Publications by authors named "Jacques Gardon"

35 Publications

Arsenic Exposure and Cancer-Related Proteins in Urine of Indigenous Bolivian Women.

Front Public Health 2020 14;8:605123. Epub 2020 Dec 14.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Indigenous people living in the Bolivian Andes are exposed through their drinking water to inorganic arsenic, a potent carcinogen. However, the health consequences of arsenic exposure in this region are unknown. The aim of this study was to evaluate associations between arsenic exposure and changes in cancer-related proteins in indigenous women ( = 176) from communities around the Andean Lake Poopó, Bolivia. Arsenic exposure was assessed in whole blood (B-As) and urine (as the sum of arsenic metabolites, U-As) by inductively coupled plasma-mass spectrometry (ICP-MS). Cancer-related proteins ( = 92) were measured in urine using the proximity extension assay. The median B-As concentration was 2.1 (range 0.60-9.1) ng/g, and U-As concentration was 67 (12-399) μg/L. Using linear regression models adjusted for age, urinary osmolality, and urinary leukocytes, we identified associations between B-As and four putative cancer-related proteins: FASLG, SEZ6L, LYPD3, and TFPI2. Increasing B-As concentrations were associated with lower protein expression of SEZ6L, LYPD3, and TFPI2, and with higher expression of FASLG in urine (no association was statistically significant after correcting for multiple comparisons). The associations were similar across groups with different arsenic metabolism efficiency, a susceptibility factor for arsenic toxicity. In conclusion, arsenic exposure in this region was associated with changes in the expression of some cancer-related proteins in urine. Future research is warranted to understand if these proteins could serve as valid biomarkers for arsenic-related toxicity.
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http://dx.doi.org/10.3389/fpubh.2020.605123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767847PMC
December 2020

Individual risk of post-ivermectin serious adverse events in subjects infected with .

EClinicalMedicine 2020 Nov 10;28:100582. Epub 2020 Oct 10.

UMI 233, Institut de Recherche pour le Développement (IRD), Montpellier, France.

Background: Implementation of onchocerciasis elimination programmes has been delayed in Central Africa because of the risk of ivermectin-related serious adverse events (SAEs) in individuals with high microfilarial densities (MFD). We developed the first statistical models enabling prediction of SAE risk in individuals with a given MFD.

Methods: We used individual participant data from two trials conducted in loiasis-onchocerciasis co-endemic areas in Cameroon. among the 10 506 ivermectin-treated subjects included in the analysis, 38 (0·36%) developed an ivermectin-related SAE. To predict individual-level risk of SAE, we developed mixed multivariate logistic models including subjects' sex, age, pre-treatment and MFDs, and study region.

Findings: The models predicted that regardless of sex, about 1% of people with 20 000 microfilariae per millilitre of blood (mf/mL), 10% of people with 50 000 mf/mL and about one third of those with 100 000 mf/mL will develop an SAE. For a given MFD, males have a three-fold higher risk of developing an SAE than females.

Interpretation: By enabling the prediction of post-ivermectin SAE risk in communities with known distribution of MFDs, our results can guide decisions on the choice of ivermectin-based treatment strategies. They also predict that 37 SAEs were prevented in 2015 by using a Test-and-Treat strategy in the Okola District of Cameroon.

Funding: UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases; Institut de Recherche pour le Développement; Mectizan Donation Program; Bill & Melinda Gates Foundation
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http://dx.doi.org/10.1016/j.eclinm.2020.100582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700892PMC
November 2020

Thyroid Doses to French Polynesians Resulting from Atmospheric Nuclear Weapons Tests: Estimates Based on Radiation Measurements and Population Lifestyle Data.

Health Phys 2021 Jan;120(1):34-55

Hydrosciences Montpellier, Research Institute for Development, CNRS, University of Montpellier, Montpellier, France.

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 (1) intake of I and of short-lived radioiodine isotopes (I, I, I) and Te, (2) external irradiation from gamma-emitting radionuclides deposited on the ground, and (3) ingestion of long-lived 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 (1) results of radiation monitoring of the environment and foodstuffs, which became available in 2013 for public access, and (2) 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 I intake ranged up to 27 mGy, while those from intake of short-lived iodine isotopes (I, I, I) and Te ranged up to 14 mGy. Thyroid doses from external exposure ranged up to 6 mGy, and those from internal exposure due to Cs ingestion did not exceed 1 mGy. Intake of 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.
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http://dx.doi.org/10.1097/HP.0000000000001262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710602PMC
January 2021

Individuals living in an onchocerciasis focus and treated three-monthly with ivermectin develop fewer new onchocercal nodules than individuals treated annually.

Parasit Vectors 2020 May 15;13(1):258. Epub 2020 May 15.

UMI 233, Institut de Recherche pour le Développement (IRD) and University of Montpellier 1, 911 avenue Agropolis, P.O. Box 64501, 34394, Montpellier Cedex 5, France.

Background: Little information is available on the effect of ivermectin on the third- and fourth-stage larvae of Onchocerca volvulus. To assess a possible prophylactic effect of ivermectin on this parasite, we compared the effects of different ivermectin regimens on the acquisition of onchocercal nodules.

Methods: We analyzed data from a controlled randomized clinical trial of ivermectin conducted in the Mbam Valley (Cameroon) between 1994 and 1998 in a cohort of onchocerciasis infected individuals. The number of nodules that appeared between the start and the end of the clinical trial was analyzed, using ANOVA and multivariable Poisson regressions, between four treatment arms: 150 µg/kg annually, 800 µg/kg annually, 150 µg/kg 3-monthly, and 800 µg/kg 3-monthly.

