Tuberculosis Patients In India Research Articles

Catastrophic costs for tuberculosis patients in India: Impact of methodological choices.

As financial risk protection is one of the goals towards universal health coverage, detailed information on costs, catastrophic costs and other economic consequences related to any disease are required for designing social protection measures. End Tuberculosis (TB) Strategy set a milestone of achieving zero catastrophic cost by 2020. However, a recent literature review noted that 7%-32% TB affected households in India faced catastrophic cost. Studies included in the review were small scale cross-sectional. We followed a cohort of 1482 notified drug-susceptible TB patients from four states in India: Assam, Maharashtra, Tamil Nadu, and West Bengal to provide a comprehensive picture of economic burden associated with TB treatment. Treatment cost was calculated using World Health Organization guidelines on TB patient cost survey and both human capital and output approaches of indirect cost (time, productivity, and income loss related to an episode) calculation were used to provide the range of households currently facing catastrophic cost. Depending on choice of indirect cost calculation method, 30%-61% study participants faced catastrophic cost. For over half of them, costs became catastrophic even before starting TB treatment as there was average 7-9 weeks delay from symptom onset to treatment initiation which was double the generally accepted delay of 4 weeks. During that period, they made average 8-11 visits to different providers and spent money on consultations, drugs, tests, and travel. Following the largest cohort of drug-susceptible TB patients till date, the study concluded that a significant proportion of study participants faced catastrophic cost and the proportion was much higher when income loss was considered as indirect cost calculation method. Therefore, ensuring uninterrupted livelihood during TB treatment is an absolute necessity. Another reason of high cost was the delay in diagnosis and costs incurred during pre-diagnosis period. This delay and consequently, economic burden, can be reduced by both supply side (intense private sector engagement, rapid diagnosis) and demand side (community engagement) initiatives. Reimbursement of expenses incurred before treatment initiation could be used as short-term measure for mitigating financial hardship.

Whole-genome sequencing of clinical isolates from tuberculosis patients in India: real-world data indicates a high proportion of pre-XDR cases.

The current study is based on real-world data on the TB drug-resistance profile by whole-genome sequencing of 600 clinical samples from patients with TB in India. This study indicates the clinicians' reasons for sending samples for WGS, which is for difficult-to-treat cases and/or relapse and treatment failure. The study reports a significant proportion of cases with pre-XDR-TB strains that warrant policy makers' attention. It reflects the current iterative nature of the diagnostic tests under programmatic conditions that leads to delays in appropriate diagnosis and empirical treatment. India had an estimated burden of 2.95 million TB cases in 2020 and 135,000 multidrug-resistant cases. However, WGS profiles of M.tb from India remains disproportionately poorly represented. This study adds a significant body of data on the mutation profiles seen in M.tb isolated from patients with TB in India, mutations outside the RRDR, disputed mutations, and resistance-conferring mutations to newer drugs such as bedaquiline and linezolid.

Landscaping tuberculosis multimorbidity: findings from a cross-sectional study in India

BackgroundMultimorbidity, the concurrent presence of two or more chronic conditions is an emerging public health challenge. Till date, most of the research have focused on the presence and interaction of selected co-morbidities in tuberculosis (TB). There exist a critical knowledge gap on the magnitude of multimorbidity among TB patients and its impact on health outcomes.MethodsWe undertook a cross-sectional study to assess the prevalence and patterns of multimorbidity among newly diagnosed TB patients in two states of India. A total of 323 patients were interviewed using a structured multimorbidity assessment questionnaire for primary care (MAQ-PC). MAQ-PC is already validated for Indian population and elicits 22 chronic conditions. We defined TB multimorbidity as the co-existence of TB with one or more chronic conditions and identified commonly occurring dyads (TB + single condition) and triads (TB + two conditions).ResultsMore than half (52%) of TB patients reported multimorbidity. Among dyads, depression, diabetes mellitus (DM), acid peptic disease (APD), hypertension, chronic alcoholism, arthritis and chronic back ache (CBA) were the most common co-occurring conditions while ‘DM + arthritis’, ‘depression + APD’, ‘depression + DM’ were the most commonly occurring triads among TB patients. Factors such as increasing age, low levels of education, alcohol abusers, drug-resistant TB and having health insurance were significantly associated with multimorbidity among TB patients.ConclusionsOur findings suggest high prevalence of multimorbidity among newly diagnosed TB patients in India. The presence of concordant and discordant conditions with TB may increase the health complexity, thus necessitating appropriate care protocols. Given, the current situation, wherein TB and non-communicable diseases (NCD) services are delivered through collaborative framework between programmes, there is a need for addressing multimorbidity at the healthcare delivery level.

