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Health care workers (HCWs) represent a vulnerable population during epidemic periods. Our cohort study aimed to estimate the risk of infection and associated factors among HCWs during the first wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Madagascar.A prospective cohort study was carried out in three hospitals that oversaw the first cases of COVID-19. Monthly ELISA-based serological tests were conducted, and nasopharyngeal swabs were collected in the case of symptoms linked to COVID-19 for RT-PCR analysis. Survival analyses were used to determine factors associated with SARS-CoV-2 infection.The study lasted 7 months from May 2020. We included 122 HCWs, 61.5% of whom were women. The median age was 31.9 years (IQR: 26.4-42.3). In total, 42 (34.4%) had SARS-CoV-2 infections, of which 20 were asymptomatic (47.6%). The incidence of SARS-CoV-2 infection was 9.3% (95% CI [6.5-13.2]) person-months. Sixty-five HCWs presented symptoms, of which 19 were positive by RT-PCR. When adjusted for exposure to deceased cases, infection was more frequent in HCWs younger than 30 years of age (RR = 4.9, 95% CI [1.4-17.2]).Our results indicate a high incidence of infection with SARS-CoV-2 among HCWs, with a high proportion of asymptomatic cases. Young HCWs are more likely to be at risk than others. Greater awareness among young people is necessary to reduce the threat of infection among HCWs.

The genus Henipavirus (family Paramyxoviridae) is currently comprised of seven viruses, four of which have demonstrated prior evidence of zoonotic capacity. These include the biosafety level 4 agents Hendra (HeV) and Nipah (NiV) viruses, which circulate naturally in pteropodid fruit bats. Here, we describe and characterize Angavokely virus (AngV), a divergent henipavirus identified in urine samples from wild, Madagascar fruit bats. We report the near-complete 16,740 nt genome of AngV, which encodes the six major henipavirus structural proteins (nucleocapsid, phosphoprotein, matrix, fusion, glycoprotein, and L polymerase). Within the phosphoprotein (P) gene, we identify an alternative start codon encoding the AngV C protein and a putative mRNA editing site where the insertion of one or two guanine residues encodes, respectively, additional V and W proteins. In other paramyxovirus systems, C, V, and W are accessory proteins involved in antagonism of host immune responses during infection. Phylogenetic analysis suggests that AngV is ancestral to all four previously described bat henipaviruses—HeV, NiV, Cedar virus (CedV), and Ghanaian bat virus (GhV)—but evolved more recently than rodent- and shrew-derived henipaviruses, Mojiang (MojV), Gamak (GAKV), and Daeryong (DARV) viruses. Predictive structure-based alignments suggest that AngV is unlikely to bind ephrin receptors, which mediate cell entry for all other known bat henipaviruses. Identification of the AngV receptor is needed to clarify the virus’s potential host range. The presence of V and W proteins in the AngV genome suggest that the virus could be pathogenic following zoonotic spillover.ImportanceHenipaviruses include highly pathogenic emerging zoonotic viruses, derived from bat, rodent, and shrew reservoirs. Bat-borne Hendra (HeV) and Nipah (NiV) are the most well-known henipaviruses, for which no effective antivirals or vaccines for humans have been described. Here we report the discovery and characterization of a novel henipavirus, Angavokely virus (AngV), isolated from wild fruit bats in Madagascar. Genomic characterization of AngV reveals all major features associated with pathogenicity in other henipaviruses, suggesting that AngV could be pathogenic following spillover to human hosts. Our work suggests that AngV is an ancestral bat henipavirus which likely uses viral entry pathways distinct from those previously described for HeV and NiV. In Madagascar, bats are consumed as a source of human food, presenting opportunities for cross-species transmission. Characterization of novel henipaviruses and documentation of their pathogenic and zoonotic potential are essential to predicting and preventing the emergence of future zoonoses that cause pandemics.

As the national reference laboratory for febrile illness in Madagascar, we processed samples from the first epidemic wave of COVID-19, between March and September 2020. We fit generalized additive models to cycle threshold (Ct) value data from our RT-qPCR platform, demonstrating a peak in high viral load, low-Ct value infections temporally coincident with peak epidemic growth rates estimated in real time from publicly-reported incidence data and retrospectively from our own laboratory testing data across three administrative regions. We additionally demonstrate a statistically significant effect of duration of time since infection onset on Ct value, suggesting that Ct value can be used as a biomarker of the stage at which an individual is sampled in the course of an infection trajectory. As an extension, the population-level Ct distribution at a given timepoint can be used to estimate population-level epidemiological dynamics. We illustrate this concept by adopting a recently-developed, nested modeling approach, embedding a within-host viral kinetics model within a population-level Susceptible-Exposed-Infectious-Recovered (SEIR) framework, to mechanistically estimate epidemic growth rates from cross-sectional Ct distributions across three regions in Madagascar. We find that Ct-derived epidemic growth estimates slightly precede those derived from incidence data across the first epidemic wave, suggesting delays in surveillance and case reporting. Our findings indicate that public reporting of Ct values could offer an important resource for epidemiological inference in low surveillance settings, enabling forecasts of impending incidence peaks in regions with limited case reporting.

International audience; In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult.

International audience; We conducted a national human serologic study of a hantavirus detected in Madagascar rodents using a commercial kit and a new ELISA targeting the virus. Our results suggest a conservative estimate of 2.7% (46/1,680) IgG seroprevalence. A second single-district study using the new ELISA revealed a higher prevalence (7.2%; 10/139).

International audience; Three epidemic waves of coronavirus disease-19 (COVID-19) occurred in Madagascar from March 2020 to May 2022, with a positivity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 21% to 33%. Our study aimed to identify the impact of COVID-19 on the epidemiology of seasonal respiratory viruses (RVs) in Madagascar. We used two different specimen sources (SpS). First, 2987 nasopharyngeal (NP) specimens were randomly selected from symptomatic patients between March 2020 and May 2022 who tested negative for SARS-CoV-2 and were tested for 14 RVs by multiplex real-time PCR. Second, 6297 NP specimens were collected between March 2020 and May 2022 from patients visiting our sentinel sites of the influenza sentinel network. The samples were tested for influenza, respiratory syncytial virus (RSV), and SARS-CoV-2. From SpS-1, 19% (569/2987) of samples tested positive for at least one RV. Rhinovirus (6.3%, 187/2987) was the most frequently detected virus during the first two waves, whereas influenza predominated during the third. From SpS-2, influenza, SARS-CoV-2, and RSV accounted for 5.4%, 24.5%, and 39.4% of the detected viruses, respectively. During the study period, we observed three different RV circulation profiles. Certain viruses circulated sporadically, with increased activity in between waves of SARS-CoV-2. Other viruses continued to circulate regardless of the COVID-19 situation. Certain viruses were severely disrupted by the spread of SARS-CoV-2. Our findings underline the importance and necessity of maintaining an integrated disease surveillance system for the surveillance and monitoring of RVs of public health interest.

