Jullien, Vincent; Valecha, Neena; Srivastava, Bina; Sharma, Bhawna; Kiechel, Jean-René
Fixed-dose combinations of artemisinin combination therapy are strongly recommended to facilitate drug administration and compliance. New fixed-dose combinations must nevertheless be evaluated in relevant populations in terms of efficacy and pharmacokinetics. A single-arm, open-label, clinical trial was performed in Indian patients with acute uncomplicated Plasmodium falciparum malaria to investigate the efficacy and the pharmacokinetics of mefloquine when combined with artesunate in a fixed-dose combination (400/200 mg of mefloquine base/artesunate). The pharmacokinetic analysis was performed using a population approach. Seventy-seven patients were included in the study. Mefloquine pharmacokinetics obeys a two-compartment model with first-order absorption and elimination. Mean parameter estimates (% inter-individual variability) were as follows: 0.16 h(-1) (75%) for the absorption rate constant, 1.13 L/h (30%) for the apparent plasma clearance, 271 L (21%) for the apparent central distribution volume, 344 L (54%) for the apparent peripheral distribution volume, and 1.43 L/h for the apparent distribution clearance. These values were consistent with the pharmacokinetic results described in Thai patients. No significant covariate was found for clearance. Body weight explained the inter-individual variability of the apparent central and peripheral distribution volumes. The PCR-adjusted efficacy of the treatment was 100%. The lack of significant covariate explaining the inter-individual variability of mefloquine clearance, combined with the excellent efficacy, supports the use of the standard 200/400 mg of artesunate-mefloquine fixed-dose combination in Indian patients with uncomplicated P. falciparum malaria. ISRCTN70618692.
Minodier, Philippe; Noël, Guilhem; Tall, Mamadou; Retornaz, Karine; Piarroux, Renaud; Parzy, Daniel; Ranque, Stephane
Children with uncomplicated Plasmodium falciparum imported malaria are treated with various antimalarial regimens including mefloquine depending on national guidelines. Little is known regarding mefloquine treatment efficacy in this setting. In this prospective study, children 3 months to 16 years of age admitted in a tertiary hospital emergency ward in France with uncomplicated P. falciparum malaria were treated with oral mefloquine. Each dose was given with an antiemetic. Between 2004 and 2009, 95 children were evaluated. In all, 94% had traveled in the Indian Ocean region (Comoros and Madagascar); 79% used a malaria chemoprophylaxis, but none was fully compliant with World Health Organization recommended regimens. Main clinical features at admission were fever (91%), vomiting (44%), and headaches (44%). Hemoglobin mefloquine, and no relapse was noted within 45 days after admission. One Plasmodium vivax relapse occurred 6 months later. Vomiting within 1 hour after dosing occurred in 20% of children. Significant features associated with early vomiting by univariate analysis were a weight ≤ 15 kg, C-reactive protein ≥ 50 mg/L, and parasitemia ≥ 1%, but only low weight was significant by multivariate analysis. Mefloquine is an effective treatment for uncomplicated imported P. falciparum malaria in children returning from countries with low mefloquine resistance. Early vomiting after mefloquine dosing is frequent, especially in children < 15 kg of weight, but a second dose can be given successfully.
BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine concentr......BACKGROUND: Achieving adequate antimalarial drug exposure is essential for curing malaria. Day 7 blood or plasma lumefantrine concentrations provide a simple measure of drug exposure that correlates well with artemether-lumefantrine efficacy. However, the 'therapeutic' day 7 lumefantrine......-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...... lumefantrine concentrations ≥200 ng/ml and high cure rates in most uncomplicated malaria patients. Three groups are at increased risk of treatment failure: very young children (particularly those underweight-for-age); patients with high parasitemias; and patients in very low transmission intensity areas...
Ünlü, Çagdas; Gunadi, Patrick M; Gerhards, Michael F; Boermeester, Marja A; Vrouenraets, Bart C
Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment of acute uncomplicated diverticulitis is feasible and safe, and which patients could benefit from outpatient care. A retrospective cohort study was carried out in two teaching hospitals using hospital registry codes for diverticulitis. All patients diagnosed with acute uncomplicated diverticulitis between January 2004 and January 2012, confirmed by imaging or colonoscopy, were included. Exclusion criteria were patients with recurrent diverticulitis, complicated diverticulitis (Hinchey stages 2, 3, and 4), and right-sided diverticulitis. Inpatient care was compared with outpatient care. Primary outcome was admission for outpatient care and the complication rate in both groups. Multivariate analysis was carried out to identify potential factors for inpatient care. Of 627 patients with diverticulitis, a total of 312 consecutive patients were identified with primary uncomplicated diverticulitis of the sigmoid colon; 194 patients had been treated as inpatients and 118 patients primarily as outpatients. In this last group, 91.5% had been treated successfully without diverticulitis-related complications or the need for hospital admission during a mean follow-up period of 48 months. Despite inherent patient selection in a retrospective cohort, ambulatory treatment of patients presenting with uncomplicated acute diverticulitis seems feasible and safe. In mildly ill and younger patients, hospital admission can be avoided.
Isba, Rachel; Zani, Babalwa; Gathu, Michael; Sinclair, David
Background The World Health Organization (WHO) recommends artemisinin-based combination therapy (ACT) for treating people with Plasmodium falciparum malaria. Five combinations are currently recommended, all administered over three days. Artemisinin-naphthoquine is a new combination developed in China, which is being marketed as a one-day treatment. Although shorter treatment courses may improve adherence, the WHO recommends at least three days of the short-acting artemisinin component to eliminate 90% P. falciparum parasites in the bloodstream, before leaving the longer-acting partner drug to clear the remaining parasites. Objectives To evaluate the efficacy and safety of the artemisinin-naphthoquine combination for treating adults and children 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; and LILACS up to January 2015. We also searched the metaRegister of Controlled Trials (mRCT) using 'malaria' and 'arte* OR dihydroarte*' as search terms. Selection criteria Randomized controlled trials comparing artemisinin-naphthoquine combinations with established WHO-recommended ACTs for the treatment of adults and children with uncomplicated malaria due to P. falciparum. Data collection and analysis Two review 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 Four trials, enrolling 740 adults and children, met the inclusion criteria. Artemisinin-naphthoquine was administered as a single dose (two
Juan Pablo Martínez
Full Text Available Introduction: Acute appendicitis is one of the main indications to abdominal surgery. When the appendicitis is not complicated, is possible to do an outpatient surgery. Objective: To describe postsurgical evolution of the patients who present uncomplicated acute appendicitis. Methods: A prospective study was carried out about the evolution of 100 patients with outpatient surgery for appendectomy by uncomplicated acute appendicitis. The study was performed in the Hospital Susana Lopez de Valencia (HSLV of Popayán, Colombia. A telephone survey was conducted during the 24 hours after surgery, to determinate potential complications like pain, nausea, vomiting and oral intolerance. Clinical histories were reviewed to determinate in case the patient has re-entered because of a possible post operative complication during 30 next days after surgical intervention. Histopathological findings were also reported. Results: During postsurgical follow up, 58% of the patients did not present any kind of pain, 95% tolerated oral route, 97% did not have vomiting and 90% did not have nausea. 3% re-entered because of type 1 infection around the surgical area, 4% because of pain. We found a histopathological concordance with the acute appendicitis diagnostic in 94% of the cases. All patients reported to be satisfied with the given attention in the postsurgery. Conclusions: Patients undergo appendectomy by uncomplicated acute appendicitis treated outpatient, has an appropriate tolerance to oral route and pain control.
Hviid, L; Kurtzhals, J A; Goka, B Q
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, re...
Kloprogge, Frank; Jullien, Vincent; Piola, Patrice; Dhorda, Mehul; Muwanga, Sulaiman; Nosten, François; Day, Nicholas P J; White, Nicholas J; Guerin, Philippe J; Tarning, Joel
Oral quinine is used for the treatment of uncomplicated malaria during pregnancy, but few pharmacokinetic data are available for this population. Previous studies have reported a substantial effect of malaria on the pharmacokinetics of quinine resulting from increased α-1-acid glycoprotein levels and decreased cytochrome P450 3A4 activity. The aim of this study was to investigate the pharmacokinetic properties of oral quinine in pregnant women with uncomplicated malaria in Uganda using a population approach. Data from 22 women in the second and third trimesters of pregnancy with uncomplicated Plasmodium falciparum malaria were analysed. Patients received quinine sulphate (10 mg of salt/kg) three times daily (0, 8 and 16 h) for 7 days. Plasma samples were collected daily and at frequent intervals after the first and last doses. A population pharmacokinetic model for quinine was developed accounting for different disposition, absorption, error and covariate models. Parasitaemia, as a time-varying covariate affecting relative bioavailability, and body temperature on admission as a covariate on elimination clearance, explained the higher exposure to quinine during acute malaria compared with the convalescent phase. Neither the estimated gestational age nor the trimester influenced the pharmacokinetic properties of quinine significantly. A population model was developed that adequately characterized quinine pharmacokinetics in pregnant Ugandan women with acute malaria. Quinine exposure was lower than previously reported in patients who were not pregnant. The measurement of free quinine concentration will be necessary to determine the therapeutic relevance of these observations. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Zani, Babalwa; Gathu, Michael; Donegan, Sarah; Olliaro, Piero L; Sinclair, David
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
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
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.
King, Welfur C; Shuaib, Waqas; Vijayasarathi, Arvind; Fajardo, Carlos G; Cabrera, Waldo E; Costa, Juan L
Despite evidence demonstrating equivalent accuracy of sonography and computed tomography (CT) in the workup of mild/uncomplicated acute diverticulitis, CT is overwhelmingly performed as the initial diagnostic test, particularly in the acute setting. Our study evaluated potential radiation and turnaround time savings associated with performing sonography instead of CT as the initial diagnostic examination in the workup of suspected uncomplicated acute diverticulitis. We retrospectively reviewed medical records from January 2010 to December 2012 for patients presenting with clinical symptoms of acute diverticulitis. Patients were categorized as a whole and subgrouped by age (>40 and 40 years and 121 diverticulitis. © 2015 by the American Institute of Ultrasound in Medicine.
Huang, Chenxi; Alamili, Mahdi; Rosenberg, Jacob
BACKGROUND: The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. METHODS: Twelve patients with uncomplicated acute diverticulitis completed this observational study...
Ng'ang'a Zipporah W
Full Text Available Abstract Background The effects of Plasmodium falciparum on B-cell homeostasis have not been well characterized. This study investigated whether an episode of acute malaria in young children results in changes in the peripheral B cell phenotype. Methods Using flow-cytofluorimetric analysis, the B cell phenotypes found in the peripheral blood of children aged 2–5 years were characterized during an episode of acute uncomplicated clinical malaria and four weeks post-recovery and in healthy age-matched controls. Results There was a significant decrease in CD19+ B lymphocytes during acute malaria. Characterization of the CD19+ B cell subsets in the peripheral blood based on expression of IgD and CD38 revealed a significant decrease in the numbers of naive 1 CD38-IgD+ B cells while there was an increase in CD38+IgD- memory 3 B cells during acute malaria. Further analysis of the peripheral B cell phenotype also identified an expansion of transitional CD10+CD19+ B cells in children following an episode of acute malaria with up to 25% of total CD19+ B cell pool residing in this subset. Conclusion Children experiencing an episode of acute uncomplicated clinical malaria experienced profound disturbances in B cell homeostasis.
Jackson, J D; Hammond, T
Acute uncomplicated diverticulitis is traditionally managed by inpatient admission for bowel rest, intravenous fluids and intravenous antibiotics. In recent years, an increasing number of publications have sought to determine whether care might instead be conducted in the community, with earlier enteral feeding and oral antibiotics. This systematic review evaluates the safety and efficacy of such an ambulatory approach. Medline, Embase and Cochrane Library databases were searched. All peer-reviewed studies that investigated the role of ambulatory treatment protocols for acute uncomplicated diverticulitis, either directly or indirectly, were eligible for inclusion. Nine studies were identified as being suitable for inclusion, including one randomised controlled trial, seven prospective cohort studies and one retrospective cohort study. All, except one, employed imaging as part of their diagnostic criteria. There was inconsistency between studies with regards to whether patients with significant co-morbidities were eligible for ambulatory care and whether bowel rest therapy was employed. Neither of these variables influenced outcome. Across all studies, 403 out of a total of 415 (97 %) participants were successfully treated for an episode of acute uncomplicated diverticulitis using an outpatient-type approach. Cost savings ranged from 35.0 to 83.0 %. Current evidence suggests that a more progressive, ambulatory-based approach to the majority of cases of acute uncomplicated diverticulitis is justified. Based on this evidence, the authors present a possible outpatient-based treatment algorithm. An appropriately powered randomised controlled trial is now required to determine its safety and efficacy compared to traditional inpatient management.
Kayitare, E; Vervaet, C; Mehuys, E; Kayumba, P C; Ntawukulilyayo, J D; Karema, C; Bortel, Van; Remon, J P
Children with uncomplicated malaria are generally treated with oral medication, except those unable to take oral drugs. Even though quinine has shown to be effective in treatment of African children with uncomplicated malaria its high bitterness limited the paediatric use. This study aimed to develop taste-masked quinine tablets suitable for children and offering dosing flexibility to adjust the quinine dose in function of body weight. Insoluble quinine pamoate was used to formulate fast-disintegrating tablets, using a specific tablet design (rectangular tablet which can be divided into 8 subunits) to allow dosing flexibility. The physical properties of tablets were evaluated in vitro, as well as the quinine bioavailability in healthy adults (n=18) and the efficacy for treatment of children with uncomplicated Plasmodium falciparum malaria (n=56) using a 7-day regimen of 8 mg quinine/kg. Quinine pamoate tablets complied with the pharmacopoeial requirements for mass uniformity, friability, content uniformity, breakability, disintegration and dissolution. The quinine pharmacokinetic parameters after single administration of a quinine pamoate tablet were similar to a commercially available quinine sulfate tablet. The fast decline in parasitemia (28.6%/24h), the reduction rate of fever (all children were apyretic after 72 h) and the steady state quinine plasma concentration (5.7-15.8 microg/ml) proved the efficacy of the quinine pamoate tablets against P. falciparum. Fast-dispersible and taste-masked quinine pamoate tablets improved dosing accuracy, allowed easy administration and resulted in a high efficacy during the treatment of children with uncomplicated malaria. Copyright 2010. Published by Elsevier B.V.
Hooton, T M; Stam, W E
Acute uncomplicated UTI is one of the most common problems for which young women seek medical attention, and it accounts for considerable morbidity and health care costs. Acute cystitis is a superficial infection of the bladder mucosa, whereas pyelonephritis involves tissue invasion of the upper urinary tract. Localization tests suggest that as many as one third of episodes of acute cystitis are associated with silent upper tract involvement. Acute cystitis or pyelonephritis in the adult patient should be considered uncomplicated if the patient is not pregnant or elderly, if there has been no recent instrumentation or antimicrobial treatment, and if there are no known functional or anatomic abnormalities of the genitourinary tract. Most of these infections are caused by E. coli, which are susceptible to many oral antimicrobials. Because of the superficial nature of cystitis, single-dose and 3-day regimens have gained wide acceptance as the preferred methods of treatment. Review of the published data suggests that a 3-day regimen is more effective than a single-dose regimen for all antimicrobials tested. Regimens with trimethoprim-sulfamethoxazole appear to be more effective than those with beta-lactams, regardless of the duration. Acute pyelonephritis does not necessarily imply a complicated infection. Upper tract infection with highly virulent uropathogens in an otherwise healthy woman may be considered an uncomplicated infection. The optimal treatment duration for acute uncomplicated pyelonephritis has not been established, and 14-day regimens are often used. We prefer to use antimicrobials that attain high renal tissue levels, such as trimethoprim-sulfamethoxazole or quinolones, for pyelonephritis. Women with frequently recurring infections can be successfully managed by continuous prophylaxis, either daily or thrice-weekly, by postcoital prophylaxis, or, in compliant patients, by early self-administration of single-dose or 3-day therapy as soon as typical
Ünlü, Çagdas; Gunadi, Patrick M.; Gerhards, Michael F.; Boermeester, Marja A.; Vrouenraets, Bart C.
Traditionally, treatment of acute diverticulitis has mostly been based on inpatient care. The question arises whether these patients can be treated on an outpatient basis as the admissions for diverticular disease have been shown to be increasing every year. We studied whether outpatient treatment
Full Text Available Nilima A Kshirsagar,1 Nithya J Gogtay,1 Diego Moran,2 Gregory Utz,3 Ashok Sethia,4 Shirsendu Sarkar,5 Pol Vandenbroucke6 1Seth G S Medical College and KEM Hospital, Mumbai, India; 2Hospital San Andrés de Tumaco, Narino, Colombia; 3US Naval Medical Research Unit 6, Lima, Peru; 4Gita Bhawan Hospital and Research Centre, Indore, 5Pfizer, Mumbai, India; 6Pfizer, New York, NY, USA Background: To explore the use of azithromycin–chloroquine (AZCQ for the treatment of malaria, we conducted double-blind, randomized, non-inferiority studies in India, Colombia, and Suriname comparing the combination of azithromycin 1 g and chloroquine (CQ 600 mg base once daily (QD for 3 days versus atovaquone–proguanil (AP or chloroquine plus sulfadoxine–pyrimethamine (SPCQ in adults with acute uncomplicated Plasmodium falciparum malaria.Methods: Patients were hospitalized until three documented negative blood smears and followed through Day 42. The primary end point was parasitologic cure at Day 28.Results: In India, parasite clearance rates were 84% and 94% for AZCQ and SPCQ, respectively (95% confidence interval [CI] for the difference: –22.6, 0.8. In Colombia and Suriname, parasite clearance rates were 57% and 99% for AZCQ and AP, respectively (95% CI: –52, –32. A subsequent open-label, non-comparative third study using a 2 g dose of azithromycin and 600 mg of CQ in India and Colombia resulted in an overall efficacy rate of 97%.Conclusion: In India, Colombia, and Suriname, 1 g azithromycin with CQ QD for 3 days was inferior to established comparator agents. An improved response rate was observed when the dose of azithromycin was increased to 2 g. Keywords: acute, uncomplicated malaria, antimalarial, azithromycin, chloroquine, malaria, parasitologic cure rate, plasmodium
Isanaka, Sheila; Langendorf, Céline; Berthé, Fatou; Gnegne, Smaila; Li, Nan; Ousmane, Nassirou; Harouna, Souley; Hassane, Hamidine; Schaefer, Myrto; Adehossi, Eric; Grais, Rebecca F
High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice. In a double-blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8. A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02). We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Médecins sans Frontières Operational Center Paris; ClinicalTrials.gov number, NCT01613547.).
Andrade, Patrícia; Ribeiro, Armando; Ramalho, Rosa; Lopes, Susana; Macedo, Guilherme
Most international guidelines recommend performing a routine colonoscopy after the conservative management of acute diverticulitis, mainly to rule out a colorectal malignancy; however, data to support these recommendations are scarce and conflicting. This study is aimed at determining the rate of advanced colonic neoplasia (ACN) found by colonoscopy, and hence the need for routine colonoscopy after CT-diagnosed acute diverticulitis. We retrospectively analyzed all patients hospitalized for acute diverticulitis between July 2008 and June 2013. Patients who underwent colonoscopy more than 1 year after the acute episode were excluded. Advanced adenoma (AA) was defined as an adenoma with: (i) ≥10 mm, (ii) ≥25% villous features, or (iii) high-grade dysplasia. ACN included cases of colorectal cancer (CRC) and AA. Of the 364 selected patients, 252 (69%) underwent colonoscopy (51% women, median age 55 ± 11 years). Adenomatous polyps were evident in 14.7% patients; 5.1% had AA and 3.2% had CRC. Patients with complicated diverticulitis had a higher number of ACN compared to those with uncomplicated diverticulitis (20.9 vs. 5.7%, p = 0.003). On multivariate analysis, age ≥50 years (OR 8.12, 95% CI 2.463-45.112; p = 0.017) and abscess on CT (OR 3.15, 95% CI 1.586-11.586; p = 0.036) were identified as significant risk factors for ACN. Patients with diverticulitis complicated with abscess have a higher risk of ACN on follow-up colonoscopy. The prevalence of ACN in patients with uncomplicated diverticulitis is quite similar to the average-risk population, and therefore an episode of CT-diagnosed uncomplicated diverticulitis, per se, does not seem to be a recommendation for colonoscopy. © 2016 S. Karger AG, Basel.
Huang, Chenxi; Alamili, Mahdi; Rosenberg, Jacob; Gögenur, Ismail
The aim of the present study was to report the trajectory of heart rate variability (HRV) indices during a low-grade acute inflammation and their associations to biomarkers for infection. Twelve patients with uncomplicated acute diverticulitis completed this observational study, which composed of 3 sessions of continuous HRV recording from 9 PM to 8 AM during ongoing diverticulitis and at complete remission (baseline). The blood samples were collected at each study session measuring C-reactive protein (CRP) and leukocytes. This study showed that the trajectories of the HRV indices were decreased both in time and frequency domains during acute diverticulitis compared to baseline. In particular, the indices reflecting the balance of sympathetic and parasympathetic activities were affected: standard deviation of normal-to-normal beats (P = .003), low-frequency power (P diverticulitis suggesting inflammatory involvement in the observed HRV alterations. We found substantial HRV depression in relation to acute uncomplicated diverticulitis, and this was associated with the elevated CRP levels. Copyright © 2015 Elsevier Inc. All rights reserved.
Jaung, Rebekah; Kularatna, Malsha; Robertson, Jason P; Vather, Ryash; Rowbotham, David; MacCormick, Andrew D; Bissett, Ian P
The management of uncomplicated (Modified Hinchey Classification Ia) acute diverticulitis (AD) has become increasingly conservative, with a focus on symptomatic relief and supportive management. Clear criteria for patient selection are required to implement this safely. This retrospective study aimed to identify risk factors for severe clinical course in patients with uncomplicated AD. Patients admitted to General Surgery at two New Zealand tertiary centres over a period of 18 months were included. Univariate and multivariate analyses were carried out in order to identify factors associated with a more severe clinical course. This was defined by three endpoints: need for procedural intervention, admission >7 days and 30-day readmission; these were analysed separately and as a combined outcome. Uncomplicated AD was identified in 319 patients. Fifteen patients (5%) required procedural intervention; this was associated with SIRS (OR 3.92). Twenty-two (6.9%) patients were admitted for >7 days; this was associated with patient-reported pain score >8/10 (OR 5.67). Thirty-one patients (9.8%) required readmission within 30 days; this was associated with pain score >8/10 (OR 6.08) and first episode of AD (OR 2.47). Overall, 49 patients had a severe clinical course, and associated factors were regular steroid/immunomodulator use (OR 4.34), pain score >8/10 (OR 5.9) and higher temperature (OR 1.51) and CRP ≥200 (OR 4.1). SIRS, high pain score and CRP, first episode and regular steroid/immunomodulator use were identified as predictors of worse outcome in uncomplicated AD. These findings have the potential to inform prospective treatment decisions in this patient group.
Full Text Available Stephen GS Vreden,1 Rakesh D Bansie,2 Jeetendra K Jitan,3 Malti R Adhin4 1Foundation for Scientific Research Suriname (SWOS, 2Department of Internal Medicine, Academic Hospital Paramaribo, 3Department of Public Health, Ministry of Health, 4Department of Biochemistry, Anton de Kom University of Suriname, Paramaribo, Suriname Background: Artemisinin resistance in Plasmodium falciparum is suspected when the day 3 parasitemia is >10% when treated with artemisinin-based combination therapy or if >10% of patients treated with artemisinin-based combination therapy or artesunate monotherapy harbored parasites with half-lives ≥5 hours. Hence, a single-arm prospective efficacy trial was conducted in Suriname for uncomplicated P. falciparum infection treated with artesunate-based monotherapy for 3 days assessing day 3 parasitemia, treatment outcome after 28 days, and parasite half-life. Methods: The study was conducted in Paramaribo, the capital of Suriname, from July 2013 until July 2014. Patients with uncomplicated Plasmodium falciparum infection were included and received artesunate mono-therapy for three days. Day 3 parasitaemia, treatment outcome after 28 days and parasite half-life were determined. The latter was assessed with the parasite clearance estimator from the WorldWide Antimalarial Resistance Network (WWARN. Results: Thirty-nine patients were included from July 2013 until July 2014. The day 3 parasitemia was 10%. Eight patients (20.5% could be followed up until day 28 and showed adequate clinical and parasitological response. Parasite half-life could only be determined from ten data series (25.7%. The median parasite half-life was 5.16 hours, and seven of these data series had a half-life ≥5 hours, still comprising 17.9% of the total data series. Conclusion: The low follow-up rate and the limited analyzable data series preclude clear conclusions about the efficacy of artesunate monotherapy in Suriname and the parasite half
Lorente, Leyre; Cots, Francesc; Alonso, Sandra; Pascual, Marta; Salvans, Silvia; Courtier, Ricard; Gil, M José; Grande, Luis; Pera, Miguel
Outpatient treatment of uncomplicated acute diverticulitis is safe and effective. The aim of this study was to determine the impact of outpatient treatment on the reduction of healthcare costs. A retrospective cohort study comparing 2 groups was performed. In the outpatient treatment group, patients diagnosed with uncomplicated acute diverticulitis were treated with oral antibiotics at home. In the hospital treatment group, patients met the criteria for outpatient treatment but were admitted to hospital and received intravenous antibiotic therapy. Cost estimates have been made using the hospital cost accounting system based on total costs, the sum of all variable costs (direct costs) plus overhead expenses divided by activity (indirect costs). A total of 136 patients were included, 90 in the outpatient treatment group and 46 in the hospital group. There were no differences in the characteristics of the patients in both groups. There were also no differences in the treatment failure rate in both groups (5.5% vs. 4.3%; P=.7). The total cost per episode was significantly lower in the outpatient treatment group (882 ± 462 vs. 2.376 ± 830 euros; P=.0001). Outpatient treatment of acute diverticulitis is not only safe and effective but also reduces healthcare costs by more than 60%. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.
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
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
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
Waqar, Talal; Khushdil, Arshad; Haque, Khalid
To ascertain the efficacy of chloroquine as first line agent in treatment of uncomplicated malaria -caused by Plasmodium vivax in children---and to determine its current treatment practice in Pakistan. This pilot study was conducted at the Paediatrics Department of Combined Military Hospital (CMH), Lahore, Pakistan. Forty-eight children between six months and twelve years of age having positive blood film for Plasmodium vivax were included. They were treated with chloroquine as a drug of - choice. Efficacy of chloroquine was assessed by clinical response, absence of parasitaemia on day seven and twenty-eight after initiation of therapy. A survey was also conducted to determine the first line therapeutic choice of Paediatricians in the treatment of uncomplicated Plasmodium vivax malaria in children in Pakistan. The results showed 100% efficacy of chloroquine in treating uncomplicated malaria caused by Plasmodium vivax in children. Artemisin was preferred by 74.28% Paediatricians' in combination therapy as 1st line treatment. Guidelines proposed by Malaria Control Programme Pakistan (MCPP) in collaboration with World Health Organization (WHO) are comprehensive but not being adhered to. The recently reported resistance of Plasmodium vivax to artemisin should urge measures to implement WHO guidelines.
Reuter, Stephanie E; Upton, Richard N; Evans, Allan M; Navaratnam, Visweswaran; Olliaro, Piero L
The determination of dosing regimens for the treatment of malaria is largely empirical and thus a better understanding of the pharmacokinetic/pharmacodynamic properties of antimalarial agents is required to assess the adequacy of current treatment regimens and identify sources of suboptimal dosing that could select for drug-resistant parasites. Mefloquine is a widely used antimalarial, commonly given in combination with artesunate. Mefloquine pharmacokinetics was assessed in 24 healthy adults and 43 patients with Plasmodium falciparum malaria administered mefloquine in combination with artesunate. Population pharmacokinetic modelling was conducted using NONMEM. A two-compartment model with a single transit compartment and first-order elimination from the central compartment most adequately described mefloquine concentration-time data. The model incorporated population parameter variability for clearance (CL/F), central volume of distribution (VC/F) and absorption rate constant (KA) and identified, in addition to body weight, malaria infection as a covariate for VC/F (but not CL/F). Monte Carlo simulations predict that falciparum malaria infection is associated with a shorter elimination half-life (407 versus 566 h) and T>MIC (766 versus 893 h). This is the first known population pharmacokinetic study to show falciparum malaria to influence mefloquine disposition. Protein binding, anaemia and other factors may contribute to differences between healthy individuals and patients. As VC/F is related to the earlier portion of the concentration-time profiles, which occurs during acute malaria, and CL/F is more related to the terminal phase during convalescence after treatment, this may explain why malaria was found to be a covariate for VC/F but not CL/F. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: firstname.lastname@example.org.
Adam, Ishag; Magzoub, Mamoun; Osman, Maha E
-sulfamethoxypyrazine-pyrimethamine (AS+SMP f) administered at time intervals of 12 hours for a 24-hour therapy was compared with the efficacy of the same drug given as a loose combination (AS+SMP l) with a dose interval of 24 hours for 3 days for the treatment of uncomplicated Plasmodium falciparum malaria in eastern Sudan. RESULTS...... of the patients. CONCLUSION: both regimens of AS+SMP were effective and safe for the treatment of uncomplicated P. falciparum malaria in eastern Sudan. Due to its simplicity, the fixed dose one-day treatment regimen may improve compliance and therefore may be the preferred choice....
Full Text Available Background Dihydroartemisinin-piperaquine (DPQ has been used since 2006 in Papua, Indonesia and is planned as an alternative artemisinin-based combination therapy for wider use in Indonesia. Confirmation of the drug’s efficacy and safety in children outside Papua is needed. Objective To measure the day-42 clinical and parasitological efficacy of DPQ in children with uncomplicated falciparum and vivax malaria. Methods This cross-sectional and observational study was held in Kalimantan and Sulawesi in 2010. Seventy and sixty children under 15 years of age with uncomplicated falciparum and vivax malaria were selected according to the 2003 WHO protocol for monitoring therapeutic efficacy of antimalarial treatments and was confirmed by microscopy and PCR. All subjects were treated with DPQ based on a dosage regimen of dihydroartemisinin 2-4 mg/kg BW/dose and piperaquine 16-32 mg/kg BW/dose, in single daily doses for 3 days and closely observed for 42 days. Data was analyzed using intention-to-treat (ITT and per protocol (PP populations. Results The mean fever and asexual parasite clearance times were 1.0 day and 1.6 days, respectively, in children with uncomplicated falciparum malaria, and 1.1 days and 1.2 days, respectively, in children with uncomplicatedvivax malaria. Clinical symptoms reduced over 50% by day 7. Hemoglobin recoveries showed improvement on days 14, 28 and 42, at 70.6%, 83.8%and 89.1%, respectively, in the falciparum malaria group, and 60.3%, 65,5% and 83.6%, respectively, in thevivax malaria group. Adequate clinical and parasitological response to DPQ on day 42 in the ITT and PP populations were reported as 98.6% (95% CI 92.3 to 99.7% and 100% (95% CI 94.7 to 100%, respectively, in the falciparum group, and 91.7% (95% CI 81.9 to 96.4% and 96.5% (95% CI 88.1 to 99.0%, respectively, the vivax group. Mild adverse events commonly noted were cough, abdominal pain, diarrhea, anorexia, and vomiting. Conclusion DPQ was effective against
Marschallek, Maria Rebekka
Background: Malaria remains one of the major causes of morbidity and mortality worldwide. Artemisinin-based combination therapies are used as first-line treatment in all endemic countries for uncomplicated P. falciparum malaria. artemether-lumefantrine was introduced as first-line treatment in Kenya in 2006. Since the first report of artemisinin-resistant P. falciparum malaria in 2009 on the Thai-Cambodian border, concerns about declining responsiveness to artemisinins have also been expresse...
Bjerrum, Lars; Gahrn-Hansen, Bente; Grinsted, Per
To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI).......To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI)....
Elhassan, I M; Hviid, L; Satti, G
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...... 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....
Bello, Shaibu O; Chika, Aminu; AbdulGafar, Jimoh O
The purpose of this study is to summarize the available data on the efficacy of Artesunate plus Amodiaquine (AS+AQ) versus Artemether -Lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa using uncorrected parasitaemia as a clinically relevant endpoint. Studies and conference abstracts identified through Pubmed, Medline, Embase, Ansinet, AJOL, Bioline, Cochrane Infectious Diseases Group trials register, The Cochrane Controlled Trials Registe...
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
A. D. Kaprin
Full Text Available Abstract:Acute pyelonephritis is one of the common diseases both in outpatient and in the hospital practice. The leading causative agent of this disease is E. coli. Obstructive uropathy, foreign body, vesicoureteral reflux, sexual activity, use of local contraceptives contribute to the upward development of urinary infection. The goals of antimicrobial therapy for acute uncomplicated pyelonephritis are: relief of symptoms, restoration of social activity, prevention of complications and relapse prevention. The choice of an antimicrobial agent in most cases is carried out empirically based on the data on the dominant pathogens and their regional resistance. In acute uncomplicated pyelonephritis duration of antimicrobial therapy should be 7–14 days. The drugs of choice for treatment of acute uncomplicated pyelonephritis non-severe in adults are ciprofloxacin and levofloxacin, ceftibuten and cefixime. Patients with acute uncomplicated pyelonephritis severe emergency hospitalization is shown in urological outpatient and parenteral antimicrobial therapy (carbapenems or protected aminopenicillins combined with or without amikacin with subsequent conversion to oral drugs and infusion therapy.
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
Ridgway, P F
Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and \\'bowel rest\\' in clinically diagnosed acute uncomplicated diverticulitis.
Knottnerus, Bart J.; Geerlings, Suzanne E.; Moll van Charante, Eric P.; ter Riet, Gerben
PURPOSE Whereas a diagnosis of acute uncomplicated urinary tract infection (UTI) in clinical practice comprises a battery of several diagnostic tests, these tests are often studied separately (in isolation from other test results). We wanted to determine the value of history and urine tests for
van Dijk, S. T.; Daniels, L.; Nio, C. Y.; Somers, I.; van Geloven, A. A. W.; Boermeester, M. A.
Since outpatient treatment and omitting antibiotics for uncomplicated acute colonic diverticulitis have been proven to be safe in the majority of patients, selection of patients that may not be suited for this treatment strategy becomes an important topic. The aim of this study is to identify
Okech, Bernard A.; Existe, Alexandre; Romain, Jean R.; Memnon, Gladys; Victor, Yves Saint; de Rochars, Madsen Beau; Fukuda, Mark
Chloroquine (CQ) has been used for malaria treatment in Haiti for several decades, but reports of CQ resistance are scarce. The efficacy of CQ in patients with uncomplicated Plasmodium falciparum undergoing treatment in Haiti was evaluated. Malaria patients were enrolled, treated with CQ, and monitored over a 42-day period. The treatment outcomes were evaluated on day 28 by microscopy. The P. falciparum slide-confirmed rate was 9.5% (121 of 1,277). Malaria infection was seasonal, with peak observations between October and January; 88% (107 of 121) of patients consented to participate. Sixty patients successfully completed the 42-day follow-up, whereas 47 patients withdrew consent or were lost to follow-up. The mean parasite density declined rapidly within the first few days after treatment. Seven patients did not clear their malaria infections and were clinically asymptomatic; therefore, they were considered late parasitological failures. About 90% (95% confidence interval = 84.20–97.90) of patients had no detectable parasitemia by day 28 and remained malaria-free to day 42. Testing for recrudescence, reinfection, and CQ serum levels was not done in the seven patients, and therefore, their CQ resistance status is unresolved. CQ resistance surveillance by patient follow-up, in vitro drug sensitivity studies, and molecular markers is urgently needed in Haiti. PMID:25601993
Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi
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
Brochmann, N D; Schultz, J K; Jakobsen, G S; Øresland, T
This study aimed to evaluate the implementation of nonantibiotic management of acute uncomplicated diverticulitis at a large university hospital in Norway with regard to management failure, disease recurrence and complications. On 1 January 2013 we implemented a new policy for the management of acute uncomplicated diverticulitis without antibiotics. Antibiotic treatment was only provided in the case of defined criteria. All patients admitted from 1 January 2013 to 30 June 2014 with a CT-verified, left-sided, acute uncomplicated diverticulitis were included in the study and evaluated retrospectively, with 12 months' follow-up. Of 244 admissions with acute uncomplicated diverticulitis, 177 (73%) were managed without antibiotics. Among these there were seven (4%) management failures, including five patients in whom a deteriorating clinical picture prompted antibiotic treatment and two readmissions within 1 month due to persisting symptoms. The only complication in this group was one fistula (diverticulitis requiring hospital care and two (1%) underwent elective surgery within the first year. Twenty (8%) patients met predefined exemption criteria and received antibiotics from admission, six (30%) of whom developed complications. The recurrence rate in this group was 10% and none had surgery performed. The 47 (20%) policy violators treated with antibiotics from admission had no complications. Their recurrence rate was 11% and one (2%) patient underwent elective surgery. This study confirms that nonantibiotic management of acute uncomplicated diverticulitis is safe and feasible. Most complications occurred in a small group of high-risk patients treated with antibiotics. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.
Full Text Available To date no comparative trials have been done, to our knowledge, of fixed-dose artemisinin combination therapies (ACTs for the treatment of Plasmodium falciparum malaria in pregnancy. Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world. The objective of this study was to compare the efficacy, tolerability, and safety of artemether-lumefantrine, the most widely used fixed ACT, with 7 d artesunate monotherapy in the second and third trimesters of pregnancy.An open-label randomised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d (AL or artesunate monotherapy 7 d (AS7 was conducted in Karen women in the border area of northwestern Thailand who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy. The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery, as estimated by Kaplan-Meier survival analysis. Infants were assessed at birth and followed until 1 y of life. Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy. Both regimens were very well tolerated. The cure rates (95% confidence interval for the intention to treat (ITT population were: AS7 89.2% (82.3%-96.1% and AL 82.0% (74.8%-89.3%, p = 0.054 (ITT; and AS7 89.7% (82.6%-96.8% and AL 81.2% (73.6%-88.8%, p = 0.031 (per-protocol population. One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up. Birth outcomes and infant (up to age 1 y outcomes did not differ significantly between the two groups. The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL.The current standard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with
Abba, Katharine; Kirkham, Amanda J; Olliaro, Piero L; Deeks, Jonathan J; Donegan, Sarah; Garner, Paul; Takwoingi, Yemisi
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. 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. 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. 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. 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 specificities are presented alongside 95% confidence intervals (95% CI). We included 47 studies
Anabwani, G; Canfield, C J; Hutchinson, D B
Malaria is a major cause of pediatric mortality in sub-Saharan Africa. Worldwide estimates of mortality among children with Plasmodium falciparum malaria range from 1 to 2 million deaths per year. Management of malaria is increasingly difficult because of the global spread of drug-resistant strains of P. falciparum. There is an urgent need for safe and effective new therapies to treat multidrug-resistant malaria. This open label, randomized trial compared atovaquone and proguanil hydrochloride with halofantrine for treatment of acute, uncomplicated P. falciparum malaria in children age 3 to 12 years (84 patients per group). Study drug dosages were adjusted by weight (approximately 20 and 8 mg/kg daily for three doses for atovaquone and proguanil hydrochloride and 8 mg/kg every 6 h for three doses for halofantrine). Patients were monitored by serial clinical and laboratory assessments for 28 days after starting treatment. Both regimens were effective (cure rate, 93.8% for atovaquone and proguanil hydrochloride and 90.4% for halofantrine) and produced prompt defervescence. Mean parasite clearance times were 50.2 h for halofantrine and 64.9 h for atovaquone and proguanil hydrochloride. More adverse experiences were reported in children treated with halofantrine (119) than with atovaquone and proguanil hydrochloride (73). In Kenyan children the combination of atovaquone and proguanil hydrochloride has efficacy comparable with that of halofantrine for treatment of acute uncomplicated multidrug-resistant falciparum malaria and is associated with a lower rate of adverse events.
Motohiro, Masayuki; Yuasa, Fumio; Hattori, Toshihiko; Sumimoto, Tsutomu; Takeuchi, Masaharu; Kaida, Mutsuhito; Jikuhara, Toshimitsu; Hikosaka, Makoto; Sugiura, Tetsuro; Iwasaka, Toshiji
This study examined the cardiovascular adaptations of an exercise training program and evaluated the role of peripheral vasodilator capacity in contributing to these adaptations after myocardial infarction. A total of 44 consecutive patients with uncomplicated myocardial infarction underwent 3 wks of exercise training. Controls (n = 12) with comparable myocardial infarction were selected from our database and were restricted to a program with minimal activity. All patients performed cardiopulmonary exercise testing with hemodynamic measurements. Forearm and calf reactive hyperemic flow were measured by venous occlusive plethysmography as indices of peripheral vasodilator capacity. Despite no change in arteriovenous oxygen difference at peak exercise after training, training resulted in significant increases in oxygen consumption, cardiac output, and stroke volume and a significant decrease in systemic vascular resistance at peak exercise (overall, P training (P training had a positive correlation with increases in peak cardiac output, stroke volume, and oxygen consumption after training and an inverse correlation with peak systemic vascular resistance. Exercise training improved exercise tolerance by improving hemodynamic responses to exercise after myocardial infarction. This improved exercise performance was linked to a training-induced increase in calf vasodilator capacity.
Ejaz, Amer; Haqnawaz, Khurram; Hussain, Zakir; Butt, Rafi; Awan, Zaheer Iqbal; Bux, Hussain
To assess the efficacy and tolerability of quinine-doxycycline combination therapy in uncomplicated falciparum malaria in terms of malarial parasite clearance from peripheral blood. One hundred adult males were included in the study. Malarial parasite counts in peripheral blood films were determined at the time of admission and then 12 hourly until clearance and thereafter weekly for 28 days (4 weeks). Treatment was started with quinine sulphate 10 mg of salt/kg body weight 8 hourly orally for a minimum period of 3 days and maximum of 7 days along with doxycycline 100 mg 12 hourly orally for 7 days. Primary efficacy outcome measure was early treatment failure, whereas secondary efficacy outcome measure was late treatment failure. Tolerability outcome measure was the development of treatment related adverse effects resulting in discontinuation from the study. The primary efficacy outcome measure of the study i.e. malarial parasite index declined from a mean of 6.34 (SD +/- 2.83) before treatment to zero at day 7 of treatment. Parasite clearance time was 1-7 days (mean 3.58, SD +/- 1.28). Mean duration of quinine treatment till clearance of malarial parasites was 4.63 days (SD +/- 1.38). Mean duration of fever was 2.96 days (range 1 to 6 days). There was no early or late treatment failure. There was no relapse during the 28 days follow up period. Drug related side effects were mild and did not warrant discontinuation of treatment in any patient. Quinine-doxycycline combination is effective in southern Pakistan. Randomized controlled trials are needed to further validate the claim.
Saavedra-Lozano, J; Calvo, C; Huguet Carol, R; Rodrigo, C; Núñez, E; Obando, I; Rojo, P; Merino, R; Pérez, C; Downey, F J; Colino, E; García, J J; Cilleruelo, M J; Torner, F; García, L
This is a Consensus Document of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediatrica), Spanish Society of Paediatric Rheumatology (Sociedad Española de Reumatología Pediátrica) and the Spanish Society of Paediatric Orthopaedics (Sociedad Española de Ortopedia Pediátrica), on the treatment of uncomplicated acute osteomyelitis and septic arthritis. A review is presented on the medical and surgical treatment of acute osteoarticular infection, defined as a process with less than 14 days of symptomatology, uncomplicated and community-acquired. The different possible options are evaluated based on the best available scientific knowledge, and a number of evidence-based recommendations for clinical practice are provided. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Taylor Walter RJ
Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is being widely promoted as a strategy to counteract the increase in Plasmodium falciparum antimalarial drug resistance. Methods A randomized, double-blind, placebo-controlled, clinical trial of the efficacy, effect on gametocytes and safety of the addition of artesunate/placebo (4 mg/kg/day × 3 d to amodiaquine (10 mg/kg/day × 3 d was conducted in Choco department, a low intensity transmission area in northwest Colombia. Results From 2,137 screened subjects, 85 entered the study: 43 in the amodiaquine plus placebo and 42 in the amodiaquine plus artesunate groups. Potentially eligible cases failed to qualify mostly because they were not available for follow-up visits (73%. Based on a per protocol analysis, the therapeutic response to both treatments was high: amodiaquine/placebo 35/36, 97.2% (95% CI 85.5–99.9, and amodiaquine/artesunate 32/32, 100% (89.1–100 after PCR genotyping. The Kaplan-Meier survival estimates based on all eligible patients enrolled (amodiaquine/placebo: n = 42; amodiaquine/artesunate: n = 41 were similar in the two study groups (P = 0.3. The addition of artesunate significantly decreased gametocyte carriage on Day 4 (OR = 0.1 95% CI 0.02–0.6, Day 7 (OR = 0.2 95%CI 0.04–0.9, Day 14 (OR = 0.09 95% CI 0–0.8, and Day 21 (OR95%CI 0–0.9. Most subjects in both groups (81% in amodiaquine/placebo and 75.6% in amodiaquine/artesunate reported at least one drug related adverse event. Symptoms were generally mild and self-limiting and there was no serious adverse event. Two patients on amodiaquine/artesunate voluntarily withdrew from study because they could not tolerate the medication. Conclusion Both drug regimens were effective in this area of Colombia. The addition of artesunate reduced gametocyte carriage and did not adversely affect tolerability. In this set of patients, the rate of adverse events was higher than in other studies. Patients' follow-up is
Mumtaz KH. Alnaser
Full Text Available Background: Acute appendicitis is one of the commonest causes of acute abdomen. There is a wide discussion and controversy on the surgical and nonsurgical treatment of acute uncomplicated appendicitis. The aim of this study was to evaluate the efficacy and outcomes of the conservative management of selected cases of acute appendicitis with an antibiotic first plan. Patients and methods: This was a single hospital-based prospective study with a duration of 25 months. Patients with clinical and radiological features of acute appendicitis presenting within 72 h of the beginning of abdominal pain with Alvarado score ≥5 were included. The patients received a therapeutic dose of broad-spectrum antibiotics and symptomatic treatment. The follow-up period was 6 months. Results: 90 patients were evaluated, 54 (60% patients were female and 36 (40% patients were male with mean age 34.4 years. Conservative treatment was successful in 68 (75.6% patients and failed in 22 (24.4% patients. No mortality recorded in this study. The main complications which occurred in those patients who failed to respond to conservative treatment were perforated appendicitis (3 patients, appendicular abscess (3 patients and appendicular mass (4 patients. Conclusion: Majority of cases of the first attack of uncomplicated acute appendicitis can be treated successfully by conservative treatment. However, conservative treatment demands precise communication, close monitoring and follow-up to recognize failure which needs to be treated immediately by surgery. Keywords: Acute appendicitis, Conservative treatment, Surgery, Antibiotics
Full Text Available A total of 112 male patients presenting with acute gonococcal urethritis were admitted to the hospital. The diagnosis was confirmed by smear, culture, oxidase reaction and sugar fermentation tests. The patients were treated with a single 300 mg capsule of rosoxacin. All patients except one showed adequate response to rosoxacin.
A N Tiwari
Full Text Available Twenty eight male patients with acute gonococcal, urethritis were treated, with rosoxacin 300 mg capsule, (Eradacil as a single- dose oral therapy. Twenty six patients were cured, while two patients did not improve. Four patients developed post-gonococcal urethritis (PGU.
Huang, Libin; Yin, Yuan; Yang, Lie; Wang, Cun; Li, Yuan; Zhou, Zongguang
Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial. To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. The PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial. Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days. Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. The primary outcome was the success rate of treatment. The hypothesis was formulated before data collection. A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a
Boermeester, Marja A; Humes, David J; Velmahos, George C; Søreide, Kjetil
Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the disease resulting in new approaches to and better evidence for the management of acute diverticulitis. We searched the Cochrane Library (years 2004-2015), MEDLINE (years 2004-2015), and EMBASE (years 2004-2015) databases. We used the search terms "diverticulitis, colonic" or "acute diverticulitis" or "divertic*" in combination with the terms "management," "antibiotics," "non-operative," or "surgery." Registers for clinical trials (such as the WHO registry and the https://clinicaltrials.gov/ ) were searched for ongoing, recruiting, or closed trials not yet published. Antibiotic treatment can be avoided in simple, non-complicated diverticulitis and outpatient management is safe. The management of complicated disease, ranging from a localized abscess to perforation with diffuse peritonitis, has changed towards either percutaneous or minimally invasive approaches in selected cases. The role of laparoscopic lavage without resection in perforated non-fecal diverticulitis is still debated; however, recent evidence from two randomised controlled trials has found a higher re-intervention in this group of patients. A shift in management has occurred towards conservative management in acute uncomplicated disease. Those with uncomplicated acute diverticulitis may be treated without antibiotics. For complicated diverticulitis with purulent peritonitis, the use of peritoneal lavage appears to be non-superior to resection.
Platelet distribution width, mean platelet volume and haematological parameters in patients with uncomplicated plasmodium falciparum and P. vivax malaria [version 1; referees: 1 approved, 2 approved with reservations
Elrazi A. Ali
Full Text Available Background: The association between the haematological profile (including abnormal platelets and malaria is not completely understood. There are few published data on haematological profiles of malaria patients in areas with unstable malaria transmission. The current study was conducted to investigate if the haematological parameters, including platelet indices, were reliable predictors for microscopically-diagnosed malaria infection. Methods: A case-control study with a total of 324 participants (162 in each arm was conducted at the out-patient clinic of New Halfa hospital during the rainy and post rainy season (August 2014 through to January 2015. The cases were patients with uncomplicated Plasmodium falciparum (107; 66.9% and P. vivax malaria (55, 34.0% infections. The controls were aparasitemic individuals. The haematological parameters were investigated using an automated hemo-analyser. Results: There was no significant difference in the mean (±SD age between the study groups; however, compared to the controls, patients with uncomplicated malaria had significantly lower haemoglobin, leucocyte and platelet counts, and significantly higher red cell distribution width (RDW, platelet distribution width (PDW and mean platelet volume (MPV. Conclusions: The study revealed that among the haematological indices, PDW and MPV were the main predictors for uncomplicated P. falciparum and P. vivax malaria infection. Abbreviations: OR: odds ratio.
Full Text Available Abstract Background Malaria in Zambia remains a public health and developmental challenge, affecting mostly children under five and pregnant women. In 2002, the first-line treatment for uncomplicated malaria was changed to artemether-lumefantrine (AL that has proved to be highly efficacious against multidrug resistant Plasmodium falciparum. Objective The study objective was to determine whether dihydroartemisinin-piperaquine (DHA/PQP had similar efficacy, safety and tolerability as AL for the treatment of children with uncomplicated P. falciparum malaria in Ndola, Zambia. Methods Between 2005 and 2006, 304 children (6-59 months old with uncomplicated P. falciparum were enrolled, randomized to AL (101 or DHA/PQP (203 and followed up for 42 days. Outcome of treatment was defined according to the standard WHO classification, i.e. early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Recurrent infections were genotyped to distinguish between recrudescence and new infection. Results No ETF was observed. At day 28, PCR-uncorrected ACPR was 92% in the DHA/PQP and 74% in the AL arm (OR: 4.05; 95%CI: 1.89-8.74; p Conclusion DHA/PQP was as efficacious, safe and well tolerated in treatment of uncomplicated malaria as AL, though in the latter group more new infections during the follow up were observed. DHA/PQP seems a potential candidate to be used as an alternative first-line or rescue treatment in Zambia. Trial Registration ISRCTN16263443, at http://www.controlled-trials.com/isrctn
Wootton, Daniel G.; Opara, Hyginus; Biagini, Giancarlo A.; Kanjala, Maxwell K.; Duparc, Stephan; Kirby, Paula L.; Woessner, Mary; Neate, Colin; Nyirenda, Maggie; Blencowe, Hannah; Dube-Mbeye, Queen; Kanyok, Thomas; Ward, Stephen; Molyneux, Malcolm; Dunyo, Sam; Winstanley, Peter A.
