Accuracy and agreement of the Tuberculin Skin Test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in the diagnosis of tuberculosis in Indian children.

PURPOSE: Accurate diagnosis of TB in children is hampered by poor specificity of symptoms in endemic countries and the paucibacillary nature of childhood TB. This study was done to compare the accuracy and agreement of the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-tube test (QFT) in diagnosing tuberculosis (TB) in a predominantly BCG-vaccinated population of children. METHODS: This retrospective cohort study enrolled all children aged 1-15 years who underwent TST and QFT testing as part of screening for TB. Children were classified according to the 2014 WHO case definition of TB, and statistical analysis was done to generate data on concordance between the TST and the QFT as well as sensitivity and specificity within WHO-defined groups. RESULTS: TST and QFT concordance was 83.9% overall (kappa 0.51), 79% in those with WHO-defined TB and 89% in those without TB. TST+/QFT-discordance was commoner than QFT+/TST- discordance across groups. The sensitivity of the TST vs. the QFT was 70.8% vs. 50% for WHO-defined TB, with comparable specificity at 89% vs. 90% respectively. CONCLUSIONS: The higher sensitivity of the cheaper and simpler TST supports its use for TB diagnosis in a normally nourished population of BCG-vaccinated children.

Resource utilization and cost effectiveness of treating acute promyelocytic leukaemia using generic arsenic trioxide.

Arsenic trioxide (ATO)-based regimens are the standard of care for treating acute promyelocytic leukaemia (APL) and have replaced chemotherapy-based approaches. However, the cost of "patented" ATO is prohibitive because of patent rights. "Generic" ATO has been used in a few countries, but its implications for health resource utilization (HRU) and cost of treatment are unknown. We hypothesized that treating APL patients using generic ATO (APL-ATO) will be cost effective compared to the chemotherapy-based regimen (APL-CT). In a single-centre retrospective study, we used a bottom-up costing method to compare the direct medical cost of treatment and HRU between APL-ATO and APL-CT. These costs and the survival and relapse probabilities were imputed in a three-state Markov decision model to estimate the cost effectiveness of APL-ATO compared to APL-CT. The mean cost of treatment for APL-ATO (n = 30, $8500 ± 2078) was significantly less than for APL-CT (n = 30, $22 600 ± 5528) (P < 0·001). APL-ATO reduced hospitalization, antibiotic and antifungal usage (P < 0·001). In the Markov model, five-year treatment costs were significantly lower for APL-ATO ($11 131) than for APL-CT ($17 926) (P < 0·001). Treatment cost and health resource utilization were significantly lower for generic ATO-treated APL patients compared to the chemotherapy-based regimen.

Utility of QuantiFERON®-TB gold In-Tube test compared with tuberculin skin test in diagnosing tuberculosis in Indian children with malnutrition.

This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette-Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (κ = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST - discordance was seen in children with TB, whereas majority of the TST+/QFT - discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.

Extremely High Mortality Rates in Patients with Carbapenem-resistant, Hypermucoviscous Klebsiella pneumoniae Blood Stream Infections.

