Léon Paul Rabarijaona

Plasmodium falciparum Drug Resistance in Madagascar: Facing the Spread of Unusual pfdhfr and pfmdr-1 Haplotypes and the Decrease of Dihydroartemisinin Susceptibility

ABSTRACT The aim of this study was to provide the first comprehensive spatiotemporal picture of Plasmodium falciparum resistance in various geographic areas in Madagascar. Additional data about the antimalarial resistance in the neighboring islands of the Comoros archipelago were also collected. We assessed the prevalence of pfcrt, pfmdr-1, pfdhfr, and pfdhps mutations and the pfmdr-1 gene copy number in 1,596 P. falciparum isolates collected in 26 health centers (20 in Madagascar and 6 in the Comoros Islands) from 2006 to 2008. The in vitro responses to a panel of drugs by 373 of the parasite isolates were determined. The results showed (i) unusual profiles of chloroquine susceptibility in Madagascar, (ii) a rapid rise in the frequency of parasites with both the pfdhfr and the pfdhps mutations, (iii) the alarming emergence of the single pfdhfr 164L genotype, and (iv) the progressive loss of the most susceptible isolates to artemisinin derivatives. In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required.

Geographic differences in hepatosplenic complications of schistosomiasis mansoni and explanatory factors of morbidity.

In a study in three neighbouring villages of southern Madagascar, where Schistosoma mansoni is hyperendemic, ultrasound examination using the Niamey protocol showed marked differences in the burden of disease from one village to another. Hepatosplenic schistosomiasis was more frequent in the village with the highest geometric mean egg counts and the earliest onset of infections, demonstrating that the morbidity induced by S. mansoni may vary greatly within a given area. True representativeness of study populations, a keystone of epidemiological studies, is mandatory to obtain a clear picture of a wide area. Ultrasound examinations in a small number of villages, or even a single one, may be a questionable approach. Using logistic regression analysis, the explanatory variables found to be significantly associated with a risk of severe hepatosplenic disease in our study were sex, age, village of residence and S. mansoni egg counts. On the other hand, a concurrent infection with an intestinal helminth seems to reduce the risk of severe hepatosplenic disease. Further studies should assess the role and possible impact of intestinal helminths on S. mansoni associated‐morbidity.

Determining areas that require indoor insecticide spraying using Multi Criteria Evaluation, a decision-support tool for malaria vector control programmes in the Central Highlands of Madagascar

BackgroundThe highlands of Madagascar present an unstable transmission pattern of malaria. The population has no immunity, and the central highlands have been the sites of epidemics with particularly high fatality. The most recent epidemic occurred in the 1980s, and caused about 30,000 deaths. The fight against malaria epidemics in the highlands has been based on indoor insecticide spraying to control malaria vectors. Any preventive programme involving generalised cover in the highlands will require very substantial logistical support. We used multicriteria evaluation, by the method of weighted linear combination, as basis for improved targeting of actions by determining priority zones for intervention.ResultsImage analysis and field validation showed the accuracy of mapping rice fields to be between 82.3% and 100%, and the Kappa coefficient was 0.86 to 0.99.A significant positive correlation was observed between the abundance of the vector Anopheles funestus and temperature; the correlation coefficient was 0.599 (p < 0.001). A significant negative correlation was observed between vector abundance and human population density: the correlation coefficient was -0.551 (p < 0.003). Factor weights were determined by pair-wise comparison and the consistency ratio was 0.04. Risk maps of the six study zones were obtained according to a gradient of risk. Nine of thirteen results of alert confirmed by the Epidemiological Surveillance Post were in concordance with the risk map.ConclusionThis study is particularly valuable for the management of vector control programmes, and particularly the reduction of the vector population with a view to preventing disease. The risk map obtained can be used to identify priority zones for the management of resources, and also help avoid systematic and generalised spraying throughout the highlands: such spraying is particularly difficult and expensive.The accuracy of the mapping, both as concerns time and space, is dependent on the availability of data. Continuous monitoring of malaria transmission factors must be undertaken to detect any changes. A regular case notification allows risk map to be verified. These actions should therefore be implemented so that risk maps can be satisfactorily assessed.

Seroprevalence of hepatitis C and associated risk factors in urban areas of Antananarivo, Madagascar

BackgroundThe risk factors for the transmission of HCV vary substantially between countries and geographic regions. The overall prevalence in south and east Africa region has been estimated to be 1.6% but limited information about the epidemiology of HCV infection in Madagascar is availableMethodsA cross-sectional survey for hepatitis C antibodies was conducted in 2,169 subjects of the general population of Antananarivo to determine seroprevalence of hepatitis C and associated risk factors.ResultsThe overall seroprevalence was 1.2% (25/2,169). The prevalence did not differ significantly according to gender but it increased with age (Chi2 tendency test, p < 10-5). The variable history of hospitalization, previous therapeutic injections, dental treatment, intravenous drug use, and abnormal ALT and AST were statistically significantly related with the presence of HCV antibodies. No relationship with past history of blood transfusion was observed.ConclusionHCV prevalence in Madagascar seems to be similar to that in most other east African countries. Age appears to be an important risk factor. Iatrogenic causes of HCV transmission need to be further evaluated because all HCV cases had a history of receiving therapeutic injections and data suggested a cumulative effect in relation with therapeutic injections.

Use of pre-packaged chloroquine for the home management of presumed malaria in Malagasy children.

