Atelier paludisme: an international malaria training course held in Madagascar

The Atelier Paludisme (Malaria Workshop) is an international training course organized by the Institut Pasteur de Madagascar, which has been held annually for the past five years. The course was designed for both young and experienced researchers, as well as for healthcare professionals, mostly from malaria-endemic countries. Its objective is to provide participants with a broad knowledge of all features of malaria, to improve their skills in project management, to break geographical isolation by using the Internet as a source of documentary information. This six-week course makes use of concepts of andragogy and problem-based learning, i.e. a relationship between participants and tutors, which promotes a process of exchange rather than the simple transmission of knowledge, where participants have to search actively for information. This approach to training, combined with the wide background and experience of those involved, creates positive dynamics and enables participants to acquire new skills, develop their critical and analytical abilities. This paper describes the course and the lessons learned from its evaluation

Plant-derived recombinant F1, V, and F1-V fusion antigens of Yersinia pestis activate human cells of the innate and adaptive immune system

Plague is still endemic in different regions of the world. Current vaccines raise concern for their side effects and limited protection, highlighting the need for an efficacious and rapidly producible vaccine. F1 and V antigens of Yersinia pestis, and F1-V fusion protein produced in Nicotiana benthamiana administered to guinea pigs resulted in immunity and protection against an aerosol challenge of virulent h pestis. We examined the effects of plant-derived F1, V, and F1-V on human cells of the innate immunity. F1, V, and F1-V proteins engaged TLR2 signalling and activated IL-6 and CXCL-8 production by monocytes, without affecting the expression of TNF-alpha, IL-12, IL-10, IL-1 beta, and CXCL10. Native F1 antigen and recombinant plant-derived F1 (rF1) and rF1-V all induced similar specific T-cell responses, as shown by their recognition by T-cells from subjects who recovered from E pestis infection. Native F1 and rF1 were equally well recognized by serum antibodies of Y. pestis-primed donors, whereas serological reactivity to rF1-V hybrid was lower, and that to rV was virtually absent. In conclusion, plant-derived F1, V, and F1-V antigens are weakly reactogenic for human monocytes and elicit cell-mediated and humoral responses similar to those raised by Y pestis infection

Longitudinal survey of malaria morbidity over 10 years in Saharevo (Madagascar): further lessons for strengthening malaria control

<p>Abstract</p> <p>Background</p> <p>Madagascar has been known for having bio-geo-ecological diversity which is reflected by a complex malaria epidemiology ranging from hyperendemic to malaria-free areas. Malaria-related attacks and infection are frequently recorded both in children and adults living in areas of low malaria transmission. To integrate this variability in the national malaria control policy, extensive epidemiological studies are required to up-date previous records and adjust strategies.</p> <p>Methods</p> <p>A longitudinal malaria survey was conducted from July 1996 to June 2005 among an average cohort of 214 villagers in Saharevo, located at 900 m above the sea. Saharevo is a typical eastern foothill site at the junction between a costal wet tropical area (equatorial malaria pattern) and a drier high-altitude area (low malaria transmission).</p> <p>Results</p> <p>Passive and active malaria detection revealed that malaria transmission in Saharevo follows an abrupt seasonal variation. Interestingly, malaria was confirmed in 45% (1,271/2,794) of malaria-presumed fevers seen at the health centre. All four <it>Plasmodia </it>that infect humans were also found: <it>Plasmodium falciparum</it>; <it>Plasmodium vivax</it>, <it>Plasmodium malariae </it>and <it>Plasmodium ovale</it>. Half of the malaria-presumed fevers could be confirmed over the season with the highest malaria transmission level, although less than a quarter in lower transmission time, highlighting the importance of diagnosis prior to treatment intake. <it>P. falciparum </it>malaria has been predominant (98%). The high prevalence of <it>P. falciparum </it>malaria affects more particularly under 10 years old children in both symptomatic and asymptomatic contexts. Children between two and four years of age experienced an average of 2.6 malaria attacks with <it>P. falciparum </it>per annum. Moreover, estimated incidence of <it>P. falciparum </it>malaria tends to show that half of the attacks (15 attacks) risk to occur during the first 10 years of life for a 60-year-old adult who would have experienced 32 malaria attacks.</p> <p>Conclusion</p> <p>The incidence of malaria decreased slightly with age but remained important among children and adults in Saharevo. These results support that a premunition against malaria is slowly acquired until adolescence. However, this claims for a weak premunition among villagers in Saharevo and by extension in the whole eastern foothill area of Madagascar. While the Malagasy government turns towards malaria elimination plans nowadays, choices and expectations to up-date and adapt malaria control strategies in the foothill areas are discussed in this paper.</p

