Search

Malaria congenital infection constitutes a major risk in malaria endemic areas. In this study, we report the prevalence of transplacental malaria in Burkina Faso. In labour and delivery units, thick and thin blood films were made from maternal, placental, and umbilical cord blood to determine malaria infection. A total of 1,309 mother/baby pairs were recruited. Eighteen cord blood samples (1.4%) contained malaria parasites (Plasmodium falciparum). Out of the 369 (28.2%) women with peripheral positive parasitemia, 211 (57.2%) had placental malaria and 14 (3.8%) had malaria parasites in their umbilical cord blood. The umbilical cord parasitemia levels were statistically associated with the presence of maternal peripheral parasitemia (OR = 9.24, P ≪ 0.001), placental parasitemia (OR = 10.74, P ≪ 0.001), high-density peripheral parasitemia (OR = 9.62, P ≪ 0.001), and high-density placental parasitemia (OR = 4.91, P = 0.03). In Burkina Faso, the mother-to-child transmission rate of malaria appears to be low.

To determine the relationship between malaria transmission intensity, clinical malaria, immune response, plasmodic index, and to furthermore characterize a malaria vaccine trial site for potential malaria vaccines candidate testing, a study was conducted in Tensobtenga and Balonguen, two villages in Burkina Faso characterized by different malaria transmission levels. The study villages are located in a Sudan savanna area. Malaria transmission is seasonal and peaks in September in these villages. Tensobtenga and Balonguen are comparables in all aspects, except the presence of an artificial lake and wetlands in Tensobtenga. The mosquitoes sampling sites were randomly selected, taking into consideration the number of potential breeding sites, and the number of households in each village. Three times a week during 12 mo mosquitoes were collected by the Center for Disease Control and Prevention light traps in sentinel sites. To assess the infectivity the mosquitoes double ELISAs tests were performed on thoraces of female Anopheles gambiae s.l. (Giles) and Anopheles funestus. A total of 54,392 female Anopheles, representing 92.71% of the total mosquitoes, were collected. The peaks of aggressiveness because of either An. gambiae s.l. or An. funestus were observed in September in each of the villages. However, these peaks were lower in Balonguen compared with Tensobtenga. Malaria cumulative aggressiveness and transmission intensity because of both species peaked in September in each of the two villages, with lower values in Balonguen in comparison to Tensobtenga From February to May, malaria transmission intensity is negligible in Balonguen and <1 bite/person/mo is observed in Tensobtenga. These results have confirmed the marked seasonality of malaria transmission in the study area.

Background: Man to mosquito transmission of malaria depends on the presence of the sexual stage parasites, gametocytes, that often circulate at low densities. Gametocyte densities below the microscopical threshold of detection may be sufficient to infect mosquitoes but the importance of submicroscopical gametocyte carriage in different transmission settings is unknown., Methodology/principal Findings: Membrane feeding experiments were carried out on 80 children below 14 years of age at the end of the wet season in an area of seasonal malaria transmission in Burkina Faso. Gametocytes were quantified by microscopy and by Pfs25-based quantitative nucleic acid sequence-based amplification assay (QT-NASBA). The children's infectiousness was determined by membrane feeding experiments in which a venous blood sample was offered to locally reared Anopheles mosquitoes. Gametocytes were detected in 30.0% (24/80) of the children by microscopy compared to 91.6% (65/71) by QT-NASBA (p<0.001). We observed a strong association between QT-NASBA gametocyte density and infection rates (p = 0.007). Children with microscopically detectable gametocytes were more likely to be infectious (68.2% compared to 31.7% of carriers of submicroscopical gametocytes, p = 0.001), and on average infected more mosquitoes (13.2% compared to 2.3%, p<0.001). However, because of the high prevalence of submicroscopical gametocyte carriage in the study population, carriers of sub-microscopical gametocytes were responsible for 24.2% of the malaria transmission in this population., Conclusions/significance: Submicroscopical gametocyte carriage is common in an area of seasonal transmission in Burkina Faso and contributes substantially to the human infectious reservoir. Submicroscopical gametocyte carriage should therefore be considered when implementing interventions that aim to reduce malaria transmission.