Evaluation of a results-based financing nutrition intervention for tuberculosis patients in Madhya Pradesh, India, implemented during the COVID-19 pandemic

BackgroundReducing malnutrition through food supplementation is a critical component of the WHO End Tuberculosis (TB) strategy. A results-based financing (RBF) initiative in Madhya Pradesh, India—called Mukti—introduced an intensive nutrition intervention, including home visits, counseling, food basket distribution, and assistance in obtaining government benefits. Phase 1 of the program (Dhar District), implemented by ChildFund India (ChildFund) and funded by USAID, coincided with the COVID-19 lockdown in 2020. Under an RBF reimbursement scheme, ChildFund was paid based on treatment retention for 6 months and weight gain of 6 kg for adults.MethodsThe evaluation used a mixed methods approach. Qualitative components included interviews with key informants and focus groups with program participants. Quantitative components included an analysis of program data (i.e., patient demographics, receipt of program services, and weight gain). An impact analysis of retention in treatment used data from a government database. A difference-in-differences model was used to compare results from baseline data and the program period for Dhar District to similar data for the adjacent Jhabua District.ResultsThe program was well implemented and appreciated by patients and providers. Patients received an average of 10.2 home visits and 6.2 food baskets. While all age and sex groups gained weight significantly over their 6-month treatment period, there was no program impact on treatment retention. Seventy-six percent of patients achieved both outcome goals. And though average program costs were under budget, ChildFund experienced a loss in the results-based financing scheme, which was covered by USAID to continue program expansion.ConclusionsImplementing a nutrition supplementation and education program for TB patients in India is feasible. The intervention improved weight gain despite COVID-19-related lockdowns. The Mukti program did not impact treatment retention, which was already high at baseline. Program costs were modest, but the results-based financing reimbursement scheme resulted in a loss for the implementer. Overall, the RBF model led to an increased focus on outcomes for program staff and other stakeholders, which led to more efficient service delivery. Future research should examine total costs (including donated staff time) more extensively to determine the cost-effectiveness of Mukti and similar interventions.

Journey of the tuberculosis patients in India from onset of symptom till one-year post-treatment.

Historically, economic studies on tuberculosis estimated out-of-pocket expenses related to tuberculosis treatment and catastrophic cost, however, no study has yet been conducted to understand the post-treatment economic conditions of the tuberculosis patients in India. In this paper, we add to this body of knowledge by examining the experiences of the tuberculosis patients from the onset of symptoms till one-year post-treatment. 829 adult drug-susceptible tuberculosis patients from general population and from two high risk groups: urban slum dwellers and tea garden families were interviewed during February 2019 to February 2021 at their intensive and continuation phases of treatment and about one-year post-treatment using adapted World Health Organization tuberculosis patient cost survey instrument. Interviews covered socio-economic conditions, employment status, income, out-of-pocket expenses and time spent for outpatient visits, hospitalization, drug-pick up, medical follow-ups, additional food, coping strategies, treatment outcome, identification of post-treatment symptoms and treatment for post-treatment sequalae/recurrent cases. All costs were calculated in 2020 Indian rupee (INR) and converted into US dollar (US$) (1 US$ = INR 74.132). Total cost of tuberculosis treatment since the onset of symptom till one-year post-treatment ranged from US$359 (Standard Deviation (SD) 744) to US$413 (SD 500) of which 32%-44% of costs incurred in pre-treatment phase and 7% in post-treatment phase. 29%-43% study participants reported having outstanding loan with average amount ranged from US $103 to US$261 during the post-treatment period. 20%-28% participants borrowed during post-treatment period and 7%-16% sold/mortgaged personal belongings. Therefore, economic impact of tuberculosis persists way beyond treatment completion. Major reasons of continued hardship were costs associated with initial tuberculosis treatment, unemployment, and reduced income. Therefore, policy priorities to reduce treatment cost and to protect patients from the economic consequences of the disease by ensuring job security, additional food support, better management of direct benefit transfer and improving coverage through medical insurances need consideration.

Impact of COVID-19 restrictive measures on income and health service utilization of tuberculosis patients in India

BackgroundThe nationwide lockdown (March 25 to June 8, 2020) to curb the spread of coronavirus infection had significant health and economic impacts on the Indian economy. There is limited empirical evidence on how COVID-19 restrictive measures may impact the economic welfare of specific groups of patients, e.g., tuberculosis patients. We provide the first such evidence for India.MethodsA total of 291 tuberculosis patients from the general population and from a high-risk group, patients from tea garden areas, were interviewed at different time points to understand household income loss during the complete lockdown, three and eight months after the complete lockdown was lifted. Income loss was estimated by comparing net monthly household income during and after lockdown with prelockdown income. Tuberculosis service utilization patterns before and during the lockdown period also were examined. Household income loss, travel and other expenses related to tuberculosis drug pickup were presented in 2020 US dollars (1 US$ = INR 74.132).Results26% of households with tuberculosis patients in tea garden areas and 51% of households in the general population had zero monthly income during the complete lockdown months (April–May 2020). Overall income loss slowly recovered during July–August compared to April–May 2020. Approximately 7% of patients in the general population and 4% in tea garden areas discontinued their tuberculosis medicines because of the complete lockdown.ConclusionDiscontinuation of medicine will have an additional burden on the tuberculosis elimination program in terms of additional cases, including multidrug resistant tuberculosis cases. Income loss for households and poor restoration of income after the lockdown will likely have an impact on the nutrition of tuberculosis patients and families. Tuberculosis patients working in the informal sector were the worst affected group during the nationwide lockdown. This emphasizes that a policy priority must continue to protect those working in informal sectors from the economic consequences of such restrictive measures, including paid sick leave, additional food support, and direct benefit transfers. Alongside ensuring widespread access to COVID-19 vaccines, these policy actions remain pivotal in ensuring the well-being of those who are unfortunate enough to be living with tuberculosis.

Baseline IL-6 is a biomarker for unfavourable tuberculosis treatment outcomes: a multisite discovery and validation study.

BackgroundBiomarkers of unfavorable tuberculosis treatment outcomes are needed to accelerate new drug and regimen development. Whether plasma cytokine levels can predict unfavorable tuberculosis treatment outcomes is unclear.MethodsWe identified and internally validated the association between 20 a-priori selected plasma inflammatory markers and unfavorable treatment outcomes of failure, recurrence and all-cause mortality among adults with drug-sensitive pulmonary tuberculosis in India. We externally validated these findings in two independent cohorts of predominantly diabetic and HIV coinfected tuberculosis patients in India and South Africa, respectively.ResultsPre-treatment IFN-γ, IL-13 and IL-6 were associated with treatment failure in the discovery analysis. Internal validation confirmed higher pre-treatment IL-6 concentrations among failure cases compared to controls. External validation among predominantly diabetic tuberculosis patients found an association between pre-treatment IL-6 concentrations and subsequent recurrence and death. Similarly, external validation among predominantly HIV coinfected tuberculosis patients found an association between pre-treatment IL-6 concentrations and subsequent treatment failure and death. In a pooled analysis of 363 tuberculosis cases from the Indian and South African validation cohorts, high pre-treatment IL-6 concentrations were associated with higher risk of failure (adjusted odds ratio [aOR]=2.16, 95%CI 1.08-4.33, p=0.02), recurrence (aOR=5.36, 95%CI 2.48-11.57, p<0.001) and death (aOR=4.62, 95%CI 1.95-10.95, p<0.001). Adding baseline IL-6 to a risk-prediction model comprising of low BMI, high smear grade and cavitation improved model performance by 15 percent (C-statistic of 0.66 versus 0.76, p=0.02).ConclusionPre-treatment IL-6 is a biomarker for unfavorable tuberculosis treatment outcomes. Future studies should identify optimal IL-6 concentrations for point-of-care risk prediction.

