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Babesia are intraerythrocytic, tick-transmitted, protozoan parasites that infect a broad range of wild and domesticated mammals including cattle, horses, dogs, and rodents. Human babesial infection is uncommon, mainly caused by B. microti in North America and B. divergens in Europe, with most infections occurring in asplenic people. Presentation is typically with non-specific ‘viral-type’ symptoms. Haemolytic anaemia is a characteristic feature and can be severe, particularly with B. divergens. Diagnosis is by discovering babesia organisms in Giemsa-stained blood smears, or detection of its DNA in blood by polymerase chain reaction. Aside from supportive care, treatment is usually with combinations of clindamycin and quinine or atovaquone and azithromycin. Mortality ranges from 5 to 40%. Prevention is by use of repellents, removing ticks from the skin, and avoidance of exposure in asplenic and immunocompromised individuals: there is no vaccine.

Avant 2006 au Senegal toute fievre sans diagnostic biologique etait consideree a priori comme un paludisme et traitee par la chloroquine. De 2004 a 2006, devant la progression de la resistance de Plasmodium falciparum au traitement par la chloroquine, le traitement par l’association amodiaquine/sulfadoxine-pyrimethamine a ete recommande. A partir de 2006, on a assiste au niveau national a l’introduction des tests de diagnostic rapide (TDR) et en 2007 a la recommandation du traitement par l’association artesunate-amodiaquine (ASAQ). Ceci a coincide avec une diminution de la prevalence des cas de paludisme et un changement de comportement pour la prise en charge des fievres. A Mlomp en Casamance, les examens microscopiques de sang (frottis et gouttes epaisses) etaient effectues systematiquement depuis 1995 chez les patients febriles presentant des signes cliniques evocateurs de paludisme et le traitement par ASAQ etait effectue a titre experimental. Entre 2000 et 2012, 70 892 patients ont consulte au dispensaire, dont 51,2 % pour une fievre. Parmi ces cas de fievre, 72,4 % etaient suspects de paludisme et 27,6 % etaient dus a des infections virales ou bacteriennes. Le nombre de cas de paludisme confirme a diminue progressivement de 1 365 en 2000 a 53 en 2012. Si l’on compare la periode 2000–2006 a 2007–2012 on constate que le nombre de cas de fievre a diminue de moitie, le nombre de cas de fievres identifiees a d’autres causes que le paludisme a double et le nombre de traitements antipaludiques a diminue de 86 %. L’amelioration de la prise en charge des fievres a Mlomp s’est traduite par une meilleure identification des causes et une diminution importante de traitements antipaludiques inappropries.

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.

Cryptosporidiosis is one of the most frequent causes of diarrhea in Haiti. Transmission in children less than five years-old, HIV-infected individuals, and people living in low socio-economic conditions is frequently due to consumption of water or food contaminated by Cryptosporidium oocysts. This study examined the circulation of Cryptosporidium oocysts in surface waters and in public water supplies in the district of Port-au-Prince. Data were gathered from December 2000 to June 2002 in 37 sites. In the district of Port-au-Prince, 24/37 samples of water collected (65%) were contaminated by Cryptosporidium oocysts and 10/11 (91%) of those collected in reservoirs used by people living in peripheral areas. The rate of contamination was 7/13 (54%) in water from public standpipes provided by the public company of water distribution. All surface water (4/4) collected was highly contaminated.

A survey conducted from May 2010 to October 2013 in five from ten departments of Haiti among 5,342 persons aged from 1 to 107 years showed a gametocytic rate = 3.2%. However, it varies greatly from one Department to another, ranging from 0.5% in Grande Anse Department to 5.9% in Southeast Department. Malaria is present in Haiti in heterogeneous coastal foci. Gametocytes occur at all ages, but two times most often in male under 20 years. Entomological studies in Haiti are needed to better characterize the relationships between man and the vector Anopheles albimanus, adapting the fight more effectively.

An epidemiologic (cross-sectional study) survey on 462 inhabitants in Corail, Haiti showed that 16.5% were infected with Mansonella ozzardi. This finding was determined from a single 20-μL sample of finger prick blood from each person. Among children, < 2% had a detectable microfilaremia. In persons > 15 years of age, the prevalence of infection for males and females was 23% and 21%, respectively. In general, the microfilaremias were low and 70% of positive persons had < 10 microfilariae per 20 μL of blood; only 5% had > 50 microfilariae. This study shows that persons living near mangrove marshes that are breeding sites for Culicoides furens and C. barbosai biting midges, which are recognized vectors of M. ozzardi in Haiti, are consequently more frequently infected than those living in downtown area of Corail or inland.

