Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.

[Effect of a large scale community-based distribution of artemether-lumefantrine on its therapeutic efficacy among children living in a rural area of Burkina Faso]. / Effet d'une distribution communautaire à large échelle de l'artéméther-luméfantrine sur son efficacité thérapeutique chez les enfants vivant en milieu rural au Burkina Faso.

This study aimed to assess the effect of an integrated community case management of malaria and pneumonia programme (iCCMmp) on the efficacy of artemether-lumefantrine (AL). Thus, we carried out two open label and unique centre clinical trials, before and after the iCCMmp, on the therapeutic efficacy of AL. A total of 210 children aged 6-59 months, were included in the study, 105 before and 105 after the iCCMmp. The adequate clinical and parasitological response was 90.5% and 86.7% respectively before and after the iCCMmp (p value = 0.516). Our findings reported no effect of iCCMmp on the therapeutic efficacy of the AL.

[Efficacy of artemether-lumefantrine in the treatment of uncomplicated malaria in children living in a rural area of Burkina Faso in 2009]. / Efficacité de l'artéméther-luméfantrine dans le traitement du paludisme simple de l'enfant en milieu rural au Burkina Faso en 2009.

In order to implement community case management of malaria strategy in a rural area of intense transmission, of children using artemether-lumefantrine combination, we assessed the therapeutic efficacy of the medicine. We conducted an open label and uncontrolled clinical trial in an unique centre from September 2009 to December 2009 in children 6-59 months old who consulted at health facilities for uncomplicated malaria. The primary endpoint was clinical and parasitological cure rate at day 28 corrected by PCR. In total 106 children were enrolled. Parasite clearance at day 2 was 99.04% and the adequate clinical and parasitological response corrected by PCR at day 28 was 90.5%. Our results confirm that artemether-lumefantrine combination is still effective.

FcγRIIa polymorphism and anti-malaria-specific IgG and IgG subclass responses in populations differing in susceptibility to malaria in Burkina Faso.

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.

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.

[Pharmaceutical black market in Burkina Faso: an illicit but socially adapted market]. / Le marché parallèle des médicaments au Burkina Faso: un marché dit illicite mais socialement construit.

In recent years the sale of pharmaceutical products by unlicensed vendors outside the official public health system has grown in Africa in general and in Burkina Faso in particular. The purpose of the present study was to identify the persons involved and their motivations, sources of supply, chains of distribution, and strengths and weaknesses of the parallel market. Data were collected using a two-part questionnaire. The first part focused on a certain category of buyer, i.e., mothers with children under the age of 5 years and the second part focused on medicine vendors working outside the official system. Accidental sample allowed contact with 41 vendors and cluster sampling obtained 340 mothers whose children presented fever within the last 30 days. Illicit sale of medicine appears to involve mainly young males with little or no formal education. The sex ratio was 0.25 including 34.1% with schooling and 65.9% with no schooling. The main motives of the vendors were money (18/41) and unemployment (12/41). The remaining 11 vendors stated that they wanted to help people who did not have access to a nearby health center. The business appears to be lucrative since the average daily income was estimated at 2.815 F CFA (ranges: 255 F CFA to 10.000 F CFA). Customers stated several reasons for buying on the illicit market but the most frequent reason was affordability. According to 98% of mothers drugs were cheaper on the illicit market than on the official market. Most mothers declared that their resources were insufficient to purchase higher-priced licit pharmaceutical products. Other factors accounted for buying drugs on the parallel market. Although it is considered as illicit, the market has the advantage of being socially adapted and responsive to consumer habits, expectations and needs.

A mathematical model for malaria involving differential susceptibility, exposedness and infectivity of human host.

The main purpose of this article is to formulate a deterministic mathematical model for the transmission of malaria that considers two host types in the human population. The first type is called "non-immune" comprising all humans who have never acquired immunity against malaria and the second type is called "semi-immune". Non-immune are divided into susceptible, exposed and infectious and semi-immune are divided into susceptible, exposed, infectious and immune. We obtain an explicit formula for the reproductive number, R(0) which is a function of the weight of the transmission semi-immune-mosquito-semi-immune, R(0a), and the weight of the transmission non-immune-mosquito-non-immune, R(0e). Then, we study the existence of endemic equilibria by using bifurcation analysis. We give a simple criterion when R(0) crosses one for forward and backward bifurcation. We explore the possibility of a control for malaria through a specific sub-group such as non-immune or semi-immune or mosquitoes.

[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.

[Genetic diversity of P. falciparum and pathogenesis of the severe malarial anaemia in children under 5 years old in the province of Boulgou, Burkina Faso]. / Diversité génétique de Plasmodium falciparum et pathogénie de l'anémie palustre sévere chez des enfants de moins de 5 ans de la province du Boulgou, Burkina Faso.

The clinical presentation of malaria mainly the severe form may be related to Plasmodium falciparum msp-2 (merozoite surface protein 2) specific family To verify this hypothesis, during the high malaria transmission season in 2001; we analyzed the allelic polymorphism of the msp-2 gene of P. falciparum in children under 5 years old with different presentation of malaria in the regional Hospital and at community level in the Boulgou Province (Burkina Faso). A total of 405 children (107 severe malarial anaemia cases, 102 severe malaria cases without severe anaemia and 196 non severe malaria cases) were enrolled in the study. The frequencies of the FC27 were 89.2% in severe malarial anaemia children group, then 89.7% and 86.9% respectively in severe malaria non anaemic children cases and non severe malaria cases (P = 0.4). The frequencies of the 3D7 were 72.5%; 84.1% and 77% respectively severe malaria non anaemic children, severe malarial anaemia cases and non severe malaria cases (P = 0.7). The complexity of the FC27 genotypes was significantly higher in children with severe malaria (with and without severe anaemia) compared to the non severe malarial children (P << 0.001). No significant difference was pointed up in the complexity of the 3D7 genotypes.