Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children.

BACKGROUND: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen. METHODS: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment. RESULTS: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups). CONCLUSIONS: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.).

Xpert MTB/RIF assay in the diagnosis of pulmonary tuberculosis in children in tertiary care setting in South India.

Xpert MTB/RIF is recommended for the diagnosis of tuberculosis (TB) in children. We determined the performance of Xpert MTB/RIF in the diagnosis of pulmonary TB in children. The characteristics of children influencing Xpert MTB/RIF positivity were explored. Children aged <15 years with symptoms suggestive of pulmonary TB were prospectively enrolled from 2013 to 2019. Two sputum/early morning gastric aspirate specimens were collected for examination by smear (fluorescence microscopy), Xpert MTB/RIF, and culture [Mycobacteria growth indicator tube (MGIT)/Lowenstein-Jensen (LJ) medium]. Diagnostic performance of Xpert MTB/RIF was evaluated using LJ and or MGIT culture positivity as the reference standard. Sensitivity, specificity with 95% confidence interval (CI) were calculated. Stratified analysis was done; P < .05 was considered statistically significant. Of the total 1727 enrolled children, 1674 (97%) with complete results for at least one sputum/gastric aspirate sample were analyzed. The sensitivity of Xpert MTB/RIF was 68.5% in sputum and 53.6% in gastric aspirate while the specificity was 99% for both. The sensitivity compared to smear was 68.5% vs. 33.7% (P < .001) and 53.6% vs. 14.5%; (P < .001) in sputum and gastric aspirate, respectively. The sensitivity of Xpert MTB/RIF was 23.9% with decision to treat as reference standard. Xpert MTB/RIF positivity was significantly influenced by sex, age, nutritional status, chest X-ray abnormality, TB infection status, and symptoms suggestive of TB. Xpert MTB/RIF as an upfront test compared to smear improves diagnosis of pulmonary TB in children yet the sensitivity is suboptimal. Newer TB diagnostic tools with improved sensitivity is warranted in children.

We evaluated the performance of Xpert MTB/RIF in the diagnosis of pulmonary TB in children and explored the characteristics influencing Xpert MTB/RIF positivity. Sputum and or early morning gastric aspirate specimen was collected from children aged <15 years with symptoms suggestive of pulmonary TB. This was examined by smear (fluorescence microscopy), Xpert MTB/RIF, and culture (Mycobacteria growth indicator tube (MGIT)/Lowenstein­Jensen (LJ) medium). Diagnostic performance of Xpert MTB/RIF was evaluated using LJ and or MGIT culture positivity as the reference standard. Of the total 1727 enrolled children, 1674 (97%) with complete results for at least one sputum/gastric aspirate sample were analyzed. The sensitivity of Xpert MTB/RIF was 68.5% in sputum and 53.6% in gastric aspirate which was higher than smear and the specificity was 99%. The sensitivity of Xpert MTB/RIF was 23.9% with decision to treat for TB as reference standard. The Xpert MTB/RIF positivity was influenced by sex, age, nutritional status, chest X-ray abnormality, TB infection status, and symptoms suggestive of TB. Xpert MTB/RIF as an upfront test compared to smear improves the diagnosis of pulmonary TB in children yet the sensitivity is suboptimal. Newer TB diagnostic tools with improved sensitivity is warranted in children.

Surveillance of adverse drug reactions and drug-drug interactions with pediatric oncology patients in a south Indian tertiary care hospital.

OBJECTIVE: The present study was conducted to evaluate the pattern of occurrence of adverse drug reactions and drug-drug interaction in a pediatric oncology unit of a tertiary care hospital. METHODS: A prospective, observational study was conducted in the Department of Pediatric Oncology, Sri Ramachandra Medical College and Hospital, India. Patients were monitored actively for the occurrences of any adverse drug reaction during the study period. Patient's demographic details, clinical, and treatment data were collected for drug-drug interaction analysis. The detected adverse drug reaction was assessed for causality, severity, and preventability. Drug-drug interaction identified was rated based on their level of urgency and the nature of actions necessary to respond to an interaction. RESULTS: Of 176 patients, 118 were detected for the occurrence of various adverse drug reaction. The majority of the cases were suffering with acute lymphocytic leukemia (67.9%). Vincristine was noted for a maximum number of adverse drug reaction in cytotoxic drugs. Rash is the most frequently occurred reaction. Assessment of causality showed that the majority of cases are "probable" (60.16%). In evaluating the severity of adverse drug reactions, 57.6% reactions were moderately severe and 74.5% of the reactions were preventable. Upon assessing the drug-drug interaction, 38.13% of the prescription needs to be monitored and 10 drug-drug interactions were under the risk category of "X." The majority of the adverse drug reaction was moderately severe in nature and those were preventable. CONCLUSION: Since pediatrics are vulnerable population, they must have a thorough surveillance system for adverse drug reaction and drug-drug interaction; thereby, a positive impact on the medication-use system and improved patient care can be achieved.

