Humoral and cell-mediated immunity to MSP3 peptides in adults immunized with MSP3 in malaria endemic area, Burkina Faso.

We performed a single-blind, randomized phase 1 trial of the long synthetic peptide (LSP) of merozoite surface protein-3 (MSP3) in adults living in Burkina Faso. Thirty eligible volunteers were randomized to receive either the MSP3-LSP candidate vaccine or tetanus toxoid vaccine as a control. A dose of each vaccine was administered on days 0, 28 and 112 and the vaccine was formulated with aluminium hydroxide. Humoral immune responses were assessed by ELISA at days 0, 28, 56, 112, 140, 252 and 365 and cell-mediated immune responses by lymphoproliferation assay and by ELISA on days 0, 56 and 140. IgG responses to four peptides of MSP3 were similar in both vaccine groups. Higher IgG concentrations were recorded after the beginning of malaria high transmission season in both vaccine groups. The lymphocyte proliferation and the production of IFN-gamma in response to stimulation with the four overlapping peptides increased following vaccination in the MSP3-LSP vaccine group, but did not change appreciably in the control group. In contrast to natural infection, MSP3-LSP did not boost humoral responses to the four overlapping peptides of MSP3 to any detectable degree in our semi-immune adult. MSP3-LSP may be more immunogenic in young children with little or no acquired immunity.

[Change of antimalarial first-line treatment in Burkina Faso in 2005]. / Les raisons d'un changement de médicaments de première intention pour le traitement du paludisme simple au Burkina Faso en 2005.

Burkina Faso has recently changed the antimalarial drug policy to artesunate/amodiaquine or artemether/lumefantrine as the first-line antimalarial drug and sulfadoxine/pyrimethamine for the intermittent preventive treatment in pregnant woman. Before the implementation of this new strategy we conducted an in vivo efficacy study with chloroquine or sulfadoxine/pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in urban area of Burkina from September to December 2003. Chloroquine (25 mg/kg over 3 days) or sulfadoxine/pyrimethamine (25 mg/kg + 0.025 mg/kg single dose) was administered respectively to 137 and 125 children aged from 6 to 59 months old in a randomized, opened study. Follow up extended over 28 days using modified WHO protocol. After adjusting the results by PCR, treatment failures rates were 63.4% (83/131) and 13.8% (17/123) respectively for chloroquine and sulfadoxine/pyrimethamine. These results with other observations have justified the change of malaria therapy policy in Burkina Faso in 2005.

Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

OBJECTIVES: To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)(5) GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. METHODS: Cross-sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. RESULTS: Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non-responders [(NANP)(5) (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46-0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48-0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50-1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32-0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38-1.05; P = 0.08). CONCLUSION: Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.

[Comparative impact of three malaria preventive regimens during pregnancy on maternal anemia due to malaria in Burkina Faso]. / Impact comparatif de trois schémas de prévention du paludisme pendant la grossesse sur l'anémie maternelle, associée à l'infection palustre au Burkina Faso.

OBJECTIVES: The main objective of this study was to compare the efficacy of three regimens of malaria prevention during pregnancy for the reduction of anemia between the first and third antenatal consultations. The first treatment arm was the classical weekly chemoprophylaxis with chloroquine; the other two were the intermittent preventive treatment using either three doses of chloroquine or sulfadoxine-pyrimethamine. DESIGN: We conducted an open, randomized, three-arm study in a rural district of Burkina Faso. A cohort was constituted by 648 pregnant women of any parity. RESULTS: The hemoglobin gain was more significant with the intermittent preventive treatment using sulfadoxine-pyrimethamine compared to the other treatment arms. The hemoglobin increased from 10.3g/dl (at the first antenatal consultation) to 11.4 g/dl (at the third antenatal consultation). In the three arms of treatment, the chemoprophylaxis reduced the prevalence of moderate anemia and severe anemia. The reduction of moderate anemia was more substantial in the sulfadoxine-pyrimethamine arm (65.6 to 36.7%) at second antenatal consultation (p=0.069) and third antenatal consultation (p=0.014). Conversely, in the two chloroquine arms, there was no significant reduction either at second antenatal consultation (p=0.72) or third antenatal consultation (p=0.55). The prevalence of peripheral parasitemia decreased in all treatment groups. However, it was significantly higher in the sulfadoxine-pyrimethamine group (44.3%). CONCLUSIONS: Intermittent preventive treatment with three doses of sulfadoxine-pyrimethamine is a more effective strategy to prevent maternal anemia during pregnancy in Burkina Faso.

Effect of zinc supplementation on malaria and other causes of morbidity in west African children: randomised double blind placebo controlled trial.

OBJECTIVE: To study the effects of zinc supplementation on malaria and other causes of morbidity in young children living in an area holoendemic for malaria in west Africa. DESIGN: Randomised, double blind, placebo controlled efficacy trial. SETTING: 18 villages in rural northwestern Burkina Faso. PARTICIPANTS: 709 children were enrolled; 685 completed the trial. INTERVENTION: Supplementation with zinc (12.5 mg zinc sulphate) or placebo daily for six days a week for six months. MAIN OUTCOME MEASURES: The primary outcome was the incidence of symptomatic falciparum malaria. Secondary outcomes were the severity of malaria episodes, prevalence of malaria parasite, mean parasite densities, mean packed cell volume, prevalence of other morbidity, and all cause mortality. RESULTS: The mean number of malaria episodes per child (defined as a temperature >/=37.5 degrees C with >/=5000 parasites/microliter) was 1.7, 99.7% due to infection with Plasmodium falciparum. No difference was found between the zinc and placebo groups in the incidence of falciparum malaria (relative risk 0.98, 95% confidence interval 0.86 to 1.11), mean temperature, and mean parasite densities during malaria episodes, nor in malaria parasite rates, mean parasite densities, and mean packed cell volume during cross sectional surveys. Zinc supplementation was significantly associated with a reduced prevalence of diarrhoea (0.87, 0.79 to 0.95). All cause mortality was non-significantly lower in children given zinc compared with those given placebo (5 v 12, P=0.1). CONCLUSIONS: Zinc supplementation has no effect on morbidity from falciparum malaria in children in rural west Africa, but it does reduce morbidity associated with diarrhoea.