White Spot Disease (WSD) caused by the White Spot Syndrome Virus (WSSV) is the most devastating viral disease threatening the shrimp culture industry worldwide, including Madagascar. WDS was first reported on the island in 2012, however, little is known about the circulation of the virus and its genetic diversity. Our study aimed at describing the molecular diversity and the spread of WSSV in the populations of Madagascan crustaceans. Farmed and wild shrimps were collected from various locations in Madagascar from 2012 to 2016 and were tested for WSSV. Amplicons from positive specimens targeting five molecular markers (ORF75, ORF94, ORF125, VR14/15 and VR23/24) were sequenced for genotyping characterizations. Four genotypes were found in Madagascar. The type-I genotype was observed in the south-west of Madagascar in April 2012, causing a disastrous epidemic, then spread to the North-West coast. Type-II strains were detected in October 2012 causing an outbreak in another Penaeus monodon farm. In 2014 and 2015, types II and III were observed in shrimp farms. Finally, in 2016, types II and IV were found in wild species including Fenneropenaeus indicus, Metapenaeus monoceros, Marsupenaeus japonicus and Macrobrachium rosenbergii. Considering the economic importance of the shrimp industry for Madagascar, our study highlights the need to maintain WSSV surveillance to quickly take appropriate countermeasures in case of outbreak and to sustain this industry.

International audience; BackgroundHouseholds are among the highest risk for the transmission of SARS-CoV-2. In sub-Saharan Africa, very few studies have described household transmission during the COVID-19 pandemic. Our work aimed to describe the epidemiologic parameters and analyze the secondary attack rate (SAR) in Antananarivo, Madagascar, following the introduction of SARS-CoV-2 in the country in March 2020.MethodsA prospective case-ascertained study of all identified close contacts of laboratory-confirmed COVID-19 infections was conducted in Antananarivo from March to June 2020. Cases and household contacts were followed for 21 days. We estimated epidemic parameters of disease transmission by fitting parametric distributions based on infector-infected paired data. We assessed factors influencing transmission risk by analyzing the SAR.FindingsOverall, we included 96 index cases and 179 household contacts. Adjusted with the best-fit normal distribution, the incubation period was 4.1 days (95% CI 0.7–7.5]). The serial interval was 6.0 days (95% CI [2.4–9.6]) after adjusting with the best-fit Weibull distribution. On average, each index case infected 1.6 family members (95%CI [0.9–2.3]). The mean SAR among close contacts was 38.8% (95% CI [19.5–58.2]) with the best-fit gamma distribution. Contacts older than 35 years old were more likely to be infected, and the highest SAR was found among them.ConclusionThe results of our study provide key insights into the epidemiology of the first wave of SARS-CoV-2 in Madagascar. High rates of household transmission were found in Antananarivo, emphasizing the need for preventive measures to reduce community transmission.

We thank the blood donors and RBTC staff who supported this work, importantly Drs Jocelyne Nirina ANDRIAMBELO (RBTC Toamasina), Léa Isabelle RAMANDIMBISOA (RBTC Toliara), Michael Marie Osé HARIOLY NIRINA (NRTC Antananarivo), Dr Danielle FITAHIANA (RBTC Fianarantsoa) and Pr Tahiry RABENANDRIANINA (RBTC Mahajanga).We thank the Immunology of Infectious Diseases unit staff for performing assays, as well as the 4 laboratories in Madagascar where RT-PCRs were run particularly the IPM virology unit.We express our gratitude to the National Institute of Statistics of Madagascar and its Director General Isaora Zefania ROMALAHY, for sharing with us the 2020 demographics of Madagascar; International audience; Background: The incidence of the 2020 COVID-19 epidemic in Africa seems to be different from that of the rest of the world, however its true extent is probably underestimated. Conducting population based sero-surveys during the epidemic has moreover been extremely challenging, driving our group and others to study blood donor samples.Methods: We collected regional epidemiological COVID-19 surveillance data, and simultaneously monitored anti-SARS-CoV-2 antibody seroprevalences monthly throughout the epidemic in 5 major Region-associated Blood Transfusion Centres of Madagascar over a period of 9 months.Findings: Soon after attaining the first epidemic peaks between May and August 2020, both crude and population-weighted test-performance-adjusted seroprevalences of anti-SARS-CoV-2 antibodies was in Malagasy blood donors rapidly increased up to over 40% positivity.Interpretation: These findings suggest a high cumulative incidence of infection and seroconversion, which may have contributed to the observed deceleration of infection rates, but was not sufficient to prevent the second epidemic wave that struck Madagascar in Spring 2021.

Background Babesiae are erythrocytic protozoans, which infect the red blood cells of vertebrate hosts to cause disease. Previous studies have described potentially pathogenic infections of Babesia vesperuginis in insectivorous bats in Europe, the Americas and Asia. To date, no babesial infections have been documented in the bats of Madagascar, or in any frugivorous bat species worldwide. Results We used standard microscopy and conventional PCR to identify babesiae in blood from the endemic Madagascan flying fox (Pteropus rufus). Out of 203 P. rufus individuals captured between November 2013 and January 2016 and screened for erythrocytic parasites, nine adult males (4.43%) were infected with babesiae. Phylogenetic analysis of sequences obtained from positive samples indicates that they cluster in the Babesia microti clade, which typically infect felids, rodents, primates, and canids, but are distinct from B. vesperuginis previously described in bats. Statistical analysis of ecological trends in the data suggests that infections were most commonly observed in the rainy season and in older-age individuals. No pathological effects of infection on the host were documented; age-prevalence patterns indicated susceptible-infectious (SI) transmission dynamics characteristic of a non-immunizing persistent infection. Conclusions To our knowledge, this study is the first report of any erythrocytic protozoan infecting Madagascan fruit bats and the first record of a babesial infection in a pteropodid fruit bat globally. Given the extent to which fruit bats have been implicated as reservoirs for emerging human pathogens, any new record of their parasite repertoire and transmission dynamics offers notable insights into our understanding of the ecology of emerging pathogens. Electronic supplementary material The online version of this article (10.1186/s13071-019-3300-7) contains supplementary material, which is available to authorized users.

International audience; BackgroundInfluenza and respiratory syncytial virus (RSV) infections are responsible for substantial global morbidity and mortality in young children and elderly individuals. Estimates of the burden of influenza- and RSV-associated hospitalization are limited in Africa.MethodsWe conducted hospital-based surveillance for laboratory-confirmed influenza- and RSV-associated severe acute respiratory illness (SARI) among patients of any age at one hospital and a retrospective review of SARI hospitalizations in five hospitals situated in Antananarivo during 2011-2016. We estimated age-specific rates (per 100 000 population) of influenza- and RSV-associated SARI hospitalizations for the Antananarivo region and then extrapolated these rates to the national level.ResultsOverall, the mean annual national number of influenza-associated SARI hospitalizations for all age groups was 6609 (95% CI: 5381-7835-rate: 30.0; 95% CI: 24.4-35.6), 4468 (95% CI: 3796-5102-rate: 127.6; 95% CI: 108.4-145.7), 2141 (95% CI: 1585-2734-rate: 11.6; 95% CI: 8.6-14.8), and 339 (95% CI: 224-459-rate: 50.0; 95% CI: 36.3-74.4) among individuals aged

Administration of many childhood vaccines requires that multiple doses be delivered within a narrow time window to provide adequate protection and reduce disease transmission. Accurately quantifying vaccination coverage is complicated by limited individual-level data and multiple vaccination mechanisms (routine and supplementary vaccination programs). We analyzed 12,541 vaccination cards from 6 districts across Madagascar for children born in 2015 and 2016. For 3 vaccines—pentavalent diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine (DTP-HB-Hib; 3 doses), 10-valent pneumococcal conjugate vaccine (PCV10; 3 doses), and rotavirus vaccine (2 doses)—we used dates of vaccination and birth to estimate coverage at 1 year of age and timeliness of delivery. Vaccination coverage at age 1 year for the first dose was consistently high, with decreases for subsequent doses (DTP-HB-Hib: 91%, 81%, and 72%; PCV10: 82%, 74%, and 64%; rotavirus: 73% and 63%). Coverage levels between urban districts and their rural counterparts did not differ consistently. For each dose of DTP-HB-Hib, the overall percentage of individuals receiving late doses was 29%, 7%, and 6%, respectively; estimates were similar for other vaccines. Supplementary vaccination weeks, held to help children who had missed routine care to catch up, did not appear to increase the likelihood of being vaccinated. Maintaining population-level immunity with multiple-dose vaccines requires a robust stand-alone routine immunization program.

