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Thyroid doses were estimated for the subjects of a population-based case-control study of thyroid cancer in a population exposed to fallout after atmospheric nuclear weapons tests conducted in French Polynesia between 1966 and 1974. Thyroid doses due to (i) intake of (131)I and of short-lived radioiodine isotopes ((132)I, (133)I, (135)I) and (132)Te, (ii) external irradiation from gamma-emitting radionuclides deposited on the ground, and (iii) ingestion of long-lived (137)Cs with foodstuffs were reconstructed for each study subject. The dosimetry model that had been used in 2008 in Phase I of the study was substantially improved with (i) results of radiation monitoring of the environment and foodstuffs, which became available in 2013 for public access, and (ii) historical data on population lifestyle related to the period of the tests, which were collected in 2016–2017 using focus-group discussions and key informant interviews. The mean thyroid dose among the study subjects was found to be around 5 mGy while the highest dose was estimated to be around 36 mGy. Doses from (131)I intake ranged up to 27 mGy, while those from intake of short-lived iodine isotopes ((132)I, (133)I, (135)I) and (132)Te ranged up to 14 mGy. Thyroid doses from external exposure ranged up to 6 mGy and those from internal exposure due to (137)Cs ingestion did not exceed 1 mGy. Intake of (131)I was found to be the main pathway for thyroid exposure accounting for 72% of the total dose. Results of this study are being used to evaluate the risk of thyroid cancer among the subjects of the epidemiologic study of thyroid cancer among French Polynesians.

Background: Ivermectin is a key anthelmintic for the control of neglected tropical diseases. The main indications for population-Level control with ivermectin through mass drug administration are onchocerciasis and Lymphatic filariasis; however, there is interest in using higher, fixed-dose regimens for the control of scabies, soil-transmitted helminths and malaria. Safety data for these higher-dose regimens are needed. Methods: A systematic Literature review and meta-analysis on the safety and doses of ivermectin was conducted. Eligible studies reported patient-Level data and, for the meta-analysis, clinical trials reporting data on doses >= 200 and >= 400 mu g/kg were included. Incidence ratios were used to compare adverse events by severity and organ system affected. Results: The systematic search identified six studies for inclusion, revealing no differences in the number of individuals experiencing adverse events. A descriptive analysis of these clinical trials for a variety of indications showed no difference in the severity of the adverse events between standard (up to 400 mu g/kg) and higher doses of ivermectin. Organ system involvement only showed an increase in ocular events in the higher-dose group in one trial for the treatment of onchocerciasis, all of them transient and mild to moderate in intensity. Conclusions: Although within this review the safety of high-dose ivermectin appears to be comparable to standard doses, there are not enough data to support a recommendation for its use in higher-than-approved doses. Ocular adverse events, despite being transient, are of concern in onchocerciasis patients. These data can inform programme managers and guide operational research activities as new approaches for the use of ivermectin are evaluated.

International audience

Background Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020/2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females, but rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. Methods Using a novel mathematical modelling approach, we analysed―at an individual participant level―longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing three-monthly with annual treatments administered for three years, in Cameroon. Results Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilising effect after 4 or more consecutive treatments, even at routine MDA doses (150 g/kg) and (annual) frequencies. The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after three years of annual or three-monthly (quarterly) exposures to ivermectin. Conclusions Our quantification of macrofilaricidal and sterilising effects of ivermectin should be incorporated into transmission models informing onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.

We use a mathematical model fit to clinical trial data to estimate the efficacy of multiple-dose ivermectin regimens against onchocerciasis. We found marked macrofilaricidal activity of regimens used in routine mass drug administration, calling for revised projections on elimination timeframes., Background Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. Methods Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon. Results Multiple doses of ivermectin have a partial macrofilaricidal and a modest permanent sterilizing effect after 4 or more consecutive treatments, even at routine MDA doses (150 µg/kg) and frequencies (annual). The life expectancy of adult O. volvulus is reduced by approximately 50% and 70% after 3 years of annual or 3-monthly (quarterly) exposures to ivermectin. Conclusions Our quantification of macrofilaricidal and sterilizing effects of ivermectin should be incorporated into transmission models to inform onchocerciasis elimination efforts in Africa and residual foci in Latin America. It also provides a framework to assess macrofilaricidal candidate drugs currently under development.

