Programmatic Management Of Drug-resistant Tuberculosis Research Articles

Progress in programmatic management of drug-resistant TB, WHO Eastern Mediterranean Region, 2018-2023

<sec><title>BACKGROUND</title>Since 2012, WHO has supported countries in scaling up programmatic management of drug-resistant tuberculosis (PMDT). We assessed progress and challenges to formulate recommendations for improvement.</sec><sec><title>METHODS</title>We reviewed the regional Green Light Committee (rGLC)mission reports and analysed data to describe the progression of programme indicators.</sec><sec><title>RESULTS</title>The proportion of TB patients initially tested using Xpert MTB/RIF rose from 5% in 2017 to 54% in 2022. Testing for rifampicin-resistant TB (RR-TB) increased from 4% in 2015 to 68% in 2022 among new patients and from 17% in 2015 to 94% in 2022 among those previously treated. Consequently, in 2021–2022, the number of multidrug-resistant (MDR)/RR-TB patients diagnosed increased by 29% and 84% of them were treated, accounting for 22% of estimated cases. By 2023, fourteen countries had implemented all-oral regimens, with three initiating the 6-month bedaquiline, pretomanid, linezolid, and moxifloxacin regimen (BPaL(M)). MDR/RR-TB treatment success increased from 64% in 2017 to 73% in 2020.</sec><sec><title>CONCLUSIONS</title>Eastern Mediterranean Region countries progressed in PMDT using Xpert MTB/RIF, increased diagnosis and treatment of MDR/RR-TB patients using all-oral regimens, and improved treatment success. They must now enhance diagnostic capacity using WHO-recommended diagnostics, decentralise services while integrating them into primary health care, and prioritise the BPaL(M) regimen.</sec>

Comparison of short term and long term multidrug resistant tuberculosis treatment outcomes in tertiary care settings

IntroductionTuberculosis is a contagious and communicable disease while drug resistant tuberculosis is difficult to treat and requires long duration. Various strategies are focused to treat the drug resistant tuberculosis focusing lesser side effects and shorter duration of treatment. ObjectiveTo compare treatment outcomes between short-term and long-term regimens among patients registered at a tertiary care hospital's Programmatic Management of Drug-Resistant TB (PMDT) site in Pakistan. MethodsA comparative prospective cohort study was conducted at IMBB, The University of Lahore, in collaboration with the Health Research Institute (HRI) TB Research Centre at King Edward Medical University/Mayo Hospital, Lahore. The study included a sample size of 136 patients, with 68 patients in each treatment regimen (long-term and short-term). Adult pulmonary MDR TB patients seeking treatment from the facility were included based on predefined criteria. Data was collected using a pre-designed questionnaire after obtaining ethical approval and informed consent. The rates of patients' cure, treatment completed, treatment failure and death were calculated. ResultsA total of 131 patients were successfully followed up and included in the final analysis. Of these, 66 patients were in the long-term treatment group and 65 patients were in the short-term treatment group. The cure rate was 74.8 %, with 98 patients successfully cured, and 13.8 % of patients completed their treatment successfully. In the long-term treatment group, the cure rate was 75.6 %, with a treatment failure rate of 6.2 %. In the short-term treatment group, the cure rate was 73.8 %, with a treatment failure rate of 6.1 %. The death rate was 4.5 % in the short-term treatment group and 6.2 % in the long-term treatment group. However, these differences in treatment outcomes were statistically insignificant (p-values > 0.05). The newer drugs, bedaquiline and delamanid, did not show significant improvements in the treatment of multidrug-resistant TB patients. Side effects at completion of treatment remained to be significantly lesser (p < 0.05) among short term treatment group as compared to long term treatment group. ConclusionThe findings suggest that short-term treatment regimens are equally effective as long-term treatment regimens, with the added benefit of presenting fewer side effects.

A Comprehensive Review on Long vs. Short Regimens in Multidrug-Resistant Tuberculosis (MDR-TB) Under Programmatic Management of Drug-Resistant Tuberculosis (PMDT).

