High Rate of Hypothyroidism in Multidrug-Resistant Tuberculosis Patients Co-Infected with HIV in Mumbai, India.

Adverse events (AEs) among HIV-infected patients with multidrug-resistant tuberculosis (MDR-TB) receiving anti-TB and antiretroviral treatments (ART) are under-researched and underreported. Hypothyroidism is a common AE associated with ethionamide, p-aminosalicylic acid (PAS), and stavudine. The aim of this study was to determine the frequency of and risk factors associated with hypothyroidism in HIV/MDR-TB co-infected patients

Derivation and external validation of a risk score for predicting HIV-associated tuberculosis to support case finding and preventive therapy scale-up: A cohort study.

BACKGROUND: Among people living with HIV (PLHIV), more flexible and sensitive tuberculosis (TB) screening tools capable of detecting both symptomatic and subclinical active TB are needed to (1) reduce morbidity and mortality from undiagnosed TB; (2) facilitate scale-up of tuberculosis preventive therapy (TPT) while reducing inappropriate prescription of TPT to PLHIV with subclinical active TB; and (3) allow for differentiated HIV-TB care. METHODS AND FINDINGS: We used Botswana XPRES trial data for adult HIV clinic enrollees collected during 2012 to 2015 to develop a parsimonious multivariable prognostic model for active prevalent TB using both logistic regression and random forest machine learning approaches. A clinical score was derived by rescaling final model coefficients. The clinical score was developed using southern Botswana XPRES data and its accuracy validated internally, using northern Botswana data, and externally using 3 diverse cohorts of antiretroviral therapy (ART)-naive and ART-experienced PLHIV enrolled in XPHACTOR, TB Fast Track (TBFT), and Gugulethu studies from South Africa (SA). Predictive accuracy of the clinical score was compared with the World Health Organization (WHO) 4-symptom TB screen. Among 5,418 XPRES enrollees, 2,771 were included in the derivation dataset; 67% were female, median age was 34 years, median CD4 was 240 cells/μL, 189 (7%) had undiagnosed prevalent TB, and characteristics were similar between internal derivation and validation datasets. Among XPHACTOR, TBFT, and Gugulethu cohorts, median CD4 was 400, 73, and 167 cells/μL, and prevalence of TB was 5%, 10%, and 18%, respectively. Factors predictive of TB in the derivation dataset and selected for the clinical score included male sex (1 point), ≥1 WHO TB symptom (7 points), smoking history (1 point), temperature >37.5°C (6 points), body mass index (BMI) 10) yielded TB prevalence of 1%, 1%, 2%, and 6% in the lowest risk group and 33%, 22%, 26%, and 32% in the highest risk group for XPRES, XPHACTOR, TBFT, and Gugulethu cohorts, respectively. At clinical score ≥2, the number needed to screen (NNS) ranged from 5.0 in Gugulethu to 11.0 in XPHACTOR. Limitations include that the risk score has not been validated in resource-rich settings and needs further evaluation and validation in contemporary cohorts in Africa and other resource-constrained settings. CONCLUSIONS: The simple and feasible clinical score allowed for prioritization of sensitivity and NPV, which could facilitate reductions in mortality from undiagnosed TB and safer administration of TPT during proposed global scale-up efforts. Differentiation of risk by clinical score cutoff allows flexibility in designing differentiated HIV-TB care to maximize impact of available resources

Longer hospital stay is associated with higher rates of tuberculosis-related morbidity and mortality within 12 months after discharge in a referral hospital in Sub-Saharan Africa

