Issa Nébié

Centre National de Recherche et de Formation sur le Paludisme, Wagadugu, Centre, Burkina Faso

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Publications (72)197.01 Total impact

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    ABSTRACT: Prior to a chimpanzee adenovirus-based (ChAd63) malaria vaccine trial, sera were collected to assess ChAd63 specific neutralizing antibody titers in Banfora (Burkina Faso). The low neutralizing antibody titers reported in both adults and children (median titer 139.1 and 35.0 respectively) is encouraging for the potential use of ChAd63 as a malaria vaccine vector.
    Clinical and vaccine Immunology: CVI 04/2014; · 2.60 Impact Factor
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    ABSTRACT: Over the past ten years, Rapid Diagnostic Tests (RDT) played a major role in improving the use of biological malaria diagnosis, in particular in poor-resources settings. In Burkina Faso, a recent Demography and Health Survey (DHS) gave the opportunity to assess the performance of the Paracheck(R) test in under five children nationwide at community level. A national representative sample of 14,947 households was selected using a stratified two-stage cluster sampling. In one out of two households, all under five children were eligible to be tested for malaria using both RDT and microscopy diagnosis. Paracheck(R) performance was assessed using miscroscopy as the gold standard. Sensitivity and specificity were calculated as well as the diagnosis accuracy (DA) and the Youden index. The malaria infection prevalence was estimated at 66% (95% CI: 64.8-67.2) according to microscopy and at 76.2% (95% CI: 75.1-77.3) according to Paracheck(R). The sensitivity and specificity were estimated at 89.9% (95% CI: 89.0-90.8) and 50.4% (95% CI: 48.3-52.6) respectively with a Diagnosis Accuracy of 77% and a Youden index of 40%. The positive predictive value for malaria infection was 77.9% (95% CI: 76.7-79.1) and the negative predictive value was 72.1% (95% CI: 69.7-74.3). Variations were found by age group, period of the year and urban and rural areas, as well as across the 13 regions of the country. While the sensitivity of the Paracheck(R) test was high, its specificity was poor in the general under five population of Burkina Faso. These results suggest that Paracheck(R) is not suitable to assess malaria infection prevalence at community level in areas with high malaria transmission. In such settings, malaria prevalence in the general population could be estimated using microscopy.
    Malaria Journal 03/2014; 13(1):101. · 3.40 Impact Factor
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    ABSTRACT: The aim of this study was to determine the incidence and seasonal pattern of malaria in children in South-West Burkina Faso, and to compare, in a randomized trial, characteristics of cases detected by active and passive surveillance. This study also enabled the planning of a malaria vaccine trial. Households with young children, located within 5 kilometers of a health facility, were randomized to one of two malaria surveillance methods. In the first group, children were monitored actively. Each child was visited twice weekly; tympanic temperature was measured, and if the child had a fever or history of fever, a malaria rapid diagnostic test was performed and a blood smear collected. In the second group, children were monitored passively. The child's parent or caregiver was asked to bring the child to the nearest clinic if he was unwell. Follow up lasted 13 months from September 2009. Incidence of malaria (Fever with parasitaemia ≥5,000/µL) was 1.18 episodes/child/year in the active cohort and 0.89 in the passive cohort (rate ratio 1.32, 95% CI 1.13-1.54). Malaria cases in the passive cohort were more likely to have high grade fever; but parasite densities were similar in the two groups. Incidence was highly seasonal; when a specific case definition was used, about 60% of cases occurred within the 4 months June-September. Passive case detection required at least a 30%-40% increase in the sample size for vaccine trials, compared to active detection, to achieve the same power. However we did not find any evidence that parasite densities were higher with passive than with active detection. The incidence of malaria is highly seasonal and meets the WHO criteria for Seasonal Malaria Chemoprevention (SMC). At least half of the malaria cases in these children could potentially be prevented if SMC was effectively deployed.