New thiazolidine-2,4-dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity

Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened

Seroprevalence of malaria in inhabitants of the urban zone of Antananarivo, Madagascar

BACKGROUND: Antananarivo, the capital of Madagascar, is located at an altitude of over 1,200 m. The environment at this altitude is not particularly favourable to malaria transmission, but malaria nonetheless remains a major public health problem. The aim of this study was to evaluate exposure to malaria in the urban population of Antananarivo, by measuring the specific seroprevalence of Plasmodium falciparum. METHODS: Serological studies specific for P. falciparum were carried out with an indirect fluorescent antibody test (IFAT). In a representative population of Antananarivo, 1,059 healthy volunteers were interviewed and serum samples were taken. RESULTS: The seroprevalence of IgG+IgA+IgM was 56.1% and that of IgM was 5.9%. The major risk factor associated with a positive IgG+IgA+IgM IFAT was travel outside Antananarivo, whether in the central highlands or on the coast. The abundance of rice fields in certain urban districts was not associated with a higher seroprevalence. CONCLUSION: Malaria transmission levels are low in Antananarivo, but seroprevalence is high. Humans come into contact with the parasite primarily when travelling outside the city. Further studies are required to identify indigenous risk factors and intra-city variations more clearly

Assessment of the efficacy of antimalarial drugs recommended by the National Malaria Control Programme in Madagascar: Up-dated baseline data from randomized and multi-site clinical trials

<p>Abstract</p> <p>Background</p> <p>In order to improve the monitoring of the antimalarial drug resistance in Madagascar, a new national network based on eight sentinel sites was set up. In 2006/2007, a multi-site randomized clinical trial was designed to assess the therapeutic efficacy of chloroquine (CQ), sulphadoxine-pyrimethamine (SP), amodiaquine (AQ) and artesunate plus amodiaquine combination (ASAQ), the antimalarial therapies recommended by the National Malaria Control Programme (NMCP).</p> <p>Methods</p> <p>Children between six months and 15 years of age, with uncomplicated falciparum malaria, were enrolled. Primary endpoints were the day-14 and day-28 risks of parasitological failure, either unadjusted or adjusted by genotyping. Risks of clinical and parasitological treatment failure after adjustment by genotyping were estimated using Kaplan-Meier survival analysis. Secondary outcomes included fever clearance, parasite clearance, change in haemoglobin levels between Day 0 and the last day of follow-up, and the incidence of adverse events.</p> <p>Results</p> <p>A total of 1,347 of 1,434 patients (93.9%) completed treatment and follow-up to day 28. All treatment regimens, except for the chloroquine (CQ) treatment group, resulted in clinical cure rates above 97.6% by day-14 and 96.7% by day-28 (adjusted by genotyping). Parasite and fever clearance was more rapid with artesunate plus amodiaquine, but the extent of haematological recovery on day-28 did not differ significantly between the four groups. No severe side-effects were observed during the follow-up period.</p> <p>Conclusion</p> <p>These findings (i) constitute an up-dated baseline data on the efficacy of antimalarial drugs recommended by the NMCP, (ii) show that antimalarial drug resistance remains low in Madagascar, except for CQ, compared to the bordering countries in the Indian Ocean region such as the Comoros Archipelago and (iii) support the current policy of ASAQ as the first-line treatment in uncomplicated falciparum malaria.</p

