Haemoglobin C (HbC; beta6Glu --> Lys) is common in malarious areas of West Africa, especially in Burkina Faso. Conclusive evidence exists on the protective role against severe malaria of haemoglobin S (HbS; beta6Glu --> Val) heterozygosity, whereas conflicting results for the HbC trait have been reported and no epidemiological data exist on the possible role of the HbCC genotype. In vitro studies suggested that HbCC erythrocytes fail to support the growth of P. falciparum but HbC homozygotes with high P. falciparum parasitaemias have been observed. Here we show, in a large case-control study performed in Burkina Faso on 4,348 Mossi subjects, that HbC is associated with a 29% reduction in risk of clinical malaria in HbAC heterozygotes (P = 0.0008) and of 93% in HbCC homozygotes (P = 0.0011). These findings, together with the limited pathology of HbAC and HbCC compared to the severely disadvantaged HbSS and HbSC genotypes and the low betaS gene frequency in the geographic epicentre of betaC, support the hypothesis that, in the long term and in the absence of malaria control, HbC would replace HbS in central West Africa.

SummaryIn rural, malaria-endemic Burkina Faso, we evaluated the impact of the use of pre-packaged antimalarial drugs (PPAM), by mothers in the home, on the progression of disease in children from uncomplicated fever to severe malaria. In each village of one province, a core group of opinion leaders (mainly older mothers) was trained in the management of uncomplicated malaria, including the administration of PPAM. Full courses of antimalarial (chloroquine) and antipyretic (aspirin) drugs were packaged in agespecific bags and made widely available through community health workers who were supplied through the existing drug distribution system. Drugs were sold under a cost-recovery scheme. Local schoolteachers conducted surveys in a random sample of 32 villages at the end of the high transmission seasons in 1998 and 1999. Disease history and the treatment received were investigated for all children under the age of 6 years having suffered from a fever episode in the previous 4 weeks. ÔUncomplicated malariaÕ was defined as every episode of fever and Ôsevere malariaÕ as every episode of fever followed by convulsions or loss of consciousness. During the study period, 56% [95% confidence interval (CI) 50-62%] of 3202 fever episodes in children under 6 years of age were treated promptly by mothers with the pre-packaged drugs made available by the study. A total of 59% of children receiving PPAM were reported to have received the drugs over the prescribed 3-day period, while 52% received the correct age-specific dose. PPAM use was similar among literate (61%) and non-literate mothers (55%) (P ¼ 0.08). The overall reported risk of developing severe malaria was 8%. This risk was lower in children treated with PPAM (5%) than in children not treated with PPAM (11%) (risk ratio ¼ 0.47; 95% CI 0.37, 0.60; P < 0.0001). This estimate of the impact of PPAM was largely unchanged when account was taken of potential confounding by age, sex, maternal literacy status, year or village. Our findings support the view that, after appropriate training and with adequately packaged drugs made available, mothers can recognize and treat promptly and correctly malarial episodes in their children and, by doing so, reduce the incidence of severe disease.

A randomized trial reported by Diadier Diallo and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes using insecticide-treated bednets provides substantial protection from malaria.

There is longstanding evidence that immunoglobulin G (IgG) has a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabè children 6 months to 15 years old were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates: apical membrane antigen 1 (AMA1), merozoite surface protein 1-19 (MSP1-19), MSP3, and glutamate-rich protein (GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year of risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (incidence rate ratio associated with a doubling of total IgG, 0.79; 95% confidence interval, 0.66 to 0.94; P ‫؍‬ 0.009.); there was a borderline statistically significant association between the level of total IgG to MSP3 and malaria incidence and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied, only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in humans, these blood-stage antigens, AMA1 and GLURP, offer good prospects for malaria vaccine development.In sub-Saharan Africa, the clinical manifestations of malaria are caused by asexual blood stages of Plasmodium falciparum, and antigens on asexual parasite stages in the bloodstream are critical in the development of protective immunity to the disease. After repeated exposure, nonsterile immunity to malaria can be acquired by people living in areas of endemicity. Strong evidence exists, from the passive transfer of antibodies between immune and nonimmune individuals, that this immunity can be antibody mediated (18,29,40). The most efficient in vivo model for this antibody-mediated parasite control in areas where the disease is endemic requires the participation of monocytes and has been called antibody-dependent cellular inhibition (ADCI) (24,26). This assay is assumed to mimic the in vivo cooperation between monocytes and cytophilic parasite-specific antibodies and is considered a surrogate marker of immunity against P. falciparum blood stages (21). BouharounTayoun and Druilhe observed profound differences in the distribution of immunoglobulin (Ig) subclasses between clinically protected and susceptible individuals, with cytophilic subclasses (immunoglobulin G1 [IgG1] and IgG3) being dominant in protected individuals (10). In different epidemiological settings, similar findings have been made, underscoring the importance of cytophilic antibodies against blood-stage antigens in ...

