections in these areas, repeated surveys should be carried out in the same areas over time to monitor changes in the susceptibility of this parasite to first-, second- and third-line drugs. In that way, national drug policies can be modified adequately.

  5. The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

    Science.gov (United States)

    Bhatt, S; Weiss, D J; Cameron, E; Bisanzio, D; Mappin, B; Dalrymple, U; Battle, K E; Moyes, C L; Henry, A; Eckhoff, P A; Wenger, E A; Briët, O; Penny, M A; Smith, T A; Bennett, A; Yukich, J; Eisele, T P; Griffin, J T; Fergus, C A; Lynch, M; Lindgren, F; Cohen, J M; Murray, C L J; Smith, D L; Hay, S I; Cibulskis, R E; Gething, P W

    2015-10-01

    Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

  6. Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria.

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    Federica Verra

    Full Text Available A recently proposed mechanism of protection for haemoglobin C (HbC; beta6Glu-->Lys links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS; ii total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria.

  7. Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes

    DEFF Research Database (Denmark)

    Garred, Peter; Nielsen, Morten A; Kurtzhals, Jørgen

    2003-01-01

    associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe...

  8. Acute P. falciparum malaria induces a loss of CD28- T IFN-¿ producing cells

    DEFF Research Database (Denmark)

    Kemp, Kåre; Akanmori, Bartholomew D; Kurtzhals, Jørgen A L

    2002-01-01

    P. falciparum malaria is associated with increased activation among peripheral lymphocytes. In the present study, we investigated markers of susceptibility to apoptosis and expression of IFN-gamma and IL-4 by CD28-and CD28+T cells in West African children with acute P. falciparum malaria. The stu...

  9. A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available BACKGROUND: Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human antibodies (from malaria-immune adults that are able to mediate a monocyte-dependent parasite killing effect. The corresponding long synthetic peptide was administered to 36 volunteers, with either alum or Montanide ISA720 as adjuvant. METHODS AND FINDINGS: Both formulations induced cellular and humoral immune responses. With alum, the responses lasted up to 12 mo. The vaccine-induced antibodies were predominantly of cytophilic classes, i.e., able to cooperate with effector cells. In vitro, the antibodies induced an inhibition of the P. falciparum erythrocytic growth in a monocyte-dependent manner, which was in most instances as high as or greater than that induced by natural antibodies from immune African adults. In vivo transfer of the volunteers' sera into P. falciparum-infected humanized SCID mice profoundly reduced or abrogated parasitaemia. These inhibitory effects were related to the antibody reactivity with the parasite native protein, which was seen in 60% of the volunteers, and remained in samples taken 12 mo postimmunisation. CONCLUSION: This is the first malaria vaccine clinical trial to clearly demonstrate antiparasitic activity by vaccine-induced antibodies by both in vitro and in vivo methods. The results, showing the induction of long-lasting antibodies directed to a fully conserved polypeptide, also challenge current concepts about malaria vaccines, such as unavoidable polymorphism, low antigenicity, and poor induction of immune memory.

  10. A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Pierre Druilhe

    2005-11-01

    Full Text Available Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human antibodies (from malaria-immune adults that are able to mediate a monocyte-dependent parasite killing effect. The corresponding long synthetic peptide was administered to 36 volunteers, with either alum or Montanide ISA720 as adjuvant.Both formulations induced cellular and humoral immune responses. With alum, the responses lasted up to 12 mo. The vaccine-induced antibodies were predominantly of cytophilic classes, i.e., able to cooperate with effector cells. In vitro, the antibodies induced an inhibition of the P. falciparum erythrocytic growth in a monocyte-dependent manner, which was in most instances as high as or greater than that induced by natural antibodies from immune African adults. In vivo transfer of the volunteers' sera into P. falciparum-infected humanized SCID mice profoundly reduced or abrogated parasitaemia. These inhibitory effects were related to the antibody reactivity with the parasite native protein, which was seen in 60% of the volunteers, and remained in samples taken 12 mo postimmunisation.This is the first malaria vaccine clinical trial to clearly demonstrate antiparasitic activity by vaccine-induced antibodies by both in vitro and in vivo methods. The results, showing the induction of long-lasting antibodies directed to a fully conserved polypeptide, also challenge current concepts about malaria vaccines, such as unavoidable polymorphism, low antigenicity, and poor induction of immune memory.

  11. [Evaluation of imported Plasmodium falciparum malaria cases: the use of polymerase chain reaction in diagnosis].

    Science.gov (United States)

    Demiraslan, Hayati; Erdoğan, Emrah; Türe, Zeynep; Kuk, Salih; Yazar, Süleyman; Metan, Gökhan

    2013-10-01

    Malaria affecting almost half of the world population continues to be an important health problem. Although domestic malaria cases have been decreasing in Turkey recently, cases caused by Plasmodium falciparum have increased due to the frequent travelling to Africa. The aims of this study were to evaluate demographic characteristics, clinical and laboratory findings in cases with falciparum malaria who attended to our clinic in 2012-2013 period, and the impact of polymerase chain reaction (PCR) for diagnosis. Nine patients evaluated were all male with a mean age of 34.3 (age range: 18-48) years, with the history of travel to Africa. Six cases did not take prophylaxis against malaria and other three cases used insufficient time. Mean duration of symptoms after return was 18.4 (range: 1-75) days, and the patients were admitted to the clinic within a mean of 5.2 (range: 1-15) days. Two patients had leucopenia, two patients had anemia, and eight patients had thrombocytopenia on admission. Alanine aminotransferase (ALT) levels in four cases and total bilirubin levels of six cases were over upper normal limits. Definitive diagnosis of cases was performed with the detection of ring and/or gametocytes forms of the parasite in Giemsa-stained peripheral blood smears. Furthermore, samples from seven patients were studied by nested PCR by using genus (Plasmodium rPLU 1 and 5) and species (rFAL 1 and 2, rVIV 1 and 2, rMAL 1 and 2, rOVA 1 and 2) specific primers. All of these seven samples yielded positive results with primers specific for P.falciparum ssrRNA. In the treatment, arthemeter/lumefantrin and doxycycline combination was used in seven patients, while intravenous artesunate and doxycycline combination was given to two patients, resulting with complete cure. Mean duration for the resolving of fever was 3.3 days, and mean duration for clearing the parasitemia from peripheral blood was 4.9 days. Initial ALT values and the duration of fever resolution (-796; p= 0.010), as

  12. Molecular Investigation into a Malaria Outbreak in Cusco, Peru: Plasmodium falciparum BV1 Lineage is Linked to a Second Outbreak in Recent Times.

    Science.gov (United States)

    Okoth, Sheila Akinyi; Chenet, Stella M; Arrospide, Nancy; Gutierrez, Sonia; Cabezas, Cesar; Matta, Jose Antonio; Udhayakumar, Venkatachalam

    2016-01-01

    In November 2013, a Plasmodium falciparum malaria outbreak of 11 cases occurred in Cusco, southern Peru, where falciparum malaria had not been reported since 1946. Although initial microscopic diagnosis reported only Plasmodium vivax infection in each of the specimens, subsequent examination by the national reference laboratory confirmed P. falciparum infection in all samples. Molecular typing of four available isolates revealed identity as the B-variant (BV1) strain that was responsible for a malaria outbreak in Tumbes, northern Peru, between 2010 and 2012. The P. falciparum BV1 strain is multidrug resistant, can escape detection by PfHRP2-based rapid diagnostic tests, and has contributed to two malaria outbreaks in Peru. This investigation highlights the importance of accurate species diagnosis given the potential for P. falciparum to be reintroduced to regions where it may have been absent. Similar molecular epidemiological investigations can track the probable source(s) of outbreak parasite strains for malaria surveillance and control purposes.

  13. [Falciform anemia and Plasmodium falciparum malaria: a threat to flap survival?].

    Science.gov (United States)

    Mariéthoz, S; Pittet, B; Loutan, L; Humbert, J; Montandon, D

    1999-02-01

    Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a hereditary disease, are two diseases affecting erythrocyte cycle, occurring with a high prevalence in tropical Africa. They may induce microthrombosis inducing vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of Plasmodium falciparum malaria, destruction of parasitized and healthy erythrocytes, release of parasite and erythrocyte material into the circulation, and secondary host reaction occur. Plasmodium falciparum infected erythrocytes also sequester in the microcirculation of vital organs and may interfere with microcirculatory flow in the flap during the postoperative period. The lower legs of homozygous sickle cell anemia patients are areas of marginal vascularity where minor abrasions become foci of inflammation. Inflammation results in decreased local oxygen tension, sickling of erythrocytes, increased blood viscosity and thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue transfer has become the procedure of choice for reconstruction of the lower third of the leg although flaps may become necrotic. The aim of this study is to analyse circumstances predisposing to surgical complications and to define preventive and therapeutic measures. A review of the literature will describe the current research and the new perspectives to treat sickle cell anemia, for example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl, buflomedil).

  14. Evasion of immunity to Plasmodium falciparum malaria by IgM masking of protective IgG epitopes in infected erythrocyte surface-exposed PfEMP1

    DEFF Research Database (Denmark)

    Barfod, Lea; Dalgaard, Michael B; Pleman, Suzan T

    2011-01-01

    Plasmodium falciparum malaria is a major cause of mortality and severe morbidity. Its virulence is related to the parasite's ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein...... epitopes not prone to IgM masking are likely to be particularly important targets of acquired protective immunity to P. falciparum malaria....

  15. Comparison of different methods for delayed post-mortem diagnosis of falciparum malaria

    Directory of Open Access Journals (Sweden)

    Fleischmann Erna

    2009-10-01

    Full Text Available Abstract Background Between 10,000 and 12,000 cases of imported malaria are notified in the European Union each year. Despite an excellent health care system, fatalities do occur. In case of advanced autolysis, the post-mortem diagnostic is impaired. Quicker diagnosis could be achieved by using rapid diagnostic malaria tests. Methods In order to evaluate different methods for the post-mortem diagnosis of Plasmodium falciparum malaria in non-immunes, a study was performed on the basis of forensic autopsies of corpses examined at variable intervals after death in five cases of fatal malaria (with an interval of four hours to five days, and in 20 cases of deaths unrelated to malaria. Detection of parasite DNA by PCR and an immunochromatographic test (ICT based upon the detection of P. falciparum histidine-rich protein 2 (PfHRP2 were compared with the results of microscopic examination of smears from cadaveric blood, histopathological findings, and autopsy results. Results In all cases of fatal malaria, post-mortem findings were unsuspicious for the final diagnosis, and autoptic investigations, including histopathology, were only performed because of additional information by police officers and neighbours. Macroscopic findings during autopsy were unspecific. Histopathology confirmed sequestration of erythrocytes and pigment in macrophages in most organs in four patients (not evaluable in one patient due to autolysis. Microscopy of cadaveric blood smears revealed remnants of intraerythrocytic parasites, and was compromised or impossible due to autolysis in two cases. PCR and ICT performed with cadaveric blood were positive in all malaria patients and negative in all controls. Conclusion In non-immune fatalities with unclear anamnesis, ICT can be recommended as a sensitive and specific tool for post-mortem malaria diagnosis, which is easier and faster than microscopy, and also applicable when microscopic examination is impossible due to autolysis

  16. Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

    Directory of Open Access Journals (Sweden)

    Edgar Leonardo Martínez-Salazar

    2014-06-01

    Full Text Available Introduction Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Methods Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8% patients infected with Plasmodium falciparum, 311 (36.1% patients infected with Plasmodium vivax and 18 (2.1% patients with mixed infections. Results The most frequently observed changes were low platelet count (PC and high platelet distribution width (PDW, which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction, renal impairment and severe hypoglycemia. The presence of thrombocytopenia (<150,000 platelets/µL was associated with a higher probability of liver dysfunction. Conclusions Young age, longer duration of illness and higher parasitemia are associated with severe thrombocytopenia. Our study showed that thrombocytopenia is related to malaria complications, especially liver dysfunction. High PDW in patients with severe malaria may explain the mechanisms of thrombocytopenia that is common in this group of patients.

  17. Population pharmacokinetics of Artemether and dihydroartemisinin in pregnant women with uncomplicated Plasmodium falciparum malaria in Uganda

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    Tarning Joel

    2012-08-01

    Full Text Available Abstract Background Malaria in pregnancy increases the risk of maternal anemia, abortion and low birth weight. Approximately 85.3 million pregnancies occur annually in areas with Plasmodium falciparum transmission. Pregnancy has been reported to alter the pharmacokinetic properties of many anti-malarial drugs. Reduced drug exposure increases the risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of artemether and its active metabolite dihydroartemisinin in pregnant women with uncomplicated P. falciparum malaria in Uganda. Methods Twenty-one women with uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy received the fixed oral combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Artemether and dihydroartemisinin plasma concentrations after the last dose administration were quantified using liquid chromatography coupled to tandem mass-spectroscopy. A simultaneous drug-metabolite population pharmacokinetic model for artemether and dihydroartemisinin was developed taking into account different disposition, absorption, error and covariate models. A separate modeling approach and a non-compartmental analysis (NCA were also performed to enable a comparison with literature values and different modeling strategies. Results The treatment was well tolerated and there were no cases of recurrent malaria. A flexible absorption model with sequential zero-order and transit-compartment absorption followed by a simultaneous one-compartment disposition model for both artemether and dihydroartemisinin provided the best fit to the data. Artemether and dihydroartemisinin exposure was lower than that reported in non-pregnant populations. An approximately four-fold higher apparent volume of distribution for dihydroartemisinin was obtained by non-compartmental analysis and separate modeling compared to that from simultaneous modeling of the drug

  18. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  19. High Rates of Asymptomatic, Sub-microscopic Plasmodium vivax Infection and Disappearing Plasmodium falciparum Malaria in an Area of Low Transmission in Solomon Islands.

    Science.gov (United States)

    Waltmann, Andreea; Darcy, Andrew W; Harris, Ivor; Koepfli, Cristian; Lodo, John; Vahi, Ventis; Piziki, David; Shanks, G Dennis; Barry, Alyssa E; Whittaker, Maxine; Kazura, James W; Mueller, Ivo

    2015-05-01

    Solomon Islands is intensifying national efforts to achieve malaria elimination. A long history of indoor spraying with residual insecticides, combined recently with distribution of long lasting insecticidal nets and artemether-lumefantrine therapy, has been implemented in Solomon Islands. The impact of these interventions on local endemicity of Plasmodium spp. is unknown. In 2012, a cross-sectional survey of 3501 residents of all ages was conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was determined by reverse transcription quantitative PCR (RT-qPCR). By qPCR, 468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax, five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P. vivax). The prevalence of P. vivax infection varied significantly among villages (range 3.0-38.5%, p<0.001) and across age groups (5.3-25.9%, p<0.001). Of 468 P. vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both sub-microscopic and afebrile. Local residency, low education level of the household head and living in a household with at least one other P. vivax infected individual increased the risk of P. vivax infection. Overall, 23.5% of P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P. falciparum infections were detected in residents of the same village, carried the same msp2 allele and four were positive for P. falciparum gametocytes. P. vivax infection remains endemic in Ngella, with the majority of cases afebrile and below the detection limit of LM. P. falciparum has nearly disappeared, but the risk of re-introductions and outbreaks due to travel to nearby islands

  20. Global histone analysis by mass spectrometry reveals a high content of acetylated lysine residues in the malaria parasite Plasmodium falciparum

    DEFF Research Database (Denmark)

    Trelle, Morten Beck; Salcedo-Amaya, Adriana M; Cohen, Adrian

    2009-01-01

    Post-translational modifications (PTMs) of histone tails play a key role in epigenetic regulation of gene expression in a range of organisms from yeast to human, however, little is known about histone proteins from the parasite that causes malaria in humans, Plasmodium falciparum. We characterize...... comprehensive map of histone modifications in Plasmodium falciparum and highlight the utility of tandem MS for detailed analysis of peptides containing multiple PTMs....

  1. Opsonising antibodies to P. falciparum merozoites associated with immunity to clinical malaria.

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    Danika L Hill

    Full Text Available Naturally acquired humoral immunity to the malarial parasite Plasmodium falciparum can protect against disease, although the precise mechanisms remain unclear. Although antibody levels can be measured by ELISA, few studies have investigated functional antibody assays in relation to clinical outcomes. In this study we applied a recently developed functional assay of antibody-mediated opsonisation of merozoites, to plasma samples from a longitudinal cohort study conducted in a malaria endemic region of Papua New Guinea (PNG. Phagocytic activity was quantified by flow cytometry using a standardized and high-throughput protocol, and was subsequently evaluated for association with protection from clinical malaria and high-density parasitemia. Opsonising antibody responses were found to: i increase with age, ii be enhanced by concurrent infection, and iii correlate with protection from clinical episodes and high-density parasitemia. Stronger protective associations were observed in individuals with no detectable parasitemia at baseline. This study presents the first evidence for merozoite phagocytosis as a correlate of acquired immunity and clinical protection against P. falciparum malaria.

  2. Within-host competition and drug resistance in the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Bushman, Mary; Morton, Lindsay; Duah, Nancy; Quashie, Neils; Abuaku, Benjamin; Koram, Kwadwo A; Dimbu, Pedro Rafael; Plucinski, Mateusz; Gutman, Julie; Lyaruu, Peter; Kachur, S Patrick; de Roode, Jacobus C; Udhayakumar, Venkatachalam

    2016-03-16

    Infections with the malaria parasite Plasmodium falciparum typically comprise multiple strains, especially in high-transmission areas where infectious mosquito bites occur frequently. However, little is known about the dynamics of mixed-strain infections, particularly whether strains sharing a host compete or grow independently. Competition between drug-sensitive and drug-resistant strains, if it occurs, could be a crucial determinant of the spread of resistance. We analysed 1341 P. falciparum infections in children from Angola, Ghana and Tanzania and found compelling evidence for competition in mixed-strain infections: overall parasite density did not increase with additional strains, and densities of individual chloroquine-sensitive (CQS) and chloroquine-resistant (CQR) strains were reduced in the presence of competitors. We also found that CQR strains exhibited low densities compared with CQS strains (in the absence of chloroquine), which may underlie observed declines of chloroquine resistance in many countries following retirement of chloroquine as a first-line therapy. Our observations support a key role for within-host competition in the evolution of drug-resistant malaria. Malaria control and resistance-management efforts in high-transmission regions may be significantly aided or hindered by the effects of competition in mixed-strain infections. Consideration of within-host dynamics may spur development of novel strategies to minimize resistance while maximizing the benefits of control measures.

  3. Paludismo por Plasmodium falciparum adquirido en África subsahariana Plasmodium falciparum malaria acquired in Subsaharian Africa

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    Ricardo Durlach

    2009-02-01

    Full Text Available El objetivo de este trabajo es presentar los casos de paludismo por Plasmodium falciparum ocurridos en viajeros provenientes del África tropical, atendidos en el Hospital Alemán. Se definió paludismo de origen africano como la infección adquirida en un país del África subsahariana, diagnosticado y tratado en la Argentina. El diagnóstico se realizó por la clínica y la microscopía óptica en frotis de sangre periférica coloreados con Giemsa. Se revieron las historias clínicas de 11 pacientes adultos -cinco turistas y seis marineros mercantes- no oriundos de área endémica, sin condición inmunosupresora, ni morbilidad asociada, internados entre 1993 y 2007. El rango de edad fue de 21 a 48 años; nueve hombres y dos mujeres. Los pacientes fueron clasificados retrospectivamente en malaria grave (seis o no grave (cinco según cumplieran con uno o más de los criterios de gravedad de la Organización Mundial de la Salud. Todos presentaron fiebre como signo más significativo. Como complicaciones graves se observaron casos de insuficiencia renal, epistaxis, hemoglobinuria, hipoglucemia, edema pulmonar, acidosis y coma. Tres pacientes requirieron internación en la unidad de terapia intensiva. Todos sobrevivieron y solamente tres habían recibido la quimioprofilaxis correcta antes de viajar. El tratamiento se realizó con una o más de las siguientes drogas: mefloquina, quinidina, clindamicina y cotrimoxazol.The purpose of this paper is to present the cases of malaria caused by Plasmodium falciparum in travelers coming from tropical Africa, who were treated at the Hospital Alemán (Buenos Aires. African malaria was defined as an infection acquired in any country within Africa, diagnosed and treated in Argentina. Diagnostic tools included clinical features and optic microscopy with Giemsa stained peripheral blood films. We reviewed the medical records of 11 adult patients -five tourists and six sailors- with no history of malaria

  4. Mitochondrial genes support a common origin of rodent malaria parasites and Plasmodium falciparum's relatives infecting great apes

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    Blanquart Samuel

    2011-03-01

    Full Text Available Abstract Background Plasmodium falciparum is responsible for the most acute form of human malaria. Most recent studies demonstrate that it belongs to a monophyletic lineage specialized in the infection of great ape hosts. Several other Plasmodium species cause human malaria. They all belong to another distinct lineage of parasites which infect a wider range of primate species. All known mammalian malaria parasites appear to be monophyletic. Their clade includes the two previous distinct lineages of parasites of primates and great apes, one lineage of rodent parasites, and presumably Hepatocystis species. Plasmodium falciparum and great ape parasites are commonly thought to be the sister-group of all other mammal-infecting malaria parasites. However, some studies supported contradictory origins and found parasites of great apes to be closer to those of rodents, or to those of other primates. Results To distinguish between these mutually exclusive hypotheses on the origin of Plasmodium falciparum and its great ape infecting relatives, we performed a comprehensive phylogenetic analysis based on a data set of three mitochondrial genes from 33 to 84 malaria parasites. We showed that malarial mitochondrial genes have evolved slowly and are compositionally homogeneous. We estimated their phylogenetic relationships using Bayesian and maximum-likelihood methods. Inferred trees were checked for their robustness to the (i site selection, (ii assumptions of various probabilistic models, and (iii taxon sampling. Our results robustly support a common ancestry of rodent parasites and Plasmodium falciparum's relatives infecting great apes. Conclusions Our results refute the most common view of the origin of great ape malaria parasites, and instead demonstrate the robustness of a less well-established phylogenetic hypothesis, under which Plasmodium falciparum and its relatives infecting great apes are closely related to rodent parasites. This study sheds light

  5. Prevalence of multiple drug-resistant Plasmodium falciparum malaria cases in Northeast India.

    Science.gov (United States)

    Sharma, Jitendra; Khan, Siraj Ahmed; Soni, Monika; Dutta, Prafulla

    2017-01-01

    Two numbers of Plasmodium falciparum field isolates from Gossingpara, Runikhata area in Chirang district of Assam had shown multiple mutations in Pfcrt-dhfr-dhps gene (up to seven mutations: One mutation in Pfcrt gene, three mutations in Pfdhfr gene and three mutations in Pfdhps gene). Similarly, two cases in Bat camp, Miao area under Changlang district of Arunachal Pradesh had shown a total of eight mutations, of which one mutation in Pfcrt gene, three mutations in Pfdhfr gene, three mutations in Pfdhps gene and one mutation in PfATPase6 gene. One case in 3 Miles, Miao area of Changlang district has shown mutations in Pfcrt(one mutation), Pfdhfr(four mutations) and Pfdhps(three mutations) gene. These results indicated that there is an existence of multiple mutant P. falciparum malaria cases in northeastern region of India.

