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Community prevalence of infection is a widely used, standardized metric for evaluating malaria endemicity. Conventional methods for measuring prevalence include light microscopy and rapid diagnostic tests (RDTs), but their detection thresholds are inadequate for diagnosing low-density infections. The significance of submicroscopic malaria infections is poorly understood in Madagascar, a country of heterogeneous malaria epidemiology. A cross-sectional community survey in the western foothills of Madagascar during the March 2014 transmission season found malaria infection to be predominantly submicroscopic and asymptomatic. Prevalence of Plasmodium infection diagnosed by microscopy, RDT, and molecular diagnosis was 2.4%, 4.1%, and 13.8%, respectively. This diagnostic discordance was greatest for Plasmodium vivax infection, which was 98.5% submicroscopic. Village location, insecticide-treated bednet ownership, and fever were significantly associated with infection outcomes, as was presence of another infected individual in the household. Duffy-negative individuals were diagnosed with P. vivax , but with reduced odds relative to Duffy-positive hosts. The observation of high proportions of submicroscopic infections calls for a wider assessment of the parasite reservoir in other regions of the island, particularly given the country's current focus on malaria elimination and the poorly documented distribution of the non- P. falciparum parasite species.

To date, 11 studies conducted in different countries to test the association between Plasmodium falciparum Na(+)/H(+) exchanger gene (pfnhe-1; PF13_0019) polymorphisms and in vitro susceptibility to quinine have generated conflicting data. In this context and to extend our knowledge of the genetic polymorphism of Pfnhe gene, we have sequenced the ms4760 locus from 595 isolates collected in the Comoros (N = 250; an area with a high prevalence of chloroquine and sulfadoxine-pyrimethamine resistance) and Madagascar (N = 345; a low drug-resistance area). Among them, 29 different alleles were observed, including 8 (27%) alleles not previously described. Isolates from the Comoros showed more repeats in block II (DNNND), which some studies have found to be positively associated with in vitro resistance to quinine, compared with isolates from Madagascar. Additional studies are required to better define the mechanisms underlying quinine resistance, which involve multiple gene interactions.

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.

We assessed the performance of two new commercially available rapid diagnostic tests (RDTs) for malaria (SD Bioline Malaria Ag Pf test and Ag Pf/Pan test) in 200 patients with uncomplicated malaria between August and October 2007 in Madagascar. Results of the two RDTs were compared with those obtained by microscopy and real-time polymerase chain reaction. The sensitivity and specificity for detection of Plasmodium falciparum were 93% and 98.9%, respectively, for the SD Bioline Malaria Ag Pf test and 92.9% and 98.9% for the SD Bioline Malaria Ag Pf/Pan test. The sensitivity of the SD Bioline Malaria Ag Pf/Pan test was much lower for detection of other species (63.6%). The sensitivity of the two new assays decreased to 77.3% at parasitemia levels < 100 parasites/microL for detection of P. falciparum.

The main purpose of this study was to assess the accuracy of various techniques available for diagnosis of malaria. Blood samples were collected from 313 patients with clinical suspicion of uncomplicated malaria in 2 primary health centers in Madagascar. The presence of Plasmodium parasites was assessed by conventional microscopy, 2 rapid diagnostic tests (one HRP2-based test, PALUTOP(+4), and one pLDH-based test, OptiMAL-IT), and real-time polymerase chain reaction (PCR), which is used as the "gold standard" method. The degree of agreement observed was very high for microscopy (0.99) and the HRP2-based test (0.93) and high for the pLDH-based test (0.82). Public-health implications are also discussed in this paper.

We report the results of clinical studies carried out at six sites in Madagascar, between January and October 2006. The aims were (i) to update our knowledge of the burden of Plasmodium malariae infection and (ii) to assess the therapeutic efficacy of chloroquine for uncomplicated quartan malaria. Our findings confirm that P. malariae is the third leading cause of malaria, accounting for 1.1% of all malarial infections. They also demonstrate that chloroquine-currently recommended for the home management of presumed malaria in children under the age of five years and commonly used by adults-remains highly effective in patients with uncomplicated P. malariae infection.

Field and laboratory studies were carried out in October and November 2005 to provide a comparative evaluation of the performance of three rapid malaria detection tests, two of which were recently introduced (the CareStart Malaria test and the SD Malaria Antigen Bioline test) and the well-known OptiMAL-IT test. Compared with microscopy, the sensitivity of the three tests to detect Plasmodium falciparum malaria was 97% for the CareStart Malaria test, 89.4% for the SD Malaria Antigen Bioline test, and 92.6% for the OptiMAL-IT test. The three tests were less sensitive in detecting non-P. falciparum infections, and the sensitivity decreased at levels of parasitemiaor=100 parasites/microL.