The Role of Heterogenous Real-world Data for Dengue Surveillance in Martinique: Observational Retrospective Study.

BACKGROUND: Traditionally, dengue prevention and control rely on vector control programs and reporting of symptomatic cases to a central health agency. However, case reporting is often delayed, and the true burden of dengue disease is often underestimated. Moreover, some countries do not have routine control measures for vector control. Therefore, researchers are constantly assessing novel data sources to improve traditional surveillance systems. These studies are mostly carried out in big territories and rarely in smaller endemic regions, such as Martinique and the Lesser Antilles. OBJECTIVE: The aim of this study was to determine whether heterogeneous real-world data sources could help reduce reporting delays and improve dengue monitoring in Martinique island, a small endemic region. METHODS: Heterogenous data sources (hospitalization data, entomological data, and Google Trends) and dengue surveillance reports for the last 14 years (January 2007 to February 2021) were analyzed to identify associations with dengue outbreaks and their time lags. RESULTS: The dengue hospitalization rate was the variable most strongly correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.70) with a time lag of -3 weeks. Weekly entomological interventions were also correlated with the increase in dengue positivity rate by real-time reverse transcription polymerase chain reaction (Pearson correlation coefficient=0.59) with a time lag of -2 weeks. The most correlated query from Google Trends was the "Dengue" topic restricted to the Martinique region (Pearson correlation coefficient=0.637) with a time lag of -3 weeks. CONCLUSIONS: Real-word data are valuable data sources for dengue surveillance in smaller territories. Many of these sources precede the increase in dengue cases by several weeks, and therefore can help to improve the ability of traditional surveillance systems to provide an early response in dengue outbreaks. All these sources should be better integrated to improve the early response to dengue outbreaks and vector-borne diseases in smaller endemic territories.

Outbreak of Chikungunya in the French Caribbean Islands of Martinique and Guadeloupe: Findings from a Hospital-Based Surveillance System (2013-2015).

Chikungunya virus (CHIKV) emerged in the Caribbean island of Saint-Martin in December 2013. We implemented a hospital-based surveillance system to detect and describe CHIKV cases including severe forms of the infection and deaths in the islands of Martinique and Guadeloupe. A case was defined as a patient with a CHIKV laboratory confirmation cared for in a public hospital for chikungunya for at least 24 hours, and a severe CHIKV case was defined as a CHIKV case presenting one or more organ failures. Sociodemographic, clinical, and laboratory data were collected and cases classified into severe or nonsevere based on medical records. From December 2013 to January 2015, a total of 1,836 hospitalized cases were identified. Rate of hospital admissions for CHIKV infection was 60 per 10,000 suspected clinical CHIKV cases and severity accounted for 12 per 10,000. A total of 74 deaths related to CHIKV infection occurred. Infants and elderly people were more frequently hospitalized compared with others and severity was more frequently reported in elderly subjects and subjects with underlying health condition. Fifteen neonatal infections consecutive to mother-to-child transmission were diagnosed, seven of which were severe. The most vulnerable groups of the population, such as the elderly, infants, individuals with comorbidities, and pregnant women, should remain the main targets of public health priorities.

Correction: Underestimation of Leptospirosis Incidence in the French West Indies.

[This corrects the article DOI: 10.1371/journal.pntd.0004668.].

Evaluation of different serological assays for early diagnosis of leptospirosis in Martinique (French West Indies).

BACKGROUND: Leptospirosis is a potentially life-threatening but curable zoonosis whose prognosis depends on accurate and timely diagnosis. Because of its non-specific clinical presentation, laboratory testing is essential to confirm the diagnosis. Here, we aimed to assess the performance of two enzyme-linked immunosorbent assays (ELISAs) (ELISA Serion and ELISA-Hb Pasteur) and one immunodot (GenBio) using quantitative PCR (qPCR) as gold standard, instead of the traditional microscopic agglutination test, for the diagnosis of acute leptospirosis in an endemic area. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2011 and December 2012, a total of 122 patients were diagnosed with leptospirosis, as confirmed by qPCR at the University Hospital of Martinique. Among them, 103 had at least one serum sample available for analysis. Performance of each serological assay was evaluated according to days' post onset of symptoms (DPO) and local species diversity (which included L. santarosai, L. interrogans, L. kirschneri, L. borgpetersenii, L. noguchii, and L. kmetyi). Several thresholds were tested to optimize accuracy. When considering the manufacturer's threshold, the sensitivity of ELISA Serion, ELISA-Hb Pasteur and GenBio immunodot was 75%, 67% and 64%, while specificity was 92%, 98% and 100%, respectively. Moreover, the threshold optimization allowed a significant improvement in specificity for the ELISA Serion from 92% to 99% (p<0.05). During the first 5 DPO, sensitivities were 35%, 30% and 42% for ELISA Serion, ELISA-Hb Pasteur and GenBio immunodot, respectively. However, between 6─10 DPO, these sensitivities dramatically increased to reach 86%, 76% and 67%, respectively. Performances of the three assays were not affected by the species studied. CONCLUSIONS/SIGNIFICANCE: All these serological assays showed the potential for diagnosing leptospirosis after (but not before) 6 days' post onset of symptoms. In a high prevalence setting, where highest specificities are needed, threshold optimizing should be performed for this purpose.

