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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. [ABSTRACT FROM AUTHOR]

Background 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 Hemisphere 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 Seventy-eight Malagasy influenza strains characterized from 2002 to 2014 were challenged with hypothetical scenarios in which the WHO's Northern Hemisphere 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 5 months. Results Malagasy influenza strains matched 54% and 44%, respectively, with the Northern Hemisphere 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 provide an optimal protection 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 programmes. [ABSTRACT FROM AUTHOR]

Understanding cell dynamics in animal models have implications for therapeutic strategies elaborated against leukemia in human. Quantification of the cell turnover in closely related primate systems is particularly important for rare and aggressive forms of human cancers, such as adult T-cell leukemia. For this purpose, we have measured the death and proliferation rates of the CD4+ T lymphocyte population in squirrel monkeys (Saimiri sciureus) infected by human T-lymphotropic virus type 1 (HTLV-1). The kinetics of in vivo bromodeoxyuridine labeling revealed no modulation of the cell turnover in HTLV-1-infected monkeys with normal CD4 cell counts. In contrast, a substantial decrease in the proliferation rate of the CD4+ T population was observed in lymphocytic monkeys (e.g. characterized by excessive proportions of CD4+ T lymphocytes and by the presence of abnormal flower-like cells). Unexpectedly, onset of HTLV-associated leukemia thus occurs in the absence of increased CD4+ T-cell proliferation. This dynamics significantly differs from the generalized activation of the T-cell turnover induced by other primate lymphotropic viruses like HIV and SIV.Oncogene (2005) 24, 7514–7523. doi:10.1038/sj.onc.1208896; published online 8 August 2005 [ABSTRACT FROM AUTHOR]

The island nation of Madagascar is home to three endemic species of Old World fruit bat in the family Pteropodidae: Pteropus rufus , Eidolon dupreanum , and Rousettus madagascariensis , all three of which are IUCN Red Listed under some category of threat. Delineation of seasonal limits in the reproductive calendar for threatened mammals can inform conservation efforts by clarifying parameters used in population viability models, as well as elucidate understanding of the mechanisms underpinning pathogen persistence in host populations. Here, we define the seasonal limits of a staggered annual birth pulse across the three species of endemic Madagascar fruit bat, known reservoirs for viruses of high zoonotic potential. Our field studies indicate that this annual birth pulse takes place in September/October for P. rufus , November for E. dupreanum , and December for R. madagascariensis in central-eastern Madagascar where the bulk of our research was concentrated. Juvenile development periods vary across the three Malagasy pteropodids, resulting in near-synchronous weaning of pups for all species in late January–February at the height of the fruiting season for this region. We here document the size range in morphological traits for the three Malagasy fruit bat species, with P. rufus and E. dupreanum among the larger of pteropodids globally and R. madagascariensis among the smaller. All three species demonstrate subtle sexual dimorphism with males being larger than females. We explore seasonal variation in adult body condition by comparing observed body mass with body mass predicted by forearm length, demonstrating that pregnant females add weight during staggered gestation periods and males lose weight during the nutritionally deficit Malagasy winter. Finally, we quantify forearm, tibia, and ear length growth rates in juvenile bats, demonstrating both faster growth and more protracted development times for P. rufus as compared with E. dupreanum and R. madagascariensis. The longer development period for the already-threatened P. rufus further undermines the conservation status of this species as human hunting is particularly detrimental to population viability during reproductive periods. Our work highlights the importance of longitudinal field studies in collecting critical data for mammalian conservation efforts and human public health alike. [ABSTRACT FROM AUTHOR]

Highlights: [•] A highly sensitive real-time PCR assay for the detection of Rift Valley Fever virus. [•] Sensibility tested on 2756 serum from Madagascar and the Comoros archipelago. [•] Comparison with a RVF specific quantitative real time RT-PCR reference technique. [•] System specific and 7.7 times more sensitive than the reference technique. [•] Diagnostic tool for the detection of low viral loads in inter-epizootic periods. [ABSTRACT FROM AUTHOR]

