Epidemiology of Mycobacterial Infections

National Institute Of Allergy And Infectious Diseases

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Abstract

This past fiscal year we had several major projects related to the above goals: 1) Nontuberculous Mycobacterial Prevalence Varies by Body Mass Index (BMI): a population-based study among Kaiser Permanente Hawaii beneficiaries, 2005-2019 Hawaii has the highest prevalence of nontuberculous mycobacterial pulmonary disease (NTM-PD) in the United States. However, NTM-PD prevalence varies among the diverse racial/ethnic groups resident in Hawaii. Persons who are underweight are at increased risk of NTM-PD, therefore the observed variation in prevalence may be confounded by body mass index (BMI) distribution across racial/ethnic groups. To investigate these patterns, we studied NTM-PD prevalence by racial/ethnic group and BMI among Kaiser Permanente Hawaii (KPH) beneficiaries. We extracted microbiologic, demographic, and clinical information from electronic health records of adult beneficiaries aged < 89 years from 2005 through 2019. An NTM-PD case was defined as one or more respiratory cultures positive for pathogenic NTM, as trends were similar among beneficiaries with 1 versus 2 positive cultures. Racial/ethnic identification was self-reported and included up to 27 racial/ethnic groups. Beneficiaries reporting white, Asian, and Native Hawaiian or Pacific Islander (NHOPI) race/ethnicity were categorized as having reported exclusively, any, or no identification with these subgroups. Based on the first available BMI, beneficiaries were categorized as underweight (< 18.5 kg/m2), normal weight (18.5 - < 25 kg/m2), or overweight ( 25 kg/m2). Beneficiaries with valid values for race/ethnicity and BMI were included in the analysis. Overall, of 281,266 persons who met analysis inclusion criteria, 803 confirmed or probable cases were identified, for a period prevalence of 286/100,000; 70% had Mycobacterium avium complex infections. NTM-PD prevalence varied by BMI, with the highest prevalence of 671/100,000 observed in the underweight group; this prevalence was 1.8-fold that for the normal weight group (371/100,000) and threefold that of the overweight group (220/100,000). This pattern of decreasing prevalence with increasing BMI was observed across all racial/ethnic groups studied (white, Asian, NHOPI). Because of small sample sizes, persons who identified as only white or only Asian were compared to those who reported any NHOPI identification. Among these groups the NTM-PD prevalence of those who were underweight was 1.4-2.4-fold those who were normal weight and 1.9-3.0-fold those who were overweight (Figure 1). Weight distributions varied across racial/ethnic groups: in our analytic subgroup with non-missing BMI values, the proportion overweight was 51% for only Asian, 58% for only white, and 79% for any NHOPI identification. The low NTM-PD prevalence previously observed among KPH beneficiaries who identify as NHOPI appears partly attributable to overall higher BMI in this subpopulation. 2) The Association of Trace Metals in Surface Water and Nontuberculous Mycobacterial Pulmonary Disease: A Population-Based Epidemiologic study in Oregon. Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that may cause chronic lung disease Environmental factors likely contribute to increased NTM concentrations with higher potential for exposure and infection. To identify water-quality constituents that influence the risk of NTM disease in Oregon, we conducted a population-based cohort study using patient data from the Oregon statewide NTM laboratory data from a public health surveillance project during 2007 to 2012. We associated patient residence with water-quality data corresponding the area of residence, extracted from the Water Quality Portal, to estimate odds of NTM infection. Using generalized linear models with Poisson-distributed discrete responses, we modeled three separate outcomes; Any NTM infection, infections due to Mycobacterium avium complex species, and infections due to Mycobacterium abscessus group species. We observed significant associations between aluminum and vanadium in surface water sources and NTM pulmonary disease among those with Mycobacterium avium complex species. For every 1- unit increase in the log concentration of aluminum in surface water, the risk of disease decreased by 29%, whereas the risk increased by 80% for every 1- unit increase in the log concentration of vanadium. We also observed a significant association with molybdenum in surface water and NTM pulmonary disease among those with Mycobacterium abscessus species infection. For every 1- unit increase in the log concentration of molybdenum in surface water, the risk of disease for those with Mycobacterium abscessus group species increased by 41%. The highest risk of disease due to Mycobacterium abscessus infection was concentrated in counties within the northwestern region of Oregon; high disease risk associated with Mycobacterium avium complex species showed a less discernable pattern across Oregon counties. We have identified molybdenum and vanadium in surface water sources as predictive factors for NTM disease in Oregon. These findings may help identify regions at higher risk of NTM disease to guide risk reduction strategies. 3) Environmental determinants of NTM in the CF population in Miami Environmental predictors of pulmonary nontuberculous mycobacteria (NTM) sputum positivity among persons with cystic fibrosis in the state of Florida Nontuberculous mycobacteria (NTM) are opportunistic human pathogens that are commonly found in soil and water, and exposure to these organisms may cause pulmonary nontuberculous mycobacterial disease. Persons with cystic fibrosis (CF) are at high risk for developing pulmonary NTM infections, and studies have shown that prolonged exposure to certain environments can increase the risk of pulmonary NTM. It is therefore important to determine the risk associated with different geographic areas. Using annualized registry data obtained from the Cystic Fibrosis Foundation Patient Registry for 2010 through 2017, we conducted a geospatial analysis of NTM infections among persons with CF in Florida. A Bernoulli model in SaTScan was used to identify clustering of ZIP codes with higher than expected numbers of NTM culture positive individuals. Generalized linear mixed models with a binomial distribution were used to test the association of environmental variables and NTM culture positivity. We identified a significant cluster of M. abscessus and predictors of NTM sputum positivity, including annual precipitation and soil mineral levels. 4) Ivacaftor and Risk of Nontuberculous Mycobacteria Positivity in Cystic Fibrosis, 2011-2018 Therapeutic use of ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, is significantly associated with a decreased risk of NTM positivity in individuals with cystic fibrosis. Ivacaftor, a cystic fibrosis transmembrane conductance regulator potentiator, has been associated with reduced lung infection with pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. Of 25,987 unique individuals with encounters in the Cystic Fibrosis Foundation Patient Registry; 17,403 individuals met inclusion criteria. During follow up, 42% of individuals received ivacaftor, and 23% had incident NTM. The median time to event was 6.1 years (IQR: 4.0 7.3 years) for those ever-receiving ivacaftor compared to 4.0 years (IQR: 1.6 6.5 years) in those never receiving ivacaftor. Ivacaftor was associated with a significantly reduced hazard of NTM culture positivity (HR: 0.86, 95% CI: 0.78, 0.94); there was no significant difference in the hazard between those receiving monotherapy vs combination therapy (combination HR: 1.01, 95% CI: 0.84, 1.21).