Maman Laminou Ibrahim

MVD. MSc. PhD.
Chef Unité Parasitologie
CERMES · Unité Parasitologie

Publications

  • Source
    Maman Laminou Ibrahim
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary Background Artemether–lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the eff ect of dosing strategy on effi cacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods We searched PubMed for clinical trials that enrolled and treated patients with artemether–lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCRunadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identifi ed using Cox’s regression model with frailty shared across the study sites. Findings We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic effi cacy was 97·6% (95% CI 97·4–97·9) at day 28 and 96·0% (95·6–96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86–0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10–15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted effi cacy (91·7%, 95% CI 86·5–96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1–3 years (PCRadjusted efficacy 94·3%, 95% CI 92·3–96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85–0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation The recommended dose of artemether–lumefantrine provides reliable effi cacy in most patients with uncomplicated malaria. However, therapeutic effi cacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.
  • Source
    Maman Laminou Ibrahim
    [Show abstract] [Hide abstract]
    ABSTRACT: Summary Background Artemether–lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the eff ect of dosing strategy on effi cacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods We searched PubMed for clinical trials that enrolled and treated patients with artemether–lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCRunadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identifi ed using Cox’s regression model with frailty shared across the study sites. Findings We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic effi cacy was 97·6% (95% CI 97·4–97·9) at day 28 and 96·0% (95·6–96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86–0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10–15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted effi cacy (91·7%, 95% CI 86·5–96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1–3 years (PCRadjusted effi cacy 94·3%, 95% CI 92·3–96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85–0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Le paludisme est un problème majeur de santé publique dans la zone intertropicale. Les souches de Plasmodium falciparum deviennent aussi de plus en plus résistantes aux molécules couramment utilisées et même contre l’artémisinine. Il devient urgent de trouver de nouvelles molécules antipaludiques. Nous avons évalué puis comparé l’activité antiplasmodiale des extraits éthanoliques dégraissés de quatre plantes issues de la médicine traditionnelle du Niger à celle d’Artemisia annua sur la souche de Plasmodium falciparum chloroquinorésistante W2. La méthode utilisée est celle de l’OMS/2001 ou test de Mark III. L’activité antiplasmodiale a été discutée à la lumière du profil phytochimique des différentes plantes, déterminé par les méthodes standards de screening chimique. Cassia nigricans, Sebastiania chamaelea et Euphorbia hirta présentent une bonne activité antiplasmodiale. Leurs IC50 respectives sont de 2,8μg/ml, 3,3μg/ml et 3,7μg/ml. Cela justifie leur utilisation contre le paludisme en pharmacopée traditionnelle du Niger. Par contre, Cassia occidentalis présente une activité modérée avec une IC50 de 10,4μg/ml.
  • Source
    Maman Laminou Ibrahim
    [Show abstract] [Hide abstract]
    ABSTRACT: L’édition 2014 du Cours National de Paludologie (CNP) s’est tenue du 17 au 28 Novembre 2013 au Centre de Formation Pierre et Anne-Marie Moussa. Cette formation est organisée par le CERMES en collaboration avec le Programme National de Lutte contre le Paludisme, la Faculté des Sciences de la Santé (FSS) et l’Hôpital National de Niamey. L’objectif général du CNP est de renforcer l’expertise des scientifiques et des agents de santé dans tous les aspects de la paludologie pour la mise à l’échelle des interventions de lutte contre le paludisme et une initiation à la recherche scientifique. Le CNP a comme objectifs spécifiques:  Connaitre les stratégies et les outils pour lutter contre le paludisme:  Savoir faire face à une épidémie palustre ou une situation d’urgence,  Maitriser les techniques d’information, d’éducation et de communication pour un changement de comportement (IEC/CCC),  Développer des aptitudes à rédiger un plan stratégique  S’initier à la recherche scientifique.