  6. Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia.

    Science.gov (United States)

    Mohd Abd Razak, Mohd Ridzuan; Sastu, Umi Rubiah; Norahmad, Nor Azrina; Abdul-Karim, Abass; Muhammad, Amirrudin; Muniandy, Prem Kumar; Jelip, Jenarun; Rundi, Christina; Imwong, Mallika; Mudin, Rose Nani; Abdullah, Noor Rain

    2016-01-01

    Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, pdiversity and contrasting genetic pattern of P. falciparum populations in the malaria declining areas of Sabah.

  7. Cost-effectiveness of three malaria treatment strategies in rural Tigray, Ethiopia where both Plasmodium falciparum and Plasmodium vivax co-dominate

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    Löfgren Curt

    2011-02-01

    Full Text Available Abstract Background Malaria transmission in Ethiopia is unstable and the disease is a major public health problem. Both, p.falciparum (60% and p.vivax (40% co-dominantly exist. The national guideline recommends three different diagnosis and treatment strategies at health post level: i the use of a p.falciparum/vivax specific RDT as diagnosis tool and to treat with artemether-lumefantrine (AL, chloroquine (CQ or referral if the patient was diagnosed with p.falciparum, p.vivax or no malaria, respectively (parascreen pan/pf based strategy; ii the use of a p.falciparum specific RDT and AL for p.falciparum cases and CQ for the rest (paracheck pf based strategy; and iii the use of AL for all cases diagnosed presumptively as malaria (presumptive based strategy. This study aimed to assess the cost-effectiveness of the recommended three diagnosis and treatment strategies in the Tigray region of Ethiopia. Methods The study was conducted under a routine health service delivery following the national malaria diagnosis and treatment guideline. Every suspected malaria case, who presented to a health extension worker either at a village or health post, was included. Costing, from the provider's perspective, only included diagnosis and antimalarial drugs. Effectiveness was measured by the number of correctly treated cases (CTC and average and incremental cost-effectiveness calculated. One-way and two-way sensitivity analyses were conducted for selected parameters. Results In total 2,422 subjects and 35 health posts were enrolled in the study. The average cost-effectiveness ratio showed that the parascreen pan/pf based strategy was more cost-effective (US$1.69/CTC than both the paracheck pf (US$4.66/CTC and the presumptive (US$11.08/CTC based strategies. The incremental cost for the parascreen pan/pf based strategy was US$0.59/CTC to manage 65% more cases. The sensitivity analysis also confirmed parascreen pan/pf based strategy as the most cost

  8. Strong gametocytocidal effect of methylene blue-based combination therapy against falciparum malaria: a randomised controlled trial.

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    Boubacar Coulibaly

    Full Text Available BACKGROUND: With the availability of new preventive and curative interventions, global malaria control has been strengthened significantly in recent years. Drugs effective in reducing malaria gametocytaemia might contribute to local elimination and possible long-term eradication. We here report on the effects of methylene blue (MB-based malaria combination therapy on gametocytaemia during a randomised-controlled trial in Burkina Faso. METHODS: An open-label randomised controlled phase II study in 180 children aged 6-10 years with uncomplicated falciparum malaria was conducted in Nouna, north-western Burkina Faso. Children were randomised to MB-artesunate (AS, MB-amodiaquine (AQ, and AS-AQ (local standard of care. Overall follow-up was for 28 days, follow-up for gametocytaemia was for 14 days. FINDINGS: The treatment groups were similar in baseline characteristics and there was only one loss to follow-up. Compared to AS-AQ, both MB-containing regimens were associated with significantly reduced gametocyte carrier rates during follow-up days 3, 7, and 14. This effect was seen both in patients with and without P. falciparum gametocytaemia at baseline. INTERPRETATION: MB reveals pronounced gametocytocidal activity which appears to act against both existing and developing P. falciparum gametocytes. MB-based combination therapy thus has the potential to reduce transmission of P. falciparum malaria in endemic regions, which has important implications for future elimination and eradication strategies. TRIAL REGISTRATION: (ClinicalTrials.gov NCT00354380.

  9. Plasmodium falciparum Malaria: Band 3 as a Possible Receptor during Invasion of Human Erythrocytes

    Science.gov (United States)

    Okoye, Vincent C. N.; Bennett, Vann

    1985-01-01

    Human erythrocyte band 3, a major membrane-spanning protein, was purified and incorporated into liposomes. These liposomes, at nanomolar concentrations of protein, inhibited invasion of human erythrocytes in vitro by the malaria parasite Plasmodium falciparum. Liposomes containing human band 3 were ten times more effective in inhibiting invasion than those with pig band 3 and six times more effective than liposomes containing human erythrocyte glycophorin. Liposomes alone or liposomes containing erythrocyte glycolipids did not inhibit invasion. These results suggest that band 3 participates in the invasion process in a step involving a specific, high-affinity interaction between band 3 and some component of the parasite.

  10. Acute renal failure in falciparum malaria: Clinical characteristics, demonstration of oxidative stress, and prognostication

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    Ch. Venkata Rama Krishna

    2012-01-01

    Full Text Available In this prospective study, we aimed to assess the clinical characteristics of acute renal failure (ARF, determine oxidative stress, as well as to predict the outcome in patients with severe falciparum malaria (FM. The study included a total of 75 subjects; there were 25 adult patients with acute severe FM and ARF, 25 adult patients with uncomplicated FM without ARF, and 25 age- and sex-matched healthy subjects who served as controls. In patients with severe FM and ARF (n = 25, renal failure was non-oliguric in 28% and oliguric in 72%. The average duration of renal failure was 10.53 ± 4.0 days. Sixty percent recovered and 40% died. All patients with non-oliguric presentation recovered. The mean serum malondialdehyde (MDA levels were 0.82 ± 0.43 μmol/L, 2.97 ± 1.11 μmol/L, and 6.86 ± 2.62 μmol/L, respectively, in healthy con-trols, in patients with uncomplicated FM, and in those with severe FM with ARF. The Acute Physiology Age and Chronic Health Evaluation II (APACHE II score, Sequential Organ Failure Assessment (SOFA score, and the Acute Tubular Necrosis-Individual Severity Index (ATN-ISI score were all significantly higher in the expired group (19 ± 5.49 when compared to the survivor group (14.4 ± 3.15 (P = 0.014. Kaplan-Meier survival analysis showed that survival was low in patients with delayed hospitalization and longer duration of symptoms. Also, we observed a high occurrence of acute respiratory distress syndrome and central nervous system involvement among the patients who expired.

  11. Impact of placental Plasmodium falciparum malaria on the profile of some oxidative stress biomarkers in women living in Yaoundé, Cameroon.

    Science.gov (United States)

    Megnekou, Rosette; Djontu, Jean Claude; Bigoga, Jude Daiga; Medou, Fabrice Mbah; Tenou, Sandrine; Lissom, Abel

    2015-01-01

    Impact of the pathophysiology of Plasmodium falciparum placental malaria (PM) on the profile of some oxidative stress biomarkers and their relationship with poor pregnancy outcomes in women remain unknown. Between 2013 and 2014, peripheral blood and placenta tissue from 120 Cameroonian women at delivery were assessed for maternal haemoglobin and, parasitaemia respectively. Parasite accumulation in the placenta was investigated histologically. The levels of oxidative stress biomarkers Malondialdehyde (MDA), Nitric Oxide (NO), Superoxide dismutase (SOD), Catalase (CAT) and Gluthatione (GSH) in the supernatant of teased placenta tissues were determined by Colorimetric enzymatic assays. Parasitaemia was inversely related to haemoglobin levels and birth weight (P <0.001 and 0.012, respectively). The level of lipid peroxide product (MDA) was significantly higher in the malaria infected (P = 0.0047) and anaemic (P = 0.024) women compared to their non-infected and non-anaemic counterparts, respectively. A similar trend was observed with SOD levels, though not significant. The levels of MDA also correlated positively with parasitaemia (P = 0.0024) but negatively with haemoglobin levels (P = 0.002). There was no association between parasitaemia, haemoglobin level and the other oxidative stress biomarkers. From histological studies, levels of MDA associated positively and significantly with placenta malaria infection and the presence of malaria pigments. The levels of SOD, NO and CAT increased with decreasing leukocyte accumulation in the intervillous space. Baby birth weight increased significantly with SOD and CAT levels, but decreased with levels of GSH. Placental P. falciparum infection may cause oxidative stress of the placenta tissue with MDA as a potential biomarker of PM, which alongside GSH could lead to poor pregnancy outcomes (anaemia and low birth weight). This finding contributes to the understanding of the pathophysiology of P. falciparum placental malaria in

  12. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDRα1 domains

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Wang, Christian W.; Mkumbaye, Sixbert I.;

    2016-01-01

    Most severe Plasmodium falciparum infections are experienced by young children. Severe symptoms are precipitated by vascular sequestration of parasites expressing a particular subset of the polymorphic P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion molecules. Parasites binding human...... endothelial protein C receptor (EPCR) through the CIDRα1 domain of certain PfEMP1 were recently associated with severe malaria in children. However, it has remained unclear to which extend the EPCR-binding CIDRα1 domains epitomize PfEMP1 expressed in severe malaria. Here, we characterized the near full......-length transcripts dominating the var transcriptome in children with severe malaria and found that the only common feature of the encoded PfEMP1 was CIDRα1 domains. Such genes were highly and dominantly expressed in both children with severe malarial anaemia and cerebral malaria. These observations support...

  13. To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India

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    Aditya Verma

    2015-01-01

    Full Text Available The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

  14. Polymorphism of Plasmodium Falciparum Dihydrofolate Reductase and Dihydropteroate Synthase Genes among Pregnant Women with Falciparum Malaria in Banjar District, South Kalimantan Province, Indonesia

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    Sukmawati Basuki

    2012-12-01

    Full Text Available Pregnant women are highly vulnerable to malaria infection in its endemic areas, particularly infection by Plasmodium falciparum that can cause premature, low birth weight, severe anemia in pregnant women, and death. Sulfadoxine-pyrimethamine (SP for Intermittent Preventive Treatment for pregnant (IPTp is used for malaria control in pregnancy recommended by the World Health Organization that has already been implemented in Africa. The P. falciparum resistance to SP has been reported in several malarial endemic areas, and mutations in the genes of Plasmodium falciparum Dihydrofolate Reductase (Pfdhfr and Dihydropteroate Synthase (Pfdhps are shown to be associated with parasite resistance to SP treatment. Genetic analysis of Pfdhfr and Pfdhps genes in pregnant women infected with P. falciparum has not yet been examined in Indonesia. The cross-sectional study was conducted at two subdistricts, Sungai Pinang and Peramasan, in Banjar district of South Kalimantan Province, where 127 pregnant women were recruited from 2008 to April 2010. Two important mutations in Pfdhfr gene (amino acid positions at N51 and S108 and three in Pfdhps gene (A437, K540 and A581 were analyzed by nested PCR-RFLP method. All of the seven pregnant women samples infected with P. falciparum presented PfDHFR 108N and PfDHPS 437G mutations. One of the samples had the additional mutation at PfDHPS 540, in which Lys is substituted by Glu. These results suggested that P. falciparum might present only some resistance to SP at Sungai Pinang and Peramasan subdistricts, Banjar District, South Kalimantan province, Indonesia. Although there were limited number of samples, this study showed only few mutations of Pfdhfr and Pfdhps genes in P. falciparum at Banjar district, South Kalimantan Province, that suggests SP might be effective for IPTp in this area. Thus, further analysis of the other mutation sites in Pfdhfr and Pfdhps genes and in vivo efficacy study of SP with more sufficient

  15. High-Dose Chloroquine for Treatment of Chloroquine-Resistant Plasmodium falciparum Malaria.

    Science.gov (United States)

    Ursing, Johan; Rombo, Lars; Bergqvist, Yngve; Rodrigues, Amabelia; Kofoed, Poul-Erik

    2016-04-15

    Due to development of multidrug-resistant Plasmodium falciparum new antimalarial therapies are needed. In Guinea-Bissau, routinely used triple standard-dose chloroquine remained effective for decades despite the existence of "chloroquine-resistant" P. falciparum. This study aimed to determine the in vivo efficacy of higher chloroquine concentrations against P. falciparum with resistance-conferring genotypes. Standard or double-dose chloroquine was given to 892 children aged <15 years with uncomplicated malaria during 3 clinical trials (2001-2008) with ≥ 35 days follow-up. The P. falciparum resistance-conferring genotype (pfcrt 76T) and day 7 chloroquine concentrations were determined. Data were divided into age groups (<5, 5-9, and 10-14 years) because concentrations increase with age when chloroquine is prescribed according to body weight. Adequate clinical and parasitological responses were 14%, 38%, and 39% after standard-dose and 66%, 84%, and 91% after double-dose chloroquine in children aged <5, 5-9, and 10-14 years, respectively, and infected with P. falciparum genotypes conferring chloroquine resistance (n = 195, P < .001). In parallel, median chloroquine concentrations were 471, 688, and 809 nmol/L for standard-dose and 1040, 1494, and 1585 nmol/L for double-dose chloroquine. Chloroquine resistance is dose dependent and can be overcome by higher, still well-tolerated doses. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  16. Large-scale growth of the Plasmodium falciparum malaria parasite in a wave bioreactor.

    Science.gov (United States)

    Dalton, John P; Demanga, Corine G; Reiling, Sarah J; Wunderlich, Juliane; Eng, Jenny W L; Rohrbach, Petra

    2012-01-01

    We describe methods for the large-scale in vitro culturing of synchronous and asynchronous blood-stage Plasmodium falciparum parasites in sterile disposable plastic bioreactors controlled by wave-induced motion (wave bioreactor). These cultures perform better than static flask cultures in terms of preserving parasite cell cycle synchronicity and reducing the number of multiple-infected erythrocytes. The straight-forward methods described here will facilitate the large scale production of malaria parasites for antigen and organelle isolation and characterisation, for the high throughput screening of compound libraries with whole cells or extracts, and the development of live- or whole-cell malaria vaccines under good manufacturing practice compliant standards. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  17. Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Goodman, Christopher D.; McFadden, Geoffrey I.

    2016-01-01

    Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs) are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle. We investigated how a pPT is targeted into the outer apicoplast membrane of the human malaria parasite P. falciparum. We showed that a transmembrane domain is likely to act as a recessed signal anchor to direct the protein into the endomembrane system, and that a tyrosine in the cytosolic N-terminus of the protein is essential for targeting, but one or more, as yet unidentified, factors are also essential to direct the protein into the outer apicoplast membrane. PMID:27442138

  18. Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Liting Lim

    Full Text Available Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle. We investigated how a pPT is targeted into the outer apicoplast membrane of the human malaria parasite P. falciparum. We showed that a transmembrane domain is likely to act as a recessed signal anchor to direct the protein into the endomembrane system, and that a tyrosine in the cytosolic N-terminus of the protein is essential for targeting, but one or more, as yet unidentified, factors are also essential to direct the protein into the outer apicoplast membrane.

  19. Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia.

    Science.gov (United States)

    Leang, Rithea; Canavati, Sara E; Khim, Nimol; Vestergaard, Lasse S; Borghini Fuhrer, Isabelle; Kim, Saorin; Denis, Mey Bouth; Heng, Pisal; Tol, Bunkea; Huy, Rekol; Duparc, Stephan; Dondorp, Arjen M; Menard, Didier; Ringwald, Pascal

    2016-07-01

    Pyronaridine-artesunate efficacy for the treatment of uncomplicated Plasmodium falciparum malaria was assessed in an area of artemisinin resistance in western Cambodia. This nonrandomized, single-arm, observational study was conducted between 2014 and 2015. Eligible patients were adults or children with microscopically confirmed P. falciparum infection and fever. Patients received pyronaridine-artesunate once daily for 3 days, dosed according to body weight. The primary outcome was an adequate clinical and parasitological response (ACPR) on day 42, estimated by using Kaplan-Meier analysis, PCR adjusted to exclude reinfection. One hundred twenty-three patients were enrolled. Day 42 PCR-crude ACPRs were 87.2% (95% confidence interval [CI], 79.7 to 92.6%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 82.1% (95% CI, 68.4 to 90.2%) for Pailin. Day 42 PCR-adjusted ACPRs were 87.9% (95% CI, 80.6 to 93.2%) for the overall study, 89.8% (95% CI, 78.8 to 95.3%) for Pursat, and 84.0% (95% CI, 70.6 to 91.7%) for Pailin (P = 0.353 by a log rank test). Day 28 PCR-crude and -adjusted ACPRs were 93.2% (95% CI, 82.9 to 97.4%) and 88.1% (95% CI, 75.3 to 94.5%) for Pursat and Pailin, respectively. A significantly lower proportion of patients achieved day 3 parasite clearance in Pailin (56.4% [95% CI, 43.9 to 69.6%]) than in Pursat (86.7% [95% CI, 76.8 to 93.8%]; P = 0.0019). Fever clearance was also extended at Pailin versus Pursat (P < 0.0001). Most patients (95.9% [116/121]) harbored P. falciparum kelch13 C580Y mutant parasites. Pyronaridine-artesunate was well tolerated; mild increases in hepatic transaminase levels were consistent with data from previous reports. Pyronaridine-artesunate efficacy was below the World Health Organization-recommended threshold at day 42 for medicines with a long half-life (90%) for first-line treatment of P. falciparum malaria in western Cambodia despite high efficacy elsewhere in Asia and Africa. (This study has been registered

  20. Modelling the dynamics of Plasmodium falciparum histidine-rich protein 2 in human malaria to better understand malaria rapid diagnostic test performance

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    Marquart Louise

    2012-03-01

    Full Text Available Abstract Background Effective diagnosis of malaria is a major component of case management. Rapid diagnostic tests (RDTs based on Plasmodium falciparumhistidine-rich protein 2 (PfHRP2 are popular for diagnosis of this most virulent malaria infection. However, concerns have been raised about the longevity of the PfHRP2 antigenaemia following curative treatment in endemic regions. Methods A model of PfHRP2 production and decay was developed to mimic the kinetics of PfHRP2 antigenaemia during infections. Data from two human infection studies was used to fit the model, and to investigate PfHRP2 kinetics. Four malaria RDTs were assessed in the laboratory to determine the minimum detectable concentration of PfHRP2. Results Fitting of the PfHRP2 dynamics model indicated that in malaria naïve hosts, P. falciparum parasites of the 3D7 strain produce 1.4 × 10-13 g of PfHRP2 per parasite per replication cycle. The four RDTs had minimum detection thresholds between 6.9 and 27.8 ng/mL. Combining these detection thresholds with the kinetics of PfHRP2, it is predicted that as few as 8 parasites/μL may be required to maintain a positive RDT in a chronic infection. Conclusions The results of the model indicate that good quality PfHRP2-based RDTs should be able to detect parasites on the first day of symptoms, and that the persistence of the antigen will cause the tests to remain positive for at least seven days after treatment. The duration of a positive test result following curative treatment is dependent on the duration and density of parasitaemia prior to treatment and the presence and affinity of anti-PfHRP2 antibodies.

  1. Pyronaridine-Artesunate combination for the treatment of acute uncomplicated Plasmodium falciparum malaria in paediatric patients in Gabon

    OpenAIRE

    Schreier, Annette

    2010-01-01

    Artemisinin-based combination therapies (ACTs) are now the recommended first-line drugs for the treatment of acute uncomplicated Plasmodium falciparum malaria in many endemic regions and the development of novel therapy options, especially for the use in children, is a major aim in malaria research. This Phase II study intended to provide first clinical data about the new combination of pyronaridine and artesunate for the use in paediatric patients. 60 children were assigned to the four s...

  2. Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Michael; Russo, Crystal; Li, Xuerong [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Chishti, Athar H., E-mail: athar.chishti@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Sackler School of Graduate Biomedical Sciences, Programs in Physiology, Pharmacology, and Microbiology, Tufts University School of Medicine, Boston, MA 02111 (United States)

    2014-08-08

    Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.

