Background Household contacts (HHC) of tuberculosis (TB) patients are at risk of TB infection and disease. The study assessed the utility of "Household contact card and register" for screening of HHC of pulmonary TB (PTB) patients for TB and explored the reasons for HHC not being screened and followed-up. Methods The "Household contact card and register" was implemented by the Health Care Workers (HCW) of the TB Control Programme in Chennai District for screening HHC of index PTB patients initiated on treatment between June and August, 2018. Contacts were required to be screened within 2 months of treatment initiation of the index patient. Details collected included age, gender, smoking, alcohol use, immunosuppressive conditions and TB treatment. Symptom screening along with chest radiograph and or sputum examination was attempted. Follow-up TB screening at 6 and 12 months were performed. Screening of HHC was compared pre and post implementation phase. Proportions were computed for the data analysed. Results HHC information was documented for 93% (1268/1364) of Index PTB patients. The main reasons of non-listing of HHC in 96 PTB patients were HCW non-availability or non-co-operation of the HHC. There were 2150 (80%) contacts who were screened for TB. Inconvenient time, feeling healthy, stigma, out-station visit were the main reasons for 537 contacts not undergoing TB screening. Anti-TB treatment was initiated in 21 (1%) of contacts diagnosed with TB. Preventive therapy was initiated in 59% (81/138) of contacts aged <6 years. The screening of HHC improved from 36% to 80% during the implementation phase. Follow-up TB screening at 12 months was performed in 50% of HHC and 2 incident TB cases were identified. Conclusion "Household contact card and register" is a useful tool for HCWs for TB screening in HHC of PTB patients. Reasons for non-adherence to contact screening needs to be addressed.
of serial smears (negative-negative [NN], negativepositive [NP], positive-negative [PN], positive-positive [PP]) during treatment follow-up of TB patients and the proportion of culture-negatives in each of these categories. STUDY POPULATION, DESIGN AND METHODSWe reviewed the records of new culture-confirmed smear-positive TB patients enrolled into four clinical trials conducted between January 2000 and July 2012 at the National Institute for Research in Tuberculosis (NIRT) in Chennai, India.The patients received the Category I 6-month rifampicin-containing intermittent regimen (2(EHRZ) 3 /4(HR) 3 *) and underwent monthly follow-up sputum examinations on three sputum specimens (two overnight specimens and one spot sample) at every visit.Sputum smear examination was performed using fluorescence microscopy and culture on Löwenstein-Jensen medium (modified Petroff's method).Smears were prepared directly from unprocessed sputum, stained with auramine rhodamine, read under fluorescence microscopy and graded as follows: <6 bacilli/high power field (HPF; 1+), 6-100 bacilli/HPF (2+), and >100 bacilli/HPF or large clumps (3+). 10We collected information on the results of sputum smear (with grading) and culture during treatment follow-up at months 1-6, including age, sex and human immunodeficiency virus (HIV) status.Data were double-entered and analysed using EpiData version 3.1 (EpiData Association, Odense, Denmark).As they were of better quality, we used the two overnight specimens for the primary analysis of the pattern of serial smear results.We also analysed other combinations of importance for the programme: a spot specimen with the first overnight specimen and then separately with the second overnight specimen.The subject was considered culture-negative only if all specimens tested were culture-negative (defined as lack of growth of tubercle bacilli after 3 months).The proportion of smear-positive, culture-negative samples was calculated for every month of follow-up.For the purposes of examining the relationship between smear grading and culture, the unit of analysis was the specimen rather than the patient.
National Institute for Research in Tuberculosis, India.To assess, among new culture-confirmed smear-positive pulmonary tuberculosis (TB) patients, the proportion of follow-up smear-positives that were culture-negative (S+C-) by month of follow-up examination, human immunodeficiency virus (HIV) status, pre-treatment drug susceptibility status and smear grading.We extracted follow-up smear (fluorescence microscopy) and culture (Löwenstein-Jensen) results of patients enrolled in clinical trials from January 2000 to August 2012 and treated with the WHO Category I regimen (2EHRZ3/4HR3).Of 520 patients, including 176 who were HIV-infected, respectively 199, 81, 47 and 43 were smear-positive at months 2, 4, 5 and 6; of these, respectively 138 (69%), 62 (75%), 32 (68%) and 27 (63%) were culture-negative. The S+C- phenomenon was more pronounced among '1+ positive' patients than in 2+ or 3+ positive patients and in 'pan-susceptible' patients than in those with any resistance, and did not vary by HIV status.Nearly two thirds of patients with follow-up smears positive at months 5 and 6 were culture-negative. Starting multidrug-resistant TB (MDR-TB) treatment empirically based on smear results, even in resource-limited settings, is incorrect and can have hazardous consequences. There is an urgent need to revisit the WHO recommendation concerning empirical MDR-TB treatment.