Background: A Phase Ia trial in European volunteers of the candidate vaccine merozoite surface protein 3 (MSP3), a Plasmodium falciparum blood stage membrane, showed that it induces biologically active antibodies able to achieve parasite killing in vitro, while a phase Ib trial in semi-immune adult volunteers in Burkina Faso confirmed that the vaccine was safe. The aim of this study was to assess the safety and immunogenicity of this vaccine candidate in children aged 12-24 months living in malaria endemic area of Burkina Faso., Methods: The study was a double-blind, randomized, controlled, dose escalation phase Ib trial, designed to assess the safety, reactogenicity and immunogenicity of three doses of either 15 or 30 microg of MSP3-LSP adsorbed on aluminum hydroxide in 45 children 12 to 24 months of age randomized into three equal groups. Each group received 3 vaccine doses (on days 0, 28 and 56) of either 15 microg of MSP3-LSP, 30 microg of MSP3-LSP or of the Engerix B hepatitis B vaccine. Children were visited at home daily for the 6 days following each vaccination to solicit symptoms which might be related to vaccination. Serious adverse events occurring during the study period (1 year) were recorded. Antibody responses to MSP3-LSP were measured on days 0, 28, 56 and 84., Results: All 45 enrolled children received three MSP3 vaccine doses. No serious adverse events were reported. Most of the adverse events reported were mild to moderate in severity. The only reported local symptoms with grade 3 severity were swelling and induration, with an apparently dose related response. All grade 3 adverse events resolved without any sequelae. Both MSP3 doses regimens were able to elicit high levels of anti-MSP3 specific IgG1 and IgG3 antibodies in the volunteers with very little or no increase in IgG2, IgG4 and IgM classes: i.e. vaccination induced predominantly the isotypes involved in the monocyte-dependent mechanism of P. falciparum parasite-killing., Conclusion: Our results support the promise of MSP3-LSP as a malaria vaccine candidate, both in terms of tolerability and of immunogenicity. Further assessment of the efficacy of this vaccine is recommended., Trial Registration: ClinicalTrials.gov NCT00452088.

Background: The weekly chemoprophylaxis of malaria during pregnancy with chloroquine (CQ) has become problematic with the increasing resistance of Plasmodium falciparum to this drug. There was a need to test the benefits of new strategies over the classical chemoprophylaxis. This study was conducted to provide data to the National Malarial Control Programme for an evidence-based policy change decision making process. It compares the efficacy of two IPT regimens, using chloroquine (CQ) or sulphadoxine/pyrimethamine (SP), with the classical chemoprophylaxis regimen using CQ in reducing the adverse outcomes of malaria infection, for the mother and the foetus., Methods: Pregnant women attending the first antenatal care visit were randomly assigned to one of the three treatment regimens. They were subsequently followed up till delivery. Maternal, placental and cord blood samples were obtained upon delivery to check for P. falciparum infection., Results: A total of 648 pregnant women were enrolled in the study. Delivery outcome were available for 423 of them. Peripheral maternal P. falciparum infection at delivery was found in 25.8% of the women. The proportion of women with maternal infection was significantly lower in the IPTp/SP group than in the CQ group (P << 0.000). The prevalence of placental malaria was 18.8% in the CWC/CQ group; 15.9% in the IPTp/CQ group and 10.6% in the IPTp/SP group. The incidence of LBW (weight < 2,500 g) was significantly higher among infants of mothers in the CWC/CQ group (23.9%) as compared with those of mothers in the IPTp/CQ (15.6%) and IPTp/SP (11.6%) groups (p = 0.02), Conclusion: Intermittent preventive treatment with SP has shown clear superiority in reducing adverse outcomes at delivery, as compared with intermittent preventive treatment with CQ and classical chemoprophylaxis with CQ.

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., Methods: Isolates collected from 75 and 89 children with uncomplicated malaria infection living in a rural and an urban area of Burkina Faso, respectively, were analysed by a nested PCR amplification of msp1 and msp2 genes to compare P. falciparum diversity., Results: The K1 allelic family was widespread in children living in the two sites, compared to other msp1 allelic families (frequency >90%). The MAD 20 allelic family of msp1 was more prevalent (p = 0.0001) in the urban (85.3%) than the rural area (63.2%). In the urban area, the 3D7 alleles of msp2 were more prevalent compared to FC27 alleles, with a high frequency for the 3D7 300bp allele (>30%). The multiplicity of infection was in the range of one to six in the urban area and of one to seven in the rural area. There was no difference in the frequency of multiple infections (p = 0.6): 96.0% (95% C.I: 91.6-100) in urban versus 93.1% (95%C.I: 87.6-98.6) in rural areas. The complexity of infection increased with age [p = 0.04 (rural area), p = 0.06 (urban area)]., Conclusion: Urban-rural area differences were observed in some allelic families (MAD20, FC27, 3D7), suggesting a probable impact of urbanization on genetic variability of P. falciparum. This should be taken into account in the implementation of malaria control measures.

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.

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.

