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Le paludisme est considere comme un probleme de sante publique majeur en Haiti. Cependant l’impact reel de cette endemie sur la sante y est mal connu. L’objectif de cette etude est de verifier l’importance du paludisme comme cause de consultation a l’hopital et le taux de portage de gametocytes dans la population dans une commune du departement de la Grande Anse ou la prevalence du paludisme est consideree la plus forte d’Haiti. L’analyse des statistiques hospitalieres de Corail (Grande Anse) montre que seulement 17,4 % des consultations pour fievre sont dues au paludisme confirme a l’examen microscopique. La fraction de la population la plus touchee est celle des adultes âges de 15 a 39 ans (55 % des cas). Les enfants âges de moins de 5 ans ne representent que 11 % des cas. Une enquete communautaire a montre la rarete du portage de gametocytes dans la population (0,9 %). En Haiti, les caracteristiques epidemiologiques du paludisme doivent etre mieux precisees par des etudes de terrain documentees en vue d’adapter la strategie de lutte pour une plus grande efficacite.

Since several years, in the area of Kabrousse in Casamance (Senegal), a neurotoxic syndrome has caused more than 50 human deaths. Field studies showed that epidemic could be due to consumption of leave decoction of Cnestis ferruginea, a tropical plant belonging to the Connaraceae family. An ethnobotanical study has been conducted in order to investigate the traditional uses of C. ferruginea, and describe the circumstances and the symptoms of this plant poisoning. As a first experimental approach, the leave decoction was tested for its ability to induce cytotoxic effects using the XTT method. A phytochemical approach revealed the presence of methionine sulfoximine (MSX), a neurotoxic amino acid, in the plant extract by gas chromatography-mass spectrometry (GC-MS). The description of this poisoning, the cytotoxic activity of the decoction and the occurence of MSX in leaves of C. ferruginea constituted the first etiological data on this poisoning.

The authors compared the viability and infectivity of Cryptosporidium parvum oocysts in chlorinated tap water at various storage durations (i.e., 2 wk, 4 wk, 6 wk, or 8 wk) and at 2 cool temperatures (i.e., 10 degrees C and 4 degrees C), using in vitro (excystation) and in vivo (suckling mouse) methods. After 8 wk, mean oocyst excystation decreased to 33.4% and 26.7% at 10 degrees C and 4 degrees C, respectively. Suckling mice infectivity was higher after storage at 10 degrees C than after storage at 4 degrees C. These data suggest that Cryptosporidium parvum oocysts can survive and remain infectious for 8 wk in cool chlorinated tap water.

Background Artesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria. Methods Individual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites. Results Forty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P

Unless new strategies are deployed to combat malaria, the already enormous health and economic burden related to the disease in tropical countries is bound to worsen. The main obstacle to malaria control is the emergence of drug resistant strains of Plasmodium falciparum. As for HIV/AIDS and tuberculosis, the use of combinations of antimalarial drugs reduces the risk of selecting for resistant mutants of the plasmodial parasites. In large field trials, the combination of an artemisinin derivative and a partner drug with an unrelated mode of action (in this case mefloquine), has shown a remarkable double effect: preventing the emergence and spread of drug resistance, and interrupting the transmission of P. falciparum. This has opened the way for a new approach to the deployment of antimalarial drugs. Coupled with early detection and confirmed diagnosis, this strategy represents the only way forward in the chemotherapy of malaria. Massive economic assistance will be needed to detect and treat adequately the estimated 500 million cases of malaria per year, but without radical action there is no prospect of 'Rolling Back' malaria.

The effects of nitazoxanide and its metabolites, tizoxanide and tizoxanide glucuronide, on the development of the asexual and sexual stages of Cryptosporidium parvum in differentiated human enterocytic HCT-8 cells were evaluated in a quantitative alkaline phosphatase immunoassay. Nitazoxanide, tizoxanide and tizoxanide glucuronide were inhibitory for up to 46 h when added after sporozoite invasion (MIC 50 1.2, 22.6 and 2.2 mg/L, respectively). Tizoxanide had only limited activity, but nitazoxanide and tizoxanide glucuronide strongly inhibited asexual and sexual stages, respectively.

