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Patillon B.,IRD UMR216 | Patillon B.,University of Paris Descartes | Patillon B.,University Paris - Sud | Luisi P.,Institute of Evolutionary Biology | And 6 more authors.
Human Biology | Year: 2014

N-Acetyltransferase 2 (NAT2) is an important enzyme involved in the metabolism of a wide spectrum of naturally occurring xenobiotics, including therapeutic drugs and common environmental carcinogens. Extensive polymorphism in NAT2 gives rise to a wide interindividual variation in acetylation capacity, which influences individual susceptibility to various drug-induced adverse reactions and cancers. Striking patterns of geographic diffferentiation have been described for the main slow acetylation variants of the NAT2 gene, suggesting the action of natural selection at this locus. In the present study, we took advantage of whole-genome sequence data available from the 1000 Genomes project to investigate the global patterns of population genetic diffferentiation at NAT2 and determine whether they are atypical compared with the remaining variation of the genome. The nonsynonymous substitution c.590G>A (rs1799930) defijining the slow NAT2*6 haplotype cluster exhibited an unusually low FST value compared with the genome average (FST = 0.006, P = 0.016). It was indicated as the most likely target of a homogenizing process of selection promoting the same allelic variant in globally distributed populations. The rs1799930 A allele has been associated with the slowest acetylation capacity in vivo, and its substantial correlation with the subsistence strategy adopted by past human populations suggests that it may have conferred a selective advantage in populations shifting from foraging to agricultural and pastoral activities in the Neolithic period. Results of neutrality tests further supported an adaptive evolution of the NAT2 gene through either balancing selection or directional selection acting on multiple standing slow acetylation variants. © 2015 Wayne State University Press, Detroit, Michigan 48201.


Hartwig S.,Sanofi S.A. | Baldauf J.-J.,Departement de gynecologie et obstetrique | Dominiak-Felden G.,Sanofi S.A. | Simondon F.,IRD UMR216 | And 4 more authors.
Papillomavirus Research | Year: 2015

Introduction: A second generation HPV vaccine has been developed for the prevention of anogenital cancers and precancerous lesions of the cervix, vulva, vagina, anus and of genital warts due to nine HPV types.We estimated the annual burden of these diseases attributable to the nine HPV types compared to HPV types from first generation vaccines in women and men in Europe. Material and methods: Incidence rates from the IARC database, cancer registries, the literature and Eurostat population data were used.The burden attributable to the HPV types targeted by both vaccines was estimated by applying the relative contribution of the respective HPV types from epidemiological studies. Results: In 2013, the number of new anogenital HPV-attributable cancers was 44,480 with 39,494 of these cases related to second vs. 33,285 to first generation vaccine types.Among the 284,373 to 541,621 new HPV-attributable anogenital precancerous lesions 235,364-448,423 and 135,025-256,830 were estimated to be related to second and first generation vaccine types, respectively.The annual number of new genital warts was 753,608-935,318, with 90% related to HPV6/11. Conclusions: These data demonstrate how the large public health impact that was achieved by the first generation HPV vaccines could be further increased by second generation vaccines. © 2015 The Authors.


Koura K.G.,IRD UMR216 | Koura K.G.,University of Paris Descartes | Koura K.G.,University Pierre and Marie Curie | Garcia A.,IRD UMR216 | And 9 more authors.
Acta Tropica | Year: 2013

In order to assess the factors related to antibiotic prescription, a cross sectional study was carried out in four school infirmaries from February to June 2008 in the district of Allada in Benin. For each patient, socio-demographic characteristics, symptoms motivating medical visits, diagnosis and therapeutic prescriptions were collected. A malaria rapid diagnostic test was used in case of fever. Data were entered and validated with Epidata® software, and analysed with STATA 11® software. One thousand six hundred and thirty medical visits occurred during the study period. Fever was reported by 57% of children. Malaria was the leading diagnosis (32%), followed by respiratory infection (17.5%). Antibiotic was prescribed to 40% of the children. Respiratory infection and skin disorders were positively related to antibiotic usage [OR=59.5 (33.4-105.7); P<10-3 and OR=6.4 (4.6-8.8); P<10-3 respectively]. Malaria [OR=0.11 (0.03-0.11); P<10-3] and fever of unknown origin [OR=0.05 (0.03-0.11); P<10-3] were negatively related to antibiotic usage. Further clinical surveys and trials aimed at rationalizing antibiotics usage in this area should focus on the management of acute respiratory illnesses. © 2013 Elsevier B.V.