  3. South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.

    Science.gov (United States)

    Griffing, Sean M; Mixson-Hayden, Tonya; Sridaran, Sankar; Alam, Md Tauqeer; McCollum, Andrea M; Cabezas, César; Marquiño Quezada, Wilmer; Barnwell, John W; De Oliveira, Alexandre Macedo; Lucas, Carmen; Arrospide, Nancy; Escalante, Ananias A; Bacon, David J; Udhayakumar, Venkatachalam

    2011-01-01

    Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites) and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000) from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase.

  4. Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria

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    Issifou Saadou

    2008-12-01

    Full Text Available Abstract Background Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM, are not yet fully understood. Both endothelin-1 (ET-1 and C-type natriuretic peptide (CNP are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties. Methods Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA technique, in Gabonese children with severe falciparum malaria (SM, n = 50, with uncomplicated malaria (UM, n = 39 and healthy controls (HC, n = 25. Results Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p p p = 0.034, whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085. Conclusion In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.

  5. A prospective study from south India to compare the severity of malaria caused by Plasmodium vivax, P. falciparum and dual infection

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    Shubhanker Mitra

    2015-01-01

    Interpretation & conclusion: This cross-sectional comparative study clearly demonstrates that clinical features, complications and case-fatality rates in vivax malaria can be as severe as in falciparum malaria. Hence, vivax malaria could not be considered benign; and appropriate preventive strategies along with antimalarial therapies should be adopted for control and elimination of this disease.

  6. Defining falciparum malaria attributable sever febrile illness in moderate to high transmission settings based on plasma PfHRP2 concentration

    NARCIS (Netherlands)

    Hendriksen, I.C.E.; White, L.J.; Veenemans, J.; Verhoef, J.C.M.

    2013-01-01

    Background. In malaria-endemic settings, asymptomatic parasitemia complicates the diagnosis of malaria. Histidine-rich protein 2 (HRP2) is produced by Plasmodium falciparum, and its plasma concentration reflects the total body parasite burden. We aimed to define the malaria-attributable fraction of

  7. Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children

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    Djimde Abdoulaye A.

    2016-01-01

    Full Text Available Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010–2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1–10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002–2004. Of 100 children enrolled in the 2010–2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002–2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0 and did not significantly decline until day 21 of follow-up (23% vs. 6%, p = 0.003. The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/μL vs. 16 gametocytes/μL, p = 0.6. Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002–2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting.

  8. The detection and treatment of Plasmodium falciparum malaria: Time for change

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    Nosten F

    2004-01-01

    Full Text Available In most countries where malaria is endemic, P. falciparum malaria is on the rise. This is primarily due to the spread of drug-resistant strains. Drug resistance is mediated by spontaneous changes in the parasite genome that allow resistant parasites to escape the action of the drugs. The spread of drug resistance increases the transmission of malaria parasites. The consequences for the populations at risk are profound both in terms of consequences for health and economy. In order to halt the progression of drug resistance, we need to change the way antimalarials are used. As in tuberculosis and HIV/AIDS, we must use a combination of drugs for the treatment of malaria. Taking into account the pharmacokinetic and pharmacodynamic properties of the various anti-malarial agents, artemisinin-based combination therapy (ACT seems to be the best option. This strategy should be used in conjunction with early diagnosis and appropriate vector control measures to achieve reduction in the emergence and spread of drug resistance.

  9. Comparative gene expression profiling of P. falciparum malaria parasites exposed to three different histone deacetylase inhibitors.

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    Katherine T Andrews

    Full Text Available Histone deacetylase (HDAC inhibitors are being intensively pursued as potential new drugs for a range of diseases, including malaria. HDAC inhibitors are also important tools for the study of epigenetic mechanisms, transcriptional control, and other important cellular processes. In this study the effects of three structurally related antimalarial HDAC inhibitors on P. falciparum malaria parasite gene expression were compared. The three hydroxamate-based compounds, trichostatin A (TSA, suberoylanilide hydroxamic acid (SAHA; Vorinostat® and a 2-aminosuberic acid derivative (2-ASA-9, all caused profound transcriptional effects, with ~2-21% of genes having >2-fold altered expression following 2 h exposure to the compounds. Only two genes, alpha tubulin II and a hydrolase, were up-regulated by all three compounds after 2 h exposure in all biological replicates examined. The transcriptional changes observed after 2 h exposure to HDAC inhibitors were found to be largely transitory, with only 1-5% of genes being regulated after removing the compounds and culturing for a further 2 h. Despite some structural similarity, the three inhibitors caused quite diverse transcriptional effects, possibly reflecting subtle differences in mode of action or cellular distribution. This dataset represents an important contribution to our understanding of how HDAC inhibitors act on malaria parasites and identifies alpha tubulin II as a potential transcriptional marker of HDAC inhibition in malaria parasites that may be able to be exploited for future development of HDAC inhibitors as new antimalarial agents.

  10. Genomics and Integrated Systems Biology in Plasmodium falciparum: A Path to Malaria Control and Eradication

    Science.gov (United States)

    Le Roch, Karine G.; Chung, Duk-Won D.; Ponts, Nadia

    2011-01-01

    The first draft of the human malaria parasite's genome was released in 2002. Since then, the malaria scientific community has witnessed a steady embrace of new and powerful functional genomic studies. Over the years, these approaches have slowly revolutionized malaria research and enabled the comprehensive, unbiased investigation of various aspects of the parasite's biology. These genome-wide analyses delivered a refined annotation of the parasite's genome, a better knowledge of its RNA, proteins, and metabolite derivatives, and fostered the discovery of new vaccine and drug targets. Despite the positive impacts of these genomic studies, most research and investment still focus on protein targets, drugs and vaccine candidates that were known before the publication of the parasite genome sequence. However, recent access to next-generation sequencing technologies, along with an increased number of genome-wide applications are expanding the impact of the parasite genome on biomedical research, contributing to a paradigm shift in research activities that may possibly lead to new optimized diagnosis and treatments. This review provides an update of Plasmodium falciparum genome sequences and an overview of the rapid development of genomics and system biology applications that have an immense potential of creating powerful tools for a successful malaria eradication campaign. PMID:21995286

  11. Plasmodium falciparum malaria in children aged 0-2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP).

    Science.gov (United States)

    Kangoye, David Tiga; Nebie, Issa; Yaro, Jean-Baptiste; Debe, Siaka; Traore, Safiatou; Ouedraogo, Oumarou; Sanou, Guillaume; Soulama, Issiaka; Diarra, Amidou; Tiono, Alfred; Marsh, Kevin; Sirima, Sodiomon Bienvenu; Bejon, Philip

    2014-01-01

    Children below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate-rich protein (GLURP), in children in their first two years of life in Burkina Faso and their risk of malaria. A cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2) on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography. A total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2) did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria. We did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.

  12. Plasmodium falciparum malaria in children aged 0-2 years: the role of foetal haemoglobin and maternal antibodies to two asexual malaria vaccine candidates (MSP3 and GLURP.

    Directory of Open Access Journals (Sweden)

    David Tiga Kangoye

    Full Text Available Children below six months are reported to be less susceptible to clinical malaria. Maternally derived antibodies and foetal haemoglobin are important putative protective factors. We examined antibodies to Plasmodium falciparum merozoite surface protein 3 (MSP3 and glutamate-rich protein (GLURP, in children in their first two years of life in Burkina Faso and their risk of malaria.A cohort of 140 infants aged between four and six weeks was recruited in a stable transmission area of south-western Burkina Faso and monitored for 24 months by active and passive surveillance. Malaria infections were detected by examining blood smears using light microscopy. Enzyme-linked immunosorbent assay was used to quantify total Immunoglobulin G to Plasmodium falciparum antigens MSP3 and two regions of GLURP (R0 and R2 on blood samples collected at baseline, three, six, nine, 12, 18 and 24 months. Foetal haemoglobin and variant haemoglobin fractions were measured at the baseline visit using high pressure liquid chromatography.A total of 79.6% of children experienced one or more episodes of febrile malaria during monitoring. Antibody titres to MSP3 were prospectively associated with an increased risk of malaria while antibody responses to GLURP (R0 and R2 did not alter the risk. Antibody titres to MSP3 were higher among children in areas of high malaria risk. Foetal haemoglobin was associated with delayed first episode of febrile malaria and haemoglobin CC type was associated with reduced incidence of febrile malaria.We did not find any evidence of association between titres of antibodies to MSP3, GLURP-R0 or GLURP-R2 as measured by enzyme-linked immunosorbent assay and early protection against malaria, although anti-MSP3 antibody titres may reflect increased exposure to malaria and therefore greater risk. Foetal haemoglobin was associated with protection against febrile malaria despite the study limitations and its role is therefore worthy further investigation.

  13. Malaria mapping: understanding the global endemicity of falciparum and vivax malaria.

    Science.gov (United States)

    Dalrymple, Ursula; Mappin, Bonnie; Gething, Peter W

    2015-06-12

    The mapping of malaria risk has a history stretching back over 100 years. The last decade, however, has seen dramatic progress in the scope, rigour and sophistication of malaria mapping such that its global distribution is now probably better understood than any other infectious disease. In this minireview we consider the main factors that have facilitated the recent proliferation of malaria risk mapping efforts and describe the most prominent global-scale endemicity mapping endeavours of recent years. We describe the diversification of malaria mapping to span a wide range of related metrics of biological and public health importance and consider prospects for the future of the science including its key role in supporting elimination efforts.

  14. Plasmodium falciparum Malaria Complicated by Symmetrical Peripheral Gangrene, Bowel Ischemia, Repeated Candidemia, and Bacteraemia

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    Emeline Masse

    2014-01-01

    Full Text Available A 63-year-old Caucasian woman developed severe Plasmodium falciparum malaria when travelling back from Cameroun. No antimalarial chemoprophylaxis had been observed. The patient was immediately admitted to the intensive care unit after evidence of multiple organ failure (coma, shock, acute respiratory distress syndrome, acute renal failure, etc.. However, initial parasitemia was less than 1%. The patient was managed by intravenous quinine and norepinephrine infusion due to refractory shock. The patient developed as an early complication ischemic lesions of both arms and feet. In addition to laboratory changes consistent with disseminated intravascular coagulation, there was also evidence for a low activity of the von Willebrand factor (VWF cleaving protease ADAMTS13. Later complications included repeated candidemia and bacteraemia despite appropriate therapy; the origin appeared to be diffuse ischemic injury of the gastrointestinal tract. The patient ultimately recovered, but quadriamputation was necessary to treat symmetrical peripheral gangrene (SPG. In severe Plasmodium falciparum malaria, ischemic changes may be due to microvascular obstruction, but, in patients with low parasitemia, other endothelial factors may also be involved as observed in other groups of thrombotic microangiopathies.

  15. DNA Repair Mechanisms and Their Biological Roles in the Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Lee, Andrew H.; Symington, Lorraine S.

    2014-01-01

    SUMMARY Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen. PMID:25184562

  16. Antigenic variation in Plasmodium falciparum malaria involves a highly structured switching pattern.

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    Mario Recker

    2011-03-01

    Full Text Available Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection.

  17. DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Lee, Andrew H; Symington, Lorraine S; Fidock, David A

    2014-09-01

    Research into the complex genetic underpinnings of the malaria parasite Plasmodium falciparum is entering a new era with the arrival of site-specific genome engineering. Previously restricted only to model systems but now expanded to most laboratory organisms, and even to humans for experimental gene therapy studies, this technology allows researchers to rapidly generate previously unattainable genetic modifications. This technological advance is dependent on DNA double-strand break repair (DSBR), specifically homologous recombination in the case of Plasmodium. Our understanding of DSBR in malaria parasites, however, is based largely on assumptions and knowledge taken from other model systems, which do not always hold true in Plasmodium. Here we describe the causes of double-strand breaks, the mechanisms of DSBR, and the differences between model systems and P. falciparum. These mechanisms drive basic parasite functions, such as meiosis, antigen diversification, and copy number variation, and allow the parasite to continually evolve in the contexts of host immune pressure and drug selection. Finally, we discuss the new technologies that leverage DSBR mechanisms to accelerate genetic investigations into this global infectious pathogen.

  18. The Clp Chaperones and Proteases of the Human Malaria Parasite Plasmodium falciparum

    Energy Technology Data Exchange (ETDEWEB)

    Bakkouri, Majida El; Pow, Andre; Mulichak, Anne; Cheung, Kevin L.Y.; Artz, Jennifer D.; Amani, Mehrnaz; Fell, Stuart; de Koning-Ward, Tania F.; Goodman, C. Dean; McFadden, Geoffrey I.; Ortega, Joaquin; Hui, Raymond; Houry, Walid A. (McMaster U.); (Melbourne); (Toronto); (Deakin); (HWMRI)

    2015-02-09

    The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum.

  19. Parasite Sequestration in Plasmodium falciparum Malaria: Spleen and Antibody Modulation of Cytoadherence of Infected Erythrocytes

    Science.gov (United States)

    David, Peter H.; Hommel, Marcel; Miller, Louis H.; Udeinya, Iroka J.; Oligino, Lynette D.

    1983-08-01

    Sequestration, the adherence of infected erythrocytes containing late developmental stages of the parasite (trophozoites and schizonts) to the endothelium of capillaries and venules, is characteristic of Plasmodium falciparum infections. We have studied two host factors, the spleen and antibody, that influence sequestration of P. falciparum in the squirrel monkey. Sequestration of trophozoite/schizont-infected erythrocytes that occurs in intact animals is reduced in splenectomized animals; in vitro, when infected blood is incubated with monolayers of human melanoma cells, trophozoite/schizont-infected erythrocytes from intact animals but not from splenectomized animals bind to the melanoma cells. The switch in cytoadherence characteristics of the infected erythrocytes from nonbinding to binding occurs with a cloned parasite. Immune serum can inhibit and reverse in vitro binding to melanoma cells of infected erythrocytes from intact animals. Similarly, antibody can reverse in vivo sequestration as shown by the appearance of trophozoite/schizont-infected erythrocytes in the peripheral blood of an intact animal after inoculation with immune serum. These results indicate that the spleen modulates the expression of parasite alterations of the infected erythrocyte membrane responsible for sequestration and suggest that the prevention and reversal of sequestration could be one of the effector mechanisms involved in antibody-mediated protection against P. falciparum malaria.

  20. An open randomized controlled trial to compare the efficacy of two fixed dose combinations of artemesinin based combinations for uncomplicated falciparum malaria in Bangladesh.

    Science.gov (United States)

    Samad, R; Rahman, M R; Yunus, E B; Hussain, M A; Arif, S M; Islam, M N; Hafiz, S A M M A; Hossain, M M; Faiz, M A

    2013-12-01

    National Malaria Control Program (NMCP) of Bangladesh has introduced Artemisinin Based Combination (ACT), Coartem(R) (Artemether-Lumefantrine (AL), fixed dose combination, in the confirmed cases of uncomplicated P. falciparum malaria since 2004. Despite the reduction of mortality due to malaria, the development and spread of anti-malarial drug resistance wordwide posing a threat to the health services and will make it difficult to control malaria in Bangladesh in future. We need to have an alternative to Coartem which could be Artesunate-amodiaquine (AA) in a fixed dose combination (FDC), a cheaper altenative not yet evidenced to be effective and safe to our population. In this study we compared the efficacy and safety of Artemether + Lumefantrene (FDC, Coartem) with Artesunate +Amodiaquine tablets (100/270 mg FDC) for the treatment of uncomplicated P. falciparum malaria in three high risk multi-drug resistant malaria prevalent areas of Bangladesh. It was an open label randomized controlled trial conducted between December 2008 and November 2009 in 4 upazillas in patients over the age 12 to 60 years diagnosed as a case of uncomplicated P. falciparum malaria. The outcome of the cases were measured as clinical response, parasitological response, defervescence time and parasite clearance time. Drug safety was assessed by comparing the adverse events. A total of 252 cases were randomized to receive Artesunate + Amodiaquine (AA group, 147 cases) and Artemether + Lumefantrene (AL group, 106 cases), one lost to follow up at day 28 in AA group. The distribution of the cases was comparable by age, sex and study sites. Treatment success' response was observed 100% in the AL group and AA group had 99%, two failures with AA were late treatment failures and the difference was not statistically significant (p > .1). The parasitological sensitive (S) response was observed in 97% of cases in AL group and 95% in the AA group, and was not a statistically significant difference

  1. Impaired systemic tetrahydrobiopterin bioavailability and increased dihydrobiopterin in adult falciparum malaria: association with disease severity, impaired microvascular function and increased endothelial activation.

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    Tsin W Yeo

    2015-03-01

    Full Text Available Tetrahydrobiopterin (BH₄ is a co-factor required for catalytic activity of nitric oxide synthase (NOS and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin (BH₂, which inhibits NOS. Depending on BH₄ availability, NOS oscillates between NO synthase and NADPH oxidase: as the BH₄/BH₂ ratio decreases, NO production falls and is replaced by superoxide. In African children and Asian adults with severe malaria, NO bioavailability decreases and plasma phenylalanine increases, together suggesting possible BH₄ deficiency. The primary three biopterin metabolites (BH₄, BH₂ and B₀ [biopterin] and their association with disease severity have not been assessed in falciparum malaria. We measured pterin metabolites in urine of adults with severe falciparum malaria (SM; n=12, moderately-severe malaria (MSM, n=17, severe sepsis (SS; n=5 and healthy subjects (HC; n=20 as controls. In SM, urinary BH₄ was decreased (median 0.16 ¼mol/mmol creatinine compared to MSM (median 0.27, SS (median 0.54, and HC (median 0.34]; p<0.001. Conversely, BH₂ was increased in SM (median 0.91 ¼mol/mmol creatinine, compared to MSM (median 0.67, SS (median 0.39, and HC (median 0.52; p<0.001, suggesting increased oxidative stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall, the median BH₄/BH₂ ratio was lowest in SM [0.18 (IQR: 0.04-0.32] compared to MSM (0.45, IQR 0.27-61, SS (1.03; IQR 0.54-2.38 and controls (0.66; IQR 0.43-1.07; p<0.001. In malaria, a lower BH₄/BH₂ ratio correlated with decreased microvascular reactivity (r=0.41; p=0.03 and increased ICAM-1 (r=-0.52; p=0.005. Decreased BH4 and increased BH₂ in severe malaria (but not in severe sepsis uncouples NOS, leading to impaired NO bioavailability and potentially increased oxidative stress. Adjunctive therapy to regenerate BH4 may have a role in improving NO

  2. Human monoclonal IgG selection of Plasmodium falciparum for the expression of placental malaria-specific variant surface antigens

    DEFF Research Database (Denmark)

    Soerli, J; Barfod, L; Lavstsen, T;

    2009-01-01

    Pregnancy-associated Plasmodium falciparum malaria (PAM) is a major cause of morbidity and mortality in African women and their offspring. PAM is characterized by accumulation of infected erythrocytes (IEs) that adhere to chondroitin sulphate A (CSA) in the placental intervillous space. We show...

  3. Serum levels of soluble urokinase plasminogen activator receptor is associated with parasitemia in children with acute Plasmodium falciparum malaria infection

    DEFF Research Database (Denmark)

    Perch, M; Kofoed, Pe; Fischer, Torge

    2004-01-01

    days after treatment. Children younger than 6 years who presented with fever or other symptoms compatible with malaria were enrolled. Blood films and samples were collected on day 0 and day 7. Twenty-five children were allocated to each of three groups according to the amount of Plasmodium falciparum...

  4. Neutrophil alterations in pregnancy-associated malaria and induction of neutrophil chemotaxis by Plasmodium falciparum

    DEFF Research Database (Denmark)

    Boström, S.; Schmiegelow, C; Abu Abed, U

    2017-01-01

    Pregnancy-associated malaria (PAM) is a severe form of the disease caused by sequestration of Plasmodium falciparum-infected red blood cells (iRBCs) in the developing placenta. Pathogenesis of PAM is partially based on immunopathology, with frequent monocyte infiltration into the placenta. Neutro...

  5. Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania.

    Science.gov (United States)

    Mwaiswelo, Richard; Ngasala, Billy; Gil, J Pedro; Malmberg, Maja; Jovel, Irina; Xu, Weiping; Premji, Zul; Mmbando, Bruno P; Björkman, Anders; Mårtensson, Andreas

    2017-08-01

    We assessed the temporal trend of artemether-lumefantrine (AL) cure rate after 8 years of its wide-scale use for treatment of uncomplicated Plasmodium falciparum malaria from 2006 to 2014 in Bagamoyo district, Tanzania. Trend analysis was performed for four studies conducted in 2006, 2007-2008, 2012-2013, and 2014. Patients with acute uncomplicated P. falciparum malaria were enrolled, treated with standard AL regimen and followed-up for 3 (2006), 28 (2014), 42 (2012-2013), or 56 (2007-2008) days for clinical and laboratory evaluation. Primary outcome was day 28 polymerase chain reaction (PCR)-adjusted cure rate across years from 2007 to 2014. Parasite clearance was slower for the 2006 and 2007-2008 cohorts with less than 50% of patients cleared of parasitemia on day 1, but was rapid for the 2012-2013 and 2014 cohorts. Day 28 PCR-adjusted cure rate was 168/170 (98.8%) (95% confidence interval [CI], 97.2-100), 122/127 (96.1%) (95% CI, 92.6-99.5), and 206/207 (99.5%) (95% CI, 98.6-100) in 2007-2008, 2012-2013, and 2014, respectively. There was no significant change in the trend of cure rate between 2007 and 2014 (χ(2)trend test = 0.06, P = 0.90). Pretreatment P. falciparum multidrug-resistant gene 1 (Pfmdr1) N86 prevalence increased significantly across years from 13/48 (27.1%) in 2006 to 183/213 (85.9%) in 2014 (P falciparum malaria despite an increase in prevalence of pretreatment Pfmdr1 N86 and Pfcrt K76 between 2006 and 2014.

