Infant neurodevelopment and behavior in Guadeloupe after lead exposure and Zika maternal infection during pregnancy.

BACKGROUND: Prenatal lead exposure is known to have neurotoxic effects on the developing fetus, while some viral infections may have a tropism for the central nervous system. Our objective was to study whether the effects of prenatal lead exposure on infant development and behaviors at 18 months of age are modified by the occurrence of a maternal infection to Zika virus (ZIKV) during pregnancy. METHODS: During the ZIKV epidemic in Guadeloupe in 2016 a cohort of pregnant women was set up. Blood samples (pregnancy, childbirth and cord) (n = 297) enabled us to measure blood lead levels aimed to determine prenatal lead exposure and the likelihood of maternal infection during pregnancy (ZIKV status + vs -). The 18 months "Ages and Stages Questionnaire" (ASQ) was used to generate scores for global development, fine and gross motor skills, communication, problem solving, and personal-social skills. The questions from a longitudinal cohort study conducted in Canada (Québec) were used to generate hyperactivity, opposition, inattention and physical aggression scores. Associations were tested by multivariate linear regressions. RESULTS: Prenatal lead exposure was associated with delays in neurodevelopment at 18 months, reflected by lower scores in ASQ totals, and in the fine motor and problem-solving domains. Some of these associations appeared to be sex-specific, observed almost exclusively in boys (ASQ total, fine motor and personal-social scores). Prenatal lead exposure was not associated with behavioral scores. ZIKV infection during pregnancy was associated with a lower fine motor ASQ score, and higher scores for hyperactivity, opposition and physical aggression. Significant interaction between prenatal lead exposure and ZIKV status was observed with a lower personal-social score in ZIKV (-) only, and for hyperactivity and inattention scores, though some of these interactions (ASQ personal-social score, inattention score) were no longer significant when children with microcephaly were excluded from the analyses. DISCUSSION/CONCLUSION: Our study confirms previous findings of associations between prenatal exposure to lead at low levels and adverse neurodevelopmental outcomes during infancy and the particular vulnerability of boys. It suggests associations between ZIKV infection during pregnancy and adverse effects on a number of neurodevelopmental functions (fine motor function) and behaviors (opposition, hyperactivity), that need to be confirmed at later age. There is no strong evidence of interaction between ZIKV infection and lead exposure but both prenatal risk factors may affect fine motor function.

Simultaneous exposure to both Zika virus and household insecticides during pregnancy, and fetal growth and infant developmental behavior outcomes at 18 months, in Guadeloupe.

BACKGROUND: Perinatal infection with Zika virus (ZIKV) could result in adverse growth, developmental and behavioral outcomes, while insecticides used to control mosquitoes are neurotoxic. OBJECTIVES: We aim to study the role played by exposure during pregnancy to both ZIKV and household insecticides in newborn health, development and behavior at age of 18 months. METHODS: Maternal and cord blood samples from a cohort of pregnant women (created during Guadeloupe's Zika epidemic of 2016) were used to identify ZIKV infection during pregnancy. A self-administered questionnaire at birth documented prenatal household use of insecticides. Birth weight and head circumference were collected from maternity records (n = 708). Infant development and behaviors were documented at 18 months of age through the Ages and Stages Questionnaire and the Quebec Longitudinal Study of Child Development (n = 409). Logistic and linear regression models were performed, taking into account confounding factors. RESULTS: Use of household insecticides was associated with smaller head circumference and lower birth weight among newborns from mothers not exposed to ZIKV: 0.3 cm (95% CI: 0.6, 0) and -82 g (95% CI: 165, 0), respectively. Similar decreases were observed with ZIKV exposure among mothers not reporting household insecticides use, and with presence of both exposures. The combined presence of ZIKV exposure and insecticide use was associated with lower ASQ fine motor scores (-3.9; 95% CI: 7.3, -0.4), and higher hyperactivity scores (0.8; 95% CI: 0.0, 1.5), compared to no exposure to either. A higher opposition score was observed in association with ZIKV exposure among non-users of insecticide (0.6; 95% CI: 0.0, 1.2). CONCLUSION: Adverse neurodevelopmental outcomes at 18 months of age were observed with prenatal ZIKV exposure, and with higher magnitude when mothers reported use of household insecticides. At birth, rates of adverse fetal growth were however similar for the combined presence of exposure and either of the exposures.