Results: The mean number of nodules that appeared during the trial was reduced by 17.7% in subjects treated 3-monthly compared to those treated annually (regardless of the dose). Poisson regression model, adjusting on subject's age and weight, initial number of nodules and intensity of O. volvulus infection in his village of residence, confirmed that the incidence of new nodules was reduced in 3-monthly treatment arms compared to annually treatment arms, and that the dosage of ivermectin does not seem to influence this effect. Furthermore, the number of newly acquired nodules was positively associated with the initial number of nodules. Analysis of disappearance of nodules did not show any significant difference between the treatment groups.

Conclusions: To our knowledge, these results suggest for the first time in humans, that ivermectin has a partial prophylactic effect on O. volvulus. Three-monthly treatment seems more effective than annual treatment to prevent the appearance of nodules.
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http://dx.doi.org/10.1186/s13071-020-04126-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229600PMC
May 2020

Safety of high-dose ivermectin: a systematic review and meta-analysis.

J Antimicrob Chemother 2020 04;75(4):827-834

Barcelona Institute for Global Health (ISGlobal) Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.

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 μg/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 μg/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.
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http://dx.doi.org/10.1093/jac/dkz524DOI Listing
April 2020

Behavior and Food Consumption Pattern of the French Polynesian Population in the 1960s -1970s.

Asian Pac J Cancer Prev 2019 Dec 1;20(12):3667-3677. Epub 2019 Dec 1.

National Institute for Health and Medical Research, Center for Research in Epidemiology and Population Health (CESP), INSERM U1018, Radiation Epidemiology Group, Villejuif, France.

Background: Reconstruction of radiation doses to the thyroid for a case-control study of thyroid cancer in French Polynesians exposed to radioactive fallout from atmospheric nuclear weapons tests during childhood and adolescence faced a major limitation on very little availability of information on lifestyle of French Polynesians in the 1960s-1970s.

Method: We use the focus group discussion and key informant interview methodology to collect historical, for the 1960s-1970s, data on behavior and food consumption for French Polynesia population exposed to radioactive fallout from nuclear weapons tests conducted between 1966 and 1974.

Results: We obtained archipelago-specific data on food consumptions by children of different ages and by pregnant and lactating women during pregnancy and breastfeeding and behaviour, including time spent outdoors and type and construction materials of residences.

Conclusions: This article presents the first detailed information on several key aspects of daily life on French Polynesian archipelagoes during the 1960s-1970s impacting radiation exposure. Important behavior and food consumptions data obtained in this study are being used to improve the radiation dose estimates and to update the risk analysis reported earlier by correcting biases from previous assumptions and by providing better estimates of the parameter values important to radiation dose assessment.
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http://dx.doi.org/10.31557/APJCP.2019.20.12.3667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7173359PMC
December 2019

Effect of a Single Standard Dose (150-200 μg/kg) of Ivermectin on Microfilaremia: Systematic Review and Meta-analysis.

Open Forum Infect Dis 2019 Apr 11;6(4):ofz019. Epub 2019 Jan 11.

IRD UMI 233-INSERM U1175- University of Montpellier, Montpellier, France.

Background: In central Africa, millions of individuals infected with have received the anthelminthic drug ivermectin (IVM) as part of mass drug administration (MDA) campaigns targeting onchocerciasis control or elimination. Nonetheless, the parasitological surveys that are occasionally conducted to evaluate the impact of IVM treatments on do not include an assessment of the extra benefits of those MDA campaigns on .

Methods: We conducted a systematic review of trials on the effect of a single standard (150-200 μg/kg) dose of IVM on microfilarial density (MFD). The dynamics of MFD over 365 days of treatment were described using multilevel regression and latent class modeling.

Results: IVM brings about a rapid, dramatic, and sustained decrease, with reduction rates of 60%, 75%, 85%, and 90% on day 1 (D1), D2, D7, and D365, respectively. At D365, no participants (0/238) with an initial MFD of <20 000 microfilariae (mf)/mL were at risk of postivermectin severe adverse events, and only 1/57 individuals with an initial MFD of ≥20 000 mf/mL presented with an MFD above this value. The main predictor of post-treatment MFD was the pretreatment value, but this post-treatment value varied little between D8 and D365 regardless of the pretreatment level.

Conclusions: A single dose of IVM is very effective at substantially reducing MFD for at least a year, irrespective of the initial level of parasitemia. Individuals treated with IVM are probably not any more at risk of severe adverse events when retreated 1 year later.
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http://dx.doi.org/10.1093/ofid/ofz019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449757PMC
April 2019

Non-Essential Trace Elements Dietary Exposure in French Polynesia: Intake Assessment, Nail Bio Monitoring and Thyroid Cancer Risk

Asian Pac J Cancer Prev 2019 Feb 26;20(2):355-367. Epub 2019 Feb 26.

Radiation Epidemiology Group, Centre for Research in Epidemiology and Population Health (CESP), UMR 1018 Inserm, Villejuif, France.