  6. A longitudinal study of human antibody responses to Plasmodium falciparum rhoptry-associated protein 1 in a region of seasonal and unstable malaria transmission

    DEFF Research Database (Denmark)

    Fonjungo, P N; Elhassan, I M; Cavanagh, D R

    1999-01-01

    . falciparum-derived RAP1 were used to analyze antibody responses to RAP1 over a period of 4 years (1991 to 1995) of 53 individuals naturally exposed to P. falciparum malaria. In any 1 year during the study, between 23 and 39% of individuals who had malaria developed immunoglobulin G (IgG) antibodies......Rhoptry-associated protein 1 (RAP1) of Plasmodium falciparum is a nonpolymorphic merozoite antigen that is considered a potential candidate for a malaria vaccine against asexual blood stages. In this longitudinal study, recombinant RAP1 (rRAP1) proteins with antigenicity similar to that of P...

  7. Variant surface antigen-specific IgG and protection against clinical consequences of pregnancy-associated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Staalsoe, Trine; Shulman, Caroline E; Bulmer, Judith N

    2004-01-01

    BACKGROUND: Pregnancy-associated malaria caused by Plasmodium falciparum adherence to chondroitin sulfate A in the placental intervillous space is a major cause of low birthweight and maternal anaemia in areas of endemic P falciparum transmission. Adhesion-blocking antibodies that specifically...... recognise parasite-encoded variant surface antigens (VSA) are associated with resistance to pregnancy-associated malaria. We looked for a possible relation between VSA-specific antibody concentrations, placental infection, and protection from low birthweight and maternal anaemia. METHODS: We used flow...... cytometry to measure VSA-specific IgG concentrations in plasma samples taken during child birth from 477 Kenyan women selected from a cohort of 910 women on the basis of HIV-1 status, gravidity, and placental histology. We measured VSA expressed by one placental P falciparum isolate and two isolates...

  8. Assessing Malaria Risks in Greater Mekong Subregion based on Environmental Parameters

    Science.gov (United States)

    Kiang, Richard; Soika, Valerii; Adimi, Farida; Nigro, Joseph

    2005-01-01

    At 4,200 km, the Mekong River is the tenth longest river in the world. It directly and indirectly influences the lives of hundreds of millions of inhabitants in its basin. The riparian countries - Thailand, Myanmar, Cambodia, Laos, Vietnam, and a small part of China - form the Greater Mekong Subregion (GMS). This geographical region has the misfortune of being the world's epicenter of falciparum malaria, which is the most severe form of malaria caused by Plasmodium falciparum. Depending on the country, approximately 50 to 90% of all malaria cases are due to this species. In the Malaria Modeling and Surveillance Project, we have been developing techniques to enhance public health s decision capability for malaria risk assessments and controls. The main objectives are: 1) identifying the potential breeding sites for major vector species; 2) implementing a malaria transmission model to identify the key factors that sustain or intensify malaria transmission; and 3) implementing a risk algorithm to predict the occurrence of malaria and its transmission intensity. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Socioeconomic factors that may influence malaria transmissions will also be incorporated into the predictive models.

  9. Assessing Malaria Risks in Greater Mekong Subregion based on Environmental Parameters

    Science.gov (United States)

    Kiang, Richard; Soika, Valerii; Adimi, Farida; Nigro, Joseph

    2005-01-01

    At 4,200 km, the Mekong River is the tenth longest river in the world. It directly and indirectly influences the lives of hundreds of millions of inhabitants in its basin. The riparian countries - Thailand, Myanmar, Cambodia, Laos, Vietnam, and a small part of China - form the Greater Mekong Subregion (GMS). This geographical region has the misfortune of being the world's epicenter of falciparum malaria, which is the most severe form of malaria caused by Plasmodium falciparum. Depending on the country, approximately 50 to 90% of all malaria cases are due to this species. In the Malaria Modeling and Surveillance Project, we have been developing techniques to enhance public health s decision capability for malaria risk assessments and controls. The main objectives are: 1) identifying the potential breeding sites for major vector species; 2) implementing a malaria transmission model to identify the key factors that sustain or intensify malaria transmission; and 3) implementing a risk algorithm to predict the occurrence of malaria and its transmission intensity. The potential benefits are: 1) increased warning time for public health organizations to respond to malaria outbreaks; 2) optimized utilization of pesticide and chemoprophylaxis; 3) reduced likelihood of pesticide and drug resistance; and 4) reduced damage to environment. Environmental parameters important to malaria transmission include temperature, relative humidity, precipitation, and vegetation conditions. The NASA Earth science data sets that have been used for malaria surveillance and risk assessment include AVHRR Pathfinder, TRMM, MODIS, NSIPP, and SIESIP. Hindcastings based on these environmental parameters have shown good agreement to epidemiological records. Socioeconomic factors that may influence malaria transmissions will also be incorporated into the predictive models.

  10. Therapeutic efficacy of artemether-lumefantrine in uncomplicated falciparum malaria in India

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    Dev Vas

    2009-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the treatment of choice for uncomplicated falciparum malaria. Artemether-lumefantrine (AL, a fixed dose co-formulation, has recently been approved for marketing in India, although it is not included in the National Drug Policy for treatment of malaria. Efficacy of short course regimen (4 × 4 tablets of 20 mg artemether plus 120 mg lumefantrine over 48 h was demonstrated in India in the year 2000. However, low cure rates in Thailand and better plasma lumefantrine concentration profile with a six-dose regimen over three days, led to the recommendation of higher dose globally. This is the first report on the therapeutic efficacy of the six-dose regimen of AL in Indian uncomplicated falciparum malaria patients. The data generated will help in keeping the alternative ACT ready for use in the National Programme as and when required. Methods One hundred and twenty four subjects between two and fifty-five years of age living in two highly endemic areas of the country (Assam and Orissa were enrolled for single arm, open label prospective study. The standard six-dose regimen of AL was administered over three days and was followed-up with clinical and parasitological evaluations over 28 days. Molecular markers msp-1 and msp-2 were used to differentiate the recrudescence and reinfection among the study subjects. In addition, polymorphism in pfmdr1 was also carried out in the samples obtained from patients before and after the treatment. Results The PCR corrected cure rates were high at both the sites viz. 100% (n = 53 in Assam and 98.6% (n = 71 in Orissa. The only treatment failure case on D7 was a malnourished child. The drug was well tolerated with no adverse events. Patients had pre-treatment carriage of wild type codons at positions 86 (41.7%, n = 91 and 184 (91.3%, n = 91 of pfmdr1 gene. Conclusion AL is safe and effective drug for the treatment of acute uncomplicated falciparum malaria

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

    OpenAIRE

    Schunk, Mirjam; Kumma, Wondimagegn P.; Barreto Miranda, Isabel; Maha E. Osman; Roewer, Susanne; Alano, Abraham; Loescher, Thomas; Bienzle, Ulrich; Mockenhaupt, Frank P

    2006-01-01

    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 assesse...

  12. A new visually improved and sensitive loop mediated isothermal amplification (LAMP) for diagnosis of symptomatic falciparum malaria.

    Science.gov (United States)

    Mohon, Abu Naser; Elahi, Rubayet; Khan, Wasif A; Haque, Rashidul; Sullivan, David J; Alam, Mohammad Shafiul

    2014-06-01

    Molecular diagnosis of malaria by nucleotide amplification requires sophisticated and expensive instruments, typically found only in well-established laboratories. Loop-mediated isothermal amplification (LAMP) has provided a new platform for an easily adaptable molecular technique for molecular diagnosis of malaria without the use of expensive instruments. A new primer set has been designed targeting the 18S rRNA gene for the detection of Plasmodium falciparum in whole blood samples. The efficacy of LAMP using the new primer set was assessed in this study in comparison to that of a previously described set of LAMP primers as well as with microscopy and real-time PCR as reference methods for detecting P. falciparum. Pre-addition of hydroxy napthol blue (HNB) in the LAMP reaction caused a distinct color change, thereby improving the visual detection system. The new LAMP assay was found to be 99.1% sensitive compared to microscopy and 98.1% when compared to real-time PCR. Meanwhile, its specificity was 99% and 100% in contrast to microscopy and real-time PCR, respectively. Moreover, the LAMP method was in very good agreement with microscopy and real-time PCR (0.94 and 0.98, respectively). This new LAMP method can detect at least 5parasites/μL of infected blood within 35min, while the other LAMP method tested in this study, could detect a minimum of 100parasites/μL of human blood after 60min of amplification. Thus, the new method is sensitive and specific, can be carried out in a very short time, and can substitute PCR in healthcare clinics and standard laboratories.

  13. Clínica de la malaria complicada debida a P. falciparum Estudio de casos y controles en Tumaco y Turbo (Colombia Clinical presentation of severe malaria due plasmodiun falciparum. casecontrol study in Tumaco and Turbo (Colombia.

    Directory of Open Access Journals (Sweden)

    2006-04-01

    Full Text Available Antecedentes y problema: son muy pocos los estudios latinoamericanos sobre malaria por Plasmodium falciparum (P falciparum complicada y se requiere estudiarla para identificar un patrón propio. OBJETIVOS. Identificar las complicaciones presentes en pacientes de Tumaco (Nariño y Turbo (Antioquia en Colombia, con malaria por P falciparum. MÉTODOS. Diseño de casos y controles. Se aplicaron los criterios diagnósticos de complicación OMS-2000 (Organización Mundial de la Salud. RESULTADOS. Se captaron 64 casos (con malaria por P. falciparum complicada y 135 controles (con malaria por P. falciparum no complicada. El tiempo de evolución de la enfermedad (promedio 5,6 días en los casos y 5,9 en los controles y la frecuencia de síntomas fueron similares en ambos grupos (p>0,05, pero ladificultad respiratoria y la ictericia fueron más frecuentes en los casos que en los controles (p<0,05. Los valores promedio de glicemia y creatinina fueron similares en ambos grupos, pero los casos tuvieron hemoglobina y recuento de plaquetas menores que los controles (p<0,05 y mayores niveles de nitrógeno ureico, aspartatoaminotransferasa y bilirrubinas total y directa (p<0,05. Las complicaciones encontradas fueron hiperparasitemia en 48%, disfunción hepática en 44%, síndrome de dificultad respiratoria aguda en 9%, falla renal en 6%, trombocitopenia grave en 5%, anemia grave en 3%, malaria cerebral en 3% e hipoglicemia grave en 2%. Los criterios de complicación malárica de OMS se comparan con otros y se discuten las implicaciones. Background: Latin American studies on severe falciparum malaria are scarce, therefore, the pattern of complications of the region is uknown. Objectives. To identify characterize severe malaria in patients from Tumaco (Nariño and Turbo (Antioquia in Colombia. Methods. The 2000 World Health Organization criteria for complicated malaria were applied in a cases and controls study. Results. 64 cases (P falciparum complicated malaria

  14. Major Burden of Severe Anemia from Non-Falciparum Malaria Species in Southern Papua: A Hospital-Based Surveillance Study

    Science.gov (United States)

    Douglas, Nicholas M.; Lampah, Daniel A.; Kenangalem, Enny; Simpson, Julie A.; Poespoprodjo, Jeanne R.; Sugiarto, Paulus; Anstey, Nicholas M.; Price, Ric N.

    2013-01-01

    Background The burden of anemia attributable to non-falciparum malarias in regions with Plasmodium co-endemicity is poorly documented. We compared the hematological profile of patients with and without malaria in southern Papua, Indonesia. Methods and Findings Clinical and laboratory data were linked for all patients presenting to a referral hospital between April 2004 and December 2012. Data were available on patient demographics, malaria diagnosis, hemoglobin concentration, and clinical outcome, but other potential causes of anemia could not be identified reliably. Of 922,120 patient episodes (837,989 as outpatients and 84,131 as inpatients), a total of 219,845 (23.8%) were associated with a hemoglobin measurement, of whom 67,696 (30.8%) had malaria. Patients with P. malariae infection had the lowest hemoglobin concentration (n = 1,608, mean = 8.93 [95% CI 8.81–9.06]), followed by those with mixed species infections (n = 8,645, mean = 9.22 [95% CI 9.16–9.28]), P. falciparum (n = 37,554, mean = 9.47 [95% CI 9.44–9.50]), and P. vivax (n = 19,858, mean = 9.53 [95% CI 9.49–9.57]); p-value for all comparisons anemia (hemoglobin anemia (adjusted odds ratio [AOR] 3.25 [95% CI 2.99–3.54]); AORs for severe anaemia associated with P. falciparum, P. vivax, and P. malariae were 2.11 (95% CI 2.00–2.23), 1.87 (95% CI 1.74–2.01), and 2.18 (95% CI 1.76–2.67), respectively, panemia was attributable to non-falciparum infections compared with 15.1% (95% CI 13.9%–16.3%) for P. falciparum monoinfections. Patients with severe anemia had an increased risk of death (AOR = 5.80 [95% CI 5.17–6.50]; panemia in early infancy, mixed P. vivax/P. falciparum infections are associated with a greater hematological impairment than either species alone, and in adulthood P. malariae, although rare, is associated with the lowest hemoglobin concentration. These findings highlight the public health importance of integrated genus-wide malaria

  15. Plasmodium falciparum malaria: Convergent evolutionary trajectories towards delayed clearance following artemisinin treatment.

    Science.gov (United States)

    Wilairat, Prapon; Kümpornsin, Krittikorn; Chookajorn, Thanat

    2016-05-01

    Malaria is a major global health challenge with 300million new cases every year. The most effective regimen for treating Plasmodium falciparum malaria is based on artemisinin and its derivatives. The drugs are highly effective, resulting in rapid clearance of parasites even in severe P. falciparum malaria patients. During the last five years, artemisinin-resistant parasites have begun to emerge first in Cambodia and now in Thailand and Myanmar. At present, the level of artemisinin resistance is relatively low with clinical presentation of delayed artemisinin clearance (a longer time to reduce parasite load) and a small decrease in artemisinin sensitivity in cultured isolates. Nevertheless, multiple genetic loci associated with delayed parasite clearance have been reported, but they cannot account for a large portion of cases. Even the most well-studied kelch 13 propeller mutations cannot always predict the outcome of artemisinin treatment in vitro and in vivo. Here we propose that delayed clearance by artemisinin could be the result of convergent evolution, driven by multiple trajectories to overcome artemisinin-induced stress, but precluded to become full blown resistance by high fitness cost. Genetic association studies by several genome-wide approaches reveal linkage disequilibrium between multiple loci and delayed parasite clearance. Genetic manipulations at some of these loci already have resulted in loss in artemisinin sensitivity. The notion presented here is by itself consistent with existing evidence on artemisinin resistance and has the potential to be explored using available genomic data. Most important of all, molecular surveillance of artemisinin resistance based on multi-genic markers could be more informative than relying on any one particular molecular marker. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Factors contributing to delay in parasite clearance in uncomplicated falciparum malaria in children

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    Sijuade Abayomi

    2010-02-01

    Full Text Available Abstract Background Drug resistance in Plasmodium falciparum is common in many endemic and other settings but there is no clear recommendation on when to change therapy when there is delay in parasite clearance after initiation of therapy in African children. Methods The factors contributing to delay in parasite clearance, defined as a clearance time > 2 d, in falciparum malaria were characterized in 2,752 prospectively studied children treated with anti-malarial drugs between 1996 and 2008. Results 1,237 of 2,752 children (45% had delay in parasite clearance. Overall 211 children (17% with delay in clearance subsequently failed therapy and they constituted 72% of those who had drug failure, i.e., 211 of 291 children. The following were independent risk factors for delay in parasite clearance at enrolment: age less than or equal to 2 years (Adjusted odds ratio [AOR] = 2.13, 95% confidence interval [CI]1.44-3.15, P 50,000/ul (AOR = 2.21, 95% CI = 1.77-2.75, P 20000/μl a day after treatment began, were independent risk factors for delay in clearance. Non-artemisinin monotherapies were associated with delay in clearance and treatment failures, and in those treated with chloroquine or amodiaquine, with pfmdr 1/pfcrt mutants. Delay in clearance significantly increased gametocyte carriage (P Conclusion Delay in parasite clearance is multifactorial, is related to drug resistance and treatment failure in uncomplicated malaria and has implications for malaria control efforts in sub-Saharan Africa.

  17. Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria

    Science.gov (United States)

    Fry, Andrew E.; Griffiths, Michael J.; Auburn, Sarah; Diakite, Mahamadou; Forton, Julian T.; Green, Angela; Richardson, Anna; Wilson, Jonathan; Jallow, Muminatou; Sisay-Joof, Fatou; Pinder, Margaret; Peshu, Norbert; Williams, Thomas N.; Marsh, Kevin; Molyneux, Malcolm E.; Taylor, Terrie E.; Rockett, Kirk A.; Kwiatkowski, Dominic P.

    2009-01-01

    There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across 3 African populations. Using population- and family-based tests we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: Case-control allelic odds ratio (OR) 1.2, 95% confidence interval (CI) 1.09 – 1.32, P=0.0003; Family-studies allelic OR 1.19, CI 1.08 – 1.32, P=0.001; Pooled across all studies allelic OR 1.18, CI 1.11 - 1.26, P=2×10−7. Analyzing the family trios we found suggestive evidence of a parent-of-origin effect at the ABO locus. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P=0.046). Finally we used HapMap data to demonstrate a region of low FST (−0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of FST across chromosome 9 (~99.5 – 99.9th centile). This low FST region may be a signal of longstanding balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum. PMID:18003641

  18. Evaluating Controlled Human Malaria Infection in Kenyan Adults with Varying Degrees of Prior Exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection

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    Susanne Helena Hodgson

    2014-12-01

    Full Text Available Background: Controlled human malaria infection (CHMI studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI to Plasmodium falciparum. Methods: We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272. Results: All participants developed blood-stage infection confirmed by qPCR. However one volunteer (110 remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR (1.3 in comparison to the other 27 volunteers (median 11.1. A significant correlation was seen between PMR and screening anti-schizont ELISA OD (p=0.044, R=-0.384 but not when volunteer 110 was excluded from the analysis (p=0.112, R=-0.313. Conclusions: PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies.

  19. Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.

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    Charles Arama

    Full Text Available The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs, and in particular dendritic cells (DCs are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR

  20. MAD 20 alleles of merozoite surface protein-1 (msp-1) are associated with severe Plasmodium falciparum malaria in Pakistan.

    Science.gov (United States)

    Ghanchi, Najia Karim; Hasan, Zahra; Islam, Muniba; Beg, Mohammad Asim

    2015-04-01

    Various factors determine the outcome of Plasmodium falciparum infection such as parasite load, sequestration, adhesion molecules, and immune mediators. P. falciparum merozoite surface protein-1 (msp-1) and msp-2 genotypes were also found associated with severe disease. We investigated the association between msp-1 and msp-2 genotypes in patients with uncomplicated malaria (UM) and severe malaria (SM). Twenty-two malaria patients with microscopy-confirmed P. falciparum infection and eight healthy endemic controls were selected for analysis. Nested polymerase chain reaction (PCR) was used to identify P. falciparum genotypes. The plasma concentration of cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ)] and chemokines [chemokine (C-X-C motif) ligand 9 (CXCL9) and CXCL10] were evaluated using enzyme-linked immunosorbent assay (ELISA). TNF-α levels were significantly higher in both UM (389 pg/mL, p = 0.020) and SM (771 pg/mL, p = 0.004) compared with healthy controls, while they were greater in SM (p = 0.012) as compared to UM. CXCL9 levels were significantly raised in SM as compared to UM and negative controls (NCs). CXCL10 levels were raised in UM (550 pg/mL, p = 0.001) and SM (1480 pg/mL, p = 0.01) as compared with NCs. Increased levels of IL-6 were found in patients carrying the FC27 allelic type of msp-2. A higher prevalence of MAD 20 and K1 msp-1 alleles was observed in the SM group compared to UM. Overall, a greater prevalence of MAD 20 alleles and increased serum TNF-α and CXCL9 levels were associated with severe outcome in malaria. Understanding the diversity of malaria genotypes is important for predicting disease-related outcomes of P. falciparum infection in endemic areas. Copyright © 2014. Published by Elsevier B.V.

  1. Interethnic differences in antigen-presenting cell activation and TLR responses in Malian children during Plasmodium falciparum malaria.

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    Arama, Charles; Giusti, Pablo; Boström, Stéphanie; Dara, Victor; Traore, Boubacar; Dolo, Amagana; Doumbo, Ogobara; Varani, Stefania; Troye-Blomberg, Marita

    2011-03-31

    The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be

  2. Effects of Aging on Parasite Biomass, Inflammation, Endothelial Activation, Microvascular Dysfunction and Disease Severity in Plasmodium knowlesi and Plasmodium falciparum Malaria.

