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Background. A previously developed, specific, rapid-format immunochromatographic card test that detects immunoglobulin G4 to the recombinant Onchocerca volvulus antigen Ov-16 was modified to detect antibodies in whole blood. Methods. Ov-16 card test results were assessed in 1511 subjects >/=2 years of age in 7 West African villages with varying histories of onchocerciasis control measures. Results. In villages in which control measures had been implemented, anti-Ov-16 antibody prevalence rates ranged from 5.2% to 65.1%. Antibody prevalence rates were close to zero among subjects born after effective control measures had been implemented. In 2 villages without a history of control measures where onchocerciasis was endemic, microfilariae (MF) prevalence rates were 82.8% and 65.1%, and antibody prevalence rates were 73.1% and 62.1%. In these 2 villages, the sensitivity of the Ov-16 card test was 81.1% and 76.5%, the specificity was 100%, and the positive predictive value was 91.8% and 80.5%. MF and antibody prevalence rates were correlated (Spearman's r=0.815; P<.038). Conclusions. The Ov-16 card test is field applicable, exhibits high sensitivity and specificity for O. volvulus infection, and has great potential as a tool for surveillance and for evaluating the success of onchocerciasis control measures. Copyright © 2006 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

OBJECTIVES: Changes to the polio vaccination schedule, first to a sequential inactivated poliovirus/oral poliovirus (IPV/OPV) schedule in 1996 and most recently to an all-IPV schedule, require infants to receive additional injections. Some surveys show parental hesitation concerning extra injections, whereas others show that parents prefer multiple simultaneous injections over extra immunization visits. This study describes parental behavior and attitudes about the poliovirus vaccine recommendations and additional injections at the 2- and 4-month immunization visits. METHODS: Beginning July 1, 1996, providers in eight public health clinics in Cobb and Douglas Counties, Georgia, informed parents of polio vaccination options and recommended the IPV/OPV sequential schedule. A cross-sectional clinic exit survey was conducted from July 15, 1996, to January 31, 1997, with parents whose infants (younger than 6 months) were eligible for a first poliovirus vaccination. RESULTS: Of approximately 405 eligible infants, parents of 293 infants were approached for an interview, and 227 agreed to participate. Of those 227 participants, 210 (92%) parents chose IPV for their infant and 17 (8%) chose OPV. Of greatest concern to most parents was vaccine-associated paralytic polio (VAPP) (155, or 68.3%); the next greatest concern was an extra injection (22, or 9.7%). These parental concerns were unrelated to the number of injections the infant actually received. CONCLUSIONS: After receiving information on polio vaccination options and a provider recommendation, parents overwhelmingly chose IPV over OPV. Concern about VAPP was more common than objection to an extra injection. The additional injection that results from using IPV for an infant's first poliovirus vaccination appears to be acceptable to most parents. [ABSTRACT FROM AUTHOR]

Problem/Conditions: Despite widespread availability of a safe and effective vaccine against tetanus, 124 cases of the disease were reported during 1995-1997. Only 13% of patients reported having received a primary series of tetanus toxoid (TT) before disease onset. Of patients with known illness outcome, the case-fatality ratio was 11%. Reporting Period Covered: 1995-1997. Description of System: Physician-diagnosed cases of tetanus are reported by state and local health departments to CDC's National Notifiable Diseases Surveillance System. In addition, since 1965, supplemental clinical and epidemiologic information for cases has been provided to CDC's National Immunization Program. Results: From 1995 through 1997, a total of 124 cases of tetanus were reported from 33 states and the District of Columbia, accounting for an average annual incidence of 0.15 cases per 1,000,000 population. Sixty percent of patients were aged 20-59 years; 35% were aged >/=60 years; and 5% were aged <20 years, including one case of neonatal tetanus. For adults aged >/=60 years, the increased risk for tetanus was nearly sevenfold that for persons aged 5-19 years and twofold that for persons aged 20-59 years. The case-fatality ratio varied from 2.3% for persons aged 20-39 years to 16% for persons aged 40-59 years and to 18% for persons aged >/=60 years. Only 13% of patients reported having received a primary series of TT before disease onset. Previous vaccination status was directly related to severity of disease, with the case-fatality ratio ranging from 6% for patients who had received one to two doses to 15% for patients who were unvaccinated. No deaths occurred among the 16 patients who previously had received three or more doses. Tetanus occurred following an acute injury in 77% of patients, but only 41% sought medical care for their injury. All patients who sought care were eligible for TT as part of wound prophylaxis, but only 39% received it. Tetanus in injecting-drug users (IDUs) with no known acute injury comprised 11% of all cases, compared with 3.6% during 1991-1994. None of the IDU-associated tetanus cases occurred among persons who were known to have been vaccinated. Sixty-nine percent of IDU-associated tetanus cases were reported from California, and 77% of these cases occurred in heroin users. Interpretation: Tetanus remains a severe disease that primarily affects unvaccinated or inadequately vaccinated persons. Adults aged >/=60 years continue to be at highest risk for tetanus and for severe disease. However, the overall incidence of tetanus has decreased slightly since the late 1980s and early 1990s, from 0.20 to 0.15, a result primarily of a decreased incidence among persons aged >/=60 and <20 years. Actions Taken: Tetanus is preventable through both routine vaccination and appropriate wound management. In addition to decennial booster doses of diphtheria and tetanus toxoids during adult life, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination visits for adolescents at age 11-12 years and for adults at age 50 years to enable health-care providers to review vaccination histories and administer any needed vaccine. Every contact with the health-care system, particularly among older adults and IDUs, should be used to review and update vaccination status as needed. [ABSTRACT FROM AUTHOR]

