The Impact of HIV Infection on TB Disparities Among US-Born Black and White Tuberculosis Patients in the United States.

BACKGROUND/OBJECTIVES: US-born non-Hispanic black persons (blacks) (12% of the US population) accounted for 41% of HIV diagnoses during 2008-2014. HIV infection significantly increases TB and TB-related mortality. TB rate ratios were 6 to 7 times as high in blacks versus US-born non-Hispanic whites (whites) during 2013-2016. We analyzed a sample of black and white TB patients to assess the impact of HIV infection on TB racial disparities. METHODS: In total, 552 black and white TB patients with known HIV/AIDS status were recruited from 10 US sites in 2009-2010. We abstracted data from the National TB Surveillance System, medical records, and death certificates and interviewed 477 patients. We estimated adjusted odds ratios (AORs) with 95% confidence intervals (CIs) for associations of TB with HIV infection, late HIV diagnosis (≤3 months before or any time after TB diagnosis), and mortality during TB treatment. RESULTS: Twenty-one percent of the sample had HIV/AIDS infection. Blacks (AOR = 3.4; 95% CI, 1.7-6.8) and persons with recent homelessness (AOR = 2.5; 95% CI, 1.5-4.3) had greater odds of HIV infection than others. The majority of HIV-infected/TB patients were diagnosed with HIV infection 3 months or less before (57%) or after (4%) TB diagnosis. Among HIV-infected/TB patients, blacks had similar percentages to whites (61% vs 57%) of late HIV diagnosis. Twenty-five percent of HIV-infected/TB patients died, 38% prior to TB diagnosis and 62% during TB treatment. Blacks did not have significantly greater odds of TB-related mortality than whites (AOR = 1.1; 95% CI, 0.6-2.1). CONCLUSIONS: Black TB patients had greater HIV prevalence than whites. While mortality was associated with HIV infection, it was not significantly associated with black or white race.

Influence of Seasonality and Circulating Cytokines on Serial QuantiFERON Discordances.

Objectives. An 18-month prospective study serially tested healthcare workers (HCWs) for tuberculosis infection (TBI) and reported discordant QuantiFERON Gold In-Tube® (QFT) results in some participants. The purpose of the current study was to investigate whether the interferon-gamma (IFN-γ) measured by QFT in discordant individuals could be influenced by other circulating cytokines that vary seasonally at the time of phlebotomy. Methods. The CDC funded TBESC Task Order 18 (TO18) project to assess the use of Interferon Gamma Release Assays (IGRAs), T-SPOT.TB® and QFT, compared to the tuberculin skin test (TST) for the serial testing of TBI in HCW at 4 US sites. Unstimulated plasma from 9 discordant TO18 participants at 4 different time points from the Houston site was multiplexed to determine the association between circulating cytokines and antigen stimulated IFN-γ levels. Results. IL-12, IL-1ß, IL-3, GCSF, and IL-7 were associated with the amount of IFN-γ measured in response to antigen stimulation. In addition to these cytokines, a significant relationship was found between a positive QFT result and the spring season. Conclusions. Allergens during the spring season can result in the upregulation of IL-1ß and IL-3, and this upregulation was observed with the amount of IFN-γ measured in discordant results.

Characteristics Associated with Negative Interferon-γ Release Assay Results in Culture-Confirmed Tuberculosis Patients, Texas, USA, 2013-2015.

Interferon-γ release assays (IGRAs) are the preferred diagnostic test for tuberculosis (TB) infection in at-risk populations in developed countries. However, IGRAs have high false-negative rates in patients with TB disease. Population-based studies assessing the factors associated with negative IGRA results in TB patients have not been performed. Using statewide TB surveillance data of culture-confirmed TB patients in Texas, USA, during 2013-2015, we describe the patient characteristics and treatment outcomes associated with false-negative IGRA results. Among 2,854 TB patients, 1,527 (53.5%) had an IGRA result; 97.4% (1,487/1,527) of those had a positive (87.7%) or negative (12.3%) result. Older age, HIV co-infection, non-Hispanic white race/ethnicity, and being tested with T-SPOT.TB were associated with negative IGRA results. TB patients with negative IGRA results had a higher mortality, potentially due to delayed treatment. Healthcare providers should consider these risk factors when making decisions for patients with suspected TB and negative IGRA results and potentially provide treatment.

Evaluation of 24-locus MIRU-VNTR genotyping in Mycobacterium tuberculosis cluster investigations in four jurisdictions in the United States, 2006-2010.

The U.S. Centers for Disease Control and Prevention (CDC) uses a combination of spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) analyses as part of the National TB Genotyping Service (NTGS). The NTGS expansion from 12-locus MIRU-VNTR (MIRU12) to 24-locus MIRU-VNTR (MIRU24) in 2009 enhanced the ability to discriminate Mycobacterium tuberculosis strains. In the current study, we investigated the MIRU24 concordance among epidemiologic-linked tuberculosis (TB) patients in four U.S. health jurisdictions. We also evaluated the programmatic benefits of combining MIRU24 and spoligotyping with epidemiologic evidence in identifying potential recent TB transmission. We examined 342 TB patients in 42 spoligotype/MIRU12 (PCRType) clusters (equivalent to 46 spoligotype/MIRU24 [GENType] clusters) to identify epidemiologic links among cases. GENType clusters, when compared to PCRType clusters, had 12 times higher odds of epidemiologic links being identified if patients were younger than 25 years and 3 times higher odds if patients resided in the same zip code, or had HIV infection. Sixty (18%) fewer PCRType-clustered patients would need investigations if clusters are defined using GENType instead of PCRType. An important advantage of defining clusters by MIRU24 is resource savings related to the reduced number of clustered cases needing investigation.

Spatial-temporal distribution of genotyped tuberculosis cases in a county with active transmission.

BACKGROUND: Harris County, Texas is the third most populous county in the United States and consistently has tuberculosis rates above the national average. Understanding jurisdictional epidemiologic characteristics for the most common Mycobacterium tuberculosis genotyped clusters is needed for tuberculosis prevention programs. Our objective is to describe the demographic, laboratory, clinical, temporal and geospatial characteristics for the most common Mycobacterium tuberculosis GENType clusters in Harris County from 2009 to 2015. METHODS: We analyzed data from the Centers for Disease Control and Prevention (CDC) Tuberculosis Genotyping Information Management System (TB GIMS). Chi-square analyses were used to determine associations between selected clusters and specific characteristics of interest. Geographical Information System (GIS) point density and hot spot maps were generated and analyzed with ArcGIS 10.4. RESULTS: In Harris County from 2009 to 2015, 1655 of 1705 (97.1%) culture positive tuberculosis cases were genotyped and assigned a GENType, and 1058 different GENTypes were identified. The analyzed genotype clusters represent 14.1% (233/1655) of all genotyped cases: G00010 (n = 118), G00014 (n = 38), G00769 (n = 33), G01521 (n = 26), and G08964 (n = 18). Male gender (p = 0.002), ethnicity (p < 0.001), homelessness (p < 0.001), excessive alcohol use (p = 0.002), and U.S.-birth (p = 0.004) were associated with the 5 GENTypes. Hot and cold spots were identified as geographic areas having high and low TB incidence. CONCLUSIONS: Of more than 1000 distinct GENTypes identified in Harris County, there were 5 common Mycobacterium tuberculosis GENType clusters seen from 2009 to 2015. The common genotypes were observed primarily in U.S.-born populations despite the large foreign-born population residing in Harris County. GENType was significant distributed spatially and temporally in Harris County in the analyzed time period indicating that there may be outbreaks caused by transmission.

The detrimental impact of persistent vs an isolated occurrence of de novo donor-specific antibodies on intermediate-term renal transplant outcomes.

BACKGROUND: De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. METHODS: A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA. RESULTS: Of 708 recipients, 22% developed dnDSA, of whom 64% had persistent dnDSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dnDSA vs the persistent dnDSA group (2% vs 22%; P<.001,) and fewer graft losses with isolated dnDSA vs persistent dnDSA (0% vs 10%; P=.03). Within the persistent dnDSA group, recipients with dnDSA ≥60% of time points, had more AR (32% vs 16%, P=.10) and more graft losses (21% vs 2%; P=.003) than those with dnDSA<60%. CONCLUSIONS: Persistence of dnDSA resulted in more AR and graft failure than a single positive value. Recipients with longer duration of dnDSA persistence had an additional increased risk of AR and graft failure.

Early clearance vs persistence of de novo donor-specific antibodies following lung transplantation.