Author(s): Randremanana, Rindra Vatosoa; Andriamandimby, Soa-Fy; Rakotondramanga, Jean Marius; Razanajatovo, Norosoa Harline; Mangahasimbola, Reziky Tiandraza; Randriambolamanantsoa, Tsiry Hasina; Ranaivoson, Hafaliana Christian; Rabemananjara, Harinirina Aina; Razanajatovo, Iony; Razafindratsimandresy, Richter; Rabarison, Joelinotahiana Hasina; Brook, Cara E; Rakotomanana, Fanjasoa; Rabetombosoa, Roger Mario; Razafimanjato, Helisoa; Ahyong, Vida; Raharinosy, Vololoniaina; Raharimanga, Vaomalala; Raharinantoanina, Sandratana Jonhson; Randrianarisoa, Mirella Malala; Bernardson, Barivola; Randrianasolo, Laurence; Randriamampionona, Lea Bricette Nirina; Tato, Cristina M; DeRisi, Joseph L; Dussart, Philippe; Vololoniaina, Manuela Christophere; Randriatsarafara, Fidiniaina Mamy; Randriamanantany, Zely Arivelo; Heraud, Jean-Michel | Abstract: BackgroundFollowing the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country.MethodsNasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced.ResultsOverall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39nyears (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49nyears and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses.ConclusionsOur study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.

Pertussis is a highly contagious infectious disease and remains an important cause of mortality and morbidity worldwide. Over the last decade, vaccination has greatly reduced the burden of pertussis. Yet, uncertainty in individual vaccination coverage and ineffective case surveillance systems make it difficult to estimate burden and the related quantity of population-level susceptibility, which determines population risk. These issues are more pronounced in low-income settings where coverage is often overestimated, and case numbers are under-reported. Serological data provide a direct characterisation of the landscape of susceptibility to infection; and can be combined with vaccination coverage and basic theory to estimate rates of exposure to natural infection. Here, we analysed cross-sectional data on seropositivity against pertussis to identify spatial and age patterns of susceptibility in children in Madagascar. A large proportion of individuals surveyed were seronegative; however, there were patterns suggestive of natural infection in all the regions analysed. Improvements in vaccination coverage are needed to help prevent additional burden of pertussis in the country.

Summary box Measles vaccination is often referred to as a ‘best buy’ in public health, because of the high case fatality rate associated with infection, alongside the existence of a safe and inexpensive vaccine. The current WHO recommendation is that all children have access to two doses of the measles vaccine.1 In 2011, countries in the WHO African region adopted a measles elimination goal to be reached by 2020. In the last decades, substantial gains have been made in numbers of cases and deaths averted. Yet, an important feature of measles epidemiology is that large outbreaks can occur following years of (apparently) successful control. This phenomenon is known as a ‘posthoneymoon period’ outbreak.2 The ‘honeymoon’ consists of the period following vaccine introduction where cases drop substantially. This ‘honeymoon’ is at …

International audience; Background: Respiratory syncytial virus is the main cause of acute respiratory infections leading to a considerable morbidity and mortality among under-5 years children. A comprehensive scheme of RSV virus evolution is of great value in implementing effective universal RSV vaccine. Objective: We investigated the clinical spectrum and molecular characteristics of detected RSV over a period of seven years (January 2011 to June 2017) in Antananarivo, the capital city of Madagascar. Study design: 671 nasopharyngeal samples taken from children aged less than 5 years suffered from ARI were screened for RSV by real-time PCR. Clinical data were retrieved from case report forms. Genotype identification was performed by reverse-transcription PCR and sequencing of the second hyper variable region (HVR2) of the G glycoprotein. Results: Amongst samples tested, 292 (43.5 %) were found positive for RSV. RSV A predominated during the study period which accounted for 62.3 % (182/292) of positive samples while RSV B represented 37.0 % (108/ 292). Phylogenetic analyses identified NA1 and ON1 genotypes among RSV A. Though NA1 widespread from 2011 to 2013, ON1 became prevalent during the following years. Among RSV B, THB, CB1 and BA9 genotypes were detected. A co-circulation of THB and CB1 strains occurred during the 2011 season that was substituted by the BA9 from 2012. Malagasy ON1 strains carried some characteristic amino acid substitutions that distinguish them from the worldwide ON1 strains. By analyzing clinical spectrum, ON1 and BA genotypes seemed to prevail in mild infections compared to NA1. Conclusion: Results obtained here will have its implication in predicting temporal evolution of RSV at the local level. Considering the insularity of the country, information obtained should help in comparative analysis with global RSV strains to optimize vaccine efficacy.