International audience

International audience

International audience; L’industrie pétrolière est reconnue comme une source potentielle de dispersion dans l’environnement de nombreux composés chimiques dont certains sont des cancérogènes avérés. Si le risque sanitaire semble bien établi dans le contexte d’expositions professionnelles, les conséquences des expositions environnementales sont difficiles à décrire et font l’objet de polémiques scientifiques et juridiques, notamment en Equateur. Cette étude vise à étudier le lien entre l’exposition résidentielle environnementale aux hydrocarbures et la santé perçue. Méthode. Cette étude s’appuie sur l’analyse des données d’une enquête menée en Equateur par le Ministère de l’Environnement auprès de la population générale, dans une zone d’intense exploitation pétrolière (N= 2943 individus). La santé perçue a été estimée par la question générale de l’OMS. Une analyse environnementale hydrologique conduite au préalable a permis de dresser une carte d’aléa potentielle d’exposition aux hydrocarbures sur l’ensemble de la zone d’étude. Un modèle de régression logistique multiniveau a été mis en œuvre pour estimer le lien entre l’intensité de l’aléa et la santé perçue. Résultats. Environ 40,7% des individus interrogés se déclarent en bonne santé. L’alea de pollution aux hydrocarbures est groupé en 3 classes (faible/moyen/fort). Parmi les individus résidant dans une zone où l’aléa est fort, seulement 27,7% d’entre eux déclarent être en bonne santé. Alors qu’ils sont près de 42% dans les autres zones (p = 0,001). Le modèle multivarié multiniveau met en évidence plusieurs déterminants individuels « classiques » fortement associés avec la santé perçue, notamment le niveau scolaire, l’âge et le sexe. Après ajustement sur ces variables individuelles, le lien entre le fait de résider dans une zone où l’aléa est élevé et la santé perçue se maintient (OR = 2,46 [1,09 - 3.82]). Conclusion. Ces résultats suggèrent que le fait de vivre à proximité ou dans une zone potentiellement fortement polluée par des hydrocarbures joue un rôle important sur la perception qu’ont les individus de leur santé.

International audience; Inorganic arsenic is a ubiquitous metalloid, with well-known toxic properties for human health. In many regions of the world, human arsenic exposure is identified as a public health problem because of its presence in drinking water and certain food. Even at relatively low levels, regular consumption of contaminated water is considered to increase the risk of cancers in different organs, such as urinary bladder, skin, and lung, probably also liver, kidney and prostate. More recently, multiple other chronic diseases have been associated with environmental arsenic exposure, such as diabetes, cardiovascular diseases, as well as impaired immune function and child development. The WHO guideline water arsenic concentration is 10 µg L-1. Certain plants, rice in particular, is known to easily take up arsenic from the soil. In the south regions of Bolivia, concentrations above 100 µg L-1 have been found in traditional wells or tube-wells used by the population on a daily basis without having a clear knowledge of the situation. This arsenic originates from leaching of arsenic in sediments and volcanic rocks of geogenic origin (Muñoz et al, Ramos OE et al). Preliminary results of an ongoing cross sectional study have confirmed the human exposure in some villages south from Poopó Lake. Concentration between 10 and 150 µg/L were observed in tap water, traditional wells and tube-wells. The concentrations in collected urines samples, a marker of the total exposure through drinking water and food, confirmed exposure in the low to medium range, known to be associated with increased risk of adverse health effects. The lack of knowledge by medical staffs of the region and the absence of overt symptoms will be discussed.

During a mass treatment with ivermectin which is contraindicated to pregnant women, authors made a screening for pregnancy by questioning 2,580 women from 15 to 45 years old. 1,409 of these women were also interrogated by a female physician assisted by a native matron to detect pregnant women. In 1,798 women, at least one immunological pregnancy test has been used in the field. A nine months follow-up was made to check answers. Women's knowledge led to a good appreciation of pregnancy as they correctly appreciated their pregnancy from the second month: specificity was good (98%) but sensitivity was moderate (71%). Conclusions made by gynecological team after detailed questionnaire were more sensitive (80%), but specificity decrease dramatically to 59%. Combinations of several items in the questionnaire showed no benefit. Sensitivity of the various immunological pregnancy tests tried was included in 70 to 90% and specificity was varying from 87 to 97%. Simple questioning of women was the most efficient method (efficiency value was 94% against 63% for interview and 92% for pregnancy tests). However, the use of this method induced the risk that about 29% of women have been treated although they were pregnant.