Local and regional spread of chikungunya fever in the Americas.

Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.

Lessons raised by the major 2010 dengue epidemics in the French West Indies.

Dengue fever has been endemo-epidemic in the whole Region of America. In 2010, Guadeloupe and Martinique experienced historical epidemics, with an estimated attack rate of 10% in two islands. When considering the temporal evolution of epidemiological indicators, an unusual increase in the number of dengue cases could be detected very early. Two main factors might have facilitated the settlement of a viral transmission despite the dry season: a low immunity of the population against the circulating serotype and particular climatic conditions, notably very high temperatures which could have improved both virus and vector efficiency. This unusual situation was considered as a warning sign, and indeed led to major outbreaks in both islands a few weeks later. This event underlines that follow-up of epidemiological indicators is necessary to detect the unusual situations as soon as possible. Furthermore, development of biological and modelling tools should be promoted, as well as integrated management strategies for dengue prevention and control.

Climatic drivers of seasonal influenza epidemics in French Guiana, 2006-2010.

OBJECTIVES: Influenza seasonality remains poorly studied in Equatorial regions. Here we assessed the seasonal characteristics and environmental drivers of influenza epidemics in French Guiana, where influenza surveillance was established in 2006. METHODS: Sentinel GPs monitored weekly incidence of Influenza-like illnesses (ILI) from January 2006 through December 2010 and collected nasopharyngeal specimens from patients for virological confirmation. Times series analysis was used to investigate relationship between ILI and climatic parameters (rainfall and specific humidity). RESULTS: Based on 1533 viruses identified during the study period, we observed marked seasonality in the circulation of influenza virus in the pre-pandemic period, followed by year-round activity in the post-pandemic period, with a peak in the rainy season. ILI incidence showed seasonal autoregressive variation based on ARIMA analysis. Multivariate dynamic regression revealed that a 1 mm increase of rainfall resulted in an increase of 0.33% in ILI incidence one week later, adjusting for specific humidity (SH). Conversely, an increase of 1 g/kg of SH resulted in a decrease of 11% in ILI incidence 3 weeks later, adjusting for rainfall. CONCLUSIONS: Increased rainfall and low levels of specific humidity favour influenza transmission in French Guiana.

[Comparison of sentinel surveillance of influenza like infections in Martinique and in Guadeloupe during influenza A(H1N) 2009 pandemic: use of a phone survey and hospital surveillance]. / Comparaison de la surveillance des syndromes grippaux par les réseaux sentinelles en Martinique et en Guadeloupe au cours de la pandémie grippale A(H1N1) 2009 : apports d'une enquête téléphonique en population générale et de la surveillance hospitalière.

