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Abstract Background Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005–2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard. Methods Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates. Results In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods. Conclusion A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics.

Abstract Background French Guiana has the highest tuberculosis (TB) burden among all French departments, with a strong increase in the TB incidence over the last few years. It is now uncertain how best to explain this incidence. The objective of this study was to compare three different methods evaluating the extent of recent TB transmission in French Guiana. Methods We conducted a population-based molecular epidemiology study of tuberculosis in French Guiana based on culture-positive TB strains (1996 to 2003, n = 344) to define molecular relatedness between isolates, i.e. potential transmission events. Phylogenetic relationships were inferred by comparing two methods: a "cluster-graph" method based on spoligotyping results, and a minimum spanning tree method based on both spoligotyping and variable number of tandem DNA repeats (VNTR). Furthermore, three indices attempting to reflect the extent of recent TB transmission (RTIn, RTIn-1 and TMI) were compared. Results Molecular analyses showed a total amount of 120 different spoligotyping patterns and 273 clinical isolates (79.4%) that were grouped in 49 clusters. The comparison of spoligotypes from French Guiana with an international spoligotype database (SpolDB4) showed that the majority of isolates belonged to major clades of M. tuberculosis (Haarlem, 22.6%; Latin American-Mediterranean, 23.3%; and T, 32.6%). Indices designed to quantify transmission of tuberculosis gave the following values: RTIn = 0.794, RTIn-1 = 0.651, and TMI = 0.146. Conclusion Our data showed a high number of Mycobacterium tuberculosis clusters, suggesting a high level of recent TB transmission, nonetheless an estimation of transmission rate taking into account cluster size and mutation rate of genetic markers showed a low ongoing transmission rate (14.6%). Our results indicate an endemic mode of TB transmission in French Guiana, with both resurgence of old spatially restricted genotypes, and a significant importation of new TB genotypes by migration of TB infected persons from neighgouring high-incidence countries.

Background: Chikungunya virus (CHIKV) caused a major two-wave seventeen-month-long outbreak in La Réunion Island in 2005-2006. The aim of this study was to refine clinical estimates provided by a regional surveillance-system using a two-stage serological assessment as gold standard.Methods: Two serosurveys were implemented: first, a rapid survey using stored sera of pregnant women, in order to assess the attack rate at the epidemic upsurge (s1, February 2006; n = 888); second, a population-based survey among a random sample of the community, to assess the herd immunity in the post-epidemic era (s2, October 2006; n = 2442). Sera were screened for anti-CHIKV specific antibodies (IgM and IgG in s1, IgG only in s2) using enzyme-linked immunosorbent assays. Seroprevalence rates were compared to clinical estimates of attack rates.Results: In s1, 18.2% of the pregnant women were tested positive for CHIKV specific antibodies (13.8% for both IgM and IgG, 4.3% for IgM, 0.1% for IgG only) which provided a congruent estimate with the 16.5% attack rate calculated from the surveillance-system. In s2, the seroprevalence in community was estimated to 38.2% (95% CI, 35.9 to 40.6%). Extrapolations of seroprevalence rates led to estimate, at 143,000 and at 300,000 (95% CI, 283,000 to 320,000), the number of people infected in s1 and in s2, respectively. In comparison, the surveillance-system estimated at 130,000 and 266,000 the number of people infected for the same periods.Conclusion: A rapid serosurvey in pregnant women can be helpful to assess the attack rate when large seroprevalence studies cannot be done. On the other hand, a population-based serosurvey is useful to refine the estimate when clinical diagnosis underestimates it. Our findings give valuable insights to assess the herd immunity along the course of epidemics. [ABSTRACT FROM AUTHOR]

Murine typhus is a flea-borne zoonotic disease that has been recently reported on Reunion Island, an oceanic volcanic island located in the Indian Ocean. Five years of survey implemented by the regional public health services have highlighted a strong temporal and spatial structure of the disease in humans, with cases mainly reported during the humid season and restricted to the dry southern and western portions of the island. We explored the environmental component of this zoonosis in an attempt to decipher the drivers of disease transmission. To do so, we used data from a previously published study (599 small mammals and 175 Xenopsylla fleas from 29 sampling sites) in order to model the spatial distribution of rat fleas throughout the island. In addition, we carried out a longitudinal sampling of rats and their ectoparasites over a 12 months period in six study sites (564 rats and 496 Xenopsylla fleas) in order to model the temporal dynamics of flea infestation of rats. Generalized Linear Models and Support Vector Machine classifiers were developed to model the Xenopsylla Genus Flea Index (GFI) from climatic and environmental variables. Results showed that the spatial distribution and the temporal dynamics of fleas, estimated through the GFI variations, are both strongly controlled by abiotic factors: rainfall, temperature and land cover. The models allowed linking flea abundance trends with murine typhus incidence rates. Flea infestation in rats peaked at the end of the dry season, corresponding to hot and dry conditions, before dropping sharply. This peak of maximal flea abundance preceded the annual peak of human murine typhus cases by a few weeks. Altogether, presented data raise novel questions regarding the ecology of rat fleas while developed models contribute to the design of control measures adapted to each micro region of the island with the aim of lowering the incidence of flea-borne diseases., Competing Interests: The authors have declared that no competing interests exist.