    Note d'information, Bulletin d'information du CERMES; 02/2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chloroquine (CQ) resistance is widespread in Africa, but few data are available for Niger. Pfcrt haplotypes (aa 56–118) and ex vivo responses to CQ and amodiaquine were characterized for 26 isolates collected in South Niger from children under 15 years of age suffering from uncomplicated falciparum malaria, six years after the introduction of artemisinin-based combinations and the withdrawal of CQ. The wild-type Pfcrt haplotype CVMNK was found in 22 of the 26 isolates, with CVIET sequences observed in only three of the samples. We also describe for the first time a new CVINT haplotype. The ex vivo responses were better for CVMNK than for CVIET parasites. Pfcrt sequence data were compared with those obtained for 26 additional parasitized blood samples collected in Gabon, from an area of CQ resistance used as a control. Our findings suggest that there has been a significant decline in CQ-resistant genotypes since the previous estimates for Niger were obtained. No such decline in molecular resistance to CQ was observed in the subset of samples collected in similar conditions from Gabon.These results have important implications for public health and support the policy implemented in Niger since 2005, which aims to increase the efficacy and availability of antimalarial drugs whilst controlling the spread of resistance.
    01/2014; 2014:7. DOI:10.1155/2014/614190
  • [Show abstract] [Hide abstract]
    ABSTRACT: Few data are available about malaria epidemiological situation in Niger. However, implementation of new strategies such as vaccination or seasonal treatment of a target population requires the knowledge of baseline epidemiological features of malaria. A population-based study was conducted to provide better characterization of malaria seasonal variations and population groups the most at risk in this particular area. From July 2007 to December 2009, presumptive cases of malaria among a study population living in a typical Sahelian village of Niger were recorded, and confirmed by microscopic examination. In parallel, asymptomatic carriers were actively detected at the end of each dry season in 2007, 2008 and 2009. Among the 965 presumptive malaria cases recorded, 29% were confirmed by microscopic examination. The incidence of malaria was found to decrease significantly with age (p < 0.01). The mean annual incidence was 0.254. The results show that the risk of malaria was higher in children under ten years (p < 0.0001). The number of malaria episodes generally followed the temporal pattern of changes in precipitation levels, with a peak of transmission in August and September. One-thousand and ninety subjects were submitted to an active detection of asymptomatic carriage of whom 16% tested positive; asymptomatic carriage decreased with increasing age. A higher prevalence of gametocyte carriage among asymptomatic population was recorded in children aged two to ten years, though it did not reach significance. In Southern Niger, malaria transmission mostly occurs from July to October. Children aged two to ten years are the most at risk of malaria, and may also represent the main reservoir for gametocytes. Strategies such as intermittent preventive treatment in children (IPTc) could be of interest in this area, where malaria transmission is highly seasonal. Based on these preliminary data, a pilot study could be implemented in Zindarou using IPTc targeting children aged two to ten years, during the three months of malaria transmission, together with an accurate monitoring of drug resistance.
    Malaria Journal 10/2013; 12(1):379. DOI:10.1186/1475-2875-12-379 · 3.49 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Individuals continuously exposed to malaria gradually acquire immunity that protects from severe disease and high levels of parasitization. Acquired immunity has been incorporated into numerous models of malaria transmission of varying levels of complexity (e.g. Bull World Health Organ 50:347, 1974; Am J Trop Med Hyg 75:19, 2006; Math Biosci 90:385--396, 1988). Most such models require prescribing inputs of mosquito biting rates or other entomological or epidemiological information. Here, we present a model with a novel structure that uses environmental controls of mosquito population dynamics to simulate the mosquito biting rates, malaria prevalence as well as variability in protective immunity of the population. A simple model of acquired immunity to malaria is presented and tested within the framework of the Hydrology, Entomology and Malaria Transmission Simulator (HYDREMATS), a coupled hydrology and agent-based entomology model. The combined model uses environmental data including rainfall, temperature, and topography to simulate malaria prevalence and level of acquired immunity in the human population. The model is used to demonstrate the effect of acquired immunity on malaria prevalence in two Niger villages that are hydrologically and entomologically very different. Simulations are conducted for the year 2006 and compared to malaria prevalence observations collected from the two villages. Blood smear samples from children show no clear difference in malaria prevalence between the two villages despite pronounced differences in observed mosquito abundance. The similarity in prevalence is attributed to the moderating effect of acquired immunity, which depends on prior exposure to the parasite through infectious bites - and thus the hydrologically determined mosquito abundance. Modelling the level of acquired immunity can affect village vulnerability to climatic anomalies. The model presented has a novel structure constituting a mechanistic link between spatial and temporal environmental variability and village-scale malaria transmission. Incorporating acquired immunity into the model has allowed simulation of prevalence in the two villages, and isolation of the effects of acquired immunity in dampening the difference in prevalence between the two villages. Without these effects, the difference in prevalence between the two villages would have been significantly larger in response to the large differences in mosquito populations and the associated biting rates.