Resume Objectifs Le paludisme est responsable de nombreuses complications pendant la grossesse. Le but de l’etude est d’evaluer la traitement preventif intermittent a base de sulfadoxine–pyrimethamine (TPI–SP), traitement preventif intermittent a base de sulfadoxine (1500 mg) et pyrimethamine (75 mg), a Oussouye, Basse-Casamance, Senegal et son impact sur les grossesses et les poids des nouveau-nes. Patientes et methodes Nous avons conduit une etude retrospective des dossiers de parturientes suivies au centre de sante d’Oussouye de decembre 2007 a octobre 2008. Chaque dossier est examine afin de relever le nombre de consultations realisees, le nombre de doses de sulfadoxine–pyrimethamine (SP) recues, les complications de la grossesse et de l’accouchement, les poids placentaires et poids de naissance des enfants. Resultats Au cours de l’etude, 151 dossiers ont ete examines. Il en ressort que 85 % de la population etudiee a au moins consulte une fois pendant la grossesse et que 63,6 % a recu les deux doses de SP recommandees pendant la grossesse. Il est note un impact positif du TPI–SP sur le poids de naissance. En effet, le poids moyen de naissance observe chez les parturientes ayant recu deux doses de SP est de 3241 g et de 2896 g chez celles n’en ayant recu aucune (p value Conclusion La couverture prophylactique des femmes enceintes est assez bonne car environ deux tiers de la population etudiee ont recu les deux doses de SP. Cependant, il importe d’identifier les determinants de l’absenteisme aux consultations prenatales afin de proposer des strategies correctives pour une meilleure couverture par le TPI–SP.

RESUME Les conditions et les perspectives pour le traitement du paludisme ont change de facon radicale depuis quelques annees. Il y a plus d’argent disponible, de nouvelles actions operationnelles, de nouveaux acteurs et plus de medicaments en voie d’utilisation. Cependant, le nombre limite de produits innovants en developpement clinique souligne a quel point il est necessaire de decouvrir de nouvelles entites chimiques permettant un controle efficace et durable du paludisme. Le developpement de nouvelles molecules actives est un processus long et complexe ; il en est de meme pour le deploiement de nouveaux medicaments.

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 human enterocytic cell lines Caco-2, HT29, HCT8 and the Caco-2 clones TC7 and PF11 were studied for their ability to support Cryptosporidium parvum development. Following the addition in cultures of either oocysts or excysted sporozoites, immunofluorescent and transmission electron microscopy revealed the presence of all stages of the parasite life cycle by both procedures, and no difference in the ratio of infected cells was found among cell lines. More oocysts were seen in cell monolayers infected with oocysts than with sporozoites (p < 0.0001). The number of meronts observed was the same after either oocysts or sporozoites inoculation. Data suggest that the two methods yield a same cell infection rate.

Haiti and the Dominican Republic, which share the island of Hispaniola, are the last locations in the Caribbean where malaria still persists. Malaria is an important public health concern in Haiti with 17,094 reported cases in 2014. Further, on January 12, 2010, a record earthquake devastated densely populated areas in Haiti including many healthcare and laboratory facilities. Weakened infrastructure provided fertile reservoirs for uncontrolled transmission of infectious pathogens. This situation results in unique challenges for malaria epidemiology and elimination efforts. To help Haiti achieve its malaria elimination goals by year 2020, the Laboratoire National de Santé Publique and Henry Ford Health System, in close collaboration with the Direction d’Épidémiologie, de Laboratoire et de Recherches and the Programme National de Contrôle de la Malaria, hosted a scientific meeting on “Elimination Strategies for Malaria in Haiti” on January 29-30, 2015 at the National Laboratory in Port-au-Prince, Haiti. The meeting brought together laboratory personnel, researchers, clinicians, academics, public health professionals, and other stakeholders to discuss main stakes and perspectives on malaria elimination. Several themes and recommendations emerged during discussions at this meeting. First, more information and research on malaria transmission in Haiti are needed including information from active surveillance of cases and vectors. Second, many healthcare personnel need additional training and critical resources on how to properly identify malaria cases so as to improve accurate and timely case reporting. Third, it is necessary to continue studies genotyping strains of Plasmodium falciparum in different sites with active transmission to evaluate for drug resistance and impacts on health. Fourth, elimination strategies outlined in this report will continue to incorporate use of primaquine in addition to chloroquine and active surveillance of cases. Elimination of malaria in Haiti will require collaborative multidisciplinary approaches, sound strategic planning, and strong ownership of strategies by the Haiti Ministère de la Santé Publique et de la Population.