Objective: Hepatitis E virus (HEV) has been scarcely investigated in the Indian Ocean. Following a nationwide serosurvey among blood donors, we conducted a population-based serosurvey to assess the magnitude of HEV exposure on Reunion Island., Methods: Four hundred and sixty-six archived frozen human sera from the 2009 CoPanFlu-RUN cohort were analysed using the Wantai HEV IgG enzyme immunoassay. HEV seropositivity was defined as an IgG titre ≥5 UI/ml. Raw and weighted seroprevalences were assessed to account for the discrepancy between the CoPanFlu-RUN subset and the general community. Prevalence proportion ratios (PPR) were measured using log-binomial models., Results: The raw and the weighted seroprevalences of HEV were 9.01% (95% CI 6.41-11.61) and 6.73% (95% CI 4.47-8.98), respectively. The presence of HEV IgG antibodies was associated with increasing age ( P  < 0.001). In a survey-adjusted model minimizing the sampling bias and adjusting for age, males were more likely to be seropositive than females (adjusted PPR 2.59, 95% CI 1.07-6.25). Seropositivity was spatially heterogeneous across the island ( P  < 0.01). Living in the neighbourhood of a pig farm within a low to intermediate slope area was associated with seropositivity in several models adjusting for age, gender, altitude of residency and interaction between slope and pig farms., Conclusion: Reunion Island is a low endemic area for HEV exposure. Despite limitations related to the retrospective study design, our findings confirm the roles of cumulative lifetime exposure and male gender in HEV exposure. The risk associated with neighbouring pig farms might also suggest environmental contamination in this setting., Competing Interests: The authors declare that they have no competing interests., (© 2019 The Authors. Published by Elsevier B.V.)

Objective: Murine typhus has been increasingly reported on Reunion island, Indian ocean, following documentation of eight autochthonous infections in 2012-2013. We conducted a serosurvey to assess the magnitude of the seroprevalence of rickettsioses in the population. Two hundred and forty-one stored frozen sera taken from the 2009 Copanflu-RUN cohort were analysed using an immunofluorescence assay allowing to distinguish typhus group (TGR) and spotted fever group Rickesttsiae (SFGR). Seropositivity was defined for a dilution titre of Rickettsia IgG antibodies ≥ 1:64. Seroprevalence was weighted to account for the discrepancy between the Copanflu-RUN subset and the general population, as to infer prevalence at community level. Prevalence proportion ratios (PPR) were measured using log-binomial models., Results: The weighted seroprevalences of typhus group rickettsioses and spotted fever group rickettsioses were of 12.71% (95% CI 8.84-16.58%) and 17.68% (95% CI 13.25-22.11%), respectively. Pooled together, data suggested that a fifth of the population had been exposed at least to one Rickettsia group. Youths (< 20 years) were less likely seropositive than adults (adjusted PPR 0.13, 95% CI 0.01-0.91). People living in the western dryer part of the island were more exposed (adjusted PPR 2.53, 95% CI 1.07-5.97). Rickettsioses are endemic on Reunion island and circulated before their first identification as murine typhus in year 2011. Surprisingly, since isolation of Rickettsia africae from Amblyomma variegatum in year 2004 or isolation of Rickettsia felis from Amblyomma loculosum, no autochthonous cases of African tick-bite fever or flea-borne spotted fever has yet been diagnosed.

After the documentation of sporadic cases of Q fever endocarditis, we conducted a serosurvey to assess Coxiella burnetii exposure on Reunion Island. Two hundred forty-one stored frozen human sera were analyzed using an immunofluorescence assay. The weighted seroprevalence of Q fever was of 6.81% (95% confidence interval, 4.02%-9.59%). Despite the absence of infection in youths <20 years of age, exposure was not driven by age or by gender. There was a spatial disparity in exposure across the island, with higher prevalence being reported in regions where ruminant farms are present. The seroprevalence pattern suggests that Q fever is endemic on Reunion Island.

