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Loiasis was long deemed to be a benign condition, but individuals with high Loa loa microfilarial densities (MFD) are at risk of serious adverse events (SAEs) including encephalopathy following ivermectin (IVM) administration. The risk of marked AE or SAE is usually considered when MFD exceeds 8000 microfilariae (mf)/mL or 30,000 mf/mL, respectively. There are no international guidelines on the treatment of loiasis, resulting in a variety of practices worldwide for the treatment of infected individuals outside endemic areas. Our objective was to determine the probabilities of SAEs after IVM administration at the usual thresholds, and to refine those thresholds using individual characteristics such as age and sex. We used data from two clinical trials conducted in Cameroon where L. loa MFD were determined before IVM administration. The risk of SAE was modeled as a logistic function of age, sex, and MFD transformed as a first-order fractional polynomial. SAEs probabilities were found to be <104 for MFD<2000 mf/mL, > 1‰ for MFD >8000 mf/mL, >1% for MFD>20,000 mf/mL, and >2.5% for MFD>30,000 mf/mL. We showed that specific categories may be at a higher risk of SAE than expected. Specifically, in order not to exceed 1% risk, the corresponding thresholds would be 18,000 mf/mL for females in the 31-40 age group; 16,000 mf/mL for males in the 21-30 age group; 12,000 mf/mL for males in the 31-40 age group; and 19,000 mf/mL for males in the 41-50 age group. Our study suggests that IVM should be used with caution for males or individuals in specific age categories with a high L. loa MFD. For these high risk groups, lowering the thresholds to 8000 mf/mL should be considered. The increased risk in males requires further investigation to understand the pathophysiological phenomena involved that are crucial to prevent and manage SAEs.

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.

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.

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.

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 μg/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.

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. 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. 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.

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. 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. 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. 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.

Importance Due to the amount of iodine 131 released in nuclear tests and its active uptake by the thyroid, differentiated thyroid carcinoma (DTC) is the most serious health risk for the population living near sites of nuclear tests. Whether low doses to the thyroid from nuclear fallout are associated with increased risk of thyroid cancer remains a controversial issue in medicine and public health, and a misunderstanding of this issue may be associated with overdiagnosis of DTCs. Design, Setting, and Participants This case-control study was conducted by extending a case-control study published in 2010 that included DTCs diagnosed between 1984 and 2003 by adding DTCs diagnosed between 2004 and 2016 and improving the dose assessment methodology. Data on 41 atmospheric nuclear tests conducted by France between 1966 and 1974 in French Polynesia (FP) were assessed from original internal radiation-protection reports, which the French military declassified in 2013 and which included measurements in soil, air, water, milk, and food in all FP archipelagos. These original reports led to an upward reassessment of the nuclear fallout from the tests and a doubling of estimates of the mean thyroid radiation dose received by inhabitants from 2 mGy to nearly 5 mGy. Included patients were diagnosed from 1984 to 2016 with DTC at age 55 years or younger and were born in and resided in FP at diagnosis; 395 of 457 eligible cases were included, and up to 2 controls per case nearest by birthdate and matched on sex were identified from the FP birth registry. Data were analyzed from March 2019 through October 2021. Exposure The radiation dose to the thyroid gland was estimated using recently declassified original radiation-protection service reports, meteorological reports, self-reported lifestyle information, and group interviews of key informants and female individuals who had children at the time of these tests. Main Outcomes and Measures The lifetime risk of DTC based on Biological Effects of Ionizing Radiation (BEIR) VII models was estimated. Results A total of 395 DTC cases (336 females [85.1%]; mean [SD] age at end of follow-up, 43.6 [12.9] years) and 555 controls (473 females [85.2%]; mean [SD] age at end of follow-up, 42.3 [12.5] years) were included. No association was found between thyroid radiation dose received before age 15 years and risk of DTC (excess relative risk [ERR] per milligray, 0.04; 95% CI, −0.09 to 0.17;P = .27). When excluding unifocal noninvasive microcarcinomas, the dose response was significant (ERR per milligray, 0.09; 95% CI, −0.03 to 0.02;P = .02), but several incoherencies with the results of the initial study reduce the credibility of this result. The lifetime risk for the entire FP population was 29 cases of DTC (95% CI, 8-97 cases), or 2.3% (95% CI, 0.6%-7.7%) of 1524 sporadic DTC cases in this population. Conclusions and Relevance This case-control study found that French nuclear tests were associated with an increase in lifetime risk of PTC in FP residents of 29 cases of PTC. This finding suggests that the number of thyroid cancer cases and the true order of magnitude of health outcomes associated with these nuclear tests were small, which may reassure populations of this Pacific territory.

Abandoned mines are a recurrent problem for nearby communities in Mediterranean regions because mine tailings represent a major source of polymetallic contamination. Metal contaminants are emitted in mining areas and dispersed by wind and water erosion in the surroundings. The goal of this literature review was to identify the specific features of polymetallic contamination arising from abandoned mines in the Mediterranean regions. Mediterranean climate conditions and local geochemical context are the most important factors that control the metal-bearing particle dispersion toward the different compartments of ecosystems. Acid mine drainage, as an important source of damage to the environment, is limited to a certain extent by the predominance of carbonate rocks in the Mediterranean regions. In opposite, aeolian contamination is specific to the semiarid conditions of the Mediterranean climate. In this context, impacts on different compartments such as agricultural soils and edible plants or human populations were underlined. The analysis of environmental laws and regulations of North and South Mediterranean countries shows that one of the main differences is the lack of identification and definition of mining waste as a public concern in the latter countries. In order to limit the transfer of contaminants from mining waste to the different components of the environment, phytostabilization of mine tailings was considered as the more adapted green technology even in the Mediterranean region where water access is limited. Finally, this review of polymetallic pollution from abandoned mines in Mediterranean regions enabled to identify priority actions for future research.

In 1995, the World Bank launched an African Programme for Onchocerciasis Control to eliminate Onchocerca volvulus disease from 19 African countries by means of community-based ivermectin treatment (CBIT). Several cases of encephalopathy have been reported after ivermectin in people heavily infected with microfilariae of Loa loa (loiasis). We assessed the incidence of serious events in an area where onchocerciasis and loiasis are both endemic. Ivermectin (at 150 μg/kg) was given to 17 877 people living in the Lékié area of Cameroon. 50 μL samples of capillary blood were taken during the daytime before treatment from all adults (aged ≥15 years), and the numbers of L loa and Mansonella perstans microfilariae in them were counted. Patients were monitored for 7 days after treatment. Adverse reactions were classified as mild, marked, or serious. Serious reactions were defined as those associated with a functional impairment that required at least a week of full-time assistance to undertake normal activities. We calculated the relative risk of developing marked or serious reactions for increasing L loa microfilarial loads. Risk factors for serious reactions were identified and assessed with a logistic regression model. 20 patients (0·11%) developed serious reactions without neurological signs but associated with a functional impairment lasting more than a week. Two other patients were in coma for 2–3 days, associated with L loa microfilariae in cerebrospinal fluid. Occurrence of serious reactions was related to the intensity of pretreatment L loa microfilaraemia. The relative risk of developing marked or serious reactions was significantly higher when the L loa load exceeded 8000 microfilariae/mL; for serious reactions, the risk is very high (odds ratio >1000) for loads above 50 000 microfilariae/mL. Epidemiological surveys aimed at assessing the intensity of infection with L loa microfilariae should be done before ivermectin is distributed for onchocerciasis control in areas where loiasis is endemic. In communities at risk, monitoring procedures should be established and adhered to during CBIT so that people developing serious reactions may receive appropriate treatment.