BACKGROUND: Sentinel general practitioner networks monitor influenza-like infections (ILI) in Martinique and in Guadeloupe (French West Indies). During the A(H1N1)2009 pandemic, they gave an ILI incidence estimation higher in Martinique than in Guadeloupe. In October 2009, a telephonic survey was launched in both islands to assess the number of ILI diagnoses performed by general practitioners since the beginning of the pandemic. This paper compares the results of sentinel surveillance, of telephonic survey and of hospital surveillance in Guadeloupe and in Martinique. METHODS: On each island, the sentinel network gathers a representative sample of voluntary general practitioners. Each week, they report the number of ILI they diagnosed the past week. Times series of these weekly numbers were modelized using the Serfling method with the upper limit of the confidence interval of the expected value representing the epidemic threshold. The telephone survey was conducted from October 2, 2009 to October 12, 2009 in Martinique and from October 13, 2009 to October 21, 2009 in Guadeloupe. The quota method was used for sampling individuals older than 14 years, leading to 507 interviews in Guadeloupe and 508 in Martinique. RESULTS: The epidemic lasted 12 weeks in both islands, from August 3 to October 25 in Martinique and from August 17 to November 8 in Guadeloupe. During August and September, estimated attack rate in Martinique was 5.52% (CI95: 5.23-5.83) from the sentinel network versus 8.3% (CI95: 6.0-11.0) from the telephone survey. In Guadeloupe, it was 2.13% (CI95: 1.97-2.24) from the sentinel network versus 6.9% (CI95: 4.8-9.5) from the telephone survey. An equivalent number of confirmed hospitalized cases was observed in the two islands. CONCLUSION: These results suggest that the sentinel network underestimates ILI incidence in Guadeloupe. According to Emergency Room activity for ILI, it seems possible that ILI incidence was actually higher in Martinique. A lower proportion of swab sampling among ILI hospitalized people could partly explain the observed differences in hospitalization ratio, in severity and in lethality between the two islands.

[Malaria in France: Mainland and territories]. / Le paludisme en France : métropole et outre-mer.

Malaria, which was eliminated first from Metropolitan France (mainland and Corsica), then in the French West Indies and the Reunion Island during the 20(th) century, remains endemic in two French territories: French Guiana and the Indian Ocean Mayotte island. Despite differences in the dominating plasmodial species and epidemiological patterns, these two territories have achieved marked quantitative improvements (in the reported number of cases and severe cases) thanks to efforts undertaken over the past decade. The situation, however, remains a concern from a qualitative standpoint with the emergence of resistance to antimalarial drugs and logistical and administrative issues which hinder access to treatment. Although malaria was eradicated in Metropolitan France half a century ago, competent vectors remain present in part or all of these territories and can give rise to limited outbreaks.

[Epidemic of influenza A(H1N1) 2009 in the French overseas territories of the Americas: epidemiological surveillance set up and main results, April 2009-January 2010]. / L'épidémie de grippe A(H1N1) 2009 dans les territoires français des Amériques: dispositif de surveillance mis en place et principaux résultats, avril 2009-janvier 2010.

Guadeloupe, French Guiana, Martinique, St. Martin and St. Barthelemy were the French territories most exposed to the new influenza A(H1N1)v, and adequate epidemiological surveillance tools were promptly developed in order to detect its emergence. The first stage, "containment phase", consisted in detection and management of individual cases. Then, when an autochthonous A(H1N1)v circulation was confirmed, its evolution has been monitored within the whole population, mainly through data collected from sentinel doctors' networks and virological surveillance. This allowed to detect very early the occurrence of epidemics, and to follow their evolution until they were over. Like all the other Caribbean countries, the five French overseas territories were hit by an outbreak of influenza A(H1N1)v. Although they had globally similar characteristics, each epidemic had its specificity in terms of scale and severity. They started between August and September 2009 in four of the five territories, while the last one, St. Barthelemy, was not affected until the end of the year. Attack rate estimates varied from 28 to 70 per 1000 inhabitants according to the territory, and hospitalisation rate varied from 4.3 to 10.3 per 1000 cases. Severity rate didn't reach 1 per 1000 cases in any of the territories. Compared to metropolitan France, the surveillance system presented several strengths, including the pre-existence of both an active sentinel network and an expert committee on emerging diseases in each territory. On the other hand, specific difficulties appeared, notably linked with logistical aspects of virological surveillance and the co-circulation of dengue virus in Guadeloupe and St. Barthelemy. Despite these difficulties, the different tools allowed early detection of the epidemics and follow-up of their evolution. All of them lead to very concordant results, suggesting that they are completely appropriate to monitor a potential new epidemic wave.

Prospective and descriptive study of adult dengue cases in an emergency department, in Martinique.

