Publications (13)33.12 Total impact
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Article: Haemoglobin variants and Plasmodium falciparum malaria in children under five years of age living in a high and seasonal malaria transmission area of Burkina Faso.
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ABSTRACT: BACKGROUND: Genetic factors play a key role in determining resistance/susceptibility to infectious disease. Susceptibility of the human host to malaria infection has been reported to be influenced by genetic factors, which could be confounders if not taken into account in the assessment of the efficacy of interventions against malaria. This study aimed to assess the relationship between haemoglobin genotypes and malaria in children under five years in a site being characterized for future malaria vaccine trials. METHODS: The study population consisted of 452 children living in four rural villages. Hb genotype was determined at enrolment. Clinical malaria incidence was evaluated over a one-year period using combined active and passive surveillance. Prevalence of infection was evaluated via bi-annual cross-sectional surveys. At each follow-up visit, children received a brief clinical examination and thick and thin blood films were prepared for malaria diagnosis. A clinical malaria was defined as Plasmodium falciparum parasitaemia >2,500 parasites/ul and axillary temperature [greater than or equal to]37.5degreesC or reported fever over the previous 24 hours. RESULTS: Frequencies of Hb genotypes were 73.2% AA; 15.0% AC; 8.2% AS; 2.2% CC; 1.1% CS and 0.2% SS. Prevalence of infection at enrolment ranged from 61.9%-54.1% among AA, AC and AS children. After one year follow-up, clinical malaria incidence (95% CI) (episodes per person-year) was 1.9 (1.7-2.0) in AA, 1.6 (1.4-2.1) in AC, and 1.7 (1.4-2.0) in AS children. AC genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 1-2 years [rate ratio (95% CI) 0.66 (0.42-1.05)] and 2-3 years [rate ratio (95% CI) 0.37 (0.18-0.75)]; an association of opposite direction was however apparent among children aged 3-4 years. AS genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 2-3 years [rate ratio (95% CI) 0.63 (0.40-1.01)]. CONCLUSIONS: In this cohort of children, AC or AS genotype was associated with lower risk of clinical malaria relative to AA genotype only among children aged one to three years. It would be advisable for clinical studies of malaria in endemic regions to consider haemoglobin gene differences as a potentially important confounder, particularly among younger children.Malaria Journal 05/2012; 11(1):154. · 3.19 Impact Factor -
Article: Haematological parameters, natural regulatory CD4 + CD25 + FOXP3+ T cells and γδ T cells among two sympatric ethnic groups having different susceptibility to malaria in Burkina Faso.
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ABSTRACT: Fulani ethnic group individuals are less susceptible than sympatric Mossi ethnic group, in term of malaria infection severity, and differ in antibody production against malaria antigens. The differences in susceptibility to malaria between Fulani and Mossi ethnic groups are thought to be regulated by different genetic backgrounds and offer the opportunity to compare haematological parameters, Tregs and γδT cell profiles in seasonal and stable malaria transmission settings in Burkina Faso. The study was conducted at two different time points i.e. during the high and low malaria transmission period. Two cross-sectional surveys were undertaken in adults above 20 years belonging either to the Fulani or the Mossi ethnic groups 1) at the peak of the malaria transmission season and 2) during the middle of the low malaria transmission season. Full blood counts, proportions of Tregs and γδ T cells were measured at both time-points.As previously shown the Fulani and Mossi ethnic groups showed a consistent difference in P. falciparum infection rates and parasite load. Differential white blood cell counts showed that the absolute lymphocyte counts were higher in the Mossi than in the Fulani ethnic group at both time points. While the proportion of CD4+CD25high was higher in the Fulani ethnic group at the peak of malaria transmission season (p = 0.03), no clear pattern emerged for T regulatory cells expressing FoxP3+ and CD127low. However CD3+γδ+ subpopulations were found to be higher in the Fulani compared to the Mossi ethnic group, and this difference was statistically significant at both time-points (p = 0.004 at low transmission season and p = 0.04 at peak of transmission). Our findings on regulatory T cell phenotypes suggest an interesting role for immune regulatory mechanisms in response to malaria. The study also suggests that TCRγδ + cells might contribute to the protection against malaria in the Fulani ethnic group involving their reported parasite inhibitory activities.BMC Research Notes 01/2012; 5:76. -
Article: Transplacental Transmission of Plasmodium falciparum in a Highly Malaria Endemic Area of Burkina Faso.
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ABSTRACT: 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.Journal of Tropical Medicine 01/2012; 2012:109705. -
Article: Temporal dynamics of malaria transmission in two rural areas of Burkina Faso with two ecological differences.
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ABSTRACT: 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.Journal of Medical Entomology 07/2010; 47(4):618-24. · 1.76 Impact Factor -
Article: Correction: Safety and Immunogenicity of the Malaria Vaccine Candidate MSP3 Long Synthetic Peptide in 12-24 Months-Old Burkinabe Children.
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ABSTRACT: [This corrects the article on p. e7549 in vol. 4.].PLoS ONE 01/2010; 5(4). · 4.09 Impact Factor -
Article: Substantial contribution of submicroscopical Plasmodium falciparum gametocyte carriage to the infectious reservoir in an area of seasonal transmission.
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ABSTRACT: 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. 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. 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.PLoS ONE 01/2009; 4(12):e8410. · 4.09 Impact Factor -
Article: Safety and immunogenicity of the malaria vaccine candidate MSP3 long synthetic peptide in 12-24 months-old Burkinabe children.
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ABSTRACT: 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. 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. 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. 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. ClinicalTrials.gov NCT00452088.PLoS ONE 01/2009; 4(10):e7549. · 4.09 Impact Factor -
Article: Seasonal patterns of Plasmodium falciparum gametocyte prevalence and density in a rural population of Burkina Faso.
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ABSTRACT: 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.Acta Tropica 02/2008; 105(1):28-34. · 2.72 Impact Factor -
Article: Safety and immunogenicity of the Plasmodium falciparum merozoite surface protein-3 long synthetic peptide (MSP3-LSP) malaria vaccine in healthy, semi-immune adult males in Burkina Faso, West Africa.
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ABSTRACT: 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. 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. 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. 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.Vaccine 04/2007; 25(14):2723-32. · 3.77 Impact Factor -
Article: Age-dependent distribution of Plasmodium falciparum gametocytes quantified by Pfs25 real-time QT-NASBA in a cross-sectional study in Burkina Faso.
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ABSTRACT: 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.The American journal of tropical medicine and hygiene 04/2007; 76(4):626-30. · 2.59 Impact Factor -
Article: Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif.
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ABSTRACT: 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.PLoS ONE 02/2007; 2(7):e645. · 4.09 Impact Factor -
Article: Humoral responses to defined malaria antigens in children living since birth under insecticide treated curtains in Burkina Faso.
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ABSTRACT: 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.Acta Tropica 10/2003; 88(1):17-25. · 2.72 Impact Factor -
Article: Correction: Safety and Immunogenicity of the Malaria Vaccine Candidate MSP3 Long Synthetic Peptide in 12–24 Months-Old Burkinabe Children
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2003–2012
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Centre National de Recherche et de Formation sur le Paludisme
Ouagadougou, Centre, Burkina Faso
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