In 1992, Brazil adopted the goal of measles elimination by the year 2000; however, in 1997, after a 4-year period of good control, there was a resurgence of measles in Brazil. In 1999, to achieve the elimination goal, Brazil implemented the Supplementary Emergency Measles Action plan, with one measles surveillance technician designated to each state. Of 10,007 suspected measles cases reported during 1999, 908 (9.1%) were confirmed, and of them 378 (42%) were confirmed by laboratory analysis. Of 8358 suspected measles cases reported in 2000, 36 (0.4%) were confirmed (30 [83%] by laboratory); 92% of the discarded cases were classified on the basis of laboratory testing. In 2001, only 1 of 5599 suspected measles cases was confirmed, and it was an imported case from Japan. The last outbreak occurred in February 2000, with 15 cases. Current data suggest interruption of indigenous measles transmission in Brazil. Copyright © 2003 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Background: Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that cause chronic lung disease. Rates of NTM pulmonary disease (NTM PD) have increased over the last several decades, yet national estimates in the United States (US) have not been assessed since 2015., Methods: We used a nationally representative population of Medicare beneficiaries aged ≥ 65 years to assess rates of NTM PD in a high-risk population from 2010 to 2019. Poisson generalized linear models were used to assess the annual percent change in incidence in the overall population and among key demographic groups such as sex, geography, and race/ethnicity. We evaluated the relative prevalence of various comorbid conditions previously found to be associated with NTM PD., Results: We identified 59,724 cases of incident NTM PD from 2010 to 2019 from an annual mean population of 29,687,097 beneficiaries, with an average annual incidence of 20.1 per 100,000 population. NTM PD incidence was overall highest in the South and among women, Asian individuals, and persons aged ≥ 80 years relative to other studied demographic groups. The annual percent change in NTM PD incidence was highest in the Northeast, at 6.5%, and Midwest, at 5.9%, and among women, at 6.5%. Several comorbid conditions were highly associated with concurrent NTM diagnosis, including allergic bronchopulmonary aspergillosis, bronchiectasis, and cystic fibrosis., Conclusions: Here we provide current estimates of NTM PD incidence and prevalence and describe increasing trends in the US from 2010 to 2019. Our study suggests a need for improved healthcare planning to handle an increased future caseload, as well as improved diagnostics and therapeutics to better detect and treat NTM PD in populations aged ≥ 65 years., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Evidence continues to accumulate regarding the potential long-term health consequences of COVID-19 in the population. To distinguish between COVID-19-related symptoms and health limitations from those caused by other conditions, it is essential to compare cases with community controls using prospective data ensuring case-control status. The RESPIRA study addresses this need by investigating the lasting impact of COVID-19 on Health-related Quality of Life (HRQoL) and symptomatology in a population-based cohort in Costa Rica, thereby providing a robust framework for controlling HRQoL and symptoms., Methods: The study comprised 641 PCR-confirmed, unvaccinated cases of COVID-19 and 947 matched population-based controls. Infection was confirmed using antibody tests on enrollment serum samples and symptoms were monitored monthly for 6 months post-enrolment. Administered at the 6-month visit (occurring between 6- and 2-months post-diagnosis for cases and 6 months after enrollment for controls), HRQoL and Self-Perceived Health Change were assessed using the SF-36, while brain fog, using three items from the Mental Health Inventory (MHI). Regression models were utilized to analyze SF-36, MHI scores, and Self-Perceived Health Change, adjusted for case/control status, severity (mild case, moderate case, hospitalized) and additional independent variables. Sensitivity analyses confirmed the robustness of the findings., Results: Cases showed significantly higher prevalences of joint pain, chest tightness, and skin manifestations, that stabilized at higher frequencies from the fourth month post-diagnosis onwards (2.0%, 1.2%, and 0.8% respectively) compared to controls (0.9%, 0.4%, 0.2% respectively). Cases also exhibited significantly lower HRQoL than controls across all dimensions in the fully adjusted model, with a 12.4 percentage-point difference [95%CI: 9.4-14.6], in self-reported health compared to one year prior. Cases reported 8.0% [95%CI: 4.2, 11.5] more physical limitations, 7.3% [95%CI: 3.5, 10.5] increased lack of vitality, and 6.0% [95%CI: 2.4, 9.0] more brain fog compared to controls with similar characteristics. Undiagnosed cases detected with antibody tests among controls had HRQoL comparable to antibody negative controls. Differences were more pronounced in individuals with moderate or severe disease and among women., Conclusions: PCR-confirmed unvaccinated cases experienced prolonged HRQoL reductions 6 months to 2 years after diagnosis, this was particularly the case in severe cases and among women. Mildly symptomatic cases showed no significant long-term sequelae., (© 2024. The Author(s).)