BACKGROUND: The natural history of de novo donor-specific antibodies (dnDSA) after lung transplantation is not well-described. We sought to determine the incidence and risk factors associated with dnDSA and compare outcomes between recipients with transient (or isolated) vs persistent dnDSA after transplantation. METHODS: A single-center review of all lung transplants from 1/2009-7/2013. DSAs were tested eight times in the first year and every 4 months thereafter. Outcomes examined included acute rejection and graft failure. RESULTS: Median follow-up was 18 months (range: 1-61 months), and 24.6% of 333 first-time lung-only transplant recipients developed a dnDSA. Ethnicity, HLA-DQ mismatches, post-transplantation platelet transfusion and Lung Allocation Score >60 were associated with dnDSA (P<.05). Overall graft survival was worse for dnDSA-positive vs negative recipients (P=.025). Of 323 recipients with 1-year follow-up, 72 (22.2%) developed dnDSA, and in 25 (34.7%), the dnDSA was transient and cleared. Recipients with transient dnDSA were less likely to develop acute rejection than those with persistent dnDSA (P=.007). CONCLUSIONS: Early post-lung transplantation, dnDSA occurred in 1/4 of recipients, was associated with peri-transplant risk factors and resulted in decreased survival. Spontaneous clearance of dnDSA, seen in one-third of recipients, was associated with a lower risk of acute rejection.

Differential positive TSPOT assay responses to ESAT-6 and CFP-10 in health care workers.

BACKGROUND: The TSPOT.TB (TSPOT) diagnostic test for latent tuberculosis infection is based on a cell-mediated response to the Mycobacteria tuberculosis antigens, ESAT-6 and/or CFP-10, producing an "interferon-gamma footprint". We investigated the within-sample and within-subject variability of positive TSPOT assays due to the individual assay antigens' reactivity. METHODS: Positive TSPOT assay frequencies due to ESAT-6 or CFP-10 among health care workers (HCWs) at 6-month intervals for 18 months were compared. Differences in result interpretation (positive or negative) for ESAT-6 and CFP10 and potential prognostic factors were investigated. RESULTS: There were 576 positive results in 8805 TSPOT assays representing 2418 participants. A significant difference was detected in positive TSPOT results due to a positive response to either ESAT-6, CFP-10 or both antigens at baseline through 12 M (p < 0.001), but not for the 18 M follow-up. Gender, ethnicity, occupation, previous positive tuberculin skin test (TST) and study site were significantly associated with specific antigen positivity. CONCLUSIONS: Among our HCW samples with positive TSPOT assays, CFP-10 induced a larger proportion of positive TSPOT results than ESAT-6. Potential causes for this finding include: BCG vaccinated subpopulations, certain jobs, history of positive TST, U.S. birth, and study site. A high proportion of single-positive specimens may reflect false-positives results.

Comparing TSPOT assay results between an Elispot reader and manual counts.

BACKGROUND: The interferon gamma release assay, TSPOT.TB (TSPOT) can be read by several methodologies, including an Elispot reader or manually by technician. We compared the results from these two counting methods. METHODS: Automated and manual TSPOT results among 2481 United States health care workers were compared. Cohen's kappa coefficient was used to determine the inter-rater agreement. Univariate and multiple logistic regression were used to investigate selected variable contributions. RESULTS: No prognostic factors were associated with agreement of TSPOT results between counting methods. Agreement between TSPOT results were 92.3%, 89.5%, 93.0%, and 93.1% at baseline, and at follow-up at 6, 12, and 18 months, respectively. The inter-rater agreement for all test results was good (kappa = 0.71). There was a significant difference between individual technicians kappa coefficients (p < 0.001), but no significant increase in agreement over time for technicians (p = 0.394). CONCLUSION: Commercial Elispot readers and manual counts have good agreement of TSPOT results in a low TB burden setting. Levels of agreement differed between individual technicians and automated reader from moderate to very good, indicating borderline results may be misinterpreted due to inter-rater variability. With no latent tuberculosis infection (LTBI) gold standard, it cannot be determined if one TSPOT reading method is better than another.

Validation of genotype cluster investigations for Mycobacterium tuberculosis: application results for 44 clusters from four heterogeneous United States jurisdictions.

BACKGROUND: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation. METHODS: The study population included Mtb culture positive patients from Georgia, Maryland, Massachusetts and Houston, Texas. Mtb isolates were genotyped by CDC's National TB Genotyping Service (NTGS) from January 2006 to October 2010. Mtb cluster investigations (CLIs) were conducted for patients whose isolates matched exactly by spoligotyping and 12-locus MIRU-VNTR. CLIs were carried out in four sequential steps: (1) Public Health Worker (PHW) Interview, (2) Contact Investigation (CI) Evaluation, (3) Public Health Records Review, and (4) CLI TB Patient Interviews. Comparison between patients whose links were identified through the study's CLI interviews (Step 4) and patients whose links were identified earlier in CLI (Steps 1-3) was conducted using logistic regression. RESULTS: Forty-four clusters were randomly selected from the four study sites (401 patients in total). Epidemiologic links were identified for 189/401 (47 %) study patients in a total of 201 linked patient-pairs. The numbers of linked patients identified in each CLI steps were: Step 1 - 105/401 (26.2 %), Step 2 - 15/388 (3.9 %), Step 3 - 41/281 (14.6 %), and Step 4 - 28/119 (30 %). Among the 189 linked patients, 28 (14.8 %) were not identified in previous CI. No epidemiologic links were identified in 13/44 (30 %) clusters. CONCLUSIONS: We validated a standardized and practical method to systematically identify epidemiologic links among patients in Mtb genotype clusters, which can be integrated into the TB control and prevention programs in public health settings. The CLI interview identified additional epidemiologic links that were not identified in previous CI. One-third of the clusters showed no epidemiologic links despite being extensively investigated, suggesting that some improvement in the interviewing methods is still needed.