Papua New Guinea (PNG) has a high burden of tuberculosis (TB), including drug-resistant TB (DR-TB). DR-TB has been identified in patients in Western Province, although there has been limited study outside the provincial capital of Daru. This study focuses on the Balimo region of Western Province, aiming to identify the proportion of DR-TB, and characterise Mycobacterium tuberculosis (MTB) drug resistance-associated gene mutations. Sputum samples were investigated for MTB infection using published molecular methods. DNA from MTB-positive samples was amplified and sequenced, targeting the rpoB and katG genes to identify mutations associated with rifampicin and isoniazid resistance respectively. A total of 240 sputum samples were collected at Balimo District Hospital (BDH). Of these, 86 were classified as positive based on the results of the molecular assays. For samples where rpoB sequencing was successful, 10.0% (5/50, 95% CI 4.4⁻21.4%) were considered rifampicin-resistant through detection of drug resistance-associated mutations. We have identified high rates of presumptive DR-TB in the Balimo region of Western Province, PNG. These results emphasise the importance of further surveillance, and strengthening of diagnostic and treatment services at BDH and throughout Western Province, to facilitate detection and treatment of DR-TB, and limit transmission in this setting., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The purpose of the study was to weigh the community burden of chikungunya determinants on Reunion island. Risk factors were investigated within a subset of 2101 adult persons from a population-based cross-sectional serosurvey, using Poisson regression models for dichotomous outcomes. Design-based risk ratios and population attributable fractions (PAF) were generated distinguishing individual and contextual (i.e. that affect individuals collectively) determinants. The disease burden attributable to contextual determinants was twice that of individual determinants (overall PAF value 89.5% vs. 44.1%). In a model regrouping both categories of determinants, the independent risk factors were by decreasing PAF values: an interaction term between the reporting of a chikungunya history in the neighbourhood and individual house (PAF 45.9%), a maximal temperature of the month preceding the infection higher than 28.5 °C (PAF 25.7%), a socio-economically disadvantaged neighbourhood (PAF 19.0%), altitude of dwelling (PAF 13.1%), cumulated rainfalls of the month preceding the infection higher than 65 mm (PAF 12.6%), occupational inactivity (PAF 11.6%), poor knowledge on chikungunya transmission (PAF 7.3%) and obesity/overweight (PAF 5.2%). Taken together, these covariates and their underlying causative factors uncovered 80.8% of chikungunya at population level. Our findings lend support to a major role of contextual risk factors in chikungunya virus outbreaks.

Background: The Pacific Islands have environmental conditions highly favourable for transmission of leptospirosis, a neglected zoonosis with highest incidence in the tropics, and Oceania in particular. Recent reports confirm the emergence and outbreaks of leptospirosis in the Pacific Islands, but the epidemiology and drivers of transmission of human and animal leptospirosis are poorly documented, especially in the more isolated and less developed islands., Methodology/principal Findings: We conducted a systematic review of human and animal leptospirosis within 25 Pacific Islands (PIs) in Polynesia, Melanesia, Micronesia, as well as Easter Island and Hawaii. We performed a literature search using four international databases for articles published between January 1947 and June 2017. We further included grey literature available on the internet. We identified 148 studies describing leptospirosis epidemiology, but the number of studies varied significantly between PIs. No data were available from four PIs. Human leptospirosis has been reported from 13 PIs, with 63% of all studies conducted in Hawaii, French Polynesia and New Caledonia. Animal leptospirosis has been investigated in 19 PIs and from 14 host species, mainly pigs (18% of studies), cattle (16%) and dogs (11%). Only 13 studies provided information on both human and animal leptospirosis from the same location. Serology results were highly diverse in the region, both in humans and animals., Conclusions/significance: Our study suggests that, as in other tropical regions, leptospirosis is widespread in the PIs while showing some epidemiological heterogeneity. Data are scarce or absent from many PIs. Rodents, cattle, pigs and dogs are all likely to be important carriers, but the relative importance of each animal species in human infection needs to be clarified. Epidemiological surveys with appropriate sampling design, pathogen typing and data analysis are needed to improve our understanding of transmission patterns and to develop effective intervention strategies., Competing Interests: The authors have declared that no competing interests exist.

Understanding the processes driving parasite assemblages is particularly important in the context of zoonotic infectious diseases. Leptospirosis is a widespread zoonotic bacterial infection caused by pathogenic species of the genus Leptospira. Despite a wide range of animal hosts, information is still lacking on the factors shaping Leptospira diversity in wild animal communities, especially in regions, such as tropical insular ecosystems, with high host species richness and complex biogeographical patterns. Using a large dataset (34 mammal species) and a multilocus approach at a regional scale, we analyzed the role of both host species diversity and geography in Leptospira genetic diversity in terrestrial small mammals (rodents, tenrecs, and shrews) and bats from 10 different islands/countries in the western Indian Ocean (WIO) and neighboring Africa. At least four Leptospira spp. (L. interrogans, L. borgpetersenii, L. kirschneri, and L. mayottensis) and several yet-unidentified genetic clades contributed to a remarkable regional Leptospira diversity, which was generally related to the local occurrence of the host species rather than the geography. In addition, the genetic structure patterns varied between Leptospira spp., suggesting different evolutionary histories in the region, which might reflect both in situ diversification of native mammals (for L. borgpetersenii) and the more recent introduction of non-native host species (for L. interrogans). Our data also suggested that host shifts occurred between bats and rodents, but further investigations are needed to determine how host ecology may influence these events.

