Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study

Citation: Das S, Mandal R, Rabidas VN, Verma N, Pandey K, Ghosh AK, et al. (2016) Chronic Arsenic Exposure and Risk of Post Kala-azar Dermal Leishmaniasis Development in India: A Retrospective Cohort Study. PLoS Negl Trop Dis 10(10): e0005060. doi:10.1371/journal.pntd.0005060
Published: October 24, 2016

Abstract
Background: Visceral leishmaniasis (VL), with the squeal of Post-kala-azar dermal leishmaniasis (PKDL), is a global threat for health. Studies have shown sodium stibogluconate (SSG) resistance in VL patients with chronic arsenic exposure. Here, we assessed the association between arsenic exposure and risk of developing PKDL in treated VL patients.
Methods: In this retrospective study, PKDL patients (n = 139), earlier treated with SSG or any other drug during VL, were selected from the study cohort. Trained physicians, unaware of arsenic exposure, interviewed them and collected relevant data in a questionnaire format. All probable water sources were identified around the patient’s house and water was collected for evaluation of arsenic concentration. A GIS-based village-level digital database of PKDL cases and arsenic concentration in groundwater was developed and individual point location of PKDL cases were overlaid on an integrated GIS map. We used multivariate logistic regression analysis to assess odds ratios (ORs) for association between arsenic exposure and PKDL development.
Results: Out of the 429 water samples tested, 403 had arsenic content of over 10 μg/L, with highest level of 432 μg/L among the seven study villages. Multivariate adjusted ORs for risk of PKDL development in comparison of arsenic concentrations of 10.1–200 μg/L and 200.1–432.0 μg/L were 1.85 (1.13–3.03) and 2.31 (1.39–3.8) respectively. Interestingly, similar results were found for daily dose of arsenic and total arsenic concentration in urine sample of the individual. The multivariate-adjusted OR for comparison of high baseline arsenic exposure to low baseline arsenic exposure of the individuals in the study cohort was 1.66 (95% CI 1.02–2.7; p = 0.04).
Conclusion: Our findings indicate the need to consider environmental factors, like long time arsenic exposure, as an additional influence on treated VL patients towards risk of PKDL development in Bihar.

Author Summary: Post-kala-azar dermal leishmaniasis (PKDL) is a sequela of visceral leishmaniasis (VL) that appears after patients have apparently been cured of visceral leishmaniasis; even been reported in patients without a history of VL. Previous clinical and epidemiological data ascertains the main risk factor associated with the development of PKDL is previous treatment for VL with antimonials (SSG); however, PKDL also occurs after treatment with other drugs like paromomycin, miltefosine etc. Here, in light of the risk of arsenic-associated dermal manifestations, we hypothesized that the long term exposure to groundwater arsenic acts as an additional risk factor for development of PKDL in patients treated for VL with SSG or other drugs. Using a cohort, we retrospectively assessed the risk of arsenic in development of PKDL in treated VL patients. Our findings support a significant association and prompts parasites might persist successfully in individuals over-exposed to arsenic and may exhibit features of dermatotropism leading to development of PKDL after treatment for VL. Further research is needed to dissect the mechanistic role of arsenic on VL, as well as PKDL development.

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