American Journal of Epidemiology Original Contribution Evidence from Chile That Arsenic in Drinking Water May Increase Mortality from Pulmonary Tuberculosis

Arsenic in drinking water causes increased mortality from several cancers, ischemic heart disease, bronchiec-tasis, and other diseases. This paper presents the first evidence relating arsenic exposure to pulmonary tuberculosis , by estimating mortality rate ratios for Region II of Chile compared with Region V for the years 1958–2000. The authors compared mortality rate ratios with time patterns of arsenic exposure, which increased abruptly in 1958 in Region II and then declined starting in 1971. Tuberculosis mortality rate ratios in men started increasing in 1968, 10 years after high arsenic exposure commenced. The peak male 5-year mortality rate ratio occurred during 1982– 1986 (rate ratio ¼ 2.1, 95% confidence interval: 1.7, 2.6; P < 0.001) and subsequently declined. Mortality rates in women were also elevated but with fewer excess pulmonary tuberculosis deaths (359 among men and 95 among women). The clear rise and fall of tuberculosis mortality rate ratios in men following high arsenic exposure are consistent with a causal relation. The findings are biologically plausible in view of evidence that arsenic is an immunosuppressant and also a cause of chronic lung disease. Finding weaker associations in women is un-surprising, because this is true of most arsenic-caused health effects. Confirmatory evidence is needed from other arsenic-exposed populations. Tuberculosis is a major public health problem worldwide. As noted by Das and Horton in 2010 (1), in the past year alone there have been 2 million deaths from tuberculosis and 9 million new infections. There is more tuberculosis today than at any other time in history. Increased susceptibility to tuberculosis has been identified with human immunodeficiency virus infection (2), diabetes mellitus (3), end-stage renal disease (4), and chronic lung diseases such as silicosis (5). Immune suppression is thought to be a mechanism involved in increasing tuberculosis rates with these conditions. Arsenic in drinking water has been found to cause immune suppression (6–8) and chronic lung diseases including bronchiecta-sis (9), but the relation between arsenic in water and pulmonary tuberculosis has not been investigated until now. Arsenic in drinking water is a serious public health problem affecting many countries, with millions of people throughout the world exposed (10). Marked increases in mortality from many different causes have been established to follow prolonged consumption of arsenic-contaminated water, with the 3 main causes of death being lung cancer, bladder cancer, and acute myocardial infarction (11–16). Surprisingly, the lung is a target organ for ingested arsenic, with …