Background: In French Polynesia, thyroid cancer mortality and incidence is reported to be the highest in the world. Excessive levels of non-essential trace elements (nETE) in the body are associated with several types of cancer. Objective: The present study aims to provide quantitative information on food contamination by mercury (Hg), lead (Pb), arsenic (As) and cadmium (Cd) in French Polynesia and its potential correlation with measurements performed in fingernails of Polynesians, and then to investigate the potential association between these nETE and different thyroid cancer risks. Methods: The study population included 229 interviewed cases and 373 interviewed controls We performed a descriptive analysis of Polynesian food and examined the association between thyroid cancer risk and daily intake levels of nETE and with fingernail nETE levels. Results: Hg contamination was mainly present in sea products, Pb contamination was present in almost all samples, Cd was detectable in starchy food and As was detectable in all sea products. No patient exceeded dietary contamination WHO limits for Pb, 2 participants exceeded it for Hg and 3 individuals (0.5%) for cadmium. In fingernail clippings, the most detectable pollutant was Pb (553 participants), then Hg (543 participants) then Cd (only in 130 participants). Thyroid cancer risk was increased more than 4 times by Pb daily intake in patients with a history of cancer in first-degree relatives than in ones without (p for interaction =0.01), and 2 times more in women with more than 3 pregnancies than in those with none or less (p for interaction =0.005); it was also increased following As intake by more than 30% in patients with a history of cancer in first-degree relatives than in ones without (p for interaction =0.05). Conclusion: Locally produced foods are not a source of nETE exposure in French Polynesia. Dieatry nETE exposure and fingernail nETE concentration are not associated to differentiated thyroid cancer risk. No correlation found between nETE dietary exposure and fingernail nETE concentration.
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http://dx.doi.org/10.31557/APJCP.2019.20.2.355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897028PMC
February 2019

Elevated arsenic exposure and efficient arsenic metabolism in indigenous women around Lake Poopó, Bolivia.

Sci Total Environ 2019 Mar 2;657:179-186. Epub 2018 Dec 2.

Hydrosciences Montpellier, Institut de Recherche pour le Développement, CNRS, University of Montpellier, France.

Elevated concentrations of inorganic arsenic, one of the most potent environmental toxicants and carcinogens, have been detected in well water around Lake Poopó, Bolivia. This study aimed to assess human exposure to arsenic in villages around Lake Poopó, and also to elucidate whether the metabolism and detoxification of arsenic in this population is as efficient as previously indicated in other Andean areas. We recruited 201 women from 10 villages around Lake Poopó. Arsenic exposure was determined as the sum concentration of arsenic metabolites (inorganic arsenic; monomethylarsonic acid, MMA; and dimethylarsinic acid, DMA) in urine (U-As), measured by HPLC-HG-ICP-MS. Efficiency of arsenic metabolism was assessed by the relative fractions of the urinary metabolites. The women had a wide variation in U-As (range 12-407 μg/L, median 65 μg/L) and a markedly efficient metabolism of arsenic with low %MMA (median 7.7%, range: 2.2-18%) and high %DMA (80%, range: 54-91%) in urine. In multivariable-adjusted linear regression models, ethnicity (Aymara-Quechua vs. Uru), body weight, fish consumption and tobacco smoking were associated with urinary arsenic metabolite fractions. On average, the Uru women had 2.5 lower % (percentage unit) iAs, 2.2 lower %MMA and 4.7 higher %DMA compared with the Aymara-Quechua women. Our study identified several factors that may predict these women's arsenic methylation capacity, particularly ethnicity. Further studies should focus on mechanisms underlying these differences in arsenic metabolism efficiency, and its importance for the risk of arsenic-related health effects.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.473DOI Listing
March 2019

Macrofilaricidal Efficacy of Repeated Doses of Ivermectin for the Treatment of River Blindness.

Clin Infect Dis 2017 Nov;65(12):2026-2034

UMI233-TransVIHMI, Institut de Recherche pour le Développement, INSERM U1175, University of Montpellier, France.

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.
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http://dx.doi.org/10.1093/cid/cix616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850622PMC
November 2017

Herbal Medicine Practices of Patients With Liver Cancer in Peru: A Comprehensive Study Toward Integrative Cancer Management.

Integr Cancer Ther 2018 03 8;17(1):52-64. Epub 2016 Dec 8.

2 Université de Toulouse, IRD, UPS, UMR 152, Toulouse, France.

Rationale: The highest burden of liver cancer occurs in developing countries, where the use of herbal medicine (HM) is still widespread. Despite this trend, few studies have been conducted to report HM practices of patients with a hepatic tumor in the developing world. Hence, this study aimed to document the use of HM among patients with liver cancer in Peru.

Study Design And Methods: A comparative behavioral epidemiological survey was conducted among liver cancer patients attending the National Cancer Institute of Peru. Information was obtained by direct interviews based on a semistructured questionnaire. The use of HM in Peruvian liver cancer patients was reported, first, regarding general consumption prior to the onset of disease, and second, after the appearance of symptoms that patients would relate to their tumor. In parallel, general consumption of HM in noncancerous people was assessed as a comparative figure. A correspondence analysis was performed to reveal potential associations between the symptoms of cancer and the specific use of HM.

Results: Eighty-eight patients and 117 noncancerous individuals participated in the survey. Overall, 68.3% of the people interviewed claimed to use HM on a regular basis for general health preservation. Furthermore, 56.8% of the patients turned to plants first to treat the disorders for which they later came to the cancer care center. When compared with the number of plant species used routinely (n = 78), a selection of plants was made by patients in response to the symptoms of cancer (n = 46). At least 2 plant species, Aloe vera and Morinda citrifolia, were significantly associated with the treatment of liver cancer-related symptoms in the patient group.