We have monitored the in vitro sensitivities of Plasmodium falciparum isolates predeployment and during the deployment of artesunate plus amodiaquine treatment in Mlomp, Casamance (southwestern Senegal) during 2000 to 2004. Parasites remained susceptible to both drugs. Chloroquine resistance levels were high but stable. Quinine continues to be effective.

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.

Malaria treatment policy has changed from presumptive treatment to targeted “test and treat” (T&T) with malaria rapid diagnostic tests (RDTs) and artemisinin combination therapy (ACT). This transition involves changing behavior among health providers, meaning delays between introduction and full implementation are recorded in almost every instance. We investigated factors affecting successful transition, and suggest approaches for accelerating uptake of T&T. Records from 2000 to 2011 from health clinics in Senegal where malaria is mesoendemic were examined (96,166 cases). The study period encompassed the implementation of national T&T policy in 2006. Analysis showed that adherence to test results is the first indicator of T&T adoption and is dependent on accumulation of experience with positive RDTs (odds ratio [OR]: 0.55 [P ≤ 0.001], 95% confidence interval [CI]: 0.53–0.58). Reliance on tests for malaria diagnosis (rather than presumptive diagnosis) followed after test adherence is achieved, and was also associated with increased experience with positive RDTs (OR: 0.60 [P ≤ 0.001], 95% CI: 0.58–0.62). Logistic models suggest that full adoption of T&T clinical practices can occur within 2 years, that monitoring these behavioral responses rather than RDT or ACT consumption will improve evaluation of T&T uptake, and that accelerating T&T uptake by focusing training on adherence to test results will reduce overdiagnosis and associated health and economic costs in mesoendemic regions.

The physico-chemical behavior of Cryptosporidium oocysts was investigated during their transfer through an alluvial formation from Les Cayes (Haiti) via batch tests. Five approximately 3 kg soil samples were collected and combined prior to batch tests from the alluvial formations. The experiments were carried out at soil pH by equilibrating different ranges of pure oocysts concentrations and soil samples with 3 mM CaCl 2 and 1 mM NaBr as electrolyte. We used the Debye–Huckel equation describing ion activity in a solution for a given ionic strength. The equilibrium adsorption mechanism is used to enumerate the oocysts in the soil. The results suggest that the oocysts behavior in porous media depends on soil characteristics such as soil pH, the nature of the mineral and organic constituents of the soil and the ionic strength and activities in solution. These results show that a total transfer in batch containing NaBr solutions against a partial one in batch containing CaCl 2 solutions depends on the oocysts media concentration. To confirm the oocysts number retained in soil, confocal microscopy was successfully used and the images demonstrate that the majority of oocysts were retained at the range of concentrations tested. The findings from this study demonstrated that the retention of C. Parvum in soils may be influenced by chemical conditions and soils characteristics, which are important for groundwater risk assessment.

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, r(2) = 0.94) in ASAQ recipients was 31 hours. CONCLUSION: Within the period covered by these studies, rapid Plasmodium falciparum clearance continues to be achieved in Sub-Saharan African patients treated with ACT, and in particular with ASAQ. The prediction formula for parasite clearance time could be a pragmatic tool for studies with binary outcomes and once-daily sampling, both for research and monitoring purposes.

It has been frequently stressed that improved methods are needed to monitor the fast spread of drug-resistant Plasmodium falciparum parasites in endemic areas. We recently developed a colourimetric microtest, double-site enzyme-linked lactate dehydrogenase enzyme immunodetection assay (DELI), to assess drug resistance in vitro. This method, which proved highly effective under laboratory conditions, was evaluated under field conditions in 2 African areas (in Senegal and Burkina Faso) in 1997 and 1998, respectively. The sensitivities of isolates from symptomatic (n = 50) and asymptomatic individuals (n = 26) infected with P. falciparum were assessed in parallel by the new DELI-microtest and the isotopic-microtest. IC50 values of the isolates determined for chloroquine, quinine, amodiaquine and mefloquine were well correlated (r = 0.79, P < 0.001). The proportions of sensitive and resistant isolates determined using the 2 methods were similar. The DELI-microtest proved to be faster to implement than the isotopic-microtest, easier to perform, and did not require sophisticated equipment. Moreover, a larger number of isolates can be tested since parasitaemias as low as 0.005% could be reliably measured with the DELI-microtest. These initial field studies thus support the value of the DELI-microtest for large-scale drug-sensitivity monitoring.