Accuracy of Timika X-ray scoring system to predict the treatment outcomes among tuberculosis patients in India

BackgroundTimika scoring system is a radiographic grading tool, widely employed for grading the severity of tuberculosis (TB). We evaluated the predictive accuracy of this tool for adverse treatment outcomes among TB patients in Indian setting. MethodsWe undertook a longitudinal analysis of cohort data under the RePORT-India consortium. Cohort having participants with active pulmonary TB were included. CXRs were independently scored by chest physicians. Timika scoring system had a total score of 140. The predictive nature of the tool was assessed using the ROC analysis. ResultsAround 364 laboratory confirmed TB patients were enrolled. The mean (SD) of overall Timika score was 62.3 (24.9). Sputum conversion was achieved among 218/260 (83.8%) patients available at end of intensive phase. AUC for Timika score was 0.53 (95% CI: 0.43–0.63) and for percent lung affected, was 0.56 (95% CI: 0.46–0.65). Unfavorable treatment outcome was observed among 67/287 (23.3%) at the end of continuation phase. AUC for percent lung affected was 0.62 (95% CI: 0.54–0.70) and for Timika score was 0.59 (95% CI: 0.51–0.67). ConclusionBoth Timika scoring system and percent lung affected had poor predictive accuracy, highlighting the inability of a single CXR scoring system to predict the treatment outcome in Indian setting.

Implementation of the new integrated algorithm for diagnosis of drug-resistant tuberculosis in Karnataka State, India: How well are we doing?

As per national policy, all diagnosed tuberculosis patients in India are to be tested using Xpert® MTB/RIF assay at the district level to diagnose rifampicin resistance. Regardless of the result, samples are transported to the reference laboratories for further testing: first-line Line Probe Assay (FL-LPA) for rifampicin-sensitive samples and second-line LPA(SL-LPA) for rifampicin-resistant samples. Based on the results, samples undergo culture and phenotypic drug susceptibility testing. We assessed among patients diagnosed with tuberculosis at 13 selected Xpert laboratories of Karnataka state, India, i) the proportion whose samples reached the reference laboratories and among them, proportion who completed the diagnostic algorithm ii) factors associated with non-reaching and non-completion and iii) the delays involved. This was a cohort study involving review of programme records. For each TB patient diagnosed between 1st July and 31st August 2018 at the Xpert laboratory, we tracked the laboratory register at the linked reference laboratory until 30th September (censor date) using Nikshay ID (a unique patient identifier), phone number, name, age and sex. Of 1660 TB patients, 1208(73%) samples reached the reference laboratories and among those reached, 1124(93%) completed the algorithm. Of 1590 rifampicin-sensitive samples, 1170(74%) reached and 1104(94%) completed the algorithm. Of 64 rifampicin-resistant samples, only 35(55%) reached and 17(49%) completed the algorithm. Samples from rifampicin-resistant TB, extra-pulmonary TB and two districts were less likely to reach the reference laboratory. Non-completion was more likely among rifampicin-resistant TB and sputum-negative samples. The median time for conducting and reporting results of Xpert® MTB/RIF was one day, of FL-LPA 5 days and of SL-LPA16 days. These findings are encouraging given the complexity of the algorithm. High non-reaching and non-completion rates in rifampicin-resistant patients is a major concern. Future research should focus on understanding the reasons for the gaps identified using qualitative research methods.

