Epidemiology of Mycobacterial Infections

National Institute Of Allergy And Infectious Diseases

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Abstract

This past fiscal year we had two major accomplishment related to the above goals: 1) Project: Molybdenum and pulmonary NTM risk among bronchiectasis patients at NIH Epidemiologic studies have demonstrated an association between trace metals in source water and water distribution systems and nontuberculous mycobacterial (NTM) pulmonary infection and disease. Specifically, molybdenum has been strongly associated with Mycobacterium abscessus and Mycobacterium avium complex (MAC) infection and disease in multiple epidemiologic studies. We aimed to determine if urinary molybdenum, chromium, and manganese concentrations were associated with pulmonary NTM infection in a bronchiectasis patient cohort. Methods: We enrolled 120 consecutive adult bronchiectasis patients participating in a bronchiectasis natural history study. We collected one urine sample per patient during routine visits and sent samples to the Centers for Disease Control (CDC) for trace metal testing. We defined three patient subgroups: 1) current NTM infection, 2) previous NTM infection, and 3) never NTM infection. Logistic regression models adjusted for age, racial/ethnic group, and cavitary disease status were used to test for differences between metal concentrations across infection statuses. Results: Forty-six (38%) patients were currently infected with NTM, 46 (38%) were previously infected, and 28 (23%) were never infected. For each increase of one standard deviation of the logarithm of molybdenum concentration, the odds of current versus never NTM infection increased significantly by 14% (OR = 1.14, 95% CI = 1.02-1.28), while manganese and chromium did not exhibit significant associations. Conclusions: This clinical study is the first to examine the relationship between trace metals and pulmonary NTM infections. These findings support those from prior population-based studies. 2) Project: NTM PD Prevalence in NYC and neighborhood level risk factors We assessed how neighborhood-level risk factors influenced NTM PD prevalence in New York City. We used outpatient claims data from hospitals participating in the Patient-Centered Outcomes Research Institute network, compiled by the INSIGHT Clinical Research Network at Weill Cornell Medicine. NTM PD period prevalence (referred to here as ‘prevalence’) was estimated by New York City neighborhood for the study period 2012 through 2022. De-identified NTM case data and demographic data were analyzed by neighborhood of residence at diagnosis. Using prevalence estimates, we detected high- and low-prevalence regions within New York City and associated these estimates with demographic, clinical, socioeconomic, and environmental neighborhood-level factors using Poisson regression and backward elimination of covariates. Results: Overall, 6,169 NTM PD cases were identified among persons receiving care across 17 private New York City hospitals. Over the study period, NTM PD prevalence increased throughout New York City, and median year built of housing units, median income, and median age of residents were neighborhood-level factors that significantly increased NTM prevalence. The highest prevalence neighborhoods were in Manhattan, while the lowest prevalence neighborhoods were in Brooklyn and Staten Island. Our findings indicate that neighborhood-level access to care may explain the heterogeneity in NTM PD prevalence between New York City neighborhoods, as higher income, newer neighborhoods exhibited the highest NTM PD prevalences. Future studies should examine the extent of undetected NTM infection in New York City, particularly in low-income areas. 3) Project: The risk of NTM pulmonary infections associated with trace metal exposure from public water distribution systems in the United States Rationale: The prevalence of nontuberculous mycobacterial (NTM) pulmonary infection (NTM PI) varies geographically in the United States (US). Previous studies indicate that trace metals in environmental source water increase NTM PI risk. Objective: To examine the effect of trace metals, chromium (Cr), cobalt (Co), molybdenum (Mo), strontium (Sr), vanadium (V), in public distribution system water on NTM PI risk among susceptible persons in the US. Methods: We studied NTM PI risk as a function of trace metal exposure from public distribution system water in two US patient populations: 1) The Cystic Fibrosis Foundation Patient Registry. 2) The Centers for Medicare and Medicaid Services. Patient data were extracted for the period 2010-2019. We obtained data on trace metal concentrations from the US Environmental Protection Agency, Third Unregulated Contaminant Monitoring Rule dataset. We used logistic and negative binomial generalized linear models to estimate risk of NTM PI as a function of trace metal exposure in treated drinking water at the county level. Our models were adjusted for patient demographics, source water type, climate variables, and the type of disinfectant used. Results: Our cystic fibrosis (CF) population comprised 14,242 persons with CF, including 4,015 NTM cases and 10,227 controls. Our Medicare population comprised 27,084,170 beneficiaries, including 84,071 NTM cases. In the Medicare analysis, V was associated with increased NTM PI risk in the Midwest, South and West, while Mo increased NTM PI risk in the West. In the CF analysis, V increased NTM PI risk in the South, while Mo was associated with increased NTM PI risk in the West. In both the CF and Medicare populations, the chloramine as a disinfectant significantly increased the risk of NTM PI. Conclusions: Mo and V in treated water was associated with increased risk among persons susceptible to NTM PI. The effect of trace metals varies by geographic region.