Impacts de l'environnement sur les diarrhées infantiles à Madagascar (Analyse du risque Campylobacter)

Les maladies diarrhéiques demeurent une cause majeure de mortalité infantile dans les pays en développement (PED). Du fait de l'insuffisance des plateaux techniques, les diagnostics étiologiques sont rarement réalisés et les traitements sont alors probabilistes. A Madagascar les données sur les diarrhées sont souvent parcellaires et anciennes. Le Réseau de surveillance sentinelle développé par l'Institut Pasteur de Madagascar à partir de 2007 nous a permis d'étudier la distribution spatio-temporelle des consultations pour diarrhée. Mais cette surveillance syndromique n'est pas couplée systématiquement à une surveillance biologique. Pour étudier les agents étiologiques des diarrhées, nous avons réalisé une enquête cas-témoins menée en 2008-2009 en milieu communautaire, chez les enfants de moins de 5 ans dans 14 districts. Nous avons pu identifier au moins un pathogène chez plus de la moitié des enfants (55%), avec une prédominance des étiologies parasitaires (37,2% des diarrhées), suivies par les bactéries (15%) puis les virus (6,7% de rotavirus). Les parasites ont été les seules étiologies pour lesquelles une pathogénicité a pu être mise en évidence. Parmi les étiologies bactériennes, l'infection à Campylobacter a été la plus fréquente (9,5%). Pour analyser le rôle de Campylobacter et les effets des facteurs environnementaux dans la survenue des diarrhées infantiles, nous avons initié et coordonné depuis 2010 une étude de cohorte dynamique d'enfants inclus avant l'âge de 24 mois et suivis jusqu'à l'âge de 36 mois à Moramanga, site où la prévalence de Campylobacter a été la plus élevée au cours de l'étude de 2008 (20,6%). Une surveillance des diarrhées a été menée 2 fois par semaine et les portages asymptomatiques évalués à l'inclusion et tous les 2 mois. Une étude de portage familial a été mise en œuvre ainsi qu'un suivi coprologique bi-annuel de la population avicole, des points d'eaux collectifs et de l'eau de boisson des familles. La recherche de Campylobacter chez les volailles portait sur les écouvillonnages rectaux. De janvier 2010 à mai 2012, 508 enfants correspondant à 256 346 enfant-jour ont participé à l'étude. La prévalence globale d'isolement de Campylobacter a été de 9,3%. Plus de 2/5 des enfants (43,3%) ont eu au moins un épisode d'infection à Campylobacter au cours de leur suivi. Les taux d'incidence annuelle des diarrhées ainsi que des infections symptomatiques ont été faibles, respectivement de 0,7 épisode /enfant et de 5,8 épisodes/100 enfant pouvant s'expliquer par le faible niveau d'exposition environnementale des enfants. Nous avons pu étudier l'importance des facteurs liés à l'hôte comme l'âge. Le pic d'infection à Campylobacter se situe entre 18 à 29 mois, celui des diarrhées entre 6 à 11 mois puis diminue ensuite. La 1ère infection à Campylobacter a été toujours pathogène chez les plus jeunes. Elle se situe vers le 8ème mois de la vie pour 10% d'entre eux. Les réinfections se font à des distances différentes de l'événement initial en fonction de l'âge. Ce profil d'infection pourrait traduire une compétence immunitaire différente selon l'âge et/ou une immunité acquise au cours du temps suite aux expositions répétées des enfants. L'environnement pourrait avoir un effet indirect dans l'entretien d'une immunité protectrice s'exprimant par un taux élevé d'infection asymptomatique. Il apparaît nécessaire de poursuivre des études de cohorte dans des zones à plus fort risque de transmission avec des données immunologiques car la compréhension actuelle des interactions entre l'hôte, le Campylobacter et l'environnement ne permet pas d'expliquer la variabilité de l'expression clinique de l'infection.Diarrheal diseases remain a major cause of infant mortality in developing countries (DCs). Due to the lack of technical platforms, the etiologic diagnoses are rarely made and treatments are then probabilistic. In Madagascar data on diarrhea are often fragmented and old. The sentinel surveillance network developed by the Institut Pasteur of Madagascar from 2007 allowed us to study the spatial and temporal distribution of consultations for diarrhea. But this syndromic surveillance cannot be coupled to biological monitoring for many diseases. In this context, we have no information on the causative agents of diarrhea. To achieve the coupling of syndromic and etiologic data, we performed a case-control study conducted in 2008-2009 in children less than 5 years in 14 districts. We have identified at least one pathogen in more than half of the children (55%), with a predominance of parasitic etiologies (37.2% diarrhea), followed by bacteria (15%) and viruses (6.7% rotavirus). Parasites were the only etiologies for which pathogenicity has been demonstrated. Among the bacterial etiologies, Campylobacter infection was the most common (9.5%). To better understand the role of Campylobacter in the occurrence of diarrhea in children and analyze the effect of environmental factors, we initiated and coordinated a dynamical cohort study including of children before the age of 24 months and followed up till the age of 36 months in Moramanga site, where the prevalence of Campylobacter was highest during the 2008 study (20.6%). Diarrhea surveillance was conducted two times per week and asymptomatic carriers assessed at baseline and every 2 months. A family study has been implemented and bi-annual stool follow-up in poultry population, water points and community drinking water for families. Campylobacter monitoring in poultry focused on rectal swabs. From January 2010 to May 2012, 508 children - corresponding to 256,346 child days -participated in the study. The overall prevalence of Campylobacter isolation was 9.3%. More than two fifths of children (43.3%) had at least one episode of Campylobacter during follow-up. The annual incidence of diarrhea and symptomatic infections were low, respectively 0.7 episodes / child and 5.8 episodes /100 children, can be explained by the low level of environmental exposure of children. We have studied the role of host factors such as age. The peak of Campylobacter infection is between 18 to 29 months, the diarrhea between 6 to 11 months then decreases. The first Campylobacter infection was always pathogen in the youngest children. It happens to the eighth month of life for 10% of them. Reinfections are at different distances from the initial event according to the age. This pattern of infection may reflect a variation of the immune competence according the age and / or acquired immunity over time after repeated exposure of the children. The local environment may have an indirect impact on maintaining protective immunity expressed by a high rate of asymptomatic infection. However, it is necessary to continue cohort study with immunologic data in a high risk transmission area as the current understanding of the interactions between the host, the environment and Campylobacter does not explain the variability of the clinical expression of infection.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Remote sensing and urban malaria: radar Envisat contribution for the determination of potential Anopheles breeding site in Antananarivo (Madagascar)