Background: Bronchiectasis is a pulmonary disease characterized by irreversible dilation of the bronchi and recurring respiratory infections. Few studies have described the microbiology and prevalence of infections in large patient populations outside of specialized tertiary care centers., Methods: We used the Cerner HealthFacts Electronic Health Record database to characterize the nature, burden, and frequency of pulmonary infections among persons with bronchiectasis. Chronic infections were defined based on organism-specific guidelines., Results: We identified 7,749 patients who met our incident bronchiectasis case definition. In this study population, the organisms with the highest rates of isolate prevalence were Pseudomonas aeruginosa with 937 (12%) individuals, Staphylococcus aureus with 502 (6%), Mycobacterium avium complex (MAC) with 336 (4%), and Aspergillus sp. with 288 (4%). Among persons with at least one isolate of each respective pathogen, 219 (23%) met criteria for chronic P. aeruginosa colonization, 74 (15%) met criteria for S. aureus chronic colonization, 101 (30%) met criteria for MAC chronic infection, and 50 (17%) met criteria for Aspergillus sp. chronic infection. Of 5,795 persons with at least two years of observation, 1,860 (32%) had a bronchiectasis exacerbation and 3,462 (60%) were hospitalized within two years of bronchiectasis diagnoses. Among patients with chronic respiratory infections, the two-year occurrence of exacerbations was 53% and for hospitalizations was 82%., Conclusions: Patients with bronchiectasis experiencing chronic respiratory infections have high rates of hospitalization., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Nontuberculous mycobacteria (NTM) are environmental bacteria which may cause chronic lung disease. The prevalence of NTM pulmonary infection and disease has been increasing in the United States and globally. The predominant clinically relevant species of NTM in the United States are Mycobacterium avium complex (MAC) species and Mycobacterium abscessus. With the development of rapid species identification methods for NTM (e.g. PCR probes), more testing for NTM is being conducted through commercial labs, such as Laboratory Corporation of America (Labcorp), which provides deidentified real-time testing data to the Centers for Disease Control (CDC) pursuant to a data sharing agreement. Because NTM lung infections are not reportable in most states, other data sources are key to understanding NTM testing patterns, positivity rates, and species distributions to track infection trends and identify clinical care needs., Methods: We obtained national Labcorp data for the period January 2019 through mid-April 2022. We subset the data to only respiratory samples sent for Acid Fast Bacilli (AFB) cultures. NTM positive results were defined as those which identified an NTM species and are not Mycobacterium tuberculosis, Mycobacterium bovis, or Mycobacterium gordonae., Results: Overall, 112,528 respiratory samples were sent for AFB testing during the study period; 26.3% were from the Southeast U.S., identified as HSS Region IV in the Labcorp dataset, and 23.0% were from the Pacific and South Pacific region (Region IX). The culture positive prevalence ranged from 20.2% in the Southeast to 9.2% in the East North Central region (Region V). In the Southeast US, M. abscessus prevalence was 4.0%. For MAC, the highest prevalence was observed in the Mountain region (Region VII) (13.5%) and the lowest proportion was in the East South Central region (7.3%, Region III). Among positive tests, the proportion which was MAC varied from 61.8% to 88.9% and was highest in the Northeast U.S. The proportion of positive samples which were M. abscessus ranged from 3.8% to 19.7% and was highest in the Southeast., Conclusions: The Southeastern region of the U.S. has the highest rate of culture positivity in Labcorp tests for total NTM and, of all positive tests, the highest proportion of M. abscessus. These estimates may underrepresent the true number of M. abscessus infections because M. absesscus-specific probes are not commercially available and not all NTM testing in the United States is done by Labcorp. Analysis of real-time testing data from commercial laboratories may provide insights into risk factors for NTM culture positivity in 'hotspot' areas., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Purpose: The RESPIRA cohort aims to describe the nature, magnitude, time course and efficacy of the immune response to SARS-CoV-2 infection and vaccination, population prevalence, and household transmission of COVID-19., Participants: From November 2020, we selected age-stratified random samples of COVID-19 cases from Costa Rica confirmed by PCR. For each case, two population-based controls, matched on age, sex and census tract were recruited, supplemented with hospitalised cases and household contacts. Participants were interviewed and blood and saliva collected for antibodies and PCR tests. Participants will be followed for 2 years to assess antibody response and infection incidence., Findings to Date: Recruitment included 3860 individuals: 1150 COVID-19 cases, 1999 population controls and 719 household contacts from 304 index cases. The age and regional distribution of cases was as planned, including four age strata, 30% rural and 70% urban. The control cohort had similar sex, age and regional distribution as the cases according to the study design. Among the 1999 controls recruited, 6.8% reported at enrolment having had COVID-19 and an additional 12.5% had antibodies against SARS-CoV-2. Compliance with visits and specimens has been close to 70% during the first 18 months of follow-up. During the study, national vaccination was implemented and nearly 90% of our cohort participants were vaccinated during follow-up., Future Plans: RESPIRA will enable multiple analyses, including population prevalence of infection, clinical, behavioural, immunological and genetic risk factors for SARS-CoV-2 acquisition and severity, and determinants of household transmission. We are conducting retrospective and prospective assessment of antibody levels, their determinants and their protective efficacy after infection and vaccination, the impact of long-COVID and a series of ancillary studies. Follow-up continues with bimonthly saliva collection for PCR testing and biannual blood collection for immune response analyses. Follow-up will be completed in early 2024., Trial Registration Number: NCT04537338., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nontuberculous mycobacterial (NTM) isolation and pulmonary disease (NTM-PD) have continued to increase in most regions of the world, driven mainly by Mycobacterium avium. Single-center studies also support increasing trends as well as a persistent burden of undiagnosed NTM among persons suspected of having tuberculosis (TB), in countries with moderate-to-high TB prevalence. Cumulative exposure to water and soil presents an increased risk to susceptible hosts, and trace metals in water supply are recently recognized risk factors. Establishing standard case definitions for subnational and national surveillance systems with mandatory notification of NTM-PD are needed to allow comparisons within and across countries and regions., (Published by Elsevier Inc.)