    Parasites & Vectors 08/2013; 6(1):226. DOI:10.1186/1756-3305-6-226 · 3.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Le Niger a adopté une nouvelle politique thérapeutique du paludisme en 2005. Elle recommande l’artémether luméfantrine (AL) en traitement du paludisme simple, la sulfadoxine pyriméthamine (SP) en traitement préventif intermittent et le retrait de la chloroquine (CQ). Pourtant, la chloroquine continue d’être prescrite et la sulfadoxine pyriméthamine est fréquemment utilisée pour traiter les enfants. Une étude comparative, randomisée, à trois bras aveugles de l’efficacité de l’artémether luméfantrine, la sulfadoxine pyriméthamine et la chloroquine est réalisée à Gaya. L’objectif de l’étude est d’évaluer l’efficacité des trois médicaments. Cette étude a porté sur 208 enfants. Le protocole OMS/2003 est utilisé. Les familles alléliques RO33 et MAD20 du marqueur msp1 puis 3D7 et FC27 du marqueur msp2 sont utilisées pour distinguer réinfestations et recrudescences. 93.6% des patients traités à l’artémether luméfantrine ont une réponse clinique et parasitologique adéquate contre 82.8% des patients traités à la sulfadoxine pyriméthamine et 72% des patients traités à la chloroquine. La différence d’efficacité est statistiquement significative (p=0.04). Au vue de ces résultats, il serait judicieux de retirer la chloroquine. La sulfadoxine pyriméthamine doit être réservée exclusivement aux femmes enceintes. L’artémether luméfantrine doit être prescrit en traitement de première intention.
  • Maman Laminou Ibrahim
    Malaria Journal 01/2013; · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The health authorities of Niger have implemented several malaria prevention and control programmes in recent years. These interventions broadly follow WHO guidelines and international recommendations and are based on interventions that have proved successful in other parts of Africa. Most performance indicators are satisfactory but, paradoxically, despite the mobilization of considerable human and financial resources, the malaria-fighting programme in Niger seems to have stalled, as it has not yet yielded the expected significant decrease in malaria burden. Indeed, the number of malaria cases reported by the National Health Information System has actually increased by a factor of five over the last decade, from about 600,000 in 2000 to about 3,000,000 in 2010. One of the weaknesses of the national reporting system is that the recording of malaria cases is still based on a presumptive diagnosis approach, which overestimates malaria incidence. An extensive nationwide survey was carried out to determine by microscopy and RDT testing, the proportion of febrile patients consulting at health facilities for suspected malaria actually suffering from the disease, as a means of assessing the magnitude of this problem and obtaining a better estimate of malaria morbidity in Niger. In total, 12,576 febrile patients were included in this study; 57% of the slides analysed were positive for the malaria parasite during the rainy season, when transmission rates are high, and 9% of the slides analysed were positive during the dry season, when transmission rates are lower. The replacement of microscopy methods by rapid diagnostic tests resulted in an even lower rate of confirmation, with only 42% of cases testing positive during the rainy season, and 4% during the dry season. Fever alone has a low predictive value, with a low specificity and sensitivity. These data highlight the absolute necessity of confirming all reported malaria cases by biological diagnosis methods, to increase the accuracy of the malaria indicators used in monitoring and evaluation processes and to improve patient care in the more remote areas of Niger. This country extends over a large range of latitudes, resulting in the existence of three major bioclimatic zones determining vector distribution and endemicity. This survey showed that the number of cases of presumed malaria reported in health centres in Niger is largely overestimated. The results highlight inadequacies in the description of the malaria situation and disease risk in Niger, due to the over-diagnosis of malaria in patients with simple febrile illness. They point out the necessity of confirming all cases of suspected malaria by biological diagnosis methods and the need to take geographic constraints into account more effectively, to improve malaria control and to adapt the choice of diagnostic method to the epidemiological situation in the area concerned. Case confirmation will thus also require a change in behaviour, through the training of healthcare staff, the introduction of quality control, greater supervision of the integrated health centres, the implementation of good clinical practice and a general optimization of the use of available diagnostic methods.