OBJECTIVE: Knowing about the clinical aspects of dengue in endemic zones is essential to implementation of appropriate case management protocols and public health interventions. PATIENTS AND METHODS: The authors made a 4-year prospective, observational study of dengue-infected patients admitted to the emergency department of the Fort-de-France University Hospital. RESULTS: Two hundred and sixty-three male and 297 female patients were included. The median age was 37 years (range: 14-91). The diagnosis was based on a positive RT-PCR (463 patients) or on the presence of specific IgM (97 patients). Two hundred and seventy-seven patients (49.5%) presented with dengue fever without complications. According to WHO criteria, 95 patients (17%) developed plasma leakage, including 39 patients (7%) diagnosed with DHF, and 10 (1.8%) diagnosed with DSS. Among the other patients without plasma leakage, 84 (15%) had isolated thrombocytopenia, 14 (2.5%) had internal bleeding, and 90 (16%) had unusual manifestations. Seven patients died (1.3%): fulminant hepatitis (two), myocarditis (one), encephalitis (one), acute respiratory failure (one), gangrenous cholecystitis (one), and post-traumatic intracranial hemorrhage (one). The other patients recovered. Seven patients were pregnant (1.3%) from 6 to 27 weeks of amenorrhea and carried their pregnancy to term without complications. CONCLUSION: With this experience, we were able to develop appropriate case management protocols for patients during dengue epidemics.

Atypical Chikungunya virus infections: clinical manifestations, mortality and risk factors for severe disease during the 2005-2006 outbreak on Réunion.

In April 2005, an outbreak of Chikungunya fever occurred on the island of Réunion in the Indian Ocean. During winter 2005, six patients developed meningoencephalitis and acute hepatitis due to Chikungunya virus. Our objectives were to determine the incidence and mortality of atypical Chikungunya viral infections and to identify risk factors for severe disease. A hospital-based surveillance system was established to collect data on atypical Chikungunya cases. Case reports, medical records and laboratory results were reviewed and analysed. We defined an atypical case as one in which a patient with laboratory-confirmed Chikungunya virus infection developed symptoms other than fever and arthralgia. We defined a severe atypical case as one which required maintenance of at least one vital function. We recorded 610 atypical cases of Chikungunya fever: 222 were severe cases, 65 affected patients died. Five hundred and forty-six cases had underlying medical conditions (of which 226 suffered from cardiovascular, 147 from neurological and 150 from respiratory disorders). Clinical features that had never been associated with Chikungunya fever were recorded, such as bullous dermatosis, pneumonia, and diabetes mellitus. Hypertension, and underlying respiratory or cardiological conditions were independent risk factors for disease severity. The overall mortality rate was 10.6% and it increased with age. This is the first time that severe cases and deaths due to Chikungunya fever have been documented. The information presented in this article may assist clinicians in identifying the disease, selecting the treatment strategy, and anticipating the course of illness.

Cancer mortality during the 1968-1994 period in a mining area in France.

We performed a geographical analysis of cancer mortality in the communes surrounding an industrial mining complex (Salsigne, France) where suspicious levels of pollution due to arsenic were measured. Compared with that observed in a control area, we showed a significant excess of mortality due to all cancer types (ratio of standard mortality ratios (ratio of SMRs)=1.1), lung cancer (ratio of SMRs=1.8), pharynx cancer (ratio of SMRs=2.1) in the whole population, and due to digestive system cancer (ratio of SMRs=1.3) among women. The results were similar after controlling for the occupation distribution in the populations. Excluding mining complex workers deaths from the deaths in the studied populations did not modify the pattern of our results. We concluded that the excess of cancer deaths could not be exclusively due to potential professional exposures among the workers of the mining complex and are probably explained by environmental contamination.

[An outbreak of appendectomies in La Désirade, Guadeloupe, August 1995-July 1996]. / Une épidémie d'appendicectomies à la Désirade, Guadeloupe, août 1995-juillet 1996.