Space-time clustering of childhood malaria at the household level: a dynamic cohort in a Mali village

BACKGROUND: Spatial and temporal heterogeneities in the risk of malaria have led the WHO to recommend fine-scale stratification of the epidemiological situation, making it possible to set up actions and clinical or basic researches targeting high-risk zones. Before initiating such studies it is necessary to define local patterns of malaria transmission and infection (in time and in space) in order to facilitate selection of the appropriate study population and the intervention allocation. The aim of this study was to identify, spatially and temporally, high-risk zones of malaria, at the household level (resolution of 1 to 3 m). METHODS: This study took place in a Malian village with hyperendemic seasonal transmission as part of Mali-Tulane Tropical Medicine Research Center (NIAID/NIH). The study design was a dynamic cohort (22 surveys, from June 1996 to June 2001) on about 1300 children (<12 years) distributed between 173 households localized by GPS. We used the computed parasitological data to analyzed levels of Plasmodium falciparum, P. malariae and P. ovale infection and P. falciparum gametocyte carriage by means of time series and Kulldorff's scan statistic for space-time cluster detection. RESULTS: The time series analysis determined that malaria parasitemia (primarily P. falciparum) was persistently present throughout the population with the expected seasonal variability pattern and a downward temporal trend. We identified six high-risk clusters of P. falciparum infection, some of which persisted despite an overall tendency towards a decrease in risk. The first high-risk cluster of P. falciparum infection (rate ratio = 14.161) was detected from September 1996 to October 1996, in the north of the village. CONCLUSION: This study showed that, although infection proportions tended to decrease, high-risk zones persisted in the village particularly near temporal backwaters. Analysis of this heterogeneity at the household scale by GIS methods lead to target preventive actions more accurately on the high-risk zones identified. This mapping of malaria risk makes it possible to orient control programs, treating the high-risk zones identified as a matter of priority, and to improve the planning of intervention trials or research studies on malaria

Hepatitis C Virus Infection May Lead to Slower Emergence of P. falciparum in Blood

International audienceBACKGROUND: Areas endemic for Plasmodium falciparum, hepatitis B virus (HBV) and hepatitis C virus (HCV) overlap in many parts of sub-Saharan Africa. HBV and HCV infections develop in the liver, where takes place the first development stage of P. falciparum before its further spread in blood. The complex mechanisms involved in the development of hepatitis may potentially influence the development of the liver stage of malaria parasites. Understanding the molecular mechanisms of these interactions could provide new pathophysiological insights for treatment strategies in Malaria. METHODOLOGY: We studied a cohort of 319 individuals living in a village where the three infections are prevalent. The patients were initially given a curative antimalarial treatment and were then monitored for the emergence of asexual P. falciparum forms in blood, fortnightly for one year, by microscopy and polymerase chain reaction. PRINCIPAL FINDINGS: At inclusion, 65 (20.4%) subjects had detectable malaria parasites in blood, 36 (11.3%) were HBV chronic carriers, and 61 (18.9%) were HCV chronic carriers. During follow-up, asexual P. falciparum forms were detected in the blood of 203 patients. The median time to P. falciparum emergence in blood was respectively 140 and 120 days in HBV- and HBV+ individuals, and 135 and 224 days in HCV- and HCV+ individuals. HCV carriage was associated with delayed emergence of asexual P. falciparum forms in blood relative to patients without HCV infection. CONCLUSIONS: This pilot study represents first tentative evidence of a potential epidemiological interaction between HBV, HCV and P. falciparum infections. Age is an important confounding factor in this setting however multivariate analysis points to an interaction between P. falciparum and HCV at the hepatic level with a slower emergence of P. falciparum in HCV chronic carriers. More in depth analysis are necessary to unravel the basis of hepatic interactions between these two pathogens, which could help in identifying new therapeutic approaches against malaria