The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil−dapsone (CPG−DDS) for the treatment of uncomplicated falciparum malaria. Methods Open-label clinical trial comparing CPG−DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years) and 107 children (median age 38 months) with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG–DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0−3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population using mean time to reduce baseline parasitemia by 90% (PC90). A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT) population. Results In the Day 3 PP population for the adult group (N = 85), mean time to PC90 was 19.1 h in the CPG−DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference −6.6 h [95%CI −11.8, −1.5]), 2 mg/kg (10.7 h; −8.4 h [95%CI −13.6, −3.2]) and 4 mg/kg (10.3 h; −8.7 h [95%CI −14.1, −3.2]) groups. For children in the Day 3 PP population (N = 92), mean time to PC90 was 21.1 h in the CPG−DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; −3.3 h [95%CI −8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG−DDS; 14.4 h (treatment difference −6.4 h [95%CI −11.7, −1.0]) and 12.8 h (−7
Daniel G Wootton
Full Text Available The objective of this study was to determine the appropriate dose of artesunate for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS for the treatment of uncomplicated falciparum malaria.Open-label clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was conducted between June 2002 and February 2005, including 116 adults (median age 27 years and 107 children (median age 38 months with acute uncomplicated Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days. Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP population using mean time to reduce baseline parasitemia by 90% (PC90. A number of secondary outcomes were also included. Appropriate artesunate dose was determined using a pre-defined decision matrix based on primary and secondary outcomes. Treatment emergent adverse events were recorded from clinical assessments and blood parameters. Safety was evaluated in the intent to treat (ITT population.In the Day 3 PP population for the adult group (N = 85, mean time to PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5], 2 mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2] and 4 mg/kg (10.3 h; -8.7 h [95%CI -14.1, -3.2] groups. For children in the Day 3 PP population (N = 92, mean time to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group (17.7 h; -3.3 h [95%CI -8.6, 2.0], though the +artesunate 2 mg/kg and 4 mg/kg groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h (treatment difference -6.4 h [95%CI -11.7, -1.0] and 12.8 h (-7.4 h [95%CI -12.9, -1.8], respectively. An analysis of mean time
Daniels, L.; de Korte, N.; van Dieren, S.; Stockmann, H. B.; Vrouenraets, B. C.; Consten, E. C.; van der Hoeven, J. A.; Eijsbouts, Q. A.; Faneyte, I. F.; Bemelman, W. A.; Dijkgraaf, M. G.; Boermeester, M. A.; Glaap, C. E M; Croonen, A.; Cuesta, M. A.; Kuijvenhoven, J.; Buijsman, R.; Den Uil, S.; De Reuver, P. R.; Tuynman, J. B.; Van de Wall, B. J M; Stam, M. A W; Roumen, R. M H; Truin, W.; Wijn, R.; Gerhards, M. F.; Kuhlmann, K. F D; Van der Zaag, E. S.; Biemond, J. E.; Klicks, R. J.; Dhar, N.; Cense, H. A.; De Groot, G. H.; Pikoulin, Y.; Van Ramshorst, G. H.; Hoornweg, L. L.; Koet, L.; Van Geloven, A. A W; Emous, M.; Claassen, A. T P M; Mollink, S.; Sonneveld, D. J A; Bouvé, L.; Diepenhorst, G. M P; Vles, W. J.; Toorenvliet, B. R.; Lange, J. F.; Mannaerts, G. H H; Grotenhuis, B. A.; tot Nederveen Cappel, R. J De Vos; Deerenberg, E. B.; Depla, A. C T M; Bruin, S.; Vos, X.; Scheepers, J. J G; Boom, M. J.; Boerma, D.; Van Esser, S.; Pruim, J.; Reitsma, J. B.
Background: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. Methods: Patients with
Daniels, L.; Unlu, C.; Korte, N. de; Dieren, S. van; Stockmann, H.B.; Vrouenraets, B.C.; Consten, E.C.; Hoeven, J.A. van der; Eijsbouts, Q.A.; Faneyte, I.F.; Bemelman, W.A.; Dijkgraaf, M.G.; Boermeester, M.A.; Reuver, P.R.; et al.,
BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. METHODS: Patients with
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.
Hviid, L; Theander, T G; Abu-Zeid, Y A
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...
Kotwani, Anita; Holloway, Kathleen
To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007-November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance. © 2014 John Wiley & Sons Ltd.
Burek, K.A.; Kirscht, J.; Topol, E.J.
In a randomized, controlled trial of early hospital discharge after acute myocardial infarction (MI), a heart rate, symptom-limited exercise thallium test was performed after the onset of MI. Patients' exercise capacity was evaluated by the exercise treadmill with accompanying thallium scintigraphy. Of 507 consecutive patients screened, the condition of 179 was classified as uncomplicated, which is defined as the absence of angina, heart failure, or serious arrhythmias at 72 hours from admission. Of the patients with uncomplicated conditions, 126 had an exercise test on day 3 and 53 did not exercise on day 3. Of the 126 patients who exercised on day 3, 36 had a positive test and 90 had a negative test for ischemia. The 36 patients with a positive test result exercised a mean time of 6.71 +/- 2.8 minutes, achieved a mean peak heart rate of 120.9 +/- 21.4 beats/min, reached a peak systolic blood pressure of 144.7 +/- 33.3 mm Hg, and achieved a double product (rate-pressure product) of 183.4 +/- 67.6. The 90 patients with a negative test result for ischemia exercised 9.45 +/- 12.7 minutes, achieved a peak heart rate of 130.2 +/- 14.4 beats/min, reached a mean systolic blood pressure of 155.5 +/- 29.4 mm Hg, and achieved a rate-pressure product of 210.5 +/- 44.0. Of the 90 patients with uncomplicated conditions who had a negative exercise test for ischemia, 85 patients received reperfusion therapy, which included thrombolysis or coronary angioplasty or both
Elfving, Kristina; Shakely, Deler; Andersson, Maria; Baltzell, Kimberly; Ali, Abdullah S; Bachelard, Marc; Falk, Kerstin I; Ljung, Annika; Msellem, Mwinyi I; Omar, Rahila S; Parola, Philippe; Xu, Weiping; Petzold, Max; Trollfors, Birger; Björkman, Anders; Lindh, Magnus; Mårtensson, Andreas
Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission. We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness) guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR) of IMCI-pneumonia classified patients, and multiple quantitative (q)PCR investigations of nasopharyngeal (NPH) (all patients) and rectal (GE) swabs (diarrhoea patients). For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated. NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98%) and 153/164 (93%) of patients and 158/166 (95%) and 144/165 (87%) of controls, respectively. Overall, 57% (387/677) had IMCI-pneumonia, but only 12% (42/342) had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%), influenza A/B (22.3%), rhinovirus (10.5%) and group-A streptococci (6.4%), CXR-confirmed pneumonia (6.2%), Shigella (4.3%) were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83) without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74%) patients, but only 152 (22%) had an infection retrospectively considered to require
Full Text Available Despite the fact that a large proportion of children with fever in Africa present at primary health care facilities, few studies have been designed to specifically study the causes of uncomplicated childhood febrile illness at this level of care, especially in areas like Zanzibar that has recently undergone a dramatic change from high to low malaria transmission.We prospectively studied the aetiology of febrile illness in 677 children aged 2-59 months with acute uncomplicated fever managed by IMCI (Integrated Management of Childhood Illness guidelines in Zanzibar, using point-of-care tests, urine culture, blood-PCR, chest X-ray (CXR of IMCI-pneumonia classified patients, and multiple quantitative (qPCR investigations of nasopharyngeal (NPH (all patients and rectal (GE swabs (diarrhoea patients. For comparison, we also performed NPH and GE qPCR analyses in 167 healthy community controls. Final fever diagnoses were retrospectively established based on all clinical and laboratory data. Clinical outcome was assessed during a 14-day follow-up. The utility of IMCI for identifying infections presumed to require antibiotics was evaluated.NPH-qPCR and GE-qPCR detected ≥1 pathogen in 657/672 (98% and 153/164 (93% of patients and 158/166 (95% and 144/165 (87% of controls, respectively. Overall, 57% (387/677 had IMCI-pneumonia, but only 12% (42/342 had CXR-confirmed pneumonia. Two patients were positive for Plasmodium falciparum. Respiratory syncytial virus (24.5%, influenza A/B (22.3%, rhinovirus (10.5% and group-A streptococci (6.4%, CXR-confirmed pneumonia (6.2%, Shigella (4.3% were the most common viral and bacterial fever diagnoses, respectively. Blood-PCR conducted in a sub-group of patients (n = 83 without defined fever diagnosis was negative for rickettsiae, chikungunya, dengue, Rift Valley fever and West Nile viruses. Antibiotics were prescribed to 500 (74% patients, but only 152 (22% had an infection retrospectively considered to require
Full Text Available Abstract Background Rosetting and cytoadherence of Plasmodium falciparum-infected red blood cells have been associated with severity of malaria. ICAM-1 and CD36 are the main host cell receptors, while PfEMP1-DBLα is a major parasite ligand, which can contribute to rosette formation. This study is aimed at demonstrating whether the highly polymorphic PfEMP1-DBLα sequences occurring among Thai isolates causing severe and uncomplicated malaria are associated with their ability to form rosettes and reflected the clinical outcome of the patients. Methods Two hundred and ninety five PfEMP1-DBLα sequences from Thai clinical isolates causing severe and uncomplicated malaria were evaluated by sequencing and direct comparison using the specific text string analysis functions in Microsoft Excel and Perl. The relationships between the PfEMP1-DBLα sequences were also analysed by network analysis. The binding abilities of parasitized red blood cells (PRBCs to CD36, wild type ICAM-1, ICAM-1Kilifi and ICAM-1S22/A under static condition were included. Results Two hundred and eighty one non-identical amino acid sequences were identified (p = 0.027. By using a simple non-phylogenetic approach to visualize the sharing of polymorphic blocks (position specific polymorphic block, PSPB and cys/PoLV among DBLα sequences, the sequence group 1 was split from the other five sequence groups. The isolates belonging to sequence group 5 gave the highest mean rosetting rate (21.31%. However, within sequence group 2 and group 6, the isolates causing severe malaria had significantly higher rosetting rate than those causing uncomplicated malaria (p = 0.014, p = 0.007, respectively. Conclusion This is the first report of PfEMP1-DBLα analysis in clinical Thai isolates using semi-conserved features (cys/PoLV and PSPBs. The cys/PoLV group 5 gave the highest rosetting rate. PfEMP1-DBLα domains in Thai isolates are highly diverse, however, clinical isolates from severe and
Nespoli, Luca; Lo Bianco, Giulia; Uggeri, Fabio; Romano, Fabrizio; Nespoli, Angelo; Bernasconi, Davide Paolo; Gianotti, Luca
To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P diverticulitis.
Full Text Available Current (1999 World Health Organization guidelines recommend giving routine antibiotics (AB for all children with severe acute malnutrition (SAM, even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation.OVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT, five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05. However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27. Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55% vs 22% (IQR 17-23% and population-weighted-means 52.9% (range 23-57% vs 35.4% (range 6.7-42%. Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM.The evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable
Valea, Innocent; Tinto, Halidou; Traore-Coulibaly, Maminata; Toe, Laeticia C; Lindegardh, Niklas; Tarning, Joel; Van Geertruyden, Jean-Pierre; D'Alessandro, Umberto; Davies, Geraint R; Ward, Stephen A
Mefloquine/artesunate has recently been developed as a fixed-dose combination, providing a promising rescue/alternative treatment for malaria during pregnancy. However, limited data are available on the effect of pregnancy on its pharmacokinetic properties. This study was conducted to assess the pharmacokinetic properties of mefloquine/carboxymefloquine and artesunate/dihydroartemisinin in pregnant and non-pregnant women with uncomplicated malaria. Twenty-four women in their second and third trimesters of pregnancy and 24 paired non-pregnant women were enrolled. All patients were treated for uncomplicated Plasmodium falciparum malaria with a standard fixed-dose combination of oral mefloquine and artesunate one daily over 3 days. Frequent blood samples were collected before treatment and at scheduled times post-dose for the drug measurements and pharmacokinetic analyses. The study was registered at www.clinicaltrials.gov (identifier: NCT00701961). The total median exposure to mefloquine and dihydroartemisinin was not significantly different between the pregnant and non-pregnant women (P>0.05). There was a trend of higher exposure to mefloquine in the pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h × ng/mL; P=0.059). However, the total exposure to carboxymefloquine was 49% lower during pregnancy (735600 versus 1499000 h × ng/mL; Pmefloquine and dihydroartemisinin appeared to be similar in both pregnant and non-pregnant women, but there were significant differences in carboxymefloquine and artesunate exposure. The data presented here do not warrant a dose adjustment in pregnant patients, but an extensive analysis of the data could provide a better understanding of these findings. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: email@example.com.
Cordel, Hugues; Cailhol, Johann; Matheron, Sophie; Bloch, Martine; Godineau, Nadine; Consigny, Paul-Henri; Gros, Hélène; Campa, Pauline; Bourée, Patrice; Fain, Olivier; Ralaimazava, Pascal; Bouchaud, Olivier
Each year, thousands of cases of uncomplicated malaria are imported into Europe by travellers. Atovaquone-proguanil (AP) has been one of the first-line regimens used in France for uncomplicated malaria for almost ten years. While AP's efficacy and tolerance were evaluated in several trials, its use in "real life" conditions has never been described. This study aimed to describe outcome and tolerance after AP treatment in a large cohort of travellers returning from endemic areas. Between September 2002 and January 2007, uncomplicated malaria treated in nine French travel clinics with AP were followed for 30 days after AP initiation. Clinical and biological data were collected at admission and during the follow-up. A total of 553 patients were included. Eighty-eight percent of them were born in Africa, and 61.8% were infected in West Africa, whereas 0.5% were infected in Asia. Migrants visiting friends and relatives (VFR) constituted 77.9% of the patients, the remainder (32.1%) were backpackers. Three-hundred and sixty-four patients (66%) fulfilled follow-up at day 7 and 265 (48%) completed the study at day 30. Three patients had treatment failure. One-hundred and seventy-seven adverse drug reactions (ADR) were reported during the follow-up; 115 (77%) of them were digestive ADR. Backpackers were more likely to experiment digestive ADR compared to VFR (OR = 3.8; CI 95% [1.8-8.2]). Twenty patients had to be switched to another regimen due to ADR. This study seems to be the largest in terms of number of imported uncomplicated malaria cases treated by AP. The high rate of reported digestive ADR is striking and should be taken into account in the follow-up of patients since it could affect their adherence to the treatment. Beside AP, artemisinin combination therapy (ACT) is now recommended as first-line regimen. A comparison of AP and ACT, in terms of efficacy and tolerance, would be useful.
Zaidi, M.A.; Nazeer, T.B.; Aziz, O.B.A.; Asad, T.; Dar, Z.S.
Objective: To compare antibiotic therapy and appendectomy in uncomplicated acute appendicitis in terms of efficacy. Study Design: Randomized controlled trial. Place and Duration of Study: Surgical Ward Forward Treatment Centre (FTC), 5 Mountain Medical Battalion Forward Kahuta Azad Jammu Kashmir (AJK), from Oct 2011 to Mar 2013. Material and Methods: A total of 103 patients with clinical diagnosis of acute appendicitis (AA) were admitted during the duration of study and divided into two groups by consecutive sampling. The antibiotic group consisted of 51 patients who received intravenous antibiotics for 48 hours and oral antibiotics for another 8 days. The appendectomy group comprised of 52 patients who all underwent standard appendectomy. All the patients were followed up at 1 month and 1 year for assessing efficacy and post treatment complications. Results: The efficacy of antibiotic treatment is 90.625 percent as compared to appendectomy which was 88.46 percent (p=0.759) at 1 month follow up after treatment. At one year post treatment, the comparison between the efficacy of antibiotic therapy (71.87 percent) and appendectomy (87.14 percent) remains statistically insignificant (p=0.055). Conclusion: Antibiotic therapy is comparable to appendectomy in AA in terms of efficacy at 1 month and 1 year post treatment. (author)
Full Text Available Feven Wudneh,1,2 Ashenafi Assefa,3 Desalegn Nega,3 Hussien Mohammed,3 Hiwot Solomon,4 Tadesse Kebede,2 Adugna Woyessa,3 Yibeltal Assefa,3 Amha Kebede,3 Moges Kassa3 1Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, 2Biomedical Department, College of Health Sciences and Medicine, Dilla University, Dilla, 3Malaria and Other Parasitological and Entomological Research Team, Bacterial, Parasitic and Zoonotic Diseases Research Directorate, Ethiopian Public Health Institute, 4Malaria Research Team, Disease Prevention and Control Directorate, Federal Ministry of Health, Addis Ababa, Ethiopia Purpose: Following the increased Plasmodium falciparum resistance to chloroquine and sulfadoxine/pyrimethamine, Ethiopia adopted artemether/lumefantrine (AL as the first-line treatment for uncomplicated P. falciparum in 2004. According to the recommendation of the World Health Organization, this study was carried out for regular monitoring of the efficacy of AL in treating the uncomplicated P. falciparum malaria in Metema district, Gondar Zone, Northwest Ethiopia.Patients and methods: This is a one-arm prospective 28-day in vivo therapeutic efficacy study among the uncomplicated P. falciparum malaria patients aged 6 months and older. The study was conducted from October 2014 to January 2015, based on the revised World Health Organization protocol of 2009 for surveillance of antimalarial drug therapeutic efficacy study. Standard six-dose regimen of AL was given twice daily for 3 days, and then the treatment outcomes were assessed on days 0, 1, 2, 3, 7, 14, 21, 28, and any other unscheduled day for emergency cases.Results: There were 91 study subjects enrolled in this study, of whom 80 study subjects completed the full follow-up schedules and showed adequate clinical and parasitological responses on day 28, with no major adverse event. Per protocol analysis, the unadjusted
Bello, Shaibu O; Chika, Aminu; Abdulgafar, Jimoh O
The purpose of this study is to summarize the available data on the efficacy of Artesunate plus Amodiaquine (AS+AQ) versus Artemether -Lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in sub-Saharan Africa using uncorrected parasitaemia as a clinically relevant endpoint. Studies and conference abstracts identified through Pubmed, Medline, Embase, Ansinet, AJOL, Bioline, Cochrane Infectious Diseases Group trials register, The Cochrane Controlled Trials Register, Science Citation Index, Lilacs, African Index Medicus, Clusty, Google, Yahoo and Microsoft search engines. Randomized controlled clinical trials comparing Artesunate-Amodiaquine versus Artemether-Lumefantrine, in Sub-Saharan Africa from January 2004 to June 2009, and which had at least 30 patients per study arm. The authors independently applied the inclusion criteria, assessed methodological quality and extracted data into a predesigned form. The outcome of interest was uncorrected day 28 parasitological failure. Data were then checked for agreement and double entered into RevMan version 5 for further analyses. Fifteen trials (4265 participants) met the inclusion criteria. Day 28 parasitological failure was lower for AL (286 of 2201 participants or 13.0 % failures) when compared with AS+AQ (446 of 2424 participants or 18.4% failures). The relative risk of parasitological failure with AS+AQ was higher when compared with AL (RR 1.65, 95% CI, 1.18-2.32). There were significant heterogeneity and inconsistencies in the studies. AL appears more effective at avoiding parasitological failure at days 28 than AS+AQ.
Serge Brice Assi
Full Text Available The objective of this study was to monitor the effectiveness of artesunate-amodiaquine fixed-dose combination tablets (ASAQ Winthrop® in the treatment of uncomplicated Plasmodium falciparum malaria in Côte d’Ivoire. Two enrolment periods (November 2009 to May 2010 and March to October 2013 were compared using an identical design. Subjects with proven monospecific P. falciparum infection according to the WHO diagnostic criteria were eligible. 290 patients during each period received a dose of ASAQ Winthrop tablets appropriate for their age. The primary outcome measure was PCR-corrected adequate clinical and parasitological response at Day 28 in the per protocol population (255 in Period 1 and 240 in Period 2. This was achieved by 95.7% of patients during Period 1 and 96.3% during Period 2. Over 95% of patients were afebrile at Day 3 and complete parasite clearance was achieved at Day 3 in >99% of patients. Nineteen adverse events in nineteen patients were considered as possibly related to treatment, principally vomiting, abnormal liver function tests, and pruritus. There was no evidence for loss of effectiveness over the three-year period in spite of strong drug pressure. This trial was registered in the US Clinical Trials Registry (clinical.trials.gov under the identifier number NCT01023399.
Unlü, Cağdaş; de Korte, Niels; Daniels, Lidewine; Consten, Esther C. J.; Cuesta, Miguel A.; Gerhards, Michael F.; van Geloven, Anna A. W.; van der Zaag, Edwin S.; van der Hoeven, Joost A. B.; Klicks, Rutger; Cense, Huib A.; Roumen, Rudi M. H.; Eijsbouts, Quirijn A. J.; Lange, Johan F.; Fockens, Paul; de Borgie, Corianne A. J. M.; Bemelman, Wilem A.; Reitsma, Johannes B.; Stockmann, Hein B. A. C.; Vrouenraets, Bart C.; Boermeester, Marja A.
Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in
C.̧. Ünlü; N. de Korte (Niels); L. Daniels (Lidewine); E.C. Consten (Esther); M.A. Cuesta (Miguel); M.F. Gerhards (Michael); A.A. van Geloven (Anna); E.S. van der Zaag (Edwin); J.A.B. van der Hoeven (Joost); R. Klicks (Rutger); H.A. Cense (Huib); R.M. Roumen (Rudi); Q.A. Eijsbouts (Quirijn); J.F. Lange (Johan); P. Fockens (Paul); C.A. de Borgie (Corianne); W.A. Bemelman (Willem); J.B. Reitsma (Johannes); H.B.A.C. Stockmann; B.C. Vrouenraets (Bart); M.A. Boermeester (Marja)
textabstractBackground. Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are
Saavedra-Lozano, J; Calvo, C; Huguet Carol, R; Rodrigo, C; Núñez, E; Pérez, C; Merino, R; Rojo, P; Obando, I; Downey, F J; Colino, E; García, J J; Cilleruelo, M J; Torner, F; García, L
This is a Consensus Document of the Sociedad Española de Infectología Pediátrica, Sociedad Española de Reumatología Pediátrica and Sociedad Española de Ortopedia Pediátrica on the aetiology and diagnosis of uncomplicated acute osteomyelitis and septic arthritis. A review is presented of the aetiopathogenesis and pathophysiology of acute osteoarticular infection defined as a process with less than 14 days of symptomatology, uncomplicated, and community-acquired. The diagnostic approach to these conditions is summarised based on the best available scientific knowledge. Based on this evidence, a number of recommendations for clinical practice are provided. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Grigg, Matthew J; William, Timothy; Menon, Jayaram; Dhanaraj, Prabakaran; Barber, Bridget E; Wilkes, Christopher S; von Seidlein, Lorenz; Rajahram, Giri S; Pasay, Cielo; McCarthy, James S; Price, Ric N
Summary Background The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate–mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. Methods We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate–mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Findings Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate–mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76–91]) of 115 patients in the artesunate–mefloquine group versus 61 (55% [45–64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0–40·8]; pmefloquine than in those given chloroquine (18·0 h [range 6·0–48·0] vs 24·0 h [6·0–60·0]; pmefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9–9·4] vs 13·8 h [12·1–15·4]; pmefloquine group (71 [62%; 95% CI 52·2–70·6]) than in
Grigg, Matthew J; William, Timothy; Menon, Jayaram; Dhanaraj, Prabakaran; Barber, Bridget E; Wilkes, Christopher S; von Seidlein, Lorenz; Rajahram, Giri S; Pasay, Cielo; McCarthy, James S; Price, Ric N; Anstey, Nicholas M; Yeo, Tsin W
The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; pmefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; pmefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; pmefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035
Huston, Jared M; Kao, Lillian S; Chang, Phillip K; Sanders, James M; Buckman, Sara; Adams, Charles A; Cocanour, Christine S; Parli, Sarah E; Grabowski, Julia; Diaz, Jose; Tessier, Jeffrey M; Duane, Therese M
Acute appendicitis is the most common abdominal surgical emergency in the United States, with a lifetime risk of 7%-8%. The treatment paradigm for complicated appendicitis has evolved over the past decade, and many cases now are managed by broad-spectrum antibiotics. We determined the role of non-operative and operative management in adult patients with uncomplicated appendicitis. Several meta-analyses have attempted to clarify the debate. Arguably the most influential is the Appendicitis Acuta (APPAC) Trial. According to the non-inferiority analysis and a pre-specified non-inferiority margin of -24%, the APPAC did not demonstrate non-inferiority of antibiotics vs. appendectomy. Significantly, however, the operations were nearly always open, whereas the majority of appendectomies in the United States are done laparoscopically; and laparoscopic and open appendectomies are not equivalent operations. Treatment with antibiotics is efficacious more than 70% of the time. However, a switch to an antimicrobial-only approach may result in a greater probability of antimicrobial-associated collateral damage, both to the host patient and to antibiotic susceptibility patterns. A surgery-only approach would result in a reduction in antibiotic exposure, a consideration in these days of focus on antimicrobial stewardship. Future studies should focus on isolating the characteristics of appendicitis most susceptible to antibiotics, using laparoscopic operations as controls and identifying long-term side effects such as antibiotic resistance or Clostridium difficile colitis.
Sippola, S; Grönroos, J; Tuominen, R; Paajanen, H; Rautio, T; Nordström, P; Aarnio, M; Rantanen, T; Hurme, S; Salminen, P
An increasing amount of evidence supports antibiotic therapy for treating uncomplicated acute appendicitis. The objective of this study was to compare the costs of antibiotics alone versus appendicectomy in treating uncomplicated acute appendicitis within the randomized controlled APPAC (APPendicitis ACuta) trial. The APPAC multicentre, non-inferiority RCT was conducted on patients with CT-confirmed uncomplicated acute appendicitis. Patients were assigned randomly to appendicectomy or antibiotic treatment. All costs were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis during the 1-year follow-up. The cost estimates were based on cost levels for the year 2012. Some 273 patients were assigned to the appendicectomy group and 257 to antibiotic treatment. Most patients randomized to antibiotic treatment did not require appendicectomy during the 1-year follow-up. In the operative group, overall societal costs (€5989·2, 95 per cent c.i. 5787·3 to 6191·1) were 1·6 times higher (€2244·8, 1940·5 to 2549·1) than those in the antibiotic group (€3744·4, 3514·6 to 3974·2). In both groups, productivity losses represented a slightly higher proportion of overall societal costs than all treatment costs together, with diagnostics and medicines having a minor role. Those in the operative group were prescribed significantly more sick leave than those in the antibiotic group (mean(s.d.) 17·0(8·3) (95 per cent c.i. 16·0 to 18·0) versus 9·2(6·9) (8·3 to 10·0) days respectively; P antibiotic therapy for uncomplicated appendicitis incurred lower costs than those who had surgery. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.
Adam, Ishag; Ibrahim, Yassin; Gasim, Gasim I
Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan. The preferred reporting items for systematic review and meta-analysis statement were used to select studies to be included in this review. A computerized systematic strategy was adopted to search articles from PubMed, Google Scholar and Science Direct databases. Unpublished materials were also included. Open Meta-Analyst software was used to perform the meta-analysis. Random effects model was used to combine the included studies and the heterogeneity of studies was assessed using Cochrane Q and I 2 (χ 2 = 73.05, df (19), P < 0.001 and I 2 = 73.99). Twenty studies fulfilled the inclusion criteria (ACT in the treatment of uncomplicated falciparum malaria) and were included in the final analysis with a total number of 4070 participants. Malaria treatment outcome was assessed using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Treatment success of all combined studies was 98% [(95% CI 97.2-98.8%), P < 0.001]. Treatment success was higher in malaria patients treated with artemether + lumefantrine (AL) than patients treated with artesunate + sulfadoxine-pyrimethamine (AS + SP) (98.9% (95% CI 98.4-99.4%) vs 97.1% (95% CI 95.5-98.6%), P < 0.001). Eleven studies reported adverse drug reactions (ADRs) to ACT (184 participants out of 3957 (4.65%). The ADRs were mild and resolved spontaneously. There was no severe
Plucinski, Mateusz M; Dimbu, Pedro Rafael; Macaia, Aleixo Panzo; Ferreira, Carolina Miguel; Samutondo, Claudete; Quivinja, Joltim; Afonso, Marília; Kiniffo, Richard; Mbounga, Eliane; Kelley, Julia S; Patel, Dhruviben S; He, Yun; Talundzic, Eldin; Garrett, Denise O; Halsey, Eric S; Udhayakumar, Venkatachalam; Ringwald, Pascal; Fortes, Filomeno
Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013. During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1). A total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91-100) for AL in Benguela, 99.9% (95-100) for ASAQ in Benguela, 88.1% (81-95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96-100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility. No evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.
Chabok, Abbas; Andreasson, Kalle; Nikberg, Maziar
First-time acute uncomplicated diverticulitis (AUD) has been considered to have an increased risk of complication, but the level of evidence is low. The aim of the present study was to evaluate the risk of complications in patients with first-time AUD and in patients with a history of diverticulitis. This paper is a population-based retrospective study at Västmanland's Hospital, Västerås, Sweden, where all patients were identified with a diagnosis of colonic diverticular disease ICD-10 K57.0-9 from January 2010 to December 2014. The records of all patients were surveyed and patients with a computed tomography (CT)-verified AUD were included. Complications defined as CT-verified abscess, perforation, colonic obstruction, fistula, or sepsis within 1 month from the diagnosis of AUD were registered. Of 809 patients with AUD, 642 (79%) had first-time AUD and 167 (21%) had a previous history of AUD with no differences in demographic or clinical characteristics. In total, 16 (2%) patients developed a complication within 1 month irrespective of whether they had a previous history of diverticulitis (P = 0.345). In the binary logistic regression analysis, first-time diverticulitis was not associated with increased risk of complications (OR 1.58; CI 0.52-4.81). The rate of antibiotic therapy was about 7-10% during the time period and outpatient management increased from 7% in 2010 to 61% in 2014. The risk for development of complications is low in AUD with no difference between patients with first-time or recurrent diverticulitis. This result strengthens existing evidence on the benign disease course of AUD.
Cunha, B A; Cunha, C B; Lam, B; Giuga, J; Chin, J; Zafonte, V F; Gerson, S
Nitrofurantoin remains a key oral antibiotic stewardship program (ASP) option in the treatment of acute uncomplicated cystitis (AUC) due to multi-drug resistant (MDR) Gram negative bacilli (GNB). However, there have been concerns regarding decreased nitrofurantoin efficacy with renal insufficiency. In our experience over the past three decades, nitrofurantoin has been safe and effective in treating AUC in hospitalized adults with renal insufficiency. Accordingly, we retrospectively reviewed our recent experience treating AUC in hospitalized adults with decreased renal function (CrCl renal insufficiency (CrCl renal insufficiency, i.e., CrCl renal insufficiency (CrCl < 30 ml/ml).
Perisse, Anne; Velut, Guillaume; Javelle, Emilie; Loarer, Gwion; Michel, Remy; Simon, F
Malaria prevention and treatment are big challenges for the French forces deployed in sub-Saharan Africa. Since December 2013, 1,800 French soldiers have been deployed at any one time in the Central African Republic in the framework of "Operation Sangaris" and European Union Force (EUFOR). Over the 2014-2015 period, about 500 cases of malaria were notified in these troops during the operation or after their return (annual incidence: 13.4 p.100 person-year). The recommendation to use dihydroartemisinin-piperaquine (DHA-PQ) as the first-line treatment for French soldiers suffering from uncomplicated Plasmodium falciparum malaria in endemic areas is not always followed in practice in the field by French military general practitioners (GPs). We conduced a retrospective Knowledge-Attitude-Practice study by self-administered questionnaire, to all military French doctors who were in mission in Central African Republic from January 2014 to July 2015 to try to understand what were the reasons for the GP not to prescribe DHA-PQ on the field. Thirty-six GPs (53%) answered to the questionnaire. Eighty-three percent of them knew about the recommendation to use DHA-PQ for un uncomplicated Pf malaria. Fifty-eight percent had a favorable attitude toward DHA-PQ. The factors associated with the prescription of another drug (Atovaquone-proguanil) were: the habit (odds ratio [OR] 0.1, confidence interval (CI) 0-0.6], the fact that Atovaquone-proguanil is more practical to use [OR 0.01, CI 0-0.1]. In practice, only 37.5% prescribed DHA-PQ the most of the time during their mission. Factors associated with a non-favorable attitude toward DHA-PQ were: the necessity to calculate a QTc interval during the treatment [OR 0.2, confidence interval 0-0.9], and the fact that DHA-PQ must be taken on an empty stomach [OR 0.3, CI 0.1-0.8]. GP who received a formation before their mission about malaria and treatment had a favorable attitude toward DHA-PQ. There is very satisfactory knowledge by the
Ibrahium, A M; Kheir, M M; Osman, M E
Artemisinin-based combination therapy (ACT) is increasingly being adopted as the first-line treatment for malaria in sub-Saharan Africa. In September-November 2005, in New Halfa, eastern Sudan, the efficacy of artesunate-sulfadoxine-pyrimethamine (AS-SP) for the treatment of uncomplicated...... of uncomplicated, P. falciparum malaria in eastern Sudan....
Mårtensson, Andreas; Strömberg, Johan; Sisowath, Christin; Msellem, Mwinyi I; Gil, J Pedro; Montgomery, Scott M; Olliaro, Piero; Ali, Abdullah S; Björkman, Anders
This is the first clinical trial comparing the efficacy of artesunate plus amodiaquine (ASAQ) and artemether-lumefantrine (AL)--the major artemisinin-based combination therapy (ACT) candidates for treatment of malaria in Africa--that involved an extended, 42-day follow-up period, polymerase chain reaction-adjusted parasitological cure rates (PCR APCRs), and systematic analyses of genetic markers related to quinoline resistance. METHODS. A total of 408 children with uncomplicated Plasmodium falciparum malaria in Zanzibar, Tanzania, were enrolled. Children who were 6-8 months of age and/or who weighed 6-8 kg were assigned to receive ASAQ for 3 days. Children who were 9-59 months of age and who weighted > or =9 kg were randomly assigned to receive either ASAQ or AL for 3 days in standard doses. Intention-to-treat analyses were performed. Age- and weight-adjusted PCR-APCRs by follow-up day 42 were 91% (188 of 206 patients) in the ASAQ group and 94% (185 of 197 patients) in the AL group (odds ratio [OR] for the likelihood of cure, 2.07; 95% confidence interval [CI], 0.84-5.10; P=.115). A total of 5 and 7 recrudescences occurred after day 28 in the ASAQ and AL groups, respectively. On the assumption that 10 malaria episodes with uncertain PCR results were recrudescences, PCR-APCRs decreased to 88% in the ASAQ group and to 92% in the AL group. Unadjusted cure rates by day 42 were 56% (116 of 206 patients) in the ASAQ group versus 77% (151 of 197 patients) in the AL group (OR, 2.55; 95% CI, 1.66-3.91; P<.001). Rates of reinfection by day 42 were 36% (65 of 181 patients) in the ASAQ arm versus 17% (31 of 182 patients) in the AL arm (OR, 0.37; 95% CI, 0.22-0.60; P<.001). A significant selection of P. falciparum multidrug resistance gene 1 allele 86N was found in isolates associated with reinfection after AL treatment, compared with isolates at baseline (2.2-fold increase; P<.001). Both treatments were highly efficacious, but AL provided stronger prevention against
Koita, Ousmane A; Sangaré, Lansana; Miller, Haiyan D; Sissako, Aliou; Coulibaly, Moctar; Thompson, Trevor A; Fongoro, Saharé; Diarra, Youssouf; Ba, Mamadou; Maiga, Ababacar; Diallo, Boubakar; Mushatt, David M; Mather, Frances J; Shaffer, Jeffrey G; Anwar, Asif H; Krogstad, Donald J
Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per μL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 μL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for
A randomized, open-label, comparative efficacy trial of artemether-lumefantrine suspension versus artemether-lumefantrine tablets for treatment of uncomplicated Plasmodium falciparum malaria in children in western Kenya
Akhwale Willis S
Full Text Available Abstract Background Artemether/lumefantrine (AL has been adopted as the treatment of choice for uncomplicated malaria in Kenya and other countries in the region. Six-dose artemether/lumefantrine tablets are highly effective and safe for the treatment of infants and children weighing between five and 25 kg with uncomplicated Plasmodium falciparum malaria. However, oral paediatric formulations are urgently needed, as the tablets are difficult to administer to young children, who cannot swallow whole tablets or tolerate the bitter taste of the crushed tablets. Methods A randomized, controlled, open-label trial was conducted comparing day 28 PCR corrected cure-rates in 245 children aged 6–59 months, treated over three days with either six-dose of artemether/lumefantrine tablets (Coartem® or three-dose of artemether/lumefantrine suspension (Co-artesiane® for uncomplicated falciparum malaria in western Kenya. The children were followed-up with clinical, parasitological and haematological evaluations over 28 days. Results Ninety three percent (124/133 and 90% (121/134 children in the AL tablets and AL suspension arms respectively completed followed up. A per protocol analysis revealed a PCR-corrected parasitological cure rate of 96.0% at Day 28 in the AL tablets group and 93.4% in the AL suspension group, p = 0.40. Both drugs effectively cleared gametocytes and were well tolerated, with no difference in the overall incidence of adverse events. Conclusion The once daily three-dose of artemether-lumefantrine suspension (Co-artesiane® was not superior to six-dose artemether-lumefantrine tablets (Coartem® for the treatment of uncomplicated malaria in children below five years of age in western Kenya. Trial registration ClinicalTrials.gov NCT00529867
Lavingia, Kedar S; Larion, Sebastian; Larion, Sebastion; Ahanchi, Sadaf S; Ammar, Chad P; Bhasin, Mohit; Mirza, Aleem K; Dexter, David J; Panneton, Jean M
Our objective was to characterize the predictive impact of computed tomography (CT) scan volumetric analysis on the natural history of acute uncomplicated type B aortic dissections (ADs). We conducted a retrospective review of patients with acute type B ADs from 2009 to 2014. On an iNtuition workstation (TeraRecon, Foster City, Calif), volume measurements were obtained using the true lumen volume (TLV), false lumen volume (FLV), and total aortic volume from the left subclavian artery to the celiac artery. Growth rate was calculated as the change in maximal diameter between first and last available CT scans during the time interval. The primary outcome of the study was delayed aortic intervention. P 14 days) thoracic endovascular aneurysm repair (29) or open repair (3). Mean age was 66 ± 12 years. Mean TLV/FLV ratio on initial CT scan was significantly higher in patients who did not eventually require an operation (1.55 vs 0.82; P = .02). The mean growth rate was higher in those eventually requiring operation (2.47 vs 0.42 mm/mo; P = .003). Patients were divided into three subgroups on the basis of their initial imaging TLV/FLV ratios (1.6). There was a significant difference in the growth rates between these three groups (4.6 vs 2.4 vs 0.8 mm/mo; P 1.6 was highly predictive for freedom from delayed operation (sensitivity, 91%; specificity, 42%; positive predictive value, 61%; negative predictive value, 86%). After Kaplan-Meier analysis, 1-year and 2-year survival free of aortic interventions was 60% and 42% with a TLV/FLV ratio 1.6 (P = .001). Initial CT scan volumetric analysis in patients presenting with uncomplicated acute type B ADs is a useful tool to predict growth and need for future intervention. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
Daniels, L; Ünlü, Ç; de Korte, N; van Dieren, S; Stockmann, H B; Vrouenraets, B C; Consten, E C; van der Hoeven, J A; Eijsbouts, Q A; Faneyte, I F; Bemelman, W A; Dijkgraaf, M G; Boermeester, M A
Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. Patients with CT-proven, primary, left-sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy. The primary endpoint was time to recovery during 6 months of follow-up. Main secondary endpoints were readmission rate, complicated, ongoing and recurrent diverticulitis, sigmoid resection and mortality. Intention-to-treat and per-protocol analyses were done. A total of 528 patients were included. Median time to recovery was 14 (i.q.r. 6-35) days for the observational and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0·91 (lower limit of 1-sided 95 per cent c.i. 0·78; P = 0·151). No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3·8 versus 2·6 per cent respectively; P = 0·377), ongoing diverticulitis (7·3 versus 4·1 per cent; P = 0·183), recurrent diverticulitis (3·4 versus 3·0 per cent; P = 0·494), sigmoid resection (3·8 versus 2·3 per cent; P = 0·323), readmission (17·6 versus 12·0 per cent; P = 0·148), adverse events (48·5 versus 54·5 per cent; P = 0·221) and mortality (1·1 versus 0·4 per cent; P = 0·432). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006). Per-protocol analyses were concordant with the intention-to-treat analyses. Observational treatment without antibiotics did not prolong recovery and can be considered appropriate in patients with uncomplicated diverticulitis. Registration number: NCT01111253 (http://www.clinicaltrials.gov). © 2016 BJS Society Ltd Published by John
Hames, Leesa; Rice, Craig E.
Objective and Participants: The authors of this retrospective case study focused on antimicrobial susceptibility of urinary tract isolates in cases of acute uncomplicated cystitis in college-aged women, aged 18 to 24 years, diagnosed at a major south-central university student health center. Methods: The authors obtained pertinent data from…
Huang, Chenxi; Alamili, Mahdi; Nielsen, Claus Henrik
. Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during...... was reduced 4% and 7% the first (p = 0.006) and second (p = 0.014) nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016), compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid...... eye movement sleep and fatigue. Conclusion. Total sleep time and rapid eye movement sleep were reduced during nights with active diverticulitis and correlated with markers of inflammation....
Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C
. However, there is no information to date, on the efficacy or safety of artemisinin combination therapy when used for malaria treatment in SCD patients. METHODS: Children with SCD and acute uncomplicated malaria (n = 60) were randomized to treatment with artesunate-amodiaquine (AA), or artemether......-lumefantrine (AL). A comparison group of non-SCD children (HbAA genotype; n = 59) with uncomplicated malaria were also randomized to treatment with AA or AL. Recruited children were followed up and selected investigations were done on days 1, 2, 3, 7, 14, 28, 35, and 42. Selected clinical and laboratory parameters...
Looareesuwan, S; Wilairatana, P; Chalermarut, K; Rattanapong, Y; Canfield, C J; Hutchinson, D B
The increasing frequency of therapeutic failures in falciparum malaria underscores the need for novel, rapidly effective antimalarial drugs or drug combinations. Atovaquone and proguanil are blood schizonticides that demonstrate synergistic activity against multi-drug-resistant Plasmodium falciparum in vitro. In an open-label, randomized, controlled clinical trial conducted in Thailand, adult patients with acute P. falciparum malaria were randomly assigned to treatment with atovaquone and proguanil/hydrochloride (1,000 mg and 400 mg, respectively, administered orally at 24-hr intervals for three doses) or mefloquine (750 mg administered orally, followed 6 hr later by an additional 500-mg dose). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was assessed by sequential clinical and laboratory assessments for 28 days. Atovaquone/proguanil was significantly more effective than mefloquine (cure rate 100% [79 of 79] vs. 86% [68 of 79]; P proguanil and mefloquine treatments did not differ with respect to PCT (mean = 65 hr versus 74 hr) or FCT (mean = 59 hr versus 51 hr). Adverse events were generally typical of malaria symptoms and each occurred in proguanil group. Transient elevations of liver enzyme levels occurred more frequently in patients treated with atovaquone/proguanil than with mefloquine, but the differences were not significant and values returned to normal by day 28 in most patients. The combination of atovaquone and proguanil was well tolerated and more effective than mefloquine in the treatment of acute uncomplicated multidrug-resistant falciparum malaria in Thailand.
Niang, Makhtar; Thiam, Laty Gaye; Sow, Abdourahmane; Loucoubar, Cheikh; Bob, Ndeye Sakha; Diop, Fode; Diouf, Babacar; Niass, Oumy; Mansourou, Annick; Varela, Marie Louise; Perraut, Ronald; Sall, Amadou A; Toure-Balde, Aissatou
Control efforts towards malaria due to Plasmodium falciparum significantly decreased the incidence of the disease in many endemic countries including Senegal. Surprisingly, in Kedougou (southeastern Senegal) P. falciparum malaria remains highly prevalent and the relative contribution of other Plasmodium species to the global malaria burden is very poorly documented, partly due to the low sensitivity of routine diagnostic tools. Molecular methods offer better estimate of circulating Plasmodium species in a given area. A molecular survey was carried out to document circulating malaria parasites in Kedougou region. A total of 263 long-term stored sera obtained from patients presenting with acute febrile illness in Kedougou between July 2009 and July 2013 were used for malaria parasite determination. Sera were withdrawn from a collection established as part of a surveillance programme of arboviruses infections in the region. Plasmodium species were characterized by a nested PCR-based approach targeting the 18S small sub-unit ribosomal RNA genes of Plasmodium spp. Of the 263 sera screened in this study, Plasmodium genomic DNA was amplifiable by nested PCR from 62.35% (164/263) of samples. P. falciparum accounted for the majority of infections either as single in 85.97% (141/164) of Plasmodium-positive samples or mixed with Plasmodium ovale (11.58%, 19/164) or Plasmodium vivax (1.21%, 2/164). All 19 (11.58%) P. ovale-infected patients were mixed with P. falciparum, while no Plasmodium malariae was detected in this survey. Four patients (2.43%) were found to be infected by P. vivax, two of whom were mixed with P. falciparum. P. vivax infections originated from Bandafassi and Ninefesha villages and concerned patients aged 4, 9, 10, and 15 years old, respectively. DNA sequences alignment and phylogenetic analysis demonstrated that sequences from Kedougou corresponded to P. vivax, therefore confirming the presence of P. vivax infections in Senegal. The results confirm the
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.
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
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.
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
Full Text Available The Republic of the Congo adopted artemisinin-based combination therapies (ACTs in 2006: artesunate-amodiaquine and artemether-lumefantrine as the first-line and second-line drugs, respectively. The baseline efficacy of artemether-lumefantrine was evaluated between March and July 2006 in Brazzaville, the capital city of Congo. Seventy-seven children aged between 6 months and 10 years were enrolled in a nonrandomized study. The children were treated under supervision with 6 doses of artemether-lumefantrine and followed up for 28 days in accordance with the 2003 World Health Organization guideline. Pretreatment (i.e., day 0 and recrudescent Plasmodium falciparum isolates between day 14 and day 28 were compared by the polymerase chain reaction to distinguish between true recrudescence and reinfection. The overall cure rate on day 28 was 96.9% after PCR correction. Reported adverse effects included pruritus and dizziness. Artemether-lumefantrine was highly efficacious in Brazzaville.
Full Text Available Introduction. Sleep disturbances are commonly found in patients in the postoperative period. Sleep disturbances may give rise to several complications including cardiopulmonary instability, transient cognitive dysfunction and prolonged convalescence. Many factors including host inflammatory responses are believed to cause postoperative sleep disturbances, as inflammatory responses can alter sleep architecture through cytokine-brain interactions. Our aim was to investigate alteration of sleep architecture during acute infection and its relationships to inflammation and clinical symptoms.Materials & Methods. In this observational study, we included patients with acute uncomplicated diverticulitis as a model to investigate the isolated effects of inflammatory responses on sleep. Eleven patients completed the study. Patients were admitted and treated with antibiotics for two nights, during which study endpoints were measured by polysomnography recordings, self-reported discomfort scores and blood samples of cytokines. One month later, the patients, who now were in complete remission, were readmitted and the endpoints were re-measured (the baseline values.Results. Total sleep time was reduced 4% and 7% the first (p = 0.006 and second (p = 0.014 nights of diverticulitis, compared to baseline, respectively. The rapid eye movement sleep was reduced 33% the first night (p = 0.016, compared to baseline. Moreover, plasma IL-6 levels were correlated to non-rapid eye movement sleep, rapid eye movement sleep and fatigue.Conclusion. Total sleep time and rapid eye movement sleep were reduced during nights with active diverticulitis and correlated with markers of inflammation.
Boermeester, Marja A.; Humes, David J.; Velmahos, George C.; Søreide, Kjetil
Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the
Varadhan, Krishna K; Neal, Keith R
Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis. PMID:22491789
D'Abramo, Alessandra; Gebremeskel Tekle, Saba; Iannetta, Marco; Scorzolini, Laura; Oliva, Alessandra; Paglia, Maria Grazia; Corpolongo, Angela; Nicastri, Emanuele
Although Plasmodium ovale is considered the cause of only mild malaria, a case of severe malaria due to P. ovale with acute respiratory distress syndrome is reported. A 37-year old Caucasian man returning home from Angola was admitted for ovale malaria to the National Institute for Infectious Diseases Lazzaro Spallanzani in Rome, Italy. Two days after initiation of oral chloroquine treatment, an acute respiratory distress syndrome was diagnosed through chest X-ray and chest CT scan with intravenous contrast. Intravenous artesunate and oral doxycycline were started and he made a full recovery. Ovale malaria is usually considered a tropical infectious disease associated with low morbidity and mortality. However, severe disease and death have occasionally been reported. In this case clinical failure of oral chloroquine treatment with clinical progression towards acute respiratory distress syndrome is described.
Piola, Patrice; Nabasumba, Carolyn; Turyakira, Eleanor; Dhorda, Mehul; Lindegardh, Niklas; Nyehangane, Dan; Snounou, Georges; Ashley, Elizabeth A; McGready, Rose; Nosten, Francois; Guerin, Philippe J
Malaria in pregnancy is associated with maternal and fetal morbidity and mortality. In 2006, WHO recommended use of artemisinin-based combination treatments during the second or third trimesters, but data on efficacy and safety in Africa were scarce. We aimed to assess whether artemether-lumefantrine was at least as efficacious as oral quinine for the treatment of uncomplicated falciparum malaria during the second and third trimesters of pregnancy in Mbarara, Uganda. We did an open-label, randomised, non-inferiority trial between October, 2006, and May, 2009, at the antenatal clinics of the Mbarara University of Science and Technology Hospital in Uganda. Pregnant women were randomly assigned (1:1) by computer generated sequence to receive either quinine hydrochloride or artemether-lumefantrine, and were followed up weekly until delivery. Our primary endpoint was cure rate at day 42, confirmed by PCR. The non-inferiority margin was a difference in cure rate of 5%. Analysis of efficacy was for all randomised patients without study deviations that could have affected the efficacy outcome. This study was registered with ClinicalTrials.gov, number NCT00495508. 304 women were randomly assigned, 152 to each treatment group. By day 42, 16 patients were lost to follow-up and 25 were excluded from the analysis. At day 42, 137 (99.3%) of 138 patients taking artemether-lumefantrine and 122 (97.6%) of 125 taking quinine were cured-difference 1.7% (lower limit of 95% CI -0.9). There were 290 adverse events in the quinine group and 141 in the artemether-lumefantrine group. Artemisinin derivatives are not inferior to oral quinine for the treatment of uncomplicated malaria in pregnancy and might be preferable on the basis of safety and efficacy. Médecins Sans Frontières and the European Commission. Copyright © 2010 Elsevier Ltd. All rights reserved.
Comparison of artesunate-mefloquine and artemether-lumefantrine fixed-dose combinations for treatment of uncomplicated Plasmodium falciparum malaria in children younger than 5 years in sub-Saharan Africa: a randomised, multicentre, phase 4 trial.
Sirima, Sodiomon B; Ogutu, Bernhards; Lusingu, John P A; Mtoro, Ali; Mrango, Zakayo; Ouedraogo, Alphonse; Yaro, Jean Baptiste; Onyango, Kevin Omondi; Gesase, Samwel; Mnkande, Ernest; Ngocho, James Samwel; Ackermann, Isabelle; Aubin, François; Vanraes, Joelle; Strub, Nathalie; Carn, Gwenaelle
WHO recommends combinations of an artemisinin derivative plus an antimalarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infection. In Africa, artemether-lumefantrine is the most widely used artemisinin-based combination therapy, whereas artesunate-mefloquine is used infrequently because of a perceived poor tolerance to mefloquine. WHO recommends reconsideration of the use of artesunate-mefloquine in Africa. We compared the efficacy and safety of fixed-dose artesunate-mefloquine with that of artemether-lumefantrine for treatment of children younger than 5 years with uncomplicated P falciparum malaria. We did this multicentre, phase 4, open-label, non-inferiority trial in Burkina Faso, Kenya, and Tanzania. Children aged 6-59 months with uncomplicated malaria were randomly assigned (1:1), via a computer-generated randomisation list, to receive 3 days' treatment with either one or two artesunate-mefloquine tablets (25 mg artesunate and 55 mg mefloquine) once a day or one or two artemether-lumefantrine tablets (20 mg artemether and 120 mg lumefantrine) twice a day. Parasitological assessments were done independently by two microscopists who were blinded to treatment allocation. The primary outcome was the PCR-corrected rate of adequate clinical and parasitological response (ACPR) at day 63 in the per-protocol population. Non-inferiority was shown if the lower limit of the 95% CI for the difference between groups was greater than -5%. Early vomiting was monitored and neuropsychiatric status assessed regularly during follow-up. This study is registered with ISRCTN, number ISRCTN17472707, and the Pan African Clinical Trials Registry, number PACTR201202000278282. 945 children were enrolled and randomised, 473 to artesunate-mefloquine and 472 to artemether-lumefantrine. The per-protocol population consisted of 407 children in each group. The PCR-corrected ACPR rate at day 63 was 90·9% (370 patients) in the artesunate
Mohamed, Abdelrahim O; Abdel Hamid, Muzamil M; Mohamed, Omer S; Elkando, Nuha S; Suliman, Abdelmaroof; Adam, Mariam A; Elnour, Fahad Awad Ali; Malik, Elfatih M
Artemisinin-based combination therapy (ACT), together with other control measures, have reduced the burden of falciparum malaria in sub-Saharan countries, including Sudan. Sudan adopted ACT in 2004 with a remarkable reduction in mortality due to falciparum malaria. However, emergence of resistance to the first-line treatment artesunate and sulfadoxine/pyrimethamine (AS/SP) has created new challenges to the control of malaria in Sudan. A search for an alternative drug of choice for treating uncomplicated malaria has become inevitable. The objective of this study was to evaluate the therapeutic efficacies of dihydroartemisinin/piperaquine (DHA-PPQ) and AS/SP in an area of unstable transmission in Blue Nile State, Sudan in 2015-16. A total of 148 patients with uncomplicated malaria were recruited in the study from November 2015 to end of January 2016. Seventy-five patients received DHA-PPQ while 73 received AS/SP. Patients were monitored for clinical and parasitological outcomes following the standard WHO protocol for a period of 42 days for DHA-PPQ and 28 days for AS/SP; nested PCR (nPCR) was performed to confirm parasite re-appearance from day 7 onwards. Fifty-five patients completed the DHA-PPQ arm protocol with success cure rate of 98.2% (95% CI 90.3-100%) and one late clinical failure 1.8% (95% CI 0.0-9.7%). The AS/SP showed adequate clinical and parasitological response (ACPR) of 83.6% (95% CI 71.9-91.8%), early treatment failure was 1.6% (95% CI 0.0-8.8%) and late parasitological failure (LPF) was 14.8% (95% CI 7-26.2%). The respective PCR uncorrected LPF was 20%. DHA-PPQ is an efficacious ACT and candidate for replacement of first-line treatment in Sudan while AS/SP showed high treatment failure rate and must be replaced.