BACKGROUND: In October 1995, over 50 cases of appendectomies among the 1.605 residents of the island La Désirade (Guadeloupe) were reported by the only island clinician to the local health authority. We describe the outbreak investigations which were implemented in order to describe the phenomenon and generate hypotheses on its cause. METHODS: An exhaustive case finding of residents having undergone appendectomy between 10 August 1995 and 22 July 1996 was conducted. We reviewed the medical charts of the cases; read pathology slides; interviewed cases and their families to retrieve detailed clinical history; studied the prevalence of markers of infection and of stool pathogens and analysed water supply quality data. RESULTS: We identified 226 cases of appendectomy (14% of the island population), 40% in May-June 1996, 46% in males and 40% under 15 years of age. Clinical, biological and pathological findings were heterogeneous and did not support the hypothesis of an outbreak of appendicitis. The study of abdominal symptoms in the families of the cases did not support person to person transmission but revealed frequent, subacute or chronic abdominal complaints. The analysis of markers of infection or of stool bacteria and parasites in a self selected sample of the island population was not suggestive. Water supply did not show any bacterial or chemical contamination. CONCLUSION: The investigation of a large outbreak of appendectomies was unable to find a single infectious or toxic origin to a high prevalence of chronic abdominal symptoms in an isolated population. An inappropriate medical answer in an isolated population probably turned heterogeneous complaints into an outbreak with major public health consequences.

[The impact of air pollution on health. The "Programme de Surveillance Air et Santé 9 villes" (Air and Health surveillance program in 9 cities)]. / Retentissement de la pollution atmosphérique sur la santé. Le Programme de Surveillance Air et Santé 9 villes.

OBJECTIVES: To quantify the short term effects of air pollution on mortality and hospitalisation for cardiovascular or respiratory disorders in the nine French cities (Bordeaux, Le Havre, Lille, Lyon, Marseille, Paris, Rouen, Strasbourg and Toulouse) of the Surveillance Air et Santé program. METHODS: Data were available on mortality and hospitalisation were available, respectively, from 1990 to 1997 and 1995 to 1999. Exposure data were the concentrations of sulphur dioxide, particles with a diameter of less than or equal to 10 mm, black smoke, nitrogen dioxide, ozone, and carbon monoxide. The analysis assessed the relationships, in each of the cities, between the daily numbers of deaths and hospitalisations and the daily levels of polluting agents, taking into account confounding factors. A combined relative risk was calculated for all the cities. The number of deaths and hospitalisations attributable to air pollution was then estimated for each of the cities, based on the relative risk. RESULTS: Significant relationships were found for mortality, from whatever cause, and for hospitalisations for respiratory disorders in children aged under 15. If the levels of air pollution were reduced to 10 microg/m3 in the nine cities, 2800 premature deaths and 750 hospitalisations for respiratory disorders in children would be avoided, every year. CONCLUSION: Today, it is possible to assess the benefits of reducing air pollution in terms of health in the short term. These analyses would provide a sanitary dimension to the strategies for the reduction of urban pollution on local and European level.

[Short-term relationships between urban atmospheric pollution and respiratory mortality: time series studies]. / Relations à court terme entre la pollution atmosphérique urbaine et la mortalité respiratoire: la place des études temporelles.

Time series studies conducted in the field of air pollution aim at testing and quantifying short-term relations which can exist between daily air pollution levels and daily health effects. The method used for this type of survey has sometimes been misunderstood mainly because individual factors and indoor exposure to air pollutants were not taken into account. The adjustment on these individual confounding factors commonly used in classic epidemiologic studies (case-control studies, cohort studies) is not adequate to times series studies which are based on aggregate data. This is different for those factors that change over time according to the levels of air pollution (meteorological conditions, influenza epidemics, trend of health cases) which, when being analysed, must be taken into account either indirectly through time modelling or directly through non-linear modelling processes. During this last decade, numerous studies using the time series method have been published and have found short-term associations between daily levels of air pollution commonly observed and daily respiratory mortality. The consistency of the numerous results published in the international literature are more arguments in favour of non-confounding short-term relations between air pollution and respiratory mortality.

Short-term effects of air pollution on mortality in the cities of Rouen and Le Havre, France, 1990-1995.