Background There are no data on the long term use of an artemisinin combination treatment in moderate or high transmission areas of Africa. Methods and findings Artesunate plus amodiaquine (AS+AQ) was used to treat slide-proven Plasmodium falciparum-infected patients of all ages in the Oussouye district, Casamance, Senegal, over a period of six years (2000 to 2005). Efficacy, by Kaplan Meier survival analysis (n = 966), and safety (adverse event rates, n = 752) were determined over 28 days. A weight-based dosing regimen was used for the loose tablets during 2000–2003 (n = 731) and a commercially available co-blister was used during 2004–2005 (n = 235). Annual crude (non PCR corrected) rates remained stable over the study period [range 88.5–96.7%; overall 94.6 (95% CI 92.9–95.9)]. Nine co-blister treated patients (0.9%) withdrew because of drug-related adverse events; seven had gastrointestinal complaints of whom two were hospitalized for vomiting. By Day 28, the mean total bilirubin (n = 72), AST (n = 94) and ALT (n = 95) values decreased. Three patients had Day 28 AST/ALT values > 40 < 200 IU/L. Changes in white cell counts were unremarkable (n = 87). Conclusion AS+AQ in combination was highly efficacious and well-tolerated in this area and justifies the decision to use it as first line treatment. Long-term monitoring of safety and efficacy should continue.

Data from experimental and human cryptosporidiosis have established a major role of specific immunity in the control of Cryptosporidium parvum infection. In this work, alterations in spleen and Peyer's patch (Pp) lymphocytes were investigated in the course of a spontaneously resolutive gut cryptosporidiosis in four-day-old suckling NMRI mice infected with either 4 x 10(5) or 30 viable oocysts. Oocysts from entire small intestines, and spleen and Pp lymphocytes were examined using flow cytometry from day 7 to day 27 post-infection. Compared to uninfected animals, a 3-5 fold increase in the numbers of spleen TCR alphabeta+, CD4+, CD8+, TCR gammadelta+ and CD45R/B220+ lymphocytes was observed on day 17 post-infection in heavily infected animals. In Pp, more than ten-fold increases were observed, except for TCR gammadelta+ lymphocytes. At termination of infection, i.e. on days 21-23 after ingestion of 4 x 105 oocysts, T and B lymphocytes decreased rapidly in both organs, and remained lower than in uninfected animals on days 19-23 post-infection. In mice infected with 30 oocysts, similar alterations were observed in Pp, but not in spleen. Data suggest that in normally developing mice, clearance of gut C. parvum infection is associated with an initial increase in systemic and local lymphocyte numbers, followed by their decrease to below control levels during the recovery phase.

Cryptosporidium parvum causes life-threatening diarrhea in immunocompromised patients, especially those with AIDS. The efficiency of currently proposed anticryptosporidial therapies is limited or doubtful. In this report, molecular candidates for curative or preventive activity were investigated in an immunocompromised rat model that mimics severe human cryptosporidiosis. No significant anticryptosporidial activity was observed when using sulfadoxine-pyrimethamine, quinacrine, trimethoprim-sulfamethoxazole, bleomycin, elliptinium, daunorubicin, pentamidine, alpha-difluoro-methylornithine, diclazuril or N-methylglucamine. Vitamin A appeared to reduce oocyst shedding. Active agents included sinefungin (2-10 mg/kg/24 h), lasalocid A (2-10 mg/kg/24 h), metronidazole (25-50 mg/kg/24 h), and sulfadimethoxine (10-100 mg/kg/24 h). Sinefungin (10 mg/kg/24 h) and lasalocid A (10 mg/kg/24 h) displayed the highest anticryptosporidial activity.