International audience

Evaluation of influenza surveillance systems is poor, especially in Africa.In 2007, the Institut Pasteur de Madagascar and the Malagasy Ministry of Public Health implemented a countrywide system for the prospective syndromic and virological surveillance of influenza-like illnesses. In assessing this system's performance, we identified gaps and ways to promote the best use of resources. We investigated acceptability, data quality, flexibility, representativeness, simplicity, stability, timeliness and usefulness and developed qualitative and/or quantitative indicators for each of these attributes.Until 2007, the influenza surveillance system in Madagascar was only operational in Antananarivo and the observations made could not be extrapolated to the entire country.By 2014, the system covered 34 sentinel sites across the country. At 12 sites, nasopharyngeal and/or oropharyngeal samples were collected and tested for influenza virus. Between 2009 and 2014, 177 718 fever cases were detected, 25 809 (14.5%) of these fever cases were classified as cases of influenza-like illness. Of the 9192 samples from patients with influenza-like illness that were tested for influenza viruses, 3573 (38.9%) tested positive. Data quality for all evaluated indicators was categorized as above 90% and the system also appeared to be strong in terms of its acceptability, simplicity and stability. However, sample collection needed improvement.The influenza surveillance system in Madagascar performed well and provided reliable and timely data for public health interventions. Given its flexibility and overall moderate cost, this system may become a useful platform for syndromic and laboratory-based surveillance in other low-resource settings.La evaluación de los sistemas de vigilancia de la gripe es escasa, sobre todo en África.En 2007, el Instituto Pasteur de Madagascar y el Ministerio de Salud Pública de Madagascar implementaron un sistema nacional para la futura vigilancia sindrómica y epidemiológica de enfermedades similares a la gripe. Al evaluar el rendimiento de este sistema, se identificaron lagunas y formas de fomentar el mejor uso de los recursos. Se investigaron la aceptación, la calidad de la información, la flexibilidad, la representación, la simplicidad, la estabilidad, el momento y la utilidad, y se desarrollaron indicadores cualitativos y/o cuantitativos para cada uno de estos atributos.Hasta 2007, el sistema de vigilancia de la gripe en Madagascar operaba únicamente en Antananarivo, y las observaciones realizadas no podían extrapolarse al resto del país.En 2014, el sistema abarcaba 34 sitios centinela en todo el país. En 12 sitios, se recogieron muestras nasofaríngeas y/o bucofaríngeas, que se sometieron a pruebas del virus de la gripe. Entre 2009 y 2014 se detectaron 177 718 casos de fiebre, 25 809 (14,5%) de los cuales se clasificaron como casos de enfermedades similares a la gripe. De las 9 192 muestras de pacientes con enfermedades similares a la gripe sometidos a pruebas del virus de la gripe, 3 573 (38,9%) resultaron positivas. La calidad de los datos para todos los indicadores evaluados se categorizó como superior al 90% y el sistema también parecía ser sólido en cuanto a su aceptación, simplicidad y estabilidad. No obstante, la recogida de muestras necesitaba mejorar.El sistema de vigilancia de la gripe en Madagascar obtuvo buenos resultados y ofreció información fiable y oportuna para las intervenciones de salud pública. Dada su flexibilidad y el coste moderado general, este sistema podría convertirse en una plataforma útil para la vigilancia sindrómica y en laboratorios en otros entornos con pocos recursos.ضعف تقييم نظم ترصد الإنفلونزا خاصةً في أفريقيا.نفذ كلاً منحتى عام 2007، تم تشغيل نظام رصد الأنفلونزا في مدغشقر في أنتاناناريفو فقط، وتعذر استقراء الملاحظات للبلد بأكمله.بحلول عام 2014، غطى النظام 34 موقعًا رصديًا في جميع أنحاء البلاد. وتم جمع عينات بلعومية و/أو فموية بلعومية واختبارها لاكتشاف فيروس الإنفلونزا في 12 موقعًا. تم اكتشاف 177,718 حالة حمى في الفترة ما بين عامي 2009 و2014، وتم تصنيف 25,809 (‏14.5‏%) حالة من هذه الحالات على أنها أمراض مماثلة للإنفلونزا. وكان من بين 9192 عينة من المرضى المصابين بأمراض مماثلة للإنفلونزا والتي تم اختبارها لاكتشاف فيروس الإنفلونزا، ثبتت إصابة 3573 (‏38.9‏%) حالة. أشار تصنيف جودة البيانات لجميع المؤشرات التي تم تقييمها إلى نسبة تتعدى 90‏‏%، كما ظهر النظام قويًا فيما يتعلق بالمقبولية والبساطة والاستقرار. ومع ذلك، يلزم إدخال التحسين على عملية جمع العينات.حقق نظام رصد الإنفلونزا في مدغشقر أداءً جيدًا وقدّم بيانات موثوقة وفي الوقت المناسب لإجراء تدخلات الصحة العامة. قد يكون هذا النظام منصة مفيدة لرصد المتلازمات المرضية وعمليات الرصد في المختبرات في المواقع الأخرى قليلة الموارد وذلك بسبب مرونة هذا النظام وتكاليفه المعقولة بشكل عام.对流感监测系统的评估不足，尤其是在非洲。.2007 年，在 2007 年以前，马达加斯加的流感监测系统仅在塔那那利佛运行，并且观察结果无法外推到整个国家。.截止 2014 年，该系统覆盖全国 34 个哨点。 我们在 12 个哨点采集了鼻咽和/或口咽样本并进行了流感病毒检测。 在 2009 年至 2014 年期间，我们发现了 177 718 宗发热病例，其中 25 809 (14.5%) 宗被归类为流感样疾病病例。 在进行流感病毒检测的 9192 个流感样疾病患者的样本中，3573 (38.9%) 个样本的检测结果呈阳性。 所有评估指标下的数据质量均超过 90%，并且系统在其可接受性、简单性和稳定性方面似乎也非常卓越。 然而，样本采集需要改进。.马达加斯加流感监测系统运行情况良好，并且为公共卫生干预提供可靠、及时的数据。 鉴于其灵活性和总体适中的成本，该系统可能会成为其他资源匮乏的地区进行综合征监测和实验室监测的有用平台。.Неудовлетворительная оценка систем эпиднадзора за гриппом, особенно в Африке.В 2007 году Институтом Пастера в Мадагаскаре (До 2007 года система эпиднадзора за гриппом на Мадагаскаре действовала только в Антананариву и полученные результаты наблюдений было невозможно экстраполировать на всю страну.К 2014 году система охватывала 34 поста наблюдения по всей стране. На 12 постах были отобраны и протестированы на наличие вируса гриппа мазки из носоглотки и/или ротоглотки. В период с 2009 по 2014 год было выявлено 177 718 случаев лихорадки, 25 809 (14,5%) из этих случаев были классифицированы как случаи гриппоподобных заболеваний. Из 9192 проб, взятых у пациентов с гриппоподобными заболеваниями и протестированных на наличие вирусов гриппа, 3573 (38,9%) дали положительный результат. Качество данных для всех оцениваемых показателей было классифицировано как превышающее 90%. Система продемонстрировала хорошие показатели с точки зрения своей приемлемости, простоты и стабильности. Тем не менее отбор проб нуждается в улучшении.Система эпиднадзора за гриппом в Мадагаскаре хорошо зарекомендовала себя и позволяла получать надежные и своевременные данные для мероприятий в области общественного здравоохранения. С учетом гибкости и умеренной стоимости этой системы она может стать полезной платформой для синдромного и лабораторного наблюдения в условиях ограниченности ресурсов.

International audience; Africa is one of the endemic regions of HBV infection. In particular, genotype E is highly endemic in most of sub-Saharan Africa such as West African countries where it represents more than 90% of total infections. Madagascar, which is classified as a high endemic area for HBV and where the most prevalent genotype is E, might play a relevant role in the dispersion of this genotype due to its crucial position in the Indian Ocean. The aim of this study was to investigate the origin, population dynamics, and circulation of HBV-E genotype in Madagascar through high-resolution phylogenetic and phylodynamic approaches. The phylogenetic tree indicated that Malagasy isolates were intermixed and closely related with sequences mostly from West African countries. The Bayesian tree highlighted three statistically supported clusters of Malagasy strains which dated back to the years 1981 (95% HPD: 1971-1992), 1986 (95% HPD: 1974-1996), and 1989 (95% HPD: 1974-2001). Population dynamics analysis showed an exponential increase in the number of HBV-E infections approximately from the year 1975 until 2000s. The migration analysis was also performed and a dynamic pattern of gene flow was identified. In conclusion, this study confirms previous observation of HBV-E circulation in Africa and expands these findings at Madagascar demonstrating its recent introduction, and highlighting the role of the African countries in the spread of HBV-E genotype. Further studies on molecular epidemiology of HBV genotype E are needed to clarify the evolutionary history of this genotype.

