Jean-Yves Le Hesran

Increase of malaria attacks among children presenting concomitant infection by Schistosoma mansoni in Senegal.

Helminthic infections concomitant with malaria are common in inter-tropical areas. A recent study showed that mice co-infected with Schistosoma mansoni and Plasmodium chabaudi develop higher P. chabaudi parasitaemia and had a higher mortality rate. This important observation deserved to be further investigated among human populations.Malaria attacks were recorded in 512 children aged 6–15 years living in Richard Toll (Northern Senegal) among whom 336 were infected by S. mansoni, and 175 were not. The incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals, particularly those carrying the highest worm loads, as compared to uninfected subjects (26.6% versus 16,4 %). In contrast, the rate of malaria attacks was lower, without reaching significance, in medium grade S. mansoni infections. Thus, infection by S. mansoni affects susceptibility to malaria, but this can vary according to the intensity of parasite load. The immunological mechanisms underlying this dual effect need to be further explored.

Demographic, Ethnic, and Geographic Differences between Human T Cell Lymphotropic Virus (HTLV) Type I-Seropositive Carriers and Persons with HTLV-I Gag-Indeterminate Western Blots in Central Africa

Using stringent Western blot (WB) criteria, human T cell lymphotropic virus (HTLV) type I seroprevalence among 3783 persons from representative rural populations of Cameroon averaged 1.1% and was higher in females (1.5%) and in Pygmies (2.0%), increasing with age. Furthermore, an HTLV-I Gag-indeterminate WB profile (HGIP), exhibiting strong reactivities to p19, p26, p28, p32, p36, and pr 53 but lacking both p24 and env reactivity, was observed in 1.6% of the same populations. The prevalence of the HGIP was similar between males and females, did not increase with age, and appeared to cluster in tropical forests of southern Cameroon, especially among Pygmies (reaching 4%). These contrasting epidemiologic features, together with the lack of detection by polymerase chain reaction of HTLV-I sequences in the peripheral blood mononuclear cells of the persons with HGIP, strongly suggest that such a WB profile does not appear to reflect an HTLV-I-related viral infection but possibly an environmental (viral or parasitic) factor endemic in tropical rain forest areas.

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

BackgroundUrban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low.MethodsOne cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district.ResultsConsiderable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts.ConclusionsSpecific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.

Monocyte Activation and Cell Inhibition in Plasmodium falciparum-Inlected Placenta

BACKGROUND During healthy pregnancy, T helper (Th) 1-type and inflammatory-type responses are down-regulated, and Th2-type and proinflammatory-type responses predominate. In Plasmodium falciparum-infected females, these responses induce enhanced production of tumor necrosis factor- alpha and interferon- gamma. METHODS To assess the respective implication of monocytes and T cells in this placental immunomodulation, we cocultured cells from delivering females living in an area where malaria is endemic. Monocytes and T cells from both peripheral and intervillous blood were crossed in in vitro cultures, to compare the proliferative response to several antigens. Moreover, monocyte cell-surface molecules were quantified by flow cytometry. RESULTS Coculture results confirmed placental immunomodulation and suggested that the most affected cells are not the intervillous monocytes, which are as able to present the antigen as the peripheral monocytes, but the intervillous T cells. Monocyte staining showed significant increases in human leukocyte antigen D-related, CD54, CD80, and CD86 surface markers in intervillous blood, compared with peripheral blood, which suggests a relative activation of monocytes in the placenta. CONCLUSION A state of T cell deactivation and monocyte activation is present at delivery. The T cell deactivation in reaction to purified protein derivative could be explained by the presence of local T cell immunoregulatory factors.

Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal.

BackgroundThe introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) association, a transitory strategy before ACT implementation in Senegal.MethodsThe study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The childs primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses.ResultsThe study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the childrens age (8–10 years) (ORa = 3.07 [1.49–6.29]; p = 0.004); and the profession of the head of household (retailer/employee versus farmer) (ORa = 2.71 [1.34–5.48]; p = 0.006). Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013), and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001) were significantly associated with good compliance.ConclusionThe results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

Adherence and effectiveness of drug combination in curative treatment among children suffering uncomplicated malaria in rural Senegal