Tuberculosis preventive treatment should be considered for all household contacts of pulmonary tuberculosis patients in India.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

Predicting the impact of patient and private provider behavior on diagnostic delay for pulmonary tuberculosis patients in India: A simulation modeling study.

BackgroundTuberculosis (TB) incidence in India continues to be high due, in large part, to long delays experienced by patients before successful diagnosis and treatment initiation, especially in the private sector. This diagnostic delay is driven by patients’ inclination to switch between different types of providers and providers’ inclination to delay ordering of accurate diagnostic tests relevant to TB. Our objective is to quantify the impact of changes in these behavioral characteristics of providers and patients on diagnostic delay experienced by pulmonary TB patients.Methods and findingsWe developed a discrete event simulation model of patients’ diagnostic pathways that captures key behavioral characteristics of providers (time to order a test) and patients (time to switch to another provider). We used an expectation-maximization algorithm to estimate the parameters underlying these behavioral characteristics, with quantitative data encoded from detailed interviews of 76 and 64 pulmonary TB patients in the 2 Indian cities of Mumbai and Patna, respectively, which were conducted between April and August 2014. We employed the estimated model to simulate different counterfactual scenarios of diagnostic pathways under altered behavioral characteristics of providers and patients to predict their potential impact on the diagnostic delay. Private healthcare providers including chemists were the first point of contact for the majority of TB patients in Mumbai (70%) and Patna (94%). In Mumbai, 45% of TB patients first approached less-than-fully-qualified providers (LTFQs), who take 28.71 days on average for diagnosis. About 61% of these patients switched to other providers without a diagnosis. Our model estimates that immediate testing for TB by LTFQs at the first visit (at the current level of diagnostic accuracy) could reduce the average diagnostic delay from 35.53 days (95% CI: 34.60, 36.46) to 18.72 days (95% CI: 18.01, 19.43). In Patna, 61% of TB patients first approached fully qualified providers (FQs), who take 9.74 days on average for diagnosis. Similarly, immediate testing by FQs at the first visit (at the current level of diagnostic accuracy) could reduce the average diagnostic delay from 23.39 days (95% CI: 22.77, 24.02) to 11.16 days (95% CI: 10.52, 11.81). Improving the diagnostic accuracy of providers per se, without reducing the time to testing, was not predicted to lead to any reduction in diagnostic delay. Our study was limited because of its restricted geographic scope, small sample size, and possible recall bias, which are typically associated with studies of patient pathways using patient interviews.ConclusionsIn this study, we found that encouraging private providers to order definitive TB diagnostic tests earlier during patient consultation may have substantial impact on reducing diagnostic delay in these urban Indian settings. These results should be combined with disease transmission models to predict the impact of changes in provider behavior on TB incidence.

Cost and operational impact of promoting upfront GeneXpert MTB/RIF test referrals for presumptive pediatric tuberculosis patients in India.

BackgroundOutreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities.MethodsXpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider’s perspective and expressed in 2015 USD.ResultsWeighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals.ConclusionsXpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions.

Tuberculin skin test and QuantiFERON-Gold In Tube assay for diagnosis of latent TB infection among household contacts of pulmonary TB patients in high TB burden setting.

BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ≥0.35 IU/ml and a positive TST as an induration of ≥5 mm. A secondary outcome of TST induration ≥10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15–40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Diabetes and pre-diabetes among household contacts of tuberculosis patients in India: is it time to screen them all?