Underestimation of Leptospirosis Incidence in the French West Indies.

BACKGROUND: Leptospirosis is a neglected zoonosis affecting mainly tropical and subtropical regions worldwide, particularly South America and the Caribbean. As in many other countries, under-reporting of cases was suspected in the French West Indies because of inadequate access to diagnostic tests for the general population. METHODOLOGY/PRINCIPAL FINDINGS: In order to estimate the real incidence of leptospirosis in Guadeloupe and Martinique, a study was performed in 2011 using the three prevailing available biological tests for diagnosis: Microscopic Agglutination Test (MAT), IgM ELISA and PCR. The study investigated inpatients and outpatients and used active case ascertainment from data provided by a general practitioners' sentinel network. The epidemiology of the disease was also described in terms of severity and demographic characteristics. Leptospirosis incidence was estimated at 69.4 (95%CI 47.6-91.1) and 60.6 (95%CI 36.3-85.0) annual cases per 100,000 inhabitants in Guadeloupe and Martinique, respectively, which was 3 and 4 times higher than previous estimations. CONCLUSION/SIGNIFICANCE: Inclusion of PCR and IgM ELISA tests for diagnosis of leptospirosis resulted in improved sensitivity in comparison with MAT alone. Our results highlighted the substantial health burden of the disease in these two territories and the importance of access to appropriate laboratory tests. Based on our results, PCR and IgM ELISA tests have now been included in the list of tests reimbursed by the national system of social security insurance in France. Our results also underline the relevance of implementing an integrated strategy for the surveillance, prevention and control of leptospirosis in the French West Indies.

Seroprevalence of Asian Lineage Chikungunya Virus Infection on Saint Martin Island, 7 Months After the 2013 Emergence.

At the end of 2013, chikungunya virus (CHIKV) emerged in Saint Martin Island, Caribbean. The Asian lineage was identified. Seven months after this introduction, the seroprevalence was 16.9% in the population of Saint Martin and 39.0% of infections remained asymptomatic. This moderate attack rate and the apparent limited size of the outbreak in Saint Martin could be explained by control measures involved to lower the exposure of the inhabitants. Other drivers such as climatic factors and population genetic factors should be explored. The substantial rate of asymptomatic infections recorded points to a potential source of infection that can both spread in new geographic areas and maintain an inconspicuous endemic circulation in the Americas.

Clinical presentation of dengue by serotype and year of epidemic in Martinique.

During the last decade Martinique experienced four dengue epidemics, each characterized by the predominance of 1 or 2 serotypes. In this retrospective database analysis, we investigated the relationship between dengue serotype and disease severity. Data on dengue were collected from 715 patients (male/female ratio 0.87), 14 to 91 years of age (median 35 years) examined in the adult emergency department between 2005 and 2010. In this series, DENV-4 infections more frequently had a milder clinical presentation. The DENV-2 infections were most often secondary infections admitted at the critical phase of dengue illness with signs of plasma leakage. The DENV-1 infections were disabling, particularly in females, and most often led to disease of intermediate severity, without overt plasma leakage. These data were consistent with there being differences in virulence between serotypes, regardless of the host's immune status. However, secondary DENV-2 infections showed an increased risk of plasma leakage.

Serovar diversity of pathogenic Leptospira circulating in the French West Indies.

BACKGROUND: Leptospirosis is one of the most important neglected tropical bacterial diseases in Latin America and the Caribbean. However, very little is known about the circulating etiological agents of leptospirosis in this region. In this study, we describe the serological and molecular features of leptospires isolated from 104 leptospirosis patients in Guadeloupe (n = 85) and Martinique (n = 19) and six rats captured in Guadeloupe, between 2004 and 2012. METHODS AND FINDINGS: Strains were studied by serogrouping, PFGE, MLVA, and sequencing 16SrRNA and secY. DNA extracts from blood samples collected from 36 patients in Martinique were also used for molecular typing of leptospires via PCR. Phylogenetic analyses revealed thirteen different genotypes clustered into five main clades that corresponded to the species: L. interrogans, L. kirschneri, L. borgpetersenii, L. noguchi, and L. santarosai. We also identified L. kmetyi in at least two patients with acute leptospirosis. This is the first time, to our knowledge, that this species has been identified in humans. The most prevalent genotypes were associated with L. interrogans serovars Icterohaemorrhagiae and Copenhageni, L. kirschneri serovar Bogvere, and L. borgpetersenii serovar Arborea. We were unable to identify nine strains at the serovar level and comparison of genotyping results to the MLST database revealed new secY alleles. CONCLUSIONS: The overall serovar distribution in the French West Indies was unique compared to the neighboring islands. Typing of leptospiral isolates also suggested the existence of previously undescribed serovars.

