Lipid mediators of inflammation and Resolution in individuals with tuberculosis and tuberculosis-Diabetes.

Individuals with concurrent tuberculosis (TB) and Type 2 diabetes (DM) have a higher risk of adverse outcomes. To better understand potential immunological differences, we utilized a comprehensive panel to characterize pro-inflammatory and pro-resolving (i.e., mediators involved in the resolution of inflammation) lipid mediators in individuals with TB and TB-DM. A nested cross-sectional study of 40 individuals (20 newly diagnosed DM and 20 without DM) was conducted within a cohort of individuals with active drug-susceptible treatment-naïve pulmonary TB. Lipid mediators were quantified in serum samples through lipid mediator profiling. We conducted correlation-based analysis of these mediators. Overall, the arachidonic acid-derived leukotriene and prostaglandin families were the most abundant pro-inflammatory lipid mediators, while lipoxins and maresins families were the most abundant pro-resolving lipid mediators in individuals with TB and TB-DM. Individuals with TB-DM had increased correlations and connectivity with both pro-inflammatory and pro-resolving lipid mediators compared to those with TB alone. We identified the most abundant lipid mediator metabolomes in circulation among individuals with TB and TB-DM; in addition, our data shows a substantial number of significant correlations between both pro-inflammatory and pro-resolving lipid mediators in individuals with TB-DM, delineating a molecular balance that potentially defines this comorbidity.

Sex Differences in TB Clinical Presentation, Drug Exposure, and Treatment Outcomes in India.

BACKGROUND: The role of sex differences in clinical presentation, TB drug pharmacokinetic variables, and treatment outcomes is unclear. RESEARCH QUESTION: What is the effect of sex on TB disease severity, drug exposure, and treatment outcome? STUDY DESIGN AND METHODS: This study was a prospective cohort study conducted in India. It assessed TB disease severity; risk of unfavorable treatment outcomes (failure, recurrence, and death) according to sex; and risk factors for unfavorable outcomes stratified according to sex. Effects of sex on the pharmacokinetic variables (maximum concentration and area under the curve) of rifampicin, isoniazid, and pyrazinamide were estimated by using noncompartmental analyses. RESULTS: Of 1,541 people with microbiologically confirmed TB, 567 (37%) were women. Women had a lower risk of high mycobacterial burden (smear grade ≥ 2 and/or time to detection < 7 days) with an adjusted OR of 0.70 (95% CI, 0.56-0.87). Among the 744 participants who were followed up prospectively, 261 (35%) were women. Women had a lower risk of unfavorable treatment outcomes (adjusted incidence risk ratio, 0.60; 95% CI, 0.43-0.85), mostly because recurrence was lower (adjusted incidence risk ratio, 0.45; 95% CI, 0.23-0.86). Isoniazid (but not rifampicin and pyrazinamide) maximum concentration and area under the curve were significantly higher among women (P < .01) than men. Among women, unfavorable outcomes were more likely among those with cavitary disease, but among men, increased risk of unfavorable outcomes was associated with alcohol use, higher BMI, and lower glycated hemoglobin level. INTERPRETATION: Women present with lower mycobacterial burden, achieve higher TB drug exposure, and are less likely to have unfavorable treatment outcomes than men. Strategies to improve TB treatment success should take into account sex differences in risk factors for unfavorable outcomes.

Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. METHODS: We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined, and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. RESULTS: Of 799 participants, 574 (72%) had TB only and 225 (28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20%, as compared with 21% for TB-only participants (adjusted hazard ratio [aHR], 1.13; 95% CI, 0.75-1.70). Mortality was higher in participants with DM (10% vs 7%), and early mortality was substantially higher among patients with DM (aHR, 4.36; 95% CI, 1.62-11.76). CONCLUSIONS: DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.

Pediatric tuberculosis in young children in India: a prospective study.