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.

Many countries in Africa are now confronted with the dilemma of shifting drug policies for uncomplicated falciparum malaria from chloroquine, which has become largely ineffective, to a new first-line drug and amodiaquine is one of the possible options. A multicentre, open-label randomized controlled trial of amodiaquine 30 mg/kg vs chloroquine 25 mg/kg over 3 days was performed in Senegal, Cameroon, Gabon, and Burkina Faso between 1996 and 1998 and patients were followed-up for 14 days. Sensitivity of isolates in vitro and whole blood levels of chloroquine and amodiaquine were also measured. The primary efficacy parameter was parasitological clearance on day 14 (parasitological success). The secondary efficacy parameter was absence of signs/symptoms of malaria on day 14 (clinical success). Among the 364 patients randomized and receiving the assigned treatment (chloroquine n = 185, amodiaquine n = 179), 137 and 139, respectively, reached the primary endpoint. Amodiaquine proved significantly more effective than chloroquine. The summary odds ratio (95% CI) was 7.79 (4.54-13.35) for parasitological success, and 6.3 (3.4-11.68) for clinical success. Sensitivity in vitro and chloroquine blood levels were good predictors of chloroquine failure. Amodiaquine remains effective for treating uncomplicated falciparum malaria in areas of West and Central Africa where chloroquine resistance is prevalent. However, measures should be taken to protect the lifespan of amodiaquine where the drug is introduced for use.

L'activite hemolytique d'un isolat de Monocercomonas spp. provenant de Tropidophis melanurus (serpent: Boidae) a ete etudiee. L'isolat a ete teste avec les hematies appartenant aux groupes sanguins humains A, B, AB et O et les hematies de six animaux adultes d'especes differentes (lapin, rat, poulet, cheval, boeuf et mouton). Les resultats ont montre que Monocercomonas spp. exerce une activite hemolytiques sur toutes les hematies testees.

Opinion and policy over the use of amodiaquine for treating malaria vary. Amodiaquine is more palatable than chloroquine and may be more effective but serious adverse events have been reported in travellers taking it as prophylaxis. It is not recommended as first-line treatment. In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria.This is a systematic review of published and unpublished randomised or pseudorandomised trials of amodiaquine. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events.40 trials met the inclusion criteria. Symptomatic patients were enrolled in 24 studies in comparisons of amodiaquine (n = 1071) with chloroquine (n = 1097). Amodiaquine was significantly more effective than chloroquine, with odds ratios and 99% confidence intervals (OR [99% CI]) of 4.29 (3.30-5.58) on day 7 and 6.00 (3.97-9.06) on day 14. Time to parasite clearance was significantly shorter with amodiaquine and fever clearance times were marginally faster. Eight studies compared amodiaquine with chloroquine in asymptomatic parasitaemia, with effects on parasitological outcomes similar to those for symptomatic malaria. At twelve sites, 692 amodiaquine and 679 sulfadoxine/pyrimethamine (S/P) recipients were enrolled. The two drugs did not differ significantly on day 7 (OR 0.74 [0.48-1.15]) but the odds ratios favoured S/P on day 14 (OR 0.51 [0.28-0.93]) and on day 28 (OR 0.30 [0.16-0.55]). The time to parasitological clearance was similar in the two groups; fever clearance times were significantly shorter with amodiaquine. Tolerability was assessed for both comparative and non-comparative trials. The rates of adverse events in controlled trials were 10.7%, 8.8%, and 14.3% with amodiaquine, chloroquine, and S/P, respectively. No life-threatening adverse events and no significant shifts in laboratory indices were reported.This systematic review of published and unpublished trials supports the use of amodiaquine in the treatment of uncomplicated malaria. However, there is partial cross-resistance between chloroquine and amodiaquine, and monitoring of the effectiveness of this drug and surveillance for evidence of toxicity must continue.Amodiaquine is more palatable than chloroquine and may be more effective in treating malaria, but serious adverse events have been reported among travellers taking it as prophylaxis. Amodiaquine is not recommended as first-line treatment. The authors report their findings from a systematic review of published and unpublished randomized or pseudorandomized trials on the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria. Observational reports were also systematically identified and reviewed to access evidence of serious adverse events. The review supports the use of amodiaquine in the treatment of uncomplicated malaria. There is, however, partial cross-resistance between chloroquine and amodiaquine. Monitoring the effectiveness of amodiaquine and surveillance for evidence of toxicity must continue.