BACKGROUND: Nosocomial transmission of pulmonary tuberculosis (PTB) is a problem in resource-limited settings. However, the degree of TB exposure and the intermediate- and long-term morbidity and mortality of hospital-associated TB is unclear. In this study we determined: 1) the nature, patterns and intensity of TB exposure occurring in the context of current TB cohorting practices in medical centre with a high prevalence of TB and HIV; 2) the one-year TB incidence after discharge; and 3) one-year TB-related mortality after hospital discharge. METHODS: Factors leading to nosocomial TB exposure were collected daily over a 3-month period. Patients were followed for 1-year after discharge. TB incidence and mortality were calculated and logistic regression was used to determine the factors associated with TB incidence and mortality during follow up. RESULTS: 1,094 patients were admitted to the medical wards between May 01 and July 31, 2010. HIV was confirmed in 690/1,094 (63.1%) of them. A total of 215/1,094 (19.7%) patients were diagnosed with PTB and 178/1,094 (16.3%) patients died during the course of their hospitalization; 12/178 (6.7%) patients died from TB-related complications. Eventually, 916 (83.7%) patients were discharged and followed for one year after it. Of these, 51 (5.6%) were diagnosed with PTB during the year of follow up (annual TB rate of 3,712 cases per 100,000 person per year). Overall, 57/916 (6.2%) patients died during the follow up period, of whom 26/57 (45.6%) died from confirmed TB. One-year TB incidence rate and TB-associated mortality were associated with the number of days that the patient remained hospitalized, the number of days spent in the cohorting bay (regardless of whether the patient was eventually diagnosed with TB or not), and the number and proximity to TB index cases. There was no difference in the performance of each of these 3 measurements of nosocomial TB exposure for the prediction of one-year TB incidence. CONCLUSION: Substantial TB exposure, particularly among HIV-infected patients, occurs in nosocomial settings despite implementation of cohorting measures. Nosocomial TB exposure is strongly associated with one-year TB incidence and TB-related mortality. Further studies are needed to identify strategies to reduce such exposure among susceptible patients

High rates of exposure to tuberculosis patients among HIV-infected health care workers in Botswana.

ObjectiveTo compare daily exposure to tuberculosis (TB) patients between HIV-infected and non-HIV-infected health care workers (HCWs), and examine the uptake of antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) among HIV-infected HCWs in Botswana.DesignWe conducted a cross-sectional study among HCWs in 30 hospitals and clinics. We determined self-reported exposure frequency to TB patients and HIV status through in-person interviews. HCWs with unknown or negative HIV status were offered rapid HIV testing. Multivariable Poisson regression modeling with robust variance was used to estimate the association between HIV status and daily exposure to TB patients.ResultsOf 1877 participants enrolled, 1388 (73.9%) with complete data were included in this study. Among 277 (20.0%) HIV-infected participants, 14.3% were newly diagnosed, 57.8% were on ART, and 34.3% reported previously receiving IPT. Daily exposure to TB patients was reported by respectively 48.4% and 52.9% of HIV-infected and non-infected participants. After adjusting for sex, age, occupation, and department, the rates of daily TB exposure remained similar between HIV-infected and non-HIV-infected participants (prevalence ratio 0.96, 95%CI 0.85-1.08).ConclusionsWe found similar rates of exposure to TB patients between HIV-infected and non-HIV-infected HCWs. Improved efforts are needed to reduce nosocomial exposure to TB among HIV-infected HCWs

Identification of a Large Pool of Microorganisms with an Array of Porphyrin Based Gas Sensors

The association between volatile compounds (VCs) and microorganisms, as demonstrated by several studies, may offer the ground for a rapid identification of pathogens. To this regard, chemical sensors are a key enabling technology for the exploitation of this opportunity. In this study, we investigated the performance of an array of porphyrin-coated quartz microbalance gas sensors in the identification of a panel of 12 bacteria and fungi. The porphyrins were metal complexes and the free base of a functionalized tetraphenylporphyrin. Our results show that the sensor array distinguishes the VC patterns produced by microorganisms in vitro. Besides being individually identified, bacteria are also sorted into Gram-positive and Gram-negative

Diagnosis of pulmonary tuberculosis and assessment of treatment response through analyses of volatile compound patterns in exhaled breath samples

OBJECTIVES: We determined the performance of a sensor array (an electronic nose) made of 8 metalloporphyrins coated quartz microbalances sensors for the diagnosis and prognosis of pulmonary tuberculosis (TB) using exhaled breath samples. METHODS: TB cases and healthy controls were prospectively enrolled. Signals from volatile organic compounds (VOCs) in breath samples were measured at days 0, 2, 7, 14, and 30 of TB therapy and correlated with clinical and microbiological measurements. RESULTS: 51 pulmonary TB cases and 20 healthy HIV-uninfected controls were enrolled in the study. 31 (61%) of the 51 pulmonary TB cases were coinfected with HIV. At day 0 (before TB treatment initiation) the sensitivity of our device was estimated at 94.1% (95% confidence interval [CI], 83.8-98.8%) and specificity was 90.0% (95% CI, 68.3-98.8%) for distinguishing TB cases from controls. Time-dependent changes in the breath signals were identified as time on TB treatment progressed. Time-dependent signal changes were more pronounced among HIV-uninfected patients. CONCLUSION: The identification of VOCs signals in breath samples using a sensor array achieved high sensitivity and specificity for the diagnosis of TB and allowed following signal changes during TB treatment