BACKGROUND: Infections caused by carbapenem resistant K. pneumoniae are increasing and associated with high mortality rates. There are increasing reports of hypermucoviscous/ hypervirulent K. pneumoniae isolated from various sources. However, there is limited data on the prevalence of hypermucoviscous strains among carbapenem-resistant K. pneumoniae from invasive infections in India and its association with mortality. rmpA, rmpA2 and magA genes are associated with these hypervirulent strains. In this study, we investigate the prevalence of hypermucoviscous strains amongst carbapenem resistant K. pneumoniae isolated from blood culture. Association of mortality rate with meropenem minimum inhibitory concentration and hypermucoviscous strains are determined. METHODS: 86 non-repetitive carbapenem resistant K. pneumoniae isolated from bacteremia underwent E-test for meropenem minimum inhibitory concentration (MIC) determination and PCR for detection of carbapenamase genes. String test, PCR for rmpA, rmpA2 and magA were performed for characterisation of hypervirulent strains. Results: 31.3% of the 86 isolates displayed hypermucoviscous phenotype as indicated by a positive string test. Among the two genotypic markers, 7% were positive for rmpA2 and all were negative for rmpA and magA. 74.1% and 67.9% mortality were seen among string test positives and isolates meropenem MIC of ≥16µg/ml respectively (p 0.036 and 0.008 respectively). Isolates with both string positivity and meropenem MIC of ≥16µg/ml had a very high mortality rate of 84.2%. CONCLUSION: String test, aids prediction of disease severity, and is independently associated with increased mortality in invasive carbapenem resistant K.pneumoniae health care-acquired infections. High meropenem MIC is a significant risk factor for mortality. Combination of string positive carbapenem resistant hypermucoviscous K. pneumoniae resulted in mortality rate of 84.2%. It is important to monitor prevalence of carbapenem resistant hypermucoviscous/hypervirulent K. pneumoniae among invasive isolates especially in a setting with high resistance rates as combination of increased virulence and decreased susceptibility to antimicrobials results in worse outcomes.

Clinical and Bacterial Risk Factors for Mortality in Children With Carbapenem-resistant Enterobacteriaceae Bloodstream Infections in India.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) are an increasing cause of nosocomial infection in hospitalized children worldwide. Few studies have investigated risk factors for mortality in children with CRE bloodstream infection (BSI). Data are particularly scarce in areas where NDM and OXA carbapenemases predominate. Here, we investigate mortality rates, clinical and microbiologic risk factors for mortality in 50 pediatric patients with CRE BSI in India. METHODS: Children younger than 17 years old with meropenem-resistant Klebsiella pneumoniae or Escherichia coli isolated from blood culture in 2014 and 2015 were identified from laboratory records. Clinical records were systematically reviewed for each child to establish mortality at 30 days and clinical details. Bacterial isolates were subjected to meropenem E test and multiplex polymerase chain reaction to determine carbapenemase gene. Data were analyzed to establish clinical and bacterial risk factors for mortality. RESULTS: All CRE BSI were hospital-acquired or associated with healthcare. A total of 84% of children had an underlying comorbidity and 46% had a malignancy. K. pneumoniae was the most common bacteria isolated; NDM was the most common carbapenemase gene detected. The mortality rate was 52%. Significant risk factors for mortality included intensive care admission, intubation, inotropic support and respiratory source. Failure to clear bacteremia and a minimum inhibitory concentration > 8 mg/L for the isolate was associated with a statistically significant increase in mortality. Mortality rates were significantly lower when two or more effective drugs were used in combination. CONCLUSIONS: CRE BSI affects children with multiple comorbidities and repeated admissions to hospital. The mortality rate is high; combination therapy may be beneficial.

Parental determinants of metabolic syndrome among adolescent Asian Indians: A cross-sectional analysis of parent-offspring trios.

BACKGROUND: The aim of the present study was to investigate the relationship between parental metabolic syndrome (MS) and the risk of MS and associated abnormalities in adolescent offspring. METHODS: This cross-sectional study was performed on 304 adolescents (12-16 years; 236 children with at least one parent and 124 father-mother-child trios) recruited from four schools representing different socioeconomic strata from Vellore, India. Anthropometric data was collected and blood pressure, blood glucose, and lipids were measured. RESULTS: The prevalence of MS in adolescent offspring, fathers, and mothers was 3.3%, 52.5%, and 48.7% respectively. The most commonly observed metabolic abnormality among adolescents was lower high-density lipoprotein. Maternal waist circumference (WC) was strongly correlated with adolescent body mass index (P = 0.007), WC (P < 0.001), serum triglycerides (P = 0.02), and systolic (P = 0.005) and diastolic (P = 0.01) blood pressure. Maternal MS status was significantly associated with a greater risk of central obesity (WC odds ratio [OR] 2.02; 95% confidence interval [CI] 1.21-3.17) in offspring. Both parents having MS conferred a significant effect on the child's WC (OR 1.21; 95% CI 1.72-2.07) and increased risk of MS (OR 6.19; 95% CI 1.64-23.26). CONCLUSIONS: This study highlights the possible heritable parental components that may contribute to the MS phenotype in offspring: MS in adolescent offspring is related to parental MS status, and maternal traits reflect offspring adiposity and metabolic traits more strongly than paternal factors. Therefore, adolescent children of parents with MS should be targets for primordial prevention of cardiometabolic disease.