Kamman, Arnoud V; Brunkwall, Jan; Verhoeven, Eric L
BACKGROUND: The high-risk patient cohort of uncomplicated type B aortic dissections (uTBADs) needs to be clarified. We compared uTBAD patients treated with best medical treatment (BMT), with and without aortic growth, from the Acute Dissection Stent Grafting or Best Medical Treatment (ADSORB) trial...... database. Furthermore, we looked for trends in outcome for aortic growth and remodeling after BMT and thoracic endovascular aortic repair (TEVAR) and BMT (TEVAR+BMT). METHODS: BMT patients with available baseline and a 1-year follow-up arterial computed tomography scan were identified. True lumen and false...
Kayumba, P C; Twagirumukiza, M; Huyghebaert, N; Ntawukuliryayo, J D; van Bortel, L; Vervaet, C; Remon, J P
Quinine sulphate (QS), like most other antimalarials, is in tablet form designed for adults. In children, treatment is based on breaking the tablets to adapt the dose to the child's bodyweight. However, poor breakability owing to the tablet design or the absence of a score line can lead to inaccurate dosage. Furthermore, QS is very bitter which reduces its acceptability to children. QS taste-masked pellets have been developed which offer more flexibility in adapting dosage to a child's weight. To evaluate the oral bio-availability of QS taste-masked pellets in healthy adult volunteers and to determine steady-state plasma concentrations in children aged available tablets. A total of 56 children <5 years with uncomplicated P. falciparum malaria were recruited among patients attending Butare University Hospital and nearby health centres and treated with QS taste-masked pellets, 10-12.5 mg/kg every 8 h for 7 days. Quinine steady-state plasma concentrations were assessed on the 4th day of treatment. Following administration of taste-masked pellets to healthy adult volunteers, peak plasma concentration (C(max)) and area-under-the-curve (AUC) (C(max) 4.7 microg x ml(-1), AUC(0-24) 63.5 microg x h x ml(-1)) were significantly higher (p<0.05) than for tablets (C(max) 3.7 microg x ml(-1), AUC(0-24) 52.4 microg x h x ml(-1)), but still within the limits reported for quinine. The steady-state concentrations in children were in the therapeutic range for quinine. All the children recovered and completed the 14-day follow-up. QS taste-masked pellets offered the possibility to easily adjust the dose to the bodyweight of the child and can be used as an alternative to dividing tablets.
Full Text Available Abstract Background The aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt, multidrug resistance 1 (pfmdr1, dihydrofolate reductase (pfdhfr, dihydropteroate synthase (pfdhps and ATPase (pfatp6 genes. Methods Patients ≥ one year of age with fever (axillary temperature ≥37.5°C or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction. Results Sixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%, and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246 was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164, and mutations in pfdhps (codons 436, 437, 540 and 581 were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K were found in 4.6% and 9.2% of parasite isolates, respectively. Conclusion Plasmodium
Adjei, George O; Goka, Bamenla Q; Kitcher, Emmanuel
Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs) with hearing...... is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n = 37), artemether-lumefantrine (n = 35), or amodiaquine (n = 8) in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared...... evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels...
Giesen, Leonie GM
Abstract Background Acute urinary tract infections (UTI) are one of the most common bacterial infections among women presenting to primary care. However, there is a lack of consensus regarding the optimal reference standard threshold for diagnosing UTI. The objective of this systematic review is to determine the diagnostic accuracy of symptoms and signs in women presenting with suspected UTI, across three different reference standards (102 or 103 or 105 CFU\\/ml). We also examine the diagnostic value of individual symptoms and signs combined with dipstick test results in terms of clinical decision making. Methods Searches were performed through PubMed (1966 to April 2010), EMBASE (1973 to April 2010), Cochrane library (1973 to April 2010), Google scholar and reference checking. Studies that assessed the diagnostic accuracy of symptoms and signs of an uncomplicated UTI using a urine culture from a clean-catch or catherised urine specimen as the reference standard, with a reference standard of at least ≥ 102 CFU\\/ml were included. Synthesised data from a high quality systematic review were used regarding dipstick results. Studies were combined using a bivariate random effects model. Results Sixteen studies incorporating 3,711 patients are included. The weighted prior probability of UTI varies across diagnostic threshold, 65.1% at ≥ 102 CFU\\/ml; 55.4% at ≥ 103 CFU\\/ml and 44.8% at ≥ 102 CFU\\/ml ≥ 105 CFU\\/ml. Six symptoms are identified as useful diagnostic symptoms when a threshold of ≥ 102 CFU\\/ml is the reference standard. Presence of dysuria (+LR 1.30 95% CI 1.20-1.41), frequency (+LR 1.10 95% CI 1.04-1.16), hematuria (+LR 1.72 95%CI 1.30-2.27), nocturia (+LR 1.30 95% CI 1.08-1.56) and urgency (+LR 1.22 95% CI 1.11-1.34) all increase the probability of UTI. The presence of vaginal discharge (+LR 0.65 95% CI 0.51-0.83) decreases the probability of UTI. Presence of hematuria has the highest diagnostic utility, raising the post-test probability of
Full Text Available Abstract Background Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days. II A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time
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.
Chêne, Arnaud; Nylén, Susanne; Donati, Daria; Bejarano, Maria Teresa; Kironde, Fred; Wahlgren, Mats; Falk, Kerstin I.
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. PMID:22039454
Objectives. To assess therapeutic efficacy of sulfadoxineyrimethamine (SP) in treatment of uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga, South Africa. Se'tting. Tonga district with a population of 116 418 and subject to seasonal malaria, with an average annual incidence ; 3 200 ...
George O. Adjei
Full Text Available Background. Plasmodium falciparum malaria, as well as certain antimalarial drugs, is associated with hearing impairment in adults. There is little information, however, on the extent, if any, of this effect in children, and the evidence linking artemisinin combination therapies (ACTs with hearing is inconclusive. Methods. Audiometry was conducted in children with uncomplicated malaria treated with artesunate-amodiaquine (n=37, artemether-lumefantrine (n=35, or amodiaquine (n=8 in Accra, Ghana. Audiometry was repeated 3, 7, and 28 days later and after 9 months. Audiometric thresholds were compared with those of a control group of children (n=57 from the same area. Findings. During the acute stage, hearing threshold levels of treated children were significantly elevated compared with controls (P<0.001. The threshold elevations persisted up to 28 days, but no differences in hearing thresholds were evident between treated children and controls after 9 months. The hearing thresholds of children treated with the two ACT regimens were comparable but lower than those of amodiaquine-treated children during acute illness. Interpretation. Malaria is the likely cause of the elevated hearing threshold levels during the acute illness, a finding that has implications for learning and development in areas of intense transmission, as well as for evaluating potential ototoxicity of new antimalarial drugs.
Artemisinin-Based Combination Therapy Versus Quinine or Other Combinations for Treatment of Uncomplicated Plasmodium falciparum Malaria in the Second and Third Trimester of Pregnancy: A Systematic Review and Meta-Analysis
Burger, Renée J.; van Eijk, Anna M.; Bussink, Milena; Hill, Jenny; ter Kuile, Feiko O.
The World Health Organization recommends artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated falciparum malaria in the second and third trimesters of pregnancy. We conducted a meta-analysis to compare efficacy, safety and tolerability of ACTs versus quinine and other
Kurtzhals, J A; Reimert, C M; Tette, E
To assess the eosinophil response to Plasmodium falciparum infection a cohort of initially parasite-free Ghanaian children was followed for 3 months. Seven of nine children who acquired an asymptomatic P. falciparum infection showed increase in eosinophil counts, while a decrease was found in sev...
Shabanzadeh, Daniel M; Wille-Jørgensen, Peer
Diverticulitis is an inflammatory complication to the very common condition diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics with reference to the microbiology, extrapolation from trials on complicated intra-abdominal infections and clinical experience....
Surowiec, Izabella; Gouveia-Figueira, Sandra; Orikiiriza, Judy; Lindquist, Elisabeth; Bonde, Mari; Magambo, Jimmy; Muhinda, Charles; Bergström, Sven; Normark, Johan; Trygg, Johan
Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism. Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA ® ) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis). Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB 2 ) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins
Antibiotics-first strategy for uncomplicated acute appendicitis in adults is associated with increased rates of peritonitis at surgery. A systematic review with meta-analysis of randomized controlled trials comparing appendectomy and non-operative management with antibiotics.
Podda, Mauro; Cillara, Nicola; Di Saverio, Salomone; Lai, Antonio; Feroci, Francesco; Luridiana, Gianluigi; Agresta, Ferdinando; Vettoretto, Nereo
Acute appendicitis is the most common surgical diagnosis in young patients, with lifetime prevalence of about 7%. Debate remains on whether uncomplicated AA should be operated or not. Aim of this meta-analysis of randomized controlled trials was to assess current evidence on antibiotic treatment for uncomplicated AA compared to standard surgical treatment. Systematic literature search was performed using PubMed, EMBASE, Medline, Google Scholar and Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing antibiotic therapy (AT) and surgical therapy-appendectomy (ST) for uncomplicated AA. Trials were reviewed for primary outcome measures: treatment efficacy based on 1 year follow-up, recurrence at 1 year follow-up, complicated appendicitis with peritonitis identified at the time of surgical operation and post-intervention complications. Secondary outcomes were length of hospital stay and period of sick leave. Five RCTs comparing AT and ST qualified for inclusion in meta-analysis, with 1.351 patients included: 632 in AT group and 719 in ST group. Higher rate of treatment efficacy based on 1 year follow-up was found in ST group (98.3% vs 75.9%, P appendicitis with peritonitis identified at time of surgical operation was higher in AT group (19.9% vs 8.5%, P = 0.02). No statistically significant differences were found when comparing AT and ST groups for the outcomes of overall post-intervention complications (4.3% vs 10.9%, P = 0.32), post-intervention complications based on the number of patients who underwent appendectomy (15.8% vs 10.9%, P = 0.35), length of hospital stay (3.24 ± 0.40 vs 2.88 ± 0.39, P = 0.13) and period of sick leave (8.91 ± 1.28 vs 10.27 ± 0.24, P = 0.06). With significantly higher efficacy and low complication rates, appendectomy remains the most effective treatment for patients with uncomplicated AA. The subgroups of patients with uncomplicated AA where antibiotics can be more
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
Ursing, Johan; Rombo, Lars; Rodrigues, Amabelia
to children aged 6 months-15 years with uncomplicated P. falciparum mono-infection. Intake was observed and AL was given with milk. Children were seen on days 0, 1, 2 and 3 and then weekly days 7-42. Recurring P. falciparum were classified as recrudescence or new infections by genotyping. Between November...... 2012 and July 2015, 312 children were randomised to AL (n = 155) or DP (n = 157). The day 42 PCR adjusted per protocol adequate clinical and parasitological responses were 95% and 100% in the AL and DP groups respectively, Mantel-Haenszel weighted odds ratio (OR) 0.22 (95% CI 0-0.68), p = 0...... an alternative second line antimalarial. Dihydroartemisinin-piperaquine (DP) was chosen as it has been shown to be safe and efficacious and to reduce the incidence of recurrent malaria. METHODS AND FINDINGS: In a multicentre randomised open-label non-inferiority clinical trial, AL or DP were given over 3 days...
Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi
In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Wolff, Bruce G; Boostrom, Sarah Y
The classifications of acute uncomplicated diverticulitis and complicated diverticulitis have served us well for many years. However, in recent years, we have noted the prevalence of variations of uncomplicated diverticulitis, which have not precisely fit under the classification of 'acute resolving uncomplicated diverticulitis', which manifests itself with the typical left lower quadrant pain, fever, diarrhea, elevated white blood count, and CT findings, such as stranding, and which resolves fairly promptly and completely on oral antibiotic therapy. For these other variations, we would suggest we use the term chronic diverticulitis, as a subset of uncomplicated diverticulitis, meaning there is no abscess, stricture, or fistula, but the episode does not respond to the usual antibiotic treatment, and there is a rebound symptomatology once the treatment has stopped, or there is continuing subliminal inflammation that continues, typically, for several weeks after the initial episode without complete resolution. This variation could also be termed 'smoldering' diverticulitis. A second variation of uncomplicated diverticulitis should be termed atypical diverticulitis, since this variant does not manifest all of the usual components of acute diverticulitis, particularly an absence of fever, and even white blood count elevation, and there may be a lack of diagnostic evidence of acute diverticulitis. This diagnosis must be compared with diarrhea-predominant irritable bowel syndrome, and it is sometimes very difficult to distinguish between these two entities. The character of the pain in irritable bowel syndrome is typically cramping intermittently, compared with the more constant pain in smoldering diverticulitis. In our study by Horgan, McConnell, Wolff and coworkers, 5% of 930 patients who underwent sigmoid resection fit into this category of atypical uncomplicated diverticulitis. These 47 patients all had diverticulosis, and 76% that had surgery had evidence of acute
Ringwald, Pascal; Meche, Fleurette Solange; Bickii, Jean; Basco, Leonardo K.
The short-term in vitro growth of Plasmodium falciparum parasites in the asexual erythrocytic stage and the in vitro activities of eight standard antimalarial drugs were assessed and compared by using RPMI 1640 medium supplemented with 10% nonimmune human serum, 10% autologous or homologous acute-phase serum, or 0.5% Albumax I (lipid-enriched bovine serum albumin). In general, parasite growth was maximal with autologous (or homologous) serum, followed by Albumax I and nonimmune serum. The 50% inhibitory concentrations (IC50s) varied widely, depending on the serum or serum substitute. The comparison of IC50s between assays with autologous and nonimmune sera showed that monodesethylamodiaquine, halofantrine, pyrimethamine, and cycloguanil had similar IC50s. Although the IC50s of chloroquine, monodesethylamodiaquine, and dihydroartemisinin were similar with Albumax I and autologous sera, the IC50s of all test compounds obtained with Albumax I differed considerably from the corresponding values obtained with nonimmune serum. Our results suggest that Albumax I and autologous and homologous sera from symptomatic, malaria-infected patients may be useful alternative sources of serum for in vitro culture of P. falciparum isolates in the field. However, autologous sera and Albumax I do not seem to be suitable for the standardization of isotopic in vitro assays for all antimalarial drugs. PMID:9986835
Hviid, L; Theander, T G; Abu-Zeid, Y A
transmission season 5 months prior to the attack, were included in the study. Lymphoproliferative responsiveness to purified soluble malarial antigens and to the unrelated antigen PPD was lost during the acute phase of the disease in most donors, but was regained during convalescence, except in four donors...... 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...
Baswin, A.; Siregar, M. L.; Jamil, K. F.
P. falciparum-induced severe malaria with life-threatening complications like acute kidney injury (AKI), jaundice, cerebral malaria, severe anemia, acidosis, and acute respiratory distress syndrome (ARDS). A 31-year-old soldier man who works in Aceh Singkil, Indonesia which is an endemic malaria area presented with a paroxysm of fever, shaking chills and sweats over four days, headache, arthralgia, abdominal pain, pale, jaundice, and oliguria. Urinalysis showed hemoglobinuria. Blood examination showed hemolytic anemia, thrombocytopenia, and hyperbilirubinemia. Falciparum malaria was then confirmed by peripheral blood smear, antimalarial medications were initiated, and hemodialysis was performed for eight times. The patient’s condition and laboratory results were quickly normalized. We report a case of P. falciparum-induced severe malaria with AKI and jaundice. The present case suggests that P. falciparum may induce severe malaria with life-threatening complications, early diagnosis and treatment is important to improve the quality of life of patients. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history in endemic areas.
Touray, Sunkaru; Bâ, Hampâté; Bâ, Ousmane; Koïta, Mohamedou; Salem, Cheikh B Ould Ahmed; Keïta, Moussa; Traoré, Doulo; Sy, Ibrahima; Winkler, Mirko S; Utzinger, Jürg; Cissé, Guéladio
The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While "malaria cases" are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures). Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea), new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures. We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season), assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6-59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children. No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker. Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory infections and diarrhea were highly prevalent. Surveys should be repeated
Results of a randomized, prospective, double-dummy, double-blind trial to compare efficacy and safety of a herbal combination containing Tropaeoli majoris herba and Armoraciae rusticanae radix with co-trimoxazole in patients with acute and uncomplicated cystitis
Full Text Available Rainer Stange,1 Berthold Schneider,2 Uwe Albrecht,3 Valentina Mueller,3 Joerg Schnitker,4 Andreas Michalsen1 1Internal and Complementary Medicine, Immanuel Krankenhaus Berlin-Wannsee, Berlin, 2Institute for Biostatistics, Medical University, 3Mediconomics GmbH, Hannover, 4Institute for Applied Statistics, Bielefeld, Germany Objectives: To demonstrate non-inferiority of an herbal combination (horseradish root and nasturtium herb to an antibiotic (co-trimoxazole in acute uncomplicated cystitis. Design: Randomized, prospective, double-blind, double-dummy, multicenter, phase III clinical study, using block randomization of 4 blocks (size 2. Setting: Twenty-six centers in Germany, from May 2011 to June 2013. Participants: Adult patients (median age, 38.5 years; 90% female with acute uncomplicated cystitis confirmed via urinalysis and bacterial counts. Interventions: Patients received the herbal combination (five tablets, four times per day or the antibiotic (two tablets daily for a period of 7 or 3 days, respectively, followed by a 21-days without drug treatment. Placebos ensured blinding. Primary and secondary outcome measures: The primary endpoint was the percentage of responders, expressed as reduction of germ count from >105 to <103 CFU/mL of pathogens between visit 1 (day 0 and 3 (day 15. Secondary endpoints included change of symptom scores, duration of symptoms, efficacy assessments, relapse frequency, and safety. A sample size of 178 patients per group was estimated. Results: Of the 96 randomized patients (intent-to-treat; 45 in the phytotherapy group, 51 in the antibiotic group, 51 were considered per-protocol patients (22 in the phytotherapy group, 29 in the antibiotic group. Responder rates were 10/22 (45.5% for the phytotherapy group and 15/29 (51.1% for the antibiotic group (group difference: –6.27% [95% CI: –33.90%–21.3%]. The study was terminated prematurely due to slow recruitment rates. Non-inferiority could not be assumed by
Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre
International audience; BACKGROUND: Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. METHODS: A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoi...
Sánchez-Velázquez, Patricia; Grande, Luis; Pera, Miguel
Acute diverticulitis occurs in up to 25% of patients with diverticulosis. The majority of cases are mild or uncomplicated and it has become a frequent reason for consultation in the emergency department. On the basis of the National Inpatient Sample database from the USA, 86% of patients admitted with diverticulitis were treated with medical therapy. However, several recent studies have shown that outpatient treatment with antibiotics is safe and effective. The aim of this systematic review is to update the evidence published in the outpatient treatment of uncomplicated acute diverticulitis. We performed a systematic review according to the PRISMA guidelines and searched in MEDLINE and Cochrane databases all English-language articles on the management of acute diverticulitis using the following search terms: 'diverticulitis', 'outpatient', and 'uncomplicated'. Data were extracted independently by two investigators. A total of 11 articles for full review were yielded: one randomized controlled trial, eight prospective cohort studies, and two retrospective cohort studies. Treatment successful rate on an outpatient basis, which means that no further complications were reported, ranged from 91.5 to 100%. Fewer than 8% of patients were readmitted in the hospital. Intolerance to oral intake and lack of family or social support are common exclusion criteria used for this approach, whereas severe comorbidities are not definitive exclusion criteria in all the studies. Ambulatory treatment of uncomplicated acute diverticulitis is safe, effective, and economically efficient when applying an appropriate selection in most reviewed studies.
Randomised controlled trial of two sequential artemisinin-based combination therapy regimens to treat uncomplicated falciparum malaria in African children: a protocol to investigate safety, efficacy and adherence
Schallig, Henk D. F. H.; Tinto, Halidou; Sawa, Patrick
Background Management of uncomplicated Plasmodium falciparum malaria relies on artemisinin-based combination therapies (ACTs). These highly effective regimens have contributed to reductions in malaria morbidity and mortality. However, artemisinin resistance in Asia and changing parasite...... susceptibility to ACT in Africa have now been well documented. Strategies that retain current ACT as efficacious treatments are urgently needed. Methods We present an open-label, randomised three-arm clinical trial protocol in three African settings representative of varying malaria epidemiology to investigate...... whether prolonged ACT-based regimens using currently available formulations can eliminate potentially resistant parasites. The protocol investigates whether a sequential course of two licensed ACT in 1080 children aged 6–120 months exhibits superior efficacy against acute P. falciparum malaria and non...
Full Text Available Abstract Background The epidemiology of malaria in the Senegal River Gorgol valley, southern Mauritania, requires particular attention in the face of ongoing and predicted environmental and climate changes. While “malaria cases” are reported in health facilities throughout the year, past and current climatic and ecological conditions do not favour transmission in the dry season (lack of rainfall and very high temperatures. Moreover, entomological investigations in neighbouring regions point to an absence of malaria transmission in mosquito vectors in the dry season. Because the clinical signs of malaria are non-specific and overlap with those of other diseases (e.g. acute respiratory infections and diarrhoea, new research is needed to better understand malaria transmission patterns in this region to improve adaptive, preventive and curative measures. Methods We conducted a multipurpose cross-sectional survey in the city of Kaédi in April 2011 (dry season, assessing three major disease patterns, including malaria. Plasmodium spp. parasite rates were tested among children aged 6–59 months who were recruited from a random selection of households using a rapid diagnostic test and microscopic examination of Giemsa-stained thick and thin blood films. Acute respiratory infection and diarrhoea were the two other diseases investigated, administering a parental questionnaire to determine the reported prevalence among participating children. Findings No Plasmodium infection was found in any of the 371 surveyed preschool-aged children using two different diagnostic methods. Acute respiratory infections and diarrhoea were reported in 43.4% and 35.0% of the participants, respectively. About two thirds of the children with acute respiratory infections and diarrhoea required medical follow-up by a health worker. Conclusions Malaria was absent in the present dry season survey in the capital of the Gorgol valley of Mauritania, while acute respiratory
Population Pharmacokinetic Analysis of Cefiderocol, a Parenteral Siderophore Cephalosporin, in Healthy Subjects, Subjects with Various Degrees of Renal Function, and Patients with Complicated Urinary Tract Infection or Acute Uncomplicated Pyelonephritis.
Kawaguchi, Nao; Katsube, Takayuki; Echols, Roger; Wajima, Toshihiro
Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. The aim of this study was to perform a population pharmacokinetic (PK) analysis based on plasma cefiderocol concentrations in healthy subjects, subjects with various degrees of renal function, and patients with complicated urinary tract infection (cUTI) or acute uncomplicated pyelonephritis (AUP) caused by Gram-negative pathogens and to calculate the fraction of the time during the dosing interval where the free drug concentration in plasma exceeds the MIC ( fT MIC ). Population PK models were developed with three renal function markers, body surface area-adjusted estimated glomerular filtration rate (eGFR), absolute eGFR, and creatinine clearance, on the basis of 2,571 plasma concentrations from 91 subjects without infection and 238 patients with infection. The population PK models with each renal function marker adequately described the plasma cefiderocol concentrations. Clear relationships of total clearance (CL) to all renal function markers were observed. Body weight and disease status (with or without infection) were also significant covariates. The CL in patients with infection was 26% higher than that in subjects without infection. The fT MIC values were more than 75% in all patients (and were 100% in most patients), suggesting that a sufficient exposure to cefiderocol was provided by the tested dose regimens (2 g every 8 h as the standard dose regimen) for the treatment of cUTI or AUP caused by Gram-negative pathogens. Copyright © 2018 Kawaguchi et al.
Kotwani, Anita; Joshi, P. C.; Jhamb, Urmila; Holloway, Kathleen
OBJECTIVE: The objective of the study was to explore the prescribing practices, knowledge, and attitudes of primary care doctors and community pharmacists, regarding antibiotic use in acute upper respiratory tract infections (URTI) and diarrhea in children to better understand causes of misuse and identify provider suggestions to change such behavior. MATERIALS AND METHODS: Two focus group discussions (FGDs) each were conducted with primary care government doctors (GDs), private general practitioners (GPs), pediatricians, and community pharmacists in Delhi. Each FGD had 8–12 participants and lasted 2 h. Furthermore, 22 individual face-to-face semi-structured interviews were conducted with providers of varying type and experience at their workplaces. Thematic and summative qualitative content analysis was done. RESULTS: All groups admitted to overusing antibiotics, GPs appearing to use more antibiotics than GDs and pediatricians for URTI and diarrhea in children. Pharmacists copy the prescribing of neighborhood doctors. Antimicrobial resistance (AMR) knowledge was poor for all stakeholders except pediatricians. Causes for prescribing antibiotics were patient pressure, profit motive, lack of follow-up and in addition for GDs, workload, no diagnostic facility, and pressure to use near-expiry medicines. Knowledge was gained through self-experience, copying others, information from pharmaceutical companies, and for some, training, continuous medical education/conferences. All groups blamed other professional groups/quacks for antibiotic overuse. Interventions suggested were sensitizing and empowering prescribers through training of providers and the public about the appropriate antibiotic use and AMR and implementing stricter regulations. CONCLUSIONS: A package of interventions targeting providers and consumers is urgently needed for awareness and change in behavior to reduce inappropriate community antibiotic use.
Garg, Charu C; Mazumder, Sarmila; Taneja, Sunita; Shekhar, Medha; Mohan, Sanjana Brahmawar; Bose, Anuradha; Iyengar, Sharad D; Bahl, Rajiv; Martines, Jose; Bhandari, Nita
Three feeding regimens-centrally produced ready-to-use therapeutic food, locally produced ready-to-use therapeutic food, and augmented, energy-dense, home-prepared food-were provided in a community setting for children with severe acute malnutrition (SAM) in the age group of 6-59 months in an individually randomised multicentre trial that enrolled 906 children. Foods, counselling, feeding support and treatment for mild illnesses were provided until recovery or 16 weeks. Costs were estimated for 371 children enrolled in Delhi in a semiurban location after active survey and identification, enrolment, diagnosis and treatment for mild illnesses, and finally treatment with one of the three regimens, both under the research and government setting. Direct costs were estimated for human resources using a price times quantity approach, based on their salaries and average time taken for each activity. The cost per week per child for food, medicines and other consumables was estimated based on the total expenditure over the period and children covered. Indirect costs for programme management including training, transport, non-consumables, infrastructure and equipment were estimated per week per child based on total expenditures for research study and making suitable adjustments for estimations under government setting. No significant difference in costs was found across the three regimens per covered or per treated child. The average cost per treated child in the government setting was estimated at US$56 (based management of SAM with a locally produced ready-to-use therapeutic food is feasible, acceptable, affordable and very cost-effective in terms of the disability-adjusted life years saved and gross national income per capita of the country. The treatment of SAM at home needs serious attention and integration into the existing health system, along with actions to prevent SAM. NCT01705769; Pre-results.
Garg, Charu C; Mazumder, Sarmila; Taneja, Sunita; Shekhar, Medha; Mohan, Sanjana Brahmawar; Bose, Anuradha; Iyengar, Sharad D; Bahl, Rajiv; Martines, Jose; Bhandari, Nita
Trial design Three feeding regimens—centrally produced ready-to-use therapeutic food, locally produced ready-to-use therapeutic food, and augmented, energy-dense, home-prepared food—were provided in a community setting for children with severe acute malnutrition (SAM) in the age group of 6–59 months in an individually randomised multicentre trial that enrolled 906 children. Foods, counselling, feeding support and treatment for mild illnesses were provided until recovery or 16 weeks. Methods Costs were estimated for 371 children enrolled in Delhi in a semiurban location after active survey and identification, enrolment, diagnosis and treatment for mild illnesses, and finally treatment with one of the three regimens, both under the research and government setting. Direct costs were estimated for human resources using a price times quantity approach, based on their salaries and average time taken for each activity. The cost per week per child for food, medicines and other consumables was estimated based on the total expenditure over the period and children covered. Indirect costs for programme management including training, transport, non-consumables, infrastructure and equipment were estimated per week per child based on total expenditures for research study and making suitable adjustments for estimations under government setting. Results No significant difference in costs was found across the three regimens per covered or per treated child. The average cost per treated child in the government setting was estimated at US$56 (<3500 rupees). Conclusion Home-based management of SAM with a locally produced ready-to-use therapeutic food is feasible, acceptable, affordable and very cost-effective in terms of the disability-adjusted life years saved and gross national income per capita of the country. The treatment of SAM at home needs serious attention and integration into the existing health system, along with actions to prevent SAM. Trial registration number NCT
Tine, Roger C K; Faye, Babacar; Sylla, Khadime; Ndiaye, Jean L; Ndiaye, Magatte; Sow, Doudou; Lo, Aminata C; Abiola, Annie; Ba, Mamadou C; Gaye, Oumar
Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Overall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Artesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.
Development of nuclear DNA markers for evolutionary studies in. Plasmodium falciparum. CELIA THOMAS, SNEH SHALINI, N. RAGHAVENDRA, MEENAKSHI CHOUDHARY, ANJU VERMA,. HEMA JOSHI, A. P. DASH and APARUP DAS*. National Institute of Malaria Research (ICMR), 22 Sham Nath Marg, Delhi 110 054, ...
William, Timothy; Menon, Jayaram; Rajahram, Giri; Chan, Leslie; Ma, Gordon; Donaldson, Samantha; Khoo, Serena; Frederick, Charlie; Jelip, Jenarun; Anstey, Nicholas M; Yeo, Tsin Wen
The simian parasite Plasmodium knowlesi causes severe human malaria; the optimal treatment remains unknown. We describe the clinical features, disease spectrum, and response to antimalarial chemotherapy, including artemether-lumefantrine and artesunate, in patients with P. knowlesi malaria diagnosed by PCR during December 2007-November 2009 at a tertiary care hospital in Sabah, Malaysia. Fifty-six patients had PCR-confirmed P. knowlesi monoinfection and clinical records available for review. Twenty-two (39%) had severe malaria; of these, 6 (27%) died. Thirteen (59%) had respiratory distress; 12 (55%), acute renal failure; and 12, shock. None experienced coma. Patients with uncomplicated disease received chloroquine, quinine, or artemether-lumefantrine, and those with severe disease received intravenous quinine or artesunate. Parasite clearance times were 1-2 days shorter with either artemether-lumefantrine or artesunate treatment. P. knowlesi is a major cause of severe and fatal malaria in Sabah. Artemisinin derivatives rapidly clear parasitemia and are efficacious in treating uncomplicated and severe knowlesi malaria.
Stapleton, Ann E
Acute uncomplicated urinary tract infection (UTI) is a common clinical problem, accounting for millions of outpatient visits in the USA annually. Although routinely obtaining urine cultures in UTI is not recommended, there are circumstances in which obtaining a pre-therapy culture may be warranted or chosen by clinicians, such as when indicated by the need for careful antimicrobial stewardship. This review focuses on understanding reasons for obtaining a pre-therapy culture, methods of collection, and appropriately interpreting urine culture data.
Lis R V Antonelli
Full Text Available Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax-infected patients display significant increase in circulating monocytes, which were defined as CD14(+CD16- (classical, CD14(+CD16(+ (inflammatory, and CD14loCD16(+ (patrolling cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16(+ cells, in particular the CD14(+CD16(+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14(+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14(+CD16(+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14(+CD16(+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection.
Full Text Available Abstract Background Severe and cerebral malaria are associated with endothelial activation. Angiopoietin-1 (ANG-1 and angiopoietin-2 (ANG-2 are major regulators of endothelial activation and integrity. The aim of this study was to investigate the clinical utility of whole blood angiopoietin (ANG levels as biomarkers of disease severity in Plasmodium falciparum malaria. Methods The utility of whole blood ANG levels was examined in Thai patients to distinguish cerebral (CM; n = 87 and severe (non-cerebral malaria (SM; n = 36 from uncomplicated malaria (UM; n = 70. Comparative statistics are reported using a non-parametric univariate analysis (Kruskal-Wallis test or Chi-squared test, as appropriate. Multivariate binary logistic regression was used to examine differences in whole blood protein levels between groups (UM, SM, CM, adjusting for differences due to ethnicity, age, parasitaemia and sex. Receiver operating characteristic curve analysis was used to assess the diagnostic accuracy of the ANGs in their ability to distinguish between UM, SM and CM. Cumulative organ injury scores were obtained for patients with severe disease based on the presence of acute renal failure, jaundice, severe anaemia, circulatory collapse or coma. Results ANG-1 and ANG-2 were readily detectable in whole blood. Compared to UM there were significant decreases in ANG-1 (p Conclusions These results suggest that whole blood ANG-1/2 levels are promising clinically informative biomarkers of disease severity in malarial syndromes.
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
Perch, M; Kofoed, P; Fischer, TK
Serum levels of soluble urokinase plasminogen activator receptor (suPAR) are significantly elevated and of prognostic value in patients suffering from serious infectious diseases such as HIV and tuberculosis. Our objective was to investigate suPAR levels during symptomatic malaria infection and 7...... an important association between suPAR and acute malaria infection in humans....
Llanos-Cuentas, A.; Campos, P.; Clendenes, M.; Canfield, C. J.; Hutchinson, D. B. A.
The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were sub...
Full Text Available The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15 or 1,500 mg chloroquine (base over a 3 day period (n=14 (phase 1. The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9 or atovaquone/proguanil as before (n=5 (phase 2. In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] versus 8% [1/13], P<0.0001. In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]. There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Full Text Available The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (MalaroneTM were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15 or 1,500 mg chloroquine (base over a 3 day period (n=14 (phase 1. The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9 or atovaquone/proguanil as before (n=5 (phase 2. In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] versus 8% [1/13], P<0.0001. In phase 2, atovaquone/proguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]. There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Llanos-Cuentas, A; Campos, P; Clendenes, M; Canfield, C J; Hutchinson, D B
The efficacy and safety of a fixed-dose combination of atovaquone and proguanil hydrochloride (Malarone) were compared with chloroquine or pyrimethamine/sulfadoxine in patients with acute falciparum malaria in northern Peru. Patients were initially randomized to receive 1,000 mg atovaquone and 400 mg proguanil hydrochloride daily for 3 days (n=15) or 1,500 mg chloroquine (base) over a 3 day period (n=14) (phase 1). The cure rate with chloroquine was lower than expected and patients were subsequently randomized to receive a single dose of 75 mg pyrimethamine and 1,500 mg sulfadoxine (n=9) or atovaquone/proguanil as before (n=5) (phase 2). In phase 1, atovaquone/proguanil was significantly more effective than chloroquine (cure rate 100% [14/14] vs. 8% [1/13], Pproguanil and pyrimethamine/sulfadoxine were both highly effective (cure rates 100% [5/5] and 100% [7/7]). There were no significant differences between treatment groups in parasite or fever clearance times. Adverse events were typical of malarial symptoms and did not differ significantly between groups. Overall efficacy of atovaquone/proguanil was 100% for treatment of acute falciparum malaria in a region with a high prevalence of chloroquine resistance.
Julius Clemence R Hafalla
Full Text Available The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA-induced experimental cerebral malaria (ECM in susceptible (C57BL/6 and resistant (BALB/c mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8(+ T cells to the brain, and augmented incidence of ECM. Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-γ or depletion of CD8(+ T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites.
Kurtzhals, J A; Rodrigues, O; Addae, M
To study the importance of bone marrow inhibition in the pathogenesis of malarial anaemia, haematological and parasitological parameters were followed in patients with acute malaria. Three patient categories were studied, severe malarial anaemia (SA), cerebral malaria (CM) and uncomplicated malar...
Efficacy of chloroquine, sulfadoxine-pyrimethamine, and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria on the north coast...Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncompli- cated Plasmodium falciparum malaria in the Amazon basin of Peru...Green MD, Bergqvist Y, Mount DL, Corbett S, D’Souza MJ (1999) Improved validated assay for the determination of mefloquine and its carboxy metabolite in
Abel, Annemieke; Steeg, Christiane; Aminkiah, Francis; Addai-Mensah, Otchere; Addo, Marylyn; Gagliani, Nicola; Casar, Christian; Yar, Denis Dekugmen; Owusu-Dabo, Ellis; Jacobs, Thomas; Mackroth, Maria Sophia
The immune response of malaria patients is a main factor influencing the clinical severity of malaria. A tight regulation of the CD4 + T cell response or the induction of tolerance have been proposed to contribute to protection from severe or clinical disease. We therefore compared the CD4 + T cell phenotypes of Ghanaian children with complicated malaria, uncomplicated malaria, asymptomatic Plasmodium falciparum (Pf) infection or no infection. Using flow cytometric analysis and automated multivariate clustering, we characterized the expression of the co-inhibitory molecules CTLA-4, PD-1, Tim-3, and LAG-3 and other molecules implicated in regulatory function on CD4 + T cells. Children with complicated malaria had higher frequencies of CTLA-4 + or PD-1 + CD4 + T cells than children with uncomplicated malaria. Conversely, children with uncomplicated malaria showed a higher proportion of CD4 + T cells expressing CD39 and Granzyme B, compared to children with complicated malaria. In contrast, asymptomatically infected children expressed only low levels of co-inhibitory molecules. Thus, different CD4 + T cell phenotypes are associated with complicated versus uncomplicated malaria, suggesting a two-sided role of CD4 + T cells in malaria pathogenesis and protection. Deciphering the signals that shape the CD4 + T cell phenotype in malaria will be important for new treatment and immunization strategies.
Dekker, E.; Romijn, J. A.; Ekberg, K.; Wahren, J.; van Thien, H.; Ackermans, M. T.; Thuy, L. T.; Chandramouli, V.; Kager, P. A.; Landau, B. R.; Sauerwein, H. P.
Although glucose production is increased in severe malaria, the influence of uncomplicated malaria on glucose production is unknown. Therefore, we measured in eight adult Vietnamese patients with uncomplicated falciparum malaria and eight healthy Vietnamese controls glucose production (by infusion
Nosseir, Sandy B; Lind, Lawrence R; Winkler, Harvey A
Recurrent urinary tract infections most often present with symptoms of irritative voiding. In most cases, they are caused by reinfection with a previously isolated organism. Patients with one or more symptoms of uncomplicated recurrent urinary tract infection should undergo thorough examination and screening for underlying comorbidities that increase susceptibility. When frequent reinfections, empiric treatment relapse, persistent infections, or risk factors for complicated infections are encountered, patients may benefit from urodynamics, cystoscopy, renal ultrasound, intravenous urogram, or voiding cystourethrogram to evaluate for anatomic, functional, or metabolic abnormalities affecting the urinary tract (e.g., stones, stricture, obstruction, vesicoureteral reflux, lesions, detrusor underactivity). These patients may benefit from culture-guided empiric treatment and further evaluation by urology, nephrology, or infectious disease specialists. In patients with a history of uncomplicated urinary tract infections, empiric treatment guided by local antimicrobial resistance may efficiently treat a suspected recurrence. After successful treatment of the acute infection, postcoital prophylaxis, continuous prophylaxis, or self-start empiric treatment may be selected based on frequency of recurrent infections, temporal relation to intercourse, and patient characteristics. Ancillary measures such as probiotics, cranberry products, or local estrogen replacement may also be considered. This article will review the current definition, epidemiology, pathogenesis, diagnosis, work-up, treatment, treatment side effects, and prevention of recurrent urinary tract infections in women. A suggested algorithm for evaluation and treatment based on current literature is provided.
Medical Prescription Pitfalls of Uncomplicated Urinary Tract Infections in Government Healthcare Facilities in Zambia. ... The PDF file you selected should load here if your Web browser has a PDF reader plug-in installed (for example, a recent version of Adobe Acrobat Reader). If you would like more information about how ...
Objectives: The aim of this evaluation was to identify pitfalls in medical prescriptions of uncomplicated urinary tract infections in government healthcare facilities in Zambia. Design: This was a cross sectional and government healthcare facilities were conveniently sampled. Main outcome measures: Rate of compliance to ...
Hommel, Benjamin; Galloula, Alexandre; Simon, Anne; Buffet, Pierre
Hyposplenism, due to splenectomy, inherited red blood cell disorders or acquired conditions such as celiac disease, has an important impact on the severity of malaria, especially in non-immune patients. Conversely, that malaria may reveal functional hyposplenism has not been described previously. A 31-year old gardener was diagnosed with an uncomplicated attack of Plasmodium malariae 11 years after leaving the endemic area. In addition to trophozoites and schizonts, thick and thin smears also showed Howell-Jolly bodies, pointing to functional hyposplenism. This was later confirmed by the presence of a calcified spleen in the context of S/β + sickle-cell syndrome in a patient previously unaware of this condition. Malaria may reveal hyposplenism. Although Howell-Jolly bodies are morphologically similar to nuclei of young Plasmodium trophozoite, distinction on smears is based on the absence of cytoplasm and irregular size of Howell-Jolly bodies. In the patient reported here, hyposplenism was revealed by the occurrence of P. malariae infection relatively late in life. Timely diagnosis of hyposplenism resulted in the implementation of appropriate measures to prevent overwhelming infection with capsulated bacteria. This observation highlights the importance of diagnosing hyposplenism in patients with malaria despite the morphological similarities between ring nuclei and Howell-Jolly bodies on thick smears.
Park, Hyoung-Chul; Kim, Byung Seup; Lee, Kwanseop; Kim, Min Jeong; Lee, Bong Hwa
Most patients with acute right colonic uncomplicated diverticulitis can be managed conservatively. The aim of this study was to assess the clinical and radiologic risk factors for recurrence in patients with right colonic uncomplicated diverticulitis. The present survey included 469 patients who were successfully managed conservatively for the first episode of right colonic uncomplicated diverticulitis between 2002 and 2012 in a referral center, and records were reviewed from collected data. Patients were divided into two groups: a nonrecurrent and a recurrent group. The clinical and radiologic features of all patients were analyzed to identify possible risk factors for recurrence. The Kaplan-Meier method and Cox regression were used. Seventy-four (15.8 %) patients had recurrence, and 15 (3.2 %) received surgery at recurrence within a median follow-up of 59 months. The mean recurrence interval after the first attack was 29 months. In univariate and multivariate analyses, risk factors for recurrence were confirmed multiple diverticula (relative risk [RR], 2.62; 95 % confidence interval [CI], 1.56-4.40) and intraperitoneally located diverticulitis (RR, 3.73; 95 % CI, 2.13-6.52). Of 66 patients with two risk factors, 36 (54.5 %) had recurrence and 10 (15.2 %) received surgery at recurrence. In patients with right colonic uncomplicated diverticulitis who have multiple diverticula and intraperitoneally located diverticulitis, the possibility of recurrence and surgical rate are high. Poor outcome may be cautioned in these patients.
Knottnerus, Bart J.; Geerlings, Suzanne E.; Moll van Charante, Eric P.; ter Riet, Gerben
Women presenting with symptoms of acute uncomplicated urinary tract infection (UTI) are often prescribed antibiotics. However, in 25 to 50% of symptomatic women not taking antibiotics, symptoms recover spontaneously within one week. It is not known how many women are prepared to delay antibiotic
Bachur, Richard G; Lipsett, Susan C; Monuteaux, Michael C
Nonoperative management (NOM) of uncomplicated pediatric appendicitis has promise but remains poorly studied. NOM may lead to an increase in resource utilization. Our objective was to investigate the trends in NOM for uncomplicated appendicitis and study the relevant clinical outcomes including subsequent appendectomy, complications, and resource utilization. Retrospective analysis of administrative data from 45 US pediatric hospitals. Patients appendicitis between 2010 and 2016 were studied. NOM was defined by an ED visit for uncomplicated appendicitis treated with antibiotics and the absence of appendectomy at the index encounter. The main outcomes included trends in NOM among children with uncomplicated appendicitis and frequency of subsequent diagnostic imaging, ED visits, hospitalizations, and appendectomy during 12-month follow-up. 99 001 children with appendicitis were identified, with a median age of 10.9 years. Sixty-six percent were diagnosed with nonperforated appendicitis, of which 4190 (6%) were managed nonoperatively. An increasing number of nonoperative cases were observed over 6 years (absolute difference, +20.4%). During the 12-month follow-up period, NOM patients were more likely to have the following: advanced imaging (+8.9% [95% confidence interval (CI) 7.6% to 10.3%]), ED visits (+11.2% [95% CI 9.3% to 13.2%]), and hospitalizations (+43.7% [95% CI 41.7% to 45.8%]). Among patients managed nonoperatively, 46% had a subsequent appendectomy. A significant increase in NOM of nonperforated appendicitis was observed over 6 years. Patients with NOM had more subsequent ED visits and hospitalizations compared with those managed operatively at the index visit. A substantial proportion of patients initially managed nonoperatively eventually had an appendectomy. Copyright © 2017 by the American Academy of Pediatrics.
Full Text Available Augmentin (Amoxycillin 3 . gm combined with 250 mg clavulanic acid and ampicillin 3.5 gin and I gm probenecid orally were evaluated in 50 patients for treatment of uncomplicated gonorrhoea. Success rates of 80% and 100% were obtained with augmentin and ampicillin with probenecid respectively in non-PPNG strains. None of 4 PPNG strains responded to ampicillin-probnecid. Augmentin in single oral dose cannot be recommended for the treatment of non-PPNG strains in India.
Kochar, Dhanpat K; Gupta, Vikas; Kochar, Abhishek; Acharya, Jyoti; Middha, Sheetal; Sirohi, Parminder; Kochar, Sanjay K
This study was conducted to assess the effect of combination treatment of quinine and rabeprazole in the treatment of uncomplicated Plasmodium falciparum malaria. The study included 50 patients of uncomplicated P. falciparum malaria. Group 1 (25 patients) received quinine and placebo (Q+P) while Group 2 (25 patients) received quinine and rabeprazole (Q+R). Diagnosis was confirmed by peripheral blood film (PBF) and rapid diagnostic test (RDT). Temperature was recorded every 6 h. All patients were followed-up on Days 7, 14, 21, 28 for detailed clinical and parasitological examination. A total of 20 patients in each group completed the treatment and followed-up for 28 days. While two patients in Group 1 (Q+P) and one patient in Group 2 (Q+R) were lost in follow-up; and seven (Q+P = 4, Q+R =3) patients were withdrawn from the study. Fever clearance time (FCT) of the two groups was also almost similar (Group 1 : 2 = 52.8 : 51.3 h). No statistically significant difference was observed in early treatment failure (ETF) either of the groups. None of the patients in both the groups showed late clinical failure (LCF) or late parasitological failure (LPF). However, there was a significant difference in the parasite clearance rates of the two groups (pquinine regimen resulted in an increase in the parasite elimination rate, which may be helpful in reducing the duration of treatment and increasing patient compliance.
Selemani, Majige; Masanja, Irene M; Kajungu, Dan; Amuri, Mbaraka; Njozi, Mustafa; Khatib, Rashid A; Abdulla, Salim; de Savigny, Don
Improving malaria case management is partially dependent on health worker compliance with clinical guidelines. This study assessed health worker factors associated with correct anti-malarial prescribing practices at two sites in rural Tanzania. Repeated cross-sectional health facility surveys were conducted during high and low malaria transmission seasons in 2010 and collected information on patient consultations and health worker characteristics. Using logistic regression, the study assessed health worker factors associated with correct prescription for uncomplicated malaria defined as prescription of artemisinin-based combination therapy (ACT) for patients with fever and Plasmodium falciparum asexual infection based on blood slide or malaria rapid diagnostic test (RDT) according to national treatment guidelines. The analysis included 685 patients with uncomplicated malaria who were seen in a health facility with ACT in stock, and 71 health workers practicing in 30 health facilities. Overall, 58% of malaria patients were correctly treated with ACT. Health workers with three or more years' work experience were significantly more likely than others to prescribe correctly (adjusted odds ratio (aOR) 2.9; 95% confidence interval (CI) 1.2-7.1; p = 0.019). Clinical officers (aOR 2.2; 95% CI 1.1-4.5; p = 0.037), and nurse aide or lower cadre (aOR 3.1; 95% CI 1.3-7.1; p = 0.009) were more likely to correctly prescribe ACT than medical officers. Training on ACT use, supervision visits, and availability of job aids were not significantly associated with correct prescription. Years of working experience and health worker cadre were associated with correct ACT prescription for uncomplicated malaria. Targeted interventions to improve health worker performance are needed to improve overall malaria case management.
India being a tropical country, parasitic infections especially with Plasmodium species are very common in this region. The present case report is that of Plasmodium vivax, Plasmodium falciparum and dengue co‑infection in a 6 months pregnant lady who was timely diagnosed and appropriately treated followed by a ...
Stam, M A W; Draaisma, W A; van de Wall, B J M; Bolkenstein, H E; Consten, E C J; Broeders, I A M J
The optimal diet for uncomplicated diverticulitis is unclear. Guidelines refrain from recommendation due to lack of objective information. The aim of the study was to determine whether an unrestricted diet during a first acute episode of uncomplicated diverticulitis is safe. A prospective cohort study was performed of patients diagnosed with diverticulitis for the first time between 2012 and 2014. Requirements for inclusion were radiologically proven modified Hinchey Ia/b diverticulitis, American Society of Anesthesiologists class I-III and the ability to tolerate an unrestricted diet. Exclusion criteria were the use of antibiotics and suspicion of inflammatory bowel disease or malignancy. All included patients were advised to take an unrestricted diet. The primary outcome parameter was morbidity. Secondary outcome measures were the development of recurrence and ongoing symptoms. There were 86 patients including 37 (43.0%) men. All patients were confirmed to have taken an unrestricted diet. There were nine adverse events in seven patients. These consisted of readmission for pain (five), recurrent diverticulitis (one) and surgery (three) for ongoing symptoms (two) and Hinchey Stage III (one). Seventeen (19.8%) patients experienced continuing symptoms 6 months after the initial episode and 4 (4.7%) experienced recurrent diverticulitis. The incidence of complications among patients taking an unrestricted diet during an initial acute uncomplicated episode of diverticulitis was in line with that reported in the literature. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.
S L Wadhwa
Full Text Available Gonorrhoea constitutes nine per cent of the sexually transmitted diseases seen at the department of Dermatology and Venereology, Nair Hospital, Bombay. Fifty cases of uncomplicated males were treated with doxycycline 200mgs iv on the first day and 100 mgs, iv for 2 more - a total of 400 mgs doxycycline. Smears for gonococci and blood V D R L were treatment. The cases were reviewed every week for a period 3 weeks. Three cases showed a positive serology and 44 cases responded well to therapy giving a success rate of 88%. Side effects were minimal.
Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys
Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.
Objective: The objective of this study is to compare the safety of early versus delayed oral feeding after uncomplicated cesarean section (CS) under spinal anesthesia. Methods: This was a randomized, controlled trial that enrolled 152 women who had uncomplicated CS under spinal anesthesia between January 2014 and ...
Five-year surveillance of molecular markers of Plasmodium falciparum antimalarial drug resistance in Korogwe District, Tanzania: accumulation of the 581G mutation in the P. falciparum dihydropteroate synthase gene
Alifrangis, Michael; Lusingu, John P; Mmbando, Bruno
In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two...
BARENNES, H.; PUSSARD, E.; MAHAMAN SANI, A.; CLAVIER, F.; KAHIATANI, F.; GRANIC, G.; HENZEL, D.; RAVINET, L.; VERDIER, F.