    PLoS ONE 01/2014; 9(1):e86936. · 3.73 Impact Factor
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    ABSTRACT: Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early response to Plasmodium parasites is still very limited. We report here the analysis of IgG1 and IgG4 subclasses among anti-gSG6 IgG responders belonging to Mossi and Fulani from Burkina Faso, two ethnic groups which are known for their differential humoral response to parasite antigens and for their different susceptibility to malaria. The IgG1 antibody response against the gSG6 protein was comparable in the two groups. On the contrary, IgG4 titers were significantly higher in the Fulani where, in addition, anti-gSG6 IgG4 antibodies appeared in younger children and the ratio IgG4/IgG1 stayed relatively stable throughout adulthood. Both gSG6-specific IgG1 and IgG4 antibodies showed a tendency to decrease with age whereas, as expected, the IgG response to the Plasmodium circumsporozoite protein (CSP) exhibited an opposite trend in the same individuals. These observations are in line with the idea that the An. gambiae gSG6 salivary protein induces immune tolerance, especially after intense and prolonged exposure as is the case for the area under study, suggesting that gSG6 may trigger in exposed individuals a Th2-oriented immune response.
    PLoS ONE 01/2014; 9(4):e96130. · 3.73 Impact Factor
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    ABSTRACT: Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum drug resistance. There is an urgent need to investigate new sources of antimalarial drugs which are more effective against Plasmodium falciparum. One of the potential sources of antimalarial drugs is traditional medicinal plants. In this work, we studied the in vitro antiplasmodial activity of chloromethylenic, methanolic, and MeOH/H2O (1/1) crude extracts and decoction obtained from eight medicinal plants collected in Burkina Faso and of total alkaloids for five plants. Extracts were evaluated in vitro for efficacy against Plasmodium falciparum strain K1, which is resistant to chloroquine, pyrimethamine and proguanil using the fluorescence-based SYBR Green I assay. The antiproliferative activity on human-derived hepatoma cell line HepG2 and Chinese hamster ovary (CHO) cells was evaluated using the 3-[4,5-dimethylthyazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test in order to determine the selectivity index. Among the plant extracts tested for in vitro antiplasmodial activity, 16 were considered to be inactive (with IC50 > 10 μg/ml), six showed a moderate activity (5 < IC50 ≤ 10 μg/ml), and six were found to have a good in vitro activity with IC50 value ≤ 5 μg/ml. The highest antiplasmodial activity was found for extracts from: the alkaloid leaf extract and the chloromethylenic extracts of Combretum fragrans (IC50 = 3 μg/ml, IC50 = 5 μg/ml), the total alkaloids and the chloromethylenic leaf extracts of Combretum collinum (IC50 = 4 μg/ml), the MeOH/H2O leaf extract of Terminalia avicennioides (IC50 = 3.5 μg/ml), and the alkaloid leaf extract of Pavetta crassipes (IC50 = 5 μg/ml). Three other extracts showed moderate antiplasmodial activity (5 < IC50 ≤ 10 μg/ml): Terminalia avicennioides and Combretum fragrans methanolic extracts and Acacia kirkii alkaloid leaf extract (IC50 = 6.5, 9 and 10 μg/ml respectively). The Terminalia avicennioides crude MeOH/H2O (80:20 v/v) extract of the leaves was submitted to a successive liquid/liquid extraction with ethylacetate and n-butanol respectively. The extracts were investigated for in vitro antiplasmodial activity and antioxidant properties using DPPH([Symbol: see text]), ABTS(+) and FRAP methods. The ethylacetate extract showed the best antiplasmodial activity (7 μg/ml) and the active constituent was isolated as ellagic acid by bioguided fractionation with an IC50 = 0.2 μM on Plasmodium falciparum and SI = 152. Besides, Terminalia avicennioides leaf extract and ellagic acid showed a good antioxidant activity. Our finding confirms the importance of investigating the antimalarial activity of plant species used in traditional medicine. Overall, two plants belonging to the Combretaceae family, Combretum fragrans and Combretum collinum appeared to be the best candidates and will be further investigated for their antiplasmodial properties, in order to isolate the molecules responsible for the antiplasmodial activity.