Background: The clinical presentation of malaria, considered as the result of a complex interaction between parasite and human genetics, is described to be different between rural and urban areas. The analysis of the Plasmodium falciparum genetic diversity in children with uncomplicated malaria, living in these two different areas, may help to understand the effect of urbanization on the distribution of P. falciparum genotypes.

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The World Health Organization recommends that pregnant women in malaria-endemic areas receive >or= 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp/SP) in the second and third trimesters of pregnancy to prevent maternal anemia, placental parasitemia, and low birth weight (LBW). In 2001, a program evaluation in Koupéla District, Burkina Faso demonstrated that despite widespread use of chloroquine chemoprophylaxis, the burden of malaria during pregnancy remained high. In 2003, the Burkina Faso Ministry of Health piloted a program of IPTp/SP (three doses) and accelerated distribution of insecticide-treated nets (ITN) to pregnant women in Koupéla District. In 2004, a follow-up program evaluation was conducted. Coverage with >or= 1 doses of IPTp/SP was high among women attending antenatal clinics (ANCs) (96.2%) and delivery units (DUs) (93.5%); ITN ownership was moderately high (ANC = 53.9%, DU = 61.6%). In multivariate analysis, >or= 1 dose of IPTp/SP was associated with a significant reduction in the prevalence of peripheral parasitemia at ANCs (risk ratio [RR] = 0.49, P = 0.008), >or= 2 doses of IPTp/SP were associated with a reduction in the prevalence of placental parasitemia (RR = 0.56, P = 0.02), and three doses of IPTp/SP were associated with a reduced risk of LBW (RR = 0.51, P = 0.04). The proportions of women at ANCs with peripheral parasitemia and anemia were significantly lower in 2004 than in 2001 (RR = 0.53, P = 0.001 and RR = 0.78, P = 0.003, respectively). The proportions of women at DUs with peripheral and placental parasitemia were also significantly lower in 2004 than in 2001 (RR = 0.66, P < 0.0001 and RR = 0.71, P = 0.0002, respectively). These data suggest that a package of IPTp/SP and ITNs is effective in reducing the burden of malaria during pregnancy in Burkina Faso.

Evidence on the impact of using diagnostic tests in community case management of febrile children is limited. This effectiveness trial conducted in Burkina Faso, Ghana, and Uganda, compared a diagnostic and treatment package for malaria and pneumonia with presumptive treatment with anti-malarial drugs; artemisinin combination therapy (ACT). We enrolled 4,216 febrile children between 4 and 59 months of age in 2009–2010. Compliance with the malaria rapid diagnostic test (RDT) results was high in the intervention arm across the three countries, with only 4.9% (17 of 344) of RDT-negative children prescribed an ACT. Antibiotic overuse was more common: 0.9% (4 of 446) in Uganda, 38.5% (114 of 296) in Burkina Faso, and 44.6% (197 of 442) in Ghana. Fever clearance was high in both intervention and control arms at both Day 3 (97.8% versus 96.9%, P = 0.17) and Day 7 (99.2% versus 98.8%, P = 0.17). The use of diagnostic tests limits overuse of ACTs. Its impact on antibiotic overuse and on fever clearance is uncertain.