Homelessness and Mortality Among Persons With Tuberculosis in Texas, 2010-2017.

OBJECTIVE: A disproportionate number of tuberculosis cases and tuberculosis deaths occur among persons experiencing homelessness in the United States. Our objective was to identify risks for homelessness and death during mycobacterial treatment among persons experiencing homelessness with tuberculosis in Texas. METHODS: Using data from the Centers for Disease Control and Prevention's TB Genotyping Information Management System, we evaluated data on demographic, laboratory, and clinical characteristics of persons experiencing homelessness in Texas during the year before tuberculosis diagnosis, from January 1, 2010, through December 31, 2017. RESULTS: Of 10 130 new diagnoses of tuberculosis among persons living in Texas during the study period, 543 were reported as being homeless in the year before tuberculosis diagnosis. The odds of dying during treatment were 2.26 (95% confidence interval, 1.68-3.03) times higher among persons with tuberculosis experiencing homelessness than among persons with tuberculosis living in homes. CONCLUSIONS: Our findings indicate that persons experiencing homelessness bear an undue burden of tuberculosis mortality in Texas. The burden may be related to poorer health caused by poverty stressors, comorbidities, or lack of access to health care.

Discordance between the QuantiFERON Gold In-Tube and QuantiFERON Gold Plus assays associated with country of birth TB incidence.

BACKGROUND: The new QuantiFERON Gold Plus (QFT+) assay is used for diagnosing tuberculosis (TB) infection and has 2 phlebotomy methods: direct (QFT + D) and single tube transfer (QFT + T). Little data is available on how the TB incidence in the country of birth (COB) of healthcare workers (HCWs) can impact the assay results. METHODS: QuantiFERON Gold In-Tube (QFT-G), QFT + D and QFT + T assays were obtained from a single blood draw and compared for HCWs annually tested for TB infection. HCWs COB was ranked as: high (≥150 per 100,000), medium (20-149), and low TB incidence (<20 TB cases). RESULTS: In 265 HCWs, QFT-G/+D/+T results from medium TB incidence COB (15.6%, 16.9% and 22.1%) were more likely to be positive than high (9.7%, 11.8% and 16.1%) or low incidence COB (6.3%, 8.4% and 10.5%). Agreement between assay results for high, medium and low TB incidence COB were: 95.7%, 83.1%, and 95.8% between QFT-G/QFT + D (p = 0.003), 91.4%, 88.3% and 95.8% between QFT-G/QFT + T (p = 0.187), and 91.4%, 76.6%, and 91.6% between QFT + D/QFT + T (p = 0.005). CONCLUSION: Lower agreement and a higher proportion of positivity were found in QFT-G/+D/+T results in individuals from medium TB incidence COB. QFT + may be more sensitive than QFT-G in HCWs from medium TB incidence COB.

Trends of tuberculosis meningitis and associated mortality in Texas, 2010-2017, a large population-based analysis.

BACKGROUND: As the most severe form of tuberculosis (TB), TB meningitis (TBM) is still associated with high mortality even in developed countries. In certain areas of the United States (U.S.), more than 50% of the TBM patients die with TB or have neurological sequelae and complications despite the availability of advanced health care. This population-based analysis aimed to determine the risk factors and trends associated with TBM morbidity and mortality using state-wide surveillance data. METHODS: De-identified surveillance data of all confirmed TB patients from the state of Texas between 01/2010 and 12/2017 reported to the National TB Surveillance System was analyzed. Spatial distribution of TBM cases was presented by Stata's Geographic Information Systems mapping. Univariate and multiple generalized linear modeling were used to identify risk factors associated with meningitis morbidity and mortality. Non-parametric testing was used to analyze morbidity and mortality trends. RESULTS: Among 10,103 TB patients reported in Texas between 2010 and 2017, 192 (1.9%) had TBM. During this 8-year period, the TBM proportion fluctuated between 1.5% and 2.7% with peaks in 2011 (2.7%) and 2016 (2.1%) and an overall non-significant trend (z = -1.32, p = 0.19). TBM had a higher mortality at diagnosis (8.9%), during treatment (14.1%) and overall (22.9%) compared to non-TBM (1.9%, 5.3%, and 7.2%, respectively, p<0.001). While mortality during treatment was unchanged over time in non-TBM patients (z = 0.5, p = 0.62), it consistently increased in TBM patients after 2013 (z = 3.09, p = 0.002). TBM patients had nearly five times the risk for overall death in multivariate analysis [aRR 4.91 (95% CI 3.71, 6.51), p<0.001]. TBM patients were younger, and more likely to present with miliary TB or HIV (+). Age ≥45 years, resident of a long-term care facility, IDU, diabetes, chronic kidney disease, abnormal chest radiography, positive AFB smear or culture and HIV (+) were independently associated with higher mortality. CONCLUSION: TBM remains challenging in Texas with significantly high mortality. Risk factors determined by multivariate modeling will inform health professionals and lay a foundation for the development of more effective strategies for TBM prevention and management.