    Parasitology Research 12/2013; · 2.85 Impact Factor
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    ABSTRACT: In malaria-endemic countries, large proportions of individuals infected with Plasmodium falciparum are asymptomatic and constitute a reservoir of parasites for infection of newly hatched mosquitoes. Two parallel studies were run in parallel in Burkina Faso to evaluate the impact of systematic identification and treatment of asymptomatic carriers of P. falciparum, detected by rapid diagnostic test, on disease transmission and susceptibility to clinical malaria episodes. A clinical study assessed the incidence of symptomatic malaria episodes with a parasite density >5,000/muL after three screening and treatment campaigns ~1 month apart before the rainy season; and an entomological study determined the effect of these campaigns on malaria transmission as measured by entomological inoculation rate. The intervention arm had lower prevalence of asymptomatic carriers of asexual parasites and lower prevalence of gametocyte carriers during campaigns 2 and 3 as compared to the control arm. During the entire follow-up period, out of 13,767 at-risk subjects, 2,516 subjects (intervention arm 1,332; control arm 1,184) had symptomatic malaria. Kaplan-Meier analysis of the incidence of first symptomatic malaria episode with a parasite density >5,000/muL showed that, in the total population, the two treatment arms were similar until Week 11--12 after campaign 3, corresponding with the beginning of the malaria transmission season, after which the probability of being free of symptomatic malaria was lower in the intervention arm (logrank p < 0.0001). Similar trends were observed in infants and children <5 years and in individuals >=5 years of age. In infants and children <5 years old who experienced symptomatic malaria episodes, the geometric mean P. falciparum density was lower in the intervention arm than the control arm. This trend was not seen in those individuals aged >=5 years. Over the year, monthly variation in mosquito density and entomological inoculation rate was comparable in both arms, with September peaks in both indices. Community screening and targeted treatment of asymptomatic carriers of P. falciparum had no effect on the dynamics of malaria transmission, but seemed to be associated with an increase in the treated community's susceptibility to symptomatic malaria episodes once the screening campaigns had finished. These results highlight the importance of further exploratory studies to better understand the dynamics of disease transmission in the context of malaria elimination.
    BMC Infectious Diseases 11/2013; 13(1):535. · 3.03 Impact Factor
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    ABSTRACT: Malariometric parameters are often primary endpoints of efficacy trials of malaria vaccine candidates. This study aims to describe the epidemiology of malaria prior to the conduct of a series of drug and vaccine trials in a rural area of Burkina Faso. Malaria incidence was prospectively evaluated over one year follow-up among two cohorts of children aged 0-5 years living in the Saponé health district. The parents of 1089 children comprising a passive case detection cohort were encouraged to seek care from the local health clinic at any time their child felt sick. Among this cohort, 555 children were randomly selected for inclusion in an active surveillance sub-cohort evaluated for clinical malaria during twice weekly home visits. Malaria prevalence was evaluated by cross-sectional survey during the low and high transmission seasons. Number of episodes per child ranged from 0 to 6 per year. Cumulative incidence was 67.4% in the passive and 86.2% in the active cohort and was highest among children 0-1 years. Clinical malaria prevalence was 9.8% in the low and 13.0% in the high season (p>0.05). Median days to first malaria episode ranged from 187 (95% CI 180-193) among children 0-1 years to 228 (95% CI 212, 242) among children 4-5 years. The alternative parasite thresholds for the malaria case definition that achieved optimal sensitivity and specificity (70-80%) were 3150 parasites/µl in the high and 1350 parasites/µl in the low season. Clinical malaria burden was highest among the youngest age group children, who may represent the most appropriate target population for malaria vaccine candidate development. The pyrogenic threshold of parasitaemia varied markedly by season, suggesting a value for alternative parasitaemia levels in the malaria case defintion. Regional epidemiology of malaria described, Sapone area field centers are positioned for future conduct of malaria vaccine trials.
    PLoS ONE 01/2013; 8(1):e50036. · 3.73 Impact Factor
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    ABSTRACT: Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa. A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 10(9), 10(10), 5X10(10), 10(11) vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140. Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35. Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies. ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459.
    PLoS ONE 01/2013; 8(11):e78679. · 3.73 Impact Factor
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    ABSTRACT: BACKGOUND: Treatment of confirmed malaria patients with Artemisinin-based Combination Therapy (ACT) at remote areas is the goal of many anti-malaria programs. Introduction of effective and affordable malaria Rapid Diagnosis Test (RDT) in remote areas could be an alternative tool for malaria case management. This study aimed to assess performance of the OptiMAL dipstick for rapid malaria diagnosis in children under five. Malaria symptomatic and asymptomatic children were recruited in a passive manner in two community clinics (CCs). Malaria diagnosis by microscopy and RDT were performed. Performance of the tests was determined. RDT showed similar ability (61.2%) to accurately diagnose malaria as microscopy (61.1%). OptiMAL showed a high level of sensitivity and specificity, compared with microscopy, during both transmission seasons (high & low), with a sensitivity of 92.9% vs. 74.9% and a specificity of 77.2% vs. 87.5%. By improving the performance of the test through accurate and continuous quality control of the device in the field, OptiMAL could be suitable for use at CCs for the management and control of malaria.