International audienceMost studies of anopheline mosquito larval ecology have been done in rural settings. However, latest data based on two cross-sectional surveys in Antananarivo, the capitol of Madagascar, shown low rate of malaria cases among febrile episodes but autochthonous malaria cases exist. Anopheles funestus constitutes the main vector of malaria in the highlands of Madagascar. This paper described the determination of their potential breeding site using remotely sensed data. A supervised classification by the classical method of maximum likelihood was used for enhanced thematic mapper image of Landsat 7. Overall accuracy of the classification was 86% and kappa index was 0.835. Determination of landscape change by subtraction of images acquired on January and July was carried out for the Advanced Synthetic Aperture Image Precision images of Envisat. Increased backscatter coefficient between the two periods made possible to raise ambiguity between rice fields and other vegetation. That may improve the determination of potential anopheles breeding sites

A systematic review of the clinical profile of patients with bubonic plague and the outcome measures used in research settings

BACKGROUND: Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone-no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease-how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.METHODOLOGY/PRINCIPAL FINDINGS: This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints-the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.CONCLUSIONS/SIGNIFICANCE: This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial's results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.</p

Susceptibility of Plasmodium falciparum to the drugs used to treat severe malaria (quinine) and to prevent malaria (mefloquine, cycloguanil) in Comoros Union and Madagascar