International audience; Bats are reservoirs for emerging human pathogens, including Hendra and Nipah henipaviruses and Ebola and Marburg filoviruses. These viruses demonstrate predictable patterns in seasonality and age structure across multiple systems; previous work suggests that they may circulate in Madagascar's endemic fruit bats, which are widely consumed as human food. We aimed to (a) document the extent of henipa- and filovirus exposure among Malagasy fruit bats, (b) explore seasonality in seroprevalence and serostatus in these bat populations and (c) compare mechanistic hypotheses for possible transmission dynamics underlying these data. To this end, we amassed and analysed a unique dataset documenting longitudinal serological henipa- and filovirus dynamics in three Madagascar fruit bat species. We uncovered serological evidence of exposure to Hendra-/Nipah-related henipaviruses in Eidolon dupreanum, Pteropus rufus and Rousettus madagascariensis, to Cedar-related henipaviruses in E. dupreanum and R. madagascariensis and to Ebola-related filoviruses in P. rufus and R. madagascariensis. We demonstrated significant seasonality in population-level seroprevalence and individual serostatus for multiple viruses across these species, linked to the female reproductive calendar. An age-structured subset of the data highlighted evidence of waning maternal antibodies in neonates, increasing seroprevalence in young and decreasing seroprevalence late in life. Comparison of mechanistic epidemiological models fit to these data offered support for transmission hypotheses permitting waning antibodies but retained immunity in adult-age bats. Our findings suggest that bats may seasonally modulate mechanisms of pathogen control, with consequences for population-level transmission. Additionally, we narrow the field of candidate transmission hypotheses by which bats are presumed to host and transmit potentially zoonotic viruses globally.

Background The increasing use of malaria diagnostic tests reveals a growing proportion of patients with fever but no malaria. Clinicians and health care workers in low-income countries have few tests to diagnose causes of fever other than malaria although several diseases share common symptoms. We propose here to assess etiologies of fever in Madagascar to ultimately improve management of febrile cases. Methodology Consenting febrile outpatients aged 6 months and older were recruited in 21 selected sentinel sites throughout Madagascar from April 2014 to September 2015. Standard clinical examinations were performed, and blood and upper respiratory specimens were taken for rapid diagnostic tests and molecular assays for 36 pathogens of interest for Madagascar in terms of public health, regardless of clinical status. Principal findings A total of 682 febrile patients were enrolled. We detected at least one pathogen in 40.5% (276/682) of patients and 6.2% (42/682) with co-infections. Among all tested patients, 26.5% (181/682) had at least one viral infection, 17.0% (116/682) had malaria and 1.0% (7/682) presented a bacterial or a mycobacterial infection. None or very few of the highly prevalent infectious agents in Eastern Africa and Asia were detected in this study, such as zoonotic bacteria or arboviral infections. Conclusions These results raise questions about etiologies of fever in Malagasy communities. Nevertheless, we noted that viral infections and malaria still represent a significant proportion of causes of febrile illnesses. Interestingly our study allowed the detection of pathogens of public health interest such as Rift Valley Fever Virus but also the first case of laboratory-confirmed leptospirosis infection in Madagascar., Author summary Febrile illnesses have many origins, but infectious agents are the most important cause. Pathogens such as viruses and bacteria can cause various diseases, but associated signs and symptoms are generally non-specific and can overlap between diseases. Treatments of infectious diseases rely on the diagnostic of the causative agent however laboratory capacities are often lacking in resources-limited settings. Thus, health care workers generally follow clinical management guidelines that are rarely supported by information on the prevalence of local infections. The main objective of our study was to describe the common causes of fever in individuals presenting at outpatient healthcare center in Madagascar. Respiratory viruses, malaria and viral infection in the blood were the main infectious agents detected. Implementation of new diagnostic tools such as bedside testing (Point of Care Testing) could help health care workers to improve diagnosis and care of febrile patients. Detection of other pathogens such as hepatitis B virus, human immunodeficiency virus (HIV) or agent responsible for tuberculosis enhances the need for extended prevention, surveillance and detection of these infections. Interestingly, our study reported cases of leptospirosis and Rift Valley Fever virus infection that are pathogens of high public health concern.

International audience; BACKGROUND:Hantavirus infection is a zoonotic disease that is associated with hemorrhagic fever with renal syndrome and cardiopulmonary syndrome in human. Anjozorobe virus, a representative virus of Thailand orthohantavirus (THAIV), was recently discovered from rodents in Anjozorobe-Angavo forest in Madagascar. To assess the circulation of hantavirus at the national level, we carried out a survey of small terrestrial mammals from representative regions of the island and identified environmental factors associated with hantavirus infection. As we were ultimately interested in the potential for human exposure, we focused our research in the peridomestic area.METHODS:Sampling was achieved in twenty districts of Madagascar, with a rural and urban zone in each district. Animals were trapped from a range of habitats and examined for hantavirus RNA by nested RT-PCR. We also investigated the relationship between hantavirus infection probability in rats and possible risk factors by using Generalized Linear Mixed Models.RESULTS:Overall, 1242 specimens from seven species were collected (Rattus rattus, Rattus norvegicus, Mus musculus, Suncus murinus, Setifer setosus, Tenrec ecaudatus, Hemicentetes semispinosus). Overall, 12.4% (111/897) of Rattus rattus and 1.6% (2/125) of Mus musculus were tested positive for THAIV. Rats captured within houses were less likely to be infected than rats captured in other habitats, whilst rats from sites characterized by high precipitation and relatively low seasonality were more likely to be infected than those from other areas. Older animals were more likely to be infected, with infection probability showing a strong increase with weight.CONCLUSIONS:We report widespread distribution of THAIV in the peridomestic rats of Madagascar, with highest prevalence for those living in humid areas. Although the potential risk of infection to human may also be widespread, our results provide a first indication of specific zone with high transmission. Gathered data will be helpful to implement policies for control and prevention of human risk infection.

International audience; BACKGROUND:Few comprehensive data exist regarding the epidemiology of severe acute respiratory infections (SARI) in low income countries. This study aimed at identifying etiologies and describing clinical features of SARI-associated hospitalization in Madagascar.METHODS:It is a prospective surveillance of SARI in 2 hospitals for 3 years. Nasopharyngeal swabs, sputum, and blood were collected from SARI patients enrolled and tested for viruses and bacteria. Epidemiological and clinical information were obtained from case report forms.RESULTS:Overall, 876 patients were enrolled in the study, of which 83.1% (728/876) were tested positive for at least one pathogen. Viral and bacterial infections occurred in 76.1% (667/876) and 35.8% (314/876) of tested samples, respectively. Among all detected viruses, respiratory syncytial virus (RSV) was the most common (37.7%; 348/924) followed by influenza virus A (FLUA, 18.4%; 170/924), rhinovirus (RV, 13.5%; 125/924), and adenovirus (ADV, 8.3%; 77/924). Among bacteria, Streptococcus pneumoniae (S. pneumoniae, 50.3%, 189/370) was the most detected followed by Haemophilus influenzae type b (Hib, 21.4%; 79/370), and Klebsiella (4.6%; 17/370). Other Streptococcus species were found in 8.1% (30/370) of samples. Compared to patients aged less than 5 years, older age groups were significantly less infected with RSV. On the other hand, patients aged more than 64 years (OR = 3.66) were at higher risk to be infected with FLUA, while those aged 15-29 years (OR = 3.22) and 30-64 years (OR = 2.39) were more likely to be infected with FLUB (influenza virus B).CONCLUSION:The frequency of influenza viruses detected among SARI patients aged 65 years and more highlights the need for health authorities to develop strategies to reduce morbidity amongst at-risk population through vaccine recommendation. Amongst young children, the demonstrated burden of RSV should guide clinicians for a better case management of children. These findings reveal the need to develop point-of-care tests to avoid overuse of antibiotics and to promote vaccine that could reduce drastically the RSV hospitalizations.