Sera from subjects vaccinated with the Pasteur Merieux (PM) inactivated hepatitis A vaccine (AVAXIM) have been analysed in order: (1) to assess comparability of the results provided by a modified radio-immunoassay (mRIA) in the different laboratories involved in testings of sera during clinical trials and by enzyme-linked immunoabsorbent assay (ELISA) used during development of other inactivated hepatitis A vaccines; (2) to describe the IgM responses elicited by this vaccine compared with one control vaccine [HAVRIX, 720 ELISA antigens units; Smithkline Beecham (SB), Rixensart, Belgium]; (3) to provide comparative data between the PM vaccine and the SB vaccine on neutralizing activities of vaccine-induced antibodies. Vaccine-induced antibody titres evaluated by a mRIA in different laboratories correlated well and validated the comparability of the results obtained in various vaccine trials conducted by PM. Geometric mean titres (GMTs) expressed as milli-international units (mlU/ml) were higher with ELISA especially after the first dose, but seroconversion rates were similar and a good correlation was found between the two assays. IgM vaccine-induced antibodies were detectable in nearly all vaccinated subjects from week 2 after vaccination, with a peak titre between weeks 2 and 4 after the first dose. Comparison of GMTs by the Student Fisher t-test was statistically significant (P < 0.05) only at week 2 with higher titres in PM vaccinees. Neutralizing antibodies were detected after vaccination with the PM inactivated hepatitis A vaccine. The titres gradually increased between the second week after the first dose and the booster dose (week 24). A strong booster effect of the second dose on neutralizing titres was observed. Seroneutralizing titres induced at week 2 in subjects vaccinated with the PM inactivated hepatitis A vaccine were statistically significantly higher (P < 0.05) from those induced by the SB vaccine.

A drug-resistance survey was conducted in the French territory of Mayotte in the Comorian Islands in the Indian Ocean where malaria is endemic. A high prevalence of resistant Plasmodium falciparum parasites was observed, not only to chloroquine (88%) and pyrimethamine (99%), but more surprisingly to quinine (17%), mefloquine (9%), and amodiaquine (24%). This leaves few treatment alternatives other than artemisine-mefloquine combinations. However, despite notification to French Health authorities three years ago, inadequate treatment (chloroquine plus sulfadoxine-pyrimethamine) is still used in this locality. Thus, people still die of malaria in this remote territory of France.

Background Congo-Brazzaville adopted artemisinin-based combination therapy (ACT) in 2006. Artesunate-amodiaquine (AS + AQ) and artemether-lumefantrine are the first-line and second-line anti-malarial drugs to treat uncomplicated Plasmodium falciparum malaria, respectively. The baseline efficacy of AS + AQ was evaluated from February to August 2005 in patients living in Brazzaville, the capital city of the Republic of Congo. Methods One hundred and ninety-seven patients (96 ≤5 years old and 101 >5 years old, including adults) were recruited in a non-randomized study, treated under supervision with AS + AQ, and were followed up for 28 days in accordance with the 2003 World Health Organization protocol. Plasmodium falciparum recrudescent isolates from day 7 to day 28 were compared to pretreatment isolates by polymerase chain reaction (PCR) to distinguish between re-infection and recrudescence. Results The overall efficacy of AS + AQ after PCR correction on day 28 was 94.4%. An adequate clinical and parasitological response was observed in 94.3% and 94.4% of children aged ≤5 years old and those aged >5 years old (including adults), respectively. The main reported adverse events were dizziness, vomiting, diarrhoea, pruritus, headache, anorexia, and abdominal pain. Conclusion This study has shown the high efficacy of AS + AQ in Congolese patients of all ages with acute uncomplicated falciparum malaria and serves as the baseline efficacy and tolerance of this ACT in Brazzaville.