Objectives. To monitor the sensitivity of Plasmodium falciparum to the drugs used to treat severe malaria and to prevent malaria in Comoros and Madagascar. Design. We used the in vitro isotopic method to test the sensitivity of P. falciparum to quinine, mefloquine and cycloguanil.Results. We tested fresh isolates of P. falciparum, collected from patients living in urban, suburban and rural areas and suffering from uncomplicated malaria in 2001, against at least one of the antimalarials cited above. In both countries all of the successfully tested isolates were sensitive to quinine (N = 243) and to cycloguanil (N = 67). The mean IC50 ranged from 85.7 to 133.7 nM for quinine. For cycloguanil, the mean IC50 ranged from 1.4 to 20.2 nM and the highest IC50 value (102.5 nM) was recorded in Comoros. Only 0.9% (1/110) of the informative isolates from Madagascar were mefloquineresistant (0/18 in Comoros). The mefloquine mean IC50s were 8.2 nM, 14.1 nM and 11.6 nM respectively in the rural, suburban and urban areas of Madagascar, and 5.9 nM in Comoros. A positive correlation was found between quinine and mefloquine IC50s (N = 127, r = 0.48, p &lt; 10 6 ), but in vitro mefloquine was 6 -16 times more potent than quinine. No correlation was noticed between the activities of quinine and cydoguanil or between the activities of mefloquine and cycloguaniL Conclusion. We therefore advocate the use of a full-course regimen of quinine, as recommended by the World Health Organisation (WHO), to treat above all severe malaria in Madagascar and Comoros. Our results also demonstrate that the use of mefloquine- and cycloguanil-based antimalarials is still justified to prevent malaria in both countries, mainly in the case of travellers

Cutting sequences on Bouw-Moeller surfaces : an S-adic characterization.

Résumé. On considère un codage symbolique des géodésiques sur une famille de surfaces de Veech (surfaces de translation riches en symétries affines) récemment découverte par Bouw et Möller. Ces surfaces, comme l’a remarqué Hooper, peuvent être réalisées en coupant et collant une collection de polygones semi-réguliers. Dans cet article, on caractérise l’ensemble des suites symboliques (“suites de coupage”) qui correspondent au codage de trajectoires linéaires, à l’aide de la suite des côtés des polygones croisés. On donne une caractérisation complète de l’adhérence de l’ensemble des suites de coupage, dans l’esprit de la caractérisation classique des suites sturmiennes et de la récente caractérisation par Smillie-Ulcigrai des suites de coupage des trajectoires linéaires dans les polygones réguliers. La caractérisation est donnée en termes d’un système fini de substitutions (connu aussi sous le nom de présentation S-adique), réglé par une transformation unidimensionnelle qui ressemble à l’algorithme de fraction continue. Comme dans le cas sturmien et dans celui des polygones réguliers, la caractérisation est basée sur la renormalisation et sur la définition d’un opérateur combinatoire de dérivation approprié. Une des nouveautés est que la dérivation se fait en deux étapes, sans utiliser directement les éléments du groupe de Veech, mais en utilisant un difféomorphisme affine qui envoie une surface de Bouw-Möller vers sa surface “duale”, qui est dans le même disque de Teichmüller. Un outil technique utilisé est la présentation des surfaces de Bouw-Möller par les diagrammes de Hooper. ABSTRACT. We consider a symbolic coding for geodesics on the family of Veech surfaces (translation surfaces rich with affine symmetries) recently discovered by Bouw and Möller. These surfaces, as noticed by Hooper, can be realized by cutting and pasting a collection of semi-regular polygons. We characterize the set of symbolic sequences (cutting sequences) that arise by coding linear trajectories by the sequence of polygon sides crossed. We provide a full characterization for the closure of the set of cutting sequences, in the spirit of the classical characterization of Sturmian sequences and the recent characterization of Smillie-Ulcigrai of cutting sequences of linear trajectories on regular polygons. The characterization is in terms of a system of finitely many substitutions (also known as an S-adic presentation), governed by a one-dimensional continued fraction-like map. As in the Sturmian and regular polygon case, the characterization is based on renormalization and the definition of a suitable combinatorial derivation operator. One of the novelties is that derivation is done in two steps, without directly using Veech group elements, but by exploiting an affine diffeomorphism that maps a Bouw- Möller surface to the dual Bouw-Möller surface in the same Teichmüller disk. As a technical tool, we crucially exploit the presentation of Bouw-Möller surfaces via Hooper diagrams