Conclusions: The present study is the first survey on the HM practices of patients with liver cancer in Latin America and, more broadly, in the developing world. Our findings confirm that HM remains one of the principal primary health care resources in Peru, even for a severe disease like liver cancer. These traditional, complementary and alternative medicine practices should be taken into consideration in Peruvian health programs aiming to educate the population in cancer prevention and treatment, as well as integrative cancer management.
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http://dx.doi.org/10.1177/1534735416681642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5950939PMC
March 2018

Metal concentration and bioaccessibility in different particle sizes of dust and aerosols to refine metal exposure assessment.

J Hazard Mater 2016 Nov 8;317:552-562. Epub 2016 Jun 8.

IRD-LCA-UMSA, CP 9214 Obrajes, La Paz, Bolivia; IRD-Hydrosciences Montpellier (HSM), Montpellier, France.

Refined exposure assessments were realized for children, 7-9yrs, in the mining/smelting city of Oruro, Bolivia. Aerosols (PM>2.5, PM1-2.5, PM0.4-1 and PM0.5) and dust (separated in different particle size fractions: 2000-200μm, 200-50μm, 50-20μm, 20-2μm and <2μm) were sampled on football fields highly frequented by children in both the mining and smelting areas. Trace element concentrations (Ag, As, Cd, Cu, Pb, Sb, Sn and Zn) in each size fraction of dust and aerosols, lung bioaccessibility of metals in aerosols, and gastric bioaccessibility of metals in dust were measured. Exposure was assessed considering actual external exposure (i.e. exposure pathways: metals inhaled and ingested) and simulated internal exposure (i.e., complex estimation using gastric and lung bioaccessibility, deposition and clearance of particles in lungs). Significant differences between external and simulated internal exposure were attributed to dissemblances in gastric and lung bioaccessibilities, as well as metal distribution within particle size range, revealing the importance of both parameters in exposure assessment.
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http://dx.doi.org/10.1016/j.jhazmat.2016.05.083DOI Listing
November 2016

Toxic trace elements in maternal and cord blood and social determinants in a Bolivian mining city.

Int J Environ Health Res 2016 16;26(2):158-74. Epub 2015 Jul 16.

h Institute of Social Medicine, Epidemiology and Health Economics , Charité - Universitätsmedizin Berlin , Berlin , Germany.

This study assessed lead, arsenic, and antimony in maternal and cord blood, and associations between maternal concentrations and social determinants in the Bolivian mining city of Oruro using the baseline assessment of the ToxBol/Mine-Niño birth cohort. We recruited 467 pregnant women, collecting venous blood and sociodemographic information as well as placental cord blood at birth. Metallic/semimetallic trace elements were measured using inductively coupled plasma mass spectrometry. Lead medians in maternal and cord blood were significantly correlated (Spearman coefficient = 0.59; p < 0.001; 19.35 and 13.50 μg/L, respectively). Arsenic concentrations were above detection limit (3.30 μg/L) in 17.9% of maternal and 34.6% of cord blood samples. They were not associated (Fischer's p = 0.72). Antimony medians in maternal and cord blood were weakly correlated (Spearman coefficient = 0.15; p < 0.03; 9.00 and 8.62 μg/L, respectively). Higher concentrations of toxic elements in maternal blood were associated with maternal smoking, low educational level, and partner involved in mining.
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http://dx.doi.org/10.1080/09603123.2015.1061114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733940PMC
October 2016

Indoor metallic pollution and children exposure in a mining city.

Sci Total Environ 2014 Jul 21;487:13-9. Epub 2014 Apr 21.

IRD (Institut de Recherche pour le Développement), La Paz, Bolivia; Universidad Mayor de San Andrés, SELADIS (Instituto de Servicios de Laboratorio para el Diagnóstico e Investigación en Salud), La Paz, Bolivia; IRD, HSM, Montpellier, France.

Mining industries are known for causing strong environmental contamination. In most developing countries, the management of mining wastes is not adequate, usually contaminating soil, water and air. This situation is a source of concern for human settlements located near mining centers, especially for vulnerable populations such as children. The aim of this study was to assess the correlations of the metallic concentrations between household dust and children hair, comparing these associations in two different contamination contexts: a mining district and a suburban non-mining area. We collected 113 hair samples from children between 7 and 12 years of age in elementary schools in the mining city of Oruro, Bolivia. We collected 97 indoor dust samples from their households, as well as information about the children's behavior. Analyses of hair and dust samples were conducted to measure As, Cd, Pb, Sb, Sn, Cu and Zn contents. In the mining district, there were significant correlations between non-essential metallic elements (As, Cd, Pb, Sb and Sn) in dust and hair, but not for essential elements (Cu and Zn), which remained after adjusting for children habits. Children who played with dirt had higher dust-hair correlations for Pb, Sb, and Cu (P=0.006; 0.022 and 0.001 respectively) and children who put hands or toys in their mouths had higher dust-hair correlations of Cd (P=0.011). On the contrary, in the suburban area, no significant correlations were found between metallic elements in dust and children hair and neither children behavior nor gender modified this lack of associations. Our results suggest that, in a context of high metallic contamination, indoor dust becomes an important exposure pathway for children, modulated by their playing behavior.
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http://dx.doi.org/10.1016/j.scitotenv.2014.03.136DOI Listing
July 2014

Child patterns of growth delay and cognitive development in a Bolivian mining city.