Background There are insufficient data on the safety in early pregnancy of the artemisinins, a new class of antimalarials. Assessment of drug teratogenicity requires large sample sizes for an adequate risk-benefit assessment. There is currently limited pharmacovigilance infrastructure in malaria-endemic countries. Monitoring drug safety in early pregnancy is especially challenging, as it requires early pregnancy detection to assess any potential increased risk of miscarriage, prospective follow-up to reduce recall and survival biases, and accurate data on gestational age assessment. Record linkage approaches for pregnancy pharmacovigilance using routinely generated health records could be a pragmatic and cost-effective approach for pharmacovigilance in early pregnancy, but has not been evaluated in resource-poor settings. Objective Our objective was to assess the feasibility of record linkage using routinely collected healthcare data as a pragmatic means of monitoring the safety in early pregnancy of artemisinin-based combination therapies (ACTs) in Senegal. Methods Data (2004-2008) from paper-based registers from outpatient clinics, antenatal care services (ANC) and the delivery unit from the St Joseph dispensary in Mlomp, south-western Senegal, were entered into databases. Record linkage based on a probabilistic matching approach was used to identify pregnancies exposed to ACTs in the first trimester of pregnancy. Two record linkage software packages (Link-Plus and FRIL) were compared and output data were reviewed independently by two investigators. Results Information on 685 pregnancies was extracted, 536 of which were from the geographic catchment area and eligible for record linkage; 94.6 % of them resulted in live births, 2.6 % in stillbirths and 2.8 % in miscarriages. Major congenital malformations were identified in 1.6 % of births. Seventy-three and 75 true matches between pregnancy outcome and the outpatient treatment registers were identified by two different record linkage software packages, respectively. Record linkage identified seven exposures to ACTs in the first trimester, all of which resulted in normal live-births. Conclusion Probabilistic record linkage is a potentially cost-effective method to assess the safety of antimalarials in early pregnancy in resource-constrained settings to assess increased risk of overall birth defects, and stillbirths in settings with good existing health records and well defined target populations.

A reversed-phase high-performance liquid chromatographic method for the determination of sinefungin, a new antiprotozoal drug, in rat plasma has been developed and validated. Sample preparation was performed at 4 degrees C by deproteinization with acetonitrile. Vidarabine was used as an internal standard. Both sinefungin and vidarabine were separated on a C18 column with a mobile phase of ammonium dihydrogenphosphate-acetonitrile (95:5, v/v) and detected by ultraviolet absorbance at 260 nm. Recoveries of sinefungin from plasma were 75 +/- 3.2% and 81 +/- 4.8% following dosage at concentrations of 10 micrograms/ml and 30 micrograms/ml, respectively. Using 250 microliters of rat plasma, the limit of quantitation was 1 microgram/ml sinefungin, and the assay was linear from 1 to 30 micrograms/ml. This method appears sensitive enough to be used in further pharmacokinetic studies of sinefungin in animal models.

In 29 patients experiencing their first P. falciparum malarial attack, blood levels of TcR gamma delta+ lymphocytes were studied from the onset of infection to up to 6-9 months later. Blood TcR gamma delta+ lymphocytes, revealed using the TcR delta 1 monoclonal antibody (MoAb), were increased both in absolute and relative numbers. Alterations lasted for up to 3-4 months following the attack. A Ti gamma A/BB3 reactive V gamma 9 subset was preferentially amplified. In vitro, TcR gamma delta+ lymphocytes from both malaria-sensitized and unprimed donors responded to P. falciparum schizont extract (PFSE). PFSE-stimulated polyclonal T cell lines consisted principally in TcR gamma delta+ cells with a Ti gamma A+/BB3+ phenotype. Several TcR gamma delta+ T cell clones obtained from patients recovering from acute malarial attack were maintained in the presence of PFSE and autologous irradiated PBL. They belong to the V gamma 9 subset. In long-term cultures, TcR gamma delta+ clones progressively lost their capacity to react to PFSE antigen while they were able to proliferate and to exert cytotoxic activity in response to autologous TcR alpha beta+, PFSE-specific T lymphocyte clones. This suggests that regulatory interactions occur between activated TcR gamma delta+ and TcR alpha beta+ cells generated by P. falciparum. Sequential variations in blood TcR gamma delta+ and TcR alpha beta+ lymphocyte levels after primary exposure to P. falciparum suggest that such regulatory interactions may occur in vivo.

Background Malaria is reportedly receding in different epidemiological settings, but local long-term surveys are limited. At Mlomp dispensary in south-western Senegal, an area of moderate malaria transmission, year-round, clinically-suspected malaria was treated with monotherapy as per WHO and national policy in the 1990s. Since 2000, there has been a staggered deployment of artesunate-amodiaquine after parasitological confirmation; this was adopted nationally in 2006. Methods Data were extracted from clinic registers for the period between January 1996 and December 2010, analysed and modelled. Results Over the 15-year study period, the risk of malaria decreased about 32-times (from 0.4 to 0.012 episodes person-year), while anti-malarial treatments decreased 13-times (from 0.9 to 0.07 treatments person-year) and consultations for fever decreased 3-times (from 1.8 to 0.6 visits person-year). This was paralleled by changes in the age profile of malaria patients so that the risk of malaria is now almost uniformly distributed throughout life, while in the past malaria used to concern more children below 16 years of age. Conclusions This study provides direct evidence of malaria risk receding between 1996-2010 and becoming equal throughout life where transmission used to be moderate. Infection rates are no longer enough to sustain immunity. Temporally, this coincides with deploying artemisinin combinations on parasitological confirmation, but other contributing causes are unclear.