Increased Plasmodium falciparum resistance to chloroquine has prompted national malaria programs to develop new policies in several African countries. Less than a year after the introduction of amodiaquine/sulfadoxine-pyrimethamine (AQ/SP) as first-line treatment in Senegal, we examined adherence rates to therapy and its efficacy among children. The study was conducted in five dispensaries in rural Senegal. Children aged 2-10 years with a presumptive diagnosis of malaria were prescribed AQ/SP. Thick blood film analyses were carried out on days 0, 3, 7, 14 and 28. Blood and urine samples were collected on day 3 for drug level measurements. The principal caregivers were questioned on treatment adherence. Among the 289 recruited children, 144 had a parasitemia >2500/microl. The results demonstrated markedly good efficacy for the treatment, as no detectable parasitemia was observed on day 28 for 97.9% of the children. However, we noticed that 35.3% of children did not comply with the recommended doses and 62.3% did not exactly adhere to the drug schedule. Despite the good efficacy of the drugs, adherence to the therapeutic scheme was poor. Strategies to promote patient adherence would improve drug performance and thus might help to prevent the rapid emergence of drug resistance.

Hidden Plasmodium falciparum parasites in human infections: different genotype distribution in the peripheral circulation and in the placenta.

Sequestration of the mature Plasmodium falciparum forms complicates detection, quantification and molecular analysis of human infections. Whether the circulating parasites represent all or only a subset of co-infecting genotypes is unclear. We have investigated this issue and compared placenta and peripheral blood msp1 and msp2 genotypes in 58 women delivering with an ICT-positive placenta in Guediawaye, Senegal. Most placenta (91%) and blood samples (98%) were multiply infected. Multiplicity of infection was positively correlated in both tissues. However, the placental and circulating genotype profiles differed markedly. Only 10% of matched peripheral blood/placenta samples had identical genotypes, whereas 74% had only partially concordant genotypes, with some alleles detected in both tissues, together with additional allele(s) detected in one tissue only. Eight women (14%) had totally discordant placental and peripheral blood genotypes. Thus, in the vast majority of cases, some sequestered genotypes remain hidden, undetected in the peripheral circulation, indicating that analysis of peripheral parasites generates a partial picture of a P. falciparum infection.

Demonstration of a High Level of Parasite Population Homology by Quantification of Plasmodium falciparum Alleles in Matched Peripheral, Placental, and Umbilical Cord Blood Samples

ABSTRACT Plasmodium falciparum msp-1 and msp-2 genes were quantified by fragment analysis in matched placental, peripheral, and cord blood samples. In the three compartments, the multiplicity of infection values were similar, and parasite populations only partially overlapped, as reported. However, identical alleles represented 80 to 95% of the overall parasite populations of each compartment, demonstrating much more homogenous parasite populations than previously thought.

Where do pharmaceuticals on the market originate? An analysis of the informal drug supply in Cotonou, Benin

This anthropological study, conducted in Cotonou, Benin between 2005 and 2007, investigates the informal pharmaceuticals market. It was carried out through a long-term participant observation of informal vendors and semi-directive and unstructured interviews. A classification of products sold in the informal market was developed. The fact that a high percentage of them come from Anglophone countries near Benin (Nigeria and Ghana) led to a comparison of the sources of pharmaceutical supply in these three countries as well as their current legislation regarding pharmaceutical distribution. Our study results highlight a new understanding of the phenomenon of the informal market. Nigeria and Ghana rely on a liberal pharmaceutical distribution system with little intervention from public authorities. Conversely, the government maintains considerable influence over pharmaceutical distribution in Benin. Hence, the differences between these three countries in terms of variety of supply sources and flexibility of access to drugs are understood through an investigation of Benins informal market. Therefore, it appears that beyond issues concerning the quality of the pharmaceuticals, this phenomenon illustrates a kind of liberalization of pharmaceutical distribution and the ensuing public health issues.

The impact of IgG antibodies to recombinant Plasmodium falciparum 732var CIDR-1α domain in mothers and their newborn babies

Different domains of a novel full-length var gene (termed 732var) isolated from a placenta of a malaria-infected woman were expressed in Escherichia coli as recombinant proteins and analysed biochemically and immunologically. Two of these, the Duffy binding-like (DBL)-3γ domain and the cysteine-rich interdomain region (CIDR)-1α were able to bind chondroitin sulfate A and CD36, respectively. The DBL-3γ domain was investigated in a previous study and confirmed here to exhibit anti-disease characteristics related to pregnancy-associated malaria. Mothers with high anti-DBL-3γ antibody levels were protected from placental infection. The novel finding in this study is that babies born to mothers carrying anti-CIDR-1α antibodies had a delayed time to the first infection.