Background: Rift Valley fever (RVF) is one of the main vector borne zoonotic diseases that affects a wide range of ruminants and human beings in Africa and the Arabian Peninsula. A rapid and specific test for RVF diagnosis at the site of a suspected outbreak is crucial for the implementation of control measures. Methodology/Principal findings: A first-line lateral flow immunochromatographic strip test (LFT) was developed for the detection of the nucleoprotein (N) of the RVF virus (RVFV). Its diagnostic performance characteristics were evaluated using reference stocks isolates recovered from different hosts and in geographic regions mimicking clinical specimens and from known RVF negative serum samples. A high level of diagnostic accuracy (DSe (35/35), DSp (167/169)) was observed, including the absence of cross-reactivity with viruses belonging to different genera. Conclusion/Significance: The fact no specialized reagents and laboratory equipment are needed, make this assay a valuable, first-line diagnostic tool in resource-poor diagnostic territories for on-site RVFV detection, however the staff require training. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Madagascar is home to three endemic species of Old World Fruit Bat, which are important pollinators and seed dispersers. We aimed to quantitatively assess population trajectories for the two largest of these species, the IUCN-listed 'Vulnerable' Eidolon dupreanum and Pteropus rufus. To this end, we conducted a longitudinal field study, in which we live-captured E. dupreanum and P. rufus , estimated species-specific fecundity rates, and generated age-frequency data via histological analysis of cementum annuli layering in tooth samples extracted from a subset of individuals. We fit exponential models to resulting data to estimate annual survival probabilities for adult bats (s A =.794 for E. dupreanum ; s A =.511 for P. rufus), then applied Lefkovitch modeling techniques to infer the minimum required juvenile survival rate needed to permit longterm population persistence. Given estimated adult survival, population persistence was only possible for E. dupreanum when field-based fecundity estimates were replaced by higher values reported in the literature for related species. For P. rufus , tooth-derived estimates of adult survival were so low that even assumptions of perfect (100%) juvenile annual survival would not permit stable population trajectories. Age-based survival analyses were further supported by longitudinal exit counts carried out from 2013 to 2018 at three local P. rufus roost sites, which demonstrated a statistically significant, faintly negative time trend, indicative of subtle regional population declines. These results suggest that Malagasy fruit bat species face significant threats to population viability, with P. rufus particularly imperiled. Immediate conservation interventions, including habitat restoration and cessation of legally sanctioned bat hunting, are needed to protect Madagascar's fruit bats into the future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a vector-borne viral disease widespread in Africa. The primary cycle involves mosquitoes and wild and domestic ruminant hosts. Humans are usually contaminated after contact with infected ruminants. As many environmental, agricultural, epidemiological, and anthropogenic factors are implicated in RVF spread, the multidisciplinary One Health approach was needed to identify the drivers of RVF epidemics in Madagascar. We examined the environmental patterns associated with these epidemics, comparing human and ruminant serological data with environmental and cattle-trade data. In contrast to East Africa, environmental drivers did not trigger the epidemics: They only modulated local Rift Valley fever virus (RVFV) transmission in ruminants. Instead, RVFV was introduced through ruminant trade and subsequent movement of cattle between trade hubs caused its long-distance spread within the country. Contact with cattle brought in from infected districts was associated with higher infection risk in slaughterhouse workers. The finding that anthropogenic rather than environmental factors are the main drivers of RVF infection in humans can be used to design better prevention and early detection in the case of RVF resurgence in the region. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Bats are reservoirs for many emerging zoonotic viruses. In this study, we screened 197 animals from 15 different bat species of the Southwest Indian Ocean for paramyxovirus infection and identified paramyxoviruses in five insectivorous bat-species from the Union of the Comoros (3/66), Mauritius (1/55) and Madagascar (4/76). Viral isolation was possible via cell culture and phylogenetic analysis revealed these viruses clustered in a Morbillivirus-related lineage, with relatively high nucleotide sequence similarity to other recently discovered insectivorous-bat paramyxoviruses but distinct from those known to circulate in frugivorous bats. [Copyright &y& Elsevier]