Leptospirosis is a zoonotic bacterial disease of global importance. A large spectrum of asymptomatic animal hosts can carry the infection and contribute to the burden of human disease. Environmental sources of human contamination also point to the importance of a hydrotelluric reservoir. Leptospirosis can be caused by as many as 15 different pathogenic or intermediate Leptospira species. However, classification of these bacteria remains complicated through the use of both serological and genetic classification systems that show poor correlation. With the advent of molecular techniques, DNA-based barcoding offers a conceptual framework that can be used for leptospirosis surveillance as well as source tracking. In this review, we summarize some of the current techniques, highlight significant successes and weaknesses and point to the future opportunities and challenges to successfully establish a widely applicable barcoding scheme for Leptospira.

Background: Tuberculosis (TB) is a serious health problem in Papua New Guinea (PNG) with an estimated 30000 new cases and 3800 deaths each year. In the Balimo region of the Western Province, diagnosis relies on clinical manifestations and on the microscopic detection of acid-fast bacilli (AFB) in sputum smears, a technique with limited sensitivity., Methods: A molecular diagnosis assay targeting DNA extracted from archived sputum smear slides collected from the Balimo region (2012-2014) was conducted, without the need for a viable culture. The presence of Mycobacterium sp on 1162 slides prepared from 345 sputum samples was assessed using a real-time PCR (qPCR) approach., Results: The qPCR technique identified the presence of mycobacteria in 35.4% of the smear slides and 59.7% of the tested sputum samples. Poor agreement was observed between the two diagnosis methods (smear AFB microscopy versus qPCR), with 100 AFB-positive sputum samples compared to 206 qPCR-positive sputum samples overall. Treatment was initiated in 90.2% of the smear-positive cases. Unnecessary treatment of 'false-positive' TB cases (AFB-negative/qPCR-negative) was very low (8.6%) and was even lower when the nine patients diagnosed with extrapulmonary TB were excluded from the analysis. However, the prevalence of false-negatives (AFB-negative/qPCR-positive) was high (28.5%)., Conclusions: Undetected smear-negative TB is occurring in the Balimo region of PNG, as well as some unnecessary empirical treatment. Molecular methods of diagnosis could greatly reduce the frequency of inappropriate clinical assessment, as well as providing point-of-care diagnosis. This may provide substantial patient and programmatic benefits, including lowering the economic burden on patients from rural areas seeking medical diagnosis in Balimo., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Leptospirosis is a bacterial zoonosis caused by pathogenic Leptospira for which rats are considered as the main reservoir. Disease incidence is higher in tropical countries, especially in insular ecosystems. Our objectives were to determine the current burden of leptospirosis in Seychelles, a country ranking first worldwide according to historical data, to establish epidemiological links between animal reservoirs and human disease, and to identify drivers of transmission., Methods: A total of 223 patients with acute febrile symptoms of unknown origin were enrolled in a 12-months prospective study and tested for leptospirosis through real-time PCR, IgM ELISA and MAT. In addition, 739 rats trapped throughout the main island were investigated for Leptospira renal carriage. All molecularly confirmed positive samples were further genotyped., Results: A total of 51 patients fulfilled the biological criteria of acute leptospirosis, corresponding to an annual incidence of 54.6 (95% CI 40.7-71.8) per 100,000 inhabitants. Leptospira carriage in Rattus spp. was overall low (7.7%) but dramatically higher in Rattus norvegicus (52.9%) than in Rattus rattus (4.4%). Leptospira interrogans was the only detected species in both humans and rats, and was represented by three distinct Sequence Types (STs). Two were novel STs identified in two thirds of acute human cases while noteworthily absent from rats., Conclusions: This study shows that human leptospirosis still represents a heavy disease burden in Seychelles. Genotype data suggests that rats are actually not the main reservoir for human disease. We highlight a rather limited efficacy of preventive measures so far implemented in Seychelles. This could result from ineffective control measures of excreting animal populations, possibly due to a misidentification of the main contaminating reservoir(s). Altogether, presented data stimulate the exploration of alternative reservoir animal hosts.

Background: Leptospirosis is a highly endemic bacterial zoonosis in French Polynesia (FP). Nevertheless, data on the epidemiology of leptospirosis in FP are scarce. We conducted molecular studies on Leptospira isolated from humans and the potential main animal reservoirs in order to identify the most likely sources for human infection., Methodology/principal Findings: Wild rats (n = 113), farm pigs (n = 181) and domestic dogs (n = 4) were screened for Leptospira infection in Tahiti, the most populated island in FP. Positive samples were genotyped and compared to Leptospira isolated from human cases throughout FP (n = 51), using secY, 16S and LipL32 sequencing, and MLST analysis. Leptospira DNA was detected in 20.4% of rats and 26.5% of pigs. We identified two Leptospira species and three sequence types (STs) in animals and humans: Leptospira interrogans ST140 in pigs only and L. interrogans ST17 and Leptospira borgpetersenii ST149 in humans and rats. Overall, L. interrogans was the dominant species and grouped into four clades: one clade including a human case only, two clades including human cases and dogs, and one clade including human cases and rats. All except one pig sample showed a unique L. interrogans (secY) genotype distinct from those isolated from humans, rats and dogs. Moreover, LipL32 sequencing allowed the detection of an additional Leptospira genotype in pigs, clearly distinct from the previous ones., Conclusions/significance: Our data confirm rats as a major potential source for human leptospirosis in FP. By contrast to what was expected, farm pigs did not seem to be a major reservoir for the Leptospira genotypes identified in human patients. Thus, further investigations will be required to determine their significance in leptospirosis transmission in FP.