    Malaria Journal 03/2012; 11:89. DOI:10.1186/1475-2875-11-89 · 3.49 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Malaria, with its width, its gravity and its economic and social consequences remains a major public health problem in tropical countries like Niger. These consequences come to be added the simultaneous or cross résistance of P.falciparum to currents drugs. The National Malaria Programme of Niger adopted artemether-lumefantrine (COARTEM®) in treatment of uncomplicated malaria in 2005. We evaluated the efficacy and safety of artémether-luméfantrine in the treatment of children less than 5 years at Gaya, Tessaoua and Agades, three sentinels’ sites of Niger. Objectives: The main objective of the study is to evaluate the efficacy and the safety of COARTEM® in the treatment of uncomplicated P.falciparum malaria in Niger. Methodology: It is a multicentric, prospective, descriptive and open study with only one arm to evaluate the efficacy and safety of artemether-lumefantrine in children less than 5 years suffering from uncomplicated malaria in Niger. OMS/2003 protocol was used. Results: 389 children were consulted and 199 children were followed for 28 days. 81 children are from Gaya, 70 from Tessaoua and 48 from Agades. After PCR, the clinical and parasitological adequate response (CPAR) of children less than 5 years is 92%. The CPAR is 96.3% at Tessaoua, 94,1% at Agades and 89.6% at Gaya. The difference of response between the three sentinels sites is not significant (p>0 05). Before PCR, the clinical and parasitological adequate response was 88.8%. The COARTEM® is well tolerated. No undesirable effect was observed during the study. Conclusion: COARTEM® is an effective drug, which reduces significantly parasitic and clinical symptoms of malaria. It can be prescribed in treatment of uncomplicated malaria as public health ministry of Niger recommends. COARTEM® is also safety and well tolerated by the patients.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ORAL PRESENTATION Open Access Controlling malaria in Niger with bednets: how to take the Big Picture Duchemin Jean-Bernard1,2*, Czeher Cyrille1, Labbo Rabiou1, Ibrahim M Lamine1, Hoyer Stefan3, Jeanne Isabelle1 From Parasite to Prevention: Advances in the understanding of malaria Edinburgh, UK. 20-22 October 2010 Background In December 2005 free long lasting insecticidal nets were distributed to mothers of children under five in a nation-wide scheme in Niger. More than 2 million bed nets were distributed, increasing the ownership of insecticide treated bed nets more than tenfold. Materials and methods Our team was in charge of the malaria survey. The malaria cases were reported through a network of 44 sites across the country. Malaria transmission was surveyed in 12 villages in the Sahel, as it was deemed the most variable zone. Results and discussion During the first year of follow-up, vector dynamics showed an overall decrease in malaria transmission, but this was highly variable from village to village. Indeed, the second year of survey showed a return to transmission levels close to the pre-intervention period. A study of microsatellite markers showed no modification of the genetic structure in the two malaria vectors An. gambiae and An. arabiensis. However, a clear increase of the resistant allele of the kdr gene - resistence to the pyrethroid insecticide used in the bed nets - was observed. This clearly demonstrated that the main target vectors were reached. As measured by ovarian tracheoles observation, the parity rate of vectors was not significantly decreased. However, the index sporozoite decreased in the first year and remained low in the second year. Indeed, the parasite prevalence and the gametocyte carriage were shown decreasing in the children under five. This continued in 2007 as the National Malaria Control Program provided free artemisinin-based combination therapies as first line treatment for malaria in children under five. The national survey network showed a decrease in malaria cases, as confirmed in our sentinelle sites. However the biological confirmation of cases by HRP2 plasmodial antigen research has increased during the two years of follow-up. This could be explained by the more accurate diagnosis by peripheral health personal with the help of rapid diagnostic tests. Conclusion Our survey system allowed the report of the malaria evolution during that important period of control reinforcement in Niger. The causative impact was difficult to confirm because several lines of malaria control have been successively implemented. Moreover, the high climatic variability in this zone needs to be taken in account in the analysis. Despite these difficulties our data reinforce the importance of malaria monitoring through multidisciplinary studies to the benefit of control operations. Acknowledgements Funded by the Global Fund and the World Health Organization. Author details 1CERMES, BP 10887, Niamey, Niger. 