Am J Hum Biol 2013 Jan-Feb;25(1):94-100. Epub 2012 Nov 7.

Department of Experimental and Health Sciences, Universitat Pompeu Fabra (UPF), Dr. Aiguader, 88 08003 Barcelona, Spain.

Objectives: This study aims to (1) follow up and characterize infant growth patterns during the first year of life in Bolivia, and (2) determine whether there exists an association between weight gain and cognitive development in children living near contaminated mining industries.

Methods: Data on 175 children participating to the ToxBol (Toxicity in Bolivia) birth cohort were analyzed. Rapid-growth during the first 6 months was defined as a change in weight z-score > 0.67 while slow-growth was defined as a weight z-score change of < -0.67. Neurodevelopment was evaluated using the Bayley Scales of Infant Development at 10.5-12.5 months of age. Mixed models were used to examine the association between cognitive development and weight gain.

Results: Rapid growers weighed less at birth (P < 0.01). However, they revealed a higher body mass index at 12 months of age (0.70 ± 0.73, P < 0.01). After adjustment for confounding, rapid growth was not associated with cognitive development (coef = 0.49, 95% confidence interval = -4.10, 5.08).

Conclusions: In this Bolivian cohort, children born smaller were more likely to grow/develop faster and attain greater weight and length. Their cognitive development was not affected by their growth patterns.
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http://dx.doi.org/10.1002/ajhb.22346DOI Listing
June 2013

Single nucleotide polymorphisms in β-tubulin selected in Onchocerca volvulus following repeated ivermectin treatment: possible indication of resistance selection.

Mol Biochem Parasitol 2012 Sep 5;185(1):10-8. Epub 2012 Jun 5.

General Biology Laboratory, Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon.

The control of onchocerciasis or river blindness by mass treatment of the population with ivermectin (IVM) has been a great success until now, so that in certain foci its elimination has become feasible. However, after more than 20 years of repeated IVM mass treatment, the disease still persists in many endemic countries. Sub-optimal responses and genetic changes have been reported in Onchocerca volvulus populations under high IVM pressure but more work is needed to determine whether resistance is developing. The situation needs to be urgently clarified to preserve the achievements of onchocerciasis control programs. In this study, O. volvulus adult worms were collected from the same individuals, before IVM exposure and following three years of annual or three-monthly treatments at 150 μg/kg or 800 μg/kg. Four single nucleotide polymorphisms (SNPs) occurring in the β-tubulin gene of these parasites were investigated. We found changes in genotype frequencies in O. volvulus β-tubulin gene associated with IVM treatments. The SNP at position 1545 (A/G) showed a significant increase in frequency of the less common nucleotide in the female worms following treatment. After 13 three-monthly treatments, female worm homozygotes with the less common genotype, prior to treatment, increased in frequency. The selected homozygotes, as well as heterozygotes, appeared to be less fertile (without or with very few embryonic stages in their uteri) than the wild-type homozygotes. These results provide additional evidence for genetic selection and strengthen the warning that selection for IVM resistance may be occurring in some O. volvulus populations.
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http://dx.doi.org/10.1016/j.molbiopara.2012.05.005DOI Listing
September 2012

Child neurodevelopment in a Bolivian mining city.

Environ Res 2012 Jan 22;112:147-54. Epub 2011 Dec 22.

Centre for Research in Environmental Epidemiology (CREAL), Barcelona Biomedical Research Park, Dr. Aiguader 88, 08003 Barcelona, Spain.

This study evaluates the neurodevelopment of children living near contaminated mining industries during their first year of life. Participants from the city of Oruro (Bolivia) were prospectively recruited during pregnancy. Follow-up occurred between May 2007 and November 2009. Information about the socioeconomic status and medical history of the pregnant women were collected using questionnaires. Neurodevelopment was evaluated for 246 children using the Bayley Scales of Infant Development (BSID) at 10.5-12.5 months of age. Exposure to trace elements (Pb, As, Cd, Sb, Cs, Zn, Fe, Cu, Se, Rb, and Sr) during prenatal life was evaluated by testing maternal blood concentrations before delivery. Almost all measured levels were lower than the control limits. The blood lead concentration of pregnant women was low, considering the contaminated environmental context. The geometric mean was 1.76 μg/dL (95% CI: 1.68-1.84), a level comparable with those observed in non-contaminated areas. The only element found to be relatively elevated was antimony, with a geometric mean of 1.03 μg/dL (95% CI: 0.96-1.11). Our results suggest that women from this mining area were not highly exposed. The Bayley Scales of Infant Development (BSID) did not reveal mental or psychomotor abnormalities. Surprisingly, at the observed low levels, lead was positively associated with the children's BSID performance.
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http://dx.doi.org/10.1016/j.envres.2011.12.001DOI Listing
January 2012

Influence of source distribution and geochemical composition of aerosols on children exposure in the large polymetallic mining region of the Bolivian Altiplano.

Sci Total Environ 2011 Dec 1;412-413:170-84. Epub 2011 Nov 1.

Université de Toulouse; IRD; CNRS; GET; F-31400 Toulouse, France.