Objectives: Multidrug-resistant tuberculosis (MDR-TB) is a threat to tuberculosis (TB) control. To guide TB control, it is essential to understand the extent to which and the circumstances in which MDR-TB will replace drug-susceptible TB (DS-TB) as the dominant phenotype. The issue was examined by assessing evidence from genomics, pharmacokinetics, and epidemiology studies. This evidence was then synthesized into a mathematical model., Methods: This model considers two TB strains, one with and one without an MDR phenotype. It was considered that intrinsic transmissibility may be different between the two strains, as may the control response including the detection, treatment failure, and default rates. The outcomes were explored in terms of the incidence of MDR-TB and time until MDR-TB surpasses DS-TB as the dominant strain., Results and Conclusions: The ability of MDR-TB to dominate DS-TB was highly sensitive to the relative transmissibility of the resistant strain; however, MDR-TB could dominate even when its transmissibility was modestly reduced (to between 50% and 100% as transmissible as the DS-TB strain). This model suggests that it may take decades or more for strain replacement to occur. It was also found that while the amplification of resistance is the early cause of MDR-TB, this will rapidly give way to person-to-person transmission., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Bidirectional signalling between the brain and the gastrointestinal tract is regulated at neural, hormonal, and immunological levels. Recent studies have shown that helminth infections can alter the normal gut microbiota. Studies have also shown that the gut microbiota is instrumental in the normal development, maturation and function of the brain. The pathophysiological pathways by which helminth infections contribute to altered cognitive function remain poorly understood., Discussion: We put forward the hypothesis that gastrointestinal infections with parasitic worms, such as helminths, induce an imbalance of the gut-brain axis, which, in turn, can detrimentally manifest in brain development. Factors supporting this hypothesis are: 1) research focusing on intelligence and school performance in school-aged children has shown helminth infections to be associated with cognitive impairment, 2) disturbances in gut microbiota have been shown to be associated with important cognitive developmental effects, and 3) helminth infections have been shown to alter the gut microbiota structure. Evidence on the complex interactions between extrinsic (parasite) and intrinsic (host-derived) factors has been synthesised and discussed. While evidence in favour of the helminth-gut microbiota-central nervous system hypothesis is circumstantial, it would be unwise to rule it out as a possible mechanism by which gastrointestinal helminth infections induce childhood cognitive morbidity. Further empirical studies are necessary to test an indirect effect of helminth infections on the modulation of mood and behaviour through its effects on the gut microbiota.

Background: Although leptospirosis is a zoonosis of major concern on tropical islands, the molecular epidemiology of the disease aiming at linking human cases to specific animal reservoirs has been rarely explored within these peculiar ecosystems., Methodology/principal Findings: Five species of wild small mammals (n = 995) as well as domestic animals (n = 101) were screened for Leptospira infection on Reunion Island; positive samples were subsequently genotyped and compared to Leptospira from clinical cases diagnosed in 2012-2013 (n = 66), using MLST analysis. We identified two pathogenic species in human cases, namely Leptospira interrogans and Leptospira borgpetersenii. Leptospira interrogans was by far dominant both in clinical samples (96.6%) and in infected animal samples (95.8%), with Rattus spp and dogs being its exclusive carriers. The genetic diversity within L. interrogans was apparently limited to two sequence types (STs): ST02, identified among most clinical samples and in all rats with complete MLST, and ST34, identified in six humans, but not in rats. Noteworthy, L. interrogans detected in two stray dogs partially matched with ST02 and ST34. Leptospira borgpetersenii was identified in two clinical samples only (3.4%), as well as in cows and mice; four haplotypes were identified, of which two seemingly identical in clinical and animal samples. Leptospira borgpetersenii haplotypes detected in human cases were clearly distinct from the lineage detected so far in the endemic bat species Mormopterus francoismoutoui, thus excluding a role for this volant mammal in the local human epidemiology of the disease., Conclusions/significance: Our data confirm rats as a major reservoir of Leptospira on Reunion Island, but also pinpoint a possible role of dogs, cows and mice in the local epidemiology of human leptospirosis. This study shows that a comprehensive molecular characterization of pathogenic Leptospira in both clinical and animal samples helps to gaining insight into leptospirosis epidemiology within a specific environmental setting.