1Three groups of seven children aged 2–14 years with acute uncomplicated Plasmodium falciparum malaria received 12.8 mg kg−1 quinine gluconate by the intrarectal route (new cream formulation) or 8 mg kg−1 Quinimax (a Cinchona alkaloid combination) by the intramuscular or intravenous (4 h infusion) route every 8 h for 3 days. Clinical and parasitological status was similar in the three groups at enrolment. 2At 36 h, body temperature of all children of the three groups was returned to normal and remained so until day 7. 3The decrease in parasitaemia did not differ between the three groups and the time required for a 50% fall in parasitaemia relative to baseline was 12.3±5.4, 18.2±6.1 and 14.5±4.2 h in the intrarectal, intramuscular and intravenous treatment groups, respectively. Parasitaemia expressed as a percentage of initial values was not significantly different in the three groups after 48 h of treatment (7.4±16.0, 4.1±4.2 and 2.2±3.8% in the intrarectal, intramuscular and intravenous treatment groups, respectively). All the patients were aparasitaemic by day 7. 4The tolerability of the three treatments was good; in particular, no rectal irritation was reported with the cream formulation. 5The tmax occurred later after intrarectal (4.1±2.4 h) and intravenous infusion (3.8±0.5 h) than after intramuscular injection (1.6±1.3 h) (P=0.02). Cmax was lower with the intrarectal (3.0±1.0 mg l−1) and intramuscular routes (3.2±0.7 mg l−1) than with the intravenous route (5.1±1.4 mg l−1) (P=0.003). Areas under the curve (AUC(0, 8 h)) were smaller with the intrarectal (17.0±7 mg l−1 h) and intramuscular routes (19.4±4.8 mg l−1 h) than with the intravenous route (27.8±8.2 mg l−1 h) (P=0.02). The approximate bioavailability of intrarectal quinine from 0 to 8 h was 36%vs intravenous quinine and 51%vs intramuscular quinine. 6The good tolerability and efficacy of this new intrarectal quinine formulation
Cuomo, Rosario; Cargiolli, Martina; Andreozzi, Paolo; Zito, Francesco P; Sarnelli, Giovanni
Symptomatic uncomplicated diverticular disease (SUDD) is one of the possible clinical manifestations of diverticular disease. It is a common disorder characterized by chronic abdominal symptoms ranging from lower left abdominal pain to alteration of bowel habit, that significantly reduce quality of life of subject affected. The present article aims to review the current data for medical management of SUDD. We analyzed the existing literature on the factors involved in the pathogenesis of SUDD and we highlighted the possible target for treatment. Treatment for SUDD should be direct to relieve chronic symptoms and prevent diverticulitis and its complications. In particular we focused on the role of probiotics, fiber-diet, mesalazine and rifaximin on these two aspects. In this setting, we conducted a PubMed search for guidelines, systematic reviews and meta-analyses and updated information to October 2016. Each topic was evaluated according to the best evidences available. Best results seemed to be obtained with combined therapies and in particular with rifaximin associated to high fiber-diet. This regimen seems to guarantee better symptoms control compared to fiber alone and it is more effective in preventing acute diverticulitis. On the contrary, no clear evidences about the efficacy of mesalazine and probiotics are available. The results of the studies available in literature are controversial and debatable, for this reason a clear and defined algorithm for treatment of SUDD has not yet been defined. Further randomized, double-blind, placebo controlled study are necessary.
Abdulla, Salim; Achan, Jane; Adam, Ishag
Background: Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are importa...
Full Text Available Abstract Artemisinin-based combination therapies (ACTs are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance.
Etoka-Beka, Mandingha Kosso; Ntoumi, Francine; Kombo, Michael; Deibert, Julia; Poulain, Pierre; Vouvoungui, Christevy; Kobawila, Simon Charles; Koukouikila-Koussounda, Felix
To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. Blood samples were collected from children aged <10 years with an axillary temperature ≥37.5 °C consulting the paediatric ward of Marien Ngouabi Hospital in Brazzaville. Parasite density was determined and all samples were screened for P. falciparum by nested polymerase chain reaction (PCR) using the P. falciparum msp-2 marker to detect submicroscopic infections and characterise P. falciparum infection. Sickle cell trait was screened by PCR. A total of 229 children with fever were recruited, of whom 10% were diagnosed with uncomplicated malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/μl of blood. The multiplicity of infection (MOI) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 ± 1.7 for children with uncomplicated malaria and 12.0 ± 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (HbAS); the rest had normal haemoglobin (HbAA). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever. © 2016 John Wiley & Sons Ltd.
Sullivan, S M
This article reviews the basic principles of patient evaluation and surgical techniques to accomplish extraction of teeth in an uncomplicated manner. Also presented are techniques for extraction-site grafting with bioactive glass.
Andersen, S B; Paerregaard, A; Larsen, K
with a diagnosis of acute uncomplicated or complicated appendicitis, and/or a registered procedure code of appendectomy. These data were computed together with data on the background population, and incidences were calculated. RESULTS: A significant decrease in the incidence of acute uncomplicated appendicitis...
Jovel, Irina T; Mejía, Rosa E; Banegas, Engels; Piedade, Rita; Alger, Jackeline; Fontecha, Gustavo; Ferreira, Pedro E; Veiga, Maria I; Enamorado, Irma G; Bjorkman, Anders; Ursing, Johan
In Honduras, chloroquine and primaquine are recommended and still appear to be effective for treatment of Plasmodium falciparum and Plasmodium vivax malaria. The aim of this study was to determine the proportion of resistance associated genetic polymorphisms in P. falciparum and P. vivax collected in Honduras. Blood samples were collected from patients seeking medical attention at the Hospital Escuela in Tegucigalpa from 2004 to 2006 as well as three regional hospitals, two health centres and one regional laboratory during 2009. Single nucleotide polymorphisms in P. falciparum chloroquine resistance transporter (pfcrt), multidrug resistance 1 (pfmdr1), dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes and in P. vivax multidrug resistance 1 (pvmdr1) and dihydrofolate reductase (pvdhfr) genes were detected using PCR based methods. Thirty seven P. falciparum and 64 P. vivax samples were collected. All P. falciparum infections acquired in Honduras carried pfcrt, pfmdr1, pfdhps and pfdhfr alleles associated with chloroquine, amodiaquine and sulphadoxine-pyrimethamine sensitivity only. One patient with parasites acquired on a Pacific Island had pfcrt 76 T and pfmdr1 86Y alleles. That patient and a patient infected in West Africa had pfdhfr 51I, 59 R and 108 N alleles. Pvmdr1 976 F was found in 7/37 and two copies of pvmdr1 were found in 1/37 samples. Pvdhfr 57 L + 58 R was observed in 2/57 samples. The results indicate that P. falciparum from Honduras remain sensitive to chloroquine and sulphadoxine-pyrimethamine. This suggests that chloroquine and sulphadoxine-pyrimethamine should be efficacious for treatment of uncomplicated P. falciparum malaria, supporting current national treatment guidelines. However, genetic polymorphisms associated with chloroquine and sulphadoxine-pyrimethamine tolerance were detected in local P. vivax and imported P. falciparum infections. Continuous monitoring of the prevalence of drug resistant/tolerant P
Yeka, Adoke; Achan, Jane; D'Alessandro, Umberto; Talisuna, Ambrose O
Several African countries that have adopted artemisinin-based combination therapy (ACT) as first-line treatment of uncomplicated Plasmodium falciparum malaria also use quinine monotherapy as second-line therapy. This policy goes against WHO recommendations for combination therapy and could be considered an inappropriate public health policy. Adherence to a 7-day quinine treatment schedule is likely to be poor and may increase the risk of selecting resistant parasites. Furthermore, because quinine has limited post-treatment prophylaxis, it will not prevent, in areas of intense transmission, recurrent malaria infections, which can lead to additional morbidity, including anaemia. Therefore, ACTs and not quinine should be used as second-line treatment, because these are well tolerated, highly efficacious, and have the advantage of reducing gametocyte carriage and consequently malaria transmissibility, particularly in areas of less intense transmission.
Cremon, Cesare; Bellacosa, Lara; Barbaro, Maria R; Cogliandro, Rosanna F; Stanghellini, Vincenzo; Barbara, Giovanni
Colonic diverticulosis is a common condition in Western industrialized countries occurring in up to 65% of people over the age of 60 years. Only a minority of these subjects (about 10-25%) experience symptoms, fulfilling Rome III Diagnostic Criteria for irritable bowel syndrome (IBS) diagnosis (IBS-like symptoms) in 10% to 66% of cases. Symptomatic uncomplicated diverticular disease (SUDD) is a syndrome characterized by recurrent abdominal symptoms attributed to diverticula in the absence of macroscopically evident alterations other than the presence of diverticula. Due to the different peak of incidence, the overlap between SUDD and IBS is predominantly present in middle-aged or older patients. In these cases, it is very complex to establish if the symptoms are related to the presence of diverticula or due to an overlapping IBS. In fact, the link between gastrointestinal symptoms and diverticula is unclear, and the mechanism by which diverticula may induce the development of IBS-like symptoms remains to be elucidated. Currently, the etiology and pathophysiology of SUDD, particularly when IBS-like symptoms are present, are not completely understood, and thus these two entities remain a diagnostic challenge not only for the general practitioner but also for the gastroenterologist. Although many issues remain open and unresolved, some minimize the importance of a distinction of these two entities as dietary and pharmacological management may be largely overlapping.
Kavishe, Reginald A; Paulo, Petro; Kaaya, Robert D
) is the recommended first-line drug in treatment of uncomplicated malaria. This study surveyed the distribution of the Plasmodium falciparum multidrug resistance protein-1 single nucleotide polymorphisms (SNPs) associated with increased parasite tolerance to ALu, in Tanzania. METHODS: A total of 687 Plasmodium...... in all regions, ranging from 17% - 26%. CONCLUSION: This is the first country-wide survey on Pfmdr1 mutations associated with ACT resistance. Distribution of individual Pfmdr1 mutations at codons 86, 184 and 1246 varies throughout Tanzanian regions. There is a general homogeneity in distribution......BACKGROUND: Resistance to anti-malarials is a major public health problem worldwide. After deployment of artemisinin-based combination therapy (ACT) there have been reports of reduced sensitivity to ACT by malarial parasites in South-East Asia. In Tanzania, artemether-lumefantrine (ALu...
Ould Ahmedou Salem, Mohamed Salem; Mohamed Lemine, Yeslim Ould; Deida, Jemila Mint; Lemrabott, Mohamed Aly Ould; Ouldabdallahi, Mohamed; Ba, Mamadou Dit Dialaw; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Abdel Aziz, Mohamed Boubacar; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sidi Mohamed
In 2006, the Mauritanian Ministry of Health adopted a new therapeutic strategy based on the systematic use of artemisinin-based combination therapy (ACT), artesunate-amodiaquine and artemether-lumefantrine, for the first- and second-line treatment of uncomplicated malaria, respectively, regardless of Plasmodium spp. In the Saharan zone of the country, recent studies have shown that Plasmodium vivax largely predominates over Plasmodium falciparum. Anti-malarial drug response of P. vivax has not been evaluated in Mauritania. The aim of the present study was to evaluate the clinical efficacy and tolerance of chloroquine to treat P. vivax malaria in Mauritanian patients. Plasmodium vivax-infected patients aged > 6 months old were enrolled in Nouakchott and Atar in September-October 2013. Chloroquine was administered at the standard dose of 25 mg base/kg body weight over three days. Patients were followed until day 28, according to the standard 2009 World Health Organization protocol. A total of 128 patients (67 in Nouakchott and 61 in Atar) were enrolled in the study. Seven patients (5.5%) were either excluded or lost to follow-up. Based on the per protocol analysis, chloroquine efficacy (adequate clinical and parasitological response) was 100%. Treatment was well-tolerated. One patient was excluded on day 1 due to urticaria and treated with artesunate-amodiaquine. Although the current national treatment guideline recommends artesunate-amodiaquine for the first-line treatment of uncomplicated malaria, including P. vivax malaria, chloroquine may still have an important role to play in anti-malarial chemotherapy in Mauritania. Further epidemiological studies are required to map the distribution of P. vivax and P. falciparum in the country.
Balasubramanian, Ishwarya; Fleming, Christina; Mohan, Helen M; Schmidt, Karl; Haglind, Eva; Winter, Des C
Management of diverticular disease has undergone a paradigm shift, with movement towards a less invasive management strategy. In keeping with this, outpatient management of uncomplicated diverticulitis (UD) has been advocated in several studies, but concerns still remain regarding the safety of this practice. To assess outcomes of out-patient management of acute UD. A comprehensive search for published studies using the search terms 'uncomplicated diverticulitis', 'mild diverticulitis' and 'out-patient' was performed. The primary outcomes were failure of medical treatment. Secondary outcomes were recurrence rate at follow up and medical cost savings. The search yielded 192 publications. Of these, 10 studies met the inclusion criteria including 1 randomized controlled trial, 6 clinical controlled trials and 3 case series. There was no difference in failure rates of medical treatment (6.5 vs. 4.6%, p = 0.32) or in recurrence rates (13.0 vs. 12.1%, p = 0.81) between those receiving ambulatory care and in-patient care for UD. Ambulatory treatment is associated with an estimated daily cost savings of between 600 and 1,900 euros per patient treated. Meta-analysis of data was not possible due to heterogeneity in study designs and inclusion criteria. Ambulatory management of acute UD is reasonable in selected patients. © 2016 S. Karger AG, Basel.
Karunaweera, Nadira D; Wijesekera, Subadra K; Wanasekera, Deepani; Mendis, Kamini N; Carter, Richard
The paroxysms of Plasmodium vivax malaria are antiparasite responses that, although distressing to the human host, almost never impart serious acute pathology. Using plasma and blood cells from P. vivax patients, the cellular and noncellular mediators of these events have been studied ex vivo. The host response during a P. vivax paroxysm was found to involve T cells, monocytes and neutrophils, and the activity, among others, of the pyrogenic cytokines tumor necrosis factor alpha and interleukin 2 in addition to granulocyte macrophage-colony stimulating factor. However, interferon gamma activity, associated with serious acute pathogenesis in other studies on malaria, was absent. Induction of the cytokines active during a P. vivax paroxysm depends upon the presence of parasite products, which are released into the plasma before the paroxysm. Chemical identification of these natural parasite products will be important for our understanding of pathogenesis and protection in malaria.
Doka, Y. A.
The aim of this study is to measure the levels of zinc and copper in children suffering from plasmodium falciparum malaria in an area of unstable malaria transmission in Eastern Sudan. The importance of the study emanates from the fact that this type of malaria is prevalent in a serious manner and causes many fatalities and problems. In this study the analytic statistical methodology was adopted using Atomic Absorption Spectroscopy. Subject target groups, confirmed microscopically to be infected with malaria, (severe malaria 35 samples and two control groups: 35 samples of uncomplicated malaria and 35 samples of apparently healthy). The study revealed that there is a significant increase in the level of copper for both types of malaria ( the severe and the uncomplicated) while uncomplicated malaria decreased the level of zinc significantly. The study recommended that zinc supplement could be used for the patients suffering from severe malaria. (Author)
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.
Ouldabdallahi, M M; Sarr, O; Basco, L K; Lebatt, S M; Lo, B; Gaye, O
Until 2006, the Mauritanian Ministry of Health recommended chloroquine and sulfadoxine-pyrimethamine for first- and second-line treatment of uncomplicated malaria, respectively. This study assessed the clinical efficacy of sulfadoxine-pyrimethamine in Kobeni as first-line treatment. This study included 55 patients with Plasmodium falciparum infections, who were treated with sulfadoxine-pyrimethamine and followed up for 28 days. Isolates were genotyped to distinguish between recrudescence and reinfection. Treatment success rates and survival were analysed per protocol to evaluate drug efficacy. After inclusion, 2 patients were excluded for protocol violations, and 3 patients were lost to follow-up. Of the remaining 50 patients (per protocol population), 43 (86%) had adequate clinical and parasitological responses. Of the 7 patients with treatment failure, 5 (10%) were early failures, while 2 (4%) had initially responded and had late clinical failure on day 7, associated with recrudescence. With the exception of one adult weighing 91 kg, all treatment failures occurred in children aged from 7 to 12 years. Sulfadoxine-pyrimethamine monotherapy was moderately effective but insufficiently reliable in view of the relatively high rate of early treatment failure. The high prevalence of chloroquine resistance found in earlier studies and the results of the present study on sulfadoxine-pyrimethamine justify the change in national policy and systematic use of artemisinin-based combination therapy for first-line treatment of P. falciparum malaria in Mauritania.
Karbwang, J; Na-Bangchang, K; Congpoung, K; Thanavibul, A; Harinasuta, T
The pharmacokinetics of artesunate and its major plasma metabolite, dihydroartemisinin, were investigated in 11 Thai male patients with acute uncomplicated falciparum malaria during the acute and recovery phases. Patients were given an oral dose of 200mg artesunate (Guilin Pharmaceutical) on the first day, followed by 100mg 12 hours later, then 100mg daily for another 4 days (total dose of 700mg). All the patients showed a rapid initial response with median (range) parasite and fever clearance times of 30 (18 to 60) and 24 (4 to 94) hours, respectively; no patients showed reappearance of parasites during the 28-day follow-up period. No significant clinical adverse effects were detected in any patient. Acute phase malaria infection significantly influenced the pharmacokinetics of artesunate and its active metabolite, dihydroartemisinin. Maximum plasma drug concentration (C(max)), absorption half-life (t((1/2)a)), area under the plasma concentration-time curve from zero to the last observed time (AUC) and terminal elimination half-life (t((1/2)z)) of artesunate were decreased, while apparent total body clearance (CL/f) was increased during the acute phase, compared with the recovery phase. In addition, a decrease in the C(max) and an increase in the AUC(DHA/ARS ) ratio were found. Optimisation of therapy with oral artesunate should therefore be based on the kinetics of the drug and dihydroartemisinin in malaria patients with acute phase infection.
Baird, J K; Purnomo; Masbar, S
We report 34 infections by Plasmodium ovale found among 15,806 blood film examinations taken between 1973 and 1989 from several sites in Indonesia. Twenty five of the P. ovale infections occurred in a single sample of 514 people living in Owi, Irian Jaya. We detected five additional infections at 3 other sites in Irian Jaya. Other infections by P. ovale occurred at two sites in West Flores. Another infection has already been reported from East Timor. Despite relatively frequent sampling of populations on Sumatra, Kalimantan, Java and Sulawesi, P. ovale has not been found on those islands. It appears that this parasite occurs only on the easternmost islands of the Indonesian archipelago where it is nonetheless a rare finding.
Full Text Available To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever.A randomized, open-label, active control trial with two parallel arms.Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal.Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria.Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days.The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse.Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval fever clearance times were 92 hours (84-114 hours for gatifloxacin recipients and 138 hours (105-164 hours for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001. 19 out of 70 (27% patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1% in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001. Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death numbered 29. They were determined to be (95% confidence interval 37.6 % (27.14%-50.2% in the cefixime group and 3.5% (2.2%-11.5% in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001. There was one death in the cefixime group.Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime.Current Controlled Trials ISRCTN75784880.
Kim, Jae-Gyum; Choi, Jeong-Yoon; Kim, Sung Un; Jung, Jin-Man; Kwon, Do-Young; Park, Moon Ho; Oh, Kyungmi
Headache may be a warning sign of subsequent stroke in patients with vertebral artery dissection (VAD). Even though the headache characteristics of VAD have been described predominantly in patients with extracranial VAD and neurological complications, headache semiology is not well known in patients with uncomplicated intracranial vertebral artery dissection (ICVAD). In the present study, we attempt to identify the headache semiology that characterizes ICVAD and validate the revised version of the International Classification of Headache Disorders (ICHD-3 beta) criteria for headache attributed to intracranial artery dissection. Six patients with neurologically uncomplicated ICVAD presented at a participating medical center, and eight similar patients were reviewed in the literature. Combining these data, we analyzed headache characteristics of patients with uncomplicated ICVAD according to their pain onset and duration, nature, intensity, location, aggravating and relieving factors, associated symptoms, response to medication, and prognosis. Headache in uncomplicated ICVAD usually has an acute mode of onset (11/14) and persistent (10/14) temporal feature. Pain that has a throbbing quality (nine of 14) and severe intensity (13/14) on the ipsilesional (10/14) and occipitonuchal area (12/14) is a headache prototype in ICVAD. Additionally, headache was intensified by head flexion and rotation (three of six), and relieved by head extension and supine positioning (five of six). Headache of all patients in the present study fulfilled the ICHD-3 beta criteria. Headache semiology of uncomplicated ICVAD is mostly homogenous in the present study. These characteristics may be helpful in the diagnosis of uncomplicated ICVAD. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Ashley Evans Nicholas
Full Text Available An uncomplicated crown fracture is a fracture that involves only the tooth enamel or the dentin and tooth enamel without any damage or exposure to the pulp. Crown fracture of the anterior teeth usually caused by traumatic forces such as falls, accidents, violence, or sports activities. Traumatic injuries of the oral region frequently involve the anterior teeth, especially maxillary incisors due to the anatomic factors which may affect the functional and aesthetical values of the teeth. The objective of this literature study was to know more about uncomplicated crown fracture of the anterior teeth and its restoration. This research was a literature study performed by researching, highlighting various interesting facts and compiling the relevant published journals. The most common and ideal direct restoration of the anterior teeth was the composite resin restoration. The anterior teeth restoration was considered to be a complex and challenging case to solves due to the fact that besides reconstructing the tooth and regaining the function, the aesthetical aspect was also becoming the main objectives. The permanent anterior teeth uncomplicated crown fracture was the most common case of tooth fractures which was mainly caused by traumatic injuries such as falls, accidents, excessive forces, violence, and also sports activities. Dental injuries of the anterior teeth also affected the aesthetical properties and the function of the tooth. Composite resin restoration was able to performed directly on the permanent anterior teeth uncomplicated crown fracture.
1Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia. C. S. ABSTRACT. Objectives: The aim of this evaluation was to identify pitfalls in medical prescriptions of uncomplicated urinary ... competences such as principles of clinical pharmacology, knowledge, skill and critical. 1 judgement, among ...
Walker, Robin L; Chen, Guanmin; McAlister, Finlay A; Campbell, Norm R C; Hemmelgarn, Brenda R; Dixon, Elijah; Ghali, William; Rabi, Doreen; Tu, Karen; Jette, Nathalie; Quan, Hude
Hospitalizations for ambulatory care sensitive conditions (ACSC) represent an indirect measure of access and quality of community care. This study explored hospitalization rates for 1 ACSC, uncomplicated hypertension, and the factors associated with hospitalization. A cohort of patients with incident hypertension, and their covariates, was defined using validated case definitions applied to International Classification of Disease administrative health data in 4 Canadian provinces between fiscal years 1997 and 2004. We applied the Canadian Institute for Health Information's case definition to detect all patients who had an ACSC hospitalization for uncomplicated hypertension. We employed logistic regression to assess factors associated with an ACSC hospitalization for uncomplicated hypertension. The overall rate of hospitalizations for uncomplicated hypertension in the 4 provinces was 3.7 per 1000 hypertensive patients. The risk-adjusted rate was lowest among those in an urban setting (2.6 per 1000; 95% confidence interval [CI], 2.3-2.7), the highest income quintile (3.4 per 1000; 95% CI, 2.8-4.2), and those with no comorbidities (3.6 per 1000; 95% CI, 3.2-3.9). Overall, Newfoundland had the highest adjusted rate (5.7 per 1000; 95% CI, 4.9-6.7), and British Columbia had the lowest (3.7 per 1000; 95% CI, 3.4-4.2). The adjusted rate declined from 5.9 per 1000 in 1997 to 3.7 per 1000 in 2004. We found that the rate of hospitalizations for uncomplicated hypertension has decreased over time, which might reflect improvements in community care. Geographic variations in the rate of hospitalizations indicate disparity among the provinces and those residing in rural regions. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Mulenga, M; Sukwa, T Y; Canfield, C J; Hutchinson, D B
Atovaquone and proguanil hydrochloride are blood schizonticides that demonstrate in vitro synergy against drug-resistant strains of Plasmodium falciparum. When coadministered, they may therefore be effective for the treatment of malaria in regions where there is known or suspected drug resistance. In an open-label, randomized, parallel-group, clinical trial conducted in Zambia, 163 patients (age range, 14 to 54 years) with acute P falciparum malaria were randomly assigned to receive treatment with atovaquone and proguanil hydrochloride (1000 and 400 mg, respectively, administered orally at 24-hour intervals for 3 doses; n = 82) or pyrimethamine/sulfadoxine (75/1500 mg administered orally as a single dose; n = 81). Efficacy was assessed by cure rate (the percentage of patients in whom parasitemia was eliminated and did not recur during 28 days of follow-up), parasite clearance time (PCT), and fever clearance time (FCT). Safety was determined by sequential clinical and laboratory assessments over 28 days. Cure rates did not differ significantly between patients treated with atovaquone and proguanil (100%) and those treated with pyrimethamine/sulfadoxine (98.8%). Patients in the atovaquone and proguanil group had a significantly shorter FCT than patients in the pyrimethamine/sulfadoxine group (mean, 30.4 vs 44.9 hours; P proguanil was equally effective and as well tolerated as pyrimethamine/sulfadoxine for the treatment of acute, uncomplicated, drug-resistant falciparum malaria in Zambia.
Hogan, John; Sehgal, Rishabh; Murphy, Dermot; O'Leary, Peter; Coffey, J Calvin
The usefulness of inflammatory indices in assessment of the severity of acute diverticulitis remains unestablished. The aim of this study was to determine whether inflammatory indices and hematological ratios could be utilised to differentiate between uncomplicated and complicated diverticulitis. Hematological and inflammatory indices were recorded for each admission with CT confirmed acute diverticulitis (101 complicated, 127 uncomplicated). Cases were divided into training (n = 57) and test sets (n = 171). A classification and regression tree (CART) analysis was employed in the training set to identify optimal inflammatory marker cut-off points associated with complicated diverticulitis. Samples (test set) were then categorized as (A) greater than and (B) less than CART identified cut-off points. The predictive properties of inflammatory marker cut-off points in distinguishing severity of diverticulitis were assessed using a univariate logistic regression analysis, summary receiver operating characteristic curves and confusion matrix generation. C-reactive protein >109 mg/ml (OR 3.07, 95% CI 1.43-6.61, p = 0.004, area under the curve; AUC = 0.64) and white cell lymphocyte ratio (WLR) >17.72 (OR 4.23, 95% CI 1.95-9.17, p 21 × 109/l (p = 0.02, AUC = 0.60) and lymphocyte count >0.55 × 109/l (p = 0.009, AUC = 0.60) were less accurate. Widely used inflammatory indices are useful in the depiction of complicated diverticulitis. The indices cut-off points highlighted in this study should be considered at the time of diagnosis in combination with radiological features of complicated diverticulitis. © 2016 S. Karger AG, Basel.
Djimde Abdoulaye A.
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.
Djimde, Abdoulaye A; Maiga, Amelia W; Ouologuem, Dinkorma; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Doumbo, Ogobara K
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. © A.A. Djimde et al., published by EDP Sciences, 2016.
Buchs, Nicolas C; Mortensen, Neil J; Ris, Frederic; Morel, Philippe; Gervaz, Pascal
While diverticular disease is extremely common, the natural history (NH) of its most frequent presentation (i.e., sigmoid diverticulitis) is poorly investigated. Relevant information is mostly restricted to population-based or retrospective studies. This comprehensive review aimed to evaluate the NH of simple sigmoid diverticulitis. While there is a clear lack of uniformity in terminology, which results in difficulties interpreting and comparing findings between studies, this review demonstrates the benign nature of simple sigmoid diverticulitis. The overall recurrence rate is relatively low, ranging from 13% to 47%, depending on the definition used by the authors. Among different risk factors for recurrence, patients with C-reactive protein > 240 mg/L are three times more likely to recur. Other risk factors include: Young age, a history of several episodes of acute diverticulitis, medical vs surgical management, male patients, radiological signs of complicated first episode, higher comorbidity index, family history of diverticulitis, and length of involved colon > 5 cm. The risk of developing a complicated second episode (and its corollary to require an emergency operation) is less than 2%-5%. In fact, the old rationale for elective surgery as a preventive treatment, based mainly on concerns that recurrence would result in a progressively increased risk of sepsis or the need for a colostomy, is not upheld by the current evidence. PMID:26649154
Barnwell John W
Full Text Available Abstract More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential.
van der Kam, Saskia; Swarthout, Todd; Niragira, Oscar; Froud, Alyson; Sompwe, Eric Mukomena; Mills, Clair; Roll, Stephanie; Tinnemann, Peter; Shanks, Leslie
Background Catch-up growth after an infection is essential for children to maintain good nutritional status. To prevent malnutrition, WHO recommends that children are given one additional healthy meal per day during the 2 weeks after onset of illness. We investigated to what extent ready-to-use therapeutic food (RUTF) promotes catch-up growth in children after an acute, uncomplicated episode of Plasmodium falciparum malaria. Methods We did an open randomised trial of children aged 6–59 months with confirmed malaria who attended a Médecins Sans Frontières-supported outpatient clinic in Katanga Province, Democratic Republic of Congo. All children received a clinical examination and malaria treatment. Patients were then randomly assigned to either an RUTF group, who received daily supplemental RUTF (a high-protein peanut-based paste) for 14 days, or to a control group, who received no supplemental food. Children were weighed at baseline and on days 14 and 28. The primary outcome was mean weight change after 14 days' RUTF. Analysis was by intention-to-treat. Results 93 children received RUTF and 87 received no food supplementation. At day 14, the RUTF group had a mean weight gain of 353 g compared with 189 g in the control group (difference 164 [95%CI 52–277], p = 0.005). However, at day 28 there was no statistically significant difference between the groups (539 g versus 414 g, respectively [p = 0.053]). Similarly, rate of weight gain per kg bodyweight per day was significantly higher at day 14 in the RUTF group (2.4 g/kg per day versus 1.3 g/kg per day, p = 0.005) but at day 28 was 1.9 g/kg per day in the RUTF group versus 1.5 g/kg per day in the control group (p = 0.076). Conclusions Children receiving RUTF for 14 days after effective treatment of an uncomplicated malaria episode had a faster weight gain than children not given supplementation, reducing the period that children were at risk of malnutrition. Trial Registration Clinical
A retrospective cohort study was carried out in a university teaching hospital to determine the prospective risk of unexpected fetal death in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies after viability. All MCDA twins delivered at or after 24 weeks\\' gestation from July 1999 to July 2007 were included. Pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence were excluded. Of the 144 MCDA twin pregnancies included in our analysis, the risk of intrauterine death was 4.9%. The prospective risk of unexpected intrauterine death was 1 in 43 after 32 weeks\\' gestation and 1 in 37 after 34 weeks\\' gestation. Our results demonstrate that despite close surveillance, the unexpected intrauterine death rate in uncomplicated MCDA twin pregnancies is high. This rate seems to increase after 34 weeks\\' gestation, suggesting that a policy of elective preterm delivery warrants evaluation.
O' Connell, AnnaMarie [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); Donoghue, Veronica B. [Children' s University Hospital, Radiology Department, Dublin 1 (Ireland); National Maternity Hospital, Radiology Department, Dublin (Ireland)
Classic metaphyseal lesion (CML) is the term given to a fracture that most often occurs in the posteromedial aspect of the distal femur, proximal tibia, distal tibia, and proximal humerus in infants; this finding is strongly associated with non-accidental injury. To demonstrate that the CML may occur following simple lower segment caesarean section (LSCS). A review of 22 years of an obstetric practice that delivers 8,500 babies per year. We identified three neonates born by elective LSCS, each with distal femoral metaphyseal fractures on postpartum radiographs. All caesarean sections were elective and uncomplicated. External cephalic version was not employed preoperatively. Postpartum radiographs demonstrated a fracture of the distal femoral metaphysis in each neonate, typical of a CML. We propose that a CML can occur in the setting of a simple, elective and uncomplicated LSCS where no external cephalic version is employed. (orig.)
Park, H C; Kim, M J; Lee, B H
Uncomplicated appendicitis may resolve spontaneously or require treatment with antibiotics or appendicectomy. The aim of this randomized trial was to compare the outcome of a non-antibiotic management strategy with that of antibiotic therapy in uncomplicated appendicitis. Patients presenting to a university teaching hospital with CT-verified uncomplicated simple appendicitis (appendiceal diameter no larger than 11 mm and without any signs of perforation) were randomized to management with a no-antibiotic regimen with supportive care (intravenous fluids, analgesia and antipyretics as necessary) or a 4-day course of antibiotics with supportive care. The primary endpoint was rate of total treatment failure, defined as initial treatment failure within 1 month and recurrence of appendicitis during the follow-up period. Some 245 patients were randomized within the trial, and followed up for a median of 19 months. The duration of hospital stay was shorter (mean 3·1 versus 3·7 days; P therapy without antibiotics. There was no difference in total treatment failure rate between the groups: 29 of 124 (23·4 per cent) in the no-antibiotic group and 25 of 121 (20·7 per cent) in the antibiotic group (P = 0·609). Eighteen patients (9 in each group) had initial treatment failure, 15 of whom underwent appendicectomy and three received additional antibiotics. Thirty-six patients (20 in the no-antibiotic group, 16 in the antibiotic group) experienced recurrence, of whom 30 underwent appendicectomy and six received further antibiotics. Treatment failure rates in patients presenting with CT-confirmed uncomplicated appendicitis appeared similar among those receiving supportive care with either a no-antibiotic regimen or a 4-day course of antibiotics. Registration number: KCT0000124 ( http://cris.nih.go.kr). © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.
Cefotaxime (Claforan) in the treatment of uncomplicated gonorrhoea in Zarian, Northern Nigeria. C.S.S Bello, O.Y Elegbe, J.D Dada. Abstract. No Abstract. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/wajpdr.v6i1.53364 · AJOL African ...
Sahin, Erdem; Madendag, Yusuf; Tayyar, Ahter Tanay; Sahin, Mefkure Eraslan; Col Madendag, Ilknur; Acmaz, Gokhan; Unsal, Deniz; Senol, Vesile
The purpose of this study is to determine the adverse perinatal outcomes in uncomplicated late preterm pregnancies with borderline oligohydramnios. A total of 430 pregnant women with an uncomplicated singleton pregnancy at a gestational age of 34 + 0-36 + 6 weeks were included. Borderline oligohydramnios was defined as an amniotic fluid index (AFI) of 5.1-8 cm, which was measured using the four-quadrant technique. Adverse perinatal outcomes were compared between the borderline and normal AFI groups. Approximately 107 of the 430 pregnant women were borderline AFI, and 323 were normal AFI. The demographic and obstetric characteristics were similar in both groups. Delivery borderline AFI group (p = .040). In addition, fetal renal artery pulsatility index pulsatility index (PI) was significantly lower in the borderline AFI group than in the normal AFI group (p = .014). Our results indicated that borderline AFI was not a risk for adverse perinatal outcomes in uncomplicated, late preterm pregnancies.
Joo, Jeong Il; Park, Hyoung-Chul; Kim, Min Jeong; Lee, Bong Hwa
The aim of the present study is to determine the feasibility and safety of antibiotics for uncomplicated simple appendicitis in pregnancy. We conducted a 6-year prospective observational study on 20 pregnant women in whom uncomplicated simple appendicitis (appendiceal diameter ≤11 mm and with no signs of appendicoliths, perforation, or abscess) was radiologically verified and managed with a 4-day course of antibiotics. Treatment failure rate, defined as the need for an appendectomy during hospitalization and recurrence in the follow-up period (median 25 months), and maternal or fetal complications during the pregnancy were evaluated. Mean age of patients was 33.4 years, and gestational age was 17.8 weeks. Three patients failed to respond to antibiotic therapy during hospitalization and underwent subsequent appendectomy (2 suppurative and 1 perforated appendicitis). There was 1 wound infection postoperatively. During follow-up, 2 patients during their ongoing pregnancy experienced recurrence at 3 and 6 months post-treatment, and a new course of antibiotics was determined. Patients also experienced recurrence at 8 and 10 months post-treatment and underwent appendectomy. Treatment failure occurred in 5 patients (25%) with no fetal complications during the pregnancy. Antibiotic therapy for uncomplicated appendicitis in pregnancy may be a feasible treatment option without severe maternal and fetal complications. Copyright © 2017 Elsevier Inc. All rights reserved.
Ramasamy, R; Ramasamy, M; Yasawardena, S
There is considerable interest in using merozoite proteins in a vaccine against falciparum malaria. Observations that antibodies to merozoite surface proteins block invasion are a basis for optimism. This article draws attention to important and varied aspects of how antibodies to Plasmodium
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
Mekonnen, Seleshi Kebede; Aseffa, Abraham; Berhe, Nega; Teklehaymanot, Tilahun; Clouse, Ronald M; Gebru, Tamirat; Medhin, Girmay; Velavan, Thirumalaisamy P
Increased resistance by Plasmodium falciparum parasites led to the withdrawal of the antimalarial drugs chloroquine and sulphadoxine-pyrimethamine in Ethiopia. Since 2004 artemether-lumefantrine has served to treat uncomplicated P. falciparum malaria. However, increasing reports on delayed parasite clearance to artemisinin opens up a new challenge in anti-malarial therapy. With the complete withdrawal of CQ for the treatment of Plasmodium falciparum malaria, this study assessed the evolution of CQ resistance by investigating the prevalence of mutant alleles in the pfmdr1 and pfcrt genes in P. falciparum and pvmdr1 gene in Plasmodium vivax in Southern and Eastern Ethiopia. Of the 1,416 febrile patients attending primary health facilities in Southern Ethiopia, 329 febrile patients positive for P. falciparum or P. vivax were recruited. Similarly of the 1,304 febrile patients from Eastern Ethiopia, 81 febrile patients positive for P. falciparum or P. vivax were included in the study. Of the 410 finger prick blood samples collected from malaria patients, we used direct sequencing to investigate the prevalence of mutations in pfcrt and pfmdr1. This included determining the gene copy number in pfmdr1 in 195 P. falciparum clinical isolates, and mutations in the pvmdr1 locus in 215 P. vivax clinical isolates. The pfcrt K76 CQ-sensitive allele was observed in 84.1% of the investigated P.falciparum clinical isolates. The pfcrt double mutations (K76T and C72S) were observed less than 3%. The pfcrt SVMNT haplotype was also found to be present in clinical isolates from Ethiopia. The pfcrt CVMNK-sensitive haplotypes were frequently observed (95.9%). The pfmdr1 mutation N86Y was observed only in 14.9% compared to 85.1% of the clinical isolates that carried sensitive alleles. Also, the sensitive pfmdr1 Y184 allele was more common, in 94.9% of clinical isolates. None of the investigated P. falciparum clinical isolates carried S1034C, N1042D and D1246Y pfmdr1 polymorphisms. All
Lopez, Ana Cecilia; Ortiz, Andres; Coello, Jorge; Sosa-Ochoa, Wilfredo; Torres, Rosa E Mejia; Banegas, Engels I; Jovel, Irina; Fontecha, Gustavo A
Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite's circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n = 77) for pvama-1; 23 (n = 84) for pvcsp; and 23 (n = 35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n = 30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n = 11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.
Kvasnovsky, Charlotte L; Leong, Lex E X; Choo, Jocelyn M; Abell, Guy C J; Papagrigoriadis, Savvas; Bruce, Kenneth D; Rogers, Geraint B
There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis. The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis. Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing. Microbiota composition was related to clinical history, symptom and inflammation measures, and demographic variables. Previous acute diverticulitis was associated with higher relative abundance of Pseudobutyrivibrio, Bifidobacterium, Christensenellaceae family, and Mollicutes RF9 order (P=0.004, 0.006, 0.010, and 0.019, respectively), but not microbiota alpha or beta diversity. A higher bloating severity score was significantly correlated with a higher relative abundance of Ruminococcus (P=0.032), and significantly inversely correlated with the relative abundance of the Roseburia (P=0.002). Fecal calprotectin levels were positively correlated with alpha diversity (Shannon index, P=0.005) and the relative abundance of Lactobacillus (P=0.004). Pain score was positively correlated with the relative abundance of Cyanobacterium (adjusted P=0.032). Patient symptoms in symptomatic diverticular disease are significantly correlated with features of the fecal microbiota. Our findings suggest the potential utility of therapies that target intestinal microbiology, such as dietary prebiotic supplements.
Full Text Available Symptomatic uncomplicated diverticular disease (SUDD is a syndrome characterized by recurrent abdominal symptoms in patients with colonic diverticula. There is some evidence that a high-fiber diet or supplemental fibers may reduce symptoms in SUDD patients and a high-fiber diet is commonly suggested for these patients. This systematic review aims to update the evidence on the efficacy of fiber treatment in SUDD, in terms of a reduction in symptoms and the prevention of acute diverticulitis. According to PRISMA, we identified studies on SUDD patients treated with fibers (PubMed and Scopus. The quality of these studies was evaluated by the Jadad scale. The main outcome measures were a reduction of abdominal symptoms and the prevention of acute diverticulitis. Nineteen studies were included, nine with dietary fiber and 10 with supplemental fiber, with a high heterogeneity concerning the quantity and quality of fibers employed. Single studies suggest that fibers, both dietary and supplemental, could be beneficial in SUDD, even if the quality is very low, with just one study yielding an optimal score. The presence of substantial methodological limitations, the heterogeneity of the therapeutic regimens employed, and the lack of ad hoc designed studies, did not permit a summary of the outcome measure. Thus, the benefit of dietary or supplemental fiber in SUDD patients still needs to be established.
Carabotti, Marilia; Annibale, Bruno; Severi, Carola; Lahner, Edith
Symptomatic uncomplicated diverticular disease (SUDD) is a syndrome characterized by recurrent abdominal symptoms in patients with colonic diverticula. There is some evidence that a high-fiber diet or supplemental fibers may reduce symptoms in SUDD patients and a high-fiber diet is commonly suggested for these patients. This systematic review aims to update the evidence on the efficacy of fiber treatment in SUDD, in terms of a reduction in symptoms and the prevention of acute diverticulitis. According to PRISMA, we identified studies on SUDD patients treated with fibers (PubMed and Scopus). The quality of these studies was evaluated by the Jadad scale. The main outcome measures were a reduction of abdominal symptoms and the prevention of acute diverticulitis. Nineteen studies were included, nine with dietary fiber and 10 with supplemental fiber, with a high heterogeneity concerning the quantity and quality of fibers employed. Single studies suggest that fibers, both dietary and supplemental, could be beneficial in SUDD, even if the quality is very low, with just one study yielding an optimal score. The presence of substantial methodological limitations, the heterogeneity of the therapeutic regimens employed, and the lack of ad hoc designed studies, did not permit a summary of the outcome measure. Thus, the benefit of dietary or supplemental fiber in SUDD patients still needs to be established. PMID:28230737
Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier
The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. © The American Society of Tropical Medicine and Hygiene.
Siv, Sovannaroth; Roca-Feltrer, Arantxa; Vinjamuri, Seshu Babu; Bouth, Denis Mey; Lek, Dysoley; Rashid, Mohammad Abdur; By, Ngau Peng; Popovici, Jean; Huy, Rekol; Menard, Didier
The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed. PMID:27708187
Of the over 156 species of Plasmodium that infect vertebrates, only four infect man: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. Other species infect other animals including birds, reptiles and rodents. The rodent malaria parasites are Plasmodium berghei, Plasmodium yoelii, ...
Ryan A. Zander
Full Text Available Effector T cells exhibiting features of either T helper 1 (Th1 or T follicular helper (Tfh populations are essential to control experimental Plasmodium infection and are believed to be critical for resistance to clinical malaria. To determine whether Plasmodium-specific Th1- and Tfh-like effector cells generate memory populations that contribute to protection, we developed transgenic parasites that enable high-resolution study of anti-malarial memory CD4 T cells in experimental models. We found that populations of both Th1- and Tfh-like Plasmodium-specific memory CD4 T cells persist. Unexpectedly, Th1-like memory cells exhibit phenotypic and functional features of Tfh cells during recall and provide potent B cell help and protection following transfer, characteristics that are enhanced following ligation of the T cell co-stimulatory receptor OX40. Our findings delineate critical functional attributes of Plasmodium-specific memory CD4 T cells and identify a host-specific factor that can be targeted to improve resolution of acute malaria and provide durable, long-term protection against Plasmodium parasite re-exposure.
Tarning, Joel; Kloprogge, Frank; Dhorda, Mehul; Jullien, Vincent; Nosten, Francois; White, Nicholas J; Guerin, Philippe J; Piola, Patrice
Pregnancy alters the pharmacokinetic properties of many drugs used in the treatment of malaria, usually resulting in lower drug exposures. This increases the risks of treatment failure, adverse outcomes for the fetus, and the development of resistance. The pharmacokinetic properties of artemether and its principal metabolite dihydroartemisinin (n = 21), quinine (n = 21), and lumefantrine (n = 26) in pregnant Ugandan women were studied. Lumefantrine pharmacokinetics in a nonpregnant control group (n = 17) were also studied. Frequently sampled patient data were evaluated with noncompartmental analysis. No significant correlation was observed between estimated gestational age and artemether, dihydroartemisinin, lumefantrine, or quinine exposures. Artemether/dihydroartemisinin and quinine exposures were generally low in these pregnant women compared to values reported previously for nonpregnant patients. Median day 7 lumefantrine concentrations were 488 (range, 30.7 to 3,550) ng/ml in pregnant women compared to 720 (339 to 2,150) ng/ml in nonpregnant women (P = 0.128). There was no statistical difference in total lumefantrine exposure or maximum concentration. More studies with appropriate control groups in larger series are needed to characterize the degree to which pregnant women are underdosed with current antimalarial dosing regimens.
Elhassan, I M; Hviid, L; Satti, G
Sudan. In addition, we measured the T cell surface expression of the interleukin-2 receptor (CD25) and the lymphocyte function-associated antigen (LFA-1; CD11a/CD18). We found that the plasma levels of all inflammation and activation markers were significantly increased in the malaria patients compared...
Lemnge, Martha M; Ali, Abdullah S; Malecela, Ezekiel K; Sambu, Edward; Abdulla, Rahma; Juma, Mohamed S; Fakih, Khatibu; Abdulla, Khafidh H; Njau, Ritha J
The efficacy of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was assessed at Kivunge and Micheweni in Zanzibar, Tanzania, in 2001. The main objective was to obtain baseline data after observations of high levels of chloroquine treatment failures. Children (6-59 months) were randomized to receive either drug. At Kivunge, SP and AQ were given to 64 and 63 cases, while for Micheweni, 61 and 70 cases were treated. Main findings were overall high rates (> 90%) of adequate clinical response (ACR) with AQ. A lower ACR was seen in the SP group at Kivunge (87.1%) compared with Micheweni (94.8%). Furthermore, in the ACR group, 16.7% AQ parasitological resistance (RI-RIII) was encountered at Kivunge. Most of the cases of SP parasitological resistance (14.5%; RI/RII) were seen at Micheweni. Notwithstanding this, the overall treatment failure was only 9.2% with SP and 5.5% with AQ. The Zanzibar Ministry of Health has since reviewed its antimalarial drug policy.
Full Text Available Measurement of malaria burden is fraught with complexity, due to the natural history of the disease, delays in seeking treatment or failure of case management. Attempts to establish an appropriate case definition for a malaria episode has often resulted in ambiguities and challenges because of poor information about treatment seeking, patterns of infection, recurrence of fever and asymptomatic infection. While the primary reason for treating malaria is to reduce disease burden, the effects of treatment are generally ignored in estimates of the burden of malaria morbidity, which are usually presented in terms of numbers of clinical cases or episodes, with the main data sources being reports from health facilities and parasite prevalence surveys. The use of burden estimates that do not consider effects of treatment, leads to under-estimation of the impact of improvements in case management. Official estimates of burden very likely massively underestimate the impact of the roll-out of ACT as first-line therapy across Africa. This paper proposes a novel approach for estimating burden of disease based on the point prevalence of malaria attributable disease, or equivalently, the days with malaria fever in unit time. The technique makes use of data available from standard community surveys, analyses of fever patterns in malaria therapy patients, and data on recall bias. Application of this approach to data from Zambia for 2009-2010 gave an estimate of 2.6 (95% credible interval: 1.5-3.7 malaria attributable fever days per child-year. The estimates of recall bias, and of the numbers of days with illness contributing to single illness recalls, could be applied more generally. To obtain valid estimates of the overall malaria burden using these methods, there remains a need for surveys to include the whole range of ages of hosts in the population and for data on seasonality patterns in confirmed case series.
Ma'ayeh, Marwan; McClennen, Evan; Chamchad, Dmitri; Geary, Michael; Brest, Norman; Gerson, Andrew
The umbilical coiling index (UCI) is a measure of the number of coils in the umbilical cord in relation to its length. Hypercoiled cords with a UCI of >0.3 coils/cm have been associated with adverse fetal and neonatal outcomes. The primary aim is to determine the accuracy of UCI measured on second trimester ultrasound in predicting UCI at birth. The secondary outcome is to investigate the association between hypercoiling of the umbilical cord on prenatal ultrasound and adverse maternal, fetal and neonatal outcomes. This was a prospective cohort study of uncomplicated singleton pregnancies. Seventy two patients were included in the study. UCI was measured in the second trimester ultrasound, and compared to UCI measured postnatally. Outcomes of patients with hypercoiled cords on ultrasound were compared to outcomes of patients with normocoiled cords. Our results failed to show a strong correlation between the UCI determined with ultrasound, and the UCI determined with examination of the umbilical cord after delivery. We also did not demonstrate that measurement of the UCI on second trimester ultrasound is able to predict adverse maternal, fetal or neonatal outcomes. This study suggests that measurement of the umbilical coiling index should not be part of routine second trimester sonography in patients with uncomplicated singleton pregnancies, with no other medical or surgical comorbidities.
Swenson, Carolyn W; Lanham, Michael S; Morgan, Daniel M; Berger, Mitchell B
To develop a model for predicting postoperative hematocrit levels after uncomplicated hysterectomy. In a retrospective study, data were analyzed from the Michigan Surgery Quality Collaborative for non-emergent hysterectomies performed for benign indications among women aged at least 18 years between January 1, 2012, and April 4, 2014. Linear mixed models were used for univariate and multivariate analyses. The model was developed with data from 4747 hysterectomies and validated on 1184 cases. In the mixed multivariate analysis, higher postoperative day 1 (POD1) hematocrit levels were associated with higher weight (B=0.03222, Phematocrit (B=0.6587, Phematocrit was associated with higher preoperative platelet count (B=-0.00457, Phematocrit within 4% points of the actual value for 91.7% of cases in the validation set. Use of the model after uncomplicated hysterectomy might help to support the practice of selectively conducting postoperative hematocrit tests after hysterectomy in a clinically thoughtful and cost-effective manner. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini
The most significant and efficient measures against Plasmodium knowlesi outbreaks are efficient anti malaria drug, biological control in form of predatory mosquitoes and culling control strategies. In this paper optimal control theory is applied to a system of ordinary differential equation. It describes the disease transmission and Pontryagin's Maximum Principle is applied for analysis of the control. To this end, three control strategies representing biological control, culling and treatment were incorporated into the disease transmission model. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for disease transmission.
Jan Alexander Hiss
Full Text Available We performed a bioinformatical analysis of protein export elements (PEXEL in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide.
Grillet, María-Eugenia; El Souki, Mayida; Laguna, Francisco; León, José Rafael
We investigated the periodicity of Plasmodium vivax and P. falciparum incidence in time-series of malaria data (1990-2010) from three endemic regions in Venezuela. In particular, we determined whether disease epidemics were related to local climate variability and regional climate anomalies such as the El Niño Southern Oscillation (ENSO). Malaria periodicity was found to exhibit unique features in each studied region. Significant multi-annual cycles of 2- to about 6-year periods were identified. The inter-annual variability of malaria cases was coherent with that of SSTs (ENSO), mainly at temporal scales within the 3-6 year periods. Additionally, malaria cases were intensified approximately 1 year after an El Niño event, a pattern that highlights the role of climate inter-annual variability in the epidemic patterns. Rainfall mediated the effect of ENSO on malaria locally. Particularly, rains from the last phase of the season had a critical role in the temporal dynamics of Plasmodium. The malaria-climate relationship was complex and transient, varying in strength with the region and species. By identifying temporal cycles of malaria we have made a first step in predicting high-risk years in Venezuela. Our findings emphasize the importance of analyzing high-resolution spatial-temporal data to better understand malaria transmission dynamics. Copyright © 2013 Elsevier B.V. All rights reserved.
Zenz, W; Trop, M; Kollaritsch, H; Reinthaler, F
Increasing tourism and growing numbers of immigrants from malaria-endemic countries are leading to a higher importation rate of rare tropical disorders in European countries. We describe, to the best of our knowledge, the first case of connatal malaria in Austria. The patient is the first child of a 24 year old mother who was born in Ghana and immigrated to Austria one and a half years before delivery. She did not stay in an endemic region during this period and did not show fever or any other signs of malaria. The boy was healthy for the first six weeks of his life. In the 8th week of life he was admitted to our hospital due to persistent fever of unknown origin. On physical examination he showed only mild splenomegaly. Routine laboratory testing revealed mild hemolytic anemia with a hemoglobin value of 8.3 g/l. In the blood smear Plasmodium falciparum and Plasmodium malariae were detected. Oral therapy with quinine hydrochloride was successful and blood smears became negative for Plasmodia within 6 days. This case shows that congenital malaria can occur in children of clinically healthy women who were born in malaria-endemic areas even one and a half year after they have immigrated to non-endemic regions.