RATIONS trial is a field-based cluster-randomized trial of nutritional support to household contacts of adults with microbiologically-confirmed pulmonary tuberculosis (PTB) in Jharkhand, India aimed at reducing their TB incidence. The patient cohort in this trial was provided nutritional support, to assess its impact on TB-mortality and other outcomes.Methods: We enrolled 2800 patients across 28 tuberculosis units and provided food rations (1200 kcal, 52 gm proteins daily) and micronutrients. We recorded body mass index (BMI), diabetes status, and performance status with Eastern Cooperative Oncology Group (ECOG) scale (0-4; normal to bed-ridden). We recorded clinical, nutritional outcomes at six months, and determined the predictors of TB-mortality with Poisson and Cox regression using adjusted rate-ratios (aRR) and adjusted Hazard ratios (aHR).Results: At enrolment, 82% patients were underweight (BMI<18·5 kg/m2), 17% had a BMI<14 kg/m2. Mean weight and BMI were 42·6kg, 16·4 kg/m2 in men; and 36·1kg & 16·2 kg/m2 in women. At six months the outcomes included treatment success (94%), TB-mortality (3·9%), loss to follow up (1.0%), and treatment failure (<1%). The median weight gain was 4·6kg, but 55% patients remained underweight. At two months, 54% gained 5% of baseline weight. Baseline weight (aRR: 0·95, 95%CI 0·90–0·99), BMI (aRR: 0·88, 95%CI 0·76–1·01), poor performance status (ECOG categories 3-4) (aRR: 5·33, 95%CI 2·90—9.79), diabetes (aRR: 3·30, 95%CI:1·65–6·72), hemoglobin (aRR: 0·85, 95CI 0·71–1.00) were predictors of TB-mortality. There was 61% reduced hazard of death (aHR:0·39, 95%CI 0·18–0·86) associated with five percent weight gain at two months.Interpretation: Nutritional support in this cohort with high prevalence of severe undernutrition was associated with substantially decreased TB-mortality, improved adherence, treatment success, and weight gain compared to other programmatic cohorts in India. Nutritional support needs to be an integral component of patient-centred care to improve treatment outcomes in such settings.Trial Registration Details: Reducing Activation of Tuberculosis Through Improvement Of Nutritional Status (RATIONS) trial is an open-label, parallel-arm cluster-RCT involving household contacts (HHCs) of adult patients with microbiologically confirmed pulmonary tuberculosis (PTB) in Jharkhand state in eastern India registered with the Clinical Trials Registry of India (CTRI; CTRI/2019/08/020490).Funding Information: This work was supported by grants from the India Tuberculosis Research Consortium, Indian Council of Medical Research, New Delhi, India vide grant no 5/8/5/57/TB consortium/Call India Project/2017/ECD-1.Declaration of Interests: We declare no competing interests.Ethics Approval Statement: Ethics clearance was obtained from the Institutional Ethics Committee of the ICMR-NIRT (IEC number: 2018020). Local oversight was provided by the ethics committee of Ekjut, a non-profit organization involved in field-based research. Field staff obtained a written informed consent.
Globally efforts are underway to shorten the existing 6-month tuberculosis (TB) treatment regimen for drug-sensitive patients, which would be equally effective and safe. At present, there is a lack of evidence on the cost implications of a shorter 4-month TB regimen in India. This economic modeling study was conducted in the Indian context with a high TB burden. We used a hybrid economic model comprising of a decision tree and Markov analysis. The study estimated the incremental costs, life years (LYs), and quality-adjusted life years (QALYs) gained by the introduction of a Moxifloxacin-based shorter 4-month treatment regimen for pulmonary TB patients. The outcomes are expressed in incremental cost-effectiveness ratios (ICERs) per QALYs gained. The cost per case to be treated under the 4-month regimen was USD 145.94 whereas for the 6-month regimen it was USD 150.39. A shorter 4-month TB regimen was cost-saving with USD 4.62 per LY and USD 5.29 per QALY. One-way sensitivity analysis revealed that the cost of the drugs for the 4-month regimen, hospitalization cost for adverse drug reactions, and human resources incurred for the 6-month regimen had a higher influence on the ICER. The probability sensitivity analysis highlighted that the joint incremental cost and effectiveness using QALY were less costly and more effective for 67% of the iteration values. The cost-effectiveness acceptability curve highlights that the 4-month regimen was dominant to both patients and the National TB Elimination Programme in India as compared to the 6-month regimen at different cost-effectiveness threshold values.