In this study, the authors examined the short-term effects of ambient air pollution on mortality across 2 French cities: Rouen and Le Havre. In Poisson regression models, which controlled for day-of-week effects, the authors used nonparametric smoothing to control for temporal trend, weather, and influenza epidemics. In Rouen, an interquartile range increase of 60.5-94.1 microg/m3 of ozone was associated with an increase of 4.1% (95% confidence interval = 0.6, 7.8) of total mortality. Daily variations in sulfur dioxide (interquartile range increase = 17.6-36.4 microg/m3) were also associated with an 8.2% increase (95% confidence interval = 0.4, 16.6) in respiratory mortality. An increase of 6.1% (95% confidence interval = 1.5, 10.9) of cardiovascular mortality was also observed with an interquartile range increase of nitrogen dioxide (i.e., 25.3-42.2 microg/m3). With respect to Le Havre, an interquartile range increase in daily levels of sulfur dioxide (11.3-35.6 microg/m3) was associated with an increase of approximately 3% (95% confidence interval = 0.8, 5) of cardiovascular mortality. For particulate matter less than or equal to 13 microm in diameter (interquartile increase = 21.5, 45.4 microg/m3), an increase of 6.2% (95% confidence interval = 0.1, 12.8) was observed. The estimates of pollutant effects and their standard deviations were slightly affected by the degree of smoothing temporal variations in this study. When low collinearity was present, the 2-pollutant models provided acceptable estimates of pollutant effects. They suggested that the ozone effect was independent of the Black Smoke effect, and that the effects of sulfur dioxide and nitrogen dioxide were unlikely to be confounded by ozone concentrations. However, high collinearity leads to large estimates of the pollutant coefficient variances and, therefore, leads to inaccurate estimates of pollutant effects. The analysis of the contributory effects of different pollutant mixtures requires further investigation in those instances in which high collinearity between pollutants is present.

Assessment of deaths attributable to air pollution: should we use risk estimates based on time series or on cohort studies?

Epidemiologic studies are crucial to the estimation of numbers of deaths attributable to air pollution. In this paper, the authors present a framework for distinguishing estimates of attributable cases based on time-series studies from those based on cohort studies, the latter being 5-10 times larger. The authors distinguish four categories of death associated with air pollution: A) air pollution increases both the risk of underlying diseases leading to frailty and the short term risk of death among the frail; B) air pollution increases the risk of chronic diseases leading to frailty but is unrelated to timing of death; C) air pollution is unrelated to risk of chronic diseases but short term exposure increases mortality among persons who are frail; and D) neither underlying chronic disease nor the event of death is related to air pollution exposure. Time-series approaches capture deaths from categories A and C, whereas cohort studies assess cases from categories A, B, and C. In addition, years of life lost can only be derived from cohort studies, where time to death is the outcome, while in time-series studies, death is a once-only event (no dimension in time). The authors conclude that time-series analyses underestimate cases of death attributable to air pollution and that assessment of the impact of air pollution on mortality should be based on cohort studies.

Air pollution and health: correlation or causality? The case of the relationship between exposure to particles and cardiopulmonary mortality.

Many epidemiologic studies have observed, in different contexts, a slight short-term relationship between particles in air and cardiopulmonary mortality, even when air quality standards were respected. The causality of this relationship is important to public health because of the number of people exposed. Our aim was to make a critical assessment of the arguments used in 15 reviews of published studies. We explain the importance of distinguishing validity from causality, and we systematically analyze the various criteria of judgment within the context of ecologic time studies. Our conclusion is that the observed relationship is valid and that most of the causality criteria are respected. It is hoped that the level of exposure of populations to these particles be reduced. In Europe, acting at the root of the problem, in particular on diesel emissions, will also enable the reduction of levels of other pollutants that can have an impact on health. In the United States, the situation is more complicated, as particles are mainly secondary. It is also essential to continue with research to become better acquainted with the determinants of personal global exposures and to better understand the toxic role of the various physicochemical factors of the particles.