Gut Microbiota Composition and Diversity Before, During, and Two Months After Rifamycin-Based Tuberculosis Preventive Therapy

Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention

The Burden of Bacteriologically Negative TB Diagnosis: A Four-Year Review of Tuberculosis Cases at a Tertiary Facility

Aim. We aimed to investigate the demographic and clinical factors associated with TB mortality in patients managed at a tertiary TB referral center. Methods. We conducted a retrospective review of the medical records of 1,933 TB patients seen between January 2017 and December 2020 at the Korle-Bu Teaching Hospital (KBTH) Chest Department in Accra, Ghana. TB mortality was defined as any TB patient who died for any reason during the course of treatment. Multivariable logistic regression was used to estimate adjusted odds ratios with 95% confidence intervals for factors associated with TB mortality. Results. A total of 1,933 patients with TB were registered at the chest clinic over the study period. Males accounted for 1,227 (63.5%), and majority of participants were between 24 and 64 years old. Pulmonary TB (PTB) and extrapulmonary TB (EPTB) cases accounted for 51% and 48.4% of the total TB cases, respectively. A significant proportion (69%) of the patients managed for TB had no bacteriological confirmation of the disease. About 34% of tested TB patients were HIV positive. Mortality among patients was 33.6%. In a multivariable regression model, patients with HIV positive status had over 3-fold increased risk of mortality, compared to those with HIV negative status. TB patients diagnosed empirically had an increased risk of death compared to those with a confirmed diagnosis. Conclusion. The proportion of clinically diagnosed TB was high among the patients seen at the chest clinic. Mortality was high among the patients with HIV/TB coinfection as well as in patients with empirical TB diagnosis

Gut microbiota composition and diversity before, during, and two months after rifamycin-based tuberculosis preventive therapy

Abstract Tuberculosis (TB) preventive therapy (TPT) is an effective strategy to eliminate TB in low-incidence settings. Shorter TPT regimens incorporating the antimicrobial class of rifamycins are designed to improve adherence and completion rates but carry the risk of modifications to the gut microbiota. We enrolled six subjects diagnosed with latent TB infection (LTBI) who accepted to initiate TPT. We also enrolled six healthy volunteers unexposed to the rifamycins. We profiled the gut microbiota using 16S rRNA amplicon sequencing (V1-V2 region) to document the immediate effect of rifamycin-based TPT on the gut microbiota composition and tracked recovery to baseline two months after TPT. Overall, TPT accounted for 17% of the variance in gut microbial community dissimilarity. This rifamycin-based TPT induced dysbiosis was characterized by a depletion of butyrate-producing taxa (Clostridium-XIVa and Roseburia) and expansion of potentially pathogenic taxa within the Firmicutes and Proteobacteria phyla. Recovery of the gut microbial composition was incomplete two months after TPT. Robust clinical studies are necessary to comprehensively catalogue TPT-induced gut microbiota dysbiosis to inform strategies to mitigate potential long-term sequelae of this important TB control intervention

Allelic Diversity of Clinical M. tuberculosis Complex Isolates in Florida, 2009–2013.

<p>Allelic Diversity of Clinical M. tuberculosis Complex Isolates in Florida, 2009–2013.</p

Spatiotemporal Clustering of <i>Mycobacterium tuberculosis</i> Complex Genotypes in Florida: Genetic Diversity Segregated by Country of Birth

<div><p>Background</p><p>Tuberculosis (TB) is caused by members of the <i>Mycobacterium tuberculosis</i> 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.</p><p>Methods</p><p>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.</p><p>Principal Findings</p><p>Among the 2,510 strains, 1,245 were reported among foreign-born persons; including 408 recent immigrants (<5 years). Strain allelic diversity (<i>h</i>) ranged from low to medium in most locations and was most diverse in urban centers where foreign-born population density was also high. Overall, 21.5% of cases among U.S.-born persons and 4.6% among foreign-born persons clustered genotypically and spatiotemporally and involved strains of the Haarlem family. One Haarlem space-time cluster identified in the mostly rural northern region of Florida included US/Canada-born individuals incarcerated at the time of diagnosis; two clusters in the mostly urban southern region of Florida were composed predominantly of foreign-born persons. Both groups had HIV prevalence above twenty percent.</p><p>Conclusions/Significance</p><p>Almost five percent of TB cases reported in Florida during 2009–2013 were potentially due to recent transmission. Improvements to TB screening practices among the prison population and recent immigrants are likely to impact TB control. Due to the monomorphic nature of available markers, whole genome sequencing is needed to conclusively delineate recent transmission events between U.S. and foreign-born persons.</p></div

Spatiotemporal Clustering of Mycobacterium <i>tuberculosis</i> complex lineages.

<p>Maps show the locations of significant space-time clusters of M. <i>tuberculosis</i> Beijing (Panel A), and Haarlem (Panel B) sublineages in Florida, 2009–2013. Clusters were adjusted for county-level foreign-born population density and HIV risk. Adjusted Beijing Clusters were non-significant and are not shown). Base map layer reprinted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153575#pone.0153575.ref028" target="_blank">28</a>] under a CC BY license, with permission from University of Florida GeoPlan Center, original copyright 2012.</p

Characteristics of Genotyped Tuberculosis Cases in Florida, 2009–2013.

<p>Characteristics of Genotyped Tuberculosis Cases in Florida, 2009–2013.</p

Assessing risk factors for latent and active tuberculosis among persons living with HIV in Florida: A comparison of self-reports and medical records.

PurposeThis 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.MethodsSelf-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.ResultsTB 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).ConclusionsTB 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

Characteristics of Cases inside the Multinomial Haarlem Clusters.

<p>Characteristics of Cases inside the Multinomial Haarlem Clusters.</p

Optimal Testing Choice and Diagnostic Strategies for Latent Tuberculosis Infection Among US-Born People Living with Human Immunodeficiency Virus (HIV).

BackgroundIncreased 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.MethodsWe 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.ResultsAmong 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.ConclusionsLTBI 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