One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India.

BACKGROUND: The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. METHODS: This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20-22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016-February 2018 were included. RESULTS: Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22-32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43-96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. CONCLUSIONS: The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

Epidemiology of Influenza among patients with influenza-like illness and severe acute respiratory illness in Pakistan: A 10-year surveillance study 2008-17.

In Pakistan, the burden of influenza was largely unknown, as no formal surveillance system was in place. In 2008, an influenza surveillance system was set up in eight sentinel sites. This study describes the epidemiology of influenza virus using a 10-year surveillance data from 2008 to 2017. Nasopharyngeal/throat swabs were collected from patients with influenza-like illness (ILI) and severe acute respiratory illness (SARI) along with relevant epidemiological information. The samples were tested using real-time reverse transcriptase-polymerase chain reaction for the detection and characterization of influenza viruses. A total of 17 209 samples were tested for influenza, out of which 3552 (20.6%) were positive; 2151/11 239 (19.1%) were patients with ILI, whereas 1401/5970 (23.5%) were patients with SARI. Influenza A/H1N1pdm09 was the predominant strain with 40.6% (n = 1442) followed by influenza B (936, 26.4%). Influenza A/H1N1pdm09 was predominant among the children (5-14 years) and adults (15-64 years). Influenza B strain was predominantly found in the elderly age group (≥ 65 years) accounting for 48% of cases followed by children (2-4 years) accounting for 37% of cases. This 10-year surveillance data provides evidence of influenza activity in the country throughout the year with seasonal winter peaks. The results could be used to strengthen the epidemic preparedness and response plan.

Preparedness of outpatient health facilities for ambulatory treatment with all-oral short DR-TB treatment regimens in Zhytomyr, Ukraine: a cross-sectional study.

BACKGROUND: Ukraine has a high burden of drug-resistant tuberculosis (DR-TB). Mental health problems, including alcohol use disorder, are common co-morbidities. One in five DR-TB patients has human immunodeficiency virus (HIV). As part of health reform, the country is moving from inpatient care to ambulatory primary care for tuberculosis (TB). In Zhytomyr oblast, Médecins Sans Frontières (MSF) is supporting care for DR-TB patients on all-oral short DR-TB regimens. This study describes the preparedness of ambulatory care facilities in Zhytomyr oblast, Ukraine, to provide good quality ambulatory care. METHODS: This is a retrospective analysis of routinely collected programme data. Before discharge of every patient from the hospital, MSF teams assess services available at outpatient facilities using a standardised questionnaire. The assessment evaluates access, human resources, availability of medicines, infection control measures, laboratory and diagnostic services, and psychosocial support. RESULTS: We visited 68 outpatient facilities in 22 districts between June 2018 and September 2019. Twenty-seven health posts, 24 TB-units, 13 ambulatories, two family doctors and one polyclinic, serving 30% of DR-TB patients in the oblast by September 2019, were included. All facilities provided directly observed treatment, but only seven (10%) provided weekend-services. All facilities had at least one medical staff member, but TB-training was insufficient and mostly limited to TB-doctors. TB-treatment and adequate storage space were available in all facilities, but only five (8%) had ancillary medicines. HIV-positive patients had to visit a separate facility to access HIV-care. Personal protective equipment was unavailable in 32 (55%) facilities. Basic laboratory services were available in TB-units, but only four (17%) performed audiometry. Only ten (42%) TB-units had psychosocial support available, and nine (38%) offered psychiatric support. CONCLUSION: Outpatient facilities in Zhytomyr oblast are not yet prepared to provide comprehensive care for DR-TB patients. Capacity of all facilities needs strengthening with trainings, infection control measures and infrastructure. Integration of psychosocial services, treatment of co-morbidities and adverse events at the same facility are essential for successful decentralisation. The health reform is an opportunity to establish quality, patient-centred care.

Suicidal ideation and attempt among school going adolescents in Bhutan - a secondary analysis of a global school-based student health survey in Bhutan 2016.