Koura G.K.,IRD UMR216 | Koura G.K.,University of Paris Descartes | Koura G.K.,University Pierre and Marie Curie | Ouedraogo S.,IRD UMR216 | And 22 more authors.
Tropical Medicine and International Health | Year: 2012

To determine the effect of maternal anaemia on pregnancy outcome and describe its impact on infant haemoglobin level in the first 18months of life, we conducted a prospective study of 617 pregnant women and their children in Benin. Prevalence of maternal anaemia at delivery was 39.5%, and 61.1% of newborns were anaemic at birth. Maternal anaemia was not associated with low birth weight [OR=1.2 (0.6-2.2)] or preterm birth [OR=1.3 (0.7-2.4)], whereas the newborn's anaemia was related to maternal anaemia [OR=1.8 (1.2-2.5)]. There was no association between an infant's haemoglobin level until 18months and maternal anaemia. However, malaria attacks during follow-up, male gender and sickle cell trait were all associated with a lower infant haemoglobin level until 18months, whereas good infant feeding practices and a polygamous family were positively associated with a higher haemoglobin level during the first 18months of life. © 2011 Blackwell Publishing Ltd.


This paper questions the current highlighted question of "fake drugs" in the media and through institutional speeches. After a brief reminder of the expressions used previously in France and in the French-speaking countries of West Africa, the realities which recover various phenomena will be discussed as well as the hotchpotch often made between them: the phenomenon of counterfeit drugs, that of substandard medicines and the recently legally defined in Europe phenomenon of falsified drugs. Then, the data of an anthropological study led from 2005 till 2007 about the informal market of pharmaceutical in Benin will allow to underline the differences which exist between this phenomenon and that of counterfeit drugs as well as that of falsified drugs. Finally, the political and economic stakes which recover these questions will be highlighted and will explain why "fantasized" speeches are often given about them. The conclusion will stop on the problem of substandard medicines and some of the ways to solve it will be sketched. © 2014 Springer-Verlag France.


Koura K.G.,IRD UMR216 | Koura K.G.,University of Paris Descartes | Koura K.G.,University Pierre and Marie Curie | Ouedraogo S.,IRD UMR216 | And 12 more authors.
PLoS ONE | Year: 2012

Background: Anaemia during pregnancy and at delivery is an important public health problem in low- and middle-income countries. Its association with the children's haemoglobin level over time remains unclear. Our goals were to identify distinct haemoglobin level trajectories using latent class analysis and to assess the association between these trajectories and maternal anaemia and other risk factors. Method: A prospective study of children from birth to 18 months of life was conducted in a rural setting in Tori-Bossito, Benin. The main outcome measure was the haemoglobin levels repeatedly measured at 3, 6, 9, 12, 15 and 18 months. Variables were collected from the mothers at delivery and from their children at birth and during the follow-up. The analyses were performed by means of Latent Class Analysis which has never been used for this kind of data. All the analyses were performed with Stata software, version 11.0, using the generalized linear latent and mixed model (GLLAMM) framework. Results: We showed that 33.7% of children followed a low haemoglobin trajectory and 66.3% a high trajectory during the first 18 months of life. Newborn anaemia, placental malaria, malaria attack, sickle cell trait and male gender were significantly associated with a lower children's haemoglobin level over time, whereas maternal age, children living in a polygamous family and with good feeding practices had a higher Hb level in the first18 months. We also showed that maternal anaemia was a predictor for 'low haemoglobin level trajectory' group membership but have no significant effect on children haemoglobin level over time. Conclusion: Latent Class Analyses framework seems well suited to analyse longitudinal data under the hypothesis that different subpopulations of subjects are present in the data, each with its own set of parameters, with distinctive evolutions that themselves may reflect distinctive aetiologies. © 2012 Koura et al.


Romero M.,IRD UMR216 | Postigo J.,IRD UMR216 | Schneider D.,University of Paris Descartes | Chippaux J.-P.,IRD UMR216 | And 2 more authors.
Tropical Medicine and International Health | Year: 2011

Objective To demonstrate the feasibility of a house-to-house screening system used for congenital Chagas disease in rural areas based on an active search for pregnant women and newborns in their homes in addition to passive case detection in health facilities. Methods Exploratory phase conducted by the research team followed by an operational period coordinated by municipal health service. A blood sample was taken for serological and parasitological tests of Trypanosoma cruzi from pregnant women who were searching antenatal care or visited at home by field investigators. Infants born to T. cruzi-infected women were examined for infection at birth and again at 1 and 7months of age. Results 64.5% of the pregnant women were infected. Congenital infection was diagnosed at birth in 4.0% (12/299) of the children born to seroreactive mothers. Twelve additional cases of infection (4%) were diagnosed in children between 1 and 7months of age. Finally, 37% of the children were lost to follow-up in the exploratory phase and 53% during the operational phase (P=0.002), significantly fewer than in most passive case detection studies. Conclusion Despite poorer outcomes after door-to-door screening activities have been transferred to the health system, a combined strategy based on active and passive case detection appeared to be efficient for identifying rural cases of congenital Chagas disease. © 2011 Blackwell Publishing Ltd.