SummaryBackground Influenza immunization still poses a critical challenge globally and specifically for tropical regions due to their complex influenza circulation pattern. Tropical regions should select the WHO's Northern or Southern hemisphere recommended vaccine composition based on local surveillance. Analyses of influenza immunization effectiveness have neglected to account for the proportion of circulating viruses prevented from causing infection each year. We investigate this question for Madagascar, where influenza vaccines are not widely available. Methods 78 Malagasy influenza strains characterized from 2002 to 2014 were challenged with hypothetical scenarios in which the WHO's Northern and Southern hemisphere recommended vaccine compositions were provided to the population. Match between circulating and vaccine strains was determined by haemagglutination inhibition assays. Strain-specific positive matches were scored assuming 9 months of protection and scenarios incorporated vaccine delays from zero to five months. Results Malagasy influenza strains matched 54% and 44% respectively with the Northern and Southern hemisphere recommended vaccine strains when the vaccine was delivered as soon as available. The matching values further decreased when additional delivery and application delays were considered. Differences between recommended compositions were not statistically significant. Conclusion Our results showed matching with the Northern hemisphere vaccine barely above 50%, even in the more favourable scenario. This suggests that if implemented, routine influenza vaccines would not protect against half of the influenza strains circulating in any epidemic season of Madagascar. We suggest that this limitation in influenza vaccine efficacy deserves greater attention, and should be considered in cost/benefit analyses of national influenza immunization programs. This article is protected by copyright. All rights reserved.

Background WHO developed a global strategy to eliminate hepatitis B by 2030 and set target to treat 80% of people with chronic hepatitis B virus (HBV) infection eligible for antiviral treatment. As a first step to achieve this goal, it is essential to conduct a situation analysis that is fundamental to designing national hepatitis plans. We therefore estimated the prevalence of chronic HBV infection, and described the existing infrastructure for HBV diagnosis in Madagascar. Methods We conducted a stratified multi-stage serosurvey of hepatitis B surface antigen (HBsAg) in adults aged ≥18 years using 28 sentinel surveillance sites located throughout the country. We obtained the list of facilities performing HBV testing from the Ministry of Health, and contacted the person responsible at each facility. Results A total of 1778 adults were recruited from the 28 study areas. The overall weighted seroprevalence of HBsAg was 6.9% (95% CI: 5.6–8.6). Populations with a low socio-economic status and those living in rural areas had a significantly higher seroprevalence of HBsAg. The ratio of facilities equipped to perform HBsAg tests per 100,000 inhabitants was 1.02 in the capital city of Antananarivo and 0.21 outside the capital. There were no facilities with the capacity to perform HBV DNA testing or transient elastography to measure liver fibrosis. There are only five hepatologists in Madagascar. Conclusion Madagascar has a high-intermediate level of endemicity for HBV infection with a severely limited capacity for its diagnosis and treatment. Higher HBsAg prevalence in rural or underprivileged populations underlines the importance of a public health approach to decentralize the management of chronic HBV carriers in Madagascar by using simple and low-cost diagnostic tools. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4630-z) contains supplementary material, which is available to authorized users.

The force of infection (FOI) is one of the key parameters describing the dynamics of transmission of vector-borne diseases. Following the occurrence of two major outbreaks of Rift Valley fever (RVF) in Madagascar in 1990–91 and 2008–09, recent studies suggest that the pattern of RVF virus (RVFV) transmission differed among the four main eco-regions (East, Highlands, North-West and South-West). Using Bayesian hierarchical models fitted to serological data from cattle of known age collected during two surveys (2008 and 2014), we estimated RVF FOI and described its variations over time and space in Madagascar. We show that the patterns of RVFV transmission strongly differed among the eco-regions. In the North-West and Highlands regions, these patterns were synchronous with a high intensity in mid-2007/mid-2008. In the East and South-West, the peaks of transmission were later, between mid-2008 and mid-2010. In the warm and humid northwestern eco-region favorable to mosquito populations, RVFV is probably transmitted all year-long at low-level during inter-epizootic period allowing its maintenance and being regularly introduced in the Highlands through ruminant trade. The RVF surveillance of animals of the northwestern region could be used as an early warning indicator of an increased risk of RVF outbreak in Madagascar.

Background Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008–2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. Methodology/Principal Findings First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p, Author Summary Rift Valley fever virus (RVFV) is a pathogen that causes a vector-borne tropical disease. The disease affects ruminants and humans and severely impacts the health and economy of affected countries. Madagascar was heavily affected by Rift Valley fever (RVF) in 2008–2009, with evidence of a large and heterogeneous spread of the disease. Our study aims at identifying environmental and human-related risk factors for RVFV transmission. First, we characterized Malagasy environments according to their putative influence on RVFV mosquito density and population dynamics. Then we statistically analyzed cattle and human serological data collected at a national level with the individual serological status as response, and Malagasy environments previously characterized by climatic and landscape variables as well as other potential risk factors as explanatory variables. Our results identified humid environments of the western, north-western and eastern parts of the island as risky areas. The identification of at-risk environments is essential to focus veterinary surveillance and control of RVFV.

Erratum in - Correction: Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination? PLoS One. 2016 May 2;11(5):e0155089. doi: 10.1371/journal.pone.0155089. Introduction: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. Methods: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with 80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. Results: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. Discussion: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate. The Global Influenza B Study is supported by an unrestricted research grant from Sanofi Pasteur. info:eu-repo/semantics/publishedVersion

International audience; West Nile virus is an arthropod-borne zoonosis transmitted by a large number of mosquito species, and birds play a key role as reservoir of the virus. Its distribution is largely widespread over Africa, Asia, the Americas and Europe. Since 1978, it has frequently been reported in Madagascar. Studies described a high seroprevalence level of the virus in humans in different areas of the island and a human fatal case of WNV infection was reported in 2011. Despite these reports, the epidemiology of WNV in Madagascar, in particular , viral circulation remains unclear. To explore the transmission of WNV in two rural human populations of Madagascar, we investigated local mosquitoes and poultry for evidence of current infections, and determined seroprevalence of candidate sentinel species among the local poultry. These 2 areas are close to lakes where domestic birds, migratory wild birds and humans coexist. Serological analysis revealed WNV antibodies in domestic birds (duck, chicken, goose, turkey and guinea fowl) sampled in both districts (Antsalova 29.4% and Mitsinjo 16.7%). West Nile virus nucleic acid was detected in one chicken and in 8 pools of mosquitoes including 2 mosquito species (Aedeomyia madagascarica and Anopheles pauliani) that have not been previously described as candidate vectors for WNV. Molecular analysis of WNV isolates showed that all viruses detected were part of the line-age 2 that is mainly distributed in Africa, and were most closely matched by the previous Malagasy strains isolated in 1988. Our study showed that WNV circulates in Madagascar amongst domestic birds and mosquitoes, and highlights the utility of poultry as a surveillance tool to detect WNV transmission in a peri-domestic setting.

