Project description:Extrapulmonary drug-resistant tuberculosis (DR-EPTB) poses a formidable diagnostic and therapeutic challenge.Besides associated with high morbidity, it is a major financial burden for the patient and the health system. In spite of this, it has often been neglected as it does not "pose" a visible public health threat. We study clinical profiles, treatment outcomes, and factors associated with unfavourable outcomes among DR-EPTB patients under programmatic settings in New Delhi, India, and evaluate how this could impact TB elimination. A retrospective analysis of all DR-EPTB patients registered at three nodal DR-TB centres in Delhi in 2016 was carried out. Of the 1261 DR-TB patients registered, 203 (16%) were DR-EPTB, with lymph nodes (118, 58%) being the most common site, followed by bone (69, 34%). Nearly 29% (n = 58) experienced adverse drug reactions with severe vomiting (26, 13 %), joint pain (21, 10%) and behavioral disorder (15, 7%). History of previous TB treatment was observed in a majority of the cases (87.7%). Nearly one-third of DR-EPTB cases (33%) had unfavourable treatment outcomes, with loss-to-follow-up (n = 40, 58%) or death (n = 14, 20%) being the most common unfavourable outcomes. In the adjusted analysis, weight band 31-50 kilograms (aRR = 1.8, 1.2-3.4) and h/o previous TB (aRR = 2.1, 1.1-4.8) were mainly associated with unfavourable outcomes. TB elimination efforts need to focus on all forms of TB, including DR-EPTB, leaving no one behind, in order to realise the dream of ending TB.
Project description:Background and objectiveWe evaluated the DR-TB component of the National Tuberculosis Elimination Program (NTEP) in a high-burden district in Kerala to identify the programmatic gaps, if any, in screening, diagnosis, treatment, and follow-up of notified DR-TB patients.MethodsA mixed-methods design was used, and the evaluation was performed in two steps. In the first step, we reviewed the program documents and conducted stakeholder interviews to develop a detailed description of the program design and developed a logical framework to evaluate program performance. Consequently, in the next step, we conducted programmatic data reviews, facility surveys, and in-depth interviews with key stakeholders to identify the programmatic gaps in implementation, guided by the logic framework.ResultsOf the 494 microbiologically confirmed TB patients during 2021-22, 342 (69%) were tested for drug sensitivity, and 30 DR-TB patients were identified. There was no separate district DR-TB treatment center with airborne infection control facilities, and only 16% (66/422) of the various categories of staff were trained in recent guidelines. Only 30% (9/30) of DR-TB patients were provided with any psychological assessment. The favorable treatment outcome was 80% Interviews revealed poor readiness and motivation from the private sector for screening, contextual barriers in human resource availability, transportation, and financial barriers to the beneficiary despite providing financial benefits.ConclusionPrioritizing the establishment of a district DR-TB treatment center and sputum transport mechanism, posting a clinical psychologist dedicated to counseling patients on therapy, and training all categories of staff on DR-TB management guidelines will significantly contribute to improving program outcomes.
Project description:BackgroundPre-diagnosis attrition needs to be addressed urgently if we are to make progress in improving MDR-TB case detection and achieve universal access to MDR-TB care. We report the pre-diagnosis attrition, along with factors associated, and turnaround times related to the diagnostic pathway among patient with presumptive MDR-TB in Bhopal district, central India (2014).MethodsStudy was conducted under the Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all registered TB cases in Bhopal district that met the presumptive MDR-TB criteria (eligible for DST) in 2014. In quarter 1, Line Probe Assay (LPA) was used if sample was smear/culture positive. Quarter 2 onwards, LPA and Cartridge-based Nucleic Acid Amplification Test (CbNAAT) was used for smear positive and smear negative samples respectively. Pre-diagnosis attrition was defined as failure to undergo DST among patients with presumptive MDR-TB (as defined by the programme).ResultsOf 770 patients eligible for DST, 311 underwent DST and 20 patients were diagnosed as having MDR-TB. Pre-diagnosis attrition was 60% (459/770). Among those with pre-diagnosis attrition, 91% (417/459) were not identified as 'presumptive MDR-TB' by the programme. TAT [median (IQR)] to undergo DST after eligibility was 4 (0, 10) days. Attrition was more than 40% across all subgroups. Age more than 64 years; those from a medical college; those eligible in quarter 1; patients with presumptive criteria 'previously treated - recurrent TB', 'treatment after loss-to-follow-up' and 'previously treated-others'; and patients with extra-pulmonary TB were independent risk factors for not undergoing DST.ConclusionHigh pre-diagnosis attrition was contributed by failure to identify and refer patients. Attrition reduced modestly with time and one factor that might have contributed to this was introduction of CbNAAT in quarter 2 of 2014. General health system strengthening which includes improvement in identification/referral and patient tracking with focus on those with higher risk for not undergoing DST is urgently required.
Project description:BackgroundDiagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India.MethodsThe study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm.Results4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment.ConclusionUpfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to present-day challenges in the diagnosis of PTB in pediatric patients.