    Parasites & Vectors 05/2012; 5:103. · 3.25 Impact Factor
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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. · 3.40 Impact Factor
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    ABSTRACT: Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.
    Malaria Journal 03/2012; 11:79. · 3.40 Impact Factor
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    ABSTRACT: FcγRIIa is known to be polymorphic; and certain variants are associated with different susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in FcγRIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have addressed these questions in Burkina Faso. This study aimed to assess the influence of FcγRIIa-R131H polymorphism on anti-falciparum malaria IgG and IgG subclass responses in the Fulani and the Mossi ethnic groups living in Burkina Faso. Healthy adults more than 20 years old belonging to the Mossi or the Fulani ethnic groups were enrolled for the assessment of selected parasitological, immunological and genetic variables in relation to their susceptibility to malaria. The prevalence of the Plasmodium falciparum infection frequency was relatively low in the Fulani ethnic group compared to the Mossi ethnic group. For all tested antigens, the Fulani had higher antibody levels than the Mossi group. In both ethnic groups, a similar distribution of FcγRIIa R131H polymorphism was found. Individuals with the R allele of FcγRIIa had higher antibody levels than those with the H allele. This study confirmed that malaria infection affected less the Fulani group than the Mossi group. FcγRIIa-R131H allele distribution is similar in both ethnic groups, and higher antibody levels are associated with the FcγRIIa R allele compared to the H allele.
    Scandinavian Journal of Immunology 01/2012; 75(6):606-13. · 2.20 Impact Factor
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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.
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    ABSTRACT: Asexual blood stages antigens of malaria parasites are critical in the development of protective immunity. It's believed that protection against malaria involves mainly humoral immune responses elicited by pre-erythrocytic and blood-stage antigens. Study aimed to investigate seasonal variation and risk of clinical malaria episodes to selected P. falciparum antigens in study population. 529 children were visited during two cross sectional surveys (January 2007 and September 2007). 5 mL of venous blood were obtained from each child during each visit to measure antibody levels by ELISA. Children were then actively followed up clinically to record the malaria episodes. Blood smears were made when child had fever or history of fever to assess parasite load and malaria infection prevalence. Antibody levels against assessed antigens increased faster in older children than in younger. No evidence of an association between the levels of antibody and parasite density was noticed. Strong seasonal variation in antibody levels for the majority of the antigens was noticed. Only antibodies to LSA1 and AS155.4 were associated with protection against clinical malaria. Seasonal variation was noticed for all assessed antigens, but few of them were reported to play a protective role.
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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.
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    ABSTRACT: One approach to investigate if human genetic variation influences the selection of Plasmodium falciparum drug resistance is to compare the frequency of resistant infections among human populations differing in their genetic background and living in the same epidemiological context. A further complementary approach consists in comparing drug resistance among subjects differing for genes involved in drug metabolism. Here we report, from malariological surveys performed in Burkina Faso, that the prevalence of P. falciparum chloroquine-resistant infections (pfcrt 76T and/or pfmdr1 86Y alleles) differs among sympatric ethnic groups, being higher in the Mossi and Rimaibé groups than in the Fulani group (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.27-3.92; P = .007). The association analysis revealed that the human CYP2C8*2 variant, known to determine a poor drug metabolizer phenotype, was associated with P. falciparum chloroquine-resistant infections (OR, 1.66; 95% CI, 1.13-2.43; P = .008). This variant is more frequent in the Mossi-Rimaibé group (23.7% ± 1.4%) than in the Fulani group (9.9% ± 2.5%; P = .0003). This study provides an example of how host genetic variation may influence the selection dynamics of a pathogen's drug resistance.