Koura K.G.,IRD UMR216 | Koura K.G.,University of Paris Descartes | Koura K.G.,University Pierre and Marie Curie | Boivin M.J.,Michigan State University | And 18 more authors.
Journal of Developmental and Behavioral Pediatrics | Year: 2013

OBJECTIVE: Few tools are available to screen or assess infant's cognitive development, especially in French-speaking Africa. This study evaluated the use of the French translation of the Mullen Scales of Early Learning (MSEL), and the "Ten Questions" questionnaire (TQ) in 1-year-old children in Benin, a francophone country. METHODS: A cross-sectional study was conducted in 3 health centers serving a semirural area in Benin. Three hundred fifty-seven children aged 12 months and their mothers were enrolled in 2011. Infant development was assessed at local health centers followed by a home visit to collect information on socioeconomic status, maternal Raven score, maternal depressive symptoms, and mother-child interactions (Home Observation for the Measurement of the Environment [HOME] Inventory), and to administer the TQ. RESULTS: The infant's gender (female), the HOME, and maternal education were associated with a higher Early Learning Composite score in multivariate analyses (p = .02, p = .004, p = .007, respectively). The HOME and family wealth were also associated with the Gross Motor Scale (p = .03 and p = .03, respectively). Mothers were more likely to report difficulties on the TQ when the child presented lower score on the MSEL. When considering the Gross Motor Scale as the gold standard to define moderate delays, the 2 combined motor-related questions on the TQ showed good sensitivity and specificity (76.5 and 75.7). CONCLUSION: In a low-resource rural setting in Africa, the TQ effectively identified 3 quarters of 1-year-old infants with delayed development. After this screening, the MSEL may be useful for further assessment as it showed good feasibility and sensitivity to known risk factors for poor child development. Copyright © 2013 Lippincott Williams & Wilkins.


PubMed | IRD UMR216
Type: Journal Article | Journal: The American journal of tropical medicine and hygiene | Year: 2010

Vector control has led to a drastic decrease in the prevalence of acquired Chagas disease in Latin America, thus redirecting attention to congenital Chagas disease. We report results of a longitudinal study of 359 pregnant women in Yacuiba in southern Bolivia, of whom 147 (40.9%) were infected with Trypanosoma cruzi, to evaluate the relationship between the patency period of the parasitemia and the risk of congenital infection. Maternal infection was assessed by using T. cruzi-specific serologic tests, and parasitemia in mothers and newborns was diagnosed by using microscopic examination of blood in heparinized microhematocrit tubes. Parasitemia was present in 28.6% of the infected women. Its prevalence increased during the third trimester, then decreased at delivery. The likelihood of congenital infection was significantly correlated with the parasite density in the mothers blood. The risk of transmission increased during the third trimester of pregnancy and could explain premature births or low-weight newborns for infected mothers.


PubMed | IRD UMR216
Type: Journal Article | Journal: Tropical medicine & international health : TM & IH | Year: 2011

To demonstrate the feasibility of a house-to-house screening system used for congenital Chagas disease in rural areas based on an active search for pregnant women and newborns in their homes in addition to passive case detection in health facilities.Exploratory phase conducted by the research team followed by an operational period coordinated by municipal health service. A blood sample was taken for serological and parasitological tests of Trypanosoma cruzi from pregnant women who were searching antenatal care or visited at home by field investigators. Infants born to T. cruzi-infected women were examined for infection at birth and again at 1 and 7 months of age.64.5% of the pregnant women were infected. Congenital infection was diagnosed at birth in 4.0% (12/299) of the children born to seroreactive mothers. Twelve additional cases of infection (4%) were diagnosed in children between 1 and 7 months of age. Finally, 37% of the children were lost to follow-up in the exploratory phase and 53% during the operational phase (P=0.002), significantly fewer than in most passive case detection studies.Despite poorer outcomes after door-to-door screening activities have been transferred to the health system, a combined strategy based on active and passive case detection appeared to be efficient for identifying rural cases of congenital Chagas disease.

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