2Genetics and Genomics Insect Vectors Unit, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France. 3Global Malaria Programme, World Health Organization, 20 Avenue Appia, CH 1211 Geneva 27, Switzerland. Published: 20 October 2010 doi:10.1186/1475-2875-9-S2-O12 Cite this article as: Jean-Bernard et al.: Controlling malaria in Niger with bednets: how to take the Big Picture. Malaria Journal 2010 9(Suppl 2):O12. 1CERMES, BP 10887, Niamey, Niger Full list of author information is available at the end of the article Jean-Bernard et al. Malaria Journal 2010, 9(Suppl 2):O12 http://www.malariajournal.com/content/9/S2/O12 © 2010 Jean-Bernard et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Malaria Journal 01/2010; 9(2-9(Suppl 2):O12). DOI:10.1186/1475-2875-9-S2-O12 · 3.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasmodium falciparum resistance to drugs remains a major public health issue in Niger. The therapeutic failure index for chloroquine and sulphadoxine-pyrimethamine are, respectively 20% and 21.9%. In December 2005, the National Malaria Control Programme promoted the use of artemisinin combination therapy (ACT) as first-line treatment of the uncomplicated malaria cases. Recently, studies have shown a relationship between the SERCA PfATPase6 gene and artemisinin efficacy, and pointed it out as a potential molecular marker for resistance. The goal of this work was to describe the baseline polymorphism of PfATPase6 gene in Niger, at a time when the national implementation of the ACT policy had just begun. The DNA polymorphism of the PfATPase6 gene of 87 P. falciparum samples from Niger was analysed by sequencing. The links between the mutation occurrence and environment and human host factors were tested by bivariate analysis. The P. falciparum PfATPase6 gene presented polymorphisms at codons 537, 561, 569, 630, 639, 716 levels. All the mutations found were rare, except the PfATPaseN569K found in 17.2% of samples. No associated factor has been observed. The P. falciparum PfATPase gene is polymorphic at the 569 codon. As ACT is getting more and more used, the PfATPase6 gene polymorphism needs to be monitored in association with phenotypic - in vivo and/or in vitro - drug efficacy tests.
    Malaria Journal 03/2009; 8:28. DOI:10.1186/1475-2875-8-28 · 3.49 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • [Show abstract] [Hide abstract]
    ABSTRACT: Over the last years, significant progress has been made in the comprehension of the molecular mechanism of malaria resistance to drugs. Together with in vivo tests, the molecular monitoring is now part of the survey strategy of the Plasmodium sensitivity. Currently, DNA-microarray analysis allows the simultaneous study of many single nucleotide polymorphisms (SNP) of Plasmodium isolates. In December 2005, the International Federation of the Red Cross distributed two million three hundred thousand long-lasting insecticide nets to pregnant women and mothers of under five years children in the whole Niger. Then, Niger adopted artemisinin-based combination therapy as first-line treatment. Thirty four SNPs of pfcrt, pfdhfr, pfdhps, pfmdr and pfATPase were analysed by DNA-microarray and PCR/RFLP in two villages - Zindarou and Banizoumbou - with different durations of malaria transmission. The main objective of the study was to measure the dynamics of Plasmodium falciparum resistant strains and associated factors. This study shows a global and clear increase of the drug-resistance associated molecular markers frequencies during a relatively short-time period of four years. Markers associated with resistance to chloroquine and sulphonamids were more frequently found in the short transmission zone than in the long transmission one. The pfcrt76T mutation is significantly more present at Banizoumbou than Zindarou (38.3% vs 25.2%, p = 0.013). This work allowed the screening of several field strains for five SNPs of PfATPase6 gene. The pfATPase6S769N, candidate mutation of resistance to artemisinin was not found. However the pfATPsaeA623E mutation was found in 4.7% of samples. A significant increase of several SNPs frequencies was highlighted over a four-year period. The polymorphism of five PfATPase6 gene SNPs was described. The global, large and fast increase of the molecular resistance is discussed in the context of current changes of health policy and malaria control in Niger.