Evaluating an Education Program to Reduce Indeterminate QuantiFERON Gold In-Tube Results.

BACKGROUND: The QuantiFERON Gold In-Tube (QFT-G) assay is used to identify individuals with tuberculosis infection and gives quantitative and qualitative results including positive, negative, or indeterminate results (that cannot be interpreted clinically). Several factors, including immunosuppression and preanalytical factors, have been suggested to be significantly associated with indeterminate QFT-G results. An online education program was designed and implemented to reduce the rate of indeterminate QFT-G test results at Houston Methodist Hospital (HMH). METHODS: Data from patients' electronic medical records having indeterminate QFT-G results between 01/2015 and 05/2016 at HMH in Houston, TX, were administratively extracted for (1) medical unit where QFT-G phlebotomy was performed, (2) demographics, and (3) ICD-9/10 diagnosis codes. Unit nurses identified with high proportions of indeterminate QFT-G results were emailed a link to an online pretest educational program with a QFT-G blood collection and handling presentation, and a posttest assessment. RESULTS: Of the 332 nurses emailed, 94 (28.4%) voluntarily completed both tests within the 6-month time allotted. The nurses that completed the education program had a significantly higher posteducation test score than on the pretest (70.2% versus 55.3%, p<0.001, effect size=0.82). Improved posttest score was seen in 67.0% of participants. No reduction in the proportion of indeterminate test results was seen overall at HMH in the 6 months after education. CONCLUSIONS: A targeted education program was able to successfully increase nurses' knowledge of blood collection and handling procedures for the QFT-G test, but no association was found between the improvement of posttest score and indeterminate QFT-G test results.

Performance and variability of QuantiFERON Gold Plus assay associated with phlebotomy type.

BACKGROUND: QuantiFERON Gold Plus (Plus) assay has two approved methods for blood collection: direct in-tube (Plus direct) or the transfer of blood from a lithium heparin tube (Plus transfer). Currently, there is little data comparing the results of Plus and the QuantiFERON Gold In-Tube (Gold) based on blood collection. METHODS: In 2017, high risk healthcare workers undergoing annual tuberculosis infection screening at Houston Methodist Hospital, a private hospital in the Texas Medical Center (Houston, TX, U.S.A.) were consented and enrolled in a study comparing the Gold-in-tube (Gold), Plus direct in-tube, and Plus transfer assays. Blood was drawn concurrently for all 3 assays. RESULTS: Phlebotomy occurred on 300 consecutive, consented and enrolled participants in the study. The proportion of positive test results for the Gold, Plus direct and Plus transfer assays were 10% (29/300), 12% (35/299) and 17% (51/299), respectively. The agreement in the results of Gold versus Plus direct, Gold versus Plus transfer, and Plus direct versus Plus transfer was 91%, kappa (κ) = 0.56; 91%, κ = 0.59; and 85%, κ = 0.37, respectively. CONCLUSIONS: Among high risk healthcare workers in a low prevalence tuberculosis setting, the Gold Plus assay had a higher proportion of positive results than the Gold in-tube assay. The agreement between the Gold, Plus direct and Plus transfer assays was unexpectedly low for simultaneously obtained samples. Blood transfer using lithium heparin offers individual clinics and public health programs greater ability to customize protocols, but variability of results still exists.