Background: The true incidence of SARS-CoV-2 infection in Costa Rica was likely much higher than officially reported, because infection is often associated with mild symptoms and testing was limited by official guidelines and socio-economic factors., Methods: Using serology to define natural infection, we developed a statistical model to estimate the true cumulative incidence of SARS-CoV-2 in Costa Rica early in the pandemic. We estimated seroprevalence from 2223 blood samples collected from November 2020 to October 2021 from 1976 population-based controls from the RESPIRA study. Samples were tested for antibodies against SARS-CoV-2 nucleocapsid and the receptor-binding-domain of the spike proteins. Using a generalized linear model, we estimated the ratio of true infections to officially reported cases. Applying these ratios to officially reported totals by age, sex, and geographic area, we estimated the true number of infections in the study area, where 70% of Costa Ricans reside. We adjusted the seroprevalence estimates for antibody decay over time, estimated from 1562 blood samples from 996 PCR-confirmed COVID-19 cases., Findings: The estimated total proportion infected ( ETPI ) was 4.0 times higher than the officially reported total proportion infected ( OTPI ). By December 16th, 2021, the ETPI was 47% [42-52] while the OTPI was 12%. In children and adolescents, the ETPI was 11.0 times higher than the OTPI ., Interpretation: Our findings suggest that nearly half the population had been infected by the end of 2021. By the end of 2022, it is likely that a large majority of the population had been infected., Funding: This work was sponsored and funded by the National Institute of Allergy and Infectious Diseases through the National Cancer Institute, the Science, Innovation, Technology and Telecommunications Ministry of Costa Rica, and Costa Rican Biomedical Research Agency-Fundacion INCIENSA (grant N/A)., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s).)

Rationale: The prevalence of nontuberculous mycobacterial (NTM) pulmonary disease varies geographically in the United States. Previous studies indicate that the presence of certain water-quality constituents in source water increases NTM infection risk., Objective: To identify water-quality constituents that influence the risk of NTM pulmonary infection in persons with cystic fibrosis in the United States., Methods: We conducted a population-based case-control study using NTM incidence data collected from the Cystic Fibrosis Foundation Patient Registry during 2010-2019. We linked patient zip code to the county and associated patient county of residence with surface water data extracted from the Water Quality Portal. We used logistic regression models to estimate the odds of NTM infection as a function of water-quality constituents. We modeled two outcomes: pulmonary infection due to Mycobacterium avium complex (MAC) and Mycobacterium abscessus species., Results: We identified 484 MAC cases, 222 M. abscessus cases and 2816 NTM-negative cystic fibrosis controls resident in 11 states. In multivariable models, we found that for every 1-standardized unit increase in the log concentration of sulfate and vanadium in surface water at the county level, the odds of infection increased by 39% and 21%, respectively, among persons with cystic fibrosis with MAC compared with cystic fibrosis-NTM-negative controls. When modeling M. abscessus as the dependent variable, every 1-standardized unit increase in the log concentration of molybdenum increased the odds of infection by 36%., Conclusions: These findings suggest that naturally occurring and anthropogenic water-quality constituents may influence the NTM abundance in water sources that supply municipal water systems, thereby increasing MAC and M. abscessus infection risk., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. E.M.L., R.A.M., J.M., A.M.Z., and D.R.P. were supported by the Division of Intramural Research, NIAID. J.F. was supported by NSF award [1915277]. M.S. was supported by NSF award [1743597]. Authors receive funding to support open access publishing. This study was classified as nonhuman subjects research by the National Institutes of Health, Office of Human Subjects Research Protection because data were de-identified and investigators could not link back to identifiable data. The water-quality dataset and the R code for the analysis are available from the first author. The patient dataset cannot be made publicly available due to unique identifiers in the data.

Background: Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance., Methods: The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review., Results: Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure., Conclusions: Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions., Competing Interests: Potential conflicts of interest. EIP site coauthors' institutions received funding from the CDC. E. H. reports receipt of consulting fees and serving on advisory boards for AN2 Therapeutics and the MannKind Corporation. K. L. W. reports receipt of grants or contracts and consulting fees from Insmed, Paratek, Red Hill Biopharma, AN2 Therapeutics, Renovion, and Spero and participation on a data and safety monitoring board or advisory board for Red Hill Biopharma. R. L. reports service on the program committee for IDWeek and receipt of travel support for conference planning and for the conference; service as associate editor for the American Academy of Pediatrics (AAP) Red Book; receipt of fees for editorial work that were donated to the Minnesota Department of Health; receipt of support to attend the AAP Committee on Infectious Disease meetings; service on the Council of State and Territorial Epidemiologists (CSTE) Executive Board and receipt of travel support to attend CSTE meetings; and service on the board of the National Foundation of Infectious Disease (NFID) and receipt of travel support to attend NFID meetings. D. R. P. reports support for this work and support for attending meetings and/or travel from the Division of Intramural Research, NIAID, NIH. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Nontuberculous mycobacteria (NTM) are ubiquitous, environmental bacteria that can cause chronic lung disease. Persons with cystic fibrosis (pwCF) are at high risk for NTM. Approximately 1 in 5 pwCF in the United States (U.S.) is affected by pathogenic NTM species, and incidence rates of NTM have been increasing among pwCF as well as in the general population. Prevalence of NTM pulmonary infections (PI) varies widely across the United States because of geographic variation in environmental exposures. This study will present updated region-level incidence of NTM infections in the cystic fibrosis (CF) population in the U.S., Methods: We used the Cystic Fibrosis Foundation Patient Registry (CFFPR) data for the period 2010 through 2019. Our study population comprised persons with CF ≥ 12 years of age who had been tested for NTM PI. We included only registry participants with NTM culture results. We defined incident cases as persons with one positive mycobacterial culture preceded by ≥ two negative mycobacterial cultures. We defined non-cases as persons with ≥ two negative mycobacterial cultures. We estimated average annual NTM PI incidence by region. Using quasi-Poisson models, we calculated annual percent change in incidence by region., Results: We identified 3,771 incident NTM infections. Of these cases, 1,816 (48.2%) were Mycobacterium avium complex (MAC) infections and 960 (25.5%) were Mycobacterium abscessus infections. The average annual incidence of NTM PI among pwCF in the U.S. was 58.0 cases per 1,000 persons. The Northeast had the highest incidence of MAC (33.5/1,000 persons tested) and the South had the highest incidence of M. abscessus (20.3/1,000 persons tested). From 2010 to 2019, the annual incidence of total NTM PI increased significantly by 3.5% per year in the U.S., Conclusions: NTM PI incidence is increasing among pwCF. Identifying high risk areas and increasing trends is important for allocating public health and clinical resources as well as evaluating interventions., (© 2023. The Author(s).)

Introduction: Variability in household secondary attack rates and transmission risks factors of SARS-CoV-2 remain poorly understood., Methods: We conducted a household transmission study of SARS-CoV-2 in Costa Rica, with SARS-CoV-2 index cases selected from a larger prospective cohort study and their household contacts were enrolled. A total of 719 household contacts of 304 household index cases were enrolled from November 21, 2020, through July 31, 2021. Blood specimens were collected from contacts within 30-60 days of index case diagnosis; and serum was tested for presence of spike and nucleocapsid SARS-CoV-2 IgG antibodies. Evidence of SARS-CoV-2 prior infections among household contacts was defined based on the presence of both spike and nucleocapsid antibodies. We fitted a chain binomial model to the serologic data, to account for exogenous community infection risk and potential multi-generational transmissions within the household., Results: Overall seroprevalence was 53% (95% confidence interval (CI) 48-58%) among household contacts. The estimated household secondary attack rate is 34% (95% CI 5-75%). Mask wearing by the index case is associated with the household transmission risk reduction by 67% (adjusted odds ratio = 0.33 with 95% CI: 0.09-0.75) and not sharing bedroom with the index case is associated with the risk reduction of household transmission by 78% (adjusted odds ratio = 0.22 with 95% CI 0.10-0.41). The estimated distribution of household secondary attack rates is highly heterogeneous across index cases, with 30% of index cases being the source for 80% of secondary cases., Conclusions: Modeling analysis suggests that behavioral factors are important drivers of the observed SARS-CoV-2 transmission heterogeneity within the household., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The National Institute of Allergy and Infectious Diseases organized a symposium in June 2022, to facilitate discussion of the environmental risks for nontuberculous mycobacteria exposure and disease. The expert researchers presented recent studies and identified numerous research gaps. This report summarizes the discussion and identifies six major areas of future research related to culture-based and culture independent laboratory methods, alternate culture media and culturing conditions, frameworks for standardized laboratory methods, improved environmental sampling strategies, validation of exposure measures, and availability of high-quality spatiotemporal data., (Published by Elsevier Ltd.)

Nontuberculous mycobacteria (NTM) are ubiquitous in the environment. Some species of NTM are pathogenic and cause lung disease in susceptible persons. Epidemiologic studies of environmental NTM infection risk rely on both culture-dependent and culture-independent techniques for NTM isolation and identification. In this review, we summarized current methods used to isolate and identify NTM from the environment. We searched PubMed, Embase, Scopus, Web of Science: Core Collection, and Global Health (CAB Direct) for peer-reviewed studies from the last 12 years. We identified 1685 unique citations and 110 studies met our inclusion and exclusion criteria. Approximately half (55%) of the studies identified in this review used a combination of culture-independent and culture-dependent methods. The most common environmental substrate analyzed was water (n = 90). Identification of current, common methods for the isolation and identification of NTM from environmental samples may contribute to the development of standard methodological practices in the future. The choice of isolation method is based on the research question, environment, and species. A summary of common methods may contribute to the development of standard practices for isolation and identification of NTM from environmental samples, which may lead to more robust and comparable results., (Published by Elsevier Ltd.)

Nontuberculous mycobacteria are ubiquitous environmental bacteria that frequently cause disease in persons with cystic fibrosis (pwCF). The risks for NTM infection vary geographically. Detection of high-risk areas is important for focusing prevention efforts. In this study, we apply five cluster detection methods to identify counties with high NTM infection risk. Four clusters were detected by at least three of the five methods, including twenty-five counties in five states. The geographic area and number of counties in each cluster depended upon the detection method used. Identifying these clusters supports future studies of environmental predictors of infection and will inform control and prevention efforts., (Published by Elsevier Ltd.)

Background: Clinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach., Methods: We used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness., Results: In 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%)., Conclusions: These effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time., (© 2022. The Author(s).)

Hawai'i 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., Objective: To identify whether trace metals influence the risk of NTM infection in O'ahu, Hawai'i., Methods: A population-based ecologic cohort study was conducted using NTM infection incidence data from patients enrolled at Kaiser Permanente Hawai'i during 2005-2019. We obtained sociodemographic, microbiologic, and geocoded residential data for all Kaiser Permanente Hawai'i 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 Hawai'i Department of Health; and (3) Brigham Young University, Department of Geological Science faculty. Data were aggregated by an aquifer and were associated with the 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., Results: 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., Conclusions: Concentrations of vanadium in groundwater were associated with MAC pulmonary infection in O'ahu, Hawai'i. These findings provide evidence that naturally occurring trace metals influence the presence of NTM in water sources that supply municipal water systems., Competing Interests: The authors declares that they have no conflicts of interest with regard to the content of this report., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Machine learning (ML) models can handle large data sets without assuming underlying relationships and can be useful for evaluating disease characteristics, yet they are more commonly used for predicting individual disease risk than for identifying factors at the population level. We offer a proof of concept applying random forest (RF) algorithms to Candida -positive hospital encounters in an electronic health record database of patients in the United States., Methods: Candida -positive encounters were extracted from the Cerner HealthFacts database; invasive infections were laboratory-positive sterile site Candida infections. Features included demographics, admission source, care setting, physician specialty, diagnostic and procedure codes, and medications received before the first positive Candida culture. We used RF to assess risk factors for 3 outcomes: any invasive candidiasis (IC) vs non-IC, within-species IC vs non-IC (eg, invasive C. glabrata vs noninvasive C. glabrata ), and between-species IC (eg, invasive C. glabrata vs all other IC)., Results: Fourteen of 169 (8%) variables were consistently identified as important features in the ML models. When evaluating within-species IC, for example, invasive C. glabrata vs non-invasive C. glabrata , we identified known features like central venous catheters, intensive care unit stay, and gastrointestinal operations. In contrast, important variables for invasive C. glabrata vs all other IC included renal disease and medications like diabetes therapeutics, cholesterol medications, and antiarrhythmics., Conclusions: Known and novel risk factors for IC were identified using ML, demonstrating the hypothesis-generating utility of this approach for infectious disease conditions about which less is known, specifically at the species level or for rarer diseases., Competing Interests: Potential conflicts of interest. The authors declare no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

To further clarify differences in the risk for nontuberculous mycobacterial pulmonary infection (NTM-PI) among ethnic populations in Hawaii, USA, we conducted a retrospective cohort study among beneficiaries of Kaiser Permanente Hawaii (KPH). We abstracted demographic, socioeconomic, clinical, and microbiological data from KPH electronic health records for 2005-2019. An NTM-PI case-patient was defined as a person from whom >1 NTM pulmonary isolate was obtained. We performed Cox proportional hazards regression to estimate incidence of NTM-PI while controlling for confounders. Across ethnic groups, risk for NTM-PI was higher among persons who were underweight (body mass index [BMI] <18.5 kg/m 2 ). Among beneficiaries who self-identified as any Asian ethnicity, risk for incident NTM-PI was increased by 30%. Low BMI may increase susceptibility to NTM-PI, and risk may be higher for persons who self-identify as Asian, independent of BMI.

Antibiotics are a modifiable iatrogenic risk factor for the most common human nosocomial fungal infection, invasive candidiasis, yet the underlying mechanisms remain elusive. We found that antibiotics enhanced the susceptibility to murine invasive candidiasis due to impaired lymphocyte-dependent IL-17A- and GM-CSF-mediated antifungal immunity within the gut. This led to non-inflammatory bacterial escape and systemic bacterial co-infection, which could be ameliorated by IL-17A or GM-CSF immunotherapy. Vancomycin alone similarly enhanced the susceptibility to invasive fungal infection and systemic bacterial co-infection. Mechanistically, vancomycin reduced the frequency of gut Th17 cells associated with impaired proliferation and RORγt expression. Vancomycin's effects on Th17 cells were indirect, manifesting only in vivo in the presence of dysbiosis. In humans, antibiotics were associated with an increased risk of invasive candidiasis and death after invasive candidiasis. Our work highlights the importance of antibiotic stewardship in protecting vulnerable patients from life-threatening infections and provides mechanistic insights into a controllable iatrogenic risk factor for invasive candidiasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Background: 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., Methods: 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., Results: 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)., Conclusions: CFTR modulator therapy is associated with a decreased risk of NTM positivity in individuals with cystic fibrosis., Competing Interests: Conflict of interest: K.N. Olivier declares a cooperative research and development agreement with Beyond Air, Inc, outside the current work. All other authors declare no competing interests., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2022.)

Rationale: 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. Objectives: To identify water-quality constituents that influence the risk of NTM infection in Oregon. Methods: 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. Conclusions: 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.