Full Text Available We examined the prevalence of specific perinatal complications of monochorionic-diamniotic twin pregnancies in cases without any abnormal findings until the second trimester of pregnancy. This was a retrospective cohort study performed at a tertiary perinatal center in Tokyo, Japan. There were 88 cases of uncomplicated monochorionic-diamniotic twin pregnancies at 28 weeks of gestation. In five of them (5.7%, there were serious complications associated with placental circulatory imbalance between the twins during the third trimester of pregnancy. Two cases were complicated by twin–twin transfusion syndrome, two cases were complicated by twin anemia–polycythemia sequence, and one case was complicated by acute twin–twin transfusion syndrome. In the five cases, no abnormal ultrasonographic findings or symptoms were recognized one or two weeks prior to the diagnosis. Fifty-eight cases (65.9% were delivered at term uneventfully. Serious complications due to placental circulatory imbalance between twins occurred in about 6% of cases during the third trimester of pregnancy.
Mahieu, J; Mansvelt, B; Veys, E
Giant colonic diverticulum (GCD) is a rare complication of colonic diverticulosis. A small number of cases has been reported in the literature. Patients with GCD have often few non-specific symptoms. Unfortunately, severe complications exist and may lead to surgical acute abdomen. Therefore, this complication of the diverticular disease must be known and properly treated. There is no gold standard diagnostic test, but an air-fluid or air-filled, rounded, pseudocystic image in relation with the colonic wall in a patient with colonic diverticula should suggest this diagnosis to the clinician. We report two cases of a 70-year-old male patient and a 44-year-old female patient having a giant sigmoid diverticulum. The treatment of choice of an uncomplicated GCD is an elective colonic resection, including the giant -diverticulum, with primary anastomosis ; while in case of complicated GCD (peritonitis, abscess or complex fistula), a two-stage resection should be considered. Copyright© Acta Chirurgica Belgica.
A. S. Golovkin
Full Text Available Abstract. We have observed thirty-six patients with coronary artery disease (CAD who have undergone coronary artery bypass graft (CABG surgery. In patients with uncomplicated clinical course post-CABG, total lymphocyte counts, T-, B- and NK-cell contents did not significantly differ from baseline levels. Meanwhile, the numbers of CD14HIGH and CD14LOW monocyte subpopulations showed significant differences from initial levels at day 1 and day 7 after surgery. The changes in monocyte subsets in blood of patients with and absence of post-surgical septic complications reflected severity of inflammatory response, and development of systemic inflammatory syndrome. In such a case, further studies of peripheral blood monocytes can be both a useful tool for studying the mechanisms of systemic inflammation, as well as a good diagnostic system, in order to assess the patient’s condition and to predict post-surgical clinical outcomes.
Hryniewiecki, Tomasz; Sitkiewicz, Dariusz; Rawczyńska-Englert, Irena
Infective endocarditis especially where blood culture is negative frequently causes problems in diagnosis despite of many nonspecific inflammation parameters. Procalcitonin (PCT) concentration is a new marker of severe bacterial and fungal infection. The aim of this study was to evaluate the usefulness of PCT concentration assessment in the diagnosis of uncomplicated infective endocarditis of bacterial etiology. The study group consisted of 30 patients with ongoing infective endocarditis in the course of acquired valvular heart disease. The diagnosis of bacterial endocarditis was established according to the Duke criteria on the basis of: clinical examination, laboratory investigations (inflammatory parameters, transthoracic and transesophageal echocardiography) and positive blood cultures. Patients with sepsis, concomitant infections and in an early postoperative period were excluded. Two control groups consisted of: 10 patients without endocarditis and other infections and another 10 patients without endocarditis and with an urinary tract infection. Serum procalcitonin concentrations were measured by an immunoluminometric assay (LUMItest PCT set). Mean serum PCT concentrations in patients with endocarditis (0.12 +/- 0.13, range 0-0.4 ng/ml) were significantly higher than in control group without infection (0.03 +/- 0.05, range 0-0.1 ng/ml) and higher than in control group with an urinary tract infection (0.02 +/- 0.04, range 0-0.1 ng/ml). However in 12 patients (of 30) were below sensitivity of the method and in the rest were within normal range (< 0.5 ng/ml). Serum PCT concentration assessment seems to have no value in the diagnosis of uncomplicated infective endocarditis.
Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N; Khan, Wasif Ali
The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0-2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3) hours for P. falciparum, 20.0 (IQR: 9.5-22.7) hours for P. vivax and 16.6 (IQR: 10.0-46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (G6PD deficiency (10-60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather than primaquine administration. ClinicalTrials.gov NCT
Full Text Available The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy.Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0-2 plus single dose primaquine (0.75mg/kg on day2 for P. falciparum infections, or with chloroquine (days 0-2 plus 14 days primaquine (3.5mg/kg total over 14 days for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374.Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections. Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2-27.3 hours for P. falciparum, 20.0 (IQR: 9.5-22.7 hours for P. vivax and 16.6 (IQR: 10.0-46.0 hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174 had severe G6PD deficiency (<10% activity, five participants (5/174 had mild G6PD deficiency (10-60% activity. The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0% and -7.4% (95%CI: -4.5 to -10.4% respectively.The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal individuals was attributable to acute malaria rather
Staelens, Anneleen S; Vonck, Sharona; Molenberghs, Geert; Malbrain, Manu L N G; Gyselaers, Wilfried
Body fluid composition changes during the course of pregnancy and there is evidence to suggest that these changes are different in uncomplicated pregnancies compared to hypertensive pregnancies. The aim of this study was to evaluate the changes in maternal body fluid composition during the course of an uncomplicated pregnancy and to assess differences in uncomplicated pregnancies versus hypertensive pregnancies by using a bio-impedance analysis technique. Body fluid composition of each patient was assessed using a multiple frequency bioelectrical impedance analyser. Measurements were performed in 276 uncomplicated pregnancies, 34 patients with gestational hypertension, 35 with late onset preeclampsia and 11 with early onset preeclampsia. Statistical analysis was performed at nominal level α=0.05. A longitudinal linear mixed model based analysis was performed for longitudinal evolutions, and ANOVA with a post-hoc Bonferroni was used to identify differences between groups. Measurements showed that total body water (TBW), intracellular (ICW) and extracellular water (ECW) and ECW/ICW significantly increase during the course of pregnancy. Late onset preeclampsia is associated with a higher TBW and ECW as compared to uncomplicated pregnancies, the ECW/ICW ratio is higher in preeclamptic patients compared to uncomplicated pregnancies and gestational hypertension, and ICW is not different between groups. Body fluid composition changes differently during the course of uncomplicated pregnancies versus hypertensive pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Full Text Available Malaria is an acute and chronic illness characterized by paroxysms of fever, chills, sweats, fatigue, anemia, and splenomegaly. It is still an important health problem in malaria-endemic countries. Children living in malaria-endemic areas have elevated Epstein-Barr Virus (EBV loads in the circulation and acute malaria infection leads to increased levels of circulating EBV that are cleared after anti-malaria treatment. There are many reports about the association of Plasmodium falciparum (P. falciparum malaria and EBV infection. Here we report a case who had coinfection of Plasmodium vivax (P. vivax malaria and EBV infection. To the best of our knowledge this is the first case indicating the association of P. vivax malaria and EBV infection.
Enevold, Anders; Lusingu, John P; Mmbando, Bruno
the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area...... measured with flow cytometry and ELISA assays, respectively. Regression analyses showed that alpha(+)-thalassemia was associated with a reduced risk of uncomplicated malaria episodes and that this advantageous effect seemed to be more predominant in children older than 5 years of age, but was independent...
Alan Kang-Wai Mu
Full Text Available Malaria is caused by parasitic protozoans of the genus Plasmodium and is one of the most prevalent infectious diseases in tropical and subtropical regions. For this reason, effective and practical diagnostic methods are urgently needed to control the spread of malaria. The aim of the current study was to identify a panel of new malarial markers, which could be used to diagnose patients infected with various Plasmodium species, including P. knowlesi, P. vivax and P. falciparum. Sera from malaria-infected patients were pooled and compared to control sera obtained from healthy individuals using the isobaric tags for relative and absolute quantitation (iTRAQ technique. Mass spectrometry was used to identify serum proteins and quantify their relative abundance. We found that the levels of several proteins were increased in pooled serum from infected patients, including cell adhesion molecule-4 and C-reactive protein. In contrast, the serum concentration of haptoglobin was reduced in malaria-infected individuals, which we verified by western blot assay. Therefore, these proteins might represent infectious markers of malaria, which could be used to develop novel diagnostic tools for detecting P. knowlesi, P. vivax and P. falciparum. However, these potential malarial markers will need to be validated in a larger population of infected individuals.
Sagara, Issaka; Piarroux, Renaud; Djimde, Abdoulaye; Giorgi, Roch; Kayentao, Kassoum; Doumbo, Ogobara K; Gaudart, Jean
In sub-Saharan Africa, artemisinin-based combination therapy (ACT) and injectable artesunate are the first-line treatments for uncomplicated and severe Plasmodium falciparum malaria, respectively. However, recent studies suggest that delayed anaemia is associated with these treatments in non-immune travellers. This paper aimed to assess the risk factors associated with delayed anaemia after falciparum malaria treatment with artemisinin-containing drugs in malaria-endemic populations. Pooled, individual malaria patient data were extracted from 13 clinical trials performed from 2002 to 2011 in various settings of Mali. Treatment regimens were artemether-lumefantrine, artesunate plus amodiaquine, artesunate plus sulphadoxine-pyrimethamine, artesunate plus sulphamethoxypyrazine-pyrimethamine, artesunate plus mefloquine, artesunate-pyronaridine, artesunate monotherapy, chloroquine, sulphadoxine-pyrimethamine, amodiaquine and sulphadoxine-pyrimethamine plus amodiaquine. Univariate and multivariate analyses were performed using the generalized linear and latent mixed model procedures to assess risk factors associated with haemoglobin concentration evolution and anaemia during the treatment follow-up. A total of 5,990 participants were recruited and followed from day 0 to day 28. The participants' median age was five years, ranging from three months to 70 years. There was a decrease in haemoglobin level on day 7 in all treatment arms, but the magnitude varied across treatments. There was a significant risk of haemoglobin level decrease on day 7 in the artemisinin-based therapy compared to the non-artemisinin treatments. The risk of haemoglobin concentration drop was associated with age group Oral artemisinin derivative treatments for uncomplicated P. falciparum malaria are associated with a transient and clinically moderate haemoglobin decrease by day 7 but not associated with a delayed severe anaemia.
Maiga, Hamma; Djimde, Abdoulaye A; Beavogui, Abdoul H; Toure, Ousmane; Tekete, Mamadou; Sangare, Cheick Papa O; Dara, Antoine; Traore, Zoumana I; Traore, Oumar B; Dama, Souleymane; N'Dong, Christelle; Niangaly, Hamidou; Diallo, Nouhoum; Dembele, Demba; Sagara, Issaka; Doumbo, Ogobara K
Plasmodium falciparum resistance to artemisinin has been reported in South-East Asia. Long half-life drugs are increasingly being used for malaria prevention. The potential spread of parasite resistance to these regimens is real and makes regular efficacy surveillance a priority. From August to December 2004 and July to December 2005, a randomized open label trial of sulphadoxine-pyrimethamine (SP) + artesunate (AS) versus SP + amodiaquine (AQ), and SP alone, was conducted in two villages of Mali. PCR was used to distinguish new infections from recrudescent P. falciparum infections. Patients were followed for 28 days to assess treatment efficacy. Overall 912 children aged between six to 59 months, with uncomplicated P. falciparum malaria were recruited. Baseline characteristics were similar in the three treatment arms. Crude ACPRs were 94.9%; 98.6% and 93.5% for SP + AS; SP + AQ and SP alone arms respectively (SP + AS versus SP + AQ, p = 0.01; SP + AS versus SP, p = 0.5; SP + AQ versus SP, p = 0.001). After PCR adjustment, cACPRs were 99%; 100% and 97.2% for SP + AS; SP + AQ and SP alone arms, respectively (SP + AS versus SP + AQ, p = 0.25; SP + AS versus SP, p = 0.12; SP + AQ versus SP, p = 0.007). Sulphadoxine-pyrimethamine + amodiaquine therapy was as efficacious as sulphadoxine-pyrimethamine + artesunate, but more efficacious than sulphadoxine-pyrimethamine alone in the treatment of uncomplicated P. falciparum malaria in Mali.
Ansari, Hifzur Rahman
Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.
Rosalind E Howes
Full Text Available Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf. Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health
Shields, Joanne; Maxwell, Alexander P
Urinary tract infection (UTI) may predominantly involve the lower urinary tract, i.e. acute cystitis, or upper urinary tract consisting of the renal pelvis and kidney,, i.e. acute pyelonephritis The incidence of acute pyelonephritis is higher in young women than in men but the incidence in men over 65 is similar to that in older women. Women have up to a 10% risk of recurrent acute pyelonephritis in the year following a first acute episode. The equivalent risk in men is 6%. Acute pyelonephritis may be uncomplicated and resolve without serious sequelae. A minority of episodes may be complicated by acute kidney injury, papillary necrosis, renal or perinephric abscess or the development of emphysematous pyelonephritis. Acute pyelonephritis is generally caused by microorganisms ascending from the urethra via the bladder into the upper urinary tract. Rarely the kidney may be seeded by blood-borne infection. Ecoli is the most common uropathogen causing pyelonephritis accounting for 70-90% of infections. Species of Enterococci, Klebsiella, Pseudomonas, Proteus and Staphylococci are responsible for the remaining infections. There is a rising incidence in the community of UTI with bacteria that produce extended spectrum beta-lactamase (ESBL) enzymes. These ESBL bacteria have developed resistance to antibiotics such as penicillin, cephalosporins and increasingly to quinolones. Risk factors for uncomplicated acute pyelonephritis include recent sexual intercourse, acute cystitis, stress incontinence and diabetes and for complicated acute pyelonephritis include pregnancy, diabetes, anatomical abnormalities of the urinary tract and renal calculi.
Full Text Available Background & aim: Jaundice is one of the most significant problems to consider in the neonatal period. The aim of this study was to determine the impact of oral zinc sulfate on uncomplicated neonatal jaundice using comparison of effect of just phototherapy with the effect of combination of phototherapy and oral zinc sulfate. Methods: The present double blind randomized clinical trial was carried out on 78 normal term neonates with the age of 2-7 days who were admitted for uncomplicated jaundice in neonatal ward of Imam Sajjad Hospital of Yasuj University of Medical Sciences. These infants were divided to experimental group (40 cases and control group (38 cases using block random allocation. In the control group, phototherapy was done alone and experimental group received elemental zinc orally as 10 mg daily for 5 days in combination with phototherapy. The total bilirubin serum levels were measured at the beginning of the study , 6 hours, 12 hours, and 24 hours after the beginning of the study, discharge, and one week after discharge. The collected data were analyzed by the Chi Square test, independent t-test, and analysis of variance with repeated measurement. Results: There were no significant statistical difference between the experimental group and control group in sex, age, birth weight, hemoglobin, reticulocyte percentage, G6PD deficiency, and of serum total bilirubin level at the beginning of study(p>0.05. Analysis of variance with repeated measurement showed that there were no significant statistical difference between the total bilirubin serum level at 6 hours, 12 hours, 24 hours after beginning of the study, discharge, and one week after discharge (p>0.05. Also, the mean of hospitalization duration was not significantly different between the two groups (p>0.05. Conclusion: Although oral zinc salts inhibit the enterohepatic circulation of bilirubin, however probably not effective in the treatment of neonatal physiologic
Miller, Loren G; Daum, Robert S; Creech, C Buddy; Young, David; Downing, Michele D; Eells, Samantha J; Pettibone, Stephanie; Hoagland, Rebecca J; Chambers, Henry F
Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear. We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment. A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups. We found no significant difference between clindamycin and TMP-SMX, with respect to either
Comparative assessment of the clinical performance of chloroquine and sulphadoxine/pyrimethamine in the treatment of Plasmodium falciparum infection in Plateau State: an open randomised study of 109 children with acute uncomplicated malaria.
Adjei, George O; Goka, Bamenla Q; Binka, Fred
Artemether-lumefantrine (AL; Coartem, Riamet) is the first fixed-dose artemisinin combination therapy (ACT) regimen to be manufactured under Good Manufacturing Practice conditions, and is the most widely adopted ACT regimen used in malaria control programs. AL is approved for the treatment...... of uncomplicated malaria in adults, children and infants, and as treatment of uncomplicated malaria in nonimmune travelers returning from malarious areas. AL is efficacious for treating uncomplicated malaria in children and the frequency of associated adverse events is not higher than other available ACT regimens....... In this review, available evidence on efficacy and safety of AL in the treatment of uncomplicated malaria, with emphasis on children where appropriate, and focusing on characteristics that are potentially important for malaria control policy decisions, are presented and discussed....
Hviid, L; Kurtzhals, J A; Dodoo, D
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...... areas where malaria is endemic, who bear the burden of malaria-related morbidity and mortality. We investigated the gamma/delta T-cell response in 19 Ghanaian children from an area of hyperendemic, seasonal malaria transmission. The children presented with cerebral malaria (n = 7), severe malarial...... anemia (n = 5), or uncomplicated malaria (n = 7) and were monitored from admission until 4 weeks later. We found no evidence of increased frequencies of gamma/delta T cells in any of the patient groups, whereas one adult expatriate studied in Ghana and three adults admitted to the hospital in Copenhagen...
Keshavarzian, A.; Gibson, R.; Guest, J.; Spencer, J.; Lavender, J.P.; Hodgson, H.J.
We have investigated the presence, duration, and clinical significance of granulocyte accumulation, using indium-111 granulocyte scanning, in patients following uncomplicated intestinal anastomosis. Eight patients underwent intestinal resection and anastomosis (right hemicolectomy, 5; sigmoid colectomy, 2; ileal resection, 1) for carcinoma, angiodysplasia, or perforation. All patients had an uneventful postoperative course, with no evidence of any leakage or infection. Indium-111 granulocyte scan and abdominal ultrasound were performed 7-20 days (12 +/- 4.7 means +/- SD) following surgery. Indium-111 granulocyte scan showed the presence of labeled granulocytes at the site of anastomosis in all patients. In three of eight, cells subsequently passed into the lumen of the bowel. In contrast, granulocytes were not visualized along the abdominal incision. Thus, in contrast to skin wounds, granulocytes continue migrating into the intestinal wall in areas of anastomosis for at least up to 20 days following surgical trauma. They may play a significant role both in healing the anastomosis and in preventing systemic bacterial infection. Moreover, indium-111 granulocyte scans following intestinal surgery should be interpreted with care, and the presence of labeled granulocytes around anastomoses does not necessarily indicate abscess formation.
Keshavarzian, A.; Gibson, R.; Guest, J.; Spencer, J.; Lavender, J.P.; Hodgson, H.J.
We have investigated the presence, duration, and clinical significance of granulocyte accumulation, using indium-111 granulocyte scanning, in patients following uncomplicated intestinal anastomosis. Eight patients underwent intestinal resection and anastomosis (right hemicolectomy, 5; sigmoid colectomy, 2; ileal resection, 1) for carcinoma, angiodysplasia, or perforation. All patients had an uneventful postoperative course, with no evidence of any leakage or infection. Indium-111 granulocyte scan and abdominal ultrasound were performed 7-20 days (12 +/- 4.7 means +/- SD) following surgery. Indium-111 granulocyte scan showed the presence of labeled granulocytes at the site of anastomosis in all patients. In three of eight, cells subsequently passed into the lumen of the bowel. In contrast, granulocytes were not visualized along the abdominal incision. Thus, in contrast to skin wounds, granulocytes continue migrating into the intestinal wall in areas of anastomosis for at least up to 20 days following surgical trauma. They may play a significant role both in healing the anastomosis and in preventing systemic bacterial infection. Moreover, indium-111 granulocyte scans following intestinal surgery should be interpreted with care, and the presence of labeled granulocytes around anastomoses does not necessarily indicate abscess formation
Full Text Available Anterior chamber aspirate cultures were done for 66 patients who underwent either an uncomplicated intracapsular cataract extraction, extracapsular cataract extraction with posterior-chamber intraocular lens implantation, or phacoemulsification with posterior-chamber intraocular lens implantation. The aspirate was obtained at the time of wound closure. The aspirates were immediately transferred to the microbiology laboratory where one drop of the aspirate was placed on a glass slide for gram stain, and the remainder was unequally divided and inoculated into blood agar, chocolate agar and thioglycolate broth. The cultures were incubated at 37° C with 5% CO2 and held for 5 days. Of 66 patients 4 (6%, had smear-positive anterior chamber aspirates. None of the aspirates showed any growth on any of the 3 culture media used. None of the eyes in the study developed endophthalmitis. This study concludes that there is no contamination of the anterior chamber by viable bacteria after cataract surgery, irrespective of the mode of intervention.
Ahmad, M.; Akhtar, M.R.; Akhtar, M.R.
To determine the microbiology of the bile culture and antimicrobial susceptibility in patients with symptomatic gallstone disease in our setup. Study Design: A descriptive study. Place and Duration of Study: Surgical Department Combined Military Hospital (CMH) Kharian from Oct, 2010 to Jun, 2011. Patients and Methods: A total of 106 patients underwent cholecystectomy due to symptomatic gallstones and their bile was cultured for aerobic and anaerobic bacteria and culture sensitivity was performed. Data was analysed by using statistical package for social sciences (SPSS) version 13. Results: Bile culture was negative in 81 patients (76.4%) and was positive in only 25 patients (23.6%). Escheria Coli was the most common cultured organism in 10 (40%) patients, Klebsiella in 5 (20%) patients, Pseudomonas in 5 (20%) patients, Proteus in 2 (8%) patients, Staphlococcus aureus in 2 (8%) patients and mixed organisms were cultured in 1 patient (4%). Cefoperazone with sulbactum and Amikacin were the most effective prophylactic antibiotics. Conclusion: Bile in majority of patients with symtomatic uncomplicated gallstone disease is sterile. E. coli is the most commonly cultured organism and cefoperazone with sulbactum and amikacin are the most appropriate antibiotics in our setup. (author)
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
Background: In areas with intense malaria transmission, individuals are often simultaneously infected with multiple parasite strains. This study assessed the effect of multiple infections on treatment response in Ugandan children with uncomplicated malaria. Methods: Four hundred and seventy six blood specimens were ...
Jakobsen, P H; Morris-Jones, S D; Hviid, L
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....
A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire
Full Text Available Abstract Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL is highly effective and well-tolerated. Artemisinin/naphtoquine (AN is a fixed-dose ACT that has recently become available in Africa. The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated falciparum malaria in a high transmission-intensity site in Ivory Coast. Methods We enrolled 122 participants aged 6 months or more with uncomplicated falciparum malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection. Results Among 125 participants enrolled, 123 (98.4% completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance. Interpretation These data suggest that Arco® could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.
Magallón-Tejada, Ariel; Machevo, Sónia; Cisteró, Pau
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 static binding assays and qPCR the cytoadhesion and var gene transcriptional profile of 86 P. falciparum isolates from Mozambican children with severe and uncomplicated malaria, as well as of a P. falciparum 3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript levels of DC8 correlated...... positively with cytoadhesion to gC1qR (rho = 0.287, P = 0.007), were higher in isolates from children with severe anemia than with uncomplicated malaria, as well as in isolates from Europeans presenting a first episode of malaria (n = 21) than Mozambican adults (n = 25), and were associated with an increased...
Ramli, Norazsida; Ahamed, Pakeer Oothuman Syed; Elhady, Hassan Mohamed; Taher, Muhammad
Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Acute oral toxicity dose at 5000 mg/kg was conducted to evaluate the safety of this extract. Twenty mice were divided into control and experimental group. All the mice were observed for signs of toxicity, mortality, weight changes and histopathological changes. Antimalarial activity of different extract doses of 50, 200, 400 and 1000 mg/kg were tested in vivo against Plasmodium berghei infections in mice (five mice for each group) during early, established and residual infections. The acute oral toxicity test revealed that no mortality or evidence of adverse effects was seen in the treated mice. The extract significantly reduced the parasitemia by the 50 (P = 0.000), 200 (P = 0.000) and 400 mg/kg doses (P = 0.000) in the in vivo prophylactic assay. The percentage chemo-suppression was calculated as 83.33% for 50 mg/kg dose, 75.62% for 200 mg/kg dose and 90.74% for 400 mg/kg dose. Body weight of all treated groups; T1, T2, T3 and T4 also showed enhancement after 7 days posttreatment. Statistically no reduction of parasitemia calculated for curative and suppressive test. Thus, this extract may give a promising agent to be used as a prophylactic agent of P. berghei infection.
Mäkelä, Jyrki T; Kiviniemi, Heikki O; Laitinen, Seppo T
The natural history of young patients admitted for acute diverticulitis in terms of the virulence of the disease and the need for surgical treatment has remained controversial. One thousand eighty-one patients with acute diverticulitis admitted to our hospital from 1986 to 2006 were identified from a computer database and their clinical course was analysed Patients under or over 50 years of age were compared regarding uncomplicated and complicated diverticulitis, the number of admissions, operative procedures performed, morbidity, mortality and recurrence of diverticulitis. Eighty-one percent of the patients aged under 50 years were admitted for uncomplicated diverticulitis, whereas 36 % of the patients aged over 50 years were admitted for complicated diverticulitis (p = 0.001). Sixty-eight percent of the patients with uncomplicated diverticulitis and 79% of those admitted for diverticular perforation were admitted only once to our hospital. The male/female ratios of patients presenting with uncomplicated diverticulitis were 114/106 for patients aged under 50 years and 181/336 for patients aged over 50 years. The respective ratios for complicated diverticulitis were 36/17 and 111/179. Overall mortality for all the admitted patients was 2%, being 0% for patients aged under 50 years, 3% for patients aged over 50 years and 5% for those admitted for diverticular perforation. Recurrent symptoms of diverticulitis developed in 34% of the patients admitted the first time for acute diverticulitis and diverticular perforation occurred in 20% of the cases. Young patients are more often admitted for uncomplicated diverticulitis than older patients. The course of the disease in patients aged less than 50 years is not more aggressive than in older patients.
Luqman, Uzair; Majeed Janjua, Omer Sefvan; Ashfaq, Misbah; Irfan, Hira; Mushtaq, Sana; Bilal, Anum
To compare single buccal articaine injection versus conventional lignocaine buccal and palatal injections for uncomplicated maxillary tooth extractions. Single blinded randomized control trial. The outpatient department of Oral and Maxillofacial Surgery, Armed Forces Institute of Dentistry, Rawalpindi, from February to September 2011. Patients aged 20 - 60 years under simple extraction in the maxillary arch were included in the study. Patients were randomly divided into two groups-A and B toss method. Maxillary teeth were divided into three groups; group-1 (posterior teeth) including first, second and third molars on either side, group-2 (middle teeth) including the premolars and group-3 (anterior teeth) including incisors and canines. Group-A (study group) received buccal infiltration of 4% articaine with 1:200,000 adrenaline and group-B (control group) received buccal and palatal infiltration of 2% lignocaine/HCl with 1:100,000 adrenaline. Faces Pain Scale (FPS) and a Visual Analogue Score (VAS) was used for objective and subjective assessment of per operative pain respectively. A total of 194 patients were included in the study. Group-A comprised of 100 patients while group-B consisted of 94 patients. The mean age of the total sample was 41.12 ± 13.6 years. Statistically significant difference was found for the VAS scores of anteriors (p=0.9), premolars (p=0.2) and molars (p=0.2) for groups A and B. The FPS scores for both groups were also statistically insignificant (p=0.864). Buccal infiltration with a single articaine injection and lignocaine buccal and palatal infiltration were equally effective for maxillary exodontia.
Full Text Available The risk factors associated with hyperparasitemia at presentation and after treatment with different antimalarial drug regimens were evaluated in 1,048 children enrolled prospectively in seven antimalarial drug trials between July 1996 and September 2003 in a hyperendemic area of southwestern Nigeria. The outcomes of treatment of hyperparasitaemia, and gametocyte carriage following treatment were also evaluated. The children were assigned to one of seven treatment groups : chloroquine (CQ only ; pyrimethamine-sulfadoxine (PS only; amodiaquine (AQ only; CQ plus chlorpheniramine (CQCP; PS combined with CQ or AQ (COM; PS combined with probenecid (PPS; and halofantrine (HF. Hyperparasitaemia was found in 100 (9,5 % of the 1,048 children at enrolment (day 0. Following oral therapy, 1.2 % of all patients (i.e. 13 patients became hypeparasitaemic, which developed in all patients by day 1 of follow-up. In a multiple regression model, age ≤ 5 years, and a core temperature (oral or rectal ≥ 39.5°C were found to be independent risk factors for hyperparasitaemia at enrolment. Following therapy, the cure rate on day 14 was significantly lower in those treated with CQ compared to other treatment groups. Severe resistance (RIII response to treatment occurred significantly more frequently in those with hyperparasitaemia at enrolment than in those without, and was seen in five and one child with hyperparasitaemia who were treated with CQ and CQCP, respectively. Gametocyte carriage was insignificantly lower at enrolment and at all times following treatment in children with hyperparasitaemia than in age- and gender- matched children without hyperparasitaemia who received the same treatment. The results are discussed in the light of management of uncomplicated hyperparasitaemia in children in endemic settings.
Full Text Available Few epidemiologic studies have investigated predictors of uncomplicated peptic ulcer disease (PUD separately from predictors of complicated PUD.To analyze risk factors associated with uncomplicated PUD and medication use after diagnosis.Patients diagnosed with uncomplicated PUD (n = 3,914 were identified from The Health Improvement Network database among individuals aged 40-84 years during 1997-2005, with no previous history of PUD. Prescription records for the year after the date of diagnosis were reviewed and a nested case-control analysis was performed to calculate the odds ratios for the association of potential risk factors with PUD.Medications associated with developing uncomplicated PUD included current use of acetylsalicylic acid (ASA, nonsteroidal anti-inflammatory drugs (NSAIDs, paracetamol, selective serotonin reuptake inhibitors, antidepressants, antihypertensives or acid suppressants. Uncomplicated PUD was significantly associated with being a current or former smoker and having had a score of at least 3 on the Townsend deprivation index. Approximately 50% of patients who were users of ASA (19% of patients or chronic users of NSAIDs (7% of patients at diagnosis did not receive another prescription of the medication in the 60 days after diagnosis, and 30% were not represcribed therapy within a year. Among patients who were current users of ASA or chronic NSAIDs at the time of the PUD diagnosis and received a subsequent prescription for their ASA or NSAID during the following year, the vast majority (80-90% also received a proton pump inhibitor coprescription.Our results indicate that several risk factors for upper gastrointestinal bleeding are also predictors of uncomplicated PUD, and that some patients do not restart therapy with ASA or NSAIDs after a diagnosis of uncomplicated PUD. Further investigation is needed regarding the consequences for these patients in terms of increased cardiovascular burden due to discontinuation of
Matthew T Aliota
Full Text Available Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG. Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness.Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria parasite infections.These results could have an
Full Text Available Symptoms and signs of acute pyelonephritis sometimes are subtle and emergency physicians attending overcrowded and busy institutions could easily miss the right diagnosis. The presence of a renal damage is decisive in the therapeutic choice. Aims of our study are: 1 to assess prevalence of renal damage in patients presenting to our ED with symptoms and signs of primary urinary tract infection (UTI; 2 to evaluate the reliability of such symptoms and signs in predicting a renal damage; 3 to assess accuracy of the contrast enhanced ultrasound (CEUS in the ED diagnosis of renal damage due to acute uncomplicated pyelonephritis. We studied 54 patients with suspected UTI. Each patient underwent clinical examination, routine blood and urine sampling and conventional renal ultrasound (US. 23 patients had confirmation of acute primary UTI, and performed renal magnetic resonance (MR to rule out renal parenchymal involvement. In 16 patients (69,6% one or more parenchymal lesions were visualized at MR, and diagnosis of acute uncomplicated pyelonephritis was confirmed (group A. The other 7 patients had a diagnosis of UTI without renal involvement (group B. Some of 23 patients presented with few atypical symptoms. Lumbar pain was the most frequent symptom (n = 21, without a statistically significant difference between group A and B (P 0,958; p = 0,328. No other symptom or sign has demonstrated statistically valid in predicting the renal involvement. Renal US was positive in only 3 patients of group A (18,7%. During this first part of our study, CEUS was performed in a limited number of patients (n = 8, and in 7 examinations data were concordant with MR. In conclusion, analysis of our preliminary data confirms that a distinction between patients with different extension of the UTI is not possible through the simple clinical examination and routine tests. CEUS is very promising and its routine employment in the ED could simplify the diagnostic practice in
Cirimotich, Chris M; Dong, Yuemei; Garver, Lindsey S; Sim, Shuzhen; Dimopoulos, George
The causative agent of malaria, Plasmodium, has to undergo complex developmental transitions and survive attacks from the mosquito's innate immune system to achieve transmission from one host to another through the vector. Here we discuss recent findings on the role of the mosquito's innate immune signaling pathways in preventing infection by the Plasmodium parasite, the identification and mechanistic description of novel anti-parasite molecules, the role that natural bacteria harbored in the mosquito midgut might play in this immune defense and the crucial parasite and vector molecules that mediate midgut infection.
Chek, J B; Okello, G B; Kyobe, J
There are four hypotheses which have been advanced to explain the pathophysiology of severe and complicated malaria such as cerebral malaria. However, none of them adequately explains all the features of cerebral malaria in man. One such hypotheses is Disseminated Intravascular Coagulation (DIC). To determine whether this condition occurs in patients with uncomplicated malaria, the authors conducted a study on fibrinogen and its degradation products, euglobulin lysis time and parasite counts in 30 cases of uncomplicated malaria. By spectrophotometric method, plasma fibrinogen in patients with uncomplicated malaria was found to be normal as compared to normal healthy adults. There were no fibrinogen degradation production (FDP) detected in either patients or healthy controls, using latex agglutination tests at a dilution of 1:5. This method for FDP estimation is significant in that a serum agglutination with 1:5 dilution indicates a concentration of FDP in the original serum in excess of 10g/ml, designated as positive results of experiment. High values of euglobulin lysis time (ELT) were noted in patients with low parasitaemia. Analysis of these results showed that disseminated intravascular coagulation did not occur in uncomplicated cases of malaria. In this study on cases of uncomplicated malaria and low parasitaemia the biochemical parameters relating to to DIC have been essentially normal, although DIC is thought to be a primary stage in the development of cerebral malaria. According to Reid, DIC is an important intermediate mechanism in the pathophysiology of severe and complicated malaria such as cerebral malaria.
Background: Laparoscopic appendectomy is a feasible and safe alternative to open appendectomy for uncomplicated appendicitis. In the past decade several laparoscopic procedures have been described using one or more ports. We report our experience in treating acute appendicitis with one-port transumbilical ...
Garg, Shilpi; Saxena, Vishal; Lumb, Vanshika; Pakalapati, Deepak; Boopathi, P A; Subudhi, Amit Kumar; Chowdhury, Shibasish; Kochar, Sanjay K; Kochar, Dhanpat K; Sharma, Y D; Das, Ashis
Plasmodium vivax is the predominant species of the human malaria parasite present in the Indian subcontinent. There have been recent reports on Chloroquine (CQ) resistance and severe manifestations shown by P. vivax from different regions of the world including India. This study focuses on Bikaner, India where during the last few years there have been continuous reports of severe manifestations by both Plasmodium falciparum and P. vivax. This region has a widespread use of Chloroquine and Sulfadoxine-Pyrimethamine for the treatment of malaria, but the resistance profiles of these drugs are not available. We report here the profile of mutations in marker genes associated with Chloroquine and antifolate drug resistance among the P. vivax parasites obtained from patients with severe (n=30) and non-severe (n=48) manifestations from this region. Most isolates showed the wild type alleles for both the Chloroquine and antifolate resistance markers (Presistance has been reported from this region. However, the single isolate with a mutation in Pvmdr-1 may suggest the beginning of the trend towards decreased susceptibility to Chloroquine. The frequency of PvDHFR-PvDHPS two locus mutations was higher among the patients showing severe manifestations than the patient group with non-severe (uncomplicated) malaria (Pexhibiting severe complications. Preliminary homology modeling and molecular docking studies predicted that these mutations apparently do not have any effect on the binding of the drug molecule to the enzyme. However, the presence of novel mutations in the PvDHPS gene indicate a degree of polymorphism of this molecule which is in contrast to available published information. Copyright © 2012 Elsevier Inc. All rights reserved.
Eisenhut, Michael; Omari, Aika A A
In children with falciparum malaria, a proprietary quinine preparation (adjusted to make it less acidic) administered rectally may be easier to use and less painful than intramuscular or intravenous administration. However, rectal quinine may be less effective. To compare intrarectal quinine with intravenous or intramuscular quinine for treating malaria caused by Plasmodium falciparum. In May 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 2), MEDLINE, EMBASE, LILACS, and CINAHL. We also searched conference proceedings, contacted individual researchers and a pharmaceutical company, and checked reference lists. Randomized and quasi-randomized controlled trials comparing intrarectal quinine with intramuscular and intravenous quinine for treating people with uncomplicated and severe Plasmodium falciparum malaria. We independently assessed each trial's risk of bias quality and extracted data, including adverse event data. We analysed dichotomous data using the odds ratio and continuous data using the mean difference. Ten randomized controlled trials, all involving children only (total of 1417 children), fulfilled the inclusion criteria. The same investigator was involved in nine of the trials. Seven trials compared proprietary intrarectal with intravenous quinine, and seven trials compared it with intramuscular treatment. We detected no statistically significant difference between intrarectal and intravenous or intramuscular routes for death, parasite clearance by 48 hours and seven days, parasite clearance time, fever clearance time, coma recovery time, duration of hospitalization, and time to drinking. The trials reporting on these outcomes were small, which resulted in large confidence intervals for all outcomes apart from duration of hospitalization. One large trial (898 children) reported that intrarectal was less painful than intramuscular administration. We detected no difference in the
Full Text Available Abstract Background Plasmodium knowlesi malaria causes severe disease in up to 10% of cases in Malaysian Borneo and has a mortality rate of 1 - 2%. However, laboratory markers with the ability to identify patients at risk of developing complications have not yet been assessed as they have for other species of Plasmodium. Methods A case control study was undertaken in two hospitals in Sarikei and Sibu, Malaysian Borneo. One hundred and ten patients with uncomplicated (n = 93 and severe (n = 17 P. knowlesi malaria were studied. Standardized pigment-containing neutrophil (PCN count, parasite density and platelet counts were determined and analysed by logistic regression and receiver operating characteristic (ROC analysis. Results The PCN count was strongly associated with risk of disease severity. Patients with high parasite density (≥ 35,000/μl or with thrombocytopaenia (≤ 45,000/μl were also more likely to develop complications (odds ratio (OR = 9.93 and OR = 5.27, respectively. The PCN count yielded the highest area under the ROC curve (AUC estimate among all markers of severity (AUC = 0.8561, 95% confidence interval: 0.7328, 0.9794. However, the difference between all parameter AUC estimates was not statistically significant (Wald test, p = 0.73. Conclusion Counting PCN is labour-intensive and not superior in predicting severity over parasitaemia and platelet counts. Parasite and platelet counts are simpler tests with an acceptable degree of precision. Any adult patient diagnosed with P. knowlesi malaria and having a parasite count ≥35,000/μl or ≥1% or a platelet count ≤45,000/μl can be regarded at risk of developing complications and should be managed according to current WHO guidelines for the treatment of severe malaria.
del Portillo Hernando A
Full Text Available Abstract Background Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. Methods Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. Results Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. Conclusion Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements.
Annibale, Bruno; Lahner, Edith; Maconi, Giovanni; Usai, Paolo; Marchi, Santino; Bassotti, Gabrio; Barbara, Giovanni; Cuomo, Rosario
Clinical features of symptomatic uncomplicated diverticular disease are poorly investigated. Abdominal symptoms may be similar to those of irritable bowel syndrome. This survey aimed to assess clinical features associated with symptomatic uncomplicated diverticular disease. This multicenter survey included consecutive outpatients with symptomatic uncomplicated diverticular disease to whom a detailed clinical questionnaire regarding demographic, lifestyle, and clinical features was administered. Diagnosis was based on the presence of diverticula and abdominal pain/discomfort. Irritable bowel syndrome and functional dyspepsia were assessed according to Rome III criteria. A total of 598 patients (50 % female, age 69 years), 71 % with newly diagnosed symptomatic uncomplicated diverticular disease and 29 % with history of colonic diverticula, were recruited. Diverticula were localized in the left colon in 78 % of the patients. Recurrent short-lived abdominal pain (24 h) in 27 %, and recurrent abdominal bloating in 61 % of the patients. Normal, loose, or hard stools were reported by 58, 29, and 13 % of patients, respectively. Irritable bowel syndrome (IBS)-like and functional dyspepsia-like symptoms were recorded in 59 and 7 % of patients, respectively. IBS-like symptoms (odds ratio, 4.3) were associated in patients with prolonged abdominal pain. Symptomatic uncomplicated diverticular disease is associated with a gender ratio of 1:1 and an unspecific clinical picture mainly characterized by normal stools, short-lived abdominal pain, abdominal bloating, IBS-like symptoms, while functional dyspepsia-like symptoms are not commonly present. These findings suggest that symptomatic uncomplicated diverticular disease often shows similar findings rather than overlaps IBS.
Jaung, Rebekah; Robertson, Jason; Vather, Ryash; Rowbotham, David; Bissett, Ian P
Acute diverticulitis (AD) is one of the most common acute admission diagnoses for general surgery, and its prevalence is increasing, in part due to the ageing population. Currently, most patients who present to a tertiary hospital are admitted for a period of treatment and observation. Simple, safe and cost-effective strategies for improving our current treatment of this condition will be invaluable in providing the most appropriate management for individual patients and for reducing the health resources expended on hospital admissions and parenteral antibiotics. AD can be categorized as uncomplicated or complicated, these two subtypes have a very different clinical course. The management of uncomplicated AD has become increasingly conservative, with a focus on symptomatic relief and supportive management. Recent research has brought into question the need for extended hospital admission and questioned the current use of antibiotics. Anti-inflammatory agents that reduce local inflammation in uncomplicated AD may be a useful means of reducing damage caused by inflammation and aiding earlier resolution of the inflammatory response and associated symptoms. Mesalazine is an anti-inflammatory agent that has been trialled in uncomplicated AD. Mesalazine has been shown to improve time to resolution of endoscopic and histological evidence of inflammation following an episode of AD and also reduce the rate of recurrence. In this literature review, we provide an overview of recent advances in AD classification, pathophysiology and management, and examine the possibility of introducing the use of anti-inflammatory agents in the management of uncomplicated AD. © 2015 Royal Australasian College of Surgeons.
Plasmodium falciparum malaria is one of the most important parasitic diseases affecting sub-Saharan Africa, despite the availability of interventions. It exerts tremendous socio-economic and medical burden on the continent, particularly in under five children and pregnant women. In this review, we have attempted to ...
Resistance patterns of plasmodium falciparum malaria to chloroquine in Kampala, Uganda. ... Sixty three (65.6%) patients showed clinical improvement, 29 (30.2%) deteriorated and four (4.2%) had no change. Adequate parasitogical response was seen in 71 (74 %), moderate in four (4.2%) and poor in 21 (21.8%) patients.
Jan 18, 2008 ... Dodoo D, Theander TG, Kurtzhals JAL, Koram K, Riley E, Akanmori. BD, Nkruma FK, Hviid L (1999). Levels of Antibody to conserve parts of Plasmodium falciparum merozoite surface protein 1 in Ghanaian children are not associated with protection from clinical malaria. Infect. Immun. 67(5): 2131-2137.
Jamie M Orengo
Full Text Available Infection of erythrocytes with the Plasmodium parasite causes the pathologies associated with malaria, which result in at least one million deaths annually. The rupture of infected erythrocytes triggers an inflammatory response, which is induced by parasite-derived factors that still are not fully characterized. Induced secretion of inflammatory cytokines by these factors is considered a major cause of malaria pathogenesis. In particular, the inflammatory cytokine tumor necrosis factor (TNF is thought to mediate most of the life-threatening pathologies of the disease. Here we describe the molecular characterization of a novel pathway that results in the secretion of TNF by host cells. We found that erythrocytes infected by Plasmodium accumulate high concentrations of hypoxanthine and xanthine. Degradation of Plasmodium-derived hypoxanthine/xanthine results in the formation of uric acid, which triggers the secretion of TNF. Since uric acid is considered a "danger signal" released by dying cells to alert the immune system, Plasmodium appears to have co-evolved to exploit this warning system. Identifying the mechanisms used by the parasite to induce the host inflammatory response is essential to develop urgently needed therapies against this disease.
Abstract. Malaria and Human Immunodeficiency Virus (HIV) infections are major public health problems in Sub-Saharan. Africa. Their overlapping geographical distribution and co-existence often result into high morbidity and mortality. This study was designed to establish the prevalence of Plasmodium falciparum malaria ...
Vik, Ingvild; Bollestad, Marianne; Grude, Nils
, controlled, double blind trial following the principles of Good Clinical Practice. Women between the ages of 18 to 60 presenting with symptoms of uncomplicated cystitis are screened for eligibility. 500 women from four sites in Norway, Sweden and Denmark are allocated to treatment with 600 mg ibuprofen three.......DiscussionIf treatment of uncomplicated cystitis with ibuprofen is as effective as mecillinam for symptom relief, we can potentially reduce the use of antibiotics on a global scale.Trial registrationEudraCTnr: 2012-002776-14. ClinicalTrials.gov: NCT01849926....
Barber Bridget E
Full Text Available Abstract Background In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy performed by an experienced research microscopist, for the diagnosis of PCR-confirmed Plasmodium falciparum, P. knowlesi, and Plasmodium vivax malaria. Results A total of 304 patients with PCR-confirmed Plasmodium infection were enrolled, including 130 with P. knowlesi, 122 with P. falciparum, 43 with P. vivax, one with Plasmodium malariae and eight with mixed species infections. Among patients with P. knowlesi mono-infection, routine and cross-check microscopy both identified 94 (72% patients as “P. malariae/P. knowlesi”; 17 (13% and 28 (22% respectively were identified as P. falciparum, and 13 (10% and two (1.5% as P. vivax. Among patients with PCR-confirmed P. falciparum, routine and cross-check microscopy identified 110/122 (90% and 112/118 (95% patients respectively as P. falciparum, and 8/122 (6.6% and 5/118 (4.2% as “P. malariae/P. knowlesi”. Among those with P. vivax, 23/43 (53% and 34/40 (85% were correctly diagnosed by routine and cross-check microscopy respectively, while 13/43 (30% and 3/40 (7.5% patients were diagnosed as “P. malariae/P. knowlesi”. Four of 13 patients with PCR-confirmed P. vivax and misdiagnosed by routine microscopy as “P. malariae/P. knowlesi” were subsequently re-admitted with P. vivax malaria. Conclusions Microscopy does not reliably distinguish between P. falciparum, P. vivax and P. knowlesi in a region where all three species frequently occur. Misdiagnosis of P. knowlesi as both P. vivax and P. falciparum, and
Benakis, A; Binh, Tran Quang; Keundjian, A; Scheiwe, M W
In recent years, Artemisinin and particularly one of its derivatives--Artesunate (ART--has become an essential alternative for treatment of both uncomplicated and severe falciparum malaria in Asia and Africa as well. Therefore, these compounds are still and inccreasingly in the focus of interest because of quick acting of this drug, is able to help even unconscious to overcome the malaria attack, when administered by injection. As an alternative, RECTOCAPS have been developed and their use is meanwhile well established. From earlier studies in children, suffering from plasmodium falciparum malaria, we obtained a high level of DHART in the blood, but as expected also a rapid decline in the levels of both DHART and ART. A second administration of ART was additionally applied 4 hours after the first administration. DHART and ART plasma levels were found to last longer on an assumed therapeutic level than those obtained after one administration only. The fever clearance and the parasitemia reduction rates were found to be effective according to this dosing regimen. In view of these findings, we decided to conduct the actual described study by administering 200 mg of ART every 3 hours (0, 3, 6 and 9 h) by the rectal route. Soft geiatine capsules (RECTOCAPS) containing 200 mg of ART GMP--type each (Artesunic acid) were administered by rectal route. Each patient received four RECTOCAPS capsules (4 x 200 mg of ART) over a 3 h period. 12 adult patients with uncomplicated malaria were selected. Age, weight, height, body temperature, parasite counts before treatment and their evolution until 96 h are determined. Blood samples were taken at short time intervals after starting with the first medication: 0, 30 min, 60 min, 3 h, 6 h, 9 h, 12 h, 24 h, 36 h, 48 h, 60 h, 72 h, 84 h, 96 h and 108 h. The aliquots of all the blood samples were used for performing parasite counts. Plasma obtained following the traditional procedure was kept at -40 degrees C until analysis. HPLC
Müller, Mattia; Schlagenhauf, Patricia
Since the initial discovery of Plasmodium knowlesi in Malaysia, cases have been reported from several neighbouring countries. Tourism has also resulted in an increasing number of cases diagnosed in Europe, America, and Oceania. In this review we focus on the risk of the travel-associated acquisition of P. knowlesi malaria. A search of the literature in PubMed was carried out to identify articles and literature on the distribution of P. knowlesi infections in Southeast Asia and details of its acquisition and importation by travellers to other continents. The cut-off date for the search was December 1, 2013. Search words used were: "Plasmodium knowlesi", "Plasmodium knowlesi infections", "Plasmodium knowlesi travellers", "Plasmodium knowlesi prevalence", "Plasmodium knowlesi host", "Plasmodium knowlesi vector" "Plasmodium knowlesi RDT", and "Plasmodium knowlesi Malaysia". Traveller numbers to Malaysia were obtained from the Tourism Malaysia website. A total of 103 articles were found. Using a selection of these and others identified from the reference lists of the papers, we based our review on a total of 66 articles. P. knowlesi malaria appears to be the most common malaria species in Malaysian Borneo and is also widely distributed on the Malaysian mainland. Furthermore, locally transmitted cases of P. knowlesi malaria have been reported in Thailand, the Philippines, Vietnam, Singapore, Myanmar, Indonesian Borneo, and Cambodia. Two cases have been reported from non-endemic countries in Asia (Japan and Taiwan) in people with a history of travel to Malaysia and the Philippines. Twelve cases were imported to their home countries by travellers from other continents: two from the USA, two from the Netherlands, two from Germany, and one each from Spain, France, Sweden, Finland, Australia, and New Zealand. In most cases, the infection was associated with a trip to or near forested areas. The symptoms were fever (n=12), headache (n=6), chills (n=6), nausea (n=4), myalgia (n
Enevold, Anders; Lusingu, John P; Mmbando, Bruno
the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area...
Full Text Available There is no approved vaccine for malaria, and precisely how human antibody responses to malaria parasite components and potential vaccine molecules are developed and maintained remains poorly defined. In this study, antibody anamnestic or memory response elicited by a single episode of P. falciparum infection was investigated.This study involved 362 malaria patients aged between 6 months to 60 years, of whom 19% were early-diagnosed people living with HIV/AIDS (PLWHA. On the day malaria was diagnosed and 42 days later, blood specimens were collected. Parasite density, CD4+ cells, and antibodies specific to synthetic peptides representing antigenic regions of the P. falciparum proteins GLURP, MSP3 and HRPII were measured.On the day of malaria diagnosis, Immunoglobulin (IgG antibodies against GLURP, MSP3 and HRP II peptides were present in the blood of 75%, 41% and 60% of patients, respectively. 42 days later, the majority of patients had boosted their serum IgG antibody more than 1.2 fold. The increase in level of IgG antibody against the peptides was not affected by parasite density at diagnosis. The median CD4+ cell counts of PLWHAs and HIV negative individuals were not statistically different, and median post-infection increases in anti-peptide IgG were similar in both groups of patients.In the majority (70% of individuals, an infection of P. falciparum elicits at least 20% increase in level of anti-parasite IgG. This boost in anti-P. falciparum IgG is not affected by parasite density on the day of malaria diagnosis, or by HIV status.
Full Text Available La apendicitis aguda es una causa típica de dolor abdominal agudo y la causa más frecuente de cirugía abdominal de urgencia. En las últimas dos décadas se ha publicado creciente evidencia sobre el uso de antibióticos como tratamiento exclusivo de la apendicitis aguda. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen cinco estudios aleatorizados. Realizamos un metanálisis y tablas de resumen de los resultados utilizando el método GRADE. Concluimos que el uso de antibióticos para el tratamiento la apendicitis aguda no complicada podría tener menor efectividad que la apendicectomía y probablemente aumente las complicaciones mayores en comparación con la apendicectomía.
Brunkwall, J; Kasprzak, P; Verhoeven, E
% of the cases. During the first 30 days, no deaths occurred in either group, but there were three crossovers from the BMT to the BMT+TAG group, all due to progression of disease within 1 week. There were two withdrawals from the BMT+TAG group. At the 1-year follow up there had been another two failures...