BACKGROUND: Suicide is one of the leading causes of death and Disability Adjusted Life Years (DALYs) worldwide. The economic, emotional and human cost of suicidal behaviour to individuals, families, communities and society makes it a serious public health issue. We aim to determine the prevalence and factors associated with self-reported suicidal behaviour (suicidal ideation and attempt) among school going adolescents (13-17 years). METHODS: This is a secondary analysis of a nationally representative data for Bhutan namely Global School Based Student Health Survey in 2016 which reports on various dimensions of adolescent health including suicidal behaviour. The survey employed a multistage sampling method to recruit participants aged 13-17 years (n = 5809) from 50 schools (25 each in rural and urban area). The survey used an anonymous self-administered pre-tested 84-item questionnaire. Weighted analysis was done. Adjusted prevalence ratios (aPRs) and adjusted Odds Ratios (aORs) have been presented with 95% confidence intervals (95% CI). RESULTS: A total of 667 (11.6%) adolescents reported considering a suicide attempt whereas 656 (11.3%) reported attempting suicide in the past 12 months. Among those reporting suicidal ideation, 388 (58.6%) reported attempting a suicide and 274 (41.4%) had ideation alone, whereas, 247 (38.9%) reported attempting a suicide without previous ideation. Female sex, food insecurity, physical attack, sexual violence, bullying, feeling of loneliness, low parental engagement, reported worry about lack of sleep, urge to use drugs/alcohol, smokeless tobacco use, drug abuse and parental smoking were the factors associated with suicidal attempt. All these factors except smokeless tobacco use and parental smoking were associated with suicidal ideation. Having helpful/close friends was found to be protective against suicide ideation. CONCLUSION: Suicidal behaviour among school going adolescents in Bhutan is high and alarming, especially among girls. Bullying, sexual violence, feeling of loneliness and drug abuse were some of the key risk factors identified. It is important to identify these risk factors early and effectively tackle them in order to prevent suicides. It requires a multi-faceted intervention with the support of the children, community, teachers and parents.

Correction: Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

[This corrects the article DOI: 10.1371/journal.pone.0264442.].

Correction: Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

[This corrects the article DOI: 10.1371/journal.pone.0263759.].

Delivering hypertension care in private-sector clinics of urban slum areas of India: the Mumbai Hypertension Project.

In India, the private sector provides 70% of the total outpatient medical care. This study describes the Mumbai Hypertension Project, which aimed to deliver a standard hypertension management package in private sector clinics situated in urban slums. The project was conducted in two wards (one "lean" and one "intensive") with 82 private providers in each. All hypertensive patients received free drug vouchers, baseline serum creatinine, adherence support, self-management counseling and follow-up calls. In the intensive-ward, project supported hub agents facilitated uptake of services. A total of 13,184 hypertensive patients were registered from January 2019 to February 2020. Baseline blood pressure (BP) control rates were higher in the intensive-ward (30%) compared with the lean-ward (13%). During the 14-month project period, 6752 (51%) patients followed-up, with participants in the intensive-ward more likely to follow-up (aOR: 2.31; p < 0.001). By project end, the 3-6-month cohort control rate changed little from baseline-29% for intensive ward and 14% for lean ward. Among those who followed up, proportion with controlled BP increased 13 percentage points in the intensive ward and 16 percentage points in the lean ward; median time to BP control was 97 days in the intensive-ward and 153 days in lean-ward (p < 0.001). Despite multiple quality-improvement interventions in Mumbai private sector clinics, loss to follow-up remained high, and BP control rates only improved in patients who followed up; but did not improve overall. Only with new systems to organize and incentivize patient follow-up will the Indian private sector contribute to achieving national hypertension control goals.

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BACKGROUND: People with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India. METHODS: This is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care. RESULTS: During the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0-36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014). CONCLUSION: In our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Acceptability of unsupervised peer-based distribution of HIV oral self-testing for the hard-to-reach in rural KwaZulu Natal, South Africa: Results from a demonstration study.

BACKGROUND: Innovative models to distribute oral HIV self-tests (HIVST) provide an opportunity to increase access to HIV testing, especially for hard-to-reach populations. This study aimed to describe the acceptability of unsupervised peer-distribution of HIVST as a method to scale-up HIV testing. METHODS: In this study, lay counsellors or community health workers provided HIVST kits to primary recipients (PRs) for distribution to their sexual partners, anyone in their social network (termed secondary recipients) or for self-testing, from September 2018 to March 2020. The study was conducted in Eshowe and Mbongolwane areas in KwaZulu-Natal, South Africa. A structured questionnaire was administered during the recruitment and passive follow-up, when people came for confirmatory HIV testing. Electronic records were retrospectively examined to determine initiation of antiretroviral treatment (ART) for all HIVST users and non-users. RESULTS: Among 36,708 people approached to be primary recipients, 9,891 (26.9%) accepted; 31,341 HIVST kits were distributed with a median of three (IQR: 2-4) per peer. PRs were predominately recruited at primary health clinics (PHCs). However, acceptability of HIVST was thrice as high at community-based testing sites compared to PHCs (64.5% vs. 21.0%; p<0.001). During the study period, 34,715 adults were tested for HIV at both PHCs and community-based testing sites; of these, 1,089 individuals reported HIVST use. Among HIVST users, 893 (82.0%) returned to the clinic for confirmatory testing after testing negative on HIVST; 196 (17.9%) were confirmed HIV positive following a positive HIVST. After excluding 36/196 (18.4%) participants for whom clinical records could not be found in electronic register and 25/160 (15.6%) who were already on ART before receiving HIVST, 129/135 (95.5%) initiated ART, whereas 2,362/2685 (88%) of HIV positive HIVST non-users-initiated ART. CONCLUSION: Unsupervised peer-distribution of HIVST was feasible and acceptable, with more than 25% accepting to be peer-distributors. Acceptability of HIVST was thrice as high in community sites compared to clinics.

Utility of the lateral flow urine lipoarabinomannan tuberculosis assay in patients with advanced HIV disease at antiretroviral therapy centres in Mumbai, India.

BACKGROUND: People with Advanced HIV Disease (AHD) are at higher risk of TB coinfection and mortality. However, there are challenges in TB diagnosis with the currently recommended diagnostic tools. WHO recommends lateral flow urine lipoarabinomannan (LF-LAM) assay to assist TB diagnosis among AHD patients. We assessed the utility and acceptability of using urine LF-LAM assay for TB diagnosis among patients at public Antiretroviral Therapy (ART) Centres in Mumbai. METHODS: The cross-sectional study was conducted among adult AHD patients accessing care from 17 ART centres during November,2020-June, 2021. Urine LF-LAM was offered as routine care for eligible patients in combination with standard diagnostic tests. We calculated the proportion of positive LF-LAM results by CD4 categories and TB symptoms and performed multivariable logistic regression to determine the factors associated with LF-LAM positivity. RESULTS: Among 2,390 patients, the majority (74.5%) had CD4 between 101-200 cells/mm3. The mean age was 43.7 years (SD:10.6), 68.6% were male, 8.4% had TB symptoms and 88.0% were on ART. The overall proportion of patients with urine LF-LAM positive results was 6.4%. Among PLHIV with CD4≤100 cells/mm3, the positivity was 43.0% and 7.7% in symptomatic and asymptomatic patients, respectively. Among PLHIV with a CD4>100 cells/mm3, the positivity was 26.7% and 2.7% in symptomatic and asymptomatic patients respectively. Urine LF-LAM positivity was higher among inpatients, ART naïve, patients on treatment for <6 months, symptomatic and in WHO clinical stage III/IV of HIV disease as compared to the reference categories. We detected an additional 131 TB cases with urine LF-LAM in combination with the standard diagnostic tests. CONCLUSION: The study demonstrated the utility of urine LF-LAM for TB diagnosis among AHD patients and the simple, user-friendly test was acceptable as part of routine care. Inclusion of urine LF-LAM test in the current diagnostic algorithm may facilitate early TB diagnosis among AHD patients.

Routine viral load monitoring and enhanced adherence counselling at a public ART centre in Mumbai, India.

BACKGROUND: Routine viral-load (VL) measurements along with enhanced adherence counselling (EAC) are recommended to achieve virological suppression among people living with HIV/AIDS (PLHA) on anti-retroviral therapy (ART). The Mumbai Districts AIDS Control Society along with Médecins Sans Frontières has provided routine VL measurements and EAC to PLHA on ART at King Edward Memorial (KEM) hospital, Mumbai since October-2016. This study aims to describe the initial VL results and impact of EAC on viral suppression and factors associated with initial viral non-suppression among patients with an initial detectable VL, in a cohort of patients tested between October-2016 and September-2018. METHODS: This is a descriptive study of PLHA on ART who received VL testing and EAC during October-2016 to September-2018. Log-binomial regression was used to identify factors associated with a high VL. RESULTS: Among 3849 PLHA who underwent VL testing, 1603(42%) were female and median age was 42 years (IQR:35-48). Majority were referred for routine testing (3432(89%)) and clinical/immunological failure (233(6%)). Overall, 3402(88%) PLHA had suppressed VL at initial testing. Among 3432 tested for routine monitoring, 3141(92%) had VL suppressed. Of 291 with VL>1000c/ml, 253(87%) received EAC and after repeat VL, 70(28%) had VL<1000c/ml. Among 233 referred for clinical/immunological failure, 122(52%) had VL>1000c/ml and 109 have been switched to second-line ART. CD4 count<500 (aOR-5.0[95%CI 3.8-6.5]), on ART for<5 years (aOR-1.5[1.1-2.0]) and age<15 years (aOR-5.2[3.0-8.9]) were associated with an initial VL>1000c/ml. Factors associated with follow-up VL suppression included EAC (p<0.05) and being on second-line ART (p<0.05). CONCLUSION: Results from a routine VL program in public sector in India were encouraging and in line with UNAIDS 90-90-90 targets. Routine VL monitoring along with EAC resulted in early switch to alternative optimised regimens while also preventing unnecessary switches. Along with the vital scale up of routine VL monitoring, implementation of enhanced adherence strategies for patients with detectable viral load should be ensured.

Yield of Systematic Longitudinal Screening of Household Contacts of Pre-Extensively Drug Resistant (PreXDR) and Extensively Drug Resistant (XDR) Tuberculosis Patients in Mumbai, India.

While risk of tuberculosis (TB) is high among household contacts (HHCs) of pre-extensively drug resistant (pre-XDR) TB and XDR-TB, data on yield of systematic longitudinal screening are lacking. We aim to describe the yield of systematic longitudinal TB contact tracing among HHCs of patients with pre-XDR-TB and XDR-TB. At the Médecins Sans Frontières (MSF) clinic, Mumbai, India a cohort comprising 518 HHCs of 109 pre-XDR and XDR index cases was enrolled between January 2016 and June 2018. Regular HHC follow-ups were done till one year post treatment of index cases. Of 518 HHCs, 23 had TB (21 on TB treatment and two newly diagnosed) at the time of first visit. Of the rest, 19% HHCs had no follow-ups. Fourteen (3.5%) TB cases were identified among 400 HHCs; incidence rate: 2072/100,000 person-years (95% CI: 1227-3499). The overall yield of household contact tracing was 3% (16/518). Of 14 who were diagnosed with TB during follow-up, six had drug susceptible TB (DSTB); six had pre-XDR-TB and one had XDR-TB. Five of fourteen cases had resistance patterns concordant with their index case. In view of the high incidence of TB among HHCs of pre-XDR and XDR-TB cases, follow-up of HHCs for at least the duration of index cases' treatment should be considered.

Seasonality of influenza and its association with meteorological parameters in two cities of Pakistan: A time series analysis.

BACKGROUND: Influenza is known to have a specific pattern of seasonality the reasons for which are yet to be fully ascertained. Temperate zones show influenza epidemic during the winter months. The tropical and subtropical regions show more diverse influenza outbreak patterns. This study explores the seasonality of influenza activity and predicts influenza peak based on historical surveillance time series data in Islamabad and Multan, Pakistan. METHODS: This is a descriptive study of routinely collected monthly influenza sentinel surveillance data and meteorological data from 2012-16 in two sentinel sites of Pakistan: Islamabad (North) and Multan (Central). RESULTS: Mean number of cases of influenza and levels of precipitation were higher in Islamabad compared to Multan. Mean temperature and humidity levels were similar in both the cities. The number of influenza cases rose with decrease in precipitation and temperature in Islamabad during 2012-16, although the same cannot be said about humidity. The relationship between meteorological parameters and influenza incidence was not pronounced in case of Multan. The forecasted values in both the cities showed a significant peak during the month of January. CONCLUSION: The influenza surveillance system gave a better understanding of the disease trend and could accurately forecast influenza activity in Pakistan.

Genotyping and outcomes of presumptive second line ART failure cases switched to third line or maintained on second line ART in Mumbai, India.

BACKGROUND: HIV programs are increasingly confronted with failing antiretroviral therapy (ART), including second-line regimens. WHO has provided guidelines on switching to third-line ART. In a Médecins Sans Frontières clinic in Mumbai, India, receiving referred presumptive second-line ART failure cases, an evidence-based protocol consisting of viral load (VL) testing, enhanced adherence counselling (EAC) and genotype for switching was implemented. OBJECTIVE: To document the outcome and genotype of presumptive second-line ART failure cases switched to third-line or maintained on second-line ART. DESIGN: Retrospective cohort study of patients referred between January 2011 and September 2017. RESULTS: The cases (n = 120) were complex with median 9.2 years of ART exposure, poor adherence at baseline, and exposure to multiple ART regimens other than recommended by WHO. Out of 90 evaluated cases, 39(43%) were maintained on second-line ART. Forty-nine (54%) were ever switched to third-line ART. Twelve months virological suppression was 72% in the second-line and 93% in the third-line ART cohort, while retention in care was 80% and 94% respectively. Genotyping showed 62% resistance for PIs, and 52% triple class resistance to NRTIs, NNRTIs and PIs. Resistance was noted for the new class of integrase inhibitors, and for different drugs without any documented previous exposure to the same drug. CONCLUSION: Adopting WHO guidelines on switching ART regimens and provision of EAC can prevent unnecessary switching/exposure to third-line ART regimens. Genotyping is urgently required in national HIV programs, which currently use only the exposure history of patients for switching to third-line ART regimens.

A country-wide evaluation of infection control for tuberculosis in health-care facilities in Armenia.

INTRODUCTION: Infection control at health facilities is an important part of TB control programmes. To assess the implementation of tuberculosis infection control (TB IC) measures and barriers hindering their implementation in TB health care facilities (HCFs) in Armenia; to report the feasibility of using the WHO recommended checklist. METHODOLOGY: A cross-sectional survey using WHO TB-IC checklist and direct observations was conducted between January and May 2018. RESULTS: The survey included all 62 TB institutions in Armenia. TB HCFs in Armenia had implemented some recommended TB IC measures: offering IC training to staff (48%), shortening time to diagnosing TB to less than one day (29%) and ensuring good ventilation (60%). N95 respirators were available in all HCFs. However, barriers that hindered implementation of TB IC measures were: lack of training, a different incentive model for primary care doctors versus TB doctors and lack of space and poor conditions of the building. CONCLUSION: The use of the standardized WHO checklist in this first evaluation of TB IC measures in Armenia was found to be useful and feasible in identifying areas of weak IC implementation and barriers to achieving good infection control. Other TB programs may benefit from the use of this model of assessment, based on the WHO checklist.

Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study.

BACKGROUND: Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa. METHODS: We retrospectively analysed a cohort of all patients who received 6-12 months of oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid twice per day) in MSF-supported projects. We report serious adverse events, QTc corrected using the Fridericia formula (QTcF) interval data, and culture conversion data during the first 6 months of treatment. FINDINGS: Between Jan 1, 2016, and Aug 31, 2016, 28 patients (median age 32·5 years [IQR 28·5-40·5], 17 men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24 patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had extensively drug-resistant tuberculosis. No patient had an increase of more than 500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF increase of more than 60 ms from baseline but none permanently discontinued the drugs. 16 serious adverse events were reported in seven patients. Of 23 individuals with positive baseline cultures, 17 (74%) converted to negative by month 6 of treatment. INTERPRETATION: Use of the bedaquiline and delamanid combination appears to reveal no additive or synergistic QTcF-prolonging effects. Access to bedaquiline and delamanid in combination should be expanded for people with few treatment options while awaiting the results of formal clinical trials. FUNDING: Médecins Sans Frontières (MSF).

Linezolid-Associated Optic Neuropathy in Drug-Resistant Tuberculosis Patients in Mumbai, India.

BACKGROUND: Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens. METHODS: This was a retrospective cohort study using routine clinical and laboratory data in Médecins Sans Frontières (MSF) HIV/DR-TB clinic in collaboration with Lilavati Hospital & Research Center, Mumbai, India. All DR-TB patients on linezolid-containing treatment regimens were included in the study and underwent routine evaluations for systemic and/or ocular complaints. Ophthalmological evaluation by a consultant ophthalmologist included visual-acuity screening, slit-lamp examination and dilated fundus examination. RESULTS: During January 2013-April 2016, 86 of 136 patients (with/without HIV co-infection) initiated linezolid-containing DR-TB treatment. The median age of these 86 patients was 25 (20-35) years and 47% were males. 20 percent of them had HIV co-infection. Of 86, 24 (27.9%) had at least one episode of ocular complaints (the majority blurred-vision) and among them, five (5.8%) had optic neuropathy. Patients received appropriate treatment and improvements were observed. None of the demographic/clinical factors were associated with optic neuropathy in Poissons or multivariate binary logistic-regression models. DISCUSSION: This is the first report focusing on optic neuropathy in a cohort of complex DR-TB patients, including patients co-infected with HIV, receiving linezolid-containing regimens. In our study, one out of four patients on linezolid had at least one episode of ocular complaints; therefore, systematic monitoring of patients by primary physicians/nurses, and access to specialized diagnostic-services by specialists are needed. As linezolid will be increasingly added to treatment regimens of DR-TB patients, programmes should allocate adequate resources for early diagnosis, prevention and management of this disabling adverse event.