An educational intervention for improving knowledge, attitude, and practice of dietary salt intake among individuals with hypertension in public sector secondary care facilities, Agra, India, 2021.

We conducted a pre-post intervention study to determine knowledge, attitude, and practice toward dietary salt intake before, immediately, and 1-month after nurse-led one-on-one counseling. We purposively selected three public health facilities in Agra, India, and enrolled all eligible hypertensive patients aged 18-60 under treatment for ≥6 months. Of the 153 patients at the 1-month follow-up, counseling improved knowledge (4% vs. 42%, p < .001), a greater prioritization of a low salt diet (34% vs. 52%, p < .001), and practice of adding less salt to the dough (48% to 41%, p < .001). The counseling intervention improved knowledge, attitude, and practice toward dietary salt intake.

Prevalence of Noncommunicable Disease (NCDs) risk factors in Tamil Nadu: Tamil Nadu STEPS Survey (TN STEPS), 2020.

BACKGROUND: Noncommunicable diseases (NCDs) account for nearly 75% of all deaths in Tamil Nadu. The government of Tamil Nadu has initiated several strategies to control NCDs under the Tamil Nadu Health Systems Reform Program (TNHSRP). We aimed to estimate the prevalence of NCD risk factors and determine the predictors of diabetes and hypertension, which will be helpful for planning and serve as a baseline for evaluating the impact of interventions. METHODS: A state-wide representative cross-sectional study was conducted among 18-69-year-old adults in Tamil Nadu in 2020. The study used a multi-stage sampling method to select the calculated sample size of 5780. We adapted the study tools based on WHO's STEPS surveillance methodology. We collected information about sociodemographic factors, NCD risk factors and measured blood pressure and fasting capillary blood glucose. The predictors of diabetes and hypertension were calculated using generalised linear models with 95% confidence intervals (95% CI). RESULTS: Due to the COVID-19 pandemic lockdown, we could cover 68% (n = 3800) of the intended sample size. Among the eligible individuals surveyed (n = 4128), we had a response rate of 92%. The mean age of the study participants was 42.8 years, and 51% were women. Current tobacco use was prevalent in 40% (95% CI: 33.7-40.0) of men and 7.9% (95% CI: 6.4-9.8) of women. Current consumption of alcohol was prevalent among 39.1% (95% CI: 36.4-42.0) of men. Nearly 28.5% (95% CI: 26.7-30.4) of the study participants were overweight, and 11.4% (95% CI: 10.1-12.7) were obese. The prevalence of hypertension was 33.9% (95% CI: 32.0-35.8), and that of diabetes was 17.6% (95% CI: 16.1-19.2). Older age, men, and obesity were independently associated with diabetes and hypertension. CONCLUSION: The burden of NCD risk factors like tobacco use, and alcohol use were high among men in the state of Tamil Nadu. The prevalence of other risk factors like physical inactivity, raised blood pressure and raised blood glucose were also high in the state. The state should further emphasise measures that reduce the burden of NCD risk factors. Policy-based and health system-based interventions to control NCDs must be a high priority for the state.

Sudden deaths due to accidental leakage of Lindane from a storage tank in a village, Sitapur, Uttar Pradesh, India, 2020: A field epidemiological investigation.

Background: Chemical leakages cause devastating health effects on humans. On 6 February 2020, seven deaths were reported following a hazardous chemical leakage in a village in Uttar Pradesh, India. We investigated the event to identify the cause and propose recommendations. Methods: We defined a case as sudden onset of breathlessness, headache, or death in the village, 6-7 February 2020. We conducted a house-to-house case search and calculated attack rate (AR) and case-fatality rate (CFR) by age and gender. We conducted an environmental investigation at the leakage site and sent the chemicals for forensic analysis. We obtained the cause of death through autopsy reports. Results: Out of 2,942 residents, we identified 23 cases (AR = 8/1,000) and seven deaths (CFR = 30%). The median age of the case was 42 years (range, 2-64 years). The AR was higher among males (14/1,000 [19/1,402]). All the 23 case-patients who were sleeping at the chemical leakage site or visited to witness the event developed symptoms, and all seven cases who were sleeping within 150 meters of the leakage site died. The environmental investigation revealed leakage of hazardous substances from the storage tank. Toxicology analysis confirmed the leaked chemical as Lindane (gamma-hexachlorocyclohexane), and autopsy reports confirmed the cause of death as asphyxia. Conclusions: Asphyxia following the leakage of Lindane from the storage tank possibly led to sudden deaths. We recommend using leak-proof tanks to ensure safe storage and disposal, law enforcement, and regulations to prevent people from staying close to chemical storage sites.

Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015-2020.

OBJECTIVES: We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India. DESIGN: A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data. SETTING: National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status. PARTICIPANTS: Each district was divided into survey units (SU) and one village/ward was randomly selected from each SU. All household members in the selected village were interviewed. Sputum from participants with a history of anti-TB therapy (ATT), those currently experiencing chest symptoms or on ATT were tested using Xpert/Rif/TrueNat. The survey continued until 30 Mycobacterium tuberculosis cases were identified in a district. OUTCOME MEASURES: We calculated a direct estimate of TB incidence based on incident cases identified in the survey. We calculated an under-reporting factor by matching these cases within the TB notification system. The TB notification adjusted for this factor was the estimate by the indirect method. We also calculated TB incidence from drug sale data in the private sector and drug utilisation data in the public sector. We compared the three estimates of TB incidence in 2020 with TB incidence in 2015. RESULTS: The estimated direct incidence ranged from 19 (Purba Medinipur, West Bengal) to 1457 (Jaintia Hills, Meghalaya) per 100 000 population. Indirect estimates of incidence ranged between 19 (Diu, Dadra and Nagar Haveli) and 788 (Dumka, Jharkhand) per 100 000 population. The incidence using drug sale data ranged from 19 per 100 000 population in Diu, Dadra and Nagar Haveli to 651 per 100 000 population in Centenary, Maharashtra. CONCLUSION: TB incidence in 1 state, 2 UTs and 35 districts had declined by at least 20% since 2015. Two districts in India were declared TB free in 2020.

Pulmonary Mycobacterium kyorinense disease: A case report and review of literature.

We report here the first case of pulmonary infection due to Mycobacterium kyorinense in a 55-year-old hypertensive woman treated for pulmonary tuberculosis earlier on two occasions. She presented with productive cough, intermittent episode of left-sided chest pain, loss of appetite, low-grade fever, and breathlessness. Sputum cultures revealed non-tuberculous mycobacteria (NTM). She remained persistently symptomatic with sputum cultures positive for acid-fast bacilli even after 6 months of treatment. Hence, a 16SrRNA gene amplification and sequencing were done that revealed M. kyorinense. Based on the guidelines of the American Thoracic Society, she was started on weight-based dosing of clarithromycin, levofloxacin, ethambutol, isoniazid and injection amikacin daily. The patient improved symptomatically and became culture-negative after 3 months of therapy with the above regimen and continued to be culture negative for 12 months of treatment. She continues to remain symptom-free without evidence of any clinical or bacteriological relapse.

Recurrence of tuberculosis among newly diagnosed sputum positive pulmonary tuberculosis patients treated under the Revised National Tuberculosis Control Programme, India: A multi-centric prospective study.

INTRODUCTION: There is lack of information on the proportion of new smear-positive pulmonary tuberculosis (PTB) patients treated with a 6-month thrice-weekly regimen under Revised National Tuberculosis Control Programme (RNTCP) who develop recurrent TB after successful treatment outcome. OBJECTIVE: To estimate TB recurrence among newly diagnosed PTB patients who have successfully completed treatment and to document endogenous reactivation or re-infection. Risk factors for unfavourable outcomes to treatment and TB recurrence were determined. METHODOLOGY: Adult (aged ≥ 18 yrs) new smear positive PTB patients initiated on treatment under RNTCP were enrolled from sites in Tamil Nadu, Karnataka, Delhi, Maharashtra, Madhya Pradesh and Kerala. Those declared "treatment success" at the end of treatment were followed up with 2 sputum examinations each at 3, 6 and 12 months after treatment completion. MIRU-VNTR genotyping was done to identify endogenous re-activation or exogenous re-infection at TB recurrence. TB recurrence was expressed as rate per 100 person-years (with 95% confidence interval [95%CI]). Regression models were used to identify the risk factors for unfavourable response to treatment and TB recurrence. RESULTS: Of the1577 new smear positive PTB patients enrolled, 1565 were analysed. The overall cure rate was 77% (1207/1565) and treatment success was 77% (1210 /1565). The cure rate varied from 65% to 86%. There were 158 of 1210 patients who had TB recurrence after treatment success. The pooled TB recurrence estimate was 10.9% [95%CI: 0.2-21.6] and TB recurrence rate per 100 person-years was 12.7 [95% CI: 0.4-25]. TB recurrence per 100 person-years varied from 5.4 to 30.5. Endogenous reactivation was observed in 56 (93%) of 60 patients for whom genotyping was done. Male gender was associated with TB recurrence. CONCLUSION: A substantial proportion of new smear positive PTB patients successfully treated with 6 -month thrice-weekly regimen have TB recurrence under program settings.