Babesia are intraerythrocytic, tick-transmitted, protozoan parasites that infect a broad range of wild and domesticated mammals including cattle, horses, dogs, and rodents. Human babesial infection is uncommon, caused by B. microti in North America and B. divergens in Europe, with most infections occurring in asplenic people. Presentation is typically with nonspecific ‘viral-type’ symptoms. Haemolytic anaemia is a characteristic feature and can be severe, particularly with ...

To further document the phenomenon of Plasmodium falciparum resistance to mefloquine formerly described in Cameroon, complementary in vivo and in vitro studies were conducted. Two hundred six P. falciparum isolates were studied in vitro using an isotopic microassay with mefloquine solutions prepared daily. Using the cutoff limit of 30 nmol, 26 (20%) of 133 isolates from the northern part of the country were defined as being resistant to mefloquine. In contrast, only one of 73 isolates collected in the southern part of the country was resistant. In vivo 7-day assays were performed in the northern area in 57 asymptomatic P. falciparum carriers (age range 1-10 years) who were given a single 25 mg/kg dose of mefloquine (Lariam). Among 46 cases in which followup was possible, P. falciparum asexual parasites were cleared within five days in 38 cases, by days 6 and 7 in two cases, and remained detectable up to day 7 in six cases. Thus, these latter patients have a RII-RIII level of resistance by in vivo criteria. No resistance was found in 40 additional patients studied similarly in the southern region. These observations were made before any mefloquine drug pressure was exerted in the country, but results of cross-resistance and drug consumption studies support the hypothesis that in the northern region, where a close correlation (r = 0.67) was found between the response to quinine and mefloquine, the more frequent use of quinine may have induced a primary quinine resistance and a secondary mefloquine resistance (without chloroquine resistance).(ABSTRACT TRUNCATED AT 250 WORDS)

The metronidazole and albendazole susceptibility of 11 clinical isolates of Giardia duodenalis from France was determined using a neonatal mouse model and compared with the outcome in patients after standard metronidazole therapy (0.75 g/day for 5 days). All isolates found to be clinically resistant to metronidazole (4/11) exhibited an ID50 > 120 mg/kg in the mouse model. This therefore appears to be a suitable animal model in which to explore drug failures in human giardiasis.

Background The use of artemisinin derivative-based combination therapy (ACT) such as artesunate plus amodiaquine is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. Fixed-dose combinations are more adapted to patients than regimens involving multiple tablets and improve treatment compliance. A fixed-dose combination of artesunate + amodiaquine (ASAQ) was recently developed. To assess the efficacy and safety of this new combination and to define its optimum dosage regimen (once or twice daily) in the treatment of uncomplicated P. falciparum malaria, a multicentre clinical study was conducted. Methods A multicentre, randomized, controlled, investigator-blinded, parallel-group study was conducted in five African centers in Cameroon, Madagascar, Mali and Senegal from March to December 2006. Efficacy and safety of ASAQ were assessed compared to those of artemether + lumefantrine (AL). The WHO protocol with a 28-day follow-up for assessing the drug therapeutic efficacy was used. Patients suffering from uncomplicated P. falciparum malaria were randomized to receive ASAQ orally once daily (ASAQ1), ASAQ twice daily (ASAQ2) or AL twice daily (AL) for three days. The primary outcome was PCR-corrected parasitological cure rate and clinical response. Results Of 941 patients initially randomized and stratified into two age groups ( Conclusion The non-inferiority of ASAQ compared with AL was demonstrated. The fixed-dose combination artesunate + amodiaquine (ASAQ) is safe and efficacious even in young children under 5 years of age. Whilst administration on a twice-a-day basis does not improve the efficacy of ASAQ significantly, a once-a-day intake of this new combination clearly appears as an effective and safe therapy in the treatment of uncomplicated P. falciparum malaria both in adults and children. Implications of such findings are of primary importance in terms of public health especially in African countries. As most national policies plan to strengthen malaria control to reach the elimination of this disease, anti-malarial drugs such as the artesunate + amodiaquine fixed-dose ACT will play a pivotal role in this process. Trial registration The protocol was registered with the www.clinicaltrials.gov open clinical trial registry under the identifier number NCT00316329.