Pre-diabetes mellitus (pre-DM) and DM increase the risk of developing tuberculosis (TB). Screening contacts of TB patients for pre-DM/DM and linking them to care may mitigate the risk of developing TB and improve DM management. To measure the prevalence of pre-DM/DM and associated factors among the adult household contacts (HHCs) of pulmonary TB patients. Between August 2014 and May 2017, adult HHCs of newly diagnosed adult PTB patients in Pune and Chennai, India, had single blood samples tested for glycosylated haemoglobin (HbA1c) at enrolment. DM was defined as previously diagnosed, self-reported DM or HbA1c 6.5%, and pre-DM as HbA1c between 5.7% and 6.4%. Latent tuberculous infection (LTBI) was defined as a positive tuberculin skin test (5 mm induration) or QuantiFERON® Gold In-Tube (0.35 international units/ml). Of 652 adult HHCs, 175 (27%) had pre-DM and 64 (10%) had DM. Forty (64%) HHCs were newly diagnosed with DM and 48 (75%) had poor glycaemic control (HbA1c 7.0%). Sixty-eight (22%) pre-DM cases were aged 18-34 years. Age 35 years, body mass index 25 kg/m2, chronic disease and current tobacco smoking were significantly associated with DM among HHCs. Adult HHCs of TB patients in India have a high prevalence of undiagnosed DM, pre-DM and LTBI, putting them at high risk for developing TB. Routine DM screening should be considered among all adult HHCs of TB.

Risk Factors Associated with Tuberculosis Infection Among Household Children Contacts of Sputum Smear Positive Tuberculosis Cases

Background: India has highest burden of tuberculosis (TB) globally. The source of infection for children is usually an adult in their household with active TB. Only few studies have been carried out among household children contacts of active TB patients in India to assess the risk factors of infection among children. Aim and Objective: To study the risk factors of TB infection among household children contacts of sputum positive patients. Material and Methods: We conducted study on 200 household children contacts (1-15 years) of sputum positive patients registered at DOTS centers in Lucknow district, Uttar Pradesh. Stratified sampling was done. A semi structured questionnaire was administered to collect the information. Infection in children was assessed by TST (Mantoux test). Results: TST positivity in children of TST positivity was associated with female index case (p=0.027), lower socioeconomic status (p=0.011), overcrowding (0.008) and duration of symptoms before treatment (p&lt;0.001). Among the factors of children, age &gt;6 years, duration of stay with index case &gt;10 hours/day and malnutrition were significantly associated. Conclusion: The study concludes that TB infection among children is significantly associated with various factors related to index case, susceptible host and environment, which can be intervened to prevent TB infection in children.

Prevalence of Multi-Drug Resistant Tuberculosis among Patients with HIV and Tuberculosis: The Indian Scenario

Introduction: Globally, India has the highest burden of tuberculosis (TB). In 2014, 2.2% of notified new cases and 15% of notified previously treated cases of pulmonary TB had multidrug resistant TB (MDR-TB). In addition, India has the second highest burden of people living with HIV and TB. However, there is paucity of data regarding the prevalence of multidrug resistant TB (MDR-TB) among HIV-positive TB patients in India. This study was undertaken to review the existing literature and assess the prevalence of MDR-TB among HIV-positive TB patients in the country. Methodology: A thorough PubMed and Google Scholar subject search was undertaken for studies conducted after the year 2000 that described the burden of MDR-TB in people living with HIV in India. The search-strategy used keywords, and was comprehensive with cross-checking of reference lists from the articles retrieved. Results: A total of 11 studies were collated that showed that the prevalence of MDR-TB among patients with HIV and TB varied widely between individual studies and ranged from 4.4% to 50%. Five studies showed that prevalence of MDR-TB among HIV-positive patients with primary TB ranged between 4.2%-11.4%. Among HIV-positive patients with pulmonary TB only, the MDR-TB prevalence ranged between 5.9% and 27.3%. In addition, prevalence of extensively drug-resistant TB (XDR-TB), ranged from 0% to 16.7% among HIV-positive TB patients. Conclusion: While the review showed no clear association between MDR-TB and HIV infection in India, there is a need for further research in this area. Scaling up of TB drug resistance testing facilities in the country will improve surveillance among people living with HIV and potentially provide programmatic trends on the burden of MDR-TB in HIV positive individuals in the future.