International audience; BACKGROUND:The seasonal drivers of influenza activity remain debated in tropical settings where epidemics are not clearly phased. Antananarivo is a particularly interesting case study because it is in Madagascar, an island situated in the tropics and with quantifiable connectivity levels to other countries.OBJECTIVES:We aimed at disentangling the role of environmental forcing and population fluxes on influenza seasonality in Madagascar.METHODS:We compiled weekly counts of laboratory-confirmed influenza-positive specimens for the period 2002 to 2012 collected in Antananarivo, with data available from sub-Saharan countries and countries contributing most foreign travelers to Madagascar. Daily climate indicators were compiled for the study period.RESULTS:Overall, influenza activity detected in Antananarivo predated that identified in temperate Northern Hemisphere locations. This activity presented poor temporal matching with viral activity in other countries from the African continent or countries highly connected to Madagascar excepted for A(H1N1)pdm09. Influenza detection in Antananarivo was not associated with travel activity and, although it was positively correlated with all climatic variables studied, such association was weak.CONCLUSIONS:The timing of influenza activity in Antananarivo is irregular, is not driven by climate, and does not align with that of countries in geographic proximity or highly connected to Madagascar. This work opens fresh questions regarding the drivers of influenza seasonality globally particularly in mid-latitude and less-connected regions to tailor vaccine strategies locally.

International audience; BACKGROUND:Bats are amongst the natural reservoirs of many coronaviruses (CoVs) of which some can lead to severe infection in human. African bats are known to harbor a range of pathogens (e.g., Ebola and Marburg viruses) that can infect humans and cause disease outbreaks. A recent study in South Africa isolated a genetic variant closely related to MERS-CoV from an insectivorous bat. Though Madagascar is home to 44 bat species (41 insectivorous and 3 frugivorous) of which 34 are endemic, no data exists concerning the circulation of CoVs in the island's chiropteran fauna. Certain Malagasy bats can be frequently found in close contact with humans and frugivorous bats feed in the same trees where people collect and consume fruits and are hunted and consumed as bush meat. The purpose of our study is to detect and identify CoVs from frugivorous bats in Madagascar to evaluate the risk of human infection from infected bats.METHODS:Frugivorous bats belonging to three species were captured in four different regions of Madagascar. We analyzed fecal and throat swabs to detect the presence of virus through amplification of the RNA-dependent RNA polymerase (RdRp) gene, which is highly conserved in all known coronaviruses. Phylogenetic analyses were performed from positive specimens.RESULTS:From 351 frugivorous bats, we detected 14 coronaviruses from two endemic bats species, of which 13 viruses were identified from Pteropus rufus and one from Eidolon dupreanum, giving an overall prevalence of 4.5%. Phylogenetic analysis revealed that the Malagasy strains belong to the genus Betacoronavirus but form three distinct clusters, which seem to represent previously undescribed genetic lineages.CONCLUSIONS:Our findings suggest that CoVs circulate in frugivorous bats of Madagascar, demonstrating the needs to evaluate spillover risk to human populations especially for individuals that hunt and consume infected bats. Possible dispersal mechanisms as to how coronaviruses arrived on Madagascar are discussed.

International audience; So far, no published data was available concerning the circulation of Bluetongue virus (BTV) in Madagascar. During a survey on Rift Valley Fever, we were able to detect a virus belonging to BTV. Therefore, we conducted a study aiming at characterizing molecularly the BTV isolated and assess the importance of circulation of BTV in Madagascar. A total of 4393 sera from ruminants selected randomly by stratification and sampled in 30 districts of Madagascar were tested for BTV. Moreover, 175 cattle were followed during 11 months.Phylogenetic analyses were performed from virus isolated from unfed pools of mosquitoes.Overall, the estimated mean seroprevalence of infection at the national level was 95.9% (95% CI: [95.2–96.5]) in cattle and 83.7% (95% CI: [81.4–85.9]) in small ruminants. Estimation of incidence rate was 54 per 100 cattle-years assuming that the incidence rate is constant allyear along. Phylogenetic analyses revealed that BTV detected belong to serotype 2.In conclusion, our results showed that BTV is endemic in Madagascar and highly prevalent among cattle. In our study we did not work on the vector involved in transmission of BTV in cattle. Thus, research should be conducted to better describe epidemiology of BTV in Madagascar including vectors and assess economic impact of the disease associated to BTV infections.

International audience; BACKGROUND:Epidemics pose major threats in resource-poor countries, and surveillance tools for their early detection and response are often inadequate. In 2007, a sentinel surveillance system was established in Madagascar, with the aim of rapidly identifying potential epidemics of febrile or diarrhoeal syndromes and issuing alerts. We present the health and process indicators for the five years during which this system was constructed, showing the spatiotemporal trends, early-warning sign detection capability and process evaluation through timely analyses of high-quality data.METHODS:The Malagasy sentinel surveillance network is currently based on data for fever and diarrhoeal syndromes collected from 34 primary health centres and reported daily via the transmission of short messages from mobile telephones. Data are analysed daily at the Institut Pasteur de Madagascar to make it possible to issue alerts more rapidly, and integrated process indicators (timeliness, data quality) are used to monitor the system.RESULTS:From 2007 to 2011, 917,798 visits were reported. Febrile syndromes accounted for about 11% of visits annually, but the trends observed differed between years and sentinel sites. From 2007 to 2011, 21 epidemic alerts were confirmed. However, delays in data transmission were observed (88% transmitted within 24 hours in 2008; 67% in 2011) and the percentage of forms transmitted each week for validity control decreased from 99.9% in 2007 to 63.5% in 2011.CONCLUSION:A sentinel surveillance scheme should take into account both epidemiological and process indicators. It must also be governed by the main purpose of the surveillance and by local factors, such as the motivation of healthcare workers and telecommunication infrastructure. Permanent evaluation indicators are required for regular improvement of the system.

International audience; Background: Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral infection with hemorrhagic manifestation and often a fatal ending. Human become infected mainly through tick bite or by crushing infected tick, by contact with blood or tissues from viraemic livestock or patient. CCHF virus (CCHFV) has been isolated once in Madagascar but data on the epidemiology of the disease in the country are very scarce. Objectives: To investigate the circulation and the geographic distribution of CCHFV infection among at risk population in Madagascar. Study design: A national cross-sectional serologic survey was performed in 2008–2009 among slaughterhouse workers. Results: A total of 1995 workers were included. A recent CCHFV infection was detected in 1 of the 1995 participants (0.5‰; 95% confidence interval [CI]: 0–0.15%), and a past CCHFV infection was detected in 15 participants (0.75%; 95% CI: 0.37–1.13%). Conclusion: Overall, the percentage of CCHFV infection seen in Madagascar among at-risk professionals is very low compared to endemic countries. An assessment of the prevalence in livestock as a sensitive indicator of CCHFV activity must be considered in order to confirm the lack or the weak endemicity of CCHF in Madagascar.

International audience; Most circulating strains of Human enterovirus 71 (EV-A71) have been classified primarily into three genogroups (A to C) on the basis of genetic divergence between the 1D gene, which encodes the VP1 capsid protein. The aim of the present study was to provide further insights into the diversity of the EV-A71 genogroups following the recent description of highly divergent isolates, in particular those from African countries, including Madagascar. We classified recent EV-A71 isolates by a large comparison of 3,346 VP1 nucleotidic sequences collected from GenBank. Analysis of genetic distances and phylogenetic investigations indicated that some recently-reported isolates did not fall into the genogroups A-C and clustered into three additional genogroups, including one Indian genogroup (genogroup D) and 2 African ones (E and F). Our Bayesian phylogenetic analysis provided consistent data showing that the genogroup D isolates share a recent common ancestor with the members of genogroup E, while the isolates of genogroup F evolved from a recent common ancestor shared with the members of the genogroup B. Our results reveal the wide diversity that exists among EV-A71 isolates and suggest that the number of circulating genogroups is probably underestimated, particularly in developing countries where EV-A71 epidemiology has been poorly studied.

