Epidemiology of Mycobacterial Infections

National Institute Of Allergy And Infectious Diseases

Investigators

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Abstract

This past fiscal year we had several major accomplishments related to the above goals: 1) Mycobacteria Avium Complex (MAC) pulmonary infection risk and vanadium in groundwater in Hawaii: Hawaii has the highest prevalence of nontuberculous mycobacterial (NTM) pulmonary disease in the United States. Previous studies indicate that certain trace metals in surface water increase the risk of NTM infection. To identify whether trace metals influence the risk of NTM infection in Oahu, Hawaii. A population-based ecologic cohort study was conducted using NTM infection incidence data from patients enrolled at Kaiser Permanente Hawaii (KPH) during 2005-2019. We obtained sociodemographic, microbiologic and geocoded residential data for all KPH beneficiaries. To estimate the risk of NTM pulmonary infection from exposure to groundwater constituents, we obtained groundwater data from three data sources: 1) Water Quality Portal, 2) the Hawaii Department of Health, and 3) Brigham Young University, Department of Geological Science faculty. Data were aggregated by aquifer and were associated with corresponding beneficiary aquifer of residence. We used Poisson regression models with backward elimination to generate models for NTM infection risk as a function of groundwater constituents. We modeled two outcomes: Mycobacterium avium complex (MAC) species and Mycobacterium abscessus group species. For every 1-unit increase in the log concentration of vanadium in groundwater at the aquifer level, infection risk increased by 22% among MAC patients. We did not observe significant associations between water-quality constituents and infection risk among M. abscessus patients. Concentrations of vanadium in groundwater were associated with MAC pulmonary infection in Oahu, Hawaii. These findings provide evidence that naturally occurring trace metals influence the presence of NTM in water sources that supply municipal water systems. 2) Nontuberculous Mycobacteria Infection Risk and Trace Metals in Surface Water: A Population-based Ecologic Epidemiologic Study in Oregon Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria, and some pathogenic species cause lung disease. Environmental factors contribute to increased NTM abundance, with higher potential for exposure and infection. We conducted a population-based cohort study using patient incidence data from the Oregon statewide NTM laboratory data collected as part of a public health surveillance project from 2007 through 2012. To estimate the risk of NTM pulmonary infection (PI) from exposure to water constituents, we extracted water-quality data from the Water Quality Portal and associated these data with corresponding patient county of residence. Using generalized linear models, we modeled two outcomes: Mycobacterium avium complex species PI and Mycobacterium abscessus group species PI. Results: For every 1-unit increase in the log concentration of vanadium in surface water, infection risk increased by 49% among persons with Mycobacterium avium complex PI. Among those with Mycobacterium abscessus PI, we observed that for every 1-unit increase in the log concentration of molybdenum in surface water, infection risk increased by 41%. The highest risk of infection due to Mycobacterium abscessus group infection was concentrated in counties within the Northwestern region of Oregon. High infection risk associated with Mycobacterium avium complex species did not show any geographic pattern. Concentrations of the trace metals molybdenum and vanadium in surface water sources were associated with NTM infection in Oregon. These findings may help identify regions at higher risk of NTM infection to guide risk reduction strategies. 3) Reduced risk of Nontuberculous mycobacterial infections among persons with Cystic Fibrosis with CFTR treatment: People with cystic fibrosis are at increased risk of pulmonary nontuberculous mycobacteria (NTM) disease. Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are associated with reduced lung infection with pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. This association has not been studied with NTM. Using encounter-level data from the US Cystic Fibrosis Foundation Patient Registry from 2011 to 2018, we identified individuals aged >12 years with one or more NTM-negative sputum culture and information on receipt of ivacaftor therapy. We used a Cox proportional hazards model to assess the relationship between CFTR modulator usage (any and monotherapy versus combination therapy) and NTM sputum culture positivity, controlling for sex, least severe class of CFTR mutation, receipt of chronic macrolides, age, body mass index and percentage predicted forced expiratory volume. Out of 25 987 unique individuals, 17 403 individuals met inclusion criteria. During follow-up, 42% of individuals received CFTR modulator therapy, and 23% had incident NTM. The median (interquartile range) time to event was 6.1 (4.0-7.3) years for those ever receiving CFTR modulators compared to 4.0 (1.6-6.5) years in those never receiving CFTR modulators. CFTR modulator use was associated with a significantly reduced hazard of NTM culture positivity (hazard ratio (HR) 0.88, 95% CI 0.79-0.97); there was no significant difference in the hazard between those receiving ivacaftor monotherapy versus combination therapy (combination HR 1.01, 95% CI 0.79-1.23).CFTR modulator therapy is associated with a decreased risk of NTM positivity in individuals with cystic fibrosis. 4) Predictors of disease progression and patient reported outcomes among persons with NTM and bronchiectasis: Bronchiectasis is a chronic lung condition frequently associated with nontuberculous mycobacteria pulmonary (NTM) disease. Persons with these conditions are at increased risk of mortality. Patient reported outcome (PRO) instruments and the 6-minute walk test (6MWT) have been shown to predict mortality for several lung conditions, but these measures have not been fully evaluated for bronchiectasis and NTM. We conducted a retrospective cohort study among adult patients enrolled in a natural history study of bronchiectasis at the National Heart, Lung, and Blood Institute. Electronic medical records were queried for demographic, clinical, microbiologic, radiographic, and PRO instrument data: St. George's Respiratory Questionnaire (SGRQ), Medical Research Council Dyspnea Scale, and the Pulmonary Symptom Severity Score (PSSS). The study baseline date was defined as the patient's first visit after January 1st, 2015 with a SGRQ or 6MWT completed. Follow-up was defined as the interval between the study baseline visit and date of death or December 31st, 2019. Sex-stratified Cox proportional-hazards regression was conducted to identify predictors of mortality. Separate models were run for each PRO and 6MWT measure, controlling for age, body mass index (BMI), fibrocavitary disease status, and M. abscessus infection. In multivariable Cox proportional-hazards regression models, the PSSS-severity (aHR 1.29, 95% CI 1.04-1.59), the 6MWT total distance walked (aHR 0.938, 95% CI 0.896-0.981) and distance saturation product (aHR 0.930, 95% CI 0.887-0.974) independently predicted mortality. In addition, BMI was significantly predictive of mortality in all models.The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients.