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Background Increased risk of progression from latent tuberculosis infection (LTBI) to tuberculosis (TB) disease among people living with human immunodeficiency virus (HIV; PLWH) prioritizes them for LTBI testing and treatment. Studies comparing the performance of interferon gamma release assays (IGRAs) and the tuberculin skin test (TST) among PLWH are lacking. Methods We used Bayesian latent class analysis to estimate the prevalence of LTBI and diagnostic characteristics of the TST, QuantiFERON Gold In-Tube (QFT), and T.SPOT-TB (TSPOT) among a prospective, multicenter cohort of US-born PLWH ≥5 years old with valid results for all 3 LTBI tests using standard US cutoffs (≥5 mm TST, ≥0.35 IU/mL QFT, ≥8 spots TSPOT). We also explored the performance of varying LTBI test cutoffs. Results Among 1510 PLWH (median CD4+ count 532 cells/mm3), estimated LTBI prevalence was 4.7%. TSPOT was significantly more specific (99.7%) and had a significantly higher positive predictive value (90.0%, PPV) than QFT (96.5% specificity, 50.7% PPV) and TST (96.8% specificity, 45.4% PPV). QFT was significantly more sensitive (72.2%) than TST (54.2%) and TSPOT (51.9%); negative predictive value of all tests was high (TST 97.7%, QFT 98.6%, TSPOT 97.6%). Even at the highest cutoffs evaluated (15 mm TST, ≥1.00 IU/mL QFT, ≥8 spots TSPOT), TST and QFT specificity was significantly lower than TSPOT. Conclusions LTBI prevalence among this cohort of US-born PLWH was low compared to non-US born persons. TSPOT’s higher PPV may make it preferable for testing US-born PLWH at low risk for TB exposure and with high CD4+ counts.

Purpose This study examined factors associated with TB among persons living with HIV (PLWH) in Florida and the agreement between self-reported and medically documented history of tuberculosis (TB) in assessing the risk factors. Methods Self-reported and medically documented data of 655 PLWH in Florida were analyzed. Data on sociodemographic factors such as age, race/ethnicity, place of birth, current marital status, education, employment, homelessness in the past year and ‘ever been jailed’ and behavioural factors such as excessive alcohol use, marijuana, injection drug use (IDU), substance and current cigarette use were obtained. Health status information such as health insurance status, adherence to HIV antiretroviral therapy (ART), most recent CD4 count, HIV viral load and comorbid conditions were also obtained. The associations between these selected factors with self-reported TB and medically documented TB diagnosis were compared using Chi-square and logistic regression analyses. Additionally, the agreement between self-reports and medical records was assessed. Results TB prevalence according to self-reports and medical records was 16.6% and 7.5% respectively. Being age ≥55 years, African American and homeless in the past 12 months were statistically significantly associated with self-reported TB, while being African American homeless in the past 12 months and not on antiretroviral therapy (ART) were statistically significantly associated with medically documented TB. African Americans compared to Whites had odds ratios of 3.04 and 4.89 for self-reported and medically documented TB, respectively. There was moderate agreement between self-reported and medically documented TB (Kappa = 0.41). Conclusions TB prevalence was higher based on self-reports than medical records. There was moderate agreement between the two data sources, showing the importance of self-reports. Establishing the true prevalence of TB and associated risk factors in PLWH for developing policies may therefore require the use of self-reports and confirmation by screening tests, clinical signs and/or microbiologic data.

Background: Whole genome sequencing (WGS) has enabled the development of new approaches to track Mycobacterium tuberculosis (Mtb) transmission between tuberculosis (TB) cases but the utility may be challenged by the discovery that Mtb diversifies within hosts. Nevertheless, there is limited data on the mechanisms of within-host evolution. Methods: We profiled a well-documented Mtb transmission cluster with three pulmonary TB cases to investigate within-host evolution and describe its impact on recent transmission estimates. We used deep sequencing to track minority allele frequencies (