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    Barber, Bridget E; Grigg, Matthew J; William, Timothy; Piera, Kim A; Boyle, Michelle J; Yeo, Tsin W; Anstey, Nicholas M

    2017-06-15

    In populations pauci-immune to malaria, risk of severe malaria increases with age. This is particularly apparent in Plasmodium knowlesi malaria. However, pathophysiological mechanisms underlying knowlesi malaria, and of the age-related increase in risk of severe malaria in general, are poorly understood. In Malaysian patients aged ≥12 years with severe (n = 47) and nonsevere (n = 99) knowlesi malaria, severe (n = 21) and nonsevere (n = 109) falciparum malaria, and healthy controls (n = 50), we measured parasite biomass, systemic inflammation (interleukin 6 [IL-6]), endothelial activation (angiopoietin-2), and microvascular function, and evaluated the effects of age. Plasmodium knowlesi parasitemia correlated with age (Spearman's correlation coefficient [rs] = 0.36; P falciparum malaria, angiopoietin-2 increased with age, independent of parasite biomass (histidine-rich protein 2 [HRP2]). Independent risk factors for severe malaria included parasitemia and angiopoietin-2 in knowlesi malaria, and HRP2, angiopoietin-2, and microvascular dysfunction in falciparum malaria. Parasite biomass, endothelial activation, and microvascular dysfunction are associated with severe disease in knowlesi malaria and likely contribute to pathogenesis. The association of each of these processes with aging may account for the greater severity of malaria observed in older adults in low-endemic regions.

  3. Malaria at Humaita county, Amazonas state, Brazil: XVII — immune response in patients with Plasmodium falciparum according to gametocytes

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    Domingos Alves Meira

    1985-10-01

    Full Text Available In August 1983 the Authors studied 36 patients with Plasmodium falciparum malaria and 14 normal individuals born in Humaita region who had never had malaria, had no spleen enlargement and had negative parasitemia as well as passive hemagglutination. Medical histories were obtained and complete physical examination were performed in all of them just as blood tests, parasite density and lymphocyte typing. The lymphocytes were separated and then frozen in liquid nitrogen for later typing by rosette formation. The patients were divided in two groups according to the presence (13 patients or abscence (23 patients of gametocytes before treatment. Severe malaria was predominant in the group without gametocytes. The results showed a decrease in the T-cell numbers in Plasmodium falciparum acute malaria patients both with or without gametocytes before the treatment, while B-cell numbers were normal only in the patients with gametocytes. These observations as like as those previously reported by the Authors, permit to associate the presence of gametocytes in peripheral blood and normal number of B-cells in patients with mild Plasmodium falciparum malaria.

  4. Gene disruption of Plasmodium falciparum p52 results in attenuation of malaria liver stage development in cultured primary human hepatocytes.

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    Ben C L van Schaijk

    Full Text Available Difficulties with inducing sterile and long lasting protective immunity against malaria with subunit vaccines has renewed interest in vaccinations with attenuated Plasmodium parasites. Immunizations with sporozoites that are attenuated by radiation (RAS can induce strong protective immunity both in humans and rodent models of malaria. Recently, in rodent parasites it has been shown that through the deletion of a single gene, sporozoites can also become attenuated in liver stage development and, importantly, immunization with these sporozoites results in immune responses identical to RAS. The promise of vaccination using these genetically attenuated sporozoites (GAS depends on translating the results in rodent malaria models to human malaria. In this study, we perform the first essential step in this transition by disrupting, p52, in P. falciparum an ortholog of the rodent parasite gene, p36p, which we had previously shown can confer long lasting protective immunity in mice. These P. falciparum P52 deficient sporozoites demonstrate gliding motility, cell traversal and an invasion rate into primary human hepatocytes in vitro that is comparable to wild type sporozoites. However, inside the host hepatocyte development is arrested very soon after invasion. This study reveals, for the first time, that disrupting the equivalent gene in both P. falciparum and rodent malaria Plasmodium species generates parasites that become similarly arrested during liver stage development and these results pave the way for further development of GAS for human use.

  5. Successful human infection with P. falciparum using three aseptic Anopheles stephensi mosquitoes: a new model for controlled human malaria infection.

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    Matthew B Laurens

    Full Text Available Controlled human malaria infection (CHMI is a powerful method for assessing the efficacy of anti-malaria vaccines and drugs targeting pre-erythrocytic and erythrocytic stages of the parasite. CHMI has heretofore required the bites of 5 Plasmodium falciparum (Pf sporozoite (SPZ-infected mosquitoes to reliably induce Pf malaria. We reported that CHMI using the bites of 3 PfSPZ-infected mosquitoes reared aseptically in compliance with current good manufacturing practices (cGMP was successful in 6 participants. Here, we report results from a subsequent CHMI study using 3 PfSPZ-infected mosquitoes reared aseptically to validate the initial clinical trial. We also compare results of safety, tolerability, and transmission dynamics in participants undergoing CHMI using 3 PfSPZ-infected mosquitoes reared aseptically to published studies of CHMI using 5 mosquitoes. Nineteen adults aged 18-40 years were bitten by 3 Anopheles stephensi mosquitoes infected with the chloroquine-sensitive NF54 strain of Pf. All 19 participants developed malaria (100%; 12 of 19 (63% on Day 11. The mean pre-patent period was 258.3 hours (range 210.5-333.8. The geometric mean parasitemia at first diagnosis by microscopy was 9.5 parasites/µL (range 2-44. Quantitative polymerase chain reaction (qPCR detected parasites an average of 79.8 hours (range 43.8-116.7 before microscopy. The mosquitoes had a geometric mean of 37,894 PfSPZ/mosquito (range 3,500-152,200. Exposure to the bites of 3 aseptically-raised, PfSPZ-infected mosquitoes is a safe, effective procedure for CHMI in malaria-naïve adults. The aseptic model should be considered as a new standard for CHMI trials in non-endemic areas. Microscopy is the gold standard used for the diagnosis of Pf malaria after CHMI, but qPCR identifies parasites earlier. If qPCR continues to be shown to be highly specific, and can be made to be practical, rapid, and standardized, it should be considered as an alternative for diagnosis

  6. Severe imported falciparum malaria: a cohort study in 400 critically ill adults.

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    Fabrice Bruneel

    Full Text Available BACKGROUND: Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit. METHODOLOGY AND PRINCIPAL FINDINGS: Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000-2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses. Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths. By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28-2.32; P = 0.0004, Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20-1.45; P<0.0001, and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22-1.62; P<0.0001. CONCLUSIONS AND SIGNIFICANCE: In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available.

  7. Iron Deficiency Protects Against Severe Plasmodium falciparum Malaria and Death in Young Children

    Science.gov (United States)

    Gwamaka, Moses; Kurtis, Jonathan D.; Sorensen, Bess E.; Holte, Sarah; Morrison, Robert; Mutabingwa, Theonest K.; Fried, Michal

    2012-01-01

    (See the Editorial Commentary by Awah and Kaneko, on pages 1145–7.) Background. Iron supplementation may increase malaria morbidity and mortality, but the effect of naturally occurring variation in iron status on malaria risk is not well studied. Methods. A total of 785 Tanzanian children living in an area of intense malaria transmission were enrolled at birth, and intensively monitored for parasitemia and illness including malaria for up to 3 years, with an average of 47 blood smears. We assayed plasma samples collected at routine healthy-child visits, and evaluated the impact of iron deficiency (ID) on future malaria outcomes and mortality. Results. ID at routine, well-child visits significantly decreased the odds of subsequent parasitemia (23% decrease, P iron status assays/child), ID reduced the prevalence of parasitemia (6.6-fold), hyperparasitemia (24.0-fold), and severe malaria (4.0-fold) at the time of sample collection (all P iron status, and therefore iron supplementation may have adverse effects even among children with ID. Future interventional studies should assess whether treatment for ID coupled with effective malaria control can mitigate the risks of iron supplementation for children in areas of malaria transmission. PMID:22354919

  8. Human population, urban settlement patterns and their impact on Plasmodium falciparum malaria endemicity

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    Kabaria Caroline W

    2008-10-01

    Full Text Available Abstract Background The efficient allocation of financial resources for malaria control and the optimal distribution of appropriate interventions require accurate information on the geographic distribution of malaria risk and of the human populations it affects. Low population densities in rural areas and high population densities in urban areas can influence malaria transmission substantially. Here, the Malaria Atlas Project (MAP global database of Plasmodium falciparum parasite rate (PfPR surveys, medical intelligence and contemporary population surfaces are utilized to explore these relationships and other issues involved in combining malaria risk maps with those of human population distribution in order to define populations at risk more accurately. Methods First, an existing population surface was examined to determine if it was sufficiently detailed to be used reliably as a mask to identify areas of very low and very high population density as malaria free regions. Second, the potential of international travel and health guidelines (ITHGs for identifying malaria free cities was examined. Third, the differences in PfPR values between surveys conducted in author-defined rural and urban areas were examined. Fourth, the ability of various global urban extent maps to reliably discriminate these author-based classifications of urban and rural in the PfPR database was investigated. Finally, the urban map that most accurately replicated the author-based classifications was analysed to examine the effects of urban classifications on PfPR values across the entire MAP database. Results Masks of zero population density excluded many non-zero PfPR surveys, indicating that the population surface was not detailed enough to define areas of zero transmission resulting from low population densities. In contrast, the ITHGs enabled the identification and mapping of 53 malaria free urban areas within endemic countries. Comparison of PfPR survey results showed

  9. Safety, efficacy and population pharmacokinetics of fixed-dose combination of artesunate-mefloquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in India.

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    Valecha, Neena; Srivastava, Bina; Dubhashi, N G; Rao, B H Krishnamoorthy; Kumar, Ashwani; Ghosh, S K; Singh, Jai Prakash Narayan; Kiechel, J R; Sharma, Bhawna; Jullien, V; Dash, A P; Taylor, W R J; Anvikar, Anupkumar R

    2013-12-01

    India has switched over to artemisinin-based combination therapy (ACT) for the treatment of acute uncomplicated Plasmodium falciparum malaria and the ACT used in the national programme is artesunate + sulphadoxine-pyrimethamine. Since the efficacy of ACT is dependent also on the partner drug, there is a need to evaluate and deploy multiple ACTs. This multicentre, single-arm, open-label clinical trial was carried out to assess the efficacy, safety and population pharmacokinetics of a fixed dose combination (FDC) artesunate mefloquine (ASMQ) in P. falciparum infected, Indian adults at Panjim, Goa, and Mangalore, Karnataka between December 2007 and November 2008. A total of 77 patients (males 74) were screened and enrolled: 42 at Goa and 35 at Mangalore with a median age of 25 yr (range 18-55 yr). One patient failed in treatment on D53, a PCR proven new infection, seven developed recurrent vivax parasitaemia and 11 did not have a parasitological endpoint. By per protocol analysis, the D63 cure rate was 58/59 (98.3; 95% C.I. 90.9-99.9%), and 58/58, with PCR correction. ASMQ was well-tolerated and no serious adverse events were reported. The study showed that the ASMQ FDC was efficacious and well-tolerated for the treatment of acute, uncomplicated P. falciparum malaria in highly endemic, chloroquine resistant areas of Goa and Mangalore. It is a viable option for India.

  10. Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management.

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    Gatton, Michelle L; Rees-Channer, Roxanne R; Glenn, Jeffrey; Barnwell, John W; Cheng, Qin; Chiodini, Peter L; Incardona, Sandra; González, Iveth J; Cunningham, Jane

    2015-03-18

    Malaria rapid diagnostic tests (RDTs) are appropriate for case management, but persistent antigenaemia is a concern for HRP2-detecting RDTs in endemic areas. It has been suggested that pan-pLDH test bands on combination RDTs could be used to distinguish persistent antigenaemia from active Plasmodium falciparum infection, however this assumes all active infections produce positive results on both bands of RDTs, an assertion that has not been demonstrated. In this study, data generated during the WHO-FIND product testing programme for malaria RDTs was reviewed to investigate the reactivity of individual test bands against P. falciparum in 18 combination RDTs. Each product was tested against multiple wild-type P. falciparum only samples. Antigen levels were measured by quantitative ELISA for HRP2, pLDH and aldolase. When tested against P. falciparum samples at 200 parasites/μL, 92% of RDTs were positive; 57% of these on both the P. falciparum and pan bands, while 43% were positive on the P. falciparum band only. There was a relationship between antigen concentration and band positivity; ≥4 ng/mL of HRP2 produced positive results in more than 95% of P. falciparum bands, while ≥45 ng/mL of pLDH was required for at least 90% of pan bands to be positive. In active P. falciparum infections it is common for combination RDTs to return a positive HRP2 band combined with a negative pan-pLDH band, and when both bands are positive, often the pan band is faint. Thus active infections could be missed if the presence of a HRP2 band in the absence of a pan band is interpreted as being caused solely by persistent antigenaemia.

  11. Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

    Science.gov (United States)

    Woehlbier, Ute; Epp, Christian; Kauth, Christian W.; Lutz, Rolf; Long, Carole A.; Coulibaly, Boubacar; Kouyaté, Bocar; Arevalo-Herrera, Myriam; Herrera, Sócrates; Bujard, Hermann

    2006-01-01

    The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria. PMID:16428781

  12. A retrospective analysis of the haemodynamic and metabolic effects of fluid resuscitation in Vietnamese adults with severe falciparum malaria.

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    Hoan Phu Nguyen

    Full Text Available BACKGROUND: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP guided, crystalloid based, resuscitation in adults. METHODS: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. RESULTS: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2 (95% Confidence interval (CI: 0.41 to 1.1, but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3. The CVP and PAoP (pulmonary artery occlusion pressure were highly inter-correlated (r(s = 0.7, p<0.0001, but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit or respiratory status (PaO(2/FiO(2 ratio. There was no correlation between the oxygen delivery (DO(2 and base deficit at the 63 time-points where they were assessed simultaneously (r(s = -0.09, p = 0.46. CONCLUSIONS: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs.

  13. Open-label trial on efficacy of artemether/lumefantrine against the uncomplicated Plasmodium falciparum malaria in Metema district, Northwestern Ethiopia

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    Wudneh, Feven; Assefa, Ashenafi; Nega, Desalegn; Mohammed, Hussien; Solomon, Hiwot; Kebede, Tadesse; Woyessa, Adugna; Assefa, Yibeltal; Kebede, Amha; Kassa, Moges

    2016-01-01

    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 cure rate of Coartem® was 98.8% (95% confidence interval: 93.3%–100%) in the study area. Recurrence of one P. falciparum case was detected on day 28, with a late parasitological failure rate of 1.2%. No early treatment failure occurred. Complete parasite and fever clearance was observed on day 3. Gametocyte carriage was 4.4% at enrollment that cleared on day 21. Although the difference is statistically not significant, a slight increase in the level of mean hemoglobin from baseline to day 28 was observed. Conclusion The study showed high efficacy and tolerability of Coartem® against uncomplicated P. falciparum malaria, suggesting the continuation as a first-line drug in the study district

  14. Safety and efficacy of dihydroartemisinin-piperaquine in falciparum malaria: a prospective multi-centre individual patient data analysis.

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    Julien Zwang

    Full Text Available BACKGROUND: The fixed dose antimalarial combination of dihydroartemisinin-piperaquine (DP is a promising new artemisinin-based combination therapy (ACT. We present an individual patient data analysis of efficacy and tolerability in acute uncomplicated falciparum malaria, from seven published randomized clinical trials conducted in Africa and South East Asia using a predefined in-vivo protocol. Comparator drugs were mefloquine-artesunate (MAS3 in Thailand, Myanmar, Laos and Cambodia; artemether-lumefantrine in Uganda; and amodiaquine+sulfadoxine-pyrimethamine and artesunate+amodiaquine in Rwanda. METHODS AND FINDINGS: In total 3,547 patients were enrolled: 1,814 patients (32% children under five years received DP and 1,733 received a comparator antimalarial at 12 different sites and were followed for 28-63 days. There was no significant heterogeneity between trials. DP was well tolerated with 1.7% early vomiting. There were less adverse events with DP in children and adults compared to MAS3 except for diarrhea; ORs (95%CI 2.74 (2.13 to 3.51 and 3.11 (2.31 to 4.18, respectively. DP treatment resulted in a rapid clearance of fever and parasitaemia. The PCR genotype corrected efficacy at Day 28 of DP assessed by survival analysis was 98.7% (95%CI 97.6-99.8. DP was superior to the comparator drugs in protecting against both P.falciparum recurrence and recrudescence (P = 0.001, weighted by site. There was no difference between DP and MAS3 in treating P. vivax co-infections and in suppressing the first relapse (median interval to P. vivax recurrence: 6 weeks. Children under 5 y were at higher risk of recurrence for both infections. The proportion of patients developing gametocytaemia (P = 0.002, weighted by site and the subsequent gametocyte carriage rates were higher with DP (11/1000 person gametocyte week, PGW than MAS3 (6/1000 PGW, P = 0.001, weighted by site. CONCLUSIONS: DP proved a safe, well tolerated, and highly effective treatment of P.falciparum

  15. An imported case of severe falciparum malaria with prolonged hemolytic anemia clinically mimicking a coinfection with babesiosis.

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    Na, Young Ju; Chai, Jong-Yil; Jung, Bong-Kwang; Lee, Hyun Jung; Song, Ji Young; Je, Ji Hye; Seo, Ji Hye; Park, Sung Hun; Choi, Ji Seon; Kim, Min Ja

    2014-12-01

    While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.

  16. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies.

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    Chim W Chan

    Full Text Available Understanding the transmission and movement of Plasmodium parasites is crucial for malaria elimination and prevention of resurgence. Located at the limit of malaria transmission in the Pacific, Vanuatu is an ideal candidate for elimination programs due to low endemicity and the isolated nature of its island setting. We analyzed the variation in the merozoite surface protein 1 (msp1 and the circumsporozoite protein (csp of P. falciparum and P. vivax populations to examine the patterns of gene flow and population structures among seven sites on five islands in Vanuatu. Genetic diversity was in general higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by greater extent of gene flow among sites and among islands. Consistent with the different patterns of gene flow, the proportion of genetic variance found among islands was substantially higher in P. falciparum (28.81-31.23% than in P. vivax (-0.53-3.99%. Our data suggest that the current island-by-island malaria elimination strategy in Vanuatu, while adequate for P. falciparum elimination, might need to be complemented with more centrally integrated measures to control P. vivax movement across islands.

  17. Plasmodium vivax and Plasmodium falciparum at the crossroads of exchange among islands in Vanuatu: implications for malaria elimination strategies.

    Science.gov (United States)

    Chan, Chim W; Sakihama, Naoko; Tachibana, Shin-Ichiro; Idris, Zulkarnain Md; Lum, J Koji; Tanabe, Kazuyuki; Kaneko, Akira

    2015-01-01

    Understanding the transmission and movement of Plasmodium parasites is crucial for malaria elimination and prevention of resurgence. Located at the limit of malaria transmission in the Pacific, Vanuatu is an ideal candidate for elimination programs due to low endemicity and the isolated nature of its island setting. We analyzed the variation in the merozoite surface protein 1 (msp1) and the circumsporozoite protein (csp) of P. falciparum and P. vivax populations to examine the patterns of gene flow and population structures among seven sites on five islands in Vanuatu. Genetic diversity was in general higher in P. vivax than P. falciparum from the same site. In P. vivax, high genetic diversity was likely maintained by greater extent of gene flow among sites and among islands. Consistent with the different patterns of gene flow, the proportion of genetic variance found among islands was substantially higher in P. falciparum (28.81-31.23%) than in P. vivax (-0.53-3.99%). Our data suggest that the current island-by-island malaria elimination strategy in Vanuatu, while adequate for P. falciparum elimination, might need to be complemented with more centrally integrated measures to control P. vivax movement across islands.

  18. Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2009-01-01

    BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from...... on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses....

  19. Defining the antigenic diversity of Plasmodium falciparum apical membrane antigen 1 and the requirements for a multi-allele vaccine against malaria.

    Directory of Open Access Journals (Sweden)

    Damien R Drew

    Full Text Available Apical Membrane Antigen 1 (AMA1 is a leading malaria vaccine candidate and a target of naturally-acquired human immunity. Plasmodium falciparum AMA1 is polymorphic and in vaccine trials it induces strain-specific protection. This antigenic diversity is a major roadblock to development of AMA1 as a malaria vaccine and understanding how to overcome it is essential. To assess how AMA1 antigenic diversity limits cross-strain growth inhibition, we assembled a panel of 18 different P. falciparum isolates which are broadly representative of global AMA1 sequence diversity. Antibodies raised against four well studied AMA1 alleles (W2Mef, 3D7, HB3 and FVO were tested for growth inhibition of the 18 different P. falciparum isolates in growth inhibition assays (GIA. All antibodies demonstrated substantial cross-inhibitory activity against different isolates and a mixture of the four different AMA1 antibodies inhibited all 18 isolates tested, suggesting significant antigenic overlap between AMA1 alleles and limited antigenic diversity of AMA1. Cross-strain inhibition by antibodies was only moderately and inconsistently correlated with the level of sequence diversity between AMA1 alleles, suggesting that sequence differences are not a strong predictor of antigenic differences or the cross-inhibitory activity of anti-allele antibodies. The importance of the highly polymorphic C1-L region for inhibitory antibodies and potential vaccine escape was assessed by generating novel transgenic P. falciparum lines for testing in GIA. While the polymorphic C1-L epitope was identified as a significant target of some growth-inhibitory antibodies, these antibodies only constituted a minor proportion of the total inhibitory antibody repertoire, suggesting that the antigenic diversity of inhibitory epitopes is limited. Our findings support the concept that a multi-allele AMA1 vaccine would give broad coverage against the diversity of AMA1 alleles and establish new tools to

  20. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India).