Intermediate-Term Outcomes of Dual Adult versus Single-Kidney Transplantation: Evolution of a Surgical Technique.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

Disparate rates of acute rejection and donor-specific antibodies among high-immunologic risk renal transplant subgroups receiving antithymocyte globulin induction.

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups.

Barriers to preemptive renal transplantation: a single center questionnaire study.

BACKGROUND: Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation. METHODS: A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis. RESULTS: One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2-444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis. CONCLUSION: The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.

Tuberculosis prevention in healthcare workers in China 10†years after the severe acute respiratory syndrome pandemic.

BSL3 and respiratory isolation wards protect healthcare workers from nosocomial TB infection in China http://ow.ly/PGvSl.

Intermediate-term graft loss after renal transplantation is associated with both donor-specific antibody and acute rejection.

BACKGROUND: Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. METHODS: The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. RESULTS: Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). CONCLUSIONS: Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

Epidemiology of tuberculosis in young children in the United States.

OBJECTIVES: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent. METHODS: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records. RESULTS: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs. 7%), Hispanic (73% vs. 37%), diagnosed through contact tracing (40% vs. 7%), and have an identified source case (61% vs. 19%); two-thirds of children were exposed in the United States. CONCLUSIONS: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population.

Interferon-γ release assays and tuberculin skin testing for diagnosis of latent tuberculosis infection in healthcare workers in the United States.

RATIONALE: IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs). OBJECTIVES: Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs. METHODS: A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011. MEASUREMENTS AND MAIN RESULTS: A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later. CONCLUSIONS: Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study.

BACKGROUND: Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA. METHODS: In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections. FINDINGS: 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation. INTERPRETATION: About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals. FUNDING: Centers for Disease Control and Prevention.

Counting the homeless: a previously incalculable tuberculosis risk and its social determinants.

Tuberculosis (TB) surveillance among the homeless is not supported by the political will necessary for TB elimination. We merged the first stakeholder-accepted enumeration of homeless persons with existing surveillance data to assess TB risk among the homeless in Houston, Texas. The average incidence per 100,000 was 411 among homeless and 9.5 among housed persons. The homeless were more likely than the housed to be US-born, clustered, and in a larger-sized cluster. Multivariate analysis revealed that TB rates among the homeless were driven not by comorbidities but by social determinants. Homeless patients were hospitalized more days than the housed and required more follow-up time. Reporting of TB rates for populations with known health disparities could help reframe TB prevention and better target limited funds.

Evaluation of large genotypic Mycobacterium tuberculosis clusters: contributions from remote and recent transmission.

Tuberculosis genotypic clustering is used as a proxy for recent transmission. The association between clustering and recent transmission becomes problematic when the genotyping method lacks specificity in defining a cluster, as well as for clusters with extensive jurisdictional histories and/or common genotypes. We investigated the four largest spoligotype/12 loci MIRU-VNTR-defined clusters in Harris County, Texas from 2006-2012 to determine their historical contribution to tuberculosis morbidity, estimate the contributions from recent and remote transmission, and determine the impact of secondary genotyping on cluster definition. The clusters contained 189, 64, 51 and 38 cases. Each cluster was linked to cluster(s) previously identified by Houston Tuberculosis Initiative; 3 since 1995 and the fourth in 2002. Among cases for which timing of Mycobacterium tuberculosis transmission relative to tuberculosis disease could be ascertained, nearly equal proportions were associated with recent and remote transmission. The extent to which genotyping with an additional 12 MIRU-VNTR loci modified the cluster definition varied from little or no impact for the two smaller clusters to moderate impact for the larger clusters. Tuberculosis control measures to reduce morbidity associated with large clusters must involve strategies to identify and treat individuals who recently acquired infection, as well as persons infected for years.