Background Treatment of latent tuberculosis infection (LTBI) in high-risk groups is an effective strategy for TB control and elimination in low incidence settings. A nine-month course of daily isoniazid (INH) has been the longest prescribed therapy; however, completion rates are suboptimal. We need data to guide TB program outreach efforts to optimize LTBI treatment completion rates. Methods We pooled seven (2009–2015) years of LTBI treatment outcome data. We computed the probability of INH treatment disruption over time by patient demographic and clinical risk factors. We used log-rank tests and Cox proportional hazards models to assess the risk factors for treatment disruption. Results We analyzed data from 12,495 persons with complete data on INH treatment initiation. Pediatric cases (0–17 years), recent contacts of active TB patients, and non-U.S.-born adults living in the United States ≤5 years represented 25.2, 13.0, and 59.2% of the study population, respectively. Overall, 48.4% failed to complete therapy. The median treatment duration was 306 days (95% CI: 297, 315). A significant drop in adherence could be observed around day 30 of treatment initiation. Indeed, by day 30 of treatment, 17.0% (95% CI: 16.4, 17.7) of patients had defaulted on therapy. Pediatric patients (HR = 0.83, 95% CI: 0.78, 0.89), recent contacts (HR = 0.74, 95% CI: 0.68, 0.81), patients with diabetes (HR = 0.77, 95% CI: 0.60, 0.98), and patients with HIV (HR = 0.39, 95% CI: 0.30, 0.51) had a lower risk of treatment default. However, black patients (HR = 1.57, 95% CI: 1.44, 1.70), Hispanic patients (HR = 1.54, 95% CI: 1.43, 1.66), and non-U.S.-born persons living in the United States ≤5 years (HR = 1.25, 95% CI: 1.18, 1.32) were significantly more likely to default on therapy. Conclusions In this analysis of INH treatment outcome, we see high levels of treatment discontinuation. On average, patients defaulted on their prescribed nine-month daily INH therapy within 30 days of initiating treatment, and those at increased risk of progression to active disease were most likely to do so. We highlight the need to introduce patient-centered programs to increase treatment adherence in this population. Electronic supplementary material The online version of this article (10.1186/s12889-019-7524-4) contains supplementary material, which is available to authorized users.

Mixed infections with genetically distinct Mycobacterium tuberculosis (MTB) strains within a single host have been documented in different settings; however, this phenomenon is rarely considered in the management and care of new and relapse tuberculosis (T.B.) cases. This study aims to establish the epidemiological and clinical features of mixed infections among culture-confirmed T.B. patients enrolled in tuberculosis care at the Florida Department of Health (FDOH) and measure its association with T.B. mortality. We analyzed de-identified surveillance data of T.B. cases enrolled in T.B. care from April 2008 to January 2018. Mixed MTB infection was determined by the presence of more than one Copy Number Variant (CNV) in at least one locus, based on the genotype profile pattern of at least one isolate using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR). The prevalence of mixed MTB infections among the 4944 culture-confirmed TB cases included in this analysis was 2.6% (129). Increased odds of mixed infections were observed among middle-aged patients, 45–64 years (AOR = 2.38; 95% CI: 0.99, 5.69; p = 0.0513), older adults 65 years and above (AOR = 3.95; 95% CI: 1.63, 9.58; p = 0.0023) and patients with diabetes (OR = 1.77; 95% CI: 1.12, 2.80; p = 0.0150). There was no significant association between mixed infections and death. Our study provides insight into the epidemiological and clinical characteristics of patients with mixed MTB infections, which is essential in the management of T.B. patients.

We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009-2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. "high-risk" populations (such as prisoners), with subsequent movement back to the general community.

As tuberculosis (TB) incidence decreases in the US, foreign-born persons continue to account for a larger proportion of the burden. In these cross-sectional analyses of 1149 culture-confirmed TB cases genotyped using spoligotyping and 24-locus MIRU, we show that over a quarter of cases among the foreign-born population in Florida resulted from recent transmission of the Mycobacterium tuberculosis complex. In addition, over a third of these cases occurred among persons who had immigrated 5 years or less prior to their diagnosis. Although recent immigration was not a significant predictor of TB transmission, younger age, birthplace in the Americas, homelessness, drug use and TB lineage are risk factors for TB transmission among the foreign-born population in Florida. These data provide actionable insights into TB transmission among the foreign-born population in Florida.