In recent years, drinking water-associated pathogens that can cause infections in immunocompromised or otherwise susceptible individuals (henceforth referred to as DWPI), sometimes referred to as opportunistic pathogens or opportunistic premise plumbing pathogens, have received considerable attention. DWPI research has largely been conducted by experts focusing on specific microorganisms or within silos of expertise. The resulting mitigation approaches optimized for a single microorganism may have unintended consequences and trade-offs for other DWPI or other interests (e.g., energy costs and conservation). For example, the ecological and epidemiological issues characteristic of Legionella pneumophila diverge from those relevant for Mycobacterium avium and other nontuberculous mycobacteria. Recent advances in understanding DWPI as part of a complex microbial ecosystem inhabiting drinking water systems continues to reveal additional challenges: namely, how can all microorganisms of concern be managed simultaneously? In order to protect public health, we must take a more holistic approach in all aspects of the field, including basic research, monitoring methods, risk-based mitigation techniques, and policy. A holistic approach will (i) target multiple microorganisms simultaneously, (ii) involve experts across several disciplines, and (iii) communicate results across disciplines and more broadly, proactively addressing source water-to-customer system management., (Copyright © 2021. Published by Elsevier Ltd.)

Rationale: Nontuberculous mycobacteria (NTM) are ubiquitous environmental bacteria that may cause chronic lung disease and are one of the most difficult-to-treat infections among persons with cystic fibrosis (pwCF). Environmental factors likely contribute to increased NTM densities, with higher potential for exposure and infection., Objective: To identify water-quality constituents that influence odds of NTM infection among pwCF in Colorado., Methods: We conducted a population-based nested case-control study using patient data from the Colorado CF Center NTM database. We associated data from pwCF and water-quality data extracted from the Water Quality Portal to estimate odds of NTM infection. Using Bayesian generalized linear models with binomial-distributed discrete responses, we modeled three separate outcomes; any NTM infection, infections due to Mycobacterium avium complex species, and infections due to M. abscessus group species., Results: We observed a consistent association with molybdenum in the source water and M. abscessus group species infection among pwCF in all models. For every 1-unit increase in the log concentration of molybdenum in surface water, the odds of infection for those with M. abscessus group species compared to those who were NTM culture-negative increased by 79%. The odds of M. abscessus group infection varied by county; the counties with the highest probability of infection are located along the major rivers., Conclusions: We have identified molybdenum in the source water as the most predictive factor of M. abscessus group infection among pwCF in Colorado. This finding will help inform patients at risk for NTM of their relative risks in residing within specific regions., (© 2021. The Author(s).)

Congenital cytomegalovirus (CMV) is a leading cause of non-genetic sensorineural hearing loss and neurodevelopmental disabilities among US children. Studies using administrative healthcare databases have identified infants with congenital CMV using diagnostic codes from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification. Using Cerner Health Facts deidentified electronic health records, we assessed the sensitivity of CMV diagnostic codes among infants with laboratory confirmed congenital CMV infection (i.e. a positive CMV laboratory test - polymerase chain reaction, direct fluorescent antibody, or culture from urine, saliva, respiratory secretion or blood samples, or IgM serology - within 21 days of life). During 2010-2017, 668 congenital CMV cases were identified among 7,517,207 infants with encounters within 21 days of life, or 0.89 cases per 10,000 infants. The sensitivity of CMV diagnostic codes assigned within 21 and 90 days of life was 10.3% (95% CI: 8.2-12.9) and 11.1% (95% CI: 8.9-13.7), respectively.

Background: 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., Methods: 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., Results: 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., Conclusions: The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients., (© 2022. The Author(s).)

Background: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been reported and is of increasing concern. No standardized epidemiologic investigation tool has been published for healthcare-associated NTM outbreak investigations. This report describes the design of an ongoing observational study to standardize the approach to NTM outbreak investigation among pwCF., Methods: This is a parallel multi-site study of pwCF within a single Center who have respiratory NTM isolates identified as being highly-similar. Participants have a history of positive airway cultures for NTM, receive care within a single Center, and have been identified as part of a possible outbreak based on genomic analysis of NTM isolates. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of a shared healthcare-associated encounter(s) among patients in a Center and identification of environmental isolates that are genetically highly-similar to respiratory isolates recovered from pwCF. Secondary endpoints include characterization of potential transmission modes and settings, as well as incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region., Discussion: We hypothesize that genetically highly-similar strains of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from environmental sources. This novel study design will establish a standardized, evidence-based epidemiologic investigation tool for healthcare-associated NTM outbreak investigation within CF Care Centers, will broaden the scope of independent outbreak investigations and demonstrate the frequency and nature of healthcare-associated NTM transmission in CF Care Centers nationwide. Furthermore, it will provide valuable insights into modeling risk factors associated with healthcare-associated NTM transmission and better inform future infection prevention and control guidelines. This study will systematically characterize clinically-relevant NTM isolates of CF healthcare environmental dust and water biofilms and set the stage to describe the most common environmental sources within the healthcare setting harboring clinically-relevant NTM isolates., Trial Registration: ClinicalTrials.gov NCT04024423. Date of registry July 18, 2019., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is an uncommon mycobacterial infection characterized by worsening lung function and increased health care resource utilization; however, the overall risk for hospitalization among patients with NTM-PD remains unclear., Research Question: What is the hospitalization risk among older adults with NTM-PD?, Study Design and Methods: A retrospective, nested, case-control study was conducted by using the Medicare claims database. Cases were defined as patients with ≥ 2 NTM-PD claims ≥ 30 days apart between January 1, 2007, and December 31, 2015. The study included individuals aged ≥ 65 years with ≥ 12 months of continuous enrollment in both Parts A and B before the first NTM-PD diagnosis. Cases were matched 1:2 to Medicare beneficiaries without NTM-PD (control subjects) according to age and sex. Hospitalizations following the first NTM-PD claim were compared between case and control subjects by using univariate and multivariate analyses., Results: A total of 35,444 case subjects and 65,467 matched control subjects (mean age, 76.6 years; 70% female; ≥ 87% White) were identified. Baseline comorbidities, particularly pulmonary comorbidities, were more common in case subjects than in control subjects (81.1% vs 17.7% for COPD; 44.6% vs 0.6% for bronchiectasis). All-cause hospitalization was observed in 65.7% of case subjects and 44.9% of control subjects. Unadjusted annual hospitalization rates were significantly (P < .05) greater among case subjects than control subjects. Case subjects also had a significantly shorter time to hospitalization than control subjects. The increased burden due to hospitalization was reflected in multivariate analysis adjusting for baseline comorbidities. All-cause hospitalization in patients with NTM-PD relative to control subjects was 1.2 times more likely (relative risk, 1.23; 95% CI, 1.21-1.25; P < .0001) with a 46% greater hazard (hazard ratio, 1.46; 95% CI, 1.43-1.50; P < .0001)., Interpretation: Patients with NTM-PD were significantly more likely to be hospitalized, had greater annualized hospitalization rates, and had shorter time to hospitalization than age- and sex-matched control subjects without NTM-PD. These findings highlight the significantly increased burden of hospitalizations among patients with NTM-PD., (Published by Elsevier Inc.)