Background: Tick paralysis, resultant from envenomation by the scrub-tick Ixodes holocyclus, is a serious threat for small companion animals in the eastern coast of Australia. We hypothesise that surveillance systems that are built on Internet search queries may provide a more timely indication of high-risk periods more effectively than current approaches., Methods: Monthly tick paralysis notifications in dogs and cats across Australia and the states of Queensland (QLD) and New South Wales (NSW) were retrieved from Disease WatchDog surveillance system for the period 2011-2013. Internet search terms related to tick paralysis in small companion animals were identified using Google Correlate, and corresponding search frequency metrics were downloaded from Google Trends. Spearman's rank correlations and time series cross correlations were performed to assess which Google search terms lead or are synchronous with tick paralysis notifications., Results: Metrics data were available for 24 relevant search terms at national level, 16 for QLD and 18 for NSW, and they were all significantly correlated with tick paralysis notifications (P < 0.05). Among those terms, 70.8, 56.3 and 50 % showed strong Spearman's correlations, at national level, for QLD, and for NSW respectively, and cross correlation analyses identified searches which lead notifications at national or state levels., Conclusion: This study demonstrates that Internet search metrics can be used to monitor the occurrence of tick paralysis in companion animals, which would facilitate early detection of high-risk periods for tick paralysis cases. This study constitutes the first application of the rapidly emerging field of Internet-based surveillance to veterinary science.

Rickettsia felis, Rickettsia typhi, and Bartonella DNA was detected by molecular tools in 12% of Rattus rattus fleas (Xenopsylla species) collected from Reunion Island. One-third of the infested commensal rodents captured during 1 year carried at least one infected flea. As clinical signs of these zoonoses are non-specific, they are often misdiagnosed., (© The American Society of Tropical Medicine and Hygiene.)

The diversity and geographical distribution of fleas parasitizing small mammals have been poorly investigated on Indian Ocean islands with the exception of Madagascar where endemic plague has stimulated extensive research on these arthropod vectors. In the context of an emerging flea-borne murine typhus outbreak that occurred recently in Reunion Island, we explored fleas' diversity, distribution and host specificity on Reunion Island. Small mammal hosts belonging to five introduced species were trapped from November 2012 to November 2013 along two altitudinal transects, one on the windward eastern and one on the leeward western sides of the island. A total of 960 animals were trapped, and 286 fleas were morphologically and molecularly identified. Four species were reported: (i) two cosmopolitan Xenopsylla species which appeared by far as the prominent species, X. cheopis and X. brasiliensis; (ii) fewer fleas belonging to Echidnophaga gallinacea and Leptopsylla segnis. Rattus rattus was found to be the most abundant host species in our sample, and also the most parasitized host, predominantly by X. cheopis. A marked decrease in flea abundance was observed during the cool-dry season, which indicates seasonal fluctuation in infestation. Importantly, our data reveal that flea abundance was strongly biased on the island, with 81% of all collected fleas coming from the western dry side and no Xenopsylla flea collected on almost four hundred rodents trapped along the windward humid eastern side. The possible consequences of this sharp spatio-temporal pattern are discussed in terms of flea-borne disease risks in Reunion Island, particularly with regard to plague and the currently emerging murine typhus outbreak.

The spatial dynamics of zoonotic arthropod-borne viruses is a fashionable though challenging topic. Inter-human local transmission of a given arbovirus during an outbreak and its spread over large distances are considered as key parameters of emergence. Here, we suggest that insular ecosystems provide ideal natural "laboratory" conditions to uncouple local transmission from long distance spread, and differentiate these two processes. Due to geographic isolation, often-limited land surface area and relatively homogenous ecosystems, oceanic islands display low species richness and often-high levels of endemism. These aspects provide the means for comprehensive entomological surveys and investigations of original host/pathogen interactions. In addition, islands are interconnected through discrete anthropogenic and non-anthropogenic exchanges: whilst islands maintain a substantial level of human and domestic animal exchange with other neighbouring or distant territories, they also comprise dispersal and migratory pathways of volant organisms (insects, birds and bats). Hence, both anthropogenic and non-anthropogenic exchanges in island systems are easier to identify and investigate than in continuous, continental systems. Finally, island ecosystems tend to be notably simpler, more prone to invasive taxa and, therefore, easier to document the colonization or displacement of vector species. These different aspects are presented and overlaid upon the spread of arboviruses within two distinct insular systems: islands of Polynesia and the south-western Indian Ocean. The former have been repeatedly affected by Dengue fever epidemics, while the latter recently suffered four successive epidemics, probably of east African origin, three of which involved the emerging viruses Chikungunya, Rift Valley and Dengue fever. Here, we review some new insights into arboviral spread and evolution associated with investigations that followed these epidemics, as well as several aspects that make insular ecosystems favourable to the investigation of arboviral transmission and spread., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: To date, there is little information that reflects the true extent of spread of the pH1N1/2009v influenza pandemic at the community level as infection often results in mild or no clinical symptoms. This study aimed at assessing through a prospective study, the attack rate of pH1N1/2009 virus in Reunion Island and risk factors of infection, during the 2009 season., Methodology/principal Findings: A serosurvey was conducted during the 2009 austral winter, in the frame of a prospective population study. Pairs of sera were collected from 1687 individuals belonging to 772 households, during and after passage of the pandemic wave. Antibodies to pH1N1/2009v were titered using the hemagglutination inhibition assay (HIA) with titers ≥ 1/40 being considered positive. Seroprevalence during the first two weeks of detection of pH1N1/2009v in Reunion Island was 29.8% in people under 20 years of age, 35.6% in adults (20-59 years) and 73.3% in the elderly (≥ 60 years) (P<0.0001). Baseline corrected cumulative incidence rates, were 42.9%, 13.9% and 0% in these age groups respectively (P<0.0001). A significant decline in antibody titers occurred soon after the passage of the epidemic wave. Seroconversion rates to pH1N1/2009 correlated negatively with age: 63.2%, 39.4% and 16.7%, in each age group respectively (P<0.0001). Seroconversion occurred in 65.2% of individuals who were seronegative at inclusion compared to 6.8% in those who were initially seropositive., Conclusions: Seroincidence of pH1N1/2009v infection was three times that estimated from clinical surveillance, indicating that almost two thirds of infections occurring at the community level have escaped medical detection. People under 20 years of age were the most affected group. Pre-epidemic titers ≥ 1/40 prevented seroconversion and are likely protective against infection. A concern was raised about the long term stability of the antibody responses.