International audience; Until now, there was only serological evidence that hantaviruses were circulating in rodents and infecting humans from Madagascar. To assess the presence of a hantavirus on the island, between October, 2008, and March, 2010, we sampled 585 rodents belonging to seven species in the Anjozorobe-Angavo forest corridor, 70 km north from the capital city Antananarivo. A hantavirus was detected from organs of the ubiquist roof rat (Rattus rattus) and of the endemic Major's tufted-tailed rat (Eliurus majori). Amazingly, sequence analysis of the S (small), M (medium), and L (large) coding DNA sequence of this virus showed that the Anjozorobe strain (proposed name) was a new genetic variant of Thailand virus (THAIV) that comprises other variants found in Southeast Asia. Because THAIV is suspected of causing hemorrhagic fever with renal syndrome in humans, ongoing studies are addressing the risk of infection by this new variant in the Malagasy population.

International audience; In recent years, Madagascar and the Comoros archipelago have been affected by epidemics of Rift Valley fever (RVF), however detection of Rift Valley fever virus (RVFV) in zebu, sheep and goats during the post epidemic periods was frequently unsuccessful. Thus, a highly sensitive real-time RT-PCR assay was developed for the detection of RVFV at low viral loads. A new RVF SYBR Green RT-PCR targeting the M segment was tested on serum from different RVF seronegative ruminant species collected from May 2010 to August 2011 in Madagascar and the Comoros archipelago and compared with a RVF specific quantitative real time RT-PCR technique, which is considered as the reference technique. The specificity was tested on a wide range of arboviruses or other viruses giving RVF similar clinical signs. A total of 38 out of 2756 serum samples tested positive with the new RT-PCR, whereas the reference technique only detected 5 out of the 2756. The described RT-PCR is an efficient diagnostic tool for the investigation of enzootic circulation of the RVF virus. It allows the detection of low viral RNA loads adapted for the investigations of reservoirs or specific epidemiological situations such as inter-epizootic periods.

Background Acute respiratory infections are a leading cause of infectious disease-related morbidity, hospitalisation and mortality among children worldwide, and particularly in developing countries. In these low-income countries, most patients with acute respiratory infection (ARI), whether it is mild or severe, are still treated empirically. The aim of the study was to evaluate the risk factors associated with the evolution and outcome of respiratory illnesses in patients aged under 5 years old. Materials and Methods We conducted a prospective study in a paediatric ward in Antananarivo from November 2010 to July 2012 including patients under 5 years old suffering from respiratory infections. We collected demographic, socio-economic, clinical and epidemiological data, and samples for laboratory analysis. Deaths, rapid progression to respiratory distress during hospitalisation, and hospitalisation for more than 10 days were considered as severe outcomes. We used multivariate analysis to study the effects of co-infections. Results From November 2010 to July 2012, a total of 290 patients were enrolled. Co-infection was found in 192 patients (70%). Co-infections were more frequent in children under 36 months, with a significant difference for the 19–24 month-old group (OR: 8.0). Sixty-nine percent (230/290) of the patients recovered fully and without any severe outcome during hospitalisation; the outcome was scored as severe for 60 children and nine patients (3%) died. Risk factors significantly associated with worsening evolution during hospitalisation (severe outcome) were admission at age under 6 months (OR = 5.3), comorbidity (OR = 4.6) and low household income (OR = 4.1). Conclusion Co-mordidity, low-income and age under 6 months increase the risk of severe outcome for children infected by numerous respiratory pathogens. These results highlight the need for implementation of targeted public health policy to reduce the contribution of respiratory diseases to childhood morbidity and mortality in low income countries.

International audience; In the context of the possible introduction of a preventive vaccine against rotaviruses in Madagascar, the G and P genotypes distribution of the rotaviruses circulating in the children in Madagascar was studied, and the presence of emerging genotypes and unusual strains were assessed. From February 2008 to May 2009, 1,679 stools specimens were collected from children ≤5 years old with diarrhea. ELISA was used for antigen detection, and molecular amplification of VP7 and VP4 gene fragments was used for genotyping. Rotavirus antigen was detected in 104 samples (6.2%). Partial sequences of VP7 and VP4 genes were obtained from 81 and 80 antigen-positive stools, respectively. The most frequent G and P types combinations detected were G9P[8] (n = 51; 64.6%), followed by G1P[8] (n = 15; 18.9%), and G1P[6] (n = 8; 10.1%). A few unusual G-P combinations, such as G4P[6] (n = 3; 3.8%), G9P[6] (n = 1; 1.3%), and G3P[9] reassortant feline human virus (n = 1; 1.3%) were identified. Both VP4 and VP7 sequences in one of the three G4P[6] isolates were closely related to those in porcine strains, and one was a reassortant human porcine virus. These findings give an overview of the strains circulating in Madagascar and should help public health authorities to define a vaccine strategy.

International audience; Hepatitis E virus (HEV) causes an orofecal disease transmitted through poor hygiene environments, contaminated food (mainly pork products), or by contacts with infected animals. Very little data are currently available regarding the disease in the Southwestern Indian Ocean Islands. We report the first sero- and viro-survey for HEV in human and swine in Madagascar. A seroprevalence rate of 14.1% (60 of 427) was measured in slaughterhouse workers. Seroprevalence to HEV in pigs was estimated to 71.2% (178 of 250), strongly suggesting the existence of a zoonotic cycle. Three out of 250 pig livers (1.2%) tested HEV RNA-positive by quantitative polymerase chain reaction. Phylogenetic analyses based on 1-kb sequences of the ORF 2-3 identified these viruses as HEV genotype 3. Sequences clustered in a distinct Malagasy sub-clade, possibly representative of a new sub-genotype, for which the date of emergence was estimated around 1989. Further studies are needed to confirm other transmission routes of HEV to humans, especially through non-zoonotic cycles.

International audience; BACKGROUND: Madagascar was one of the first African countries to be affected by the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection. The outbreak started in the capital city, Antananarivo, and then spread throughout the country from October 2009 through February 2010. METHODS: Specimens from patients presenting with influenza-like illness were collected and shipped to the National Influenza Center in Madagascar for analyses, together with forms containing patient demographic and clinical information. RESULTS: Of the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and seasonal influenza virus, respectively. Most specimens (42.0%) received were collected from patients 50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1; 95% confidence interval, 1.7-2.6; P < .01). Although phylogenetic analyses of A(H1N1)pdm09 suggested multiple introductions of the virus into Madagascar, no antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and those that circulated worldwide were observed. CONCLUSIONS: The high proportion of respiratory specimens positive for A(H1N1)pdm09 is consistent with a widespread transmission of the pandemic in Madagascar. The age distribution of cases of A(H1N1)pdm09 infection suggests that children and young adults could be targeted for interventions that aim to reduce transmission during an influenza pandemic.