Project description:IntroductionMultidrug-resistant Tuberculosis (MDR TB) is emerging public health concern globally. Lost to follow-up (LTFU) is one of the key challenge in MDRTB treatment. In 2013, 18% of MDR TB patients were reported LTFU in India. A qualitative study was conducted to obtain better understanding of both patient and provider related factors for LTFU among MDR TB treatment.MethodsQualitative semi-structured personal interviews were conducted with 20 MDRTB patients reported as LTFU and 10 treatment providers in seven districts linked to Nagpur Drug resistant TB Centre (DRTBC) during August 2012-February 2013. Interviews were transcribed and inductive content analysis was performed to derive emergent themes.ResultsWe found multiple factors influencing MDR TB treatment adherence. Barriers to treatment adherence included drug side effects, a perceived lack of provider support, patient financial constraints, conflicts with the timing of treatment services, alcoholism and social stigma.ConclusionsPatient adherence to treatment is multi-factorial and involves individual patient factors, provider factors, and community factors. Addressing issue of LTFU during MDRTB treatment requires enhanced efforts towards resolving medical problems like adverse drug effects, developing short duration treatment regimens, reducing pill burden, motivational counselling, flexible timings for DOT services, social, family support for patients & improving awareness about disease.
Project description:BackgroundEven though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory.Methods & findings2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples).ConclusionsMODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest.
Project description:Identifying and reducing TB-related costs is necessary for achieving the End TB Strategy's goal that no family is burdened with catastrophic costs. This study explores costs during the pre-diagnosis period and assesses the potential for using coping costs as a proxy indicator for catastrophic costs when comprehensive surveys are not feasible. Detailed interviews about TB-related costs and productivity losses were conducted with 196 pulmonary TB patients in Kampala, Uganda. The threshold for catastrophic costs was defined as 20% of household income. Multivariable regression analyses were used to assess the influence of patient characteristics on economic burden, and the positive predictive value (PPV) of coping costs was estimated. Over 40% of patients experienced catastrophic costs, with average (median) pre-diagnosis costs making up 30.6% (14.1%) of household income. Low-income status (AOR = 2.91, 95% CI = 1.29, 6.72), hospitalisation (AOR = 8.66, 95% CI = 2.60; 39.54), and coping costs (AOR = 3.84, 95% CI = 1.81; 8.40) were significantly associated with the experience of catastrophic costs. The PPV of coping costs as an indicator for catastrophic costs was estimated to be 73% (95% CI = 58%, 84%). TB patients endure a substantial economic burden during the pre-diagnosis period, and identifying households that experience coping costs may be a useful proxy measure for identifying catastrophic costs.
Project description:BackgroundTuberculosis (TB) poses a significant social and economic burden to households of persons with TB (PwTB). Despite free diagnosis and care under the National TB Elimination Programme (NTEP), individuals often experience significant out-of-pocket expenditure and lost productivity, causing financial catastrophe. We estimated the costs incurred by the PwTB during TB care and identified the factors associated with the costs.MethodsIn our cross-sectional study, we used multi-stage sampling to select PwTB notified under the NTEP, whose treatment outcome was declared between May 2022 and February 2023. Total patient costs were measured through direct medical, non-medical and indirect costs. Catastrophic costs were defined as expenditure on TB care > 20% of the annual household income. We determined the factors influencing the total cost of TB care using median regression. We plotted concentration curves to depict the equity in distribution of catastrophic costs across income quintiles. We used a cluster-adjusted, generalized model to determine the factors associated with catastrophic costs.ResultsThe mean (SD) age of the 1407 PwTB interviewed was 40.8 (16.8) years. Among them, 865 (61.5%) were male, and 786 (55.9%) were economically active. Thirty-four (2.4%) had Drug Resistant TB (DRTB), and 258 (18.3%) had been hospitalized for TB. The median (Interquartile range [IQR] and 95% confidence interval [CI]) of total costs of TB care was US$386.1 (130.8, 876.9). Direct costs accounted for 34% of the total costs, with a median of US$78.4 (43.3, 153.6), while indirect costs had a median of US$279.8 (18.9,699.4). PwTB < 60 years of age (US$446.1; 370.4, 521.8), without health insurance (US$464.2; 386.7, 541.6), and those hospitalized(US$900.4; 700.2, 1100.6) for TB experienced higher median costs. Catastrophic costs, experienced by 45% of PwTB, followed a pro-poor distribution. Hospitalized PwTB (adjusted prevalence ratio [aPR] = 1.9; 1.6, 2.2) and those notified from the private sector (aPR = 1.4; 1.1, 1.8) were more likely to incur catastrophic costs.ConclusionsPwTB in India incur high costs mainly due to lost productivity and hospitalization. Nearly half of them experience catastrophic costs, especially those from poorer economic quintiles. Enabling early notification of TB, expanding the coverage of health insurance schemes to include PwTB, and implementing TB sensitive strategies to address social determinants of TB may significantly reduce catastrophic costs incurred by PwTB.
Project description:The struggle against tuberculosis (TB) is still far from over. TB, caused by Mycobacterium tuberculosis, is one of the deadliest infections worldwide. Co-infection with human immunodeficiency virus (HIV) and the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains have further increased the burden for this disease. Herein, we report the discovery of 2-(4-chlorobenzyl)-3-methyl-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitrile as an effective antitubercular agent and the structural modifications of this molecule that have led to analogues with improved potency and lower toxicity. A number of these derivatives were also active at sub-micromolar concentrations against resistant TB strains and devoid of apparent toxicity to Vero cells, thereby underscoring their value as novel scaffolds for the development of new anti-TB drugs.