    Malaria Journal 03/2009; 8:32. DOI:10.1186/1475-2875-8-32 · 3.49 Impact Factor
    This article is viewable in ResearchGate's enriched format
  • Source
    IBRAHIM M.laminou
    [Show abstract] [Hide abstract]
    ABSTRACT: La résistance de P.falciparum à la chloroquine est associée à une forte augmentation de la mortalité en Afrique tropicale où le risque de décès palustre chez les enfants de 0 à 9 ans a été multiplié par 2 à 5 dans la plupart des contextes épidémiologiques. Au Niger, les données sur la chimiosensibilité aux antipaludiques sont fragmentaires et les récentes études in vivo effectuées à Niamey font état d’un niveau préoccupant de 20% d’échec clinique et parasitologique chez les enfants de 1-5 ans. A l’instar de certains pays d’Afrique de l’Est et d’Afrique centrale qui ont remplacé la chloroquine par l’association sulfadoxine-pyriméthamine et plus récemment par les combinaisons thérapeutiques à base d’artémisinine, le ministère de la santé publique du Niger vient d’adopter une combinaison thérapeutique à base d’artémisinine (COARTEM®) pour le traitement de première intention du paludisme simple sans toutefois retirer la chloroquine et l’association sulfadoxine-pyriméthamine en traitement préventif intermittent chez la femme enceinte. En raison de l’adoption des ACT et de la distribution massive de moustiquaires imprégnées, il nous a paru opportun de surveiller la résistance à la chloroquine, la pyriméthamine, les sulfamides et les ACT en utilisant les récentes avancées technologiques de la biologie moléculaire. L’objectif général de ce travail est d’étudier la résistance moléculaire de P.falciparum aux antipaludiques selon le profil clinique des porteurs (accès palustre grave, simple et porteurs asymptomatiques) et selon le faciès de transmission anophélienne (stable vs instable) au Niger. La recherche de mutations ponctuelles (Single Nucleotid Polymorphism ou SNPs) associées à la résistance à la chloroquine (Pfcrt), à la sulfadoxine pyriméthamine (Dhfr et dhps) et à l’artémisinine (pf ATPase) a été effectuée par PCR/RLFP, puces à ADN et par séquençage. La prévalence de la mutation pfcrt76T-corrélée à la chloroquinorésistance- est de 45.4% à l’hôpital National de Niamey. Celle de la mutation pfdhfr108N- corrélée à la pyriméthaminorésistance- est de 61.9%. La mutation dhfr108N est positivement corrélée à l’anémie sévère (p=0.002). En effet, la moyenne de l’hémoglobine tend à baisser significativement de 6.59g/dl à 5.40g/dL en présence de cette mutation (n=84, p=0.023). Les souches sauvages pfcrtK76 par contre sont associées au neuropaludisme et aux symptômes nerveux tels la convulsion et le coma (p=0.043). Le risque de décès par neuropaludisme diminue (p=0.012) en présence de pfcrt76T. La cartographie de la résistance moléculaire a été établie dans la vallée du fleuve Niger où la prévalence de la mutation K76T du gène pfcrt est de 50,8% et celle de la mutation S108N du gène pfdhfr est de 57.7%. L’analyse de 34 SNPs de cinq marqueurs de résistance (pfcrt, pfdhfr, pfdhps, pfmdr et pfATPase) entre deux villages (Banizoumbou et Zindarou) où l’intensité de transmission est différente, révèle que la résistance est plus forte lorsque la transmission est faible. La prévalence de la mutation pfcrtK76T est de 38.3% à Banizoumbou contre 25.2% à Zindarou (p=0.012). La méthode des puces à ADN a révélé une dynamique marquée dans la fréquence des mutations conférant la résistance à plusieurs molécules antipaludiques au cours des 4 ans d’étude. Au moment où la plupart des états Africain ont adoptés les ACT, un screening moléculaire du gène pfATPase est d’une grande importance. Le polymorphisme du gène pfATPase6 a été décrit pour la première fois au Niger où 6 mutations dont 3 nouvelles (537, 561, 716) ont été mises en évidence. La mutation pfATPaseSer769Asn candidate de la résistance à l’artémisinine est absente des souches de Plasmodium falciparum séquencées. Parmi les 6 SNPs du gène pfATPase décrits, la mutation PfATPaseAsn569Lys est la plus fréquente (17.2%). Cette mutation n’est pas neutre. Serait-elle la cible de cette résistance à l’artémisinine ? Des investigations fonctionnelles futures sont indispensables pour élucider son rôle et mettre en place des outils moléculaires de son diagnostic.