Background The emergence and spread of Plasmodium falciparum and Plasmodium vivax resistance to available anti-malarial drugs represents a major drawback in the control of malaria and its associated morbidity and mortality. The aim of this study was to evaluate the chemoresistance profile of P. falciparum and P. vivax to commonly used anti-plasmodial drugs in a malaria-endemic area in the Brazilian Amazon. Methods The study was carried out in Manaus (Amazonas state), in the Brazilian Amazon. A total of 88 P. falciparum and 178 P. vivax isolates was collected from 2004 to 2007. The sensitivity of P. falciparum isolates was determined to chloroquine, quinine, mefloquine and artesunate and the sensitivity of P. vivax isolates was determined to chloroquine and mefloquine, by using the colorimetric DELI test. Results As expected, a high prevalence of P. falciparum isolates resistant to chloroquine (78.1%) was observed. The prevalence of isolates with profile of resistance or decreased sensitivity for quinine, mefloquine and artesunate was 12.7, 21.2 and 11.7%, respectively. In the case of P. vivax, the prevalence of isolates with profile of resistance for chloroquine and mefloquine was 9.8 and 28%, respectively. No differences in the frequencies of isolates with profile of resistance or geometric mean IC50s were seen when comparing the data obtained in 2004, 2005, 2006 and 2007, for all tested anti-malarials. Conclusions The great majority of P. falciparum isolates in the Brazilian malaria-endemic area remain resistant to chloroquine, and the decreased sensitivity to quinine, mefloquine and artesunate observed in 10–20% of the isolates must be taken with concern, especially for artesunate. Plasmodium vivax isolates also showed a significant proportion of isolates with decreased sensitivity to chloroquine (first-line drug) and mainly to mefloquine. The data presented here also confirm the usefulness of the DELI test to generate results able to impact on public health policies.

Background Knowing the safety profile of anti-malarial treatments in routine use is essential; millions of patients receive now artemisinin combination therapy (ACT) annually, but the return on information through current systems is as yet inadequate. Cohort event monitoring (CEM) is a WHO (World Health Organization)-recommended practice; testing its performance and feasibility in routine practice in malaria-endemic is important. Methods A nine-year CEM-based study of the safety of artesunate-amodiaquine (ASAQ) at five peripheral health facilities in a rural district of South-western Senegal. Staff (nurses, health workers) were trained to collect actively and systematically information on the patient, treatment and events on a purposely designed questionnaire. The occurrence and severity of events was collected before, during and after treatment up to 28 days in order to generate information on all adverse events (AEs) as well as treatment-emerging signs/symptoms (TESS). Laboratory tests (haematology, liver and renal) was planned for at least 10% of cases. Results During 2001–2009, 3,708 parasitologically-confirmed malaria cases (mean age = 16.0 ± 12.7 years) were enrolled (26% and 52% of all and parasitologically-confirmed ASAQ treatments, respectively). Treatment was supervised in 96% of cases. Products changed over time: 49% were a loose combination of individually-packaged products (available 2001–03), 42% co-blistered products (2004–09) and 9% a fixed-dose co-formulation (2006–09); dosing was age-based for 42%, weight-based for 58%. AS and AQ were correctly dosed in 97% and 82% of cases with the loose and 93% and 86% with the fixed combination, but only 50% and 42% with the co-blistered product. Thirty-three per cent (33%) of patients had at least one sign/symptom pre-treatment, 12% had at least one AE and 9% a TESS (total events 3,914, 1,144 and 693, respectively). AEs overestimated TESS by 1.2-2 fold (average 1.7). Changes in laboratory value were insignificant. Over-dosing more than doubled the risk of TESS, though statistical significance was reached only during 2003–2007. The incidence of serious events (including death) was five per thousand. Conclusions The study was successful in quantifying and characterizing known reactions and has benchmarking value. Health staff performance varied. Investments in training, motivating and providing a quality control system would be needed. The study proved that a CEM-based system is feasible in this setting but more research is needed to assess whether it is sustainable and what conditions would make it cost-effective, including the amount and quality of data generated, and the use thereof for decision-making.