The Bolivian Altiplano (Highlands) region is subject to intense mining, tailing and smelting activities since centuries because of the presence of large and unique polymetallic ore deposits (Ag, Au, Cu, Pb, Sn, Sb, Zn). A large scale PM(10), PM(2.5) aerosol monitoring survey was conducted during the dry season in one of the largest mining cities of this region (Oruro, 200,000 inhabitants). Aerosol fractions, source distribution and transport were investigated for 23 elements at approximately 1 km(2) scale resolution, and compared to children exposure data obtained within the same geographical space. As, Cd, Pb, Sb, W and Zn in aerosols are present at relatively high concentrations when compared to studies from other mining regions. Arsenic exceeds the European council PM(10) guide value (6 ng/m(3)) for 90% of the samples, topping 200 ng/m(3). Ag, As, Cd, Cu, Pb and Sb are present at significantly higher levels in the district located in the vicinity of the smelter zone. At the city level, principal component analysis combined with the mapping of factor scores allowed the identification and deconvolution of four individual sources: i) a natural magmatic source (Co, Cs, Fe, K, Mn, Na, Rb and U) originating from soil dust, resuspended by the traffic activity; ii) a natural sedimentary source (Mg, Ca, Sr, Ba and Th) resulting from the suspension of evaporative salt deposits located South; iii) an anthropogenic source specifically enriched in mined elements (As, Cd, Cu, Pb, Sb and Zn) mainly in the smelting district of the city; and iv) a Ni-Cr source homogenously distributed between the different city districts. Enrichment factors for As, Cd and Sb clearly show the impact of smelting activities, particularly in the finest PM(2.5) fraction. Comparison to children's hair metal contents collected in five schools from different districts shows a direct exposure to smelting activity fingerprinted by a unique trace elements pattern (Ag, As, Cu, Pb, Sb).
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http://dx.doi.org/10.1016/j.scitotenv.2011.09.065DOI Listing
December 2011

Indoor metallic pollution related to mining activity in the Bolivian Altiplano.

Environ Pollut 2011 Oct 26;159(10):2870-5. Epub 2011 May 26.

Departamento de Ciencias Ecológicas, Facultad de Ciencias, Universidad de Chile, Santiago, Chile.

The environmental pollution associated with mining and metallurgical activities reaches its greatest extent in several Andean cities and villages. Many locations in this area have accumulated through centuries a large amount of mining wastes, often disregarding the magnitude of this situation. However, in these naturally mineralized regions, there is little information available stating the exact role of mining and metallurgical industries in urban pollution. In this study, we demonstrated that the various metallic elements present in indoor dust (As, Cd, Cu, Pb, Sb, Sn, Zn) had a common origin and this contamination was increased by the proximity to the mines. Lead dust concentration was found at concerning levels for public health. In addition, wrong behaviors such as carrying mining workwear home contributed to this indoor dust pollution. Consequently, the constant exposure of the population could represent a potential health hazard for vulnerable groups, especially children.
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http://dx.doi.org/10.1016/j.envpol.2011.04.039DOI Listing
October 2011

Hair trace elements concentration to describe polymetallic mining waste exposure in Bolivian Altiplano.

Biol Trace Elem Res 2011 Jan 9;139(1):10-23. Epub 2010 Mar 9.

Instituto de Servicios de Laboratorio de Diagnóstico e Investigaciones en Salud (SELADIS), Universidad Mayor de San Andrés, La Paz, Bolivia.

Severe polymetallic contamination is frequently observed in the mining communities of Bolivian Altiplano. We evaluated hair trace elements concentrations at the population level to characterise exposure profile in different contexts of contact with mining and metallurgical pollution. We sampled 242 children aged 7 to 12 years in schools from five Oruro districts located in different contexts of potential contamination. Hair trace elements concentrations were measured using ICP-MS (Pb, As, Hg, Cd, Sb, Sn, Bi, Ag, Ni, Se, Cu, Cr, Mn, Co and Zn). We compared concentration according to school areas and gender. Concentrations were markedly different depending on school areas. Children from schools near industrial areas were far more exposed to non essential elements than children from downtown and suburban schools, as well as the rural school. The most concentrated non-essential element was Pb (geometric means (SD): 1.6 (1.3) µg/g in rural school; 2.0 (2.3) µg/g in suburban school; 2.3 (3.0) µg/g in downtown school; 14.1 (2.7) µg/g in the mine school and 21.2 (3.3) µg/g in the smelter school). Boys showed higher levels for all non-essential elements while girls had higher levels of Zn. Hair trace elements concentrations highlighted the heterogeneity of exposure profiles, identifying the most contaminated districts.
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http://dx.doi.org/10.1007/s12011-010-8641-1DOI Listing
January 2011

Mercury exposure in a high fish eating Bolivian Amazonian population with intense small-scale gold-mining activities.

Int J Environ Health Res 2009 Aug;19(4):267-77

Servicios de Laborotorio de Diagnostico e Investigcion en Salud, La Paz, Bolivia.

Methylmercury exposure in Amazonian communities through fish consumption has been widely documented in Brazil. There is still a lack of data in other Amazonian countries, which is why we conducted this study in the Bolivian Amazon basin. Simple random sampling was used from a small village located in the lower Beni River, where there is intense gold mining and high fish consumption. All participants were interviewed and hair samples were taken to measure total mercury concentrations. The hair mercury geometric mean in the general population was 3.02 microg/g (CI: 2.69-3.37; range: 0.42-15.65). Age and gender were not directly associated with mercury levels. Fish consumption showed a positive relation and so did occupation, especially small-scale gold mining. Hair mercury levels were lower than those found in Brazilian studies, but still higher than in non-exposed populations. It is necessary to assess mercury exposure in the Amazonian regions where data is still lacking, using a standardized indicator.
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http://dx.doi.org/10.1080/09603120802559342DOI Listing
August 2009

Hair mercury levels in Amazonian populations: spatial distribution and trends.