Many debates surround the generalization of Rapoport's rule (i.e., the presence of a positive correlation between range size and latitude); however, little attention has been devoted to this spatial pattern (1) worldwide and (2) for pathogenic microorganisms. In this study, we analyzed this relationship for 290 human pathogenic species dispersed throughout the world to test whether pathogenic organisms with different ecological niches and strategies will show this trend. The midpoint method was used to calculate the correlation between the geographical range size and the latitude applied to different subsets of pathogens, including taxonomic subdivisions (bacteria, viruses, helminths, protozoans, and fungi) and categories based on transmission mode and host specificity. It is assumed that Rapoport's spatial pattern may exist for human infectious diseases, whatever hemisphere is considered, for 5 to 7 of 8 of the selected groups, depending on the pathogen species included. This is the first study performed to investigate Rapoport's pattern at a global scale for various pathogenic organisms. We also discuss how three well-known spatial patterns of diversity, i.e., latitudinal gradient, nested species pattern, and Rapoport's rule, may vary together to produce the actual large-scale geographical distribution of human pathogenic species observed on Earth. These findings have important messages for understanding the distribution and the diffusion of human pathogenic species; however, further studies are needed to investigate the exact underlying mechanisms responsible for those patterns.

Background: French Guiana has the highest tuberculosis (TB) burden among all French departments, with a strong increase in the TB incidence over the last few years. It is now uncertain how best to explain this incidence. The objective of this study was to compare three different methods evaluating the extent of recent TB transmission in French Guiana., Methods: We conducted a population-based molecular epidemiology study of tuberculosis in French Guiana based on culture-positive TB strains (1996 to 2003, n = 344) to define molecular relatedness between isolates, i.e. potential transmission events. Phylogenetic relationships were inferred by comparing two methods: a "cluster-graph" method based on spoligotyping results, and a minimum spanning tree method based on both spoligotyping and variable number of tandem DNA repeats (VNTR). Furthermore, three indices attempting to reflect the extent of recent TB transmission (RTIn, RTIn-1 and TMI) were compared., Results: Molecular analyses showed a total amount of 120 different spoligotyping patterns and 273 clinical isolates (79.4%) that were grouped in 49 clusters. The comparison of spoligotypes from French Guiana with an international spoligotype database (SpolDB4) showed that the majority of isolates belonged to major clades of M. tuberculosis (Haarlem, 22.6%; Latin American-Mediterranean, 23.3%; and T, 32.6%). Indices designed to quantify transmission of tuberculosis gave the following values: RTIn = 0.794, RTIn-1 = 0.651, and TMI = 0.146., Conclusion: Our data showed a high number of Mycobacterium tuberculosis clusters, suggesting a high level of recent TB transmission, nonetheless an estimation of transmission rate taking into account cluster size and mutation rate of genetic markers showed a low ongoing transmission rate (14.6%). Our results indicate an endemic mode of TB transmission in French Guiana, with both resurgence of old spatially restricted genotypes, and a significant importation of new TB genotypes by migration of TB infected persons from neighgouring high-incidence countries.