We conducted a cross-sectional study to describe clinical characteristics of patients with pulmonary tuberculosis with and without evidence of pulmonary cavitation on chest radiography and assess whether cavitation is associated with infection with Mycobacterium tuberculosis Beijing strain. Cases were selected from the Tuberculosis Registry (January 1, 2008-November 1, 2011) of the Florida Department of Health (FDOH). Molecular characterization was performed by spoligotyping and MIRU-VNTR. We analyzed 975 cases, where 144 (14.8%) were infected with the Beijing strain. Cavitation was not associated with disease caused by the Beijing strain. Alcohol use (OR = 1.7; 95%CI: 1.249-2.313) was associated with increased risk of cavitation in the unadjusted analyses. Multivariable analyses showed that older age (⩾ 65 years) (OR = 0.5; 95%CI: 0.233-0.871), Hispanic ethnicity (OR = 0.6; 95%CI: 0.312-0.962), and co-infection with HIV (OR = 0.1; 95%CI: 0.068-0.295) demonstrated protective effects to cavitation. Understanding the factors associated with cavitation among pulmonary cases is essential toward improved tuberculosis management and control.

Background Mycobacterium tuberculosis is characterized into four global lineages with strong geographical restriction. To date one study in the United States has investigated M. tuberculosis lineage association with tuberculosis (TB) disease presentation (extra-pulmonary versus pulmonary). We update this analysis using recent (2009–2015) data from the State of Florida to measure lineage association with pulmonary TB, the infectious form of the disease. Methods M. tuberculosis lineage was assigned based on the spacer oligonucleotide typing (spoligotyping) patterns. TB disease site was defined as exclusively pulmonary or extra-pulmonary. We used ORs to measure the association between M. tuberculosis lineages and pulmonary compared to extra-pulmonary TB. The final multivariable model was adjusted for patient socio-demographics, HIV and diabetes status. Results We analyzed 3061 cases, 83.4% were infected with a Euro-American lineage, 8.4% Indo-Oceanic and 8.2% East-Asian lineage. The majority of the cases (86.0%) were exclusively pulmonary. Compared to the Indo-Oceanic lineage, infection with a Euro-American (AOR = 1.87, 95% CI: 1.21, 2.91) or an East-Asian (AOR = 2.11, 95% CI: 1.27, 3.50) lineage favored pulmonary disease compared to extra-pulmonary. In a sub-analysis among pulmonary cases, strain lineage was not associated with sputum smear positive status, indicating that the observed association with pulmonary disease is independent of host contagiousness. Conclusion As an obligate pathogen, M. tuberculosis' fitness is directly correlated to its transmission potential. In this analysis, we show that M. tuberculosis lineage is associated with pulmonary disease presentation. This association may explain the predominance in a region of certain lineages compared to others.

Background Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. Methods In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. Findings The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%). A total of 29 (25%) isolates were identified as orphan. The most abundant SITs were SIT53/T1 and SIT42/LAM9 with 10 isolates each and SIT50/H3 with eight isolates. Fifty-two spoligotype patterns, twenty-seven clusters and ten clonal complexes were observed, demonstrating an important genetic diversity of drug and multidrug-resistant tuberculosis isolates in circulation and transmission level of these aggravated forms of tuberculosis. Being defined as orphan or as part of an orphan cluster, was a risk factor for multidrug resistant-tuberculosis (OR 2.5, IC 1.05–5.86 and OR 3.3, IC 1–11.03, respectively). Multiple correspondence analyses showed association of some clusters and SITs with specific geographical locations. Conclusions Our study provides one of the most detailed description of the genetic structure of drug and multidrug-resistant tuberculosis strains in southeast Mexico, establishing for the first time a baseline of the genotypes observed in resistant isolates circulating, however further studies are required to better elucidate the genetic structure of tuberculosis in region and the factors that could be participating in their dispersion.

BACKGROUND:Tuberculosis (TB) is caused by members of the Mycobacterium tuberculosis complex (MTBC). Although the MTBC is highly clonal, between-strain genetic diversity has been observed. In low TB incidence settings, immigration may facilitate the importation of MTBC strains with a potential to complicate TB control efforts. METHODS:We investigated the genetic diversity and spatiotemporal clustering of 2,510 MTBC strains isolated in Florida, United States, between 2009 and 2013 and genotyped using spoligotyping and 24-locus MIRU-VNTR. We mapped the genetic diversity to the centroid of patient residential zip codes using a geographic information system (GIS). We assessed transmission dynamics and the influence of immigration on genotype clustering using space-time permutation models adjusted for foreign-born population density and county-level HIV risk and multinomial models stratified by country of birth and timing of immigration in SaTScan. PRINCIPAL FINDINGS:Among the 2,510 strains, 1,245 were reported among foreign-born persons; including 408 recent immigrants (