Childhood-onset Takayasu arteritis -- experience from a tertiary care center in South India.

OBJECTIVE: To study the clinical profile and outcome of Asian Indian children with childhood-onset Takayasu arteritis (c-TA). METHODS: Records were studied of patients with c-TA onset prior to age 16. Disease Extent Index-Takayasu (DEI.TAK), Indian Takayasu Arteritis Score 2010, and Takayasu Arteritis Damage Score (TADS) were calculated retrospectively from electronic records. Cumulative incidence of sustained remission was estimated using the Kaplan-Meier curve. RESULTS: There were 40 patients with c-TA, with median age of onset of 12.5 years (range 1-16) and median diagnostic delay of 11.3 months (range 1-60). The most common presenting features were hypertension, headache, malaise, and fever. Pulseless disease was observed in 25 cases (62.5%). The majority (n = 28) had active disease with raised inflammatory markers, high baseline median DEI.TAK score of 10 (range 3-24), and high median TADS of 7 (range 1-14). Of the 34 patients followed for 21.5 months (range 3-192), remission was attained in 30. However, cumulative sustained remission was achieved in only 29% of them at 5 years. Median period of sustained remission was 22.5 months (95% CI 17.1-26.8). New areas of vessel involvement were observed in 13 patients (38%). Disease progression was arrested in the majority (n = 22, 66%) through aggressive medical management and endovascular intervention. All 11 patients with an increment in TADS of ≥ 4 during followup had persistently active or relapsing disease. There was a single fatality. CONCLUSION: Despite aggressive immunosuppression, damage progressed in one-third of patients with c-TA in association with persistent inflammation, warranting surveillance with clinical instruments and followup imaging.

Prevalence and risk factors for human papillomavirus and cervical intraepithelial neoplasia among HIV-positive women at a tertiary level hospital in India.

OBJECTIVES: The hypothesis to be tested was that the prevalence of human papillomavirus (HPV) and cervical intraepithelial neoplasia would be significantly higher in HIV seropositive women as compared with seronegative controls. Secondary aims were to determine the risk factors for HPV and cervical intraepithelial neoplasia and the HPV types in HIV-positive women. MATERIALS AND METHODS: A cross-sectional study of women 18 to 49 years old was done. Seventy-five women who were HIV seropositive and 58 seronegative women, of whom 27 had HIV-positive partners, participated in the study. A Pap smear and a cervical swab for HPV were done. Women with Pap smear abnormality underwent colposcopy and large loop excision procedures if indicated. RESULTS: Ten (13.3%) HIV-positive women had high-grade squamous intraepithelial lesion as compared with 2 (3.4%) seronegative women (odds ratio [OR] 4.3; 95% CI = 0.9-41.7; p =.048). Among the HIV-positive women, 28 (37.3%) had high-risk HPV, whereas only 9 (15.5%) had high-risk HPV among seronegative women (OR 3.2; 95% CI = 1.3-8.3; p =.009). Among women who were positive for high-risk HPV, the HIV-positive women were significantly more likely to have more than 1 HPV type (OR 7.4; 95% CI = 1.4-43.7; p =.005). Women who had coitus at less than 18 years of age were more likely to have high-risk HPV infection (OR 2.9; 95% CI = 1.2-6.2; p =.013) even after controlling for HIV status. CONCLUSIONS: HIV-positive women have a higher risk for multiple HPV infections as compared with seronegative women. Behavioral factors dominate HIV in determining HPV infections and resultant cervical neoplasia.