    Science.gov (United States)

    Khan, Haris M; Shujatullah, Fatima; Ashfaq, Mohammad; Raza, Adil

    2011-01-01

    To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002. High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  1. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India)

    Institute of Scientific and Technical Information of China (English)

    Haris M Khan; Fatima Shujatullah; Mohammad Ashfaq; Adil Raza

    2011-01-01

    Objective: To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Methods: Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Results: Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002.Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.

  2. Malaria vaccine candidate antigen targeting the pre-erythrocytic stage of Plasmodium falciparum produced at high level in plants.

    Science.gov (United States)

    Voepel, Nadja; Boes, Alexander; Edgue, Güven; Beiss, Veronique; Kapelski, Stephanie; Reimann, Andreas; Schillberg, Stefan; Pradel, Gabriele; Fendel, Rolf; Scheuermayer, Matthias; Spiegel, Holger; Fischer, Rainer

    2014-11-01

    Plants have emerged as low-cost production platforms suitable for vaccines targeting poverty-related diseases. Besides functional efficacy, the stability, yield, and purification process determine the production costs of a vaccine and thereby the feasibility of plant-based production. We describe high-level plant production and functional characterization of a malaria vaccine candidate targeting the pre-erythrocytic stage of Plasmodium falciparum. CCT, a fusion protein composed of three sporozoite antigens (P. falciparum cell traversal protein for ookinetes and sporozoites [PfCelTOS], P. falciparum circumsporozoite protein [PfCSP], and P. falciparum thrombospondin-related adhesive protein [PfTRAP]), was transiently expressed by agroinfiltration in Nicotiana benthamiana leaves, accumulated to levels up to 2 mg/g fresh leaf weight (FLW), was thermostable up to 80°C and could be purified to >95% using a simple two-step procedure. Reactivity of sera from malaria semi-immune donors indicated the immunogenic conformation of the purified fusion protein consisting of PfCelTOS, PfCSP_TSR, PfTRAP_TSR domains (CCT) protein. Total IgG from the CCT-specific mouse immune sera specifically recognized P. falciparum sporozoites in immunofluorescence assays and induced up to 35% inhibition in hepatocyte invasion assays. Featuring domains from three promising sporozoite antigens with different roles (attachment and cell traversal) in the hepatocyte invasion process, CCT has the potential to elicit broader immune responses against the pre-erythrocytic stage of P. falciparum and represents an interesting new candidate, also as a component of multi-stage, multi-subunit malaria vaccine cocktails.

  3. Evaluation of a rapid whole blood immunochromatographic assay for the diagnosis of Plasmodium falciparum and Plasmodium vivax malaria.

    Science.gov (United States)

    Fernando, S D; Karunaweera, N D; Fernando, W P

    2004-03-01

    Microscopic examination of blood smears is the 'gold standard' for malaria diagnosis, but is labour intensive and requires skilled operators. Plasmodium vivax malaria accounts for up to 70% of infections in Sri Lanka. The objective of this study was to determine the effectiveness of an immunochromatographic test which can detect both the species of Plasmodium, P. vivax and P. falciparum, present in Sri Lanka. Prospective study from May 2001 to March 2002. All persons above 5 years of age who presented to the Malaria Research Station, Kataragama or the Anti-malaria Clinic, Kurunegala, with a history of fever were recruited to the study. Thick and thin blood smears were examined for malarial parasites. The rapid diagnostic test (RDT), ICT Malaria P.f/P.v (AMRAD ICT, Australia) was performed simultaneously by an independent investigator. The severity of clinical disease of all patients was evaluated. The study sample comprised 328 individuals of whom 126 (38%) were infected, 102 with P. vivax (31.1%) and 24 with P. falciparum (7.3%). The RDT was found to be highly sensitive (100%) and specific (100%) for the diagnosis of P. falciparum when compared with field microscopy. The sensitivity for the diagnosis of P. vivax malaria was only 70%. When P. vivax parasitaemia was greater than 5000 parasites/microL the RDT was 96.2% sensitive. A significant association was noted between the band intensity on the dipstick and both peripheral blood parasitaemia (p ICT Malaria P.f/P.v test can be used in Sri Lanka in the absence of microscopists.

  4. B-cell responses to pregnancy-restricted and -unrestricted Plasmodium falciparum erythrocyte membrane protein 1 antigens in Ghanaian women naturally exposed to malaria parasites

    DEFF Research Database (Denmark)

    Ampomah, Paulina; Stevenson, Liz; Ofori, Michael F

    2014-01-01

    Protective immunity to Plasmodium falciparum malaria acquired after natural exposure is largely antibody mediated. IgG-specific P. falciparum EMP1 (PfEMP1) proteins on the infected erythrocyte surface are particularly important. The transient antibody responses and the slowly acquired protective...

  5. Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Afridi Sarwat

    2012-09-01

    Full Text Available Abstract Background HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. Methods In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. Results After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i haemoglobin C with IgG levels; ii the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii TNF-863 with IgG3 levels; iv TNF-857 with IgG levels; and, v TNF1304 with IgG3, IgG4, and IgG levels. Conclusion Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.

  6. Efficacy of artesunate-amodiaquine for the treatment of acute uncomplicated falciparum malaria in southern Mauritania.

    Science.gov (United States)

    Ouldabdallahi, Mohamed; Alew, Ismail; Salem, Mohamed Salem Ould Ahmedou; Dit Dialaw Ba, Mamadou; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Aziz, Mohamed Boubacar Abdel; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sid Mohamed

    2014-12-16

    A regular evaluation of therapeutic efficacy in sentinel sites and a system of surveillance are required to establish treatment guidelines and adapt national anti-malarial drug policy to the rapidly changing epidemiology of drug-resistant malaria. The current anti-malarial treatment guideline in Mauritania, officially recommended since 2006, is based on artemisinin-based combination therapy. The aim of the present study was to evaluate clinical efficacy and tolerance of artesunate-amodiaquine, the first-line treatment for acute uncomplicated malaria, in Mauritanian paediatric and adult patients to validate its continued use in the country. Plasmodium falciparum-infected symptomatic patients aged > six months were enrolled in Kobeni and Timbedra in southern Mauritania in September to October 2013. Co-formulated artesunate-amodiaquine was administered at the recommended dose over three days. Patients were followed until day 28. Parasitological and clinical response was classified according to the standard 2009 World Health Organization protocol. A total of 130 patients (65 in Kobeni and 65 in Timbedra) were enrolled in the study. Seventeen patients (13.1%) were either excluded (before PCR correction) or lost to follow-up. Based on the per protocol analysis, artesunate-amodiaquine efficacy (i.e., the proportion of adequate clinical and parasitological response) was 96.6% in Kobeni and 98.2% in Timbedra before PCR correction. Late clinical failure was observed in two patients in Kobeni and one patient in Timbedra. After PCR correction, the efficacy rate in the two study sites was 98.2%. On day 3, all patients were afebrile and had negative smears. Treatment was well tolerated. Artesunate-amodiaquine is well tolerated and highly efficacious for the treatment of uncomplicated P. falciparum malaria. In the majority of patients, fever and parasitaemia were rapidly cleared before day 3. The results support the national anti-malarial drug guideline for a continued use of

  7. PfEMP1 - A Parasite Protein Family of Key Importance in Plasmodium falciparum Malaria Immunity and Pathogenesis.

    Science.gov (United States)

    Hviid, Lars; Jensen, Anja T R

    2015-04-01

    Plasmodium falciparum causes the most severe form of malaria and is responsible for essentially all malaria-related deaths. The accumulation in various tissues of erythrocytes infected by mature P. falciparum parasites can lead to circulatory disturbances and inflammation, and is thought to be a central element in the pathogenesis of the disease. It is mediated by the interaction of parasite ligands on the erythrocyte surface and a range of host receptor molecules in many organs and tissues. Among several proteins and protein families implicated in this process, the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family of high-molecular weight and highly variable antigens appears to be the most prominent. In this chapter, we aim to provide a systematic overview of the current knowledge about these proteins, their structure, their function, how they are presented on the erythrocyte surface, and how the var genes encoding them are regulated. The role of PfEMP1 in the pathogenesis of malaria, PfEMP1-specific immune responses, and the prospect of PfEMP1-specific vaccination against malaria are also covered briefly. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Métodos proteómicos aplicados al estudio de la malaria: plasmodium falciparum

    OpenAIRE

    2012-01-01

    La malaria es una de las enfermedades parasitarias que causa  mayor  impacto en la salud pública en países en desarrollo. La secuenciación del genoma de Plasmodium falciparum y el desarrollo de la proteómica han permitido un gran avance en el conocimiento de la biología del parasito. La proteómica ha permitido caracterizar cualitativa y cuantitativamente la expresión de proteínas del parásito y ha proveído información de la expresión relativa de proteínas bajo condiciones de stress como presi...

  9. Landscape and Dynamics of Transcription Initiation in the Malaria Parasite Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Sophie H. Adjalley

    2016-03-01

    Full Text Available A comprehensive map of transcription start sites (TSSs across the highly AT-rich genome of P. falciparum would aid progress toward deciphering the molecular mechanisms that underlie the timely regulation of gene expression in this malaria parasite. Using high-throughput sequencing technologies, we generated a comprehensive atlas of transcription initiation events at single-nucleotide resolution during the parasite intra-erythrocytic developmental cycle. This detailed analysis of TSS usage enabled us to define architectural features of plasmodial promoters. We demonstrate that TSS selection and strength are constrained by local nucleotide composition. Furthermore, we provide evidence for coordinate and stage-specific TSS usage from distinct sites within the same transcription unit, thereby producing transcript isoforms, a subset of which are developmentally regulated. This work offers a framework for further investigations into the interactions between genomic sequences and regulatory factors governing the complex transcriptional program of this major human pathogen.

  10. Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

    DEFF Research Database (Denmark)

    Murungi, Linda M; Sondén, Klara; Llewellyn, David

    2016-01-01

    Severe malaria (SM) is a life-threatening complication of infection withPlasmodium falciparum Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging...... and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within...... a longitudinal birth cohort of children (n= 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1...

  11. Quinine levels in patients with uncomplicated falciparum malaria in the Amazon region of Brazil

    Directory of Open Access Journals (Sweden)

    José Luiz Fernandes Vieira

    2008-10-01

    Full Text Available We examined the plasmatic concentrations of quinine in patients with uncomplicated falciparum malaria in an endemic area of the Amazon region in Brazil in a prospective clinical trial, in which a standard three-day course of oral quinine plus doxycycline was used. We measured the quinine in the plasma samples on days 0 and 3by high performance liquid chromatography. The mean concentration of quinine was 6.04 ±2.21 µg/mL in male patients and 5.98 ±1.95 µg/mL in female patients. No significant differences in quinine concentration were observed between these two groups. All samples collected before starting treatment were negative for quinine. This information could help in the development of strategies for the rational use of antimalarial drugs in Brazil.

  12. FMÉTODOS PROTEÓMICOS APLICADOS AL ESTUDIO DE LA MALARIA: Plasmodium falciparum

    OpenAIRE

    YESID CUESTA ASTROZ; CESAR SEGURA LATORRE

    2012-01-01

    La malaria es una de las enfermedades parasitarias que causa mayor impacto en la salud pública en países en desarrollo. La secuenciación del genoma de Plasmodium falciparum y el desarrollo de la proteómica han permitido un gran avance en el conocimiento de la biología del parásito. La proteómica ha permitido caracterizar cualitativa y cuantitativamente la expresión de proteínas del parásito y ha proveído información de la expresión relativa de proteínas bajo condiciones de estrés como presión...

  13. 5-Aminopyrazole-4-carboxamide analogues are selective inhibitors of Plasmodium falciparum microgametocyte exflagellation and potential malaria transmission blocking agents.

    Science.gov (United States)

    Huang, Wenlin; Hulverson, Matthew A; Zhang, Zhongsheng; Choi, Ryan; Hart, Kevin J; Kennedy, Mark; Vidadala, Rama Subba Rao; Maly, Dustin J; Van Voorhis, Wesley C; Lindner, Scott E; Fan, Erkang; Ojo, Kayode K

    2016-11-15

    Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) is essential for the exflagellation of male gametocytes. Inhibition of PfCDPK4 is an effective way of blocking the transmission of malaria by mosquitoes. A series of 5-aminopyrazole-4-carboxamide analogues are demonstrated to be potent inhibitors of PfCDPK4. The compounds are also able to block exflagellation of Plasmodium falciparum male gametocytes without observable toxicity to mammalian cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Diversidad genética de Plasmodium falciparum y sus implicaciones en la epidemiología de la malaria.

    OpenAIRE

    Judy Natalia Jiménez; Carlos Enrique Muskus; Iván Darío Vélez

    2005-01-01

    La diversidad genética le confiere a Plasmodium falciparum la capacidad de evadir la respuesta inmune del hospedero y producir variantes resistentes a medicamentos y a vacunas, aspectos que juegan un papel importante en el establecimiento de medidas de control contra la malaria. Diferentes autores han documentado la existencia de diversas cepas o clones de P. falciparum, cuya diversidad genética se ha confirmado a través de distintos ensayos de PCR (reacción en cadena de la polimerasa). Numer...

  15. High-throughput tri-colour flow cytometry technique to assess Plasmodium falciparum parasitaemia in bioassays

    DEFF Research Database (Denmark)

    Tiendrebeogo, Regis W; Adu, Bright; Singh, Susheel K

    2014-01-01

    BACKGROUND: Unbiased flow cytometry-based methods have become the technique of choice in many laboratories for high-throughput, accurate assessments of malaria parasites in bioassays. A method to quantify live parasites based on mitotracker red CMXRos was recently described but consistent...... distinction of early ring stages of Plasmodium falciparum from uninfected red blood cells (uRBC) remains a challenge. METHODS: Here, a high-throughput, three-parameter (tri-colour) flow cytometry technique based on mitotracker red dye, the nucleic acid dye coriphosphine O (CPO) and the leucocyte marker CD45...

  16. In vivo efficacy of artemether–lumefantrine against uncomplicated Plasmodium falciparum malaria in Dembia District, northwest Ethiopia

    Science.gov (United States)

    Deressa, Tekalign; Seid, Mengistu Endris; Birhan, Wubet; Aleka, Yetemwork; Tebeje, Biniam Mathewos

    2017-01-01

    Background Artemether–lumefantrine (AL) has been used as a first-line treatment for uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. Antimalarial drug resistance is one of the major obstacles for malaria control and curtails the lifespan of several drugs. Thus, continued monitoring of the efficacy of AL is of great public health importance in malaria endemic areas. Objective This study aimed to investigate the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum malaria in the Dembia district, northwest Ethiopia. Methods A prospective study was conducted from April 2015 to February 2016 at Kola Diba Health Center (KHC) in the Dembia district to determine the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum monoinfection. Patients were treated with the six-dose regimen of AL over 3 days and followed up for 28 days as per the World Health Organization protocol. Results Of the total 80 patients enrolled in the AL efficacy study, 75 patients completed the 28 days follow-up. None of the participants reported major adverse events. No early treatment failure or late clinical failure were observed during the study, but there were 6 (8.0%) late parasitological failures. The uncorrected per protocol cure rate of AL was 92.0 (95% CI: 85.7–98.3). Treatment with AL cleared parasitemia and fever in >95% of the patients by day 3. Conclusion This study showed that AL is well tolerated and remains efficacious for treatment of uncomplicated P. falciparum malaria in northwest Ethiopia. However, the observed late parasitological failures in this study are of a concern and warrant continued monitoring of drug efficacy as per the World Health Organization recommendations. PMID:28243110

  17. The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target of functional and protective human antibodies against malaria.

    Directory of Open Access Journals (Sweden)

    Linda Reiling

    Full Text Available BACKGROUND: Acquired antibodies are important in human immunity to malaria, but key targets remain largely unknown. Plasmodium falciparum reticulocyte-binding-homologue-4 (PfRh4 is important for invasion of human erythrocytes and may therefore be a target of protective immunity. METHODS: IgG and IgG subclass-specific responses against different regions of PfRh4 were determined in a longitudinal cohort of 206 children in Papua New Guinea (PNG. Human PfRh4 antibodies were tested for functional invasion-inhibitory activity, and expression of PfRh4 by P. falciparum isolates and sequence polymorphisms were determined. RESULTS: Antibodies to PfRh4 were acquired by children exposed to P. falciparum malaria, were predominantly comprised of IgG1 and IgG3 subclasses, and were associated with increasing age and active parasitemia. High levels of antibodies, particularly IgG3, were strongly predictive of protection against clinical malaria and high-density parasitemia. Human affinity-purified antibodies to the binding region of PfRh4 effectively inhibited erythrocyte invasion by P. falciparum merozoites and antibody levels in protected children were at functionally-active concentrations. Although expression of PfRh4 can vary, PfRh4 protein was expressed by most isolates derived from the cohort and showed limited sequence polymorphism. CONCLUSIONS: Evidence suggests that PfRh4 is a target of antibodies that contribute to protective immunity to malaria by inhibiting erythrocyte invasion and preventing high density parasitemia. These findings advance our understanding of the targets and mechanisms of human immunity and evaluating the potential of PfRh4 as a component of candidate malaria vaccines.

  18. FMÉTODOS PROTEÓMICOS APLICADOS AL ESTUDIO DE LA MALARIA: Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    YESID CUESTA ASTROZ

    2012-01-01

    Full Text Available La malaria es una de las enfermedades parasitarias que causa mayor impacto en la salud pública en países en desarrollo. La secuenciación del genoma de Plasmodium falciparum y el desarrollo de la proteómica han permitido un gran avance en el conocimiento de la biología del parásito. La proteómica ha permitido caracterizar cualitativa y cuantitativamente la expresión de proteínas del parásito y ha proveído información de la expresión relativa de proteínas bajo condiciones de estrés como presión por antimaláricos. Dada la complejidad de su ciclo de vida, el cual se lleva a cabo en el hospedero vertebrado y el mosquito, se ha caracterizado la expresión de proteínas para cada estadio del parásito con el fin de determinar el proteoma que media diversos procesos metabólicos, fisiológicos y energéticos. Técnicas de electroforesis bidimensional, cromatografía líquida y espectrometría de masas, han sido útiles para evaluar los efectos de antimaláricos sobre la expresión de proteínas del parásito y caracterizar el proteoma de diferentes formas y organelas de P. falciparum. El propósito de esta revisión es presentar el estado del arte de los avances en proteómica aplicada al estudio de la malaria, y plantear las diferentes estrategias experimentales empleadas para el estudio del proteoma del parásito con el fin de describir las ventajas y desventajas de cada una de estas metodologías.

  19. Systematic analysis of FKBP inducible degradation domain tagging strategies for the human malaria parasite Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Mauro Ferreira de Azevedo

    Full Text Available Targeted regulation of protein levels is an important tool to gain insights into the role of proteins essential to cell function and development. In recent years, a method based on mutated forms of the human FKBP12 has been established and used to great effect in various cell types to explore protein function. The mutated FKBP protein, referred to as destabilization domain (DD tag when fused with a native protein at the N- or C-terminus targets the protein for proteosomal degradation. Regulated expression is achieved via addition of a compound, Shld-1, that stabilizes the protein and prevents degradation. A limited number of studies have used this system to provide powerful insight into protein function in the human malaria parasite Plasmodium falciparum. In order to better understand the DD inducible system in P. falciparum, we studied the effect of Shld-1 on parasite growth, demonstrating that although development is not impaired, it is delayed, requiring the appropriate controls for phenotype interpretation. We explored the quantified regulation of reporter Green Fluorescent Protein (GFP and luciferase constructs fused to three DD variants in parasite cells either via transient or stable transfection. The regulation obtained with the original FKBP derived DD domain was compared to two triple mutants DD24 and DD29, which had been described to provide better regulation for C-terminal tagging in other cell types. When cloned to the C-terminal of reporter proteins, DD24 provided the strongest regulation allowing reporter activity to be reduced to lower levels than DD and to restore the activity of stabilised proteins to higher levels than DD29. Importantly, DD24 has not previously been applied to regulate proteins in P. falciparum. The possibility of regulating an exported protein was addressed by targeting the Ring-Infected Erythrocyte Surface Antigen (RESA at its C-terminus. The tagged protein demonstrated an important modulation of its

  20. Biochemical and genetic analysis of the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Reynolds, Jennifer M; Takebe, Sachiko; Choi, Jae-Yeon; El Bissati, Kamal; Witola, William H; Bobenchik, April M; Hoch, Jeffrey C; Voelker, Dennis R; Mamoun, Choukri Ben

    2008-03-21

    The PfPMT enzyme of Plasmodium falciparum, the agent of severe human malaria, is a member of a large family of known and predicted phosphoethanolamine methyltransferases (PMTs) recently identified in plants, worms, and protozoa. Functional studies in P. falciparum revealed that PfPMT plays a critical role in the synthesis of phosphatidylcholine via a plant-like pathway involving serine decarboxylation and phosphoethanolamine methylation. Despite their important biological functions, PMT structures have not yet been solved, and nothing is known about which amino acids in these enzymes are critical for catalysis and binding to S-adenosyl-methionine and phosphoethanolamine substrates. Here we have performed a mutational analysis of PfPMT focused on 24 residues within and outside the predicted catalytic motif. The ability of PfPMT to complement the choline auxotrophy of a yeast mutant defective in phospholipid methylation enabled us to characterize the activity of the PfPMT mutants. Mutations in residues Asp-61, Gly-83 and Asp-128 dramatically altered PfPMT activity and its complementation of the yeast mutant. Our analyses identify the importance of these residues in PfPMT activity and set the stage for advanced structural understanding of this class of enzymes.

  1. 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...... and effective for the treatment of P. falciparum malaria and is recommended for treatment of worldwide acquired P. falciparum malaria, although patients should be monitored closely to disclose resistance....