Background Artesunate and amodiaquine (AS&AQ) is at present the world's second most widely used artemisinin-based combination therapy (ACT). It was necessary to evaluate the efficacy of ACT, recently adopted by the World Health Organization (WHO) and deployed over 80 countries, in order to make an evidence-based drug policy. Methods An individual patient data (IPD) analysis was conducted on efficacy outcomes in 26 clinical studies in sub-Saharan Africa using the WHO protocol with similar primary and secondary endpoints. Results A total of 11,700 patients (75% under 5 years old), from 33 different sites in 16 countries were followed for 28 days. Loss to follow-up was 4.9% (575/11,700). AS&AQ was given to 5,897 patients. Of these, 82% (4,826/5,897) were included in randomized comparative trials with polymerase chain reaction (PCR) genotyping results and compared to 5,413 patients (half receiving an ACT). AS&AQ and other ACT comparators resulted in rapid clearance of fever and parasitaemia, superior to non-ACT. Using survival analysis on a modified intent-to-treat population, the Day 28 PCR-adjusted efficacy of AS&AQ was greater than 90% (the WHO cut-off) in 11/16 countries. In randomized comparative trials (n = 22), the crude efficacy of AS&AQ was 75.9% (95% CI 74.6–77.1) and the PCR-adjusted efficacy was 93.9% (95% CI 93.2–94.5). The risk (weighted by site) of failure PCR-adjusted of AS&AQ was significantly inferior to non-ACT, superior to dihydroartemisinin-piperaquine (DP, in one Ugandan site), and not different from AS+SP or AL (artemether-lumefantrine). The risk of gametocyte appearance and the carriage rate of AS&AQ was only greater in one Ugandan site compared to AL and DP, and lower compared to non-ACT (p = 0.001, for all comparisons). Anaemia recovery was not different than comparator groups, except in one site in Rwanda where the patients in the DP group had a slower recovery. Conclusion AS&AQ compares well to other treatments and meets the WHO efficacy criteria for use against falciparum malaria in many, but not all, the sub-Saharan African countries where it was studied. Efficacy varies between and within countries. An IPD analysis can inform general and local treatment policies. Ongoing monitoring evaluation is required.

Background Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP) is recommended for reducing the risk of malaria in pregnancy and its consequences on mothers and babies (IPTp-SP). Indicators of implementation and effects of IPTp-SP were collected in a rural clinic in Southern Senegal. Methods Women seen routinely at the antenatal clinic (ANC) of a rural dispensary during 2000–2007. Deployment of IPTp-SP started in January 2004. Inspection of antenatal and outpatient clinic registries of the corresponding period. Results Between 1st January 2000 and 30th April 2007, 1,781 women of all gravitidities and parities attended the ANC with 965 deliveries (606 and 398 respectively since 1st January 2004, when IPTp-SP was started.) 69% of women were seen ≥ 3 times; 95% received at least one dose and 70% two doses of SP (from 61% in 2004 to 86% in 2007). The first visit, first and second dose of SP occurred at a median week 20, 22 and 31. The probability of receiving two doses was > 80% with ≥ 3 antenatal visits and a first dose of SP by week 20. The prevalence of maternal malaria was low and similar pre- (0.7%) and during IPTp (0.8%). Effects on of low birth weight (LBW, < 2.5 kg) were non-statistically significant. The prevalence of LBW was 10.8% pre- and 7.7% during IPTp deployment (29% risk reduction, p = 0.12). Unfavourable pregnancy outcomes numbered 72 (7.5% of pregnancies with known outcome), including 30 abortions and 42 later deaths (late foetal deaths, stillbirth, peri-natal) of which 13 with one or more malformations (1.35% of all recorded deliveries). Conclusion The implementation of IPTp-SP was high. Early attendance to ANC favours completion of IPTp-SP. The record keeping system in place is amenable to data extraction and linkage. A model was developed that predicts optimal compliance to two SP doses, and could be tested in other settings. Maternal malaria was infrequent and unaffected by IPTp-SP. The risk of LBW was lower during IPT implementation but the difference was non-significant and could have other explanations.

Prospects for new and effective antimalarial treatments have improved significantly in the past few years. There are more funds, new operational paradigms and actors, and more products in the pipeline. However, the limited novelty of the products currently in clinical development means that more emphasis therefore needs to be placed on the discovery of novel chemical entities to achieve effective, sustainable control. The development and deployment of new products is both lengthy and complex.