BACKGROUND: India has one of the highest tuberculosis (TB) burdens globally. However, few studies have focused on TB in young children, a vulnerable population, where lack of early diagnosis results in poor outcomes. METHODS: Young children (≤ 5 years) with suspected TB were prospectively enrolled at a tertiary hospital in Pune, India. Detailed clinical evaluation, HIV testing, mycobacterial cultures, and drug susceptibility testing were performed. RESULTS: 223 children with suspected TB were enrolled. The median age was 31 months, 46% were female, 86% had received BCG, 57% were malnourished, and 10% were HIV positive. 12% had TB disease (definite or probable), 35% did not have TB, while TB could not be ruled out in 53%. Extrapulmonary disease was noted in 46%, which was predominantly meningeal. Tuberculin skin test (TST) was positive in 20% of children with TB. Four of 7 (57%) children with culture-confirmed TB harbored drug-resistant (DR) strains of whom 2 (50%) were multi-DR (MDR). In adjusted analyses, HIV infection, positive TST, and exposure to household smoke were found to be significantly associated with children with TB (P ≤ 0.04). Mortality (at 1 year) was 3 of 26 (12%) and 1 of 79 (1%), respectively, in children with TB and those without TB (P < 0.05). CONCLUSIONS: Diagnosis of TB is challenging in young children, with high rates of extra-pulmonary and meningeal disease. While the data on DR-TB are limited by the small sample size, they are however concerning, and additional studies are needed to more accurately define the prevalence of DR strains in this vulnerable population.

Drug resistance profiles of Mycobacterium tuberculosis isolates to first line anti-tuberculous drugs: A five years study.

BACKGROUND: Drug resistance is a major problem in the treatment of tuberculosis (TB). An estimate of drug resistance is extremely important in the epidemiology and control of TB. However, an assessment of the magnitude of drug resistance in TB is not very well described globally and data remains scantier for India. In view of this, we reviewed our data over last five years. MATERIALS AND METHODS: Six hundred and seventy-three Mycobacterium tuberculosis isolates were subjected to drug susceptibility against primary anti-tuberculosis drugs by economic variant proportion method. All isolates resistant to isoniazid and rifampicin were taken as multi-drug resistant (MDR). RESULTS: Out of the 673 strains tested, 95 (14.11%) showed monoresistance, 365 (54.23%) strains were found to be resistant to more than one drug. A total of 118 (17.53%) strains were found to be resistant to all the four drugs tested. MDR was seen with 320 (47.54%) isolates. This study observed maximum resistance with rifampicin (74.4%) followed by streptomycin (70.0%), isoniazid (53.2%), and ethambutol (21.7%). CONCLUSION: While this information may not reflect true prevalence of drug resistance in the region, this may help in further planning long term surveillance studies to know the trend of drug resistance in this area.

A clinical and mycological study of onychomycosis in HIV infection.

BACKGROUND: Onychomycosis is one of the early manifestations of HIV infection with a prevalence of 15-40%. Multiple nail involvement, isolation of both common and rare species and resistance to treatment are the characteristics of onychomycosis in HIV. AIM: To study the epidemiology, clinical manifestations of onychomycosis in HIV-infected individuals and to identify the various causative fungi microbiologically. METHODS: A total of 250 HIV infected patients, diagnosed by ELISA, were screened for nail involvement; of which 60 patients i.e, 40 males and 20 females, who had clinically suspected untreated fungal infection were included in this study. RESULTS: Of the 60 respondents, 34 (56.66%) were from the 31-40 years age group. Amongst the 40 males, there were 20 manual laborers and 14 farmers; while 18 of 20 females were housewives. Toenail involvement was seen in 38 patients (63.33%), fingernail in 12 patients (20%) while 10 (16.66%) patients had involvement of both. Twenty eight (46.66%) patients gave history of some trauma, 6 (10%) had diabetes mellitus and only 1 patient (1.66%) had history of peripheral vascular disease. Nineteen (31.66%) patients had associated tinea pedis, 5 (8.33%) had tinea manuum, 10 (16.66%) had tinea corporis and 7 (11.66%) had tinea cruris. Twenty one (35%) respondents had distal and lateral superficial onychomycosis (DLSO), 5 (8.33%) had proximal subungual onychomycosis (PSO), 1 (1.66%) had superficial white onychomycosis (SWO), while 33 (55%) had total dystrophic onychomycosis (TDO). Fungal elements were demonstrated by KOH mount in 49 patients (81.66%) and growth was seen in 32 (53.33%) cultures. Dermatophytes were isolated in 13 (21.66%) and nondermatophytic molds (NDM) in 19 (31.66%). Out of the 13 positive dermatophyte cultures, Trichophyton rubrum was isolated on 11 and Trichophyton mentagrophytes on 2 cultures. Of the 19 non-dermatophytic cultures, Aspergillus niger was isolated on 3 and Candida spp. on 12 while Cladosporium spp, Scytalidium hyalinum, Penicillium spp. and Gymnoascus dankaliensis on 1 each. CONCLUSIONS: Total dystrophic onychomycosis was the most common clinical type and NDM were the predominant causative organisms.