Evaluation of factors influencing Mycobacterium tuberculosis complex recovery and contamination rates in MGIT960.

BACKGROUND: Tuberculosis (TB) is a major public health problem worldwide. Contamination rate and poor recovery of Mycobacterium tuberculosis complex (MTBC) in MGIT960 culture may affect the early diagnosis of TB. Evidence is needed to determine the factors associated with contamination rates and MTBC recovery in MGIT960. Hence, we undertook this study to compare the factors influencing MTBC culture positivity and contamination rates in MGIT960 in patients with Pulmonary tuberculosis (PTB). METHODS: A total of 849 sputum samples from newly diagnosed smear-positive TB cases enrolled into the Regional Prospective Observational Research for Tuberculosis India cohort between May 2014 to March 2017 were analyzed. Samples were inoculated into MGIT960 and positive cultures were examined for the presence of MTBC by immunochromatographic test for detection of MPT64 antigen. RESULTS: Of the 849 cases, 811 (95.5%) were culture positive for MTBC, 23 (2.7%) were culture negative and 15 (1.8%) were contaminated. Salivary sputum showed significantly less culture yield compared to mucopurulent/blood stained samples (p = 0.021). Sputum from individuals <20 or ≥60 years showed lower culture yield of 93.9%, compared to those aged 20-59years (98.2%) (p = 0.002). Based on smear grading, culture isolation of MTBC by MGIT960 was 86.1%, 93.6% and 99.5% for negative, scanty and positive (1+/2+/3+) samples, respectively (p ≤ 0.0001). Sputum from HIV negative patients showed higher culture yield, compared to HIV positive patients (p ≤ 0.0001). Chest X-Ray revealed that patient with cavity showed higher culture isolation of MTBC compared to patients without cavity (p = 0.035). Contamination rates were higher in smear negatives (6.0%), compared to scanty (2.1%) and smear positives (1.1%) (p = 0.007). However, delay in transport of the specimen to the laboratory was the only independent factor significantly associated with increase in culture contamination. CONCLUSION: Our results highlight that extremes of age, smear negativity, HIV infection, sputum quality and cavitation significantly influence the culture yield of MTBC, whereas transport duration and smear grading affected the contamination rates in MGIT960. Hence, addressing these factors may improve the diagnostic performance of MGIT960.

Existing blood transcriptional classifiers accurately discriminate active tuberculosis from latent infection in individuals from south India.

Several studies have identified blood transcriptomic signatures that can distinguish active from latent Tuberculosis (TB). The purpose of this study was to assess how well these existing gene profiles classify TB disease in a South Indian population. RNA sequencing was performed on whole blood PAXgene samples collected from 28 TB patients and 16 latently TB infected (LTBI) subjects enrolled as part of an ongoing household contact study. Differential gene expression and clustering analyses were performed and compared with explicit predictive testing of TB and LTBI individuals based on established gene signatures. We observed strong predictive performance of TB disease states based on expression of known gene sets (ROC AUC 0.9007-0.9879). Together, our findings indicate that previously reported classifiers generated from different ethnic populations can accurately discriminate active TB from LTBI in South Indian patients. Future work should focus on converting existing gene signatures into a universal TB gene signature for diagnosis, monitoring TB treatment, and evaluating new drug regimens.

Comorbidities in pulmonary tuberculosis cases in Puducherry and Tamil Nadu, India: Opportunities for intervention.

BACKGROUND: We aimed to define characteristics of TB patients in Puducherry and two districts of Tamil Nadu, India and calculate the population attributable fractions (PAF) of TB from malnutrition and alcohol. METHODS: New smear-positive TB cases were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT India) cohort. Census and National Family Health Survey data were used for comparisons. RESULTS: Data were analyzed for 409 participants enrolled between May 2014-June 2016; 307 (75.1%) were male, 60.2% were malnourished (body mass index [BMI] <18.5 kg/m2), and 29.1% severely malnourished (BMI <16). "Hazardous" alcohol use (based on AUDIT-C score) was reported by 155/305 (50.8%) of males. Tuberculosis cases were more likely than the Puducherry population to be malnourished (62.6% v 10.2% males and 71.7% v 11.3% of females; both p<0.001), and male cases were more likely to use alcohol than male non-cases (84.4% v 41%; p < .001). The PAF of malnutrition was 57.4% in males and 61.5% in females; the PAF for alcohol use was 73.8% in males and 1.7% in females. CONCLUSIONS: Alcohol use in men and malnutrition are helping drive the TB epidemic in Southern India. Reducing the TB burden in this population will require efforts to mitigate these risk factors.

Predictors of delayed care seeking for tuberculosis in southern India: an observational study.

BACKGROUND: Reducing delay to accessing care is necessary to reduce the Tuberculosis (TB) burden in high incidence countries such as India. This study aimed to identify factors associated with delays in seeking care for TB in Southern India. METHODS: We analyzed data from newly diagnosed, smear-positive, culture-confirmed, pulmonary TB patients in the Regional Prospective Observational Research for TB (RePORT) cohort in Puducherry and Tamil Nadu, India. Data were collected on demographic characteristics, symptom duration, and TB knowledge, among other factors. Delay was defined as cough ≥4 weeks before treatment initiation. Risky alcohol use was defined by the AUDIT-C score which incorporates information about regular alcohol use and binge drinking. TB knowledge was assessed by knowing transmission mode or potential curability. RESULTS: Of 501 TB patients, 369 (73.7%) subjects delayed seeking care. In multivariable analysis, risky alcohol use was significantly associated with delay (aOR 2.20, 95% CI: 1.31, 3.68). Delay was less likely in lower versus higher income groups (<3000 versus >10,000 rupees/month, aOR 0.31, 95% CI: 0.12, 0.78). TB knowledge was not significantly associated with delay. CONCLUSIONS: Local TB programs should consider that risky alcohol users may delay seeking care for TB. Further studies will be needed to determine why patients with higher income delay in seeking care.

The relationship between gun ownership and stranger and nonstranger firearm homicide rates in the United States, 1981-2010.

OBJECTIVES: We examined the relationship between gun ownership and stranger versus nonstranger homicide rates. METHODS: Using data from the Supplemental Homicide Reports of the Federal Bureau of Investigation's Uniform Crime Reports for all 50 states for 1981 to 2010, we modeled stranger and nonstranger homicide rates as a function of state-level gun ownership, measured by a proxy, controlling for potential confounders. We used a negative binomial regression model with fixed effects for year, accounting for clustering of observations among states by using generalized estimating equations. RESULTS: We found no robust, statistically significant correlation between gun ownership and stranger firearm homicide rates. However, we found a positive and significant association between gun ownership and nonstranger firearm homicide rates. The incidence rate ratio for nonstranger firearm homicide rate associated with gun ownership was 1.014 (95% confidence interval=1.009, 1.019). CONCLUSIONS: Our findings challenge the argument that gun ownership deters violent crime, in particular, homicides.