    Biologie, Université Cheick Anta Diop, 01/2009, Degree: PhD.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Plasmodium falciparum resistance to chloroquine first arose in Africa 25 years ago. Nowadays most of African malaria control programmes have switched their first-line treatment of uncomplicated malaria cases towards artemisinin derivatives combination. After WHO guidelines, a survey network for malaria treatment resistance has been set up in the Niger valley around Niamey since December 2004. The association of the Niger national malaria control programme with the CERMES research center allowed collecting of samples from both health centers and hospitals of this region. Blood finger-pricks on filter papers were tested for detection of plasmodial antigen in health center without biological diagnosis capacity. Specimens found positive either in hospital laboratory or by using antigen method were tested by PCR/RFLP to detect K76T mutations on the pfcrt gene and S108N mutation on the pfdhfr gene. This simple procedure allows the screening of a large number of specimens. Moreover, a spatial distribution of mutations and evidence of resistance clusters were searched integrating the data in a geographic information system. The 76T mutation of pfcrt and 108N of pfdhfr were respectively found in 50.8% and 57% of the specimens tested. No statistically significant difference was found according to the level of sanitary formations or the age of the patients. No resistance cluster was identified and the prevalence of mutation seems homogeneous in the zone. By completing the clinical efficacy studies we think that our simple method for collecting and testing blood samples associated with clinical efficacy studies may be useful for building a network of malaria drug resistance in Africa.
    Bulletin de la Société de pathologie exotique 03/2008; 101(1):47-9.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the framework of the monitoring and evaluation of the Nigerian schistosomiasis and soil-transmitted helminth control programme, a follow-up of children took place in eight sentinel sites. The objective of the study was to assess the evolution of Schistosoma haematobium infection and anaemia in schoolchildren after a single administration of praziquantel (PZQ) and albendazole. Pre-treatment examination and follow-up at one year post-treatment of schoolchildren aged 7, 8, and 11 years, including interview, urine examination, ultrasound examination of the urinary tract, and measurement of haemoglobin. Before treatment, the overall prevalence of S. heamatobium infection was 75.4% of the 1,642 enrolled children, and 21.8% of children excreted more than 50 eggs/10 ml urine. Prevalence increased with age. The overall prevalence of anaemia (haemoglobin <11.5 g/dl) was 61.6%, decreasing significantly with increasing age. The mean haemoglobinemia was 11 g/dl. In bivariate analysis, anaemia was significantly more frequent in children infected with S. haematobium, although it was not correlated to the intensity of infection. Anaemia was also associated with micro-haematuria and to kidney distensions. In a sub-sample of 636 children tested for P. falciparum infection, anaemia was significantly more frequent in malaria-infected children. In multivariate analysis, significant predictors of anaemia were P. falciparum infection, kidney distension, and the village. One year after a single-dose praziquantel treatment (administered using the WHO PZQ dose pole) co-administered with albendazole (400 mg single dose) for de-worming, the prevalence of S. haematobium infection was 38%, while the prevalence of anaemia fell to 50.4%. The mean haemoglobinemia showed a statistically significant increase of 0.39 g/dl to reach 11.4 g/dl. Anaemia was no longer associated with S. haematobium or to P. falciparum infections, or to haematuria or ultrasound abnormalities of the urinary tract. The high prevalence of anaemia in Nigerian children is clearly a result of many factors and not of schistosomiasis alone. Nevertheless, treatment of schistosomiasis and de-worming were followed by a partial, but significant, reduction of anaemia in schoolchildren, not explainable by any other obvious intervention.