  2. Helminth Infection and Eosinophilia and the Risk of Plasmodium falciparum Malaria in 1- to 6-Year-Old Children in a Malaria Endemic Area

    Science.gov (United States)

    Bejon, Philip; Mwangi, Tabitha W.; Lowe, Brett; Peshu, Norbert; Hill, Adrian V. S.; Marsh, Kevin

    2008-01-01

    Background Helminth infection is common in malaria endemic areas, and an interaction between the two would be of considerable public health importance. Animal models suggest that helminth infections may increase susceptibility to malaria, but epidemiological data has been limited and contradictory. Methodology/Principal Findings In a vaccine trial, we studied 387 one- to six-year-old children for the effect of helminth infections on febrile Plasmodium falciparum malaria episodes. Gastrointestinal helminth infection and eosinophilia were prevalent (25% and 50% respectively), but did not influence susceptibility to malaria. Hazard ratios were 1 for gastrointestinal helminth infection (95% CI 0.6–1.6) and 0.85 and 0.85 for mild and marked eosinophilia, respectively (95% CI 0.56–1.76 and 0.69–1.96). Incident rate ratios for multiple episodes were 0.83 for gastro-intestinal helminth infection (95% CI 0.5–1.33) and 0.86 and 0.98 for mild and marked eosinophilia (95% CI 0.5–1.4 and 0.6–1.5). Conclusions/Significance There was no evidence that infection with gastrointestinal helminths or urinary schistosomiasis increased susceptibility to Plasmodium falciparum malaria in this study. Larger studies including populations with a greater prevalence of helminth infection should be undertaken. PMID:18265875

  3. Plasma Plasmodium falciparum histidine-rich protein-2 concentrations are associated with malaria severity and mortality in Tanzanian children.

    Directory of Open Access Journals (Sweden)

    Matthew P Rubach

    Full Text Available Plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP-2 concentrations, a measure of parasite biomass, have been correlated with malaria severity in adults, but not yet in children. We measured plasma PfHRP-2 in Tanzanian children with uncomplicated (n = 61 and cerebral malaria (n = 45; 7 deaths. Median plasma PfHRP-2 concentrations were higher in cerebral malaria (1008 [IQR 342-2572] ng/mL than in uncomplicated malaria (465 [IQR 36-1426] ng/mL; p = 0.017. In cerebral malaria, natural log plasma PfHRP-2 was associated with coma depth (r = -0.42; p = 0.006 and mortality (OR: 3.0 [95% CI 1.03-8.76]; p = 0.04. In this relatively small cohort study in a mesoendemic transmission area of Africa, plasma PfHRP-2 was associated with pediatric malaria severity and mortality. Further studies among children in areas of Africa with higher malaria transmission and among children with different clinical manifestations of severe malaria will help determine the wider utility of quantitative PfHRP-2 as a measure of parasite biomass and prognosis in sub-Saharan Africa.

  4. Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety

    Directory of Open Access Journals (Sweden)

    Hatz Christoph

    2010-10-01

    Full Text Available Abstract Background Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. Methods A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d and mefloquine (125 mg/d. Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. Results From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. Conclusion African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed.

  5. Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial

    Directory of Open Access Journals (Sweden)

    Fernando De la Hoz Restrepo

    2012-12-01

    Full Text Available INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5% clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%. There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group, typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group was significantly shorter (p=0.002. Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68 and 1% and 13.3% after treatment (p<0.001. CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

  6. Does the Use of Dihydroartemisinin-Piperaquine in Treating Patients with Uncomplicated falciparum Malaria Reduce the Risk for Recurrent New falciparum Infection More Than Artemether-Lumefantrine?

    Directory of Open Access Journals (Sweden)

    Wisdom Akpaloo

    2014-01-01

    Full Text Available Malaria contributes significantly to the global disease burden. The World Health Organization recommended the use of artemisinin-based combination therapies (ACTs for treatment of uncomplicated falciparum malaria a decade ago in response to problems of drug resistance. This review compared two of the ACTs—Dihydroartemisinin-Piperaquine (DP and Artemether-Lumefantrine (AL to provide evidence which one has the ability to offer superior posttreatment prophylaxis at 28 and 42 days posttreatment. Four databases (MEDLINE, EMBASE, Cochrane Database and Global Health were searched on June 2, 2013 and a total of seven randomized controlled trials conducted in sub-Sahara Africa were included. Results involving 2, 340 participants indicates that reduction in risk for recurrent new falciparum infections (RNIs was 79% at day 28 in favour of DP [RR, 0.21; 95% CI: 0.14 to 0.32, P<0.001], and at day 42 was 44% favouring DP [RR, 0.56; 95% CI: 0.34 to 0.90; P=0.02]. No significant difference was seen in treatment failure rates between the two drugs at days 28 and 42. It is concluded that use of DP offers superior posttreatment prophylaxis compared to AL in the study areas. Hence DP can help reduce malaria cases in such areas more than AL.

  7. Genetic variability and population structure of Plasmodium falciparum parasite populations from different malaria ecological regions of Kenya.

    Science.gov (United States)

    Ingasia, Luicer A; Cheruiyot, Jelagat; Okoth, Sheila Akinyi; Andagalu, Ben; Kamau, Edwin

    2016-04-01

    Transmission intensity, movement of human and vector hosts, biogeographical features, and malaria control measures are some of the important factors that determine Plasmodium falciparum parasite genetic variability and population structure. Kenya has different malaria ecologies which might require different disease intervention methods. Refined parasite population genetic studies are critical for informing malaria control and elimination strategies. This study describes the genetic diversity and population structure of P. falciparum parasites from the different malaria ecological zones in Kenya. Twelve multi-locus microsatellite (MS) loci previously described were genotyped in 225 P. falciparum isolates collected between 2012 and 2013 from five sites; three in lowland endemic regions (Kisumu, Kombewa, and Malindi) and two in highland, epidemic regions (Kisii and Kericho). Parasites from the lowland endemic and highland epidemic regions of western Kenya had high genetic diversity compared to coastal lowland endemic region of Kenya [Malindi]. The Kenyan parasites had a mean genetic differentiation index (FST) of 0.072 (p=0.011). The multi-locus genetic analysis of the 12 MS revealed all the parasites had unique haplotypes. Significant linkage disequilibrium (LD) was observed in all the five parasite populations. Kisumu had the most significant index of association values (0.16; pmalaria has been on the decline. The presence of significant LD suggests that there is occurrence of inbreeding in the parasite population. Parasite populations from Kisii showed the strongest evidence for epidemic population structure whereas the rest of the regions showed panmixia. Defining the genetic diversity of the parasites in different ecological regions of Kenya after introduction of the artemether-lumefantrine is important in refining the spread of drug resistant strains and malaria transmission for more effective control and eventual elimination of malaria in Kenya. Copyright

  8. South American Plasmodium falciparum after the malaria eradication era: clonal population expansion and survival of the fittest hybrids.

    Directory of Open Access Journals (Sweden)

    Sean M Griffing

    Full Text Available Malaria has reemerged in many regions where once it was nearly eliminated. Yet the source of these parasites, the process of repopulation, their population structure, and dynamics are ill defined. Peru was one of malaria eradication's successes, where Plasmodium falciparum was nearly eliminated for two decades. It reemerged in the 1990s. In the new era of malaria elimination, Peruvian P. falciparum is a model of malaria reinvasion. We investigated its population structure and drug resistance profiles. We hypothesized that only populations adapted to local ecological niches could expand and repopulate and originated as vestigial populations or recent introductions. We investigated the genetic structure (using microsatellites and drug resistant genotypes of 220 parasites collected from patients immediately after peak epidemic expansion (1999-2000 from seven sites across the country. The majority of parasites could be grouped into five clonal lineages by networks and AMOVA. The distribution of clonal lineages and their drug sensitivity profiles suggested geographic structure. In 2001, artesunate combination therapy was introduced in Peru. We tested 62 parasites collected in 2006-2007 for changes in genetic structure. Clonal lineages had recombined under selection for the fittest parasites. Our findings illustrate that local adaptations in the post-eradication era have contributed to clonal lineage expansion. Within the shifting confluence of drug policy and malaria incidence, populations continue to evolve through genetic outcrossing influenced by antimalarial selection pressure. Understanding the population substructure of P. falciparum has implications for vaccine, drug, and epidemiologic studies, including monitoring malaria during and after the elimination phase.

  9. A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria.

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    Chanaki Amaratunga

    Full Text Available BACKGROUND: In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs. A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified. METHODS AND FINDINGS: We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs, monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1 on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs. CONCLUSIONS: Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.

  10. Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles.

    Science.gov (United States)

    Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti; Bansal, Geetha P; Angov, Evelina; Kumar, Nirbhay

    2015-09-22

    Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV. Pfs25 has a complex tertiary structure characterized by four EGF-like repeat motifs formed by 11 disulfide bonds, and it has been rather difficult to obtain Pfs25 as a homogenous product in native conformation in any heterologous expression system. Recently, we have reported expression of codon-harmonized recombinant Pfs25 in Escherichia coli (CHrPfs25) and which elicited highly potent malaria transmission-blocking antibodies in mice. In the current study, we investigated CHrPfs25 along with gold nanoparticles of different shapes, size and physicochemical properties as adjuvants for induction of transmission blocking immunity. The results revealed that CHrPfs25 delivered with various gold nanoparticles elicited strong transmission blocking antibodies and suggested that gold nanoparticles based formulations can be developed as nanovaccines to enhance the immunogenicity of vaccine antigens.

  11. H2O2 dynamics in the malaria parasite Plasmodium falciparum

    Science.gov (United States)

    Rahbari, Mahsa; Bogeski, Ivan

    2017-01-01

    Hydrogen peroxide is an important antimicrobial agent but is also crucially involved in redox signaling and pathogen-host cell interactions. As a basis for systematically investigating intracellular H2O2 dynamics and regulation in living malaria parasites, we established the genetically encoded fluorescent H2O2 sensors roGFP2-Orp1 and HyPer-3 in Plasmodium falciparum. Both ratiometric redox probes as well as the pH control SypHer were expressed in the cytosol of blood-stage parasites. Both redox sensors showed reproducible sensitivity towards H2O2 in the lower micromolar range in vitro and in the parasites. Due to the pH sensitivity of HyPer-3, we used parasites expressing roGFP2-Orp1 for evaluation of short-, medium-, and long-term effects of antimalarial drugs on H2O2 levels and detoxification in Plasmodium. None of the quinolines or artemisinins tested had detectable direct effects on the H2O2 homeostasis at pharmacologically relevant concentrations. However, pre-treatment of the cells with antimalarial drugs or heat shock led to a higher tolerance towards exogenous H2O2. The systematic evaluation and comparison of the two genetically encoded cytosolic H2O2 probes in malaria parasites provides a basis for studying parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity. PMID:28369083

  12. Optimization of an in vitro system to study the exo-erythrocytic stage of the human malaria parasite, Plasmodium falciparum

    CSIR Research Space (South Africa)

    Rossouw, C

    2010-02-01

    Full Text Available scaffold and harvesting cells via the temperature change is currently being scaled up and a prototype bioreactor has been developed. Optimization of an in vitro system to study the exo-erythrocytic stage of the human Malaria Parasite, Plasmodium... hepatocyte line that supports in vitro development of the exo-erythrocytic stages of the malaria parasites Plasmodium falciparum and P. vivax. American Journal of Tropical Medicine and Hygeine 74:708-715. [4] Shor L, Güçeri S, Wen X, Gandhi M, Sun W. 2007...

  13. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

    OpenAIRE

    Kayentao Kassoum; Doumbo Ogobara K; Pénali Louis K; Offianan André T; Bhatt Kirana M; Kimani Joshua; Tshefu Antoinette K; Kokolomami Jack HT; Ramharter Michael; de Salazar Pablo Martinez; Tiono Alfred B; Ouédraogo Alphonse; Bustos Maria Dorina G; Quicho Frederick; Borghini-Fuhrer Isabelle

    2012-01-01

    Abstract Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to 90% (P 3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). Conclusions The pyron...

  14. Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions

    Science.gov (United States)

    Kokwaro, Gilbert O; Ogutu, Bernhards R; Muchohi, Simon N; Otieno, Godfrey O; Newton, Charles R J C

    2003-01-01

    Aims Phenobarbital is commonly used to treat status epilepticus in resource-poor countries. Although a dose of 20 mg kg−1 is recommended, this dose, administered intramuscularly (i.m.) for prophylaxis, is associated with an increase in mortality in children with cerebral malaria. We evaluated a 15-mg kg−1 intravenous (i.v.) dose of phenobarbital to determine its pharmacokinetics and clinical effects in children with severe falciparum malaria and status epilepticus. Methods Twelve children (M/F: 11/1), aged 7–62 months, received a loading dose of phenobarbital (15 mg kg−1) as an i.v. infusion over 20 min and maintenance dose of 5 mg kg−1 at 24 and 48 h later. The duration of convulsions and their recurrence were recorded. Vital signs were monitored. Plasma and cerebrospinal fluid (CSF) phenobarbital concentrations were measured with an Abbott TDx FLx® fluorescence polarisation immunoassay analyser (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, USA). Simulations were performed to predict the optimum dosage regimen that would maintain plasma phenobarbital concentrations between 15 and 20 mg l−1 for 72 h. Results All the children achieved plasma concentrations above 15 mg l−1 by the end of the infusion. Mean (95% confidence interval or median and range for Cmax) pharmacokinetic parameters were: area under curve [AUC (0, ∞) ]: 4259 (3169, 5448) mg l−1.h, t½: 82.9 (62, 103) h, CL: 5.8 (4.4, 7.3) ml kg−1 h−1, Vss: 0.8 (0.7, 0.9) l kg −1, CSF: plasma phenobarbital concentration ratio: 0.7 (0.5, 0.8; n = 6) and Cmax: 19.9 (17.9–27.9) mg l−1. Eight of the children had their convulsions controlled and none of them had recurrence of convulsions. Simulations suggested that a loading dose of 15 mg kg−1 followed by two maintenance doses of 2.5 mg kg−1 at 24 h and 48 h would maintain plasma phenobarbital concentrations between 16.4 and 20 mg l−1 for 72 h. Conclusions Phenobarbital, given as an i.v. loading dose, 15 mg kg−1

  15. Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan

    DEFF Research Database (Denmark)

    Iriemenam, Nnaemeka C; Khirelsied, Atif H; Nasr, Amre

    2009-01-01

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We...

  16. Antibodies to the N-terminal block 2 of Plasmodium falciparum merozoite surface protein 1 are associated with protection against clinical malaria

    DEFF Research Database (Denmark)

    Cavanagh, David R; Dodoo, Daniel; Hviid, Lars

    2004-01-01

    This longitudinal prospective study shows that antibodies to the N-terminal block 2 region of the Plasmodium falciparum merozoite surface protein 1 (MSP-1) are associated with protection against clinical malaria in an area of stable but seasonal malaria transmission of Ghana. Antibodies to the bl...

  17. The genetic risk of acute seizures in African children with falciparum malaria

    Science.gov (United States)

    Kariuki, Symon M; Rockett, Kirk; Clark, Taane G; Reyburn, Hugh; Agbenyega, Tsiri; Taylor, Terrie E; Birbeck, Gretchen L; Williams, Thomas N; Newton, Charles R J C

    2013-01-01

    Purpose It is unclear why some children with falciparum malaria develop acute seizures and what determines the phenotype of seizures. We sought to determine if polymorphisms of malaria candidate genes are associated with acute seizures. Methods Logistic regression was used to investigate genetic associations with malaria-associated seizures (MAS) and complex MAS (repetitive, prolonged, or focal seizures) in four MalariaGEN African sites, namely: Blantyre, Malawi; Kilifi, Kenya; Kumasi, Ghana; and Muheza, Tanzania. The analysis was repeated for five inheritance models (dominant, heterozygous, recessive, additive, and general) and adjusted for potential confounders and multiple testing. Key Findings Complex phenotypes of seizures constituted 71% of all admissions with MAS across the sites. MAS were strongly associated with cluster of differentiation-ligand-rs3092945 in females in Kilifi (p = 0.00068) and interleukin (IL)-17 receptor E-rs708567 in the pooled analysis across the sites (p = 0.00709). Complex MAS were strongly associated with epidermal growth factor module-containing mucin-like hormone receptor (EMR)1-rs373533 in Kumasi (p = 0.00033), but none in the pooled analysis. Focal MAS were strongly associated with IL-20 receptor A-rs1555498 in Muheza (p = 0.00016), but none in the pooled analysis. Prolonged MAS were strongly associated with complement receptor 1-rs17047660 in Kilifi (p = 0.00121) and glucose-6-phosphate dehydrogenase-rs1050828 in females in the pooled analysis (p = 0.00155). Repetitive MAS were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00003) and cystic fibrosis transmembrane conductance receptor-rs17140229 in the pooled analysis (p = 0.00543). MAS with coma/cerebral malaria were strongly associated with EMR1-rs373533 in Kumasi (p = 0.00019) and IL10-rs3024500 in the pooled analysis across the sites (p = 0.00064). Significance We have identified a number of genetic associations that may explain the risk of seizures in >2,000 cases

  18. In silico multiple-targets identification for heme detoxification in the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Phaiphinit, Suthat; Pattaradilokrat, Sittiporn; Lursinsap, Chidchanok; Plaimas, Kitiporn

    2016-01-01

    Detoxification of hemoglobin byproducts or free heme is an essential step and considered potential targets for anti-malaria drug development. However, most of anti-malaria drugs are no longer effective due to the emergence and spread of the drug resistant malaria parasites. Therefore, it is an urgent need to identify potential new targets and even for target combinations for effective malaria drug design. In this work, we reconstructed the metabolic networks of Plasmodium falciparum and human red blood cells for the simulation of steady mass and flux flows of the parasite's metabolites under the blood environment by flux balance analysis (FBA). The integrated model, namely iPF-RBC-713, was then adjusted into two stage-specific metabolic models, which first was for the pathological stage metabolic model of the parasite when invaded the red blood cell without any treatment and second was for the treatment stage of the parasite when a drug acted by inhibiting the hemozoin formation and caused high production rate of heme toxicity. The process of identifying target combinations consisted of two main steps. Firstly, the optimal fluxes of reactions in both the pathological and treatment stages were computed and compared to determine the change of fluxes. Corresponding enzymes of the reactions with zero fluxes in the treatment stage but non-zero fluxes in the pathological stage were predicted as a preliminary list of potential targets in inhibiting heme detoxification. Secondly, the combinations of all possible targets listed in the first step were examined to search for the best promising target combinations resulting in more effective inhibition of the detoxification to kill the malaria parasites. Finally, twenty-three enzymes were identified as a preliminary list of candidate targets which mostly were in pyruvate metabolism and citrate cycle. The optimal set of multiple targets for blocking the detoxification was a set of heme ligase, adenosine transporter, myo

  19. High heterogeneity in Plasmodium falciparum risk illustrates the need for detailed mapping to guide resource allocation: a new malaria risk map of the Lao People's Democratic Republic

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    Phompida Samlane

    2010-02-01

    Full Text Available Abstract Background Accurate information on the geographical distribution of malaria is important for efficient resource allocation. The Lao People's Democratic Republic has experienced a major decline in malaria morbidity and mortality in the past decade. However, efforts to respond effectively to these changes have been impeded by lack of detailed data on malaria distribution. In 2008, a countrywide survey on Plasmodium falciparum diagnosed in health centres and villages was initiated to develop a detailed P. falciparum risk map with the aim to identify priority areas for malaria control, estimate population at risk, and guide resource allocation in the Lao People's Democratic Republic. Methods P. falciparum incidence data were collected from point-referenced villages and health centres for the period 2006-2008 during a country-wide survey between December 2008 and January 2009. Using the highest recorded annual rate, continuous surfaces of P. falciparum incidence were produced by the inverse distance weighted interpolation technique. Results Incidence rates were obtained from 3,876 villages and 685 health centres. The risk map shows that P. falciparum is highly heterogeneous in the northern and central regions of the country with large areas of no transmission. In the southern part, transmission is pervasive and the risk of P. falciparum is high. It was estimated that 3.4 million people (60% of the population live at risk of malaria. Conclusions This paper presents the first comprehensive malaria risk map of the Lao People's Democratic Republic based entirely on empirical data. The estimated population at risk is substantially lower than previous estimates, reflecting the presence of vast areas with focal or no malaria transmission as identified in this study. These findings provide important guidance for malaria control interventions in the Lao People's Democratic Republic, and underline the need for detailed data on malaria to accurately

  20. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    LENUS (Irish Health Repository)

    Larkin, Deirdre

    2009-03-01

    Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF) and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20) and cerebral (n = 13) P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag) level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB) was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU\\/ml versus 1.9 IU\\/ml; p<0.005). This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005). Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1). These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  1. Severe Plasmodium falciparum malaria is associated with circulating ultra-large von Willebrand multimers and ADAMTS13 inhibition.