Int J Health Geogr 2009 Dec 21;8:71. Epub 2009 Dec 21.

IRD - SELADIS, La Paz, Bolivia.

Background: Mercury is present in the Amazonian aquatic environments from both natural and anthropogenic sources. As a consequence, many riverside populations are exposed to methylmercury, a highly toxic organic form of mercury, because of their intense fish consumption. Many studies have analysed this exposure from different approaches since the early nineties. This review aims to systematize the information in spatial distribution, comparing hair mercury levels by studied population and Amazonian river basin, looking for exposure trends.

Methods: The reviewed papers were selected from scientific databases and online libraries. We included studies with a direct measure of hair mercury concentrations in a sample size larger than 10 people, without considering the objectives, approach of the study or mercury speciation. The results are presented in tables and maps by river basin, displaying hair mercury levels and specifying the studied population and health impact, if any.

Results: The majority of the studies have been carried out in communities from the central Amazonian regions, particularly on the Tapajós River basin. The results seem quite variable; hair mercury means range from 1.1 to 34.2 microg/g. Most studies did not show any significant difference in hair mercury levels by gender or age. Overall, authors emphasized fish consumption frequency as the main risk factor of exposure. The most studied adverse health effect is by far the neurological performance, especially motricity. However, it is not possible to conclude on the relation between hair mercury levels and health impact in the Amazonian situation because of the relatively small number of studies.

Conclusions: Hair mercury levels in the Amazonian regions seem to be very heterogenic, depending on several factors. There is no obvious spatial trend and there are many areas that have never been studied. Taking into account the low mercury levels currently handled as acceptable, the majority of the Amazonian populations can be considered exposed to methylmercury contamination. The situation for many of these traditional communities is very complex because of their high dependence on fish nutrients. It remains difficult to conclude on the Public Health implication of mercury exposure in this context.
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http://dx.doi.org/10.1186/1476-072X-8-71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816200PMC
December 2009

P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus.

Mol Biochem Parasitol 2008 Apr 14;158(2):101-11. Epub 2007 Dec 14.

Institute of Parasitology, McGill University, 21 111 Lakeshore Road, Sainte Anne-de-Bellevue, Quebec, Canada H9X3V9.

Ivermectin (IVM) is the only safe drug for mass-treatment of onchocerciasis. IVM resistance has been reported in gastrointestinal nematode parasites of animals. A reduction in response to IVM in Onchocerca volvulus could have significant consequences for the onchocerciasis control programs. We have found evidence that, in O. volvulus, repeated IVM treatment selects for specific alleles, of P-glycoprotein-like protein (PLP), a half-sized ABC transporter. In this study, O. volvulus samples were derived from a clinical trial in Cameroon, in which patients were sampled before, and following 3 years (1994-1997) of IVM treatments. There were four treatment groups: 150 microg/kg (1 x p.a. or 4 x p.a.) and 800 microg/kg (1 x p.a. or 4 x p.a.). DNA of O. volvulus macrofilariae was genotyped over a 476bp region of the PLP gene and at two control genes. Of the six polymorphic positions found in the PLP amplicon, three of them showed significant selection after 4 x p.a. treatment with IVM (total of 13 IVM treatments) in female worms, and one of the same single nucleotide polymorphisms (SNPs) showed significant selection in the male worms. One of the selected SNPs in the female worms caused an amino acid coding change in the putative protein sequence. We found a clear selection of some genotypes, a high SNPs association and a loss of polymorphism following 4 x p.a. treatment with IVM. These PLP SNPs and genotypes could be useful markers to follow selection for IVM resistance in the field.
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http://dx.doi.org/10.1016/j.molbiopara.2007.11.017DOI Listing
April 2008

Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment.

PLoS Negl Trop Dis 2007 Aug 30;1(1):e72. Epub 2007 Aug 30.

Institute of Parasitology, McGill University, Sainte Anne-de-Bellevue, Quebec, Canada.

Background: Onchocerca volvulus is the causative agent of onchocerciasis, or "river blindness". Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure.

Methods And Findings: O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 microg/kg or 800 microg/kg. Genotype frequencies were determined in beta-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between beta-tubulin genotype and female parasite fertility. We found a significant selection for beta-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the beta-tubulin "aa" homozygotes from 68.6% to 25.6%, while the "ab" heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the beta-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p = 0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly.

Conclusions: The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes.
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http://dx.doi.org/10.1371/journal.pntd.0000072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2041821PMC
August 2007

A randomized, double-blind, controlled trial of the effects of ivermectin at normal and high doses, given annually or three-monthly, against Onchocerca volvulus: ophthalmological results.

Trans R Soc Trop Med Hyg 2005 Apr;99(4):279-89

Service d'Ophtalmologie, Hôpital Central de Yaoundé, Yaoundé, Cameroun.