Felipe Moraga; Vanessa Ahumada; Fernando Crovari
La apendicitis aguda es una causa típica de dolor abdominal agudo y la causa más frecuente de cirugía abdominal de urgencia. En las últimas dos décadas se ha publicado creciente evidencia sobre el uso de antibióticos como tratamiento exclusivo de la apendicitis aguda. Utilizando la base de datos Epistemonikos, la cual es mantenida mediante búsquedas en 30 bases de datos, identificamos nueve revisiones sistemáticas que en conjunto incluyen cinco estudios aleatorizados. Realizamos un metanálisi...
Fox, Annette; Than Manh Hung; Wertheim, Heiman; Le Nguyen Minh Hoa; Vincent, Angela; Lang, Bethan; Waters, Patrick; Nguyen Hong Ha; Nguyen Vu Trung; Farrar, Jeremy; Nguyen Van Kinh; Horby, Peter
Background The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam. Methods and Findings Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008?2010. Stand...
Mayxay, Mayfong; Khanthavong, Maniphone; Chanthongthip, Odai; Imwong, Mallika; Lee, Sue J.; Stepniewska, Kasia; Soonthornsata, Bongkot; Pongvongsa, Tiengkham; Phompida, Samlane; Hongvanthong, Bouasy; Ringwald, Pascal; White, Nicholas J.; Newton, Paul N.
We conducted an open-label, randomized clinical trial to assess parasite clearance times (PCT) and the efficacy of 4 mg/kg (group 1, n = 22) and 2 mg/kg (group 2, n = 22) of oral artesunate for three days followed by artemether-lumefantrine in patients with uncomplicated Plasmodium falciparum malaria at Xepon Interdistrict Hospital, Savannakhet Province in southern Laos. Slides were read in duplicate. The overall mean (95% confidence interval; range) PCT in hours was 23.2 (21.2–25.3; 12–46) and 22.4 (20.3–24.5; 12–46) for the first and second microscopists, respectively (P = 0.57). Ten (23%) patients remained parasitemic on day 1 after treatment (4 [18%] in group 1 and 6 [27%] in group 2; P = 0.47). No patient had patent asexual parasitemia on the second and third days of treatment. The 42-day polymerase chain reaction–corrected cure rates were 100% in both treatment groups. Serious adverse events did not develop during or after treatment in any patients. In conclusion, no evidence of P. falciparum in vivo resistance to artesunate was found in southern Laos. PMID:22403308
This study is part of the Ethio Nether Land AIDS. Research Project (ENARP), which is a collaborative project of EHNRI. ENARP is financially supported by. The Netherlands Ministry of Foreign Affairs and the. Ethiopian Ministry of Health under a bilateral agreement. The researchers would like to thank all the participants.
de Vries, P. J.; Bich, N. N.; van Thien, H.; Hung, L. N.; Anh, T. K.; Kager, P. A.; Heisterkamp, S. H.
Combinations of artemisinin and quinine for uncomplicated falciparum malaria were studied. A total of 268 patients were randomized to 7 days of quinine at 10 mg/kg of body weight three times a day (Q) or to artemisinin at 20 mg/kg of body weight followed by 3 (AQ3) or 5 (AQ5) days of quinine.
Wakefield, Jerome C.; Schmitz, Mark F.
Purpose: To evaluate the claim, made repeatedly during "Diagnostic and Statistical Manual of Mental Disorders", Fifth Edition debates over eliminating the bereavement exclusion (BE), that ''uncomplicated'' depressive reactions have elevated suicidality like other major depressive disorder (MDD), so exclusions risk…
Hummers-Pradier, E; Denig, P; Oke, T; Lagerlov, P; Wahlstrom, R; Haaijer-Ruskamp, FM
Background. Non-adherence to recommendations for treatment of uncomplicated urinary tract infections (UTI) is common, but the reasons are not sufficiently understood. Objectives. We aimed to assess and compare the influence of specific patient characteristics on GPs' treatment decisions for UTI in
Jamil, M.N.; Khan, R.M.; Sultan, B.; Farooq, U.
Uncomplicated urinary tract infections (UTIs) are the most common bacterial infections among women presenting to primary care causing rapidly increasing strains of resistant bacteria to the growing antibiotic industry. Restricting antibiotics to necessary indications is the only solution. The objectives of the study were to compare the efficacy of symptomatic treatment vs antibiotic in patients with uncomplicated UTI, in terms of individual symptom score, i.e., frequency, urgency, dysuria, supra pubic pain scores and total symptoms scores. Methods: A randomized control trial (RCT) in 100 women (15-50 years) with symptoms of urinary frequency, urgency, dysuria and pain supra pubic region, associated with uncomplicated UTI, at Urology department, AMI, Abbottabad. Two treatment strategies were compared in uncomplicated UTI patient). Patients were randomized to antibiotic or symptomatic treatment groups on consecutive non-probability basis (50 in each group) given for 05 days. Efficacy of medications was assessed by comparing pre and post treatment symptom scores along with the post treatment scores of both groups compared to see statistical significance of difference by independent samples t-test. Results: There was a statistically significant difference in symptoms improvement in both treatment arms of all scores, i.e., p-value=0.000. Whereas only dysuria score was able to show a statistically significance of difference in post Rx scores comparison of both groups, p-value=0.004. Conclusions: Symptomatic treatment is not inferior to antibiotic treatment when proper patient selection is undertaken, resulting in decreased need for unnecessary antibiotics use. (author)
McQuiston Haslund, Josephine; Rosborg Dinesen, Marianne; Nielsen, Anni Brit Sternhagen
OBJECTIVE: Uncomplicated urinary tract infection (uUTI) is a common reason for antibiotic treatment in primary health care. Due to the increasing prevalence of antibiotic-resistant uropathogens it is crucial to use the most appropriate antibiotics for first-choice empiric treatment of u...
Christoffersen, Thea; Bjerrum, Lars; Nielsen, Anni Brit Sternhagen
INTRODUCTION: Uncomplicated urinary tract infection (uUTI) is a common reason for seeing a GP. In Denmark, it is debated if sulfamethizole or pivmecillinam should be recommended for empirical treatment of uUTIs. We evaluated sulfamethizole and pivmecillinam use in the five Danish regions from 2007...
Seklehner, Stephan; Sievert, Karl-Dietrich; Lee, Richard; Engelhardt, Paul F; Riedl, Claus; Kunit, Thomas
To evaluate the outcome and the costs of stenting in uncomplicated semirigid ureteroscopic stone removal. A decision tree model was created to evaluate the economic impact of routine stenting versus non-stenting strategies in uncomplicated ureteroscopy (URS). Probabilities of complications were extracted from twelve randomized controlled trials. Stone removal costs, costs for complication management, and total costs were calculated using Treeage Pro (TreeAge Pro Healthcare version 2015, Software, Inc, Williamstown Massachusetts, USA). Stone removal costs were higher in stented URS (€1512.25 vs. €1681.21, respectively). Complication management costs were higher in non-stented procedures. Both for complications treated conservatively (€189.43 vs. €109.67) and surgically (€49.26 vs. €24.83). When stone removal costs, costs for stent removal, and costs for complication management were considered, uncomplicated URS with stent placement yielded an overall cost per patient of €1889.15 compared to €1750.94 without stent placement. The incremental costs of stented URS were €138.25 per procedure. Semirigid URS with stent placement leads to higher direct procedural costs. Costs for managing URS-related complications are higher in non-stented procedures. Overall, a standard strategy of deferring routine stenting uncomplicated ureteroscopic stone removal is more cost efficient.
Knottnerus, Bart J; Geerlings, Suzanne E; Moll van Charante, Eric P; ter Riet, Gerben
Women presenting with symptoms of acute uncomplicated urinary tract infection (UTI) are often prescribed antibiotics. However, in 25 to 50% of symptomatic women not taking antibiotics, symptoms recover spontaneously within one week. It is not known how many women are prepared to delay antibiotic treatment. We investigated how many women presenting with UTI symptoms were willing to delay antibiotic treatment when asked by their general practitioner (GP). From 18 April 2006 until 8 October 2008, in a prospective cohort study, patients were recruited in 20 GP practices in and around Amsterdam, the Netherlands. Healthy, non-pregnant women who contacted their GP with painful and/or frequent micturition for no longer than seven days registered their symptoms and collected urine for urinalysis and culture. GPs were requested to ask all patients if they were willing to delay antibiotic treatment, without knowing the result of the culture at that moment. After seven days, patients reported whether their symptoms had improved and whether they had used any antibiotics. Of 176 women, 137 were asked by their GP to delay antibiotic treatment, of whom 37% (51/137) were willing to delay. After one week, 55% (28/51) of delaying women had not used antibiotics, of whom 71% (20/28) reported clinical improvement or cure. None of the participating women developed pyelonephritis. More than a third of women with UTI symptoms are willing to delay antibiotic treatment when asked by their GP. The majority of delaying women report spontaneous symptom improvement after one week.
Schousboe, Mette L; Rajakaruna, Rupika S; Salanti, Ali
into the level of drug pressure caused by SP use and presumably other antifolate drugs. In Sri Lanka, chloroquine (CQ) with primaquine (PQ) and SP with PQ is used as first and second line treatment, respectively, against uncomplicated Plasmodium falciparum and/or P. vivax infections. CQ/PQ is still efficacious...... against P. vivax infections, thus SP is rarely used and it is assumed that the prevalence of SNPs related to P. vivax SP resistance is low. However, this has not been assessed in Sri Lanka as in most other parts of Asia. This study describes the prevalence and distribution of SNPs related to P. vivax SP...... resistance across Sri Lanka. SUBJECTS AND METHODS: P. vivax-positive samples were collected from subjects presenting at government health facilities across nine of the major malaria endemic districts on the island. The samples were analysed for SNPs/haplotypes at codon 57, 58, 61 and 117 of the Pvdhfr gene...
Nielsen, Morten A; Grevstad, Berit; A-Elgadir, Thoraya M E
BACKGROUND: The acquisition of immunoglobulin (Ig) G to variant surface antigens (VSAs) seems important for the development of protective immunity against malaria. Unlike VSAs expressed by parasite isolates associated with uncomplicated malaria, VSAs expressed by parasite isolates associated...... with severe malaria (VSA(SM)) are frequently recognized by IgG. METHODS: We analyzed levels of anti-VSA IgG in 57 individuals in Daraweesh, Sudan, before and after the transmission season. IgG responses to 79 Plasmodium falciparum isolates from children with defined malaria syndromes and exposed to high......G. CONCLUSIONS: Anti-VSA IgG levels decrease in the absence of infection, and an episode of clinical malaria induces IgG against a range of VSAs, particularly VSAs(SM)....
Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto
The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.
Gomes-Santos, Carina S. S.; Itoe, Maurice A.; Afonso, Cristina; Henriques, Ricardo; Gardner, Rui; Sepúlveda, Nuno; Simões, Pedro D.; Raquel, Helena; Almeida, António Paulo; Moita, Luis F.; Frischknecht, Friedrich; Mota, Maria M.
Plasmodium sporozoites are transmitted by Anopheles mosquitoes and infect hepatocytes, where a single sporozoite replicates into thousands of merozoites inside a parasitophorous vacuole. The nature of the Plasmodium-host cell interface, as well as the interactions occurring between these two organisms, remains largely unknown. Here we show that highly dynamic hepatocyte actin reorganization events occur around developing Plasmodium berghei parasites inside human hepatoma cells. Actin reorganization is most prominent between 10 to 16 hours post infection and depends on the actin severing and capping protein, gelsolin. Live cell imaging studies also suggest that the hepatocyte cytoskeleton may contribute to parasite elimination during Plasmodium development in the liver. PMID:22238609
Full Text Available A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.
Full Text Available The study of the morphology of a species of Plasmodium is difficult because these organisms have relatively few characters. The size of the schizont, for example, which is easy to assess is important at the specific level but is not always of great phylogenetic significance. Factors reflecting the parasite’s metabolism provide more important evidence. Thus the position of the parasite within the host red cell (attachment to the host nucleus or its membrane, at one end or aligned with it has been shown to be constant for a given species. Another structure of essential significance that is often ignored is a globule, usually refringent in nature, that was first described in Plasmodium vaughani Novy & MacNeal, 1904 and that we consider to be characteristic of the sub-genus Novyella. Species without this structure, previously classified in this sub-genus, are now included in the new sub-genus Papernaia n. sg.
Full Text Available Abstract A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed.
The immunoglobulin profiles of 126 Nigerian children infected with Plasmodium falciparum in their peripheral blood were investigated. The mean malarial parasitaemia was 4699.17 ± 3695.2 ìl. The mean immunoglobulin profile of these infected children were 2.68 ± 0.019 mg/dl for IgA, 0.031 ± 0.01 mg/dl for IgD, 1358.29 ...
Lelièvre, J; Berry, A; Benoit-Vical, F
Since the synchronization of Plasmodium falciparum has become an essential tool in research, we have investigated the use of a commercial gelatine solution, Plasmion, to replace Plasmagel, which is now difficult to obtain. This method also avoids the use of techniques based on Percoll-glucose gradients. The Plasmion-based technique proved to be a good method and could become an alternative to Plasmagel.
Scaccabarozzi, Diletta; Deroost, Katrien; Corbett, Yolanda; Lays, Natacha; Corsetto, Paola; Salè, Fausta Omodeo; Van den Steen, Philippe E; Taramelli, Donatella
Cerebral malaria and severe anaemia are the most common deadly complications of malaria, and are often associated, both in paediatric and adult patients, with hepatopathy, whose pathogenesis is not well characterized, and sometimes also with acute respiratory distress syndrome (ARDS). Here, two species of murine malaria, the lethal Plasmodium berghei strain NK65 and self-healing Plasmodium chabaudi strain AS which differ in their ability to cause hepatopathy and/or ARDS were used to investigate the lipid alterations, oxidative damage and host immune response during the infection in relation to parasite load and accumulation of parasite products, such as haemozoin. Plasma and livers of C57BL/6J mice injected with PbNK65 or PcAS infected erythrocytes were collected at different times and tested for parasitaemia, content of haemozoin and expression of tumour necrosis factor (TNF). Hepatic enzymes, antioxidant defenses and lipids content and composition were also evaluated. In the livers of P. berghei NK65 infected mice both parasites and haemozoin accumulated to a greater extent than in livers of P. chabaudi AS infected mice although in the latter hepatomegaly was more prominent. Hepatic enzymes and TNF were increased in both models. Moreover, in P. berghei NK65 infected mice, increased lipid peroxidation, accumulation of triglycerides, impairment of anti-oxidant enzymes and higher collagen deposition were detected. On the contrary, in P. chabaudi AS infected mice the antioxidant enzymes and the lipid content and composition were normal or even lower than uninfected controls. This study demonstrates that in C57BL/6J mice, depending on the parasite species, malaria-induced liver pathology results in different manifestations, which may contribute to the different outcomes. In P. berghei NK65 infected mice, which concomitantly develop lethal acute respiratory distress syndrome, the liver tissue is characterized by an excess oxidative stress response and reduced
Hestbaek, Lise; Kongsted, Alice; Jensen, Tue Secher
to agree on the number, frequency and duration of chiropractic treatment. RESULTS: Thirty-four chiropractors from nine European countries participated. They described the characteristics of an acute, uncomplicated facet syndrome as follows: local, ipsilateral pain, occasionally extending into the thigh...... that there would be no signs of neurologic involvement or antalgic posture and no aggravation of pain from sitting, flexion or coughing/sneezing. CONCLUSION: The chiropractors attending the workshop described the characteristics of an acute, uncomplicated lumbar facet syndrome in much the same way as chronic pain......ABSTRACT: BACKGROUND: The term 'acute facet syndrome' is widely used and accepted amongst chiropractors, but poorly described in the literature, as most of the present literature relates to chronic facet joint pain. Therefore, research into the degree of consensus on the subject amongst a large...
Daniela Camargos Costa
Full Text Available Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4% and in wild Alouatta clamitans monkeys (n = 20, 35% from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.
Full Text Available Abstract Background A practical and simple regimen for all malaria species is needed towards malaria elimination in Indonesia. It is worth to compare the efficacy and safety of a single dose of artemisinin-naphthoquine (AN with a three-day regimen of dihydroartemisinin-piperaquine (DHP, the existing programme drug, in adults with uncomplicated symptomatic malaria. Methods This is a phase III, randomized, open label using sealed envelopes, multi-centre, comparative study between a single dose of AN and a three-day dose of DHP in Jayapura and Maumere. The modified WHO inclusion and exclusion criteria for efficacy study were used in this trial. A total of 401 eligible adult malaria subjects were hospitalized for three days and randomly treated with AN four tablets single dose on day 0 or DHP three to four tablets single daily dose for three days, and followed for 42 days for physical examination, thick and thin smears microscopy, and other necessary tests. The efficacy of drug was assessed by polymerase chain reaction (PCR uncorrected and corrected. Results There were 153 Plasmodium falciparum, 158 Plasmodium vivax and 90 P. falciparum/P. vivax malaria. Mean of fever clearance times were similar, 13.0 ± 10.3 hours in AN and 11.3 ± 7.3 hours in DHP groups. The mean of parasite clearance times were longer in AN compared with DHP (28.0 ± 11.7 hours vs 25.5 ± 12.2 hours, p = 0.04. There were only 12 PCR-corrected P. falciparum late treatment failures: seven in AN and five in DHP groups. The PCR uncorrected and corrected on day −42 of adequate clinical and parasitological responses for treatment of any malaria were 93.7% (95% Cl: 90.3–97.2 and 96.3% (95% Cl: 93.6–99.0 in AN, 96.3% (95% Cl: 93.5–99.0 and 97.3% (95% Cl: 95.0–99.6 in DHP groups. Few and mild adverse events were reported. All the abnormal haematology and blood chemistry values had no clinical abnormality. Conclusion AN and DHP are confirmed very effective
Abba, Katharine; Deeks, Jonathan J; Olliaro, Piero; Naing, Cho-Min; Jackson, Sally M; Takwoingi, Yemisi; Donegan, Sarah; Garner, Paul
Rapid diagnostic tests (RDTs) for Plasmodium falciparum malaria use antibodies to detect either HRP-2 antigen or pLDH antigen, and can improve access to diagnostics in developing countries. To assess the diagnostic accuracy of RDTs for detecting P. falciparum parasitaemia in persons living in endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria by type and brand. We undertook a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; MEDION; Science Citation Index; Web of Knowledge; African Index Medicus; LILACS; IndMED; to January 14, 2010. 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 P. falciparum endemic areas. For each study, a standard set of data was extracted independently by two authors, using a tailored data extraction form. Comparisons were grouped hierarchically by target antigen, and type and brand of RDT, and combined in meta-analysis where appropriate. We identified 74 unique studies as eligible for this review and categorized them according to the antigens they detected. Types 1 to 3 include HRP-2 (from P. falciparum) either by itself or with other antigens. Types 4 and 5 included pLDH (from P. falciparum) either by itself or with other antigens. In comparisons with microscopy, we identified 71 evaluations of Type 1 tests, eight evaluations of Type 2 tests and five evaluations of Type 3 tests. In meta-analyses, average sensitivities and specificities (95% CI) were 94.8% (93.1% to 96.1%) and 95.2% (93.2% to 96.7%) for Type 1 tests, 96.0% (94.0% to 97.3%) and 95.3% (87.3% to 98.3%) for Type 2 tests, and 99.5% (71.0% to 100.0%) and 90.6% (80.5% to 95.7%) for Type 3 tests, respectively. Overall for HRP-2, the meta-analytical average sensitivity and
A prospective comparative study of knowlesi, falciparum, and vivax malaria in Sabah, Malaysia: high proportion with severe disease from Plasmodium knowlesi and Plasmodium vivax but no mortality with early referral and artesunate therapy.
Barber, Bridget E; William, Timothy; Grigg, Matthew J; Menon, Jayaram; Auburn, Sarah; Marfurt, Jutta; Anstey, Nicholas M; Yeo, Tsin W
Plasmodium knowlesi commonly causes severe malaria in Malaysian Borneo, with high case-fatality rates reported. We compared risk, spectrum, and outcome of severe disease from P. knowlesi, Plasmodium falciparum, and Plasmodium vivax and outcomes following introduction of protocols for early referral and intravenous artesunate for all severe malaria. From September 2010 to October 2011 we prospectively assessed nonpregnant patients aged ≥12 years admitted to Queen Elizabeth Hospital (QEH), Sabah, with polymerase chain reaction-confirmed Plasmodium monoinfection. Standardized referral and prereferral intravenous artesunate were instituted at district hospitals. Severe malaria occurred in 38 of 130 (29%) patients with P. knowlesi, 13 of 122 (11%) with P. falciparum, and 7 of 43 (16%) with P. vivax. The commonest severity criteria in knowlesi malaria included parasitemia >100 000/µL (n = 18), jaundice (n = 20), respiratory distress (n = 14), hypotension (n = 13), and acute kidney injury (n = 9). On multivariate analysis, P. knowlesi was associated with a 2.96-fold (95% confidence interval, 1.19-7.38-fold) greater risk of severity than P. falciparum (P = .020); only parasitemia and schizontemia >10% independently predicted knowlesi severity. Risk of severe knowlesi malaria increased 11-fold with parasitemia >20 000/µL, and 28-fold with parasitemia >100 000/µL. Nearly all (92%) knowlesi malaria patients received oral artemisinin therapy; 36 of 38 (95%) and 39 of 92 (42%) with severe and nonsevere disease, respectively, also received ≥1 dose of intravenous artesunate. No deaths occurred from any species. Plasmodium knowlesi is the commonest cause of severe malaria at QEH, with parasitemia the major risk factor for severity. Early referral and treatment with artesunate was highly effective for severe malaria from all species and associated with zero mortality.
Caruso, Anna Maria; Pane, Alessandro; Garau, Roberto; Atzori, Pietro; Podda, Marcello; Casuccio, Alessandra; Mascia, Luigi
An accurate diagnosis of acute appendicitis is important to avoid severe outcome or unnecessary surgery but management is controversial. The aim of study was to evaluate, in younger and older children, the efficacy of conservative management for uncomplicated appendicitis and the outcome of complicated forms underwent early surgery. Children with acute appendicitis were investigated by clinical, laboratory variables and abdominal ultrasound and divided in two groups: complicated and uncomplicated. Complicated appendicitis underwent early surgery; uncomplicated appendicitis started conservative treatment with antibiotic. If in the next 24-48h it was worsening, the conservative approach failed and patients underwent late surgery. A total of 362 pediatric patients were included. One hundred sixty-five underwent early appendectomy; 197 patients were at first treated conservatively: of these, 82 were operated within 24-48h for failure. The total percentage of operated patients was 68.2%. An elevated association was found between surgery and ultrasound. Conservative treatment for uncomplicated appendicitis had high percentage of success (58%). Complications in operated patients were infrequent. Our protocol was effective in order to decide which patients treat early surgically and which conservatively; specific red flags (age and onset) can identified patients at most risk of complications or conservative failure. treatment study. II. Copyright © 2016 Elsevier Inc. All rights reserved.
Artemisinin derivatives constitute a key component of the present-day treatment for Plasmodium falciparum malaria. Resistance with artemisinins is generally associated with S769N point mutation in the sarco-endoplasmic reticulumdependant ATPase6 (SERCA ATPase6) gene of Plasmodium falciparum, few studies have ...
Infectious Diseases and Environmental Health Research Group, Department of ... Conclusion: There is high genetic diversity in MSP – 2 and GLURP allelic families of Plasmodium falciparum isolates from Okelele. Health Centre, Ilorin, Nigeria. Keywords: Plasmodium falciparum, Merozoite Surface Protein, genetic diversity.
Background: Plasmodium falciparum, the most dangerous malaria parasite species to humans remains an important public health concern in Okelele, a rural community in Ilorin, Kwara State, Nigeria. There is however little information about the genetic diversity of Plasmodium falciparum in Nigeria. Objective: To determine ...
Full Text Available Abstract Background Artemether/Lumefantrine (Coartem® has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2004 in Ethiopia. In the present study the therapeutic efficacy of artemether/lumefantrine for the treatment of uncomplicated P. falciparum infection at Kersa, Jima zone, South-west Ethiopia, has been assessed. Methods A 28 day therapeutic efficacy study was conducted between November 2007 and January 2008, in accordance with the 2003 WHO guidelines. Outcomes were classified as early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Results 90 patients were enrolled and completed the 28 day follow-up period after treatment with artemether/lumefantrine. Cure rate was very high, 96.3%, with 95% CI of 0.897-0.992 (PCR uncorrected. Age-stratified data showed adequate clinical and parasitological response (ACPR to be 100% for children under 5 and 97.4% and 87.3% for children aged 5-14, and adults, respectively. There was no early treatment failure (ETF in all age groups. Fever was significantly cleared on day 3 (P 0.05. No major side effect was observed in the study except the occurrence of mouth ulcers in 7% of the patients. Conclusions The current study proved the excellent therapeutic efficacy of artemether/lumefantrine in the study area and the value of using it. However, the proper dispensing and absorption of the drug need to be emphasized in order to utilize the drug for a longer period of time. This study recommends further study on the toxicity of the drug with particular emphasis on the development of oral ulcers in children.
Afolabi Bangmboye B
Full Text Available Abstract Background In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs and antinuclear IgG antibodies (ANA. The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Methods Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. Results The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. Conclusion The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative
Konaté Amadou T
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.
Kiaco, Kinanga; Teixeira, Joana; Machado, Marta; do Rosário, Virgílio; Lopes, Dinora
Drug resistance in Plasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem(®)). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99%. 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, the pfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 of pfmdr1 gene, and 769 of pfatp6 gene were assessed by PCR-RFLP and sequencing for pfk13-propeller genotype. The cure rate was 91.3%. The obtained results showed that from 103 patients, 12.6% (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4% (n = 69) for pfmdr1 N86Y position and only one sample carried the mutant allele (Y) for pfmdr1 1246; 14% of these samples showed increased pfmdr1 copy number; 100% (n = 21) had wild-type allele of k13 gene in all the studied positions. These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.
Plucinski, Mateusz M; Talundzic, Eldin; Morton, Lindsay; Dimbu, Pedro Rafael; Macaia, Aleixo Panzo; Fortes, Filomeno; Goldman, Ira; Lucchi, Naomi; Stennies, Gail; MacArthur, John R; Udhayakumar, Venkatachalam
The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February through May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uíge Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and the main outcome was a PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13 propeller gene. In the 320 children finishing the study, 25 treatment failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to 95%) in Zaire and 97% (91 to 100%) in Uíge. For DP, the proportions were 100% (95 to 100%) in Zaire, and 100% (96 to 100%) in Uíge. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL late-treatment failures had markers associated with lumefantrine resistance on the day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
K. N. Mendis
Full Text Available The cytokine tumor necrosis factor and other as yet unidentified factor(s which together mediate the killing of intraerythrocytic malaria parasites are transiently elevated in sera during paroxysms in human Plasmodium vivax infections in non-immunes. These factors which included TNF and parasite killing factor(s are associated with the clinical disease in malaria to the extent that their transient presence in infection sera coincided with paroxysms, the most pronounced clinical disturbances of P. vivax malaria and secondly because their levels were markedly lower in paroxysm sera of semi-immune patients who were resident of an endemic area. Further, a close parallel was obtained between serum TFN levels and changes in body temperature that occur during a P. vivax paroxysm in non-immune patients, suggesting a causative role for TNF in the fever in malaria. P. vivax rarely if ever cause complicated clinical syndromes. Nevertheles serum TFN levels reached in acutely ill P. vivax patients were as high as in patients suffering from cerebral complications of P. falciparum malaria as reported in studies from the Gambia. Cytokine profiles and other changes accompanying clinical disease in P. vivax and P. falciparum malaria are compared in this paper with a view to discussing the potential role of cytokines in the causation of disease in malaria.
Gerald, Noel; Mahajan, Babita; Kumar, Sanjai
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
Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki
Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.
Comparative analysis of the safety and tolerability of fixed-dose artesunate/amodiaquine versus artemether/lumefantrine combinations for uncomplicated falciparum malaria in pregnancy: a randomized open label study
Full Text Available Osede I Iribhogbe,1 Igue Emmanuel,2 Marylove Odianosen2 1Department of Pharmacology and Therapeutics, 2Department of Human Physiology College of Medicine, Ambrose Alli University Ekpoma, Edo State, Nigeria Abstract: A comparative clinical study was conducted to evaluate the safety and tolerability of two commonly used fixed dose artemisinin-based combinations for the treatment of uncomplicated Plasmodium falciparum malaria in the second and third trimester of pregnancy. To achieve this, a total of 155 participants were recruited for the study. Eighty of these were drawn from pregnant women who came for routine antenatal care while 40 nonpregnant participants were recruited from apparently healthy females in the community. Eighty pregnant participants with uncomplicated P. falciparum malaria were randomized into artesunate/amodiaquine (AA and artemether/lumefantrine (AL treatment arms while 40 nonpregnant and 35 nonmalarious pregnant women were used as control. The interventional groups received standard fixed dose combinations of AA (100/270 mg daily or AL (20/120 mg twice daily for 3 days. Blood samples were collected on day 4 and patients were followed-up closely to ascertain the safety of the drugs. The study showed a significant (p<0.0001 elevation of alkaline phosphatase in the AA and AL group compared to the nonpregnant control and a significant (p<0.05 elevation of alanine transaminase and aspartate transaminase level in the AL combination group when compared with the AA group. The elevated hepatic enzymes were within the normal range for pregnancy and were not clinically significant. Adverse event rate was higher in the AA group (n=28 [70%] when compared to the AL group (n=4 [10%] although the drugs were well-tolerated in both treatment arms. In conclusion, the use of these combinations is safe in the second and third trimester of pregnancy. However, we recommend active pharmacovigilance and spontaneous drug reporting of the agents in
Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity.
Na-Bangchang, Kesara; Muhamad, Phunuch; Ruaengweerayut, Ronnatrai; Chaijaroenkul, Wanna; Karbwang, Juntra
A markedly high failure rate of three-day artesunate-mefloquine was observed in the area along the Thai-Myanmar border. Identification of Plasmodium falciparum isolates with intrinsic resistance to each component of the artesunate-mefloquine combination was analysed with integrated information on clinico-parasitological response, together with systemic drug exposure (area under blood/plasma concentration-time curves (AUC)) of dihydroartemisinin and mefloquine, and in vitro sensitivity of P. falciparum in a total of 17 out of 29 P. falciparum isolates from patients with acute uncomplicated falciparum malaria. Analysis of the contribution of in vitro parasite sensitivity and systemic drug exposure and relationship with pfmdr1 copy number in the group with sensitive response was performed in 21 of 69 cases. Identification of resistance and/or reduced intrinsic parasitocidal activity of artesunate and/or mefloquine without pharmacokinetic or other host-related factors were confirmed in six cases: one with reduced sensitivity to artesunate alone, two with resistance to mefloquine alone, and three with reduced sensitivity to artesunate combined with resistance to mefloquine. Resistance and/or reduced intrinsic parasitocidal activity of mefloquine/artesunate, together with contribution of pharmacokinetic factor of mefloquine and/or artesunate were identified in seven cases: two with resistance to mefloquine alone, and five with resistance to mefloquine combined with reduced sensitivity to artesunate. Pharmacokinetic factor alone contributed to recrudescence in three cases, all of which had inadequate whole blood mefloquine levels (AUC0-7days). Other host-related factors contributed to recrudescence in one case. Amplification of pfmdr1 (increasing of pfmdr1 copy number) is a related molecular marker of artesunate-mefloquine resistance and seems to be a suitable molecular marker to predict occurrence of recrudescence. Despite the evidence of a low level of a decline in
Ostri, Christoffer; Holfort, Stig K; Fich, Marianne S
PURPOSE: To compare automated refraction 1 week and 1 month after uncomplicated cataract surgery. METHODS: In this prospective cohort study, we recruited patients in a 2-month period and included consecutive patients scheduled for bilateral small-incision phacoemulsification cataract surgery....... The exclusion criteria were (i) corneal and/or retinal pathology that could lead to automated refraction miscalculation and (ii) surgery complications. Automated refraction was measured 1 week and 1 month after surgery. RESULTS: Ninety-five patients met the in- and exclusion criteria and completed follow......-test). CONCLUSION: Automated refraction is stabile 1 week after uncomplicated cataract surgery, but there is a trend towards instability, if the refractive target is missed with 1.0 D or more....
Full Text Available Abstract Background By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam. Methods From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS (2mg/kg/day versus 4 mg/kg/day for three days followed by dihydroartemisinin-piperaquine (DHA-PPQ and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. Results 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg, 2.72 (AS 4mg/kg, and 2.98 hours (DHA-PPQ (p=0.19. The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02. The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4% and late clinical failure occurred in one (2% of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR rates in the three groups were 94%, 100%, and 100% (p=0.04. Conclusions This study demonstrated faster P. falciparum parasite
Wong, Carmen Ka Man; Kung, Kenny; Au-Doung, Philip Lung Wai; Ip, Margaret; Lee, Nelson; Fung, Alice; Wong, Samuel Yeung Shan
Uncomplicated urinary tract infections (UTI) are common in primary care. Whilst primary care physicians are called to be antimicrobial stewards, there is limited primary care antibiotic resistance surveillance and physician antibiotic prescription data available in southern Chinese primary care. The study aimed to investigate the antibiotic resistance rate and antibiotic prescription patterns in female patients with uncomplicated UTI. Factors associated with antibiotic resistance and prescrip...
Full Text Available Colonic diverticula are located predominantly on the right side in Asia and on the left side in Europe and the United States. Factors associated with uncomplicated colonic diverticulosis and its distribution pattern have been unknown. Our aims are to investigate the prevalence and risk factors for uncomplicated colonic diverticulosis. We conducted a prospective cross-sectional study in adults who underwent colonoscopy. Alcohol, alcohol related flushing, smoking, medications, and comorbidities were assessed by interview on the colonoscopy day. Alcohol consumption was categorized as nondrinker, light (1-180 g/week, moderate (181-360 g/week, and heavy (≥361 g/week. Smoking index was defined as the number of cigarettes per day multiplied by the number of smoking years and categorized as nonsmoker, <400, 400-799, and ≥800. A total of 2,164 consecutive patients were enrolled. Overall, 542 patients (25.1% had uncomplicated colonic diverticulosis located on the right side (50%, bilaterally (29%, and on the left side (21%. Univariate analysis revealed age, male, smoking index, alcohol consumption, aspirin use, anticoagulants use, corticosteroid use, hypertension, and atherosclerotic disease as factors significantly associated with diverticulosis. Alcohol related flushing was not associated with the disease. Multivariate analysis showed increasing age (P<0.01, increasing alcohol consumption (P<0.01 and smoking (P<0.01, and atherosclerotic disease (P<0.01 as significantly associated factors. Alcohol and smoking were associated with right-sided and bilateral diverticula. In conclusion, one in four Japanese adults have colonic diverticulosis (50% right-sided. Age, alcohol consumption, and smoking were found to be significant risk factors for uncomplicated colonic diverticulosis, particularly right-sided and bilateral.
Tarning, Joel; Rijken, Marcus J.; McGready, Rose; Phyo, Aung Pyae; Hanpithakpong, Warunee; Day, Nicholas P. J.; White, Nicholas J.; Nosten, François; Lindegardh, Niklas
Pregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boar...
Choi, Soo Ran
To determine perinatal outcomes in uncomplicated term pregnancies with a borderline amniotic fluid index (AFI). A retrospective review was conducted of uncomplicated singleton pregnancies at term (>37 weeks). Borderline and normal AFI were defined as 5.1 ≤ AFI ≤ 8.0 cm and 8.1 ≤ AFI ≤ 24 cm, respectively. Adverse perinatal outcomes, cesarean delivery for non-reassuring fetal heart rate testing, meconium-stained amniotic fluid, a 5-min Apgar score of borderline and normal AFI groups. Borderline AFI was not significantly associated with cesarean delivery for non-reassuring fetal heart rate testing (p = 0.513), meconium-stained amniotic fluid (p = 0.641), admission to the NICU (p = 0.368), or a 5-min Apgar score of borderline group. Multiple logistic regression analysis showed that borderline AFI was not associated with cesarean delivery for non-reassuring fetal heart rate testing (odds ratio [OR] = 0.72, 95% confidence interval [CI] 0.27-1.91, p = 0.52). In uncomplicated term pregnancies, a borderline AFI does not increase the risk of adverse perinatal outcomes.
Nagata, Naoyoshi; Niikura, Ryota; Shimbo, Takuro; Kishida, Yoshihiro; Sekine, Katsunori; Tanaka, Shohei; Aoki, Tomonori; Watanabe, Kazuhiro; Akiyama, Junichi; Yanase, Mikio; Itoh, Toshiyuki; Mizokami, Masashi; Uemura, Naomi
Colonic diverticula are located predominantly on the right side in Asia and on the left side in Europe and the United States. Factors associated with uncomplicated colonic diverticulosis and its distribution pattern have been unknown. Our aims are to investigate the prevalence and risk factors for uncomplicated colonic diverticulosis. We conducted a prospective cross-sectional study in adults who underwent colonoscopy. Alcohol, alcohol related flushing, smoking, medications, and comorbidities were assessed by interview on the colonoscopy day. Alcohol consumption was categorized as nondrinker, light (1-180 g/week), moderate (181-360 g/week), and heavy (≥361 g/week). Smoking index was defined as the number of cigarettes per day multiplied by the number of smoking years and categorized as nonsmoker, diverticulosis located on the right side (50%), bilaterally (29%), and on the left side (21%). Univariate analysis revealed age, male, smoking index, alcohol consumption, aspirin use, anticoagulants use, corticosteroid use, hypertension, and atherosclerotic disease as factors significantly associated with diverticulosis. Alcohol related flushing was not associated with the disease. Multivariate analysis showed increasing age (Pdiverticulosis (50% right-sided). Age, alcohol consumption, and smoking were found to be significant risk factors for uncomplicated colonic diverticulosis, particularly right-sided and bilateral.
Weld, Lancaster R; Nwoye, Uzoamaka O; Knight, Richard B; Baumgartner, Timothy S; Ebertowski, James S; Stringer, Matthew T; Kasprenski, Matthew C; Weld, Kyle J
To determine predictors of fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis performed by urology residents during the first 2 years of residency. The patient charts and computed tomography scans of consecutive, unilateral, uncomplicated ureteroscopy cases for urolithiasis were retrospectively reviewed. The cases were performed by beginning urology residents over the course of their first 2 years of urology residency training. A total of 200 ureteroscopy cases were reviewed. The mean stone diameter was 7.1 (±3.2) mm. Forty-three percent of cases were performed for renal stones and 58 % for ureteral stones. The mean operative time was 80.2 (±36.9) min. The mean fluoroscopy time was 69.1 (±38.2) s. No significant differences existed between cases performed by each of the two residents, and no statistical differences in case difficulty were observed throughout the study period. Linear regression analysis revealed the strongest association with lower fluoroscopy time to be increasing resident experience (p fluoroscopy time decreased by 79 % from 135 to 29 s per case. Other significant factors associated with increasing fluoroscopy time were placement of a postoperative stent under fluoroscopic guidance (p Fluoroscopy time during uncomplicated, unilateral ureteroscopy for urolithiasis decreases with increasing urology resident operative experience. Other technical options during ureteroscopy were also found to influence fluoroscopy time.
Lahner, Edith; Esposito, Gianluca; Zullo, Angelo; Hassan, Cesare; Cannaviello, Claudio; Paolo, Maria Carla Di; Pallotta, Lorella; Garbagna, Nicoletta; Grossi, Enzo; Annibale, Bruno
To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms. This study was a multicentre, 6-mo randomized, controlled, parallel-group intervention with a preceding 4-wk washout period. Consecutive outpatients with symptomatic uncomplicated diverticular disease, aged 40-80 years, evaluated in 4 Gastroenterology Units, were enrolled. Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B. Treatment A (n = 24 patients) received 1 symbiotic sachet Flortec(©) (Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo. Treatment B (n = 21 patients) received high-fibre diet alone for 6 mo. The primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment. In group A, the proportion of patients with abdominal pain 24 h decreased from 60% to 20% then 5% after 3 and 6 mo, respectively in group A (P diverticular disease. This treatment may be implemented by combining the high-fibre diet with Flortec(©).
Prieto, L; Esteban, M; Salinas, J; Adot, J M; Arlandis, S; Peri, L; Cozar, J M
The clinical manifestations of urinary infections, commonly mild and uncomplicated, have resulted in a generally empirical therapeutic decision-making process, which does not help fight resistances to antibacterial agents, thus causing a high rate of recurrence. This study seeks to reduce the clinical variability in the diagnosis and treatment of uncomplicated recurrent urinary tract infections (RUTIs). The consensus document was developed using a nominal group methodology, using scientific evidence on RUTIs extracted from a systematic (noncomprehensive) literature review, along with the expert judgment of specialists and their experience in clinical practice. RUTIs are considered the manifestation of at least 3 episodes of uncomplicated infection, with a positive culture in the past 12 months, in addition to (for men) the absence of structural or functional abnormalities. We maintain that the treatment should be empiric when suspecting RUTIs (prior to obtaining a urine sample for culture) in those patients who have a high probability of recurrence, associated risk factors and/or urinary or general symptoms, such as fever and chills. Homogeneous criteria are recommended for the diagnosis and treatment in order to fight the increased rates of resistance that the microorganisms develop against antimicrobial agents. Imprecision in the identification of the infection requires a search for agreements on homogenized criteria and decision algorithms that guide the management of these patients. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.
Full Text Available Abstract Background Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Methods Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Results Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum
Karunaweera, Nadira; Wanasekara, Deepani; Chandrasekharan, Vishvanath; Mendis, Kamini; Carter, Richard
Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum indicating that the parasite activity involved may be
Fröberg, Gabrielle; Jörnhagen, Louise; Morris, Ulrika; Shakely, Delér; Msellem, Mwinyi I; Gil, José P; Björkman, Anders; Mårtensson, Andreas
Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT) and integrated vector control. Artesunate-amodiaquine (ASAQ) was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP) alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy.The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002-2003 (n = 208) and seven years after wide scale use of ASAQ in 2010 (n = 122). There was a statistically significant decrease of pfcrt 76T (96-63%), pfmdr1 86Y (75-52%), 184Y (83-72%), 1246Y (28-16%) and the most common haplotypes pfcrt/pfmdr1 TYYD (46-26%) and TYYY (17-8%), while an increase of pfcrt/pfmdr1 KNFD (0.4-14%) and KNYD (1-12%). This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by artesunate per se and/or an associated fitness cost might represent contributing
Full Text Available Abstract Background Zanzibar has recently undergone a rapid decline in Plasmodium falciparum transmission following combined malaria control interventions with artemisinin-based combination therapy (ACT and integrated vector control. Artesunate-amodiaquine (ASAQ was implemented as first-line treatment for uncomplicated P. falciparum malaria in Zanzibar in 2003. Resistance to amodiaquine has been associated with the single nucleotide polymorphism (SNP alleles pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y. An accumulation of these SNP alleles in the parasite population over time might threaten ASAQ efficacy. The aim of this study was to assess whether prolonged use of ASAQ as first-line anti-malarial treatment selects for P. falciparum SNPs associated with resistance to the ACT partner drug amodiaquine. Methods The individual as well as the combined SNP allele prevalence were compared in pre-treatment blood samples from patients with uncomplicated P. falciparum malaria enrolled in clinical trials conducted just prior to the introduction of ASAQ in 2002–2003 (n = 208 and seven years after wide scale use of ASAQ in 2010 (n = 122. Results There was a statistically significant decrease of pfcrt 76T (96–63%, pfmdr1 86Y (75–52%, 184Y (83–72%, 1246Y (28–16% and the most common haplotypes pfcrt/pfmdr1 TYYD (46–26% and TYYY (17–8%, while an increase of pfcrt/pfmdr1 KNFD (0.4–14% and KNYD (1–12%. Conclusions This is the first observation of a decreased prevalence of pfcrt 76T, pfmdr1 86Y, 184Y and 1246Y in an African setting after several years of extensive ASAQ use as first-line treatment for uncomplicated malaria. This may support sustained efficacy of ASAQ on Zanzibar, although it was unexpected considering that all these SNPs have previously been associated with amodiaquine resistance. The underlying factors of these results are unclear. Genetic dilution by imported P. falciparum parasites from mainland Tanzania, a de-selection by
Okonko, I. O.
Full Text Available This study reports the prevalence of malaria caused by plasmodium between genders in Abeokuta, the capital city of Ogun State located in the forest zone of southwestern Nigeria between January 2002 and December 2004. Blood film examination for malaria parasites in 708 patients; 366 males and 342 females. Microscopic examination of thick films techniques was employed for this study. Of the 708 (100% patients examined, 577 (81.5% were Plasmodium-positive. A high malaria parasite prevalence rate of 81.5% was noted in this study. Female subjects were more infected (42.4% than males (41.9% however, there was no significant difference in the sex of the subjects studied (p=0.05. A high malaria parasite prevalence rate of 86.9% was noted in samples collected in year 2003 than in other years studied. There was significant difference in the years under study (p=0.05. This study shows that a good percentage of people were infested by malaria Plasmodium. This could be attributed to lack of adequate accommodation and poor sanitary conditions in the area under study. Although several efforts have been made to effectively control the high incidence of malaria in Nigeria, these have been largely unsuccessful due to a number of reasons such as irrigated urban agriculture which can be the malaria vector’s breeding ground in the city, stagnant gutters and swamps in our environment where mosquitoes breed in millions, and lack of political will and commitment of the government in its disease management program, low awareness of the magnitude of malaria problem, poor health practices by individuals and communities and resistance to drugs. Therefore, future interventions in Nigeria should be directed toward controlling malaria in the context of a moderate transmission setting; thus, large-scale distribution of insecticide-treated nets or widespread use of indoor residual spraying may be less cost-effective than enhanced surveillance with effective case management or
Full Text Available Abstract Background Haemozoin crystals, produced by Plasmodium during its intra-erythrocytic asexual reproduction cycle, can generate UV light via the laser-induced, non-linear optical process of third harmonic generation (THG. In the current study the feasibility of using haemozoin, constitutively stored in the parasite’s food vacuole, to kill the parasite by irradiation with a near IR laser was evaluated. Methods Cultured Plasmodium parasites at different stages of development were irradiated with a pulsed NIR laser and the viability of parasites at each stage was evaluated from their corresponding growth curves using the continuous culture method. Additional testing for germicidal effects of haemozoin and NIR laser was performed by adding synthetic haemozoin crystals to Escherichia coli in suspension. Cell suspensions were then irradiated with the laser and small aliquots taken and spread on agar plates containing selective agents to determine cell viability (CFU. Results Parasites in the late-trophozoites form as well as trophozoites in early-stage of DNA synthesis were found to be the most sensitive to the treatment with ~4-log reduction in viability after six passes through the laser beam; followed by parasites in ring phase (~2-log reduction. A ~1-log reduction in E. coli viability was obtained following a 60 min irradiation regimen of the bacteria in the presence of 1 μM synthetic haemozoin and a ~2-log reduction in the presence of 10 μM haemozoin. Minimal (≤15% cell kill was observed in the presence of 10 μM haemin. Conclusions Laser-induced third-harmonic generation by haemozoin can be used to inactivate Plasmodium. This result may have clinical implications for treating severe malaria symptoms by irradiating the patient’s blood through the skin or through dialysis tubing with a NIR laser.
Fayh, Ana Paula Trussardi; Krause, Mauricio; Rodrigues-Krause, Josianne; Ribeiro, Jerri Luiz; Ribeiro, Jorge Pinto; Friedman, Rogério; Moreira, José Cláudio Fonseca; Reischak-Oliveira, Alvaro
Vascular disease is the principal cause of death and disability in patients with diabetes, and endothelial dysfunction seems to be the major cause in its pathogenesis. Since L-arginine levels are diminished in conditions such as type 1 and type 2 diabetes, in this work we aimed to verify the effects of L-arginine supplementation (7 g/day) over the endothelial function and oxidative stress markers in young male adults with uncomplicated type 1 diabetes. We also investigated the influences of L-arginine administration on vascular/oxidative stress responses to an acute bout of exercise. Ten young adult male subjects with uncomplicated type 1 diabetes and twenty matched controls volunteered for this study. We analysed the influence of L-arginine supplementation (7 g/day during 1 week) over lower limb blood flow (using a venous occlusion plethysmography technique), oxidative stress marker (TBARS, Carbonyls), anti-oxidant parameters (uric acid and TRAP) and total tNOx in rest conditions and after a single bout of submaximal exercise (VO₂ at 10 % below the second ventilatory threshold). Data described as mean ± standard error (SE). Alpha level was P L-Arginine supplementation completely recovered basal blood flow to normal levels in type 1 diabetics' subjects (2.66 ± 0.3 to 4.74 ± 0.86 ml 100 ml⁻¹ min⁻¹) but did not interfere in any parameter of redox state or exercise. Our findings highlight the importance of L-arginine for the improvement of vascular function in subjects with diabetes, indicating that L-arginine supplementation could be an essential tool for the treatment for the disease complications, at least in non-complicated diabetes. However, based on our data, it is not possible to draw conclusions regarding the mechanisms by which L-arginine therapy is inducing improvements on cardiovascular function, but this important issue requires further investigations.
Fuehrer, Hans-Peter; Starzengruber, Peter; Swoboda, Paul; Khan, Wasif Ali; Matt, Julia; Ley, Benedikt; Thriemer, Kamala; Haque, Rashidul; Yunus, Emran Bin; Hossain, Shah Monir; Walochnik, Julia; Noedl, Harald
In spite of the high prevalence of malaria in Southeastern Bangladesh, there remains a significant shortage of information regarding the presence of three of five human malaria parasites: Plasmodium ovale, P. malariae, and P. knowlesi. The presence of P. ovale and P. knowlesi has previously never been reported from Bangladesh. We used a genus- and species-specific nested polymerase chain reaction, targeting highly conserved regions of the small subunit ribosomal RNA (SSU rRNA) gene, to investigate the presence of malaria parasites in a total number of 379 patient samples in a survey of patients with febrile illnesses in the Chittagong Hill Tracts in Southeastern Bangladesh. We identified the first cases of P. ovale in Bangladesh. They were confirmed by sequence analysis; 189 of 379 samples (49.9%; 95% confidence interval = 44.9-54.9%) were positive for Plasmodium sp. by PCR. P. falciparum monoinfections accounted for 68.3% (61.3-74.5%), followed by P. vivax (15.3%; 10.9-21.2%), P. malariae (1.6%; 0.5-4.6%), P. ovale (1.6%; 0.5-4.6%), and mixed infections (13.2%; 9.1-18.8%). We found no evidence of P. knowlesi in this region.
SUMMARY Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection. PMID:23554413
Brutus, Laurent; Santalla, José; Schneider, Dominique; Avila, Juan Carlos; Deloron, Philippe
Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.
Dréanic, Johann; Sion, Elena; Dhooge, Marion; Dousset, Bertrand; Camus, Marine; Chaussade, Stanislas; Coriat, Romain
Acute diverticulitis is a common disease with increasing incidence. In most of cases, diagnosis is made at an uncomplicated stage offering a curative attempt under medical treatment and use of antibiotics. There is a risk of diverticulitis recurrence. Uncomplicated diverticulitis is opposed to complicated forms (perforation, abscess or fistula). Recent insights in the pathophysiology of diverticulitis, the natural history, and treatments have permitted to identify new treatment strategies. For example, the use of antibiotics tends to decrease; surgery is now less invasive, percutaneous drainage is preferred, peritoneal lavage is encouraged. Treatments of the diverticulitis are constantly evolving. In this review, we remind the pathophysiology and natural history, and summarize new recommendations for the medical and surgical treatment of acute diverticulitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Full Text Available Abstract Background The capacity of Plasmodium falciparum-infected erythrocytes to bind uninfected erythrocytes (rosetting is associated with severe malaria in African children. Rosetting is mediated by a subset of the variant surface antigens PfEMP1 targeted by protective antibody responses. Analysis of the response to rosette-forming parasites and their PfEMP1 adhesive domains is essential for understanding the acquisition of protection against severe malaria. To this end, the antibody response to a rosetting variant was analysed in children recruited with severe or uncomplicated malaria or asymptomatic P. falciparum infection. Methods Serum was collected from Beninese children with severe malaria, uncomplicated malaria or P. falciparum asymptomatic infection (N = 65, 37 and 52, respectively and from immune adults (N = 30 living in the area. Infected erythrocyte surface-reactive IgG, rosette disrupting antibodies and IgG to the parasite crude extract were analysed using the single variant Palo Alto VarO-infected line. IgG, IgG1 and IgG3 to PfEMP1-varO-derived NTS-DBL1α1, CIDRγ and DBL2βC2 recombinant domains were analysed by ELISA. Antibody responses were compared in the clinical groups. Stability of the response was studied using a blood sampling collected 14 months later from asymptomatic children. Results Seroprevalence of erythrocyte surface-reactive IgG was high in adults (100% and asymptomatic children (92.3% but low in children with severe or uncomplicated malaria (26.1% and 37.8%, respectively. The IgG, IgG1 and IgG3 antibody responses to the varO-derived PfEMP1 domains were significantly higher in asymptomatic children than in children with clinical malaria in a multivariate analysis correcting for age and parasite density at enrolment. They were essentially stable, although levels tended to decrease with time. VarO-surface reactivity correlated positively with IgG reactivity to the rosetting domain varO-NTS-DBL1α1. None of the
Otchwemah Rowland N
Full Text Available Abstract Background Both chloroquine (CQ and sulfadoxine-pyrimethamine (SP are failing drugs in much of sub-Saharan Africa. Previous findings suggest an association between resistance to CQ and to SP in vivo, in vitro, and on the molecular level. Methods In 126 Ghanaian children with uncomplicated malaria, associations between mutations conferring resistance in the Plasmodium falciparum dihydrofolate reductase (dhfr; SP and chloroquine resistance transporter (crt; CQ genes, concentrations of residual antimalarial drugs, and gametocyte carriage were examined. Results Mutant dhfr alleles and the CQ-resistance allele crt T76 were strongly associated with each other. Isolates exhibiting the dhfr triple mutation seven times more likely also contained crt T76 parasites as compared to isolates without the dhfr triple variant (P = 0.0001. Moreover, both, isolates with the dhfr triple mutation (adjusted OR, 3.2 (95%CI, 1.0–10.4 and with crt T76 (adjusted OR, 14.5 (1.4–150.8 were associated with an increased likelihood of pre-treatment gametocytaemia. However, crt T76 did not correlate with gametocytaemia following SP treatment and no selection of crt T76 in SP treatment failure isolates was observed. Conclusion These results confirm an association between CQ and SP resistance markers in isolates from northern Ghana. This could indicate accelerated development of resistance to SP if CQ resistance is already present, or vice versa. Considering the enhanced transmission potential as reflected by the increased proportion of isolates containing gametocytes when resistant parasites are present, co-resistance can be expected to spread in this area. However, the underlying mechanism leading to this constellation remains obscure.