Gametocytes are the malaria parasite stages that secure the transmission from the human host to the mosquito. The identification of natural parameters that influence gametocyte carriage can contribute to a better understanding of the dynamics of the sexual stage parasites for transmission reducing strategies. A total of 3400 blood slide readings were done during four cross-sectional surveys (2002-2003) including all age groups to determine the effect of season on Plasmodium falciparum gametocytes in a seasonal malaria transmission area of Burkina Faso. Entomological data were collected to determine the malaria transmission intensity in relation to seasons. Transmission intensity was estimated by monthly EIRs, averaging 28 and 32 infective bites/person/month in the wet seasons of 2002 and 2003, respectively. The EIR in the dry seasons was below one infective bite/person/month. The gametocyte prevalence was significantly higher at the start and peak of the wet season compared to the dry season when corrected for asexual parasite density and age. Gametocyte density significantly increased during the wet season after correction for asexual parasite density and age. In this study, season appears to be an independent parameter that determines gametocyte prevalence and density and should be considered to be included in epidemiological studies on malaria transmission.

To identify malaria antigens for vaccine development, we selected alpha-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally "native" epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high alpha-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.

Sexual stages of Plasmodium falciparum play a key role in the transmission of malaria. Studies on gametocytes are generally based on microscopic detection, but more sensitive detection methods for P. falciparum gametocytes frequently detect sub-patent gametocytes. We used Pfs25 mRNA quantitative-nucleic acid sequence-based amplification (QT-NASBA) to quantify gametocytes in 412 samples from a cross-sectional study in Burkina Faso, covering all age groups, to determine age-related patterns in gametocyte carriage and gametocyte density. The more sensitive QT-NASBA technique gave estimates of gametocyte prevalence 3.3-fold higher than microscopy (70.1% versus 21.4%, respectively). Prevalence of gametocytes significantly decreased with age. Our data suggest that asexual parasite densities are primarily responsible for the age-related decrease of gametocyte prevalence, possibly because of developing asexual stage immunity. Gametocyte densities decrease also with age, primarily because of decreasing asexual parasite densities; only a small but significant age effect on gametocyte density may be caused by developing sexual stage-specific immunity.

Unlabelled: The merozoite surface protein-3 long synthetic peptide (MSP3-LSP) comprises the amino acid sequence 186-276 of the Plasmodium falciparum protein MSP3. It is currently in development as an erythrocytic stage (blood stage) malaria vaccine candidate. We report here the first data on the safety, reactogenicity and immunogenicity of three doses of MSP3-LSP, adjuvanted with aluminium hydroxide, in healthy male adults living in a malaria endemic area., Methods: A phase 1b single-blind controlled trial was performed in the village of Balonghin in Burkina Faso. Thirty male volunteers aged 18-40 years were randomised to receive either three doses of 30 microg MSP3-LSP or 0.5 ml of tetanus toxoid vaccine. The second and third vaccine doses were given 28 and 112 days after the first dose. We followed participants for 1 year., Results: There were no serious adverse events in either vaccine group. In both groups participants reported local reactions at the site of injection when compared to an earlier trial in European volunteers. Only one systemic adverse event (tachycardia) was identified which occurred immediately after the first vaccination in one individual receiving MSP3-LSP. No clinically significant biological abnormalities following vaccination were observed. Humoral immune responses (IgG, IgG subclasses, IgM) to MSP3-LSP peptide were similar in the two groups following vaccination. Some cell-mediated immune responses appeared to differ between the two vaccine groups. After the second dose of MSP3-LSP, there appeared to be a marked increase in the lymphocyte proliferation index and IFN-gamma in response to stimulation with MSP3-LSP., Conclusion: These data suggest that three doses of 30 microg MSP3-LSP when administered subcutaneously on days 0, 28 and 112 are well-tolerated by adult males previously exposed to natural P. falciparum infection. They also suggest that MSP3-LSP is able to stimulate an enhanced cell-mediated immune response in individuals with some degree of preexisting immunity.

Insecticide treated materials (ITM) are considered a useful malaria control measure for endemic countries, but whether they also delay the acquisition of immunity to malaria remains unclear. This study investigates plasma antibody levels in 160 children aged 3-6 years from five villages protected by insecticide treated curtains (ITC) over 6 years and in 184 children of the same age group from five villages in the same area never covered by ITC. The antigens to which antibodies were investigated were: the Plasmodium falciparum circumsporozoite protein (CSP) repetitive sequence (NANP)5; the C-terminal domain of the P. falciparum exported protein 1 (Cter-PfExp1); three fragments of the glutamate rich protein (GLURP), referred to as R0, R1 and R2; the merozoite surface protein 3 (MSP3). The level of antibodies was lower in children from the ITC area than in children from the non-ITC area for (NANP)5, R0, R2 and MSP3. Prevalence and intensity of P. falciparum infection were similar in the two groups of children. These findings suggest that reducing the level of malaria transmission over a long period may affect the level of antibodies in children to both sporozoite and blood stage malaria antigens.