ObjectiveThe main objective of this study was to assess the quality of home malaria management with pre-packaged chloroquine in two areas in the Moramanga district of Madagascar. The knowledge, attitude and practices of care providers in terms of home treatment options were evaluated and compared. The availability of treatment options by studying retailers and community-based service providers was also investigated.MethodsA cross-sectional investigation in two communities, in the hamlets and villages located close to carers, retailers, community-based service providers and primary health centres was carried out.ResultsCarers in the two districts were equally well aware of the use of pre-packaged chloroquine. Their first response to the onset of fever was to treat children with this antimalarial drug at home. The dose administered and treatment compliance were entirely satisfactory (100%) with pre-packaged chloroquine and rarely satisfactory (1.6% to 4.5%) with non pre-packaged chloroquine. In cases of treatment failure, the carers took patients to health centres. Chloroquine was supplied principally by private pharmacies and travelling salesmen selling unpackaged chloroquine tablets. Non pre-packaged chloroquine was the most common drug used at health centres. The frequency of positive rapid malaria tests (P = 0.01) was significantly higher in children treated with non pre-packaged chloroquine (38%) than in children treated with pre-packaged chloroquine (1.3%).ConclusionHome malaria management should be improved in Madagascar. Efforts should focus on communication, the training of community-based service providers, access to pre-packaged drugs and the gradual withdrawal of pre-packaged chloroquine and its replacement by pre-packaged artemisinin-based combination therapies.

Low autochtonous urban malaria in Antananarivo (Madagascar)

BackgroundThe study of urban malaria is an area undergoing rapid expansion, after many years of neglect. The problem of over-diagnosis of malaria, especially in low transmission settings including urban areas, is also receiving deserved attention. The primary objective of the present study was to assess the frequency of malaria among febrile outpatients seen in private and public primary care facilities of Antananarivo. The second aim was to determine, among the diagnosed malaria cases, the contribution of autochthonous urban malaria.MethodsTwo cross-sectional surveys in 43 health centres in Antananarivo in February 2003 (rainy season) and in July 2003 (dry season) were conducted. Consenting clinically suspected malaria patients with fever or history of fever in the past 48 hours were included. Malaria rapid diagnostic tests and microscopy were used to diagnose malaria. Basic information was collected from patients to try to identify the origin of the infection: autochthonous or introduced.ResultsIn February, among 771 patients, 15 (1.9%) positive cases were detected. Three malaria parasites were implicated: Plasmodium. falciparum (n = 12), Plasmodium vivax (n = 2) and Plasmodium. ovale (n = 1). Only two cases, both P. falciparum, were likely to have been autochthonous (0.26%). In July, among 739 blood smears examined, 11 (1.5%) were positive: P. falciparum (n = 9) and P. vivax (n = 2). Three cases of P. falciparum malaria were considered to be of local origin (0.4%).ConclusionThis study demonstrates that malaria cases among febrile episodes are low in Antananarivo and autochthonous malaria cases exist but are rare.

Drug-resistant malaria parasites introduced into Madagascar from Comoros Islands.

To determine risk for drug-resistant malaria parasites entering Madagascar from Comoros Islands, we screened travelers. For the 141 Plasmodium falciparum isolates detected by real-time PCR, frequency of mutant alleles of genes associated with resistance to chloroquine and pyrimethamine was high. International-level antimalarial policy and a regional antimalarial forum are needed.

Mass vaccination campaigns to eradicate poliomyelitis in Madagascar: oral poliovirus vaccine increased immunity of children who missed routine programme

To assess the impact of mass vaccination campaigns using oral poliovirus vaccine (OPV) in Madagascar, serum neutralizing antibodies and geometrical mean titres (GMTs) to poliovirus were measured among 472 children aged up to 59 months, before and after the mass campaign, regardless of their previous history of routine vaccination. In this study, overall coverage with three routine and two mass campaign OPV doses was 69.9 and 93.4%, respectively. Seroprevalences to all poliovirus types were significantly higher after the mass campaign among the children who were not vaccinated through routine programme: 67.5% vs. 90.2% (P < 0.001) for type 1; 66.7% vs. 95.1% (P < 0.001) for type 2; and 55.3% vs. 82.9% (P < 0.001) for type 3. Geometrical mean titres to all poliovirus types also significantly increased after the mass campaign among the same study group: 34.5 vs. 238.9 (P < 0.001) for type 1; 35.1 vs. 402.6 (P < 0.001) for type 2; and 13.3 vs. 92.6 (P < 0.001) for type 3. Post‐mass campaign seroprevalences and GMTs for poliovirus, especially types 1 and 3, among children who received up to two routine and two mass campaign OPV doses were significantly higher than pre‐mass campaign seroprevalences among children who received three routine OPV doses. Reasons for lack of adherence to the vaccination programme and the mass campaign are discussed. The findings strongly support the WHO strategy of conducting mass campaign in all endemic countries. However, as the mass campaign strategy now has been discontinued, it is crucial to increase the routine coverage and to improve acute flaccid paralysis surveillance in order to fulfil the goal of poliomyelitis eradication.

Seroepidemiology of human plague in the Madagascar highlands.

Summary We conducted a seroepidemiological survey of human plague in the general population using random sampling in the area of Ambositra, the main focus of plague in the central highlands of Madagascar (520 confirmed and presumptive cases notified during the past 10 years). Sera were tested using an ELISA IgG F1 assay. Considering the internal validity of the assay and the sampling method, the overall corrected prevalence of F1 antibodies was 0.6% (95% CI: 0.2%‐1.8%). Being nearly 0 up to the age of 40, the corrected prevalence increased markedly after 45 years to 6.2%. Six of 20 individuals who declared to have been treated for clinical suspicion of bubonic plague in the past had F1 antibodies. The seroprevalence did not differ according to gender except in individuals > 60, where antibodies were significantly more frequent in males. This study suggests that the number of clinically suspected cases of plague provided by the surveillance network was plausible, despite some true cases being missed and a significant number of false positives. We also confirm that Yersinia pestis infections may occur without marked clinical manifestations and patients may recover without treatment, in accordance with old observations of pestis minor.