    PLoS Neglected Tropical Diseases 02/2008; 2(5):e241. DOI:10.1371/journal.pntd.0000241 · 4.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Drug resistance has been shown to increase malaria mortality and morbidity in both community- and hospital-based studies. We investigated the association between two Plasmodium falciparum drug resistance-related molecular markers and clinical profiles of severe malaria in children hospitalised in Niger. PCR-RFLP analysis showed that the codon 108 mutation of the pfdhfr gene was positively linked to severe malarial anaemia. These findings are consistent with persistent parasite infection leading to unbalanced anaemia in young children. No significant relationship was found between the molecular markers and hypoglycaemia or hyperparasitaemia. Conversely, the pfcrt T76 mutation was found to be negatively associated with cerebral malaria and neurological symptoms, such as convulsions and coma. These results have implications for the strain-specific virulence hypothesis and for parasite fitness and evolution. Our findings are discussed in regard to the local malaria transmission level.
    Microbes and Infection 05/2007; 9(5):599-604. DOI:10.1016/j.micinf.2007.02.003 · 2.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the framework of the Human Immunodeficiency Virus (HIV) surveillance, seroprevalence and behavioural survey was conducted in 2002 in Dirkou, a place of concentration of female sex workers (FSW) in Niger The global HIV seroprevalence found was 50% (CI at 95%: 40.6-59.36%). The behavioural survey revealed that 98% of FSW had heard about HIV whereas 78.7% know at least one HIV transmission way and 76.9% know at least one HIV prevention means. Only 33.3% declared using condom, what show that sensitisation efforts are needed to induce a behaviour change in FSW and their clients.
    Bulletin de la Société de pathologie exotique 04/2006; 99(1):49-51.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Malaria takes a heavy toll in Niger, one of the world's poorest countries. Previous evaluations conducted in the context of the strategy for the Integrated Management of Childhood Illness, showed that 84% of severe malaria cases and 64 % of ordinary cases are not correctly managed. The aim of this survey was to describe epidemiological, clinical and biological features of malaria among <5 year-old children in the paediatric department of the National Hospital of Niamey, Niger's main referral hospital. The study was performed in 2003 during the rainy season from July 25th to October 25th. Microscopic diagnosis of malaria, complete blood cell counts and measurement of glycaemia were performed in compliance with the routine procedure of the laboratory. Epidemiological data was collected through interviews with mothers. 256 children aged 3-60 months were included in the study. Anthropometrics and epidemiological data were typical of a very underprivileged population: 58% of the children were suffering from malnutrition and all were from poor families. Diagnosis of malaria was confirmed by microscopy in 52% of the cases. Clinical symptoms upon admission were non-specific, but there was a significant combination between a positive thick blood smear and neurological symptoms, and between a positive thick blood smear and splenomegaly. Thrombopaenia was also statistically more frequent among confirmed cases of malaria. The prevalence of severe malaria was 86%, including cases of severe anaemia among < 2 year-old children and neurological forms after 2 years of age. Overall mortality was 20% among confirmed cases and 21% among severe cases. The study confirmed that malaria was a major burden for the National Hospital of Niamey. Children hospitalized for malaria had an underprivileged background. Two distinctive features were the prevalence of severe malaria and a high mortality rate. Medical and non-medical underlying factors which may explain such a situation are discussed.
    Malaria Journal 02/2005; 4(1):10. DOI:10.1186/1475-2875-4-10 · 3.49 Impact Factor
    This article is viewable in ResearchGate's enriched format

27 Following View all

26 Followers View all