Theander Thor G
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.
Alexis N LaCrue
Full Text Available Artemisinin (ART is the recommended first line therapy for treating uncomplicated and drug-resistant Plasmodium falciparum, the most pathogenic form of malaria. However, treatment failure following ART monotherapy is not uncommon and resistance to this rapidly acting drug has been reported in the Thai-Cambodian border. Recent in vitro studies have shown that following treatment with dihydroartemisinin (DHA, the development of ring-stage parasites is arrested for up to 20 days. These arrested (i.e. dormant rings could be responsible for the recrudescence of infection that is observed following ART monotherapy. To develop a better understanding of the stage-specific effects of ART and determine if dormancy occurs in vivo, the ART derivative artesunate (AS was used to treat mice infected with the synchronous rodent malaria parasites P. vinckei petteri (non-lethal and P. v. vinckei (lethal. Results show that in both the non-lethal and lethal strains, ring-stage parasites are the least susceptible to treatment with AS and that the day of treatment has more of an impact on recrudescence than the total dose administered. Additionally, 24 hrs post-treatment with AS, dormant forms similar in morphology to those seen in vitro were observed. Finally, rate of recrudescence studies suggest that there is a positive correlation between the number of dormant parasites present and when recrudescence occurs in the vertebrate host. Collectively, these data suggest that dormancy occurs in vivo and contributes to recrudescence that is observed following AS treatment. It is possible that this may represent a novel mechanism of parasite survival following treatment with AS.
Full Text Available Cecal perforation is an uncommon phenomenon in a pediatric population. It has been linked to a number of underlying medical conditions, which may result in focal inflammation or relative ischemia including hematologic malignancy, infection, and inflammatory bowel disease. We present an otherwise healthy 16-year-old male diagnosed with acute uncomplicated appendicitis on ultrasound, who was found to have cecal perforation with normal appendix intraoperatively, ultimately requiring ileocectomy. With this report, we aim to present the numerous pathophysiologic etiologies of cecal perforation, and to promote a comprehensive differential diagnosis despite the clinical and radiologic findings consistent with uncomplicated appendicitis.
José Felipe Reoyo-Pascual
Full Text Available Malaria is a pathology caused by a parasite called Plasmodium, characteristic of tropical countries. The most frequent symptomatology includes cerebral malaria, jaundice, convulsive crisis, anemia, hypoglycemia, kidney failure and metabolic acidosis, among others. We are presenting the case of a patient diagnosed with malaria who suffered from acute hemorrhagic necrotizing pancreatitis and evolved poorly, as an example of this combination of symptoms, rarely found in our country.
Walker, Robin L; Chen, Guanmin; McAlister, Finlay A; Campbell, Norm R C; Hemmelgarn, Brenda R; Dixon, Elijah; Ghali, William; Rabi, Doreen; Tu, Karen; Jette, Nathalie; Quan, Hude
Hospitalizations for ambulatory care-sensitive conditions (ACSCs) represent an indirect measure of access and quality of community care. The purpose of this study was to examine the association between one ACSC, uncomplicated hypertension, and previous primary care physician (PCP) utilization. A cohort of patients with hypertension was identified using administrative databases in Alberta between fiscal years 1994 and 2008. We applied the Canadian Institute for Health Information's case definition to detect patients with uncomplicated hypertension as the most responsible reason for hospitalization and/or Emergency Department (ED) visit. We assessed hypertension-related and all-cause PCP visits. The overall adjusted rate of ACSC hospitalizations and ED visits for uncomplicated hypertension was 7.1 and 13.9 per 10,000 hypertensive patients, respectively. The likelihood of ACSC hospitalization for uncomplicated hypertension was associated with age, household income quintile, region of residence, and Charlson comorbidity status (all P hypertension increased from 4.8 per 10,000 hypertensive patients for those without hypertension-related PCP visits before diagnosis to 10.5 per 10,000 hypertensive patients for those with 5 or more hypertension-related PCP visits. The rate of ACSC hospitalizations and/or ED visits for uncomplicated hypertension increased as the number of hypertension-related PCP visits increased even after stratifying according to demographic and clinical characteristics. As the frequency of hypertension-related PCP visits increased, the rate of ACSC hospitalizations and/or ED visits for uncomplicated hypertension increased. This suggests that ACSC hospitalization for uncomplicated hypertension might not be a particularly good indicator for access to primary care. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Soulard, Valérie; Bosson-Vanga, Henriette; Lorthiois, Audrey; Roucher, Clémentine; Franetich, Jean-François; Zanghi, Gigliola; Bordessoulles, Mallaury; Tefit, Maurel; Thellier, Marc; Morosan, Serban; Le Naour, Gilles; Capron, Frédérique; Suemizu, Hiroshi; Snounou, Georges; Moreno-Sabater, Alicia; Mazier, Dominique
Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans.
Val, Fernando; Machado, Kim; Barbosa, Lisiane; Salinas, Jorge Luis; Siqueira, André Machado; Costa Alecrim, Maria Graças; Portillo, Hernando Del; Bassat, Quique; Monteiro, Wuelton Marcelo; Guimarães Lacerda, Marcus Vinícius
Malaria, a major global public health problem, is mainly caused by Plasmodium falciparum and Plasmodium vivax , and is responsible for nearly half a million deaths annually. Although P. vivax malaria was not believed to cause severe disease, recent robust studies have proved otherwise. However, the clinical spectrum and pathogenesis of severe vivax malaria and, especially, its respiratory complications remain poorly understood. A systematic search for articles reporting respiratory complications associated with vivax malaria was performed in Lilacs, Cochrane, Scielo, Web of Science, and Medline databases irrespective of publication date. Prevalence of acute respiratory distress syndrome ( ARDS) and associated mortality among vivax patients were calculated from cross-sectional and longitudinal studies, whereas factors associated with mortality were calculated from data pooled from case reports and series of cases. A total of 101 studies were included (49 cross-sectional or longitudinal and 52 case reports or series of cases). Prevalence of ARDS was 2.8% and 2.2% in children and adults, respectively, with nearly 50% mortality. Moreover, female sex ( P = 0.013), having any comorbidity ( P = 0.036), lower body temperature ( P = 0.032), lower hemoglobin ( P = 0.043), and oxygen saturation ( P = 0.053) values were significantly associated with mortality. Plasmodium vivax malaria respiratory complications included ARDS and were associated with high mortality. Demographics and clinical characteristics upon presentation to hospital were associated with mortality among patients with respiratory complications in vivax malaria. This study reaffirms the evidence of severe and fatal complications of P. vivax malaria and its associated respiratory complications.
Valmaseda, Aida; Bassat, Quique; Aide, Pedro; Cisteró, Pau; Jiménez, Alfons; Casellas, Aina; Machevo, Sonia; Aguilar, Ruth; Sigaúque, Betuel; Chauhan, Virander S; Langer, Christine; Beeson, James; Chitnis, Chetan; Alonso, Pedro L; Gaur, Deepak; Mayor, Alfredo
Plasmodium falciparum proteins involved in erythrocyte invasion are main targets of acquired immunity and important vaccine candidates. We hypothesized that anti-parasite immunity acquired upon exposure would limit invasion-related gene (IRG) expression and affect the clinical impact of the infection. 11 IRG transcript levels were measured in P. falciparum isolates by RT-PCR, and IgG/IgM against invasion ligands by Luminex®, in 50 Mozambican adults, 25 children with severe malaria (SM) and 25 with uncomplicated malaria (UM). IRG expression differences among groups and associations between IRG expression and clinical/immunologic parameters were assessed. IRG expression diversity was higher in parasites infecting children than adults (p = 0.022). eba140 and ptramp expression decreased with age (p = 0.003 and 0.007, respectively) whereas p41 expression increased (p = 0.022). pfrh5 reduction in expression was abrupt early in life. Parasite density decreased with increasing pfrh5 expression (p immune escape when tested in malaria-exposed individuals.
Jensen, Anja T R; Magistrado, Pamela; Sharp, Sarah
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...... in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA......(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var...
Lau, Tiek Ying; Sylvi, Mersumpin; William, Timothy
The sulphadoxine/pyrimethamine (SDX/PYR) combination had been chosen to treat uncomplicated falciparum malaria in Malaysia for more than 30 years. Non-silent mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes are responsible for the resistance to pyrimethamine and sulphadoxine, respectively. This study reports the mutational analysis of pfdhfr and pfdhps in single Plasmodium falciparum infection isolates from the interior division of Sabah, Malaysian Borneo. A total of 22 P. falciparum single infection isolates collected from two districts of the interior division of Sabah from February to November 2010 were recruited for the mutational study of pfdhfr and pfdhps. Both genes were amplified by nested PCR prior to DNA sequencing and mutational analysis. A total of three pfdhfr and four pfdhps alleles were identified. The most prevalent pfdhfr allele is ANRNL (86%) involving triple mutation at position 108(S to N), 59(C to R) and 164(I to L). In pfdhps, two novel alleles, SGTGA (73%) and AAKAA (5%) were identified. Alleles involving triple mutation in both pfdhfr (ANRNL) and pfdhps (SGTGA), which were absent in Sabah in a study conducted about 15 years ago, are now prevalent. High prevalence of mutations in SDX/PYR associated drug resistance genes are reported in this study. This mutational study of pfdhps and pfdhfr indicating that SDX/PYR should be discontinued in this region.
Adam Mayyada B
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.
Jhorawat, Rajesh; Beniwal, Pankaj; Malhotra, Vinay
We are reporting a case of hemolytic uremic syndrome, a rare manifestation of Plasmodium vivax malaria. A young driver was admitted with acute febrile illness, decreased urine output, anemia, thrombocytopenia, jaundice, and increased serum lactate dehydrogenase. He showed a partial response to antimalarial drugs. However, he was readmitted with worsening renal parameters. His kidney biopsy revealed chronic thrombotic microangiopathy. He remained dialysis dependent and later underwent renal transplantation successfully, with excellent graft function at 1-year.
Kvasnovsky, Charlotte L; Bjarnason, Ingvar; Donaldson, Ana Nora; Sherwood, Roy A; Papagrigoriadis, Savvas
Diverticular disease is a significant burden on healthcare systems that is managed, surgically or medically, mainly as an emergency or acute condition. There are no standardized treatment recommendations for symptomatic uncomplicated disease. We hypothesized that a probiotic would reduce abdominal pain in such patients. We conducted a single-center, double-blind, placebo-controlled trial of probiotic treatment (Symprove) in adult patients with moderate-to-severe chronic, non-acute symptomatic diverticular disease. 143 patients were randomized to receive 1 mL/kg/day of probiotic liquid (N = 72) or placebo (N = 71) daily for 3 months. The primary endpoint was abdominal pain severity. Secondary endpoints consisted of the change in the frequency of eight abdominal symptoms and the level of intestinal inflammation (fecal calprotectin). 120 patients completed the trial. Abdominal pain score, the primary end point, decreased in both groups, but no significant difference between the groups was found (P = 0.11). In relation to placebo, the probiotic significantly decreased the frequency of four of the eight secondary endpoints: constipation, diarrhea, mucorrhea, and back pain (P diverticular disease.
Full Text Available Acute bacterial sinusitis is a common infectious condition. Patients may initially present with an uncomplicated infection and later, despite appropriate initial antibiotic therapy, develop a potentially life-threatening complication. Interventions aimed at alleviating such unexpected events need be prompt and adequate. We describe a case of a patient who initially presented with signs and symptoms of acute sinusitis later to be diagnosed with a frontal epidural abscess.
Saharan Africa and they increase the prevalence of anaemia in pregnancy with resultant poor pregnancy outcomes. This study was carried out to assess the impact of Plasmodium falciparum and hookworm infections on.
Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the
Yuan, Z; He, C; Yan, S; Ke, Y; Tang, W
We assessed the efficacy of fosfomycin trometamol in treating uncomplicated gonococcal urethritis in men. We conducted an open randomized controlled trial in 152 consecutive men with any main complaints suggestive of uncomplicated gonococcal urethritis in Dujiangyan Medical Center between 1 September 2013 and 31 August 2015. In total, 126 patients completed all aspects of this study. Sixty were provided therapy with fosfomycin trometamol 3 g orally on days 1, 3 and 5 in the intervention group; the other 61 were provided ceftriaxone 250 mg intramuscularly plus azithromycin 1 g orally simultaneously as a single dose in the control group. The primary outcomes involved clinical and microbiologic cure on days 7 and 14 after receipt of all the study medications. At the day 7 follow-up visit, all the 121 participants had complete resolution of clinical symptoms and signs. In addition, five patients (two in the intervention group and three in the control group) discontinued intervention because of unsuccessful treatment. After receipt of all the study medications, these five patients still had urethral purulent discharge and were switched to other unknown treatment regimens by other doctors. The bacterial smears and cultures of urethral or urine specimens in the 121 patients who completed all aspects of the study were negative on a test-of-cure visit. In the per-protocol analysis, both clinical and microbiologic cure were experienced by 96.8% (60/62 patients) in the intervention group and 95.3% (61/64 patients) in the control group. There were no recurrences at the day 14 test-of-cure visit. This trial indicates that fosfomycin trometamol exhibits excellent efficacy for treatment of uncomplicated gonococcal urethritis in men. Serious adverse effects are rare. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Tarning, Joel; Rijken, Marcus J; McGready, Rose; Phyo, Aung Pyae; Hanpithakpong, Warunee; Day, Nicholas P J; White, Nicholas J; Nosten, François; Lindegardh, Niklas
Pregnant women are particularly vulnerable to malaria. The pharmacokinetic properties of antimalarial drugs are often affected by pregnancy, resulting in lower drug concentrations and a consequently higher risk of treatment failure. The objective of this study was to evaluate the population pharmacokinetic properties of piperaquine and dihydroartemisinin in pregnant and nonpregnant women with uncomplicated malaria. Twenty-four pregnant and 24 matched nonpregnant women on the Thai-Myanmar boarder were treated with a standard fixed oral 3-day treatment, and venous plasma concentrations of both drugs were measured frequently for pharmacokinetic evaluation. Population pharmacokinetics were evaluated with nonlinear mixed-effects modeling. The main pharmacokinetic finding was an unaltered total exposure to piperaquine but reduced exposure to dihydroartemisinin in pregnant compared to nonpregnant women with uncomplicated malaria. Piperaquine was best described by a three-compartment disposition model with a 45% higher elimination clearance and a 47% increase in relative bioavailability in pregnant women compared with nonpregnant women. The resulting net effect of pregnancy was an unaltered total exposure to piperaquine but a shorter terminal elimination half-life. Dihydroartemisinin was best described by a one-compartment disposition model with a 38% lower relative bioavailability in pregnant women than nonpregnant women. The resulting net effect of pregnancy was a decreased total exposure to dihydroartemisinin. The shorter terminal elimination half-life of piperaquine and lower exposure to dihydroartemisinin will shorten the posttreatment prophylactic effect and might affect cure rates. The clinical impact of these pharmacokinetic findings in pregnant women with uncomplicated malaria needs to be evaluated in larger series.
Ouedraogo, Dieu-Donné; Eti, Edmond; Daboiko, Jean-Claude; Simon, Frankz; Chuong, Van Tuan; Zué, Marcel Kouakou N
To study the epidemiologic and semiotic characteristics of uncomplicated sciatica in patients in a university hospital in Côte d'Ivoire. This retrospective study included 143 patients with an uncomplicated herniated disc hospitalized in the Cocody University Hospital from 1998 through 2002; patients were excluded if they were excessively sensitive to pain, had related motor deficits, cauda equina syndrome, or were resistant to medical treatment. Patients' average age was 42.5 years (range: 15-81), 58% were women, and mean body mass index (BMI) was 26.16. Ninety-nine (69.2%) reported relatively sedentary work. The disorder was characterized by an antalgic position (in 46.9%), an abnormal Schöber index in 117 (81.8%), the "bell sign" (in 63.6%) and a cough impulse in 58.7%. Lasègue's sign was homolateral at 114 (79.7%), and the average amplitude 42.2 degrees (range: 10 to 80). Paresis of 3/5 or higher was observed in 32 patients (22.4%). Radiography showed a disc disorder in 63% of cases; posterior osteoarthritis in 39.2% and a narrowed lumbar channel in 14 %. Computed tomography was performed for 56 patients and confirmed the presence of a hernia (median: 42,8%; paramedian: 48,2%; foraminal: 8,0%) of L4-l5 in 43 patients (77%); a large hernia, defined by a size greater than half of the rachidian channel, was found in eight (14,3%). After medical treatment, the course was favourable during this hospitalisation. Contrary to preconceived ideas, uncomplicated sciatica of black subjects has the same characteristics as in the white population.
Corten, Lieselotte; Jelsma, Jennifer; Human, Anri; Rahim, Sameer; Morrow, Brenda M
Pneumonia is the most important respiratory problem in low-to-middle income countries. Airway clearance therapy continues to be used in children with pneumonia and secretion retention; however, there is lack of evidence to support or reject this treatment. This study aimed to investigate the feasibility of a randomized controlled trial (RCT) on the efficacy and safety of assisted autogenic drainage (AAD) compared to standard nursing care in children hospitalized with uncomplicated pneumonia. A single-blinded pilot RCT was conducted on 29 children (median age 3.5 months, IQR 1.5-9.4) hospitalized with uncomplicated pneumonia. The intervention group received standard nursing care with additional bi-daily AAD, for 10 to 30 min. The control group only received standard nursing care, unless otherwise deemed necessary by the physician or physiotherapist. The primary outcome measure was duration of hospitalization. The secondary outcome measures included days of fever and supplemental oxygen support; respiratory rate (RR) and heart rate adjusted for age; RR and oxygen saturation pre-, post-, and 1-hr post-treatment; oxygen saturation; adverse events; and mortality. No difference was found for duration of hospitalization (median 7.5 and 7.0 days for the control and intervention groups, respectively); however, Kaplan-Meier analysis revealed a strong tendency towards a shorter time to discharge in the intervention group (p = .06). No significant differences were found for the other outcome measures at time of discharge. No adverse events were reported. Within the intervention group, a significant reduction in RR adjusted for age was found. As no adverse events were reported, and AAD did not prolong hospitalization; AAD might be considered as safe and effective in young children with uncomplicated pneumonia. However, a larger multicentred RCT is warranted to determine the efficacy of AAD compared to standard nursing care. Copyright © 2017 John Wiley & Sons, Ltd.
Milisavljević, Nemanja; Cvetković, Mirjana; Nikolić, Goran; Filipović, Branka; Milinić, Nikola
The association between celiac disease and eating disorders has been very rarely reported. This is the first report on celiac disease associated with bulimia in this part of Europe. An adult female patient with history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department, due to long lasting dyspeptic symptoms, constipation, major weight loss and fatigue. After positive serological screening, the diagnosis of celiac disease was confirmed with histopathology examination of duodenal biopsy specimen. Complicated interactions between celiac disease and bulimia can make them difficult to diagnose and treat. It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.
Obonyo, Charles O; Juma, Elizabeth A
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. 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. 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. 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 artemisinin-based combinations.
Qin, Xianhui; Li, Youbao; Sun, Ningling; He, Mingli; Tang, Genfu; Yin, Delu; Wang, JiGuang; Liang, Min; Wang, Binyan; Huo, Yong; Xu, Xin; Xu, Xiping; Hou, Fan Fan
We aimed to test the impact of achieved blood pressure (BP) on first stroke among patients with grade 1 hypertension and without cardiovascular diseases in the China Stroke Primary Prevention Trial. A total of 3187 patients with uncomplicated grade 1 hypertension were included. The risk of outcomes was assessed according to: (1) the proportion of visits in which BP was reduced to hypertension subtypes (isolated systolic hypertension or systolic-diastolic hypertension). However, a time-averaged SBP hypertension. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
Bisgaard, T; Støckel, M; Klarskov, B
fundoplication for gastro-oesophageal reflux disease. Patients were recommended to convalesce for 2 days after operation. Duration of convalescence, dysphagia, fatigue, nausea, vomiting and different pain components were registered daily during the first week and on days 10 and 30 after fundoplication. RESULTS...... or severe dysphagia during the study period. Fatigue scores were significantly increased for 6 days after surgery (P ... and dysphagia are significant problems after uncomplicated total laparoscopic fundoplication. The time taken off work and away from recreational activity exceeded the recommended 2 days of convalescence, justifying further efforts to optimize early clinical outcome after total laparoscopic fundoplication....
Reid, Esther W; McNeill, Jenny A; Alderdice, Fiona A; Tully, Mark A; Holmes, Valerie A
to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia. a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing ≥ 4000 g (study group) or macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks. Copyright © 2014 Elsevier Ltd. All rights reserved.
Full Text Available Thirty cases of uncomplicated duodenal ulcer treated by anterior superficial lesser curvature seromyotomy and posterior truncal vagotomy were studied to evaluate the efficacy of this procedure. There was completeness of vagotomy in all the cases as shown by endoscopic Congo Red test. Twenty-seven cases were asymptomatic at 1-48 months (Mean 22.3 follow up, while 3 patients had controllable side effects such as dumping and diarrhoea. There was no mortality. This procedure is safe, effective and is a favourable alternative to highly selective vagotomy.
Myat P Kyaw
Full Text Available Plasmodium falciparum resistance to artemisinins, the first line treatment for malaria worldwide, has been reported in western Cambodia. Resistance is characterized by significantly delayed clearance of parasites following artemisinin treatment. Artemisinin resistance has not previously been reported in Myanmar, which has the highest falciparum malaria burden among Southeast Asian countries.A non-randomized, single-arm, open-label clinical trial of artesunate monotherapy (4 mg/kg daily for seven days was conducted in adults with acute blood-smear positive P. falciparum malaria in Kawthaung, southern Myanmar. Parasite density was measured every 12 hours until two consecutive negative smears were obtained. Participants were followed weekly at the study clinic for three additional weeks. Co-primary endpoints included parasite clearance time (the time required for complete clearance of initial parasitemia, parasite clearance half-life (the time required for parasitemia to decrease by 50% based on the linear portion of the parasite clearance slope, and detectable parasitemia 72 hours after commencement of artesunate treatment. Drug pharmacokinetics were measured to rule out delayed clearance due to suboptimal drug levels.The median (range parasite clearance half-life and time were 4.8 (2.1-9.7 and 60 (24-96 hours, respectively. The frequency distributions of parasite clearance half-life and time were bimodal, with very slow parasite clearance characteristic of the slowest-clearing Cambodian parasites (half-life longer than 6.2 hours in approximately 1/3 of infections. Fourteen of 52 participants (26.9% had a measurable parasitemia 72 hours after initiating artesunate treatment. Parasite clearance was not associated with drug pharmacokinetics.A subset of P. falciparum infections in southern Myanmar displayed markedly delayed clearance following artemisinin treatment, suggesting either emergence of artemisinin resistance in southern Myanmar or spread
Full Text Available Abstract Background Maps of malaria distribution are vital for optimal allocation of resources for anti-malarial activities. There is a lack of reliable contemporary malaria maps in endemic countries in sub-Saharan Africa. This problem is particularly acute in low malaria transmission countries such as those located in the horn of Africa. Methods Data from a national malaria cluster sample survey in 2005 and routine cluster surveys in 2007 were assembled for Somalia. Rapid diagnostic tests were used to examine the presence of Plasmodium falciparum parasites in finger-prick blood samples obtained from individuals across all age-groups. Bayesian geostatistical models, with environmental and survey covariates, were used to predict continuous maps of malaria prevalence across Somalia and to define the uncertainty associated with the predictions. Results For analyses the country was divided into north and south. In the north, the month of survey, distance to water, precipitation and temperature had no significant association with P. falciparum prevalence when spatial correlation was taken into account. In contrast, all the covariates, except distance to water, were significantly associated with parasite prevalence in the south. The inclusion of covariates improved model fit for the south but not for the north. Model precision was highest in the south. The majority of the country had a predicted prevalence of Conclusion The maps showed that malaria transmission in Somalia varied from hypo- to meso-endemic. However, even after including the selected covariates in the model, there still remained a considerable amount of unexplained spatial variation in parasite prevalence, indicating effects of other factors not captured in the study. Nonetheless the maps presented here provide the best contemporary information on malaria prevalence in Somalia.
Noor, Abdisalan M; Clements, Archie C A; Gething, Peter W; Moloney, Grainne; Borle, Mohammed; Shewchuk, Tanya; Hay, Simon I; Snow, Robert W
Maps of malaria distribution are vital for optimal allocation of resources for anti-malarial activities. There is a lack of reliable contemporary malaria maps in endemic countries in sub-Saharan Africa. This problem is particularly acute in low malaria transmission countries such as those located in the horn of Africa. Data from a national malaria cluster sample survey in 2005 and routine cluster surveys in 2007 were assembled for Somalia. Rapid diagnostic tests were used to examine the presence of Plasmodium falciparum parasites in finger-prick blood samples obtained from individuals across all age-groups. Bayesian geostatistical models, with environmental and survey covariates, were used to predict continuous maps of malaria prevalence across Somalia and to define the uncertainty associated with the predictions. For analyses the country was divided into north and south. In the north, the month of survey, distance to water, precipitation and temperature had no significant association with P. falciparum prevalence when spatial correlation was taken into account. In contrast, all the covariates, except distance to water, were significantly associated with parasite prevalence in the south. The inclusion of covariates improved model fit for the south but not for the north. Model precision was highest in the south. The majority of the country had a predicted prevalence of or = 5% prevalence were predominantly in the south. The maps showed that malaria transmission in Somalia varied from hypo- to meso-endemic. However, even after including the selected covariates in the model, there still remained a considerable amount of unexplained spatial variation in parasite prevalence, indicating effects of other factors not captured in the study. Nonetheless the maps presented here provide the best contemporary information on malaria prevalence in Somalia.
Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E
Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria. Copyright © 2015. Published by Elsevier Ltd.
Full Text Available Malaria parasites dramatically alter the rheological properties of infected red blood cells. In the case of Plasmodium vivax, the parasite rapidly decreases the shear elastic modulus of the invaded RBC, enabling it to avoid splenic clearance. This study highlights correlation between rosette formation and altered membrane deformability of P. vivax-infected erythrocytes, where the rosette-forming infected erythrocytes are significantly more rigid than their non-rosetting counterparts. The adhesion of normocytes to the PvIRBC is strong (mean binding force of 440pN resulting in stable rosette formation even under high physiological shear flow stress. Rosetting may contribute to the sequestration of PvIRBC schizonts in the host microvasculature or spleen.
Paloque, Lucie; Ramadani, Arba P; Mercereau-Puijalon, Odile; Augereau, Jean-Michel; Benoit-Vical, Françoise
Plasmodium falciparum resistance to artemisinins, the most potent and fastest acting anti-malarials, threatens malaria elimination strategies. Artemisinin resistance is due to mutation of the PfK13 propeller domain and involves an unconventional mechanism based on a quiescence state leading to parasite recrudescence as soon as drug pressure is removed. The enhanced P. falciparum quiescence capacity of artemisinin-resistant parasites results from an increased ability to manage oxidative damage and an altered cell cycle gene regulation within a complex network involving the unfolded protein response, the PI3K/PI3P/AKT pathway, the PfPK4/eIF2α cascade and yet unidentified transcription factor(s), with minimal energetic requirements and fatty acid metabolism maintained in the mitochondrion and apicoplast. The detailed study of these mechanisms offers a way forward for identifying future intervention targets to fend off established artemisinin resistance.
Sim, Jae Eun; Choi, Young-Chul; Kim, Won-Joo
Facial diplegia has diverse etiologies, including viral and bacterial infections such as diphtheria, syphilis and Lyme disease, and also protozoal infection in very rarely cases. A 20-year-old male patient was admitted to our hospital due to bilateral weakness of the upper and lower facial muscles. Examination revealed that the patient had a facial diplegia of the peripheral type. A peripheral blood smear demonstrated the presence of the asexual trophozoite stage of Plasmodium vivax with ring-form trophozoites, which led to a diagnosis of malaria. A serum work-up revealed increased IgG titers of antibodies to myelin-associated glycoprotein and ganglioside GD1b. The patient was administered antimalarial treatment, 1 week after which he showed signs of recovery. To our knowledge, this is the first case of facial diplegia after malaria infection, providing evidence that the mechanism underlying the condition is related to immune-mediated disease. Facial diplegia can manifest after P. vivax infection.
Full Text Available Mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. Recent clarifications on the definition of regulated or accidental cell death by The Nomenclature Committee on Cell Death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context of malaria drug resistance, considering lack of really new drugs in the pipeline. Deciphering the mechanisms of death may help in detection of new drug targets and the design of innovative drugs. However, classifications have been evolving rapidly since initial description of “programmed cell death”, leading to some uncertainty as to whether Plasmodium cell death is accidental or regulated.
Full Text Available Abstract The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum.
Fançony, Cláudia; Brito, Miguel; Gil, Jose Pedro
Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.
The diagnostic approach of patients with suspected acute diverticulitis remains debated. On the one hand, a scoring system with the best predictive value in diagnosing acute diverticulitis has been developed in order to reduce the use of computed tomography (CT) scan, while, on the other hand, patients with a high probability of acute diverticulitis should benefit from CT scan from a clinical viewpoint, ensuring that they will receive the most appropriate treatment. The place and classification of CT scan for acute diverticulitis need to be reassessed. If the management of uncomplicated acute diverticulitis, abscess, and fecal peritonitis is now well codified, urgent surgical or medical treatment of hemodynamically stable patients presenting with intraperitoneal air or fluid without uncontrolled sepsis is still under discussion. Furthermore, the indications for laparoscopic lavage are not yet well established. It is known for years that episode(s) of acute uncomplicated diverticulitis may induce painful recurrent bowel symptoms, known as symptomatic uncomplicated diverticular disease and irritable bowel syndrome-like diverticular disease. These two clinical expressions of diverticular disease, that may darken quality of life, are treated medically aimed at symptom relief. The possible place of surgery should be discussed. Clinical and CT scan classifications should be separated entities. PMID:27574459
Full Text Available Patrick Ambrosetti Department of Surgery, Clinique Générale Beaulieu, Geneva, Switzerland Abstract: The diagnostic approach of patients with suspected acute diverticulitis remains debated. On the one hand, a scoring system with the best predictive value in diagnosing acute diverticulitis has been developed in order to reduce the use of computed tomography (CT scan, while, on the other hand, patients with a high probability of acute diverticulitis should benefit from CT scan from a clinical viewpoint, ensuring that they will receive the most appropriate treatment. The place and classification of CT scan for acute diverticulitis need to be reassessed. If the management of uncomplicated acute diverticulitis, abscess, and fecal peritonitis is now well codified, urgent surgical or medical treatment of hemodynamically stable patients presenting with intraperitoneal air or fluid without uncontrolled sepsis is still under discussion. Furthermore, the indications for laparoscopic lavage are not yet well established. It is known for years that episode(s of acute uncomplicated diverticulitis may induce painful recurrent bowel symptoms, known as symptomatic uncomplicated diverticular disease and irritable bowel syndrome-like diverticular disease. These two clinical expressions of diverticular disease, that may darken quality of life, are treated medically aimed at symptom relief. The possible place of surgery should be discussed. Clinical and CT scan classifications should be separated entities. Keywords: diverticulitis, urgent treatment, chronic symptoms, clinical and CT scan classifications
Flávia Carolina F de Araujo
Full Text Available BACKGROUND: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. METHODOLOGY/PRINCIPAL FINDINGS: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10. Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse showed haplotypes that were distinct from those of primary infections. Plasmodium vivax relapse was characterized by temporal variations in the predominant parasite clones. CONCLUSIONS/SIGNIFICANCE: The high rate of low frequency alleles observed in both primary and relapse infections, along with temporal variation in the predominant alleles, might be the source of reported heterologous hypnozoite activation. Our findings complicate the concept of heterologous activation, suggesting the involvement of undetermined mechanisms based on host or environmental factors in the simultaneous activation of multiple clones of hypnozoites.
Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.
Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639
Amoah, L. E.; Nuvor, S. V.; Obboh, E. K.
patients living in the Central Region of Ghana and to determine whether naturally occurring antibody levels against P. falciparum GLURP (PF3D7-1035300) and MSP3 (PF3D7-1035400) antigens are associated with decreased parasite load. Methods: Dried filter paper blood blots were obtained from children......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...... 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...
Prevalence of Single Nucleotide Polymorphisms in the Plasmodium falciparum Multidrug Resistance Gene (Pfmdr-1) in Korogwe District in Tanzania Before and After Introduction of Artemisinin-Based Combination Therapy
Thomsen, Thomas T; Ishengoma, Deus S; Mmbando, Bruno P
, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum-positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr.......9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.......Abstract. Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance...
Ahmad, Hesham M; Abdel-Azim, Eman S; Abdel-Aziz, Rasha T
Many medications are available for scabies treatment including oral and topical ivermectin. However, studies comparing these two forms as a scabies treatment are few. This study compares efficacy and safety of topical versus oral ivermectin as scabies treatment. The study included 62 confirmed uncomplicated scabies patients, divided into: Group I (32 patients, received topical ivermectin) and Group II (30 patients, received oral ivermectin). Patients were assessed, clinically and by KOH smear at 1, 2 and 4 weeks. Treatment was repeated after one week in patients with persistent infection. Adverse events were recorded. Most patients (87.5% and 73.5% in group I and group II respectively) were symptom free after a single treatment. A second treatment was required in 4 patients of group I and 8 patients of group II. However, 2 weeks after treatment symptoms and signs completely resolved in all cases with no recurrence at 4 weeks. This study suggests that both topical and oral ivermectin are safe and equally effective in treatment of uncomplicated scabies. Single treatment, whether topical or oral, is associated with high cure rate in a week post treatment. However, repeating treatment after one week may be required to achieve 100% cure. © 2015 Wiley Periodicals, Inc.
Marabotti, Claudio; Scalzini, Alessandro; Chiesa, Ferruccio
The presence of circulating gas bubbles has been repeatedly reported after uncomplicated SCUBA dives. The clinical and pathophysiological relevance of this phenomenon is still under debate but some experimental data suggest that silent bubbles may have a damaging potential on pulmonary endothelial cells. The aim of the present study was to evaluate the possible hemodynamic effect on pulmonary circulation of post-dive circulating gas bubbles. To this aim, 16 experienced divers were studied by Doppler-echocardiography in basal conditions and 2.0 ± 0.15 h after an uncomplicated, unrestricted recreational SCUBA dive. At the post-dive examination, circulating bubbles were present in 10/16 subjects (62.5%). Divers with circulating bubbles showed a significant post-dive increase of pulmonary systolic arterial pressure (evaluated by the maximal velocity of the physiological tricuspid regurgitation; P dive decrease of transmitral E/A ratio (index of left ventricular diastolic function: subjects with bubbles P dive diastolic function changes, observed in both groups, may be explained by a preload reduction due to immersion natriuresis. The results of the present study add some evidence that post-dive circulating bubbles, although symptomless, have an easily detectable pathogenetic potential, inducing unfavorable hemodynamic changes in the lesser circulation. Copyright © 2013 Elsevier Ltd. All rights reserved.
Full Text Available Objective To explore the effects of gastric motility (GM related hormones on the GM of uncomplicated obese binge eater, and to explore the effect of electroacupuncture on weight loss. Methods Thirty-two obese subjects with habit of immoderate eating and 20 healthy subjects with normal weight were enrolled. Venous blood samples were collected at 8:00p.m. after an overnight fast and collected again 30min after meal, then stored at -70℃. Serum ghrelin and GLP-1 were determined with ELISA method and motilin and leptin levels were determined by radioimmunoassay. 30min stimulation of electroacupuncture was performed daily on the obese persons for a week. On the eighth day, blood samples of the obese were collected again. Results Whether before or after meal, serum motilin and leptin levels were higher in obese group than in the control group (P0.05, and serum GLP-1 increased significantly in comparison with those before stimulation (P<0.01 in the obese group. Conclusion Electroacupuncture stimulation gives a certain therapeutic effect on loss of body weight in uncomplicated obese population with immoderate eating by affecting the endocrines related to GM. DOI: 10.11855/j.issn.0577-7402.2015.09.10
Carrino, John A. [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Outpatient Center, Baltimore, MD (United States); Swathwood, Todd C. [Blue Ridge Orthopedic Associates, Seneca (United States); Morrison, William B. [Thomas Jefferson University Hospital, Department of Radiology, Philadelphia, PA (United States); Glover, J.M. [Northern Arizona Orthopaedics, Flagstaff, AZ (United States)
Postdiscography infection is an uncommon complication. Magnetic resonance (MR) imaging is often the modality of choice for evaluating spinal infection. Discography entails disc access and fluid injection that could alter the baseline MR imaging appearance of the spine and be confounded for infection. Our purpose was to describe the MR imaging findings of the lumbar spine subsequent to uncomplicated discography and to determine if this may mimic infection. In a prospective cohort study of eight adults (age 22-64 years, mean 45 years) with 22 intradiscal injections, all subjects underwent routine unenhanced and contrast-enhanced MR imaging during the 2-3 week interval postdiscography. A subset of four returned for additional MR imaging during the 4-8 week interval postdiscography. MR images were reviewed for intradiscal, endplate, marrow, and epidural findings and then compared with prediscography examinations. Infection was excluded by clinical documentation. Postdiscography MR imaging showed that almost all levels were similar to baseline prediscography examinations. No levels developed new vertebral marrow edema, fluid-like intradiscal signal, endplate irregularity, or epidural abnormality. Two subjects simulated potential discitis, but these findings were unchanged from prediscography and were related to prior surgery. Uncomplicated lumbar spine discography does not cause MR imaging changes that simulate discitis. (orig.)
Y. El Harrech
Full Text Available Objectives. We compared outcome and complications after uncomplicated ureteroscopic treatment of distal ureteral calculi with or without the use of ureteral stents. Materials and Methods. 117 patients, prospectively divided into three groups to receive a double j stent (group 1, 42 patients, ureteral stent (group 2, 37 patients, or no stent (group 3, 38 patients, underwent ureteroscopic treatment of distal ureteral calculi. Stone characteristics, operative time, postoperative pain, lower urinary tract symptoms (LUTS, analgesia need, rehospitalization, stone-free rate, and late postoperative complications were all studied. Results. There were no significant differences in preoperative data. There was no significant difference between the three groups regarding hematuria, fever, flank pain, urinary tract infection, and rehospitalisation. At 48 hours and 1 week, frequency/urgency and dysuria were significantly less in the nonstented group. When comparing group 1 and group 3, patients with double j stents had statistically significantly more bladder pain (P=0.003, frequency/urgency (P=0.002, dysuria (P=0.001, and need of analgesics (P=0.001. All patients who underwent imaging postoperatively were without evidence of obstruction or ureteral stricture. Conclusions. Uncomplicated ureteroscopy for distal ureteral calculi without intraoperative ureteral dilation can safely be performed without placement of a ureteral stent.
Ansbach, Robert K.; Dybus, Karen; Bergeson, Rachel
Treatment of uncomplicated urinary tract infections (UTIs) has changed in the past few years with researchers advocating empiric treatment for shorter periods of time without the use of cultures. Researchers report that antibiotic resistance of Escherichia coli (E coli) to commonly prescribed antibiotics in uncomplicated UTIs has been increasing.…
Theander, T G; Bygbjerg, I C; Andersen, B J
The present longitudinal study was designed to characterize immunosuppression during acute Plasmodium falciparum infection, during the treatment and up to 1 month after the acute stage. The proliferative responses of blood mononuclear cells (BMNC) isolated from non-immune and semi-immune malaria...... from controls showed a significantly higher response. The SPag responses were also low in BMNC isolated on day 0 and increased in both the non-immune and the semi-immune patients during the observation period. These findings indicate that during malaria there is a depression of the parasite...
Chloroquine is still a first-line antimalarial drug in uncomplicated falciparum malaria. Increasing resistance to chloroquine has been reported in many parts of Nigeria. Clinical and parasitological responses and classes of resistance to chloroquine in falciparum malaria in five communities in Delta region, southern Nigeria ...
Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.
Leung, Alexander K C; Wong, Alex H C
Acute otitis media is a common childhood infection. Prompt diagnosis and appropriate treatment are very important. To review in depth the epidemiology, pathophysiology, clinical manifestations, diagnosis, complications and particularly treatment of acute otitis media in children. A PubMed search was completed in Clinical Queries using the key term "acute otitis media". Patents were searched using the key term "acute otitis media" from www.google.com/patents, http://espacenet.com, and www.freepatentsonline.com. Acute otitis media affects over 80% of children before their third birthday and 30 to 45% of these children have suffered two or more episodes. Streptococcus pneumoniae, nontypable Haemophilus influenzae, and Moraxella catarrhalis are the most frequently isolated middle-ear pathogens. The diagnosis is based on acute onset of symptoms such as otalgia and fever, middle ear inflammation such as erythema of the tympanic membrane, and middle ear effusion. The choice of treatment method depends on the age of the child, laterality, and the severity of the disease. Recent patents related to the management of acute otitis media are also retrieved and discussed. Antimicrobial treatment is recommended for all children less than two years of age, as well as in children ≥ two years of age who have a temperature ≥ 39oC; are toxic looking; have otalgia > 48 hours; have bilateral otitis media or otorrhea; have craniofacial abnormalities; are immunocompromised; or have uncertain access to follow-up. Amoxicillin is the drug of choice. Observation without antibiotic is an option in immunocompetent children ≥ two years of age who have an acute uncomplicated otitis media and non-severe illness if appropriate follow-up can be arranged. Copyright© Bentham Science Publishers; For any queries, please email at firstname.lastname@example.org.
Telford, Sam R; Telford, Sam R
Plasmodium pifanoi Scorza and Dagert B., known only from the type host, Ameiva ameiva, is redescribed from Kentropyx calcarata collected in Territorio Amazonas, Venezuela. Schizonts, 6.2 x 4.5 (4-8 x 3-6), produce on average 11.9 (7-16) merozoites. Gametocytes average 12.4 x 6.0 (8-16 x 4-10), with length x width (LW) 72.9 (52-112) and L/W 2.18 (1.1-3.3), and always contain 1-5 prominent vacuoles. Macrogametocytes in active infection are longer than microgametocytes, with greater LW, but gametocytes in chronic infection are not sexually dimorphic in dimension and are slightly smaller. Two additional malarial parasites are described from K. calcarata. Plasmodium lepidoptiformis has small schizonts, 4.6 x 3.2 (3-6 x 2.5-3), that produce 5.1 (4-8) merozoites and commonly resemble a butterfly in appearance. Gametocytes are elongate, 9.0 x 4.3 (7-10 x 3-6), with LW 38.3 (24-51) and L/W 2.2 (1.3-3.3), and sexually dimorphic, with macrogametocytes longer than microgametocytes, with greater LW. Plasmodium minasense calcaratae is characterized by very small, usually fan-shaped, schizonts. 3.4 x 2.6 (2.5-4.5 x 2.0-3.0), that produce 3.9 (3-4) merozoites. Gametocytes are spherical or ovoid, 6.7 x 5.0 (4.5-9.0 x 3.0-7.0), with LW 33.7 (15-54) and L/W 1.4 (1.0-2.3), with no sexual dimorphism in dimensions.
Full Text Available A malária é causada pela infeção por protozoários do género Plasmodium, sendo uma importante causa de doença, especialmente em países tropicais. O diagnóstico de malária é baseado na suspeita clínica e na deteção dos parasitas no sangue. O P. falciparum é a espécie que causa maior morbilidade e mortalidade. O efeito da co-infeção por múltiplas espécies sobre a evolução clínica não é certo. Se os doentes não forem tratados eficazmente na fase inicial, a doença pode evoluir para malária grave, cujas manifestações mais comuns no adulto são coma, acidose metabólica, insuficiência renal, icterícia grave, lesão pulmonar aguda e ARDS. A malária grave apresenta uma taxa de mortalidade alta, mesmo com tratamento adequado. Apresentamos o caso de um doente com malária grave, secundária a co-infecção pelo P. falciparum e P. ovale, com disfunção multiorgânica, que evoluiu favoravelmente após internamento na Unidade de Cuidados Intensivos. Malaria is caused by infection by protozoa of the genus Plasmodium, and is a major cause of disease, especially in tropical areas. The diagnosis of malaria is based on clinical suspicion and detection of the parasites in the blood. Plasmodium falciparum is the specie that causes most morbidity and mortality. The effect of multiple species co-infection on clinical outcomes of malaria is uncertain. If patients are not effectively treated in the early stages, the disease may progress to severe malaria, whose most common manifestations in adults are coma, metabolic acidosis, renal failure, severe jaundice, acute lung injury and ARDS. Severe malaria has a high mortality, even with appropriate treatment. We present a patient with severe malaria, secondary to co-infection by P. falciparum and P. ovale, with multiorgan dysfunction, which dramatically improved after admission on Intensive Care Unit.
Vanstreels, Ralph Eric Thijl; Capellino, Félix; Silveira, Patricia; Braga, Érika M; Rodríguez-Heredia, Sergio Andres; Loureiro, Julio; Catão-Dias, José Luiz
We report two cases of lethal avian malaria in Magellanic Penguins (Spheniscus magellanicus) captive at San Clemente del Tuyú, Argentina, approximately 560 km north of Argentinean breeding colonies of Magellanic Penguins. Blood smears revealed both penguins were concurrently infected by Plasmodium (Haemamoeba) tejerai, Plasmodium (Huffia) sp., and Plasmodium (Novyella) sp.
Full Text Available Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.
Duval, Linda; Nerrienet, Eric; Rousset, Dominique; Sadeuh Mba, Serge Alain; Houze, Sandrine; Fourment, Mathieu; Le Bras, Jacques; Robert, Vincent; Ariey, Frederic
Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.
Zwang, Julien; D'Alessandro, Umberto; Ndiaye, Jean-Louis; Djimdé, Abdoulaye A; Dorsey, Grant; Mårtensson, Andreas A; Karema, Corine; Olliaro, Piero L
Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models. Eight thousand eight hundred ninety-seven patients (77.0% <5 years-old) followed-up through 28 days treated with artemisinin combination therapy (ACT, 90%, n = 7968) or non-ACT. At baseline, under 5's had the highest risk of anaemia (77.6% vs. 32.8%) and higher parasitaemia (43,938 μl) than older subjects (2784 μl). Baseline anaemia increased the risk of parasitological recurrence. Hb began to fall after treatment start. In under 5's the estimated nadir was ~35 h (range 29-48), with a drop of -12.8% from baseline (from 9.8 g/dl to 8.7 g/dl, p = 0.001); in under 15's, the mean Hb decline between day 0-3 was -4.7% (from 9.4 to 9.0 g/dl, p = 0.001). The degree of Hb loss was greater in patients with high pre-treatment Hb and parasitaemia and with slower parasite reduction rates, and was unrelated to age. Subsequently, Hb increased linearly (+0.6%/day) until day 28, to reach +13.8% compared to baseline. Severe anaemia (<5 g/dl, 2 per 1000 patients) was transient and all patients recovered after day 14, except one case of very severe anaemia associated with parasite recurrence at day 28. There was no systematic difference in Hb concentrations between treatments and no case of delayed anaemia. On presentation with acute malaria young children with high parasitaemia have the highest risk of anaemia. The majority of patients experience a drop in Hb while on treatment as early as day 1-2, followed by a linear increase through follow-up. The degree of the early Hb dip is
Mangham-Jefferies, Lindsay; Hanson, Kara; Mbacham, Wilfred; Onwujekwe, Obinna; Wiseman, Virginia
As agents for their patients, providers often make treatment decisions on behalf of patients, and their choices can affect health outcomes. However, providers operate within a network of relationships and are agents not only for their patients, but also other health sector actors, such as their employer, the Ministry of Health, and pharmaceutical suppliers. Providers' stated preferences for the treatment of uncomplicated malaria were examined to determine what factors predict their choice of treatment in the absence of information and institutional constraints, such as the stock of medicines or the patient's ability to pay. 518 providers working at non-profit health facilities and for-profit pharmacies and drug stores in Yaoundé and Bamenda in Cameroon and in Enugu State in Nigeria were surveyed between July and December 2009 to elicit the antimalarial they prefer to supply for uncomplicated malaria. Multilevel modelling was used to determine the effect of financial and non-financial incentives on their preference, while controlling for information and institutional constraints, and accounting for the clustering of providers within facilities and geographic areas. 69% of providers stated a preference for artemisinin-combination therapy (ACT), which is the recommended treatment for uncomplicated malaria in Cameroon and Nigeria. A preference for ACT was significantly associated with working at a for-profit facility, reporting that patients prefer ACT, and working at facilities that obtain antimalarials from drug company representatives. Preferences were similar among colleagues within a facility, and among providers working in the same locality. Knowing the government recommends ACT was a significant predictor, though having access to clinical guidelines was not sufficient. Providers are agents serving multiple principals and their preferences over alternative antimalarials were influenced by patients, drug company representatives, and other providers working at the
de Almeida, Afonso; Arez, Ana Paula; Cravo, Pedro VL; do Rosário, Virgílio E
Background In response to chloroquine (CQ) resistance, the policy for the first-line treatment of uncomplicated malaria in the Democratic Republic of East Timor (DRET) was changed in early 2000. The combination of sulphadoxine-pyrimethamine (SP) was then introduced for the treatment of uncomplicated falciparum malaria. Methods Blood samples were collected in two different periods (2003–2004 and 2004–2005) from individuals attending hospitals or clinics in six districts of the DRET and checked for Plasmodium falciparum infection. 112 PCR-positive samples were inspected for genetic polymorphisms in the pfcrt, pfmdr1, pfdhfr and pfdhps genes. Different alleles were interrogated for potential associations that could be indicative of non-random linkage. Results Overall prevalence of mutations associated with resistance to CQ and SP was extremely high. The mutant form of Pfcrt (76T) was found to be fixed even after five years of alleged CQ removal. There was a significant increase in the prevalence of the pfdhps 437G mutation (X2 = 31.1; p = 0.001) from the first to second survey periods. A non-random association was observed between pfdhfr51/pfdhps437 (p = 0.001) and pfdhfr 59/pfdhps 437 (p = 0.013) alleles. Conclusion Persistence of CQ-resistant mutants even after supposed drug withdrawal suggests one or all of the following: local P. falciparum may still be inadvertently exposed to the drug, that mutant parasites are being "imported" into the country, and/or reduced genetic diversity and low parasite transmission help maintain mutant haplotypes. The association between pfdhfr51/pfdhps437 and pfdhfr 59/pfdhps 437 alleles indicates that these are undergoing concomitant positive selection in the DRET. PMID:19358729
Full Text Available Uncomplicated urinary tract infections (UTI in women are very common. Regular analysis of bacterial flora is important to formulate updated guidelines. The objective of this study is to determine and compare the microbiology of UTIs and their susceptibility patterns in a quaternary care hospital. In a seven-year review, the urine culture results of 480 female patients with uncomplicated UTIs were analyzed. Patients were divided into three groups according to their diagnosis and treatment characteristics: Group 1, cystitis at outpatient basis; group 2, cystitis at the Emergency Unit; and group 3, pyelonephritis. Group 1 included older patients, with a higher incidence of concomitant diabetes mellitus and recurrent UTIs. E. coli was the most common pathogen, responsible for 75.1% of cases, mainly for pyelonephritis (87.3%. Of the oral antimicrobials tested for cystitis, amoxicillin/clavulanate and nitrofurantoin had the highest susceptibility profiles (84.4% and 87.3%, respectively. For E. coli only, their susceptibility profiles were as high as 90.8% and 97.4%, respectively. For pyelonephritis treatment, fluoroquinoles had a susceptibility profile <90%, while ceftriaxone and gentamicin had susceptibility >90%. Uncomplicated UTI treatment is becoming more challenging because the susceptibility profiles of oral antimicrobials are increasingly resistant. In our environment, cystitis can still be managed with nitrofurantoin. Uncomplicated pyelonephritis should be managed with ceftriaxone or gentamicin.