Background: Invasive candidiasis (IC) is a growing concern among US healthcare facilities. A large-scale study evaluating incidence and trends of IC in the United States by species and body site is needed to understand the distribution of infection., Methods: An electronic medical record database was used to calculate incidence and trends of IC in the United States by species and infection site from 2009 through 2017. Hospital incidence was calculated using total unique inpatient hospitalizations in hospitals reporting at least 1 Candida case as the denominator. IC incidence trends were assessed using generalized estimating equations with exchangeable correlation structure to fit Poisson regression models, controlling for changes in hospital characteristics and case mix over time., Results: Candida albicans remains the leading cause of IC in the United States, followed by Candida glabrata. The overall incidence of IC was 90/100 000 patients, which did not change significantly over time. There were no changes in incidence among C. albicans, C. glabrata, C. parapsilosis, or C. tropicalis; the incidence of other Candida spp. as a whole increased 7.2% annually. While there was no change in candidemia 2009-2017, abdominal and nonabdominal sterile site IC increased significantly., Conclusions: Nonbloodstream IC is increasing in the United States. Understanding the epidemiology of IC should facilitate improved management of infected patients., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Nontuberculous mycobacteria (NTM) cause pulmonary and extrapulmonary infections in susceptible persons. To characterize the epidemiology of skin and soft tissue (SST) and disseminated extrapulmonary infections caused by NTM in the United States, we used a large electronic health record database to examine clinical, demographic, and laboratory data for hospitalized patients with NTM isolated from extrapulmonary sources during 2009-2014. Using all unique inpatients as the denominator, we estimated prevalence and summarized cases by key characteristics. Of 9,196,147 inpatients, 831 had confirmed extrapulmonary NTM. The 6-year prevalence was 11 cases/100,000 inpatients; source-specific prevalence was 4.4 SST infections/100,000 inpatients and 3.7 disseminated infections/100,000 inpatients. NTM species varied across geographic region; rapidly growing NTM were most prevalent in southern states. Infection with Mycobacterium avium complex was more common among patients with concurrent HIV and fungal infection, a relevant finding because treatment is more effective for M. avium complex than for other NTM infections.

We studied 31 US healthcare facilities to characterize trends in mycobacterial testing. During 2009-2015, testing for acid-fast bacilli increased 3.2% annually, and prevalence of pathogenic nontuberculous mycobacteria increased 4.5% annually. These increases were highest for subpopulations at high risk of infection, including older women, Asians, and patients with concurrent conditions.

Nontuberculous mycobacteria (NTM) are environmental bacteria that may cause chronic lung disease. Environmental factors that favor NTM growth likely increase the risk of NTM exposure within specific environments. We aimed to identify water-quality constituents (Al, As, Cd, Ca, Cu, Fe, Pb, Mg, Mn, Mo, Ni, K, Se, Na, Zn, and pH) associated with NTM disease across Colorado watersheds. We conducted a geospatial, ecological study, associating data from patients with NTM disease treated at National Jewish Health and water-quality data from the Water Quality Portal. Water-quality constituents associated with disease risk were identified using generalized linear models with Poisson-distributed discrete responses. We observed a highly robust association between molybdenum (Mo) in the source water and disease risk. For every 1- unit increase in the log concentration of molybdenum in the source water, disease risk increased by 17.0%. We also observed a statistically significant association between calcium (Ca) in the source water and disease risk. The risk of NTM varied by watershed and was associated with watershed-specific water-quality constituents. These findings may inform mitigation strategies to decrease the overall risk of exposure., Competing Interests: The authors declare no conflicts of interest.