Counting Tuberculosis Patients in India: A Continued Imbroglio?

Counting Tuberculosis Patients in India: A Continued Imbroglio?

The Tuberculosis Cascade of Care in India’s Public Sector: A Systematic Review and Meta-analysis

BackgroundIndia has 23% of the global burden of active tuberculosis (TB) patients and 27% of the world’s “missing” patients, which includes those who may not have received effective TB care and could potentially spread TB to others. The “cascade of care” is a useful model for visualizing deficiencies in case detection and retention in care, in order to prioritize interventions.Methods and FindingsThe care cascade constructed in this paper focuses on the Revised National TB Control Programme (RNTCP), which treats about half of India’s TB patients. We define the TB cascade as including the following patient populations: total prevalent active TB patients in India, TB patients who reach and undergo evaluation at RNTCP diagnostic facilities, patients successfully diagnosed with TB, patients who start treatment, patients retained to treatment completion, and patients who achieve 1-y recurrence-free survival. We estimate each step of the cascade for 2013 using data from two World Health Organization (WHO) reports (2014–2015), one WHO dataset (2015), and three RNTCP reports (2014–2016). In addition, we conduct three targeted systematic reviews of the scientific literature to identify 39 unique articles published from 2000–2015 that provide additional data on five indicators that help estimate different steps of the TB cascade. We construct separate care cascades for the overall population of patients with active TB and for patients with specific forms of TB—including new smear-positive, new smear-negative, retreatment smear-positive, and multidrug-resistant (MDR) TB.The WHO estimated that there were 2,700,000 (95%CI: 1,800,000–3,800,000) prevalent TB patients in India in 2013. Of these patients, we estimate that 1,938,027 (72%) TB patients were evaluated at RNTCP facilities; 1,629,906 (60%) were successfully diagnosed; 1,417,838 (53%) got registered for treatment; 1,221,764 (45%) completed treatment; and 1,049,237 (95%CI: 1,008,775–1,083,243), or 39%, of 2,700,000 TB patients achieved the optimal outcome of 1-y recurrence-free survival.The separate cascades for different forms of TB highlight different patterns of patient attrition. Pretreatment loss to follow-up of diagnosed patients and post-treatment TB recurrence were major points of attrition in the new smear-positive TB cascade. In the new smear-negative and MDR TB cascades, a substantial proportion of patients who were evaluated at RNTCP diagnostic facilities were not successfully diagnosed. Retreatment smear-positive and MDR TB patients had poorer treatment outcomes than the general TB population. Limitations of our analysis include the lack of available data on the cascade of care in the private sector and substantial uncertainty regarding the 1-y period prevalence of TB in India.ConclusionsIncreasing case detection is critical to improving outcomes in India’s TB cascade of care, especially for smear-negative and MDR TB patients. For new smear-positive patients, pretreatment loss to follow-up and post-treatment TB recurrence are considerable points of attrition that may contribute to ongoing TB transmission. Future multisite studies providing more accurate information on key steps in the public sector TB cascade and extension of this analysis to private sector patients may help to better target interventions and resources for TB control in India.

Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult tuberculosis patients in India

Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult tuberculosis patients in India

Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult tuberculosis patients in India.

To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics. Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction. RMP peak concentration (Cmax) was sub-therapeutic (<8 μg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB patients with diabetes mellitus than in non-diabetics. Significant associations were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug doses; RMP with category of treatment; INH with smoking, body mass index and N-acetyl transferase 2 genotype; and PZA with sex and smoking. Several risk factors for drug concentration variations were identified. Two-hour post-dosing drug concentrations mimicked Cmax. A high proportion of TB patients had RMP Cmax below the expected range, which is a matter of concern.