Investigation of a sudden malaria outbreak in the isolated Amazonian village of Saul, French Guiana, January-April 2009.

Malaria is endemic in French Guiana. Plasmodium falciparum and Plasmodium vivax are the predominant species responsible and Anopheles darlingi is described as the major vector. In mid-August 2008, an increase in malaria incidence was observed in Saül. A retrospective cohort survey was performed. In vitro susceptibility profiles to antimalarials were determined on P. falciparum isolates. Collections of mosquitoes were organized. The malaria attack rate reached 70.6/100. The risk of malaria increased for people between 40 and 49 years of age, living in a house not subjected to a recent indoor residual insecticide spraying or staying overnight in the surrounding forest. All isolates were susceptible. Anopheles darlingi females and larvae were collected in the village suggesting a local transmission. Our results strongly support a role of illegal mining activities in the emergence of new foci of malaria. Therefore, public health authorities should define policies to fight malaria at a transborder level.

Outbreak of leptospirosis after a race in the tropical forest of Martinique.

Three athletes who participated in a race in the tropical forest of the Caribbean island of Martinique were subsequently diagnosed with leptospirosis using polymerase chain reaction (PCR). We investigated an outbreak to evaluate possible risk factors, and to determine the appropriate public health recommendations. Of 230 athletes, we contacted 148 (64%) and 20 (13.5%) met our case definition. Five were hospitalized and none were fatal. Ten (91%) of the 11 ill athletes who were tested were confirmed by PCR or serology. Serogroup Pyrogenes was commonly found. Cutaneous cuts, reported by 14 (73.7%), was the only potential risk factor using univariate analysis. Sporting event participants in tropical areas should be made aware of specific warnings and recommendations concerning the risk of leptospirosis, especially after periods of heavy rainfall or flooding. Rapid diagnostic assays such as PCR are particularly appropriate in this setting for early diagnosis and for formulating public health recommendations.

Predictors of severe manifestations in a cohort of adult dengue patients.

BACKGROUND: Key symptoms observed during the febrile phase of dengue may identify patients who are likely to progress to severe disease. OBJECTIVES: To test this hypothesis, we examined the relationships between symptoms reported by patients at presentation and the development of severe outcomes. STUDY DESIGN: Retrospective analysis of data recorded prospectively in 560 adult dengue patients admitted to an emergency department. A logistic regression analysis was used to quantify the association between symptoms reported at presentation and outcome. RESULTS: Plasma leakage was observed in 95 patients (17%), severe thrombocytopenia (platelet counts <20 x 10(9)/L) in 93 patients (16.6%) and acute hepatitis in 42 patients (7.5%). Severe thrombocytopenia developed in 57% of patients with plasma leakage and 40.5% of patients with hepatitis. Patients who developed a plasma leakage syndrome were older, mainly male, and reported more often an abdominal pain and a cough. Diarrhea and taking paracetamol >60 mg/kg/day before admission were associated with the development of acute hepatitis. Seven patients died. The mortality rate was 6/95 (6.3%) in patients who developed plasma leakage, 3/42 (7.1%) in patients who developed hepatitis, 5/93 (5.4%) in patients with severe thrombocytopenia, and 3/12 (25%) in the patients who demonstrated together all these severe manifestations. CONCLUSION: Plasma leakage, severe thrombocytopenia and acute hepatitis identified subgroups of adult dengue patients with increased mortality rates. Key symptoms reported by the patients at presentation such as abdominal pain, cough or diarrhea were significantly associated with the development of severe manifestations and should be considered as warning signs.

Evolution of resistance under insecticide selection pressure in Culex pipiens quinquefasciatus (Diptera, Culicidae) from Martinique.

Population surveys of Culex pipiens quinquefasciatus carried out in 1991 and 1999 were compared with data collected in 1990 before the beginning of the control program against this mosquito. Larval samples collected in 1999 displayed resistance to the four tested insecticides: permethrin, propoxur, temephos, and chlorpyrifos. Temephos resistance ratio at LC50 (RR50) ranged between 8.1- and 42-fold compared with 2.9- and 4.6-fold in 1990, and chlorpyrifos RR50 ranged between 8.6- and 123-fold compared with 6.4- and 19-fold in 1990. This increased resistance to organophosphorus insecticides was associated with a sharp decrease of susceptible genotypes at two loci (Ester and ace-1), as well as to an allele replacement at the Ester locus.