Globalization has facilitated the spread of numerous infectious agents to all corners of the planet. Analysis of the Global Infectious Disease and Epidemiology Network (GIDEON) database quantitatively illustrates that the globalization of human infectious agents depends significantly on the range of hosts used. Infectious agents specific to humans are broadly and uniformly distributed, whereas zoonotic infectious agents are far more localized in their geographical distribution. Moreover, these patterns vary depending on transmission mode and infectious agent taxonomy. This dichotomy is unlikely to persist if certain aspects of globalization (for example, exotic species introductions) continue unabated. This raises a serious concern for public health and leaves nations with the task of determining the infectious agents that have the greatest potential to establish within their borders. At the advent of a century characterized by an apparent increase in emerging infectious diseases, these results have critical implications for public-health policy and future research pathways of infectious disease ecology.

In order to estimate the level of under-reporting and to improve estimates of the incidence of tuberculosis (TB) in the vicinity of Cayenne, French Guiana, we performed capture-recapture analysis from 1996 through 2003. We cross-linked data from the Institut Pasteur, the Département d'Information Médicale of Cayenne Hospital, and the Service de Lutte Anti-Tuberculeuse. The estimate of 381 TB cases obtained after matching those three sources was revised to 425 (95% confidence interval: 407, 453) using the capture-recapture model based on sample coverage. The corresponding average annual incidence was 63.1 TB cases per 100,000 population. The evaluated sensitivity of the compulsory notification system was 35.3%, indicating wide under-notification of TB in the vicinity of Cayenne. The estimated coverage reported by the three sources was fairly accurate (i.e. 85.9%), but not sufficient to evaluate the risk of transmission of TB in the Ile-de-Cayenne (Cayenne and its suburbs).

The three French overseas departments of the Americas are characterized both by insular (Guadeloupe and Martinique) and continental (French Guiana) settings with a tuberculosis case detection rate that varies from less than 10 per 100,000 per year in insular areas to an estimated incidence of more than 55 per 100,000 in French Guiana. Under a long-term genotyping program, more than three-fourths of all the Mycobacterium tuberculosis isolates (n = 744) received from the three settings were fingerprinted over a 10-year period (1994 to 2003) by spoligotyping and variable number of tandem DNA repeats (VNTRs) in order to understand the current trends in their detection rates, drug resistance, and groups and subpopulations at risk of contracting the disease and to pinpoint the circulating phylogeographical clades of the bacilli. The major difference in the study populations was the nationality of the patients, with a high percentage of immigrants from high-incidence neighboring countries in French Guiana and a low but increasing percentage in the French Caribbean. The rate of recent transmission was calculated to be 49.3% in French Guiana, compared to 27.2% and 16.9% in Guadeloupe and Martinique, respectively. At the phylogeographic level, 77.9% of the isolates studied belonged to four major clades (Haarlem, Latin-American and Mediterranean, T, and X) which are already reported from neighboring Caribbean islands in an international database and may underline potential interregional transmission events.

The human leukocyte antigen (HLA; known as MHC in other vertebrates) plays a central role in the recognition and presentation of antigens to the immune system and represents the most polymorphic gene cluster in the human genome [1]. Pathogen-driven balancing selection (PDBS) has been previously hypothesized to explain the remarkable polymorphism in the HLA complex, but there is, as yet, no direct support for this hypothesis [2 and 3]. A straightforward prediction coming out of the PDBS hypothesis is that populations from areas with high pathogen diversity should have increased HLA diversity in relation to their average genomic diversity. We tested this prediction by using HLA class I genetic diversity from 61 human populations. Our results show that human colonization history explains a substantial proportion of HLA genetic diversity worldwide. However, between-population variation at the HLA class I genes is also positively correlated with local pathogen richness (notably for the HLA B gene), thus providing support for the PDBS hypothesis. The proportion of variations explained by pathogen richness is higher for the HLA B gene than for the HLA A and HLA C genes. This is in good agreement with both previous immunological and genetic data suggesting that HLA B could be under a higher selective pressure from pathogens.

Identifying the factors underlying the origin and maintenance of the latitudinal diversity gradient is a central problem in ecology, but no consensus has emerged on which processes might generate this broad pattern. Interestingly, the vast majority of studies exploring the gradient have focused on free-living organisms, ignoring parasitic and infectious disease (PID) species. Here, we address the influence of environmental factors on the biological diversity of human pathogens and their global spatial organization. Using generalized linear multivariate models and Monte Carlo simulations, we conducted a series of comparative analyses to test the hypothesis that human PIDs exhibit the same global patterns of distribution as other taxonomic groups. We found a significant negative relationship between latitude and PID species richness, and a nested spatial organization, i.e., the accumulation of PID species with latitude, over large spatial scales. Additionally, our results show that climatic factors are of primary importance in explaining the link between latitude and the spatial pattern of human pathogens. Based on our findings, we propose that the global latitudinal species diversity gradient might be generated in large part by biotic interactions, providing strong support for the idea that current estimates of species diversity are substantially underestimated. When parasites and pathogens are included, estimates of total species diversity may increase by more than an order of magnitude., Competing Interests: The authors have declared that no conflicts of interest exist.