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.

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.

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.

Re-engagement in HIV Care: A Clinical and Public Health Priority.

As many as 40-50% of persons living with HIV (PLWH) who once were in HIV care are no longer in care. It is estimated that these individuals account for over 60% of HIV transmissions. So, preventing the leaving of care and re-engaging PLWH with care are crucial if the HIV epidemic is to be brought under control. Clinicians can improve retention by keeping in close contact with patients. Governmental public health agencies have great expertise in finding and engaging in care persons with sexually transmitted infections. This expertise can be used to re-engage PLWH with HIV care, but it can only be utilized if the agencies know that someone is out of care. Data on who has left care are in the hands of HIV providers. This requires a close working relationship between HIV providers and public health agencies.

Modes of infant feeding and the occurrence of coughing/wheezing in the first year of life.

BACKGROUND: Controversies regarding infant feeding and childhood wheezing may result from insufficient differentiation among various feeding modes. OBJECTIVES: We conducted prospective analyses of associations between the repeated ascertainment of feeding mode and wheezing in infancy. METHODS: The Infant Feeding Practices Study II (2833 infants) provided data on coughing/wheezing episodes (CWEs) at 8 time points and feeding modes at 9 time points from months 1 to 12. Feeding modes were defined as direct breastfeeding, indirect breastfeeding (IBF, bottled breast milk), formula feeding (FF), and their combinations. In concurrent and delayed models using repeated measurements, the relative risks (RR) and their 95% confidence intervals (95% CI) of different feeding modes for CWEs were estimated. In the delayed models, only infants without symptoms were considered at risk for consequent CWE. RESULTS: In a model with a 1-month delay, compared to direct breastfeeding, any other feeding mode showed a statistically significant risk for CWEs (IBF: RR = 1.69, 95% CI [1.05, 2.72]; FF: RR = 1.26, 95% CI [1.08, 1.47]; mixed breast feeding plus FF: RR = 1.25, 95% CI [1.01, 1.55]; and FF and direct breastfeeding: RR = 1.38, 95% CI [1.14, 1.68]). In a concurrent effect model, FF, the combination of FF and IBF, and mixed breastfeeding plus formula were risk factors (RR = 1.38, 95% CI [1.19, 1.59], RR = 1.83, 95% CI [1.27, 2.63], and RR=1.35, 95% CI [1.11, 1.65]; respectively). CONCLUSIONS: Any mode of feeding that includes formula or bottled breast milk seems to be a moderate risk for cough or wheezing episodes in the first 12 months of life.

Immune markers in breast milk and fetal and maternal body fluids: a systematic review of perinatal concentrations.

Breastfeeding represents the continued exposure of the infant to the maternal immune environment.Uterine, perinatal, and postnatal exposure to immune factors may contribute to an infant's risk of developing immune-mediated disorders, including allergies. A PubMed search was conducted to review studies in humans and analyze concentrations of immune markers (TGF-beta, IFN-gamma, eotaxin, CCL5, CXCL10, TNF-alpha, MCP-1, IL-1beta, IL-4, IL-5, IL-6,IL-8, IL-10, IL-12, IL-13, sCD14, sIgA, IgG4, IgM) found in maternal serum, amniotic fluid, cord serum, colostrum, transition and mature milk. Concentrations of immune markers showed large variations across samples and studies. Reports documented conflicting results. Small sample sizes, differences in population characteristics, inconsistent sample collection times, and various sample collection and measurement methods may have led to wide variations in the concentrations of immune markers. Studies analyzing the associations between immune markers in maternal fluids and infant allergies remain inconclusive because of gaps in knowledge and a lack of standardized methods.