    Directory of Open Access Journals (Sweden)

    Deirdre Larkin

    2009-03-01

    Full Text Available Plasmodium falciparum infection results in adhesion of infected erythrocytes to blood vessel endothelium, and acute endothelial cell activation, together with sequestration of platelets and leucocytes. We have previously shown that patients with severe infection or fulminant cerebral malaria have significantly increased circulatory levels of the adhesive glycoprotein von Willebrand factor (VWF and its propeptide, both of which are indices of endothelial cell activation. In this prospective study of patients from Ghana with severe (n = 20 and cerebral (n = 13 P. falciparum malaria, we demonstrate that increased plasma VWF antigen (VWF:Ag level is associated with disproportionately increased VWF function. VWF collagen binding (VWF:CB was significantly increased in patients with cerebral malaria and severe malaria (medians 7.6 and 7.0 IU/ml versus 1.9 IU/ml; p<0.005. This increased VWF:CB correlated with the presence of abnormal ultra-large VWF multimers in patient rather than control plasmas. Concomitant with the increase in VWF:Ag and VWF:CB was a significant persistent reduction in the activity of the VWF-specific cleaving protease ADAMTS13 (approximately 55% of normal; p<0.005. Mixing studies were performed using P. falciparum patient plasma and normal pooled plasma, in the presence or absence of exogenous recombinant ADAMTS13. These studies demonstrated that in malarial plasma, ADAMTS13 function was persistently inhibited in a time-dependent manner. Furthermore, this inhibitory effect was not associated with the presence of known inhibitors of ADAMTS13 enzymatic function (interleukin-6, free haemoglobin, factor VIII or thrombospondin-1. These novel findings suggest that severe P. falciparum infection is associated with acute endothelial cell activation, abnormal circulating ULVWF multimers, and a significant reduction in plasma ADAMTS13 function which is mediated at least in part by an unidentified inhibitor.

  2. Malaria during pregnancy in a reference centre from the Brazilian Amazon: unexpected increase in the frequency of Plasmodium falciparum infections

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    Martínez-Espinosa Flor Ernestina

    2004-01-01

    Full Text Available Malaria remains globally the most important parasitic disease of man. Data on its deleterious effects during pregnancy have been extensively documented in hyperendemic, holoendemic, and mesoendemic areas from Africa and Asia where Plasmodium falciparum is responsible for almost all infections. However, knowledge about malaria during pregnancy in areas where transmission is unstable and P. vivax is the most prevalent species, such as the Brazilian Amazon, is scarce. Here, we report a preliminary cross sectional descriptive study, carried out at the Fundação de Medicina Tropical do Amazonas, a reference centre for diagnosis and treatment of tropical diseases in the west-Amazon (Manaus, Brazil. A total of 1699 febrile childbearing age women had positive thick blood smears to Plasmodium species, between January and November 1997: 1401 (82.5% were positive for P. vivax , 286 (16.8% for P. falciparum and 12 (0.07% carried mixed infections. From the malarious patients, 195 were pregnant. The ratio of P. falciparum to P. vivax infections in the group of non-pregnant infected women was 1:5.6 while it was 1:2.3 in that of pregnant infected ones. Similar rates or even proportionally more vivax infections during pregnancy were expected to occur, in function of the contraindication of primaquine with the resulting increased P. vivax relapse rates. Such an observation suggests that the mechanism of resistance/susceptibility to infection and/or malaria pathogenesis in pregnant women may differ according to Plasmodium species and that the extensively described increase in the frequencies of malaria infection during pregnancy may be specifically due to P. falciparum infection.

  3. Oral artesunate-amodiaquine and artemether-lumefantrine in the treatment of uncomplicated hyperparasitaemic Plasmodium falciparum malaria in children.

    Science.gov (United States)

    Gbotosho, Grace O; Sowunmi, Akintunde; Okuboyejo, Titilope M; Happi, Christian T

    2012-04-01

    The therapeutic efficacy, changes in haematocrit and declines in parasitaemias were evaluated in 56 children with uncomplicated falciparum hyperparasitaemia after oral artesunate-amodiaquine or artemether-lumefantrine. All children recovered clinically within 2 days and without progression to severe malaria. Falls in haematocrit in the first 3 days after treatment began were similar and <5%. Declines in parasitaemias were monoexponential with both treatments with an estimated half-life of 1 h.

  4. Plasmodium falciparum genotypes diversity in symptomatic malaria of children living in an urban and a rural setting in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Konaté Amadou T

    2009-06-01

    Full Text Available Abstract Background The clinical presentation of malaria, considered as the result of a complex interaction between parasite and human genetics, is described to be different between rural and urban areas. The analysis of the Plasmodium falciparum genetic diversity in children with uncomplicated malaria, living in these two different areas, may help to understand the effect of urbanization on the distribution of P. falciparum genotypes. Methods Isolates collected from 75 and 89 children with uncomplicated malaria infection living in a rural and an urban area of Burkina Faso, respectively, were analysed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum diversity. Results The K1 allelic family was widespread in children living in the two sites, compared to other msp1 allelic families (frequency >90%. The MAD 20 allelic family of msp1 was more prevalent (p = 0.0001 in the urban (85.3% than the rural area (63.2%. In the urban area, the 3D7 alleles of msp2 were more prevalent compared to FC27 alleles, with a high frequency for the 3D7 300bp allele (>30%. The multiplicity of infection was in the range of one to six in the urban area and of one to seven in the rural area. There was no difference in the frequency of multiple infections (p = 0.6: 96.0% (95% C.I: 91.6–100 in urban versus 93.1% (95%C.I: 87.6–98.6 in rural areas. The complexity of infection increased with age [p = 0.04 (rural area, p = 0.06 (urban area]. Conclusion Urban-rural area differences were observed in some allelic families (MAD20, FC27, 3D7, suggesting a probable impact of urbanization on genetic variability of P. falciparum. This should be taken into account in the implementation of malaria control measures.

  5. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania

    OpenAIRE

    Balthazary Sakurani T; Malisa Allen L; Mutayoba Benezeth M; Mbugi Erasto V; Nyambo Thomas B; Mshinda Hassan

    2006-01-01

    Abstract Background Sulphadoxine-pyrimethamine (SP) has been and is currently used for treatment of uncomplicated Plasmodium falciparum malaria in many African countries. Nevertheless, the response of parasites to SP treatment has shown significant variation between individuals. Methods The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 years. Parasite DNA was extracte...

  6. Plasmodium falciparum-like parasites infecting wild apes in southern Cameroon do not represent a recurrent source of human malaria.

    Science.gov (United States)

    Sundararaman, Sesh A; Liu, Weimin; Keele, Brandon F; Learn, Gerald H; Bittinger, Kyle; Mouacha, Fatima; Ahuka-Mundeke, Steve; Manske, Magnus; Sherrill-Mix, Scott; Li, Yingying; Malenke, Jordan A; Delaporte, Eric; Laurent, Christian; Mpoudi Ngole, Eitel; Kwiatkowski, Dominic P; Shaw, George M; Rayner, Julian C; Peeters, Martine; Sharp, Paul M; Bushman, Frederic D; Hahn, Beatrice H

    2013-04-23

    Wild-living chimpanzees and gorillas harbor a multitude of Plasmodium species, including six of the subgenus Laverania, one of which served as the progenitor of Plasmodium falciparum. Despite the magnitude of this reservoir, it is unknown whether apes represent a source of human infections. Here, we used Plasmodium species-specific PCR, single-genome amplification, and 454 sequencing to screen humans from remote areas of southern Cameroon for ape Laverania infections. Among 1,402 blood samples, we found 1,000 to be Plasmodium mitochondrial DNA (mtDNA) positive, all of which contained human parasites as determined by sequencing and/or restriction enzyme digestion. To exclude low-abundance infections, we subjected 514 of these samples to 454 sequencing, targeting a region of the mtDNA genome that distinguishes ape from human Laverania species. Using algorithms specifically developed to differentiate rare Plasmodium variants from 454-sequencing error, we identified single and mixed-species infections with P. falciparum, Plasmodium malariae, and/or Plasmodium ovale. However, none of the human samples contained ape Laverania parasites, including the gorilla precursor of P. falciparum. To characterize further the diversity of P. falciparum in Cameroon, we used single-genome amplification to amplify 3.4-kb mtDNA fragments from 229 infected humans. Phylogenetic analysis identified 62 new variants, all of which clustered with extant P. falciparum, providing further evidence that P. falciparum emerged following a single gorilla-to-human transmission. Thus, unlike Plasmodium knowlesi-infected macaques in southeast Asia, African apes harboring Laverania parasites do not seem to serve as a recurrent source of human malaria, a finding of import to ongoing control and eradication measures.

  7. Construction of a human functional single-chain variable fragment (scFv) antibody recognizing the malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Wajanarogana, Sumet; Prasomrothanakul, Teerawat; Udomsangpetch, Rachanee; Tungpradabkul, Sumalee

    2006-04-01

    Falciparum malaria is one of the most deadly and profound human health problems around the tropical world. Antimalarial drugs are now considered to be a powerful treatment; however, there are drugs currently being used that are resistant to Plasmodium falciparum parasites spreading in different parts of the world. Although the protective immune response against intraerythrocytic stages of the falciparum malaria parasite is still not fully understood, immune antibodies have been shown to be associated with reduced parasite prevalence. Therefore antibodies of the right specificity present in adequate concentrations and affinity are reasonably effective in providing protection. In the present study, VH (variable domain of heavy chain) and VL (variable domain of light chain) were isolated from human blood lymphocytes of P. falciparum in one person who had high serum titre to RESA (ring-infected erythrocyte surface antigen). Equal amounts of VH and VL were assembled together with universal linker (G4S)3 to generate scFvs (single-chain variable fragments). The scFv antibodies were expressed with a phage system for the selection process. Exclusively, an expressed scFv against asynchronous culture of P. falciparum-infected erythrocytes was selected and characterized. Sequence analysis of selected scFv revealed that this clone could be classified into a VH family-derived germline gene (VH1) and Vkappa family segment (Vkappa1). Using an indirect immunofluorescence assay, we could show that soluble expressed scFv reacted with falciparum-infected erythrocytes. The results encourage the further study of scFvs for development as a potential immunotherapeutic agent.

  8. Diversidad genética de Plasmodium falciparum y sus implicaciones en la epidemiología de la malaria.

    Directory of Open Access Journals (Sweden)

    Judy Natalia Jiménez

    2005-12-01

    Full Text Available La diversidad genética le confiere a Plasmodium falciparum la capacidad de evadir la respuesta inmune del hospedero y producir variantes resistentes a medicamentos y a vacunas, aspectos que juegan un papel importante en el establecimiento de medidas de control contra la malaria. Diferentes autores han documentado la existencia de diversas cepas o clones de P. falciparum, cuya diversidad genética se ha confirmado a través de distintos ensayos de PCR (reacción en cadena de la polimerasa. Numerosas investigaciones realizadas en poblaciones con diferente grado de transmisión de malaria han mostrado la relación existente entre la estructura de la población de P. falciparum y la epidemiología de la enfermedad. En este artículo se describen las fases del ciclo de vida en las que los eventos de recombinación originan la diversidad genética de P. falciparum, se revisan los estudios realizados sobre este aspecto en regiones con diferentes grados de endemicidad, así como sobre sus implicaciones en la adquisición de inmunidad y en el desarrollo de medidas de control.

  9. Haplotypes associated with resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum in two malaria endemic locations in Colombia.

    Science.gov (United States)

    Hernández, Diana Carolina; Guerra, Angela Patricia; Cucunubá, Zulma Milena; Nicholls, Ruben Santiago; Barrera, Sandra Milena

    2013-08-01

    Colombia has four main malaria transmission zones. In vivo efficacy studies carried out in these areas showed big differences in the response of Plasmodium falciparum to treatment with sulphadoxine-pyrimethamine. In addition, there is still insufficient information about the genetics of P. falciparum populations. The objective of this study was to determine the haplotypes in dhfr and dhps genes of P. falciparum circulating in two distinct endemic zones. Samples from patients with non-complicated P. falciparum malaria were collected: 135 from Tumaco and 206 from Tierralta. Alleles 108 and 51 of the dhfr gene, and 437 and 540 of the dhps gene were analyzed by PCR/enzymatic restriction, while alleles 59 and 164 (dhfr), and 581(dhps) by PCR/dot blot/hybridization. Five different haplotypes were found, of which the triple mutant 51I/C59/108N/I164/437G/K540/A581 was the most frequent (54.6%). In Tumaco, the parasites with wild haplotype predominated, while mutant parasites predominated in Tierralta. Another interesting finding is the presence of the C59R mutation in the dhfr gene in two samples, a mutation rarely found in South America. These data provide information about parasite population genetics and highlight the importance of starting a long term molecular surveillance program.

  10. Patterns and dynamics of genetic diversity in Plasmodium falciparum: what past human migrations tell us about malaria.

    Science.gov (United States)

    Mita, Toshihiro; Jombart, Thibaut

    2015-06-01

    Plasmodium falciparum is the main agent of malaria, one of the major human infectious diseases affecting millions of people worldwide. The genetic diversity of P. falciparum populations is an essential factor in the parasite's ability to adapt to changes in its environment, enabling the development of drug resistance and the evasion from the host immune system through antigenic variation. Therefore, characterizing these patterns and understanding the main drivers of the pathogen's genetic diversity can provide useful inputs for informing control strategies. In this paper, we review the pioneering work led by Professor Kazuyuki Tanabe on the genetic diversity of P. falciparum populations. In a first part, we recall basic results from population genetics for quantifying within-population genetic diversity, and discuss the main mechanisms driving this diversity. Then, we show how these approaches have been used for reconstructing the historical spread of malaria worldwide, and how current patterns of genetic diversity suggest that the pathogen followed our ancestors in their journey out of Africa. Because these results are robust to different types of genetic markers, they provide a baseline for predicting the pathogen's diversity in unsampled populations, and some useful elements for predicting vaccine efficacy and informing malaria control strategies.

  11. Genotyping of chloroquine resistant Plasmodium falciparum in wild caught Anopheles minimus mosquitoes in a malaria endemic area of Assam, India.

    Science.gov (United States)

    Sarma, D K; Mohapatra, P K; Bhattacharyya, D R; Mahanta, J; Prakash, A

    2014-09-01

    We validated the feasibility of using Plasmodium falciparum, the human malaria parasite, DNA present in wild caught vector mosquitoes for the characterization of chloroquine resistance status. House frequenting mosquitoes belonging to Anopheles minimus complex were collected from human dwellings in a malaria endemic area of Assam, Northeast India and DNA was extracted from the head-thorax region of individual mosquitoes. Anopheles minimus complex mosquitoes were identified to species level and screened for the presence of Plasmodium sp. using molecular tools. Nested PCR-RFLP method was used for genotyping of P. falciparum based on K76T mutation in the chloroquine resistance transporter (pfcrt) gene. Three of the 27 wild caught An. minimus mosquitoes were harbouring P. falciparum sporozoites (positivity 11.1%) and all 3 were had 76T mutation in the pfcrt gene, indicating chloroquine resistance. The approach of characterizing antimalarial resistance of malaria parasite in vector mosquitoes can potentially be used as a surveillance tool for monitoring transmission of antimalarial drug resistant parasite strains in the community.

  12. pfk13-Independent Treatment Failure in Four Imported Cases of Plasmodium falciparum Malaria Treated with Artemether-Lumefantrine in the United Kingdom.

    Science.gov (United States)

    Sutherland, Colin J; Lansdell, Paul; Sanders, Mandy; Muwanguzi, Julian; van Schalkwyk, Donelly A; Kaur, Harparkash; Nolder, Debbie; Tucker, Julie; Bennett, Hayley M; Otto, Thomas D; Berriman, Matthew; Patel, Trupti A; Lynn, Roderick; Gkrania-Klotsas, Effrossyni; Chiodini, Peter L

    2017-03-01

    We present case histories of four patients treated with artemether-lumefantrine for falciparum malaria in UK hospitals in 2015 to 2016. Each subsequently presented with recurrent symptoms and Plasmodium falciparum parasitemia within 6 weeks of treatment with no intervening travel to countries where malaria is endemic. Parasite isolates, all of African origin, harbored variants at some candidate resistance loci. No evidence of pfk13-mediated artemisinin resistance was found. Vigilance for signs of unsatisfactory antimalarial efficacy among imported cases of malaria is recommended. Copyright © 2017 Sutherland et al.

  13. Selective upregulation of a single distinctly structured var gene in chondroitin sulphate A-adhering Plasmodium falciparum involved in pregnancy-associated malaria

    DEFF Research Database (Denmark)

    Salanti, Ali; Staalsoe, Trine; Lavstsen, Thomas

    2003-01-01

    Cytoadhesion of infected red blood cells (iRBC) is mediated through parasite-encoded, clonally variant surface antigens (VSA) and is a central process in the pathogenesis of Plasmodium falciparum malaria. Pregnancy-associated malaria (PAM) has been linked to VSA-mediated adhesion of i...... implicated in PfEMP1-mediated adhesion to CD36 and CSA. We also show that var2csa was transcribed at higher levels in three placental parasite isolates compared with transcription in parasites from peripheral blood of two children with P. falciparum malaria. This var gene thus has the properties expected...

  14. Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey

    Science.gov (United States)

    Rosas-Aguirre, Angel; Speybroeck, Niko; Llanos-Cuentas, Alejandro; Rosanas-Urgell, Anna; Carrasco-Escobar, Gabriel; Rodriguez, Hugo; Gamboa, Dionicia; Contreras-Mancilla, Juan; Alava, Freddy; Soares, Irene S.; Remarque, Edmond; D´Alessandro, Umberto; Erhart, Annette

    2015-01-01

    Background With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon. Material and Methods After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR) and antibodies against P. vivax (PvMSP119, PvAMA1) and P. falciparum (PfGLURP, PfAMA1) antigens by ELISA. Risk factors for malaria infection (positive PCR) and malaria exposure (seropositivity) were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ). SaTScan was used to detect spatial clusters of serology-positive individuals within each site. Results The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site) were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure. Conclusion The use of a single parasitological and serological malaria survey has proven to be an efficient

  15. Hotspots of Malaria Transmission in the Peruvian Amazon: Rapid Assessment through a Parasitological and Serological Survey.

    Directory of Open Access Journals (Sweden)

    Angel Rosas-Aguirre

    Full Text Available With low and markedly seasonal malaria transmission, increasingly sensitive tools for better stratifying the risk of infection and targeting control interventions are needed. A cross-sectional survey to characterize the current malaria transmission patterns, identify hotspots, and detect recent changes using parasitological and serological measures was conducted in three sites of the Peruvian Amazon.After full census of the study population, 651 participants were interviewed, clinically examined and had a blood sample taken for the detection of malaria parasites (microscopy and PCR and antibodies against P. vivax (PvMSP119, PvAMA1 and P. falciparum (PfGLURP, PfAMA1 antigens by ELISA. Risk factors for malaria infection (positive PCR and malaria exposure (seropositivity were assessed by multivariate survey logistic regression models. Age-specific seroprevalence was analyzed using a reversible catalytic conversion model based on maximum likelihood for generating seroconversion rates (SCR, λ. SaTScan was used to detect spatial clusters of serology-positive individuals within each site.The overall parasite prevalence by PCR was low, i.e. 3.9% for P. vivax and 6.7% for P. falciparum, while the seroprevalence was substantially higher, 33.6% for P. vivax and 22.0% for P. falciparum, with major differences between study sites. Age and location (site were significantly associated with P. vivax exposure; while location, age and outdoor occupation were associated with P. falciparum exposure. P. falciparum seroprevalence curves showed a stable transmission throughout time, while for P. vivax transmission was better described by a model with two SCRs. The spatial analysis identified well-defined clusters of P. falciparum seropositive individuals in two sites, while it detected only a very small cluster of P. vivax exposure.The use of a single parasitological and serological malaria survey has proven to be an efficient and accurate method to characterize the

  16. Genetic polymorphism of merozoite surface protein-1 in Plasmodium falciparum isolates from patients with mild to severe malaria in Libreville, Gabon.

    Science.gov (United States)

    Bouyou-Akotet, Marielle Karine; M'Bondoukwé, Noé Patrick; Mawili-Mboumba, Denise Patricia

    2015-01-01

    We assessed Plasmodium (P.) falciparum allelic diversity based on clinical severity and age. The study was conducted from 2011 to 2012 in Libreville, Gabon where malaria prevalence was 24.5%. The polymorphism of the merozoite surface protein-1 (msp1) locus was analyzed in isolates from patients with complicated and uncomplicated malaria. Blood was collected on filter paper. After DNA extraction, genotyping of the msp1 gene was performed using nested PCR. The K1, Ro33, and Mad20 allelic families were detected in 71 (63%), 64 (57%), and 38 (34%) of the 112 analyzed samples, respectively. Overall, 17 K1 and 11 Mad20 alleles were detected. There was no association between msp1 allelic families and age. Mad20 allelic diversity increased with the severity of malaria. The number of K1 and Mad20 alleles decreased with age. The multiplicity of infection (MOI) was 1-6 genotypes and the complexity of infection (COI) 1.8 ± 1. The COI differed based on age: it was 1.9 (±1.1) in the isolates from adults, 1.8 (±1.1) in those from 0-5 year-old children, whereas it tended to be lower (1.6 ± 0.8) in those from 6-15 year-old children. Extensive genetic diversity is found in P. falciparum strains circulating in Libreville. The number of specific msp1 alleles increased with clinical severity, suggesting an association between the diversity and the severity of malaria.

  17. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    Science.gov (United States)

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  18. External quality assessment of malaria microscopy in the Democratic Republic of the Congo

    Directory of Open Access Journals (Sweden)

    Lokombe Jean

    2011-10-01

    Full Text Available Abstract Background External quality assessments (EQA are an alternative to cross-checking of blood slides in the quality control of malaria microscopy. This study reports the findings of an EQA of malaria microscopy in the Democratic Republic of the Congo (DRC. Methods After validation, an EQA slide panel and a questionnaire were delivered to diagnostic laboratories in four provinces of D