Introduction India has the largest burden of cases and deaths related to tuberculosis (TB). Undernutrition is the leading risk factor accounting for TB incidence, while severe undernutrition is a common risk factor for mortality in patients with TB in India. The impact of nutritional supplementation on TB incidence is unknown, while few underpowered studies have assessed its impact on TB mortality. We designed an open-label, field-based cluster randomised trial to assess the impact of nutritional supplementation (with food rations) on TB incidence in a group at higher risk of TB infection and disease, viz household contacts (HHC) of patients with microbiologically confirmed pulmonary TB (PTB) in Jharkhand, a state with a high prevalence of undernutrition. Methods and analysis We shall enrol 2800 adult patients with PTB of the national TB programme, across 28 treatment units in 4 districts, and their approximately 11 200 eligible contacts. The sample size has 80% power to detect the primary outcome of 50% reduction in incidence of active TB in HHC over 2 years of follow-up. Patients and HHC in both the arms will undergo nutritional assessment and counselling. Patients will receive monthly food rations (supplying 1200 kcal and 52 g proteins/day) and multivitamins along with antitubercular treatment. The HHC in the intervention arm will receive food rations (supplying 750 kcal and 23 g proteins/day) and multivitamins while HHC in control arm will be on usual diet. The secondary outcomes in HHC will include effects on nutritional status, non-TB infections. Secondary outcomes in patients are effects on TB mortality, adherence, adverse effects, nutritional and performance status. Substudies will examine micronutrient status and effects on dietary intake, body composition, muscle strength and immune function. Ethics and dissemination The institutional ethics committee of ICMR-NIRT, Chennai, approved the study (289/NIRT-IEC/2018). The results will be disseminated in publications and presentations. Trial registration number Clinical Trial Registry of India: CTRI/2019/08/020490.
Malegaonkar et al. have raised concerns on two issues with reference to our paper entitled ‘4-month moxifloxacin containing regimens in the treatment of patients with sputum-positive pulmonary tuberculosis in South India – a randomised clinical trial’ in the letter ‘False equivalence of four month and six-month ATT regimen: A case of comparing apples and oranges’. They have flagged the use of an intermittent 6-month regimen as the control arm and questioned the rationality of using moxifloxacin in the treatment of drug-susceptible tuberculosis (TB). With reference to the first issue, the 6-month intermittent regimen was the standard of care in the Revised National TB Control Programme (RNTCP) throughout the recruitment phase of our clinical trial (May 2007 to October 2016). The change to the daily 6-month regimen was implemented in the RNTCP after study enrolment was completed. We have clearly and explicitly acknowledged this issue in our manuscript and have identified it as one of the limitations of the trial [1]. Also, having said that, a shorter 4-month regimen with all its inherent advantages with a high cure rate at end of treatment and a TB recurrence rate of less than 5% after 24 months of follow-up is a benchmark that most TB programme managers would accept, we believe. The concern about the need to preserve moxifloxacin for the treatment of drug-resistant TB is well taken. But we followed the philosophy that the best way to manage drug-resistant TB is to prevent it. And towards this goal, the search for a shorter treatment regimen has been a crucial research priority. Globally, there has been an interest in shorter regimens for drug-susceptible TB using the fluroquinolones for the last decade [2-4]. And recently a 4-month regimen of moxifloxacin and rifapentine was successful against drug-susceptible TB [5]. Moreover, we now have newer drugs in the TB treatment armamentarium and so need not be constrained with judicious use of the fluroquinolones in treating drug-susceptible TB. According to the National drug resistance survey, the majority (77%) of newly diagnosed TB patients are drug-sensitive and 2–3% of them are resistant to quinolones [6]. Hence, newly diagnosed TB patients would benefit from a regimen with quinolone. We reiterate that in spite of the limitations in our study the conclusions drawn within the scope of these limitations are valid and an important contribution to the quest for improving TB treatment and management.
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