Bosmans, Judith E; Coupé, Veerle M H; Knottnerus, Bart J; Geerlings, Suzanne E; Moll van Charante, Eric P; Ter Riet, Gerben
BACKGROUND: Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low rates of multidrug-resistant bacteria. OBJECTIVE: To compare
Bosmans, Judith E.; Coupé, Veerle M. H.; Knottnerus, Bart J.; Geerlings, Suzanne E.; Moll van Charante, Eric P.; ter Riet, Gerben
Uncomplicated Urinary Tract Infections (UTIs) are common in primary care resulting in substantial costs. Since antimicrobial resistance against antibiotics for UTIs is rising, accurate diagnosis is needed in settings with low rates of multidrug-resistant bacteria. To compare the cost-effectiveness
Conclusions: There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.
Markus, Miles B
A curious aspect of the evolution of the hypnozoite theory of malarial relapse is its transmogrification from theory into 'fact', this being of historical, linguistic, scientific and sociological interest. As far as it goes, the hypnozoite explanation for relapse is almost certainly correct. I contend, however, that many of the genotypically homologous, non-reinfection, relapse-like Plasmodium vivax recurrences that researchers ascribe to hypnozoite activation are probably hypnozoite-independent. Indeed, some malariologists are starting to recognize that homologous P. vivax recurrences have most likely been overattributed to activation of hypnozoites. Hitherto identified, non-hypnozoite, possible plasmodial sources of recurrence that must be considered, besides circulating erythrocytic stages, include parasites in splenic dendritic cells, other cells in the spleen (in addition to infected erythrocytes there), bone marrow (importantly) and the skin. I argue that we need to take into account the possibility of a dual or multiple extra-vascular origin of P. vivax non-reinfection recurrences, not arbitrarily discount it. The existence of a P. vivax reservoir(s) is a topical subject and one of practical importance for malaria eradication. Pertinent drug-associated matters are also discussed, as is the dormancy-related significance of clues provided by blood-stage-induced malarial infection.
Full Text Available Plasmodium falciparum is the causative agent of deadly malaria disease. It is an intracellular eukaryote and completes its multi-stage life cycle spanning the two hosts viz, mosquito and human. In order to habituate within host environment, parasite conform several strategies to evade host immune responses such as surface antigen polymorphism or modulation of host immune system and it is mediated by secretion of proteins from parasite to the host erythrocyte and beyond, collectively known as, malaria secretome. In this review, we will discuss about the deployment of parasitic secretory protein in mechanism implicated for immune evasion, protein trafficking, providing virulence, changing permeability and cyto-adherence of infected erythrocyte. We will be covering the possibilities of developing malaria secretome as a drug/vaccine target. This gathered information will be worthwhile in depicting a well-organized picture for host-pathogen interplay during the malaria infection and may also provide some clues for development of novel anti-malarial therapies.
Rodent malaria parasites (RMPs) serve as tractable models for experimental genetics, and as valuable tools to study malaria parasite biology and host-parasitevector interactions. Plasmodium vinckei, one of four RMPs adapted to laboratory mice, is the most geographically widespread species and displays considerable phenotypic and genotypic diversity amongst its subspecies and strains. The phenotypes and genotypes of P. vinckei isolates have been relatively less characterized compared to other RMPs, hampering its use as an experimental model for malaria. Here, we have studied the phenotypes and sequenced the genomes and transcriptomes of ten P. vinckei isolates including representatives of all five subspecies, all of which were collected from wild thicket rats (Thamnomys rutilans) in sub-Saharan Central Africa between the late 1940s and mid 1960s. We have generated a comprehensive resource for P. vinckei comprising of five high-quality reference genomes, growth profiles and genotypes of P. vinckei isolates, and expression profiles of genes across the intra-erythrocytic developmental stages of the parasite. We observe significant phenotypic and genotypic diversity among P. vinckei isolates, making them particularly suitable for classical genetics and genomics-driven studies on malaria parasite biology. As part of a proof of concept study, we have shown that experimental genetic crosses can be performed between P. vinckei parasites to potentially identify genotype-phenotype relationships. We have also shown that they are amenable to genetic manipulation in the laboratory.
Mwangi Jonathan M
Full Text Available Abstract Background Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. Methods Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. Results Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. Conclusions The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle.
Cuesta Astroz, Yesid; Segura Latorre, Cesar
Malaria is a parasitic disease that has a high impact on public health in developing countries. The sequencing of the plasmodium falciparum genome and the development of proteomics have enabled a breakthrough in understanding the biology of the parasite. Proteomics have allowed to characterize qualitatively and quantitatively the parasite s expression of proteins and has provided information on protein expression under conditions of stress induced by antimalarial. Given the complexity of their life cycle, this takes place in the 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 antimalarial on parasite protein expression and to characterize the proteomic profile of different 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.
Background Artemisinin-based combination therapy (ACT) is the recommended first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide but decreased artemisinin susceptibility, phenotypically characterized as slow parasite clearance time (PCT), has now been reported in Southeast Asia. This makes it all too important to measure the dynamics of parasite clearance in African patients treated with ACT over time, to understand trends and detect changes early enough to intervene Methods Individual patient data from 27 clinical trials of artesunate-amodiaquine (ASAQ) vs comparators conducted between 1999 and 2009 were analysed for parasite clearance on modified intent-to-treat (ITT) basis. Results Overall 15,017 patients treated for uncomplicated P. falciparum malaria at 44 sites in 20 sub-Saharan African countries were included in the analysis; 51% (n=7,660) vs 49% (n=7,357) were treated with ASAQ and comparator treatments, respectively. Seventy-seven per cent (77%) were children under six years of age. The proportion of the patients treated with ASAQ with persistent parasitaemia on Day 2 was 8.6%, and 1.5% on Day 3. Risk factor for not clearing parasites on Day 2 and Day 3 calculated by multivariate logistic regression with random effect on site and controlling for treatment were: high parasitaemia before treatment was (adjusted risk ratios (AOR) 2.12, 95% CI 1.91-2.35, AOR 2.43, 95% CI 1.98-3.00, respectively); non-ACT treatment (p=0.001, for all comparisons). Anaemia (p=0.001) was an additional factor for Day 2 and young age (p=0.005) for Day 3. In patients treated with ASAQ in studies who had complete parasitaemia data every 24 hours up to Day 3 and additionally Day 7, the parasite reduction ratio was 93.9% by Day 1 and 99.9% by Day 2. Using the median parasitaemia before treatment (p0=27,125 μL) and a fitted model, the predicted PCT (pPCT = 3.614*ln (p0) – 6.135, r² = 0.94) in ASAQ recipients was 31 hours. Conclusion Within the period covered by
Full Text Available Introduction. The association between celiac disease and eating disorders has been very rarely reported. This is the first report on celiac disease associated with bulimia in this part of Europe. Case report. An adult female patient with history of bulimia and one uncomplicated pregnancy was admitted to the Gastroenterology Department, due to long lasting dyspeptic symptoms, constipation, major weight loss and fatigue. After positive serological screening, the diagnosis of celiac disease was confirmed with histopathology examination of duodenal biopsy specimen. Conclusion. Complicated interactions between celiac disease and bulimia can make them difficult to diagnose and treat. It is important to consider the presence of celiac disease in patients with bulimia and gastrointestinal symptoms.
Uncomplicated, recurrent urinary tract infections (RUTIs) in heal-thy, premenopausal women are a common health complaint. This article discusses risk factors, diagnostic techniques, medical management, and referral information to help clinicians manage RUTIs in the primary care setting. This article cites research articles, systematic reviews, and current guidelines. The majority of RUTIs in healthy premenopausal women can be managed by using individualized plans of care. Referrals are usually not useful nor cost effective. This article discusses treatments based on increasing antimicrobial resistance and examines nonmicrobial options in RUTI prevention. This article serves as a foundation for guiding primary care providers in managing this common problem using current research and guidelines. ©2014 American Association of Nurse Practitioners.
Vieira, José Luiz Fernandes; Borges, Larissa Maria Guimarães; Nascimento, Margareth Tavares Silva; Gomes, Andreza de L S
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 3 by high performance liquid chromatography. The mean concentration of quinine was 6.04 +/-2.21 microg/mL in male patients and 5.98 +/-1.95 microg/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.
José Luiz Fernandes Vieira
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.
Channon Keith M
Full Text Available Abstract Aims Obese subjects with insulin resistance and hypertension have abnormal aortic elastic function, which may predispose them to the development of left ventricular dysfunction. We hypothesised that obesity, uncomplicated by other cardiovascular risk factors, is independently associated with aortic function. Methods and results We used magnetic resonance imaging to measure aortic compliance, distensibility and stiffness index in 27 obese subjects (BMI 33 kg/m2 without insulin resistance and with normal cholesterol and blood pressure, and 12 controls (BMI 23 kg/m2. Obesity was associated with reduced aortic compliance (0.9 ± 0.1 vs. 1.5 ± 0.2 mm2/mmHg in controls, p -1 × 10-3, p Conclusion Aortic elastic function is abnormal in obese subjects without other cardiovascular risk factors. These findings highlight the independent importance of obesity in the development of cardiovascular disease.
Noor Abdisalan M
Full Text Available Abstract Background Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services. Methods We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset. Results 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF, and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1, children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash
Fenny, Ama P; Hansen, Kristian S; Enemark, Ulrika
INTRODUCTION: The National Health Insurance Act, 2003 (Act 650) established the National Health Insurance Scheme (NHIS) in Ghana with the aim of increasing access to health care and improving the quality of basic health care services for all citizens. The main objective is to assess the effect...... of health insurance on the quality of case management for patients with uncomplicated malaria, ascertaining any significant differences in treatment between insured and non-insured patients. METHOD: A structured questionnaire was used to collect data from 523 respondents diagnosed with malaria...... prescribed ACTs which is in adherence to the drug of choice for malaria treatment in Ghana. However, there were no significant differences in the quality of malaria treatment given to the uninsured and insured patients. CONCLUSION: Adherence to the standard protocol of malaria treatment is low...
Oliveira, Giselle A.; Andersen, John F.; Oliveira, Marcus F.; Oliveira, Pedro L.; Barillas-Mury, Carolina
Background Mitochondria perform multiple roles in cell biology, acting as the site of aerobic energy-transducing pathways and as an important source of reactive oxygen species (ROS) that modulate redox metabolism. Methodology/Principal Findings We demonstrate that a novel member of the mitochondrial transporter protein family, Anopheles gambiae mitochondrial carrier 1 (AgMC1), is required to maintain mitochondrial membrane potential in mosquito midgut cells and modulates epithelial responses to Plasmodium infection. AgMC1 silencing reduces mitochondrial membrane potential, resulting in increased proton-leak and uncoupling of oxidative phosphorylation. These metabolic changes reduce midgut ROS generation and increase A. gambiae susceptibility to Plasmodium infection. Conclusion We provide direct experimental evidence indicating that ROS derived from mitochondria can modulate mosquito epithelial responses to Plasmodium infection. PMID:22815925
Cox-Singh, Janet; Culleton, Richard
Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits. Copyright © 2015 Elsevier Ltd. All rights reserved.
Reddy, Vikram K.; Girish, K.; Lakshmi, Pandit; Vijendra, R.; Kumar, Ajay; Harsha, R.
Objectives: Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acidB (GABAB) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS. Materials and Methods: This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient's perspective and third-party perspective. Results: The average cost-effectiveness ratio (ACER) in patient's perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03). Conclusion: Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide. PMID:25097273
Dimitropoulos, Konstantinos; Bargiota, Alexandra; Mouzas, Odysseas; Melekos, Michael; Tzortzis, Vassilios; Koukoulis, Georgios
Current studies indicate that women with type 1 diabetes (T1DM) have a high prevalence of sexual disorders although data on the prevalence of sexual dysfunction are limited when sexual distress is included. The frequency and the possible correlates of distressful sexual disorders in a highly selected group of type 1 diabetic women. The sexual function, sexual distress, and general health status were assessed in 44 premenopausal women with uncomplicated T1DM and 47 healthy controls, using the Female Sexual Function Index (FSFI), the Female Sexual Distress Scale (FSDS), and the General Health Questionnaire-28 (GHQ-28). The impact of sexual distress on the frequency of female sexual dysfunction (FSD). The frequency of sexual disorders according to the FSFI was significantly higher in diabetic compared to control women (25% vs. 8.5%, respectively, P Diabetic women had significantly lower median (first to third quartile) total FSFI score compared to control group (30.55 [26.08-33.08] vs. 33.50 [30.70-34.30], P = 0.001). Desire, arousal, and satisfaction were the sexual domains significantly affected in the diabetic group. Diabetic women had significantly higher median (first to third quartile) FSDS score compared to control group (6.5 [2.3-15.8] vs. 4.0 [1.0-10.5] P = 0.043). FSD (combined pathological FSFI and FSDS scores) was present in higher proportion of diabetic women (15.9%) compared to controls (2.1%) (P = 0.020). GHQ-28 score was comparable between the groups. However, in the diabetic group, FSD was related with anxiety, depression, and low educational level. Diabetes-related factors were not associated with FSD. Pre-menopausal women with uncomplicated T1DM have significantly higher frequency of FSD compared to healthy controls, when the criterion of sexual distress is included. Psychosomatic and contextual factors implicated in sexual distress are correlates of FSD. © 2012 International Society for Sexual Medicine.
Full Text Available Purpose. To evaluate the clinical outcomes after uncomplicated cataract surgery with implantation of an aspheric toric intraocular lens (IOL during a 6-month follow-up. Methods. Prospective study including 27 consecutive eyes of 18 patients (mean age: 66.1±11.4 years with a visually significant cataract and corneal astigmatism ≥ 0.75 D and undergoing uncomplicated cataract surgery with implantation of the Tecnis ZCT toric IOL (Abbott Medical Optics. Visual, refractive, and keratometric outcomes as well as IOL rotation were evaluated during a 6-month follow-up. At the end of the follow-up, patient satisfaction and perception of optical/visual disturbances were also evaluated using a subjective questionnaire. Results. At 6 months after surgery, mean LogMAR uncorrected (UDVA and corrected distance visual acuity (CDVA were 0.19±0.12 and 0.14±0.10, respectively. Postoperative UDVA of 20/40 or better was achieved in 92.6% of eyes. Mean refractive cylinder decreased significantly from −3.73±1.96 to −1.42±0.88 D (p<0.001, while keratometric cylinder did not change significantly (p=0.44. Mean absolute IOL rotation was 1.1±2.4°, with values of more than 5° in only 2 eyes (6.9%. Mean patient satisfaction score was 9.70±0.46, using a scale from 0 (not at all satisfied to 10 (very satisfied. No postoperative optical/visual disturbances were reported. Conclusion. Cataract surgery with implantation of the Tecnis toric IOL is an effective method of refractive correction in eyes with corneal astigmatism due to the good IOL positional stability, providing high levels of patient’s satisfaction.
Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini
Plasmodium Knowlesi malaria is a parasitic mosquito-borne disease caused by a eukaryotic protist of genus Plasmodium Knowlesi transmitted by mosquito, Anopheles leucosphyrus to human and macaques. We developed and analyzed a deterministic Mathematical model for the transmission of Plasmodium Knowlesi malaria in human and macaques. The optimal control theory is applied to investigate optimal strategies for controlling the spread of Plasmodium Knowlesi malaria using treatment and culling as control strategies. The conditions for optimal control of the Plasmodium Knowlesi malaria are derived using Pontryagin's Maximum Principle. Finally, numerical simulations suggested that the combination of the control strategies is the best way to control the disease in any community.
Full Text Available 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.
... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... well it can be treated. Complications of acute pancreatitis may include: Acute kidney failure Long-term lung damage (ARDS) Buildup ...
Full Text Available The dissemination of mutant and resistant strains of Plasmodium falciparum makes a considerable contribution to the spread of drug-resistant malaria. Populations around harbours and airports could be particularly exposed to Plasmodium isolates introduced with imported cases of malaria. The use of chloroquine as well as the use of and sulfadoxine/pyrimethamine is currently an effective method for treating uncomplicated cases of malaria in Madagascar. As part of a monitoring programme, in vitro methods were used to assess the sensitivity of P. falciparum isolates in two coastal towns in Madagascar: Mahajanga on the west coast and Toamasina on the east coast. All of the isolates from both sites were sensitive to amodiaquine, quinine, pyrimethamine and cycloguanil. All of the isolates from Mahajanga were sensitive to chloroquine (n = 25; mean IC50 = 22.6 nM, 95 % confidence interval: 16.8-28.7 nM, whereas three of the isolates from Toamasina were resistant to chloroquine (n = 18; mean IC50 = 66.3 nM; 95 % confidence interval : 42.6-90 nM, The frequency of the Pfcrt Thr-76 and the dhfr Asn- 108 mutations was estimated by PCR/RFLP. The 43 P. falciparum isolates examined, including the three in vitro chloroquine-resistant isolates from Toamasina were all wild-type (Lys-76. Phenotyping and genotyping studies suggested that the prevalence of chloroquine- and pyrimethamine-resistant isolates and of mutant strains of P. falciparum is very low. These results showed that in vitro test and genotyping of resistance markers approaches could be successfully used to monitor the emergence of drug-resistant malaria and to try to alleviate the lack of medical teams able to carry out in vivo test. The possible hazard/risk associated with imported cases of malaria is discussed.
Full Text Available BACKGROUND: Natural immunity to Plasmodium falciparum has been widely studied, but its effects on parasite dynamics are poorly understood. Acquisition and clearance rates of untreated infections are key elements of the dynamics of malaria, but estimating these parameters is challenging because of frequent super-infection and imperfect detectability of parasites. Consequently, information on effects of host immune status or age on infection dynamics is fragmentary. METHODS: An age-stratified cohort of 347 individuals from Northern Ghana was sampled six times at 2 month intervals. High-throughput capillary electrophoresis was used to genotype the msp-2 locus of all P. falciparum infections detected by PCR. Force of infection (FOI and duration were estimated for each age group using an immigration-death model that allows for imperfect detection of circulating parasites. RESULTS: Allowing for imperfect detection substantially increased estimates of FOI and duration. Effects of naturally acquired immunity on the FOI and duration would be reflected in age dependence in these indices, but in our cohort data FOI tended to increase with age in children. Persistence of individual parasite clones was characteristic of all age-groups. Duration peaked in 5-9 year old children (average duration 319 days, 95% confidence interval 318;320. CONCLUSIONS: The main age-dependence is on parasite densities, with only small age-variations in the FOI and persistence of infections. This supports the hypothesis that acquired immunity controls transmission mainly by limiting blood-stage parasite densities rather than changing rates of acquisition or clearance of infections.
The case of a middle aged(39 years) man admitted with severe malaria in the male ward of the Federal Medical Centre, Owerri, Imo State, Nigeria is reported. The infecting species was Plasmodium falciparum and the patient was febrile, developed acute renal failure, severe thrombocytopenia and hepatic failure. Treatment ...
Cserti-Gazdewich Christine M
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.
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
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
John J Aponte
Full Text Available BACKGROUND: Naturally acquired malaria immunity has many determinants and, in the absence of immunological markers of protection, studies assessing malaria incidence through clinical endpoints remain an approach to defining immunity acquisition. We investigated the role of age in disease incidence and the effects of chemoprophylaxis on clinical immunity development to Plasmodium falciparum during a randomised controlled trial. METHODS AND FINDINGS: A total of 415 Tanzanian infants were randomly assigned to receive weekly malaria prophylaxis with Deltaprim (3.125 mg of pyrimethamine plus 25 mg of dapsone or placebo between the ages of 2 and 12 mo. Children were followed up until 4 y of age. Uncomplicated febrile malaria, severe malaria, and anaemia morbidity were assessed through hospital-based passive surveillance. Compared with the group of control participants, there was a marked reduction in the incidence of clinical malaria, severe malaria, and anaemia in the group of children who had received chemoprophylaxis during the first year of life. After discontinuing the intervention, there was a significant increase in the incidence of clinical malaria for 2 y. The cumulative rates of clinical malaria, by age 4 y, were slightly higher in the group of children who had previously received chemoprophylaxis: 3.22 episodes versus 3.02 episodes in the group of control participants; rate difference 0.20 (95% confidence interval [CI]: -0.21 to 0.59. By age 4 y, the cumulative rates of severe malaria, however, were slightly lower in chemosuppressed children (0.47 versus 0.59 (rate difference -0.12 [95% CI: -0.27 to 0.03]. The number of episodes of anaemia was also slightly lower in chemosuppressed children by age 4 y: 0.93 episodes (95% CI: 0.79 to 0.97 versus 1.12 episodes in the group of control participants (95% CI: 0.97 to 1.28 (rate difference -0.19 [95% CI: -0.40 to 0.01], respectively. CONCLUSIONS: Reducing exposure to P. falciparum antigens through
Anvikar Anupkumar R
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
Brasil, Larissa W; Areas, André L L; Melo, Gisely C; Oliveira, Cintia M C; Alecrim, Maria G C; Lacerda, Marcus V G; O'Brien, Connor; Oelemann, Walter M R; Zalis, Mariano G
Anti-malarial drug resistance has emerged as one of the biggest challenges confronting the worldwide effort to control malaria. The appearance of chloroquine and multi-drug resistance had devastating effects on therapeutic efficacy of former first-line agents. Artemisinin has proven to be an excellent therapeutic alternative to fill the void in chemotherapeutic options left by resistance mechanisms. At the time of introduction, no resistance to artemisinins had been recorded, and artemisinins demonstrated excellent parasite reduction rates. In an attempt to protect artemisinin efficacy, the World Health Organization (WHO) made artemisinin-based combination therapy (ACT) its official first-line treatment recommendation for uncomplicated Plasmodium falciparum in 2006. In Brazil, artemether/lumefantrine became the Brazilian Malaria Control Programme's official treatment recommendation in 2007. The sarco/endoplasmic reticulum Ca2+ - ATPase ortholog of P. falciparum (pfatp6) has been suggested as one of the targets of artemisinins. Consequently, pfatp6 gene polymorphisms are being investigated as markers of artemisinin resistance elsewhere. The goal of this work was to describe the molecular profile of pfatp6 in P. falciparum isolates from different localities in the Amazonas State. DNA polymorphisms of the pfatp6 gene in 80 P. falciparum isolates from 11 municipalities of the Amazonas State (Western Brazilian Amazon), before and after the introduction of ACT in the Brazilian anti-malarial guidelines, were analysed by automatic sequencing. Mutations in the pfatp6 gene were searched using Mutation Surveyor v3.25 software. The P. falciparum pfatp6 gene presented polymorphisms at codons 37, 630 and 898. The R37K mutation was found in 16% of the samples, A630S in 32% and I898I in 52%. No S769N mutation, however, was detected in the analysed samples. Despite the small number of samples, data presented here provide baseline information about polymorphisms of pfatp6 gene
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
Foumane Ngane, Vincent; Allico Djaman, Joseph; Culeux, Cécile; Piette, Nathalie; Carnevale, Pierre; Besnard, Patrick; Fortes, Filomeno; Basco, Leonardo K; Tahar, Rachida
The malaria situation has been worsening in Angola, partly due to armed conflict until the recent past and drug-resistant Plasmodium falciparum. Malaria transmission is heterogeneous within the country, and data on drug-resistant malaria in different parts of the country are incomplete. The aim of the present study was to evaluate resistance to 4-aminoquinolines and antifolate drugs in P. falciparum isolates collected in Benguela province, central Angola, using molecular markers. Fingerprick capillary blood was collected from asymptomatic children aged less than 15 years old during a household survey in and around Balombo town in 2010-2011. Samples were screened for P. falciparum by nested PCR. Molecular markers (P. falciparum dihydrofolate reductase [pfdhfr], P. falciparum dihydropteroate synthase [pfdhps], P. falciparum chloroquine resistance transporter [pfcrt], and P. falciparum multidrug-resistance gene 1 [pfmdr1]) were sequenced to determine the key codons associated with drug resistance. A total of 60 blood samples were positive for P. falciparum. Most isolates with successful PCR amplification had mutant pfdhfr alleles, with either double mutant AICNI (69%) or triple mutant AIRNI (21%) haplotypes. A16V, S108T, and I164L substitutions were not found. Many of the isolates were carriers of either SGKAA (60%) or AGKAA (27%) pfdhps haplotype. K540E substitution was absent. There were only two pfcrt haplotypes: wild-type CVMNK (11%) and mutant CVIET (89%). Wild-type pfmdr1 NYSND haplotype was found in 19% of the isolates, whereas single mutant pfmdr1 YYSND and NFSND haplotypes occurred in 48% and 11%, respectively. Double mutant pfmdr1 haplotypes (YFSND and YYSNY) occurred rarely. The results suggest that the high prevalence of mutant pfcrt CVIET haplotype is in agreement with low clinical efficacy of chloroquine observed in earlier studies and that the double pfdhfr mutant AICNI and single pfdhps mutant SGKAA are currently the predominant haplotypes associated
Brasil Larissa W
Full Text Available Abstract Background Anti-malarial drug resistance has emerged as one of the biggest challenges confronting the worldwide effort to control malaria. The appearance of chloroquine and multi-drug resistance had devastating effects on therapeutic efficacy of former first-line agents. Artemisinin has proven to be an excellent therapeutic alternative to fill the void in chemotherapeutic options left by resistance mechanisms. At the time of introduction, no resistance to artemisinins had been recorded, and artemisinins demonstrated excellent parasite reduction rates. In an attempt to protect artemisinin efficacy, the World Health Organization (WHO made artemisinin-based combination therapy (ACT its official first-line treatment recommendation for uncomplicated Plasmodium falciparum in 2006. In Brazil, artemether/lumefantrine became the Brazilian Malaria Control Programme's official treatment recommendation in 2007. The sarco/endoplasmic reticulum Ca2+ - ATPase ortholog of P. falciparum (pfatp6 has been suggested as one of the targets of artemisinins. Consequently, pfatp6 gene polymorphisms are being investigated as markers of artemisinin resistance elsewhere. The goal of this work was to describe the molecular profile of pfatp6 in P. falciparum isolates from different localities in the Amazonas State. Methods DNA polymorphisms of the pfatp6 gene in 80 P. falciparum isolates from 11 municipalities of the Amazonas State (Western Brazilian Amazon, before and after the introduction of ACT in the Brazilian anti-malarial guidelines, were analysed by automatic sequencing. Mutations in the pfatp6 gene were searched using Mutation Surveyor v3.25 software. Results The P. falciparum pfatp6 gene presented polymorphisms at codons 37, 630 and 898. The R37K mutation was found in 16% of the samples, A630S in 32% and I898I in 52%. No S769N mutation, however, was detected in the analysed samples. Conclusion Despite the small number of samples, data presented here
O'Leary, D Peter; Lynch, Noel; Clancy, Cillian; Winter, Desmond C; Myers, Eddie
This Delphi study provides consensus related to many aspects of acute diverticulitis and identifies other areas in need of research. To generate an international, expert-based, consensus statement to address controversies in the management of acute diverticulitis. This study was conducted using the Delphi technique from April 3 through October 21, 2014. A survey website was used and a panel of acute diverticulitis experts was formed via the snowball method. The top 5 acute diverticulitis experts in 5 international geographic regions were identified based on their number of publications related to acute diverticulitis. The Delphi study used 3 rounds of questions, after which the consensus statement was collated. A consensus statement related to the management of acute diverticulitis. Twenty items were selected for inclusion in the consensus statement following 3 rounds of questioning. A clear definition of uncomplicated and complicated diverticulitis is provided. In uncomplicated diverticulitis, consensus was reached regarding appropriate laboratory and radiological evaluation of patients as well as nonsurgical, surgical, and follow-up strategies. A number of important topics, including antibiotic treatment, failed to reach consensus. In addition, consensus was reached regarding many nonsurgical and surgical treatment strategies in complicated diverticulitis. Controversy continues internationally regarding the management of acute diverticulitis. This study demonstrates that there is more nonconsensus among experts than consensus regarding most issues, even in the same region. It also provides insight into the status quo regarding the treatment of acute diverticulitis and provides important direction for future research.
The incidence of asymptomatic Plasmodium falciparum infection among orphans between age groups, gender and blood groups was investigated. Standard microscopic methods were used to screen for malaria parasites in the blood specimens obtained from eighty-five (85) subjects in three orphanages in Kaduna and ...
Aug 19, 2011 ... Resistance to antifolates in Plasmodium falciparum is well described and has been observed in clinical set- tings for decades. At the molecular level, point muta- tions in the dhfr gene that lead to resistance have been identified, and the crystal structure of the wildtype and mutant dihydrofolate reductase ...
... the burden of infection on man and the prevention and control options can we understand the disease better and so be better prepare for the future management of this disease. Keywords: Plasmodium infection, Malaria, Epidemiology, Symptoms, Treatment, Control, Man Animal Research International Vol. 3 (3) 2006 pp.
Sulfadoxine-pyrimethamine (SP), the current first line antimalarial drug in Tanzania, is compromised by evolution and spread of mutations in the parasite's dhfr and dhps genes. In the present study we established the baseline frequencies of Plasmodium falciparum dihydrofolate reductase (pfdhfr) and dihydropteroate ...
The evolutionary landscape of antifolate resistance in Plasmodium falciparum. Marna S. Costanzo Daniel L. Hartl. Perspectives Volume 90 Issue 2 August 2011 ... Author Affiliations. Marna S. Costanzo1 Daniel L. Hartl1. Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA ...
Nov 8, 2010 ... The purpose of this study is to determine whether the apoptotic responses to Plasmodium chabaudi malaria in spleen and liver via mRNA expression of three genes involved in apoptosis (Bax, Bcl-2 and. Caspase-3) are similar or not and to detect if these genes could be a good marker for apoptosis due to.
Background: The World Health Organization (WHO) considers early and rapid diagnosis as one of the strategies to control malaria. This study compared the performance of Quantitative Buffy Coat (QBC) test and the Plasmodium lactate dehydrogenase (pLDH) rapid diagnostic test (RDT) with microscopy as the gold ...
De Vries, Jutte J. C.; Van Assen, Sander; Mulder, André B.; Kampinga, Greetje A.
An adult traveler presented with fever and malaise after returning from Sierra Leone. Young trophozoites of Plasmodium falciparum were seen in a blood smear, with parasitemia being 10%. Moreover, blood cultures drawn on admission signaled as "positive" after 1 day of incubation, but no bacteria were
Malaria and Human Immunodeficiency Virus (HIV) infections are major public health problems in Sub-Saharan Africa. Their overlapping geographical distribution and co-existence often result into high morbidity and mortality. This study was designed to establish the prevalence of Plasmodium falciparum malaria among HIV ...
Bahia, Ana C; Dong, Yuemei; Blumberg, Benjamin J; Mlambo, Godfree; Tripathi, Abhai; BenMarzouk-Hidalgo, Omar J; Chandra, Ramesh; Dimopoulos, George
SUMMARY Malaria parasite transmission requires the successful development of Plasmodium gametocytes into flagellated microgametes upon mosquito blood ingestion, and the subsequent fertilization of microgametes and macrogametes for the development of motile zygotes, called ookinetes, which invade and transverse the Anopheles vector mosquito midgut at around 18-36 h after blood ingestion. Within the mosquito midgut, the malaria parasite has to withstand the mosquito's innate immune response and the detrimental effect of its commensal bacterial flora. We have assessed the midgut colonization capacity of 5 gut bacterial isolates from field-derived, and 2 from laboratory colony, mosquitoes and their effect on Plasmodium development in vivo and in vitro, along with their impact on mosquito survival. Some bacterial isolates activated the mosquito's immune system, affected the mosquito's life span, and were capable of blocking Plasmodium development. We have also shown that the ability of these bacteria to inhibit the parasites is likely to involve different mechanisms and factors. A Serratia marcescens isolate was particularly efficient in colonizing the mosquitoes’ gut, compromising mosquito survival, and inhibiting both sexual- and asexual-stage Plasmodium through secreted factors, thereby rendering it a potential candidate for the development of a malaria transmission intervention strategy. PMID:24428613
Background Malaria parasites are frequently trans- mitted by unscreened blood transfusions in Africa. Pathogen reduction methods in whole blood would thus greatly improve blood safety. We aimed to determine the efficacy of riboflavin plus irradiation for treatment of whole blood infected with Plasmodium falciparum.
... of Giemsa and Leishman stained smears. Results showed that the prevalence rate of malaria parasite in the area was 62.0%. Only two species namely Plasmodium falciparum and P. vivax were identified with the former predominating (99.2%). International Journal of Natural and Applied Sciences Vol. 2 (4) 2006: pp.
Populations of exotic and indigenous domestic chickens and guinea fowls in northeastern Nigeria were surveyed for Plasmodium sp by examining their stained blood samples. The packed cel volumes of all blood samples were estimated. During the period of study (March to September 2006), raina data were collected.
Liu, Weimin; Li, Yingying; Learn, Gerald H; Rudicell, Rebecca S; Robertson, Joel D; Keele, Brandon F; Ndjango, Jean-Bosco N; Sanz, Crickette M; Morgan, David B; Locatelli, Sabrina; Gonder, Mary K; Kranzusch, Philip J; Walsh, Peter D; Delaporte, Eric; Mpoudi-Ngole, Eitel; Georgiev, Alexander V; Muller, Martin N; Shaw, George M; Peeters, Martine; Sharp, Paul M; Rayner, Julian C; Hahn, Beatrice H
Plasmodium falciparum is the most prevalent and lethal of the malaria parasites infecting humans, yet the origin and evolutionary history of this important pathogen remain controversial. Here we develop a single-genome amplification strategy to identify and characterize Plasmodium spp. DNA sequences in faecal samples from wild-living apes. Among nearly 3,000 specimens collected from field sites throughout central Africa, we found Plasmodium infection in chimpanzees (Pan troglodytes) and western gorillas (Gorilla gorilla), but not in eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus). Ape plasmodial infections were highly prevalent, widely distributed and almost always made up of mixed parasite species. Analysis of more than 1,100 mitochondrial, apicoplast and nuclear gene sequences from chimpanzees and gorillas revealed that 99% grouped within one of six host-specific lineages representing distinct Plasmodium species within the subgenus Laverania. One of these from western gorillas comprised parasites that were nearly identical to P. falciparum. In phylogenetic analyses of full-length mitochondrial sequences, human P. falciparum formed a monophyletic lineage within the gorilla parasite radiation. These findings indicate that P. falciparum is of gorilla origin and not of chimpanzee, bonobo or ancient human origin.
Wrenger, Carsten; Mueller, Ingrid B.; Schifferdecker, Anna J.; Jain, Rishabh; Jordanova, Rositsa; Groves, Matthew R.
Aspartate aminotransferases (AspATs; EC 220.127.116.11) catalyze the conversion of aspartate and α-ketoglutarate into oxaloacetate and glutamate and are key enzymes in the nitrogen metabolism of all organisms. Recent findings suggest that the plasmodial enzyme [Plasmodium falciparum aspartate
Hogh, B; Petersen, E; Dziegiel, Morten Hanefeld
A Plasmodium falciparum antigen gene coding for a 220-kD glutamate-rich protein (GLURP) has been cloned, and the 783 C-terminal amino acids of this protein (GLURP489-1271) have been expressed as a beta-galactosidase fusion protein in Escherichia coli. The encoded 783 amino acid residues contain two...
Full Text Available Actins are highly conserved proteins and key players in central processes in all eukaryotic cells. The two actins of the malaria parasite are among the most divergent eukaryotic actins and also differ from each other more than isoforms in any other species. Microfilaments have not been directly observed in Plasmodium and are presumed to be short and highly dynamic. We show that actin I cannot complement actin II in male gametogenesis, suggesting critical structural differences. Cryo-EM reveals that Plasmodium actin I has a unique filament structure, whereas actin II filaments resemble canonical F-actin. Both Plasmodium actins hydrolyze ATP more efficiently than α-actin, and unlike any other actin, both parasite actins rapidly form short oligomers induced by ADP. Crystal structures of both isoforms pinpoint several structural changes in the monomers causing the unique polymerization properties. Inserting the canonical D-loop to Plasmodium actin I leads to the formation of long filaments in vitro. In vivo, this chimera restores gametogenesis in parasites lacking actin II, suggesting that stable filaments are required for exflagellation. Together, these data underline the divergence of eukaryotic actins and demonstrate how structural differences in the monomers translate into filaments with different properties, implying that even eukaryotic actins have faced different evolutionary pressures and followed different paths for developing their polymerization properties.
van der Meer, Jan-Ytzen; Hirsch, Anna K. H.
Due to the increase in resistance of Plasmodium spp. against available antimalarials, there is a need for new, effective and innovative drugs. The non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, which is absent in humans, is suggested as an attractive source of
This study was aimed at examining existing relationship between peripheral parasitaemia of Plasmodium falciparum and anemia among pregnant women in a secondary hospital and a tertiary hospital in Osogbo, South-Western, Nigeria. Two hundred and twenty five (225) patients were enrolled into this study, one hundred ...
Lunev, Sergey; Bosch, Soraya S.; Batista, Fernando de Assis; Wrenger, Carsten; Groves, Matthew R.
The de novo pyrimidine-biosynthesis pathway of Plasmodium falciparum is a promising target for antimalarial drug discovery. The parasite requires a supply of purines and pyrimidines for growth and proliferation and is unable to take up pyrimidines from the host. Direct (or indirect) inhibition of de
Mar 18, 2008 ... ISSN 1684–5315 © 2008 Academic Journals. Full Length Research Paper. Variation of nitric oxide levels in imported Plasmodium falciparum malaria episodes. De Sousa, Karina*, Silva, Marcelo S. and Tavira, Luís T. Instituto de Higiene e Medicina Tropical, Centro de Malária e outras Doenças Tropicais, ...
SUMMARY. Background: We investigated the prevalence of sub-microscopic Plasmodium falciparum infections and gameto- cyte carriage in asymptomatic individuals in Navrongo in northern Ghana, an area of seasonal malaria transmission. Design: A cross sectional study of 209 randomly selected participants of all ...
Background: The ability of the host immune system to efficiently clear Plasmodium falciparum parasites during a malaria infection ... infection, in an attempt to identify immunological signs indicative of the development of natural immunity against malaria in Ibadan, ..... Stephens R, Langhorne J. Priming of CD4+ T cells and.
Therefore, these glycoproteins appear to be potential candidates for a vector- directed transmission-blocking vaccine (TBV). [Chugh M, Gulati B R and Gakhar S K 2010 Monoclonal antibodies AC-43 and AC-29 disrupt Plasmodium vivax development in the Indian malaria vector Anopheles culicifacies (Diptera: culicidae); J.
We have initiated such a study and presented herewith the results from the in silico understanding of a seventh chromosomal region of the malarial parasite Plasmodium falciparum encompassing the antigenic var genes (coding pfemp1) and the drug-resistant gene pfcrt located at a specified region of the chromosome 7.
Mockenhaupt, Frank P.; Ehrhardt, Stephan; Eggelte, Teunis A.; Markert, Miriam; Anemana, Sylvester; Otchwemah, Rowland; Bienzle, Ulrich
In 366 Ghanaian children with symptomatic Plasmodium falciparum malaria, low haemoglobin levels and severe anaemia were associated with a high multiplicity of infection (MOI) and with distinct merozoite surface protein alleles. High MOI not only reflects premunition but may also contribute to
Human Leukocyte Antigen (HLA), particularly HLA-B and class II alleles have been differentially associated with disease outcomes in different populations following infection with the malaria Plasmodium falciparum. However, the effect of HLA-A on malaria infection and/or disease is not fully understood. Recently, HLA-A ...
Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline
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...
Fine-scale genetic characterization of Plasmodium falciparum chromosome 7 encompassing the antigenic var and the drug-resistant pfcrt genes. RUCHI BAJAJ1, SUJATA MOHANTY2, A. P. DASH1 and APARUP DAS1, ∗. 1Evolutionary Genomics and Bioinformatics Laboratory, National Institute of Malaria Research,.
This study was carried out to determine the efficiency of two reagents, RNAlater and RNAwiz, for their ability to stabilize Plasmodium falciparum RNA in infected whole blood and saponin lysed parasite pellets for use in DNA microarrays. Eight infected blood samples were stored in each of the reagents, and RNA extracted at ...
Background: Malaria is endemic in many parts of the world. Various strategies have been planned to control malaria from time to time in many places. Whatever may be the strategy the prevalence of symptomatic and asymptomatic plasmodium parasitaemics has been of prime importance as useful parameter for its control.
Hogh, B; Petersen, E; Dziegiel, Morten Hanefeld
A Plasmodium falciparum antigen gene coding for a 220-kD glutamate-rich protein (GLURP) has been cloned, and the 783 C-terminal amino acids of this protein (GLURP489-1271) have been expressed as a beta-galactosidase fusion protein in Escherichia coli. The encoded 783 amino acid residues contain t...
Changing the malaria epidemiology will affect the genetic diversity of Plasmodium falciparum. We studied the association between diversity at the merozoite surface protein 2 loci and the severity of disease in childhood malaria in two populations and at different time periods in Ibadan, southwest Nigeria. Population A ...
Mombo-Ngoma, Ghyslain; Remppis, Jonathan; Sievers, Moritz; Zoleko Manego, Rella; Endamne, Lilian; Kabwende, Lumeka; Veletzky, Luzia; Nguyen, The Trong; Groger, Mirjam; Lötsch, Felix; Mischlinger, Johannes; Flohr, Lena; Kim, Johanna; Cattaneo, Chiara; Hutchinson, David; Duparc, Stephan; Joerg, Moehrle; Velavan, Thirumalaisamy P; Lell, Bertrand; Ramharter, Michael; Adegnika, Ayola Akim; Mordmüller, Benjamin; Kremsner, Peter G
Fosmidomycin-piperaquine is being developed as non-artemisinin-based combination therapy to meet the challenge of emerging artemisinin resistance. The study was a phase 2 single arm open label proof of concept study of the efficacy, tolerability and safety of fosmidomycin-piperaquine for the treatment of uncomplicated Plasmodium falciparum mono-infection in Gabon. Adults and children of both sexes with initial parasite counts between 1,000 and 150,000/µL were eligible for oral treatment with fosmidomycin (twice daily doses of 30mg/kg), and piperaquine (once daily dose of 16mg/kg) for three days and followed-up for 63 days. The primary efficacy endpoint was the per protocol PCR-corrected Day 28 adequate clinical and parasitological response (ACPR). 100 patients were enrolled. The PCR-corrected Day 28 ACPR rate was 83/83 or 100% (95% CI: 96-100). Fourteen patients had asexual parasitaemia between Day 28 and Day 63; all were typed by PCR as new infections. Fosmidomycin-piperaquine therapy led to rapid parasite clearance (median: 36h; IQR: 6-60) and fever clearance time (median: 12h; IQR: 6-48). The electrocardiogram assessments showed two subjects with QT corrected from the formula of Bazett (QTcB) >500msec following study drug administration. The majority of adverse events affected the gastrointestinal and respiratory tracts and were transient and mild to moderate in severity. This is the first report of the use of the combination fosmidomycin-piperaquine, a non-artemisinin-based combination therapy in clinical development. The combination appeared to have high efficacy, to be safe and well tolerated despite observed transient changes in electrocardiogram with prolongation of the QT interval.
Sanne S Berger
Full Text Available Members of the Plasmodium falciparum Erythrocyte Membrane protein 1 (PfEMP1 family expressed on the surface of malaria-infected erythrocytes mediate binding of the parasite to different receptors on the vascular lining. This process drives pathologies, and severe childhood malaria has been associated with the expression of particular subsets of PfEMP1 molecules. PfEMP1 are grouped into subtypes based on upstream sequences and the presence of semi-conserved PfEMP1 domain compositions named domain cassettes (DCs. Earlier studies have indicated that DC5-containing PfEMP1 (DC5-PfEMP1 are more likely to be expressed in children with severe malaria disease than in children with uncomplicated malaria, but these PfEMP1 subtypes only dominate in a relatively small proportion of the children with severe disease. In this study, we have characterised the genomic sequence characteristic for DC5, and show that two genetically different parasite lines expressing DC5-PfEMP1 bind PECAM1, and that anti-DC5-specific antibodies inhibit binding of DC5-PfEMP1-expressing parasites to transformed human bone marrow endothelial cells (TrHBMEC. We also show that antibodies against each of the four domains characteristic for DC5 react with native PfEMP1 expressed on the surface of infected erythrocytes, and that some of these antibodies are cross-reactive between the two DC5-containing PfEMP1 molecules tested. Finally, we confirm that anti-DC5 antibodies are acquired early in life by individuals living in malaria endemic areas, that individuals having high levels of these antibodies are less likely to develop febrile malaria episodes and that the antibody levels correlate positively with hemoglobin levels.
Barrera, Sandra Milena; Pérez, Manuel Alberto; Knudson, Angélica; Nicholls, Rubén Santiago; Guerra, Angela Patricia
The genetic diversity of Plasmodium falciparum has been one of the major obstacles for the success of anti-malaria drug therapy. It provides the parasite an ability to evade the host's immune response by generating changes in its antigenic composition and resistance to antimalarial drugs. The genetic diversity of P.falciparum was characterized in 4 Colombian localities through the analysis of polymorphic genes. Eighty-one samples were obtained from patients with uncomplicated P. falciparum malaria and screened for polymorphic variants of msp1, msp2 (merozoite surface proteins) and glurp (glutamate-rich protein) with a multiplex PCR assay. The geographic regions sampled were Tierralta (Córdoba), in northwestern Colombia and in the Orinoco river watershed of eastern Colombia--Inírida (Guainía), La Carpa (Guaviare), and Casuarito (Vichada). The MAD20 variant was detected in all samples analyzed for the msp1 gene. For the msp2 gene, the IC allelic family was found in 96.3% of the samples as compared to 4.9% of the samples with the FC family. Both families showed size polymorphism with bands between 467 and 513 basepairs (bp) for IC and 286 and 300 bp for FC. PCR products of differing sizes were detected for the glurp gene and grouped into 5 size classes: I (600-699 bp) 2.5%, II (700-799 bp) 19.8%, III (800-899 bp) 72.8%, IV (900-999 bp) 1.2% and V (1000-1099 bp) 3.7%. The msp1 molecular marker did not provide information for differentiating P. falciparum parasite populations. The msp2 gene was more suitable for studying the genetic diversity, however, further studies are required to identify polymorphisms within the two allelic families. The glurp gene showed a great genetic diversity of circulating P. falciparum populations, and suggested that this gene may be useful for distinguishing between recrudescence and reinfection.
Abdul-Ghani, Rashad; Farag, Hoda F; Allam, Amal F; Shawky, Sherine M; Al-Mekhlafi, Abdulsalam M
Malaria still represents a major health problem in Yemen, particularly in Hodeidah, despite continuing efforts to eliminate it. With the absence of clinically proven vaccines, chemotherapy with antimalarials is still greatly needed. Chloroquine (CQ) has been popular as the drug of choice for malaria control. However, Plasmodium falciparum resistance to CQ has been one of the main obstacles in malaria control and elimination. Although CQ is no longer the recommended antimalarial chemotherapy, it has remained the number one over-the-counter antimalarial drug in many endemic areas, including Yemen, and is still used for self-medication. In addition, promising reports on CQ efficacy reversal in many African countries brought it again into the scene. This has led to a growing interest in the possibility of its re-introduction, particularly with the concerns raised about the parasite resistance to artemisinin-based combination therapies. Therefore, the present study aimed at analyzing the CQ-associated pfcrt 76T mutation in P. falciparum isolates from patients with uncomplicated falciparum malaria in Hodeidah, west of Yemen. The association of treatment-seeking behaviors and antimalarial drug use with the pfcrt 76T mutant allele was also studied. It was revealed that there is still a sustained high frequency of this molecular marker among parasite isolates associated with younger age, decreased parasite density and the presence of gametocytes in blood. Delay in seeking treatment and frequent use of antimalarials were the behaviors significantly associated with the presence of the pfcrt 76T mutant allele among patients reporting a history of malaria treatment. Copyright © 2013 Elsevier B.V. All rights reserved.
Warhurst David C
Full Text Available Abstract Background Parasite resistance to the anti-malarial drug chloroquine is common in eastern Sudan. Dynamic within-host changes in the relative abundance of both sensitive and resistant Plasmodium falciparum parasites were examined in a cohort of chloroquine-treated patients presenting with uncomplicated falciparum malaria, using a novel allele-specific quantitative approach. Methods Treatment outcomes were determined for 93 patients of all ages in a per protocol cohort using a modified 14-day WHO protocol. Parasite DNA samples at days 0, 1, 2, 3, 7 and 14 following treatment were analysed using real-time quantitative PCR methods that distinguished resistant and sensitive genotypes at amino acids 72 - 76 of the pfcrt locus. Results Chloroquine treatment was not efficacious, and of 93 assessable patients, only 10 individuals (10.7%; 95% C.I. 4.34 - 17.2% enjoyed an adequate clinical and parasitological response. Resistant parasites with the haplotype CVIET at codons 72-76 of the pfcrt locus were dominant in the starting population. Chloroquine sensitive parasites with the haplotype CVMNK were detected in 19 individuals prior to treatment (20.43%; 95% C.I. 5.14 - 18.5%. In these patients, CQ treatment rapidly selected CVIET parasites, and this haplotype overwhelmingly dominated the parasite population in each individual by day 2 after treatment. Conclusions Such rapid intra-host selection of particular genotypes after the introduction of drug will cause frequent misidentification of parasite genotypes present in the starting population. This will have a potentially serious confounding effect on clinical trials which employ PCR-corrected estimates of treatment failure, as resistant parasites below the detection threshold in the pre-treatment sample can be erroneously classified as "new" infections during follow-up, over-estimating drug efficacy.
Full Text Available Abstract Background Strains of Plasmodium falciparum genetically resistant to chloroquine (CQ due to the presence of pfcrt 76T appear to have been recently introduced to the island of Madagascar. The prevalence of such resistant genotypes is reported to be low (P. falciparum isolates on the island. Previously, minority variant chloroquine resistant parasites were described in Malawian patients using an isotopic heteroduplex tracking assay (HTA, which can detect pfcrt 76T-bearing P. falciparum minority variants in individual patients that were undetectable by conventional PCR. However, as this assay required a radiolabeled probe, it could not be used in many resource-limited settings. Methods This study describes a digoxigenin (DIG-labeled chemiluminescent heteroduplex tracking assay (DIG-HTA to detect pfcrt 76T-bearing minority variant P. falciparum. This assay was compared to restriction fragment length polymorphism (RFLP analysis and to the isotopic HTA for detection of genetically CQ-resistant parasites in clinical samples. Results Thirty one clinical P. falciparum isolates (15 primary isolates and 16 recurrent isolates from 17 Malagasy children treated with CQ for uncomplicated malaria were genotyped for the pfcrt K76T mutation. Two (11.7% of 17 patients harboured genetically CQ-resistant P. falciparum strains after therapy as detected by HTA. RFLP analysis failed to detect any pfcrt K76T-bearing isolates. Conclusion These findings indicate that genetically CQ-resistant P. falciparum are more common than previously thought in Madagascar even though the fitness of the minority variant pfcrt 76T parasites remains unclear. In addition, HTAs for malaria drug resistance alleles are promising tools for the surveillance of anti-malarial resistance. The use of a non-radioactive label allows for the use of HTAs in malaria endemic countries.
Full Text Available Abstract Background Since a large focus of human infection with Plasmodium knowlesi, a simian malaria parasite naturally found in long-tailed and pig tailed macaques, was reported in Sarawak, Malaysian Borneo, it was pertinent to study the situation in peninsular Malaysia. A study was thus initiated to screen human cases of Plasmodium malariae using molecular techniques, to determine the presence of P. knowlesi in non- human primates and to elucidate its vectors. Methods Nested polymerase chain reaction (PCR was used to identify all Plasmodium species present in the human blood samples sent to the Parasitology laboratory of Institute for Medical Research. At the same time, non-human primates were also screened for malaria parasites and nested PCR was carried out to determine the presence of P. knowlesi. Mosquitoes were collected from Pahang by human landing collection and monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites and nested PCR was carried out on positive glands. Sequencing of the csp genes were carried on P. knowlesi samples from humans, monkeys and mosquitoes, positive by PCR. Results and Discussion Plasmodium knowlesi was detected in 77 (69.37% of the 111 human samples, 10 (6.90% of the 145 monkey blood and in 2 (1.7% Anopheles cracens. Sequence of the csp gene clustered with other P. knowlesi isolates. Conclusion Human infection with Plasmodium knowlesi is occurring in most states of peninsular Malaysia. An. cracens is the main vector. Economic exploitation of the forest is perhaps bringing monkeys, mosquitoes and humans into increased contact. A single bite from a mosquito infected with P. knowlesi is sufficient to introduce the parasite to humans. Thus, this zoonotic transmission has