A three-year randomized, controlled, double-blind trial was conducted in Cameroon to determine whether ivermectin, given at three-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard doses (150 microg/kg annually). As several patients complained of transitory subjective visual problems after treatment, some of them being of an unexpected type, we organized two series of detailed ophthalmological examinations to evaluate whether they were associated with ocular lesions. Analysis showed that these complaints were significantly more frequent in the two groups treated with high doses of ivermectin than in the reference group. In the ophthalmological examinations, the only differences recorded between the groups were a lower prevalence and mean number of microfilariae in the anterior chamber in the groups treated three-monthly, and, at the first examination round, a higher prevalence of early lesions of the iris in the group treated at high doses annually. These findings do not allow us to explain the cause of the transitory ocular complaints, nor why they were more frequent in the groups treated at high doses. However, one may conclude that using doses of ivermectin higher than the standard one should be considered with caution.
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http://dx.doi.org/10.1016/j.trstmh.2004.04.003DOI Listing
April 2005

Mapping the distribution of Loa loa in Cameroon in support of the African Programme for Onchocerciasis Control.

Filaria J 2004 Aug 6;3(1). Epub 2004 Aug 6.

Liverpool School of Tropical Medicine, Liverpool, UK, L3 5QA.

BACKGROUND: Loa loa has recently emerged as a filarial worm of significant public health importance as a consequence of its impact on the African Programme for Onchocerciasis Control (APOC). Severe, sometimes fatal, encephalopathic reactions to ivermectin (the drug of choice for onchocerciasis control) have occurred in some individuals with high Loa loa microfilarial counts. Since high density of Loa loa microfilariae is known to be associated with high prevalence rates, a distribution map of the latter may determine areas where severe reactions might occur. The aim of the study was to identify variables which were significantly associated with the presence of a Loa microfilaraemia in the subjects examined, and to develop a spatial model predicting the prevalence of the Loa microfilaraemia. METHODS: Epidemiological data were collected from 14,225 individuals living in 94 villages in Cameroon, and analysed in conjunction with environmental data. A series of logistic regression models (multivariate analysis) was developed to describe variation in the prevalence of Loa loa microfilaraemia using individual level co-variates (age, sex, microl of blood taken for examination) and village level environmental co-variates (including altitude and satellite-derived vegetation indices). RESULTS: A spatial model of Loa loa prevalence was created within a geographical information system. The model was then validated using an independent data set on Loa loa distribution. When considering both data sets as a whole, and a prevalence threshold of 20%, the sensitivity and the specificity of the model were 81.7 and 69.4%, respectively. CONCLUSIONS: The model developed has proven very useful in defining the areas at risk of post-ivermectin Loa-related severe adverse events. It is now routinely used by APOC when projects of community-directed treatment with ivermectin are examined.
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http://dx.doi.org/10.1186/1475-2883-3-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514498PMC
August 2004

Dengue spatial and temporal patterns, French Guiana, 2001.

Emerg Infect Dis 2004 Apr;10(4):615-21

Institut de Recherche pour le Développement Guyane, Cayenne, Guyane.

To study a 2001 dengue fever outbreak in Iracoubo, French Guiana, we recorded the location of all patients' homes and the date when symptoms were first observed. A geographic information system (GIS) was used to integrate the patient-related information. The Knox test, a classic space-time analysis technique, was used to detect spatiotemporal clustering. Analysis of the relative-risk (RR) variations when space and time distances vary, highlighted the maximum space and time extent of a dengue transmission focus. The results show that heterogeneity in the RR variations in space and time corresponds to known entomologic and epidemiologic factors, such as the mosquito feeding cycle and host-seeking behavior. This finding demonstrates the relevance and potential of the use of GIS and spatial statistics for elaborating a dengue fever surveillance strategy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323097PMC
http://dx.doi.org/10.3201/eid1004.030186DOI Listing
April 2004

Adverse systemic reactions to treatment of onchocerciasis with ivermectin at normal and high doses given annually or three-monthly.

Trans R Soc Trop Med Hyg 2004 Aug;98(8):496-504

Laboratoire mixte IRD-CPC d'Epidémiologie et de Santé publique, Centre Pasteur du Cameroun, B.P. 1274, Yaoundé, Cameroon.

In Cameroon, a 3-year randomized, double-blind controlled trial was conducted to determine if ivermectin, given at 3-monthly intervals and/or at high doses (800 microg/kg), had a greater effect on adult Onchocerca volvulus than standard annual doses of 150 microg/kg. Adverse reactions were recorded and analysed in a logistic regression model with random effects to assess the influence of the dose and rhythm of treatment on their occurrence. After the first dose, 3-monthly treatment was associated with a clearly reduced risk of reactions, especially oedematous swellings, pruritus and back-pain. Oedematous swellings and subjective ocular troubles were found to be associated with high doses of ivermectin. These results reinforce former parasitological conclusions that it would be desirable to evaluate the feasibility and effects on transmission of large-scale 3-monthly treatments with standard doses of ivermectin for onchocerciasis control. Owing to the unexpected ocular reactions, the use of high doses to counteract any future resistance of O. volvulus to ivermectin should be considered with caution.
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http://dx.doi.org/10.1016/j.trstmh.2003.10.018DOI Listing
August 2004

Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon.

Filaria J 2003 Oct 24;2 Suppl 1:S4. Epub 2003 Oct 24.

Institut de Recherche pour le Développement (IRD), DSS, 213 rue La Fayette, 75480 Paris Cedex 10, France.

In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12-24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3-6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition.
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http://dx.doi.org/10.1186/1475-2883-2-S1-S4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2147657PMC
October 2003