Management of uncomplicated malaria in febrile under five-year-old children by community health workers in Madagascar: reliability of malaria rapid diagnostic tests.

BACKGROUND: Early diagnosis, as well as prompt and effective treatment of uncomplicated malaria, are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria, reduce mortality and limit malaria transmission. The purpose of this study was to assess the performance of the malaria rapid diagnostic tests (RDTs) used by community health workers (CHWs) by comparing RDT results with two reference methods (microscopy and Polymerase Chain Reaction, PCR). METHODS: Eight CHWs in two districts, each with a different level of endemic malaria transmission, were trained to use RDTs in the management of febrile children under five years of age. RDTs were performed by CHWs in all febrile children who consulted for fever. In parallel, retrospective parasitological diagnoses were made by microscopy and PCR. The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs. The stability of the RDTs stored by CHWs was also evaluated. RESULTS: Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010, 89.5% were found to be positive for malaria parasites by PCR, 51.6% were positive by microscopy and 55.8% were positive by RDT. The performance accuracy of the RDTs used by CHWs in terms of sensitivity, specificity, positive and negative predictive values was greater than 85%. Concordance between microscopy and RDT, estimated by the Kappa value was 0.83 (95% CI: 0.75-0.91). RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/µl. CONCLUSION: Introduction of easy-to-use diagnostic tools, such as RDTs, at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs.

Analysis of circulating populations of Plasmodium falciparum in mild and severe malaria in two different epidemiological patterns in Madagascar.

OBJECTIVE: To investigate whether the severity of Plasmodium falciparum attack in endemic areas was associated with the multiplicity of infection (MOI) and/or with a particular genotype(s). METHOD: In two areas of different malaria transmission pattern in Madagascar (Sainte-Marie - mesoendemic and Tsiroanomandidy - hypoendemic) the number and the proportions of msp-2 genotypes within isolates were determined for each patient using a capillary electrophoresis genotyping method. DNA sequencing was performed to identify the msp-2 allelic family of dominant clones. RESULTS: Eighty six uncomplicated and 33 severe cases were included in Sainte-Marie and 48 uncomplicated and 69 severe cases were included in Tsiroanomandidy. We found no association between the MOI and severity of malaria as the same mean number of msp-2 genotypes was found in isolates from uncomplicated and from severe malaria cases (3.72 and 3.73, respectively, P>0.05). The study of the association of dominant clones with clinical status showed no particular genotype or allelic family associated with malaria severity. CONCLUSIONS: Severity of malaria was not associated with higher MOI in our study. Severity did not appear restricted to some particular genotypes either. On the contrary, severe malaria appeared to be caused by very common genotypes in the studied areas. More comprehensive explorations including immunity and genetic factors of the host are needed to acquire new information about this complex condition.

[Therapeutic efficacy of amodiaquine against uncomplicated malaria in Madagascar]. / Efficacité thérapeutique de l'amodiaquine dans le traitement du paludisme à Madagascar.

We report the results of a preliminary study carried out in 2004 to assess the therapeutic efficacy of amodiaquine in patients aged 5 years or older in Sainte Marie and Saharevo, in eastern Madagascar. Consenting patients with uncomplicated Plasmodium falciparum malaria were enrolled and followed up for 14 days: 46 were treated with chloroquine (25 mg/kg for 3 days) and 25 with amodiaquine (30 mg/kg for 3 days). No early treatment failure was observed with chloroquine but the overall late treatment failure rate was 17.4% (4.4% late clinical failures and 13% late parasitological failures). Amodiaquine was not associated with any cases of treatment failure through day 14. These preliminary results indicate that compared with chloroquine, amodiaquine is significantly more effective in treating uncomplicated malaria in our study sites. Amodiaquine is therefore recommended in combination with other antimalarial drugs. To generate useful data for decisions about drug use, further studies based on the WHO protocol should assess the clinical efficacy and also the safety of amodiaquine-containing antimalarial drugs in different regions in Madagascar, especially among children under 5 years.

Compliance, safety, and effectiveness of fixed-dose artesunate-amodiaquine for presumptive treatment of non-severe malaria in the context of home management of malaria in Madagascar.

Home management of malaria is recommended for prompt, effective antimalarial treatment in children less than five years of age. Compliance, safety, and effectiveness of the new fixed-dose artesunate-amodiaquine regimen used to treat suspected malaria were assessed in febrile children enrolled in a 24-month cohort study in two settings in Madagascar. Children with fever were asked to visit community health workers. Presumptive antimalarial treatment was given and further visits were scheduled for follow-up. The primary endpoint was the risk of clinical/parasitologic treatment failure. Secondary outcomes included fever/parasite clearance, change in hemoglobin levels, and frequency of adverse events. The global clinical cure rate was 98.4% by day 28 and 97.9% by day 42. Reported compliance was 83.4%. No severe adverse effects were observed. This study provides comprehensive data concerning the clinical cure rate obtained with artesunate-amodiaquine and evidence supporting the scaling up of home management of malaria.