This comprehensive review delves into the intricate landscape of multidrug-resistant tuberculosis (MDR-TB) treatment within the programmatic management of drug-resistant tuberculosis (PMDT) framework. MDR-TB poses a substantial global health threat, necessitating targeted approaches for effective management. The analysis explores the historical evolution, efficacy, safety profiles, and implementation challenges associated with long and short regimens. The findings underscore the importance of individualized clinical practices, considering patient-specific factors, and the need for ongoing monitoring within PMDT programs. Recommendations advocate for integrating advanced diagnostics, continuous surveillance, and training for healthcare professionals. The review concludes with a nuanced outlook on long versus short regimens, emphasizing a balanced approach and the imperative role of collaborative efforts in shaping the future of MDR-TB treatment. This synthesis contributes to the ongoing discourse, providing valuable insights for healthcare practitioners, policymakers, and researchers working towardoptimizing outcomes for individuals afflicted with MDR-TB.

Sputum Culture Conversion among Patients with Drug-Resistant Tuberculosis: A Study of Various Predictors

Introduction: Conversion of a positive sputum culture to a negative culture is an important parameter in the management of drug-resistant tuberculosis (TB), as the failure to convert was related to dismal posttreatment outcomes and elevated mortality rates by almost eight times when compared to victims of multidrug-resistant TB (MDR-TB) who did so. In the patients of MDR-TB, it is an important sign of treatment success to have sputum culture converted from positive to negative, and helps in determining the duration of treatment. The goal of this study was to examine and compare the length of time it took to convert an initial sputum culture with predictors of treatment outcomes for patients with MDR-TB, as well as to pinpoint the variables that affected the length of time. Materials and Methods: The mixed method (records review and qualitative approach) was used to understand the patient’s perspective for accepting the Programmatic Management of Drug-resistant TB (PMDT) services and the provider’s perspective for rendering services in a public-private mix model setup. This study was undertaken as a retrospective analysis and studied the patients drug-resistant TB who were admitted to a tertiary care hospital in central India. This study was carried out on the patients of Rifampicin-Resistant TB (RR-TB) and MDR-TB (Resistant to both INH and Rifampicin) with positive baseline culture, pretreatment evaluation, and appropriate anti-MDR-TB treatment. As per the PMDT guidelines, sputum smear and culture reports were collected and analyzed. Results: In this study, the time and predictors to convert an initial positive sputum culture to negative and factors influencing treatment outcome were evaluated, compared, and identified. A total of 163 patients were evaluated and analyzed. Of these, 111 (68.09%) were rifampicin and INH-resistant (MDR-TB), whereas 52 (31.90%) were rifampicin resistant (RR-TB) only. Overall 68 (41.71%) patients with baseline positive culture were converted within 3 months. Conclusions: It was concluded that malnourishment, human immunodeficiency virus positivity, associated extra pulmonary TB, and bilateral cavitation were found to be significant predictors of longer time of sputum culture conversion and thereby treatment outcome.

Adverse drug reactions due to linezolid in the programmatic management of drug-resistant tuberculosis in India: A retrospective multicenter study

BackgroundMonitoring and managing adverse drug reactions (ADR) are critical for treating drug-resistant tuberculosis (TB). ObjectiveTo study symptomatic, linezolid-attributable ADRs in TB patients initiated on all oral longer bedaquiline-based treatment regime for multidrug-resistant/rifampicin-resistant (MDR/RR)-TB under programmatic conditions. MethodsIt was a multicenter, retrospective study of people with MDR/RR-TB in nine TB units in Nagpur, India, from March 2020 to April 2022. ResultsThe study consisted of a sample size of 106 individuals with multidrug-resistant and rifampicin-resistant tuberculosis out of a total of 110 individuals with the disease. Of these, 45 (42.45%) experienced linezolid ADRs, with an incidence of 11.37 cases per 1000 person-weeks. These patients were significantly younger (31.24 ± 11.13 years) and more likely to be female (27, 50%) than those without ADRs. ADR severity was mild in 20 (44.45%), moderate in 15 (33.33%), and severe in 10 (22.22%) patients. The most common ADR was peripheral neuropathy (42, 93.33%), followed by lactic acidosis (3, 6.67%), anemia (2, 4.44%), and optic neuritis (2, 4.44%). Dosing was reduced in 17 (37.78%) patients, and linezolid was withdrawn entirely in 19 (42.22%) patients. Only 9 (20%) patients continued linezolid unmodified. For mild to moderate linezolid-associated symptomatic peripheral neuropathy, symptom management with or without dose reduction is an effective strategy; however, immediate linezolid withdrawal is necessary in severe or life-threatening peripheral neuropathy cases. After a mean follow-up of 41 ± 21.33 weeks, ADR symptoms resolved completely in 4 (6.67%) patients and decreased in 42 (93.33%) patients. ConclusionLinezolid ADRs, often neuropathy, frequently occur in patients on an all-oral bedaquiline-based treatment regime for MDR/RR-TB. Women and younger patients are more likely to experience these ADRs, usually mild to moderate in severity. Management of symptomatic linezolid-associated peripheral neuropathy should be based on ADR severity. These ADRs often affect linezolid dosing, so it is important to identify and manage them early.

Prevalence of pre-extensively drug-resistant tuberculosis (Pre XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) among extra pulmonary (EP) multidrug resistant tuberculosis (MDR-TB) at a tertiary care center in Mumbai in pre Bedaquiline (BDQ) era.

Drug-resistant tuberculosis (DR-TB) is the most exigent and calamitous challenge encountered in treatment of TB. Extra pulmonary (EP) DR-TB poses a complex diagnostic and therapeutic challenge owing to myriad of presentations and paucibacillary nature. Data available on this subset is limited. We studied the prevalence of EPDR-TB cases among the total DR-TB cases visiting our Programmatic management of Drug-Resistant TB (PMDT) site. We also studied the demographic and microbiological profile of these cases and analyzed the prevalence of pre-extensively drug-resistant TB (pre XDR-TB) and extensively drug-resistant TB (XDR-TB) among patients of EPDR-TB in pre Bdq era. Of the 1086 DR-TB patients, 64 (5.89%) were cases of EPDR-TB. Seven out of 64 (10.93%) were primary EPDR-TB. The site wise distribution of cases was 34 (53.125%) lymph node DR-TB, 18 (28.125%) pleural DR-TB, 9 (14.0625%) spinal DR-TB/paraspinal abscess/psoas abscess, 1 case (1.5625%) each of abdominal DR-TB, sternal and gluteal abscess. On the basis of the second-line drug susceptibility testing (DST), patients were grouped into: (1) multidrug-resistant TB (MDR-TB), (2) MDR-TB with fluoroquinolone (FQ) resistance {pre XDR XDR-TB (FQ)}, (3) MDR-TB with second-line injectable (SLI) resistance {pre XDR XDR-TB (SLI)}, (4) XDR-TB. Of the 64 patients, 43 (67.185%) had MDR-TB, 19 (29.687%) had preXDR-TB (FQ), none had preXDR-TB (SLI) and 2 (3.125%) had XDR-TB. Gastro esophageal reflux disease (GERD) was the most common comorbidity seen in 26 (40.6%) patients, followed by anemia in 5 (7.8%), psychiatry problems 5 (7.8%), hypertension in 3 (4.6%), renal disorders in 2 (3.1%) while thyroid disorder, HIV and thalassemia in 1 each (1.5%). EPDR-TB forms a small but significant proportion of total DR-TB. Lymph node DR-TB is its most common subclass. Our study emphasises the momentousness and essentiality of baseline DST to FQ and SLI in patients of DR-TB. This enables an appropriate modification of therapy at baseline itself to better the treatment outcomes. We observed a strikingly high proportion of preXDR-TB (FQ) in our study group.

Whole-genome sequencing of presumptive MDR-TB isolates from a tertiary healthcare setting in Mumbai

Whole-genome sequencing (WGS) of Mycobacterium tuberculosis (MTB), proven to be a better alternative when compared with the combined sensitivity and specificity of all other modalities for diagnosis of tuberculosis (TB), aids epidemiological surveillance investigations by combining the current research with diagnostics.This study was conducted to identify and resolve operational challenges in performing WGS-based drug resistance testing (DRT) for MTB in a TB culture and drug susceptibility testing (DST) laboratory. Three critical, non-redundant steps for WGS-based DRT were tested: viz. DNA extraction, high-throughput paired-end next-generation sequencing (NGS), and genomic analysis pipeline for automated reporting of WGS-based DRT. DNA was extracted from 100 liquid culture isolates on a mycobacterial growth indicator tube (MGIT) using DNEASY Ultraclean Microbial Kit (Qiagen, USA) as per the manufacturer's instructions. Illumina paired-end sequencing was performed. All analysis steps were automated using custom python scripts, requiring no intervention. Variant calling was performed as per the World Health Organization (WHO) technical guide. The number of cultures resistant to rifampicin, isoniazid, pyrazinamide, ethambutol, and streptomycin was 89, 88, 35, 67, and 73, respectively. Resistance to amikacin, kanamycin, and capreomycin was found in 15, 17, and 15 cultures, respectively. Seventy cultures were resistant to fluoroquinolones, four were resistant to ethionamide, and 12 were resistant to linezolid. Six cultures were resistant to only one of the 18 drugs tested. Seventy-five cultures were resistant to more than three anti-TB drugs. One culture was resistant to 13 of the 18 anti-TB drugs tested for this study. The maximum number of variants were observed in the rpoB gene (n=93, 93%), wherein the Ser450Leu was the predominant mutation (n=68, 73%). Ser315Thr was the most common variant (n=86, 97%) that encoded resistance to isoniazid. The Lys43Arg variant encodes resistance to streptomycin and was the third most predominant variant (n=65, 89%). In addition to the high levels of resistance observed in the dataset, we also observed a high proportion of Beijing strains (n=63, 63%). Compared with results from routine diagnostics based on the 'Guidelines on Programmatic Management of Drug-Resistant TB (PMDT) in India', none of the samples had DST available for all 18 drugs. This represents a gap in PMDT guidelines. The WGS-DRT must be considered as the primary DST method after a sample is flagged rifampicin-resistant by cartridge-based nucleic acid amplification testing (CBNAAT).With several research studies currently underway globally to identify novel variants associated with drug resistance and classifiy their minimum inhibitory coefficients, WGS-DRT presents a scalable technology that updates analytical pipelines, relegating the need for changing microbiological protocols.

Optimizing outcomes for drug resistant tuberculosis patients through provision of a comprehensive care package

Background: The paper presents the salient features of a comprehensive treatment package for drug resistant tuberculosis (DR-TB), its adaptation and implementation in two indoor care hospital settings in Pakistan, and lessons learned from this implementation. Methods: A pilot study was undertaken on a group of 100 patients at two Programmatic Management of Drug-Resistant TB (PMDT) sites. Fifty patients each were selected from the Samli Sanatorium Murree and the Lady Reading Hospital, Peshawar by the National Tuberculosis Control authorities, and delivered a comprehensive package of services, including psychosocial and food support. Data were collected using standard TB tools and surveillance indicators. The results were compared between intervention and a historical cohort of DR-TB patients. Results: Among the total 100 patients, the treatment success rate was 88%, the failure rate was 4%, while there were 7% deaths. A patient was transferred out while none were lost to follow-up, indicating much improvement over the historical cohort. Patients ranked the economic support, free medicines and nutritional support as most helpful, while majority of providers found the intervention sustainable. Conclusion: A comprehensive package including the psychosocial support can be crucial in enhancing DR-TB outcomes. Regular interaction with patients and improved nutrition leads to improved treatment adherence, while capacity building of psychologists and home visits can further benefit the DR-TB patients leading to their cure.

Supporting tuberculosis program in active contact tracing: a case study from Pakistan

Tuberculosis (TB) is on the rise in Pakistan and there could be multiple reasons including poverty, difficulty in access to TB treatment services, non-compliance with treatment, social stigma etc. According to the TB program managers, limited treatment and testing sites for tuberculosis and lack of trained human resources play a major role in compromising TB management. A major lacuna in the TB control program is the absence of active contact tracing strategy. This is essential for a disease where positive cases are known to be able to infect a further 10‒15 individuals in a year. Tackling tuberculosis in Pakistan has been beleaguered by funding challenges and other systems’ bottlenecks such as lack of skilled human resources and insufficient supply of medicines, despite the fact that disease burden is one of the highest in the world. Although it is a notifiable disease, active case finding, contact tracing and reporting is notoriously low throughout the country. Access to diagnostics and treatment facilities has been limited and stigma attached to the disease remains deeply entrenched among the communities. Researchers have shown that enhanced and active approaches to contact investigation effectively identifies additional patients with TB among household contacts at a relatively modest cost. USAID’s Integrated Health Systems Strengthening and Service Delivery Activity extended support to the Health Departments of Sindh and Khyber Pakhtunkhwa provinces. In collaboration with the two provincial TB programs, community based active contact tracing was conducted on 17,696 individuals, based on the index cases. Among the contacts traced, 243 cases were diagnosed as drug sensitive or drug resistant TB. Awareness sessions were conducted to sensitize people on the various aspects of disease and importance of getting tested. The project also supported establishing three satellite Programmatic Management of Drug Resistant Tuberculosis (PMDT) sites for drug resistant TB treatment, enhancing the programs’ diagnostic and testing capacity.

Treatment Outcomes of the Standardized Shorter MDR-TB Regimen Under Programmatic Setting: A Retrospective Study from a Tertiary Care Centre, India

Background: The shorter regimen was widely accepted and advocated for MDR-TB treatment compared tothe conventional longer regimen. Evaluating the performance of both regimens in a programmatic setting will help in tailoring the treatment regimen of MDR-TB. Objectives: To estimate the duration of sputum smear conversion in the shorter MDR-TB regimen. 2. To compare the treatment outcomes of the shorter MDR-TB regimen with that of the longer conventional MDR regimen in a programmatic set up in India. 3. To estimate the adverse drug reactions in the shorter MDR-TB regimen. Methods: A retrospective cross-sectional study was conducted on 320 patients enrolled under programmatic management of drug resistant tuberculosis (PMDT) from April 2017 to May 2019 at a nodal DRTB center and a tertiary care hospital in India. Demographic and clinical characteristics of those who received a shorter MDR-TB regimen were recorded. Treatment outcomes of both regimens were recorded. Treatment success is defined as ‘disease cured and treatment completed’, whereas treatment failure was considered when the treatment was either terminated or changed due to lack of bacteriological conversion at the end of an extended intensive phase or culture reversion in the continuation phase. Results: The treatment success observed in the shorter MDR-TB regimen was 61.25%, which was significantly higher than the conventional longer regimen (p=0.0007). Treatment failures were higher with a shorter MDR-TB regimen (p=0.0001). Conclusion: Treatment success with the shorter MDR-TB regimen though higher than the conventional regimen, is still way behind the target treatment success rate. Improving treatment adherence remains pivotal for achieving end TB targets.

Effectiveness and Safety of 9-Month Treatment Regimen for Multidrug-Resistant Tuberculosis in the Philippines

Background: The Philippines has a burden of drug-resistant tuberculosis (DR-TB). One of the key challenges in the programmatic management of DR-TB (PMDT) is the high rate of loss to follow-up (38% in the 2010 cohort). An urgent need for a shorter, more tolerable, less expensive treatment regimen exists. The aim of the operational study is to determine the efficacy and safety of the short treatment regimen among drug resistant TB. Methods: This is a prospective single-arm cohort study evaluating the effectiveness and safety of a shorter 9 - 11-month treatment regimen (9MTR) for rifampicin-resistant/multi-drug resistant TB (RR/MDR-TB) in 10 PMDT facilities. All eligible consenting adult patients with rifampicin-resistant TB were enrolled and received the standardized 9-month treatment regimen (9MTR), including injectables, with a follow-up after 12 months of treatment completion. Results: A total of 329 patients were enrolled from July 2015 to December 2016. At the 6th month post-enrollment, 256 (77.8%) of them had culture-negative test results. The end-of-treatment success rate was 74.1% (224 [68.0%] were cured and 20 [6.1%] completed the treatment). On the other hand, 10 (3.0%) died, 41 (12.5%) lost to follow-up, 33 (10.0%) withdrawn, 1 (0.3%) treatment failure. In the 12th month after 9MTR completion, among the 244 patients with successful treatment, 198 (81.1%) had culture-negative results, while there were 46 patients whose culture tests were not done. One patient developed TB relapse with fluoroquinolone resistance. The majority of the adverse events were mild that occurred mostly during the first 6 months of treatment. Conclusion: The 9-month treatment regimen had a high treatment success rate with a favorable safety profile. The loss to follow-up was reduced; however, it was still a challenge. The introduction of the 9MTR via operational research had a major impact on building national capacity and infrastructure for the programmatic adoption of a new regimen. Ten PMDT centers received training and experience, created diagnostic pathways, and active drug safety monitoring and management were built.

Rifampicin Resistance by Xpert MTB/RIF Assay in Pulmonary Tuberculosis- Is there a Need for Confirmation by Retesting?

Introduction: Xpert Mycobacterium tuberculosis/ resistance to Rifampicin (MTB/RIF) assay detects MTB complex (MTBC) and rifampicin resistance simultaneously. In high prevalence countries like India, detection of rifampicin resistance in sputum specimen of a newly diagnosed case of pulmonary TB with a low pretest probability needs to be confirmed by retesting. Aim: To evaluate the results of retesting of rifampicin resistant specimens in newly diagnosed pulmonary TB cases. Materials and Methods: A retrospective analysis of the data of Xpert assay was performed on specimens received in Department of Microbiology, Seth G.S. Medical College and KEM Hospital, Mumbai, Maharashtra, India. If rifampicin resistance was detected in a newly diagnosed case of Tuberculosis (TB), a second specimen was retested by Xpert assay for confirmation. Concordance of retesting was seen with results of Line Probe Assay (LPA). Results: Total 27,429 specimens were processed by Xpert assay of which 803 specimens showed rifampicin resistance, 157 sputum specimens fulfilling criteria of Programmatic Management of Drug resistant Tuberculosis (PMDT) guidelines were retested. High, medium, low and very low bacterial load was observed in 30, 51, 34 and 42 specimens’ respectively. All specimens having high or medium bacillary load showed rifampicin resistant result on retesting. On retesting 34 sputum specimens with low bacterial load, rifampicin resistance was confirmed in 30 specimens. LPA done after growing them by liquid culture confirmed rifampicin resistance in remaining four specimens. Conclusion: Xpert assay is recommended when the bacterial load identified by Xpert assay is very low and when there is discordance between Xpert results of rifampicin resistance and the reflex LPA testing.

High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis

BackgroundThere was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan.MethodsThis was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of “cured” and “treatment completed” were collectively grouped as successful, whereas “death”, “treatment failure” and “lost to follow-up” were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings.ResultsA total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10–14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1–4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02).ConclusionsIn this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.

Challenges and perceptions of depression amongst multi drug resistant TB cases: qualitative study among medical officers of tuberculosis units across the Ahmedabad city, India

Background: Drug resistant tuberculosis (DR-TB), is usually associated with adverse socioeconomic and psychological outcomes. Such patients with co-morbid depression have lower treatment adherence and poor outcomes. Programmatic management of drug resistant tuberculosis (PMDT) guidelines recommend screening of DR-TB patients for mental illnesses at baseline and Follow-up (FU). The objectives were to explore perceptions and experiences of service providers about depression amongst MDR TB cases, review current strategies for screening for depression at Tuberculosis units (TUs) and recommend measures to address depression among MDR TB cases.Methods:This qualitative study was conducted across all TUs of Ahmedabad Municipal Corporation wherein 26 Key informant interviews (KIIs) were conducted using thematic guidelines and subsequently categorized in to subtheme for thematic analysis.Results: MOs had mixed experiences about encountering depression among MDR-TB cases, ranging from 1%-50%. Long duration and side effects of treatment, financial burden due to unemployment and societal stigma were contributory factors. Ensuring compliance was a major challenge. Counselling is an effective intervention for this but lack of counsellors in the program was another challenge. MOs stated that pre-treatment screening for depression is done at DR TB centre, but there is no structured, process. However, most of them don’t do subsequent follow up for depression.Conclusions:More counsellors need to be included in the program and a structured method needs to be devised for screening of depression among MDR TB patients. Both MO TUs and Counsellors need to be sensitized and trained for screening and monitoring depression amongst MDR TB in a systematic way.

Culture conversion and six months interim outcomes in retreatment cases of pulmonary MDRTB - a six month interim analysis.

To estimate the time to culture conversion and factors associated with failure to culture conversion, six-month interim outcomes and associated risk factors with poor interim outcomes in multi-drug resistant tuberculosis patients previously treated with second-line drugs. The prospective clinical case series study was conducted from March 2016 to January 2017 at the Indus Hospital Tuberculosis Clinic and seven other sites that are part of the hospital's Programmatic Management of Drug Resistant Tuberculosis initiative. All bacteriologically confirmed multi-drug resistant tuberculosis retreatment patients were enrolled. Data was collected on age, gender, site of enrollment, detailed history of previous treatment with anti-tuberculosis drugs, medical history, history of first-line drugs, history of second-line drugs, treatment outcomes, baseline sputum smear microscopy and monthly follow-up sputum smear microscopy and culture results. Data was subjected to univariate and multiple logistic regression analyses, and risk factors for failure to culture conversion were assessed using Cox Proportional Hazards Model. Out of 266 patients, 143(53.8%) were males, the overall largest age group was 5-24 years 97(36.5%), and 250 (94%) patients had previous history of treatment with first-line drugs. Overall, 101(40.1%) patients experienced poor interim outcome. Poor interim outcomes were significantly associated with higher number of drugs on the regimen, (odds ratio: 1.27; 95% confidence interval: 1.03-1.58) and high sputum smear grading (odds ratio: 4.56; 95% confidence interval: 3.30-18.71). Besides, 186(70.3%) patients experienced culture conversion within the initial six months of treatment. The success rate of re-treatment of multi-drug resistant tuberculosis with conventional regimen was found to be unacceptably low.

Receiving healthcare for drug-resistant TB: a cross-sectional survey from Pakistan.

To describe and quantify patients' self-reported experiences of receiving healthcare from Pakistan's Programmatic Management of Drug-Resistant Tuberculosis (PMDT) model of care, and to understand these experiences within the broader context of Pakistan's health system. This was a cross-sectional survey of patients attending three PMDT clinics in Khyber-Pakhtunkhwa Province in Pakistan. The median consultation time at the PMDT clinics was 10 minutes. In their most recent visit to the PMDT clinic, 34.9% of patients spent >40% of their monthly income to access treatment. To specify, 71% of patients reported spending out-of-pocket for ancillary medicines and 44.7% for laboratory tests. In 10.5% of cases, medicines for drug-resistant TB (DR-TB) were dispensed without the patient attending the clinic. Only 43.7% of treatment supporters regularly accompanied patients to the clinic, and 6% supervised the patient's intake of medicines. Disbursement of financial support was irregular in 98.6% of cases. Only 6.2% of patients received their daily injections from a public facility, the rest went elsewhere. Several shortcomings in PMDT services, including hurried consultations, irregularities in financial support, and gaps in Pakistan's broader health system undermined healthcare experience of patients with DR-TB. To improve health outcomes and patients' care experience these service gaps need to be addressed.

An observational study of adverse drug reactions in hospitalized patients of drug resistance tuberculosis taking PMDT therapy in a tertiary care hospital

Background: Drug resistant tuberculosis is an important public health issue in India. The treatment regimen followed is Programmatic Management of Drug resistant Tuberculosis (PMDT) approach. Adverse drug reactions (ADRs) are a serious issue which increases the risk of defaulter rate if poorly managed. Thus study was undertaken to assess the ADRs caused by PMDT therapy in indoor patients of Department of Respiratory Medicine in a tertiary care hospital at Surat.Methods: The prospective and observational study was carried out for one year period. The causality was determined by World Health Organization (WHO) Uppasala Monitoring Centre (UMC) scale and severity was determined by Modified Hartwig and Siegel scale. Fisher exact test was applied for statistical analysis.Results: Among 24 drug resistant tuberculosis patients, 12 (50%) patients developed ADRs due to second line antitubercular drugs. Occurrence of ADRs was more among Category V (100%) as compared to Category IV (36.8%). Occurrence of ADRs was more among females (60%). The commonly involved systems are auditory system (33.3%). Majority of ADRs developed within 61-90 days (66.7%) of initiation of drug therapy. Highest percentage of ADRs causing drugs was pyrazinamide (27.8%). On evaluation of the causality of ADRs, majority were found to be possible (53.3%). The severity assessment showed that most of the patients ADRs were of moderate level (73.3%).Conclusions: PMDT therapy is complicated but early management and reporting of ADRs decreases default rate.

‘Personalizing’ shorter regimens: Need of the hour

IntroductionThe launch of injectable shorter regimens under Programmatic Management of Drug Resistant Tuberculosis (PMDT) guidelines 2017 under Revised National Tuberculosis Control Program (RNTCP) was a welcome step as it decreased the duration of treatment significantly in Drug Resistant Tuberculosis (DRTB) patients.The objective of the present study was to evaluate the treatment outcomes of patients started on injectable shorter regimens from March 2018 to May, 2019. MethodsRetrospective study which scrutinized medical records of 85 patients started on injectable shorter regimen was conducted. Necessary information on possible patient and disease related predicting factors like age, gender, weight, HIV status, presence of diabetes mellitus (DM), anemia, gap between diagnosis and initiation of treatment, duration of intensive phase (IP) and time of sputum conversion was retrieved, and analyzed for possible association with treatment outcomes. Results56.5% had successful treatment outcomes. Age, gender, BMI, diabetic/anemic status and gap between diagnosis and initiation of treatment had no statistically significant relationship with the final outcomes. Duration of IP, sputum conversion and time of outcome during the course of illness emerged as significant factors in successful outcomes. ConclusionThe injectable shorter regimens were suitable for a variety of population irrespective of demographic disparities. Patients need to be followed closely as microbiological parameters serve as early indicators of unsuccessful outcomes. These regimens can serve as an alternate choice in patients not tolerating the all oral shorter Bedaquiline containing shorter regimen. Similar such options with combinations of different drugs for individualizing treatment regimens is the need of the hour.

Situational analysis of 10 countries with a high burden of drug-resistant tuberculosis 2 years post-UNHLM declaration: progress and setbacks in a changing landscape

ObjectivesGlobally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018–2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). MethodsAn ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. ResultsMost countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. ConclusionTriggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

The study of adverse drug reactions in indoor patients of tuberculosis taking standardized antitubercular therapy (directly observed treatment short-course and programmatic management of drug resistant tuberculosis) in a tertiary care hospital at Surat

Background: Tuberculosis is a serious public health issue in India. The treatment regimen followed is Directly observed treatment short-course (DOTS) and Programmatic Management of Drug resistant Tuberculosis (PMDT) approach. In a long period of treatment adverse drug reactions (ADRs) can be an important programmatic issue. Thus, study was undertaken to assess the ADRs caused by antitubercular therapy in indoor patients in a tertiary care hospital at Surat.Methods: The Observational, prospective study was carried out for one year period. The causality was determined by WHO UMC scale and severity was determined by Modified Hartwig and Siegel scale. Chi square test was applied for statistical analysis.Results: Among 255 tuberculosis patients, 85 (33.3%) patients developed ADRs. Occurrence of ADRs was more among females (46.6%). The commonly involved systems are gastrointestinal (40.6%) followed by haematological (17.9%). The most common ADRs observed were nausea and vomiting (21.7%). High percentage of ADRs causing drugs were isoniazid (30.6%) followed by rifampicin (26.1%). Causality assessment showed 60.4% ADRs were possible, 37.7% ADRs were probable and 1.9% ADRs was certain. Severity assessment scale showed 81.1% of moderate, 12.3% of mild and 6.6% of severe grading. Occurrence of ADRs was more among PMDT (60%) in comparison to DOTS therapy (31.06%) [p value = 0.0084 (significant p value &lt; 0.05)].Conclusions: Antitubercular treatment is safer but early detection, management and reporting of ADRs is required to prevent it at initial stage and helps to decrease default rate.