Determining areas that require indoor insecticide spraying using Multi Criteria Evaluation, a decision-support tool for malaria vector control programmes in the Central Highlands of Madagascar

BACKGROUND: The highlands of Madagascar present an unstable transmission pattern of malaria. The population has no immunity, and the central highlands have been the sites of epidemics with particularly high fatality. The most recent epidemic occurred in the 1980s, and caused about 30,000 deaths. The fight against malaria epidemics in the highlands has been based on indoor insecticide spraying to control malaria vectors. Any preventive programme involving generalised cover in the highlands will require very substantial logistical support. We used multicriteria evaluation, by the method of weighted linear combination, as basis for improved targeting of actions by determining priority zones for intervention. RESULTS: Image analysis and field validation showed the accuracy of mapping rice fields to be between 82.3% and 100%, and the Kappa coefficient was 0.86 to 0.99. A significant positive correlation was observed between the abundance of the vector Anopheles funestus and temperature; the correlation coefficient was 0.599 (p < 0.001). A significant negative correlation was observed between vector abundance and human population density: the correlation coefficient was -0.551 (p < 0.003). Factor weights were determined by pair-wise comparison and the consistency ratio was 0.04. Risk maps of the six study zones were obtained according to a gradient of risk. Nine of thirteen results of alert confirmed by the Epidemiological Surveillance Post were in concordance with the risk map. CONCLUSION: This study is particularly valuable for the management of vector control programmes, and particularly the reduction of the vector population with a view to preventing disease. The risk map obtained can be used to identify priority zones for the management of resources, and also help avoid systematic and generalised spraying throughout the highlands: such spraying is particularly difficult and expensive. The accuracy of the mapping, both as concerns time and space, is dependent on the availability of data. Continuous monitoring of malaria transmission factors must be undertaken to detect any changes. A regular case notification allows risk map to be verified. These actions should therefore be implemented so that risk maps can be satisfactorily assessed

Longitudinal survey of malaria morbidity over 10 years in Saharevo (Madagascar): further lessons for strengthening malaria control

<p>Abstract</p> <p>Background</p> <p>Madagascar has been known for having bio-geo-ecological diversity which is reflected by a complex malaria epidemiology ranging from hyperendemic to malaria-free areas. Malaria-related attacks and infection are frequently recorded both in children and adults living in areas of low malaria transmission. To integrate this variability in the national malaria control policy, extensive epidemiological studies are required to up-date previous records and adjust strategies.</p> <p>Methods</p> <p>A longitudinal malaria survey was conducted from July 1996 to June 2005 among an average cohort of 214 villagers in Saharevo, located at 900 m above the sea. Saharevo is a typical eastern foothill site at the junction between a costal wet tropical area (equatorial malaria pattern) and a drier high-altitude area (low malaria transmission).</p> <p>Results</p> <p>Passive and active malaria detection revealed that malaria transmission in Saharevo follows an abrupt seasonal variation. Interestingly, malaria was confirmed in 45% (1,271/2,794) of malaria-presumed fevers seen at the health centre. All four <it>Plasmodia </it>that infect humans were also found: <it>Plasmodium falciparum</it>; <it>Plasmodium vivax</it>, <it>Plasmodium malariae </it>and <it>Plasmodium ovale</it>. Half of the malaria-presumed fevers could be confirmed over the season with the highest malaria transmission level, although less than a quarter in lower transmission time, highlighting the importance of diagnosis prior to treatment intake. <it>P. falciparum </it>malaria has been predominant (98%). The high prevalence of <it>P. falciparum </it>malaria affects more particularly under 10 years old children in both symptomatic and asymptomatic contexts. Children between two and four years of age experienced an average of 2.6 malaria attacks with <it>P. falciparum </it>per annum. Moreover, estimated incidence of <it>P. falciparum </it>malaria tends to show that half of the attacks (15 attacks) risk to occur during the first 10 years of life for a 60-year-old adult who would have experienced 32 malaria attacks.</p> <p>Conclusion</p> <p>The incidence of malaria decreased slightly with age but remained important among children and adults in Saharevo. These results support that a premunition against malaria is slowly acquired until adolescence. However, this claims for a weak premunition among villagers in Saharevo and by extension in the whole eastern foothill area of Madagascar. While the Malagasy government turns towards malaria elimination plans nowadays, choices and expectations to up-date and adapt malaria control strategies in the foothill areas are discussed in this paper.</p

Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB), an infectious disease caused by the <it>Mycobacterium tuberculosis </it>is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had a non-random spatial distribution in this setting, with clustering in the poorer areas. The aim of this study was to explore this pattern further by a Bayesian approach, and to measure the associations between the spatial variation of TB risk and national control program indicators for all neighbourhoods.</p> <p>Methods</p> <p>Combination of a Bayesian approach and a generalized linear mixed model (GLMM) was developed to produce smooth risk maps of TB and to model relationships between TB new cases and national TB control program indicators. The TB new cases were collected from records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city from 2004 to 2006. And five TB indicators were considered in the analysis: number of cases undergoing retreatment, number of patients with treatment failure and those suffering relapse after the completion of treatment, number of households with more than one case, number of patients lost to follow-up, and proximity to a DTC.</p> <p>Results</p> <p>In Antananarivo, 43.23% of the neighbourhoods had a standardized incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly higher than the average. Identified high TB risk areas were clustered and the distribution of TB was found to be associated mainly with the number of patients lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households with more than one case (SIR: 1.13, CI 95%: 1.03-1.24).</p> <p>Conclusion</p> <p>The spatial pattern of TB in Antananarivo and the contribution of national control program indicators to this pattern highlight the importance of the data recorded in the TB registry and the use of spatial approaches for assessing the epidemiological situation for TB. Including these variables into the model increases the reproducibility, as these data are already available for individual DTCs. These findings may also be useful for guiding decisions related to disease control strategies.</p

The impact of COVID-19 on clinical research for Neglected Tropical Diseases (NTDs): A case study of bubonic plague.

BACKGROUND: Among the many collaterals of the COVID-19 pandemic is the disruption of health services and vital clinical research. COVID-19 has magnified the challenges faced in research and threatens to slow research for urgently needed therapeutics for Neglected Tropical Diseases (NTDs) and diseases affecting the most vulnerable populations. Here we explore the impact of the pandemic on a clinical trial for plague therapeutics and strategies that have been considered to ensure research efforts continue. METHODS: To understand the impact of the COVID-19 pandemic on the trial accrual rate, we documented changes in patterns of all-cause consultations that took place before and during the pandemic at health centres in two districts of the Amoron'I Mania region of Madagascar where the trial is underway. We also considered trends in plague reporting and other external factors that may have contributed to slow recruitment. RESULTS: During the pandemic, we found a 27% decrease in consultations at the referral hospital, compared to an 11% increase at peripheral health centres, as well as an overall drop during the months of lockdown. We also found a nation-wide trend towards reduced number of reported plague cases. DISCUSSION: COVID-19 outbreaks are unlikely to dissipate in the near future. Declining NTD case numbers recorded during the pandemic period should not be viewed in isolation or taken as a marker of things to come. It is vitally important that researchers are prepared for a rebound in cases and, most importantly, that research continues to avoid NTDs becoming even more neglected