    The Journal of Infectious Diseases 12/2011; 204(11):1772-8. · 5.85 Impact Factor
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    ABSTRACT: Acquisition of immunity to Plasmodium falciparum sexual stages is a key determinant for reducing human-mosquito transmission by preventing the fertilization and the development of the parasite in the mosquito midgut. Naturally acquired immunity against sexual stages may therefore form the basis for the development of transmission-blocking vaccines, but studies conducted to date offer little in the way of consistent findings. Here, we describe the acquisition of antigametocyte immune responses in malaria-exposed individuals in Burkina Faso. A total of 719 blood samples were collected in a series of three cross-sectional surveys at the start, peak, and end of the wet season. The seroprevalence of antibodies with specificity for the sexual stage antigens Pfs48/45 and Pfs230 was 2-fold lower (22 to 28%) than that for an asexual blood stage antigen glutamate-rich protein (GLURP) (65%) or for the preerythrocytic stage antigen circumsporozoite protein (CSP) (54%). The youngest children responded at frequencies similar to those for all four antigens but, in contrast with the immune responses to GLURP and CSP that increased with age independently of season and area of residence, there was no evidence for a clear age dependence of responses to Pfs48/45 and Pfs230. Anti-Pfs230 antibodies were most prevalent at the peak of the wet season (P < 0.001). Our findings suggest that naturally acquired immunity against Pfs48/45 and Pfs230 is a function of recent exposure rather than of cumulative exposure to gametocytes.
    Infection and immunity 12/2011; 79(12):4957-64. · 4.21 Impact Factor
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    ABSTRACT: A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.
    Vaccine 07/2011; 29(40):7090-9. · 3.77 Impact Factor
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    ABSTRACT: Abstract: The aim of this study was to evaluate the in vitro antiplasmodial activities of four plants used in traditional medicine. Hydroethanolic extract, hydroacetonic extract and aqueous extract of Mitragyna inermis (Willd.) O. Kuntze (Rubiaceae), Combretum sericeum G. Don (Combretaceae), Alternanthera pungens H.B. and K (Amaranthaceae) and Ampelocissus grantii (Baker) Planch (Vitaceae) have been tested in vitro against chloroquine-resistant strain (K1) and chloroquine-sensitve strain (3D7) of Plasmodium falciparum using pLDH assay. Aqueous extracts exhibited the best results against K1 with the 50% inhibitory concentration (IC50) values of 0.54±0.18, 1.72±0.99, 1.54±0.04 :g/mL for respectively, M. inermis leaves, C. sericeum leaves and whole plant of A. pungens. Hydroethanolic extract from the leaves of M. inermis gave also IC50 value of 0.87±0.10 :g/mL with 3D7. Extracts showed antiplasmodial activity against both chloroquine-sensitive and chloroquine-resistant P. falciparum strains. Our study justifies the use of these plants in traditional medicine and leads to further investigations.
    Current Research Journal of Biological Sciences. 05/2011; 3(3):216-222.
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    ABSTRACT: The Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmission in tropical Africa is sustained by three main vectors (A. gambiae, Anopheles arabiensis and Anopheles funestus) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the A. gambiae species complex whereas the A. funestus homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6. The A. funestus SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large A. gambiae prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed. According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level. Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The Anopheles stephensi SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the A. gambiae protein may also be useful to assess human exposure to several Asian malaria vectors.
    Malaria Journal 01/2011; 10:206. · 3.40 Impact Factor

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Institutions

  • 1999–2012
    • Centre National de Recherche et de Formation sur le Paludisme
      Wagadugu, Centre, Burkina Faso
  • 2011
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland
  • 1995–2011
    • Sapienza University of Rome
      • • Department of Public Health and Infectious Diseases
      • • Department of Experimental Medicine
      Roma, Latium, Italy
  • 2009
    • Swiss Tropical and Public Health Institute
      Bâle, Basel-City, Switzerland
  • 2008
    • University of Florence
      • Dipartimento di Scienze Biomediche, Sperimentali e Cliniche
      Florence, Tuscany, Italy
  • 2004–2008
    • University of Lausanne
      • Department of Biochemistry
      Lausanne, VD, Switzerland
  • 1998–1999
    • University of Camerino
      Camerino, The Marches, Italy
  • 1994
    • Ministero degli Affari Esteri
      Roma, Latium, Italy
    • Ministère de la Santé du Burkina Faso
      Wagadugu, Centre, Burkina Faso