Correction: Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

[This corrects the article DOI: 10.1371/journal.pone.0234651.].

Correction: Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

[This corrects the article DOI: 10.1371/journal.pone.0248408.].

Challenging drug-resistant TB treatment journey for children, adolescents and their care-givers: A qualitative study.

BACKGROUND: Childhood multidrug-resistant TB (MDR-TB) still affects around 25000 children every year across the globe. Though the treatment success rates for drug-resistant TB (DR-TB) in children are better than adults, children and adolescents face unique hurdles during DR-TB (MDR-TB, Pre-XDR TB and XDR-TB) treatment. This study aimed to understand the patients, guardians and healthcare providers' perspectives about DR-TB treatment journey of patients and caregivers. METHODS: This is a qualitative study involving in depth-interviews of purposively selected adolescents (n = 6), patients guardians (for children and adolescents, n = 5) and health care providers (n = 8) of Médecins Sans Frontières (MSF) clinic, Mumbai, India. In-depth face to face interviews were conducted in English or Hindi language using interview guides during September-November 2019. The interviews were audio-recorded after consent. Thematic network analysis was used to summarize textual data. ATLAS.ti (version 7) was used for analysis. RESULT: The age of adolescent patients ranged from 15-19 years and four were female. Five guardians (of three child and two adolescent patients) and eight healthcare providers (including clinicians- 2, DOT providers-2, counselors-2 and programme managers-2) were interviewed. The overarching theme of the analysis was: Challenging DR-TB treatment journey which consisted of four sub-themes: 1) physical-trauma, 2) emotional-trauma, 3) unavailable social-support and 4) non-adapted healthcare services. Difficulties in compounding of drugs were noted for children while adolescents shared experiences around disruption in social life due to disease and treatment. Most of the patients and caregivers experienced treatment fatigue and burnout during the DR-TB treatment. Participants during interviews gave recommendations to improve care. DISCUSSION: The TB programmes must consider the patient and family as one unit when designing the package of care for paediatric DR-TB. Child and adolescent friendly services (paediatric-formulations, age-specific counselling tools and regular interaction with patients and caregivers) will help minimizing burnout in patients and caregivers.

Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India.

BACKGROUND: Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB. METHODS: This is a descriptive study including children (0-9 years) and adolescents (10-19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020. RESULT: A total of 268 patients were included; 16 (6%) of them were children (0-9 years). The median(min-max) age was 17(4-19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10-25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3-4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3-4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3-13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome. CONCLUSION: High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.

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.

Ambulatory management of pre- and extensively drug resistant tuberculosis patients with imipenem delivered through port-a-cath: A mixed methods study on treatment outcomes and challenges.

BACKGROUND: Imipenem, an intravenous antibiotic is recommended for use in drug resistant tuberculosis (DR-TB) when an effective regimen with combination of other second line drugs is not possible. Though the treatment success rates with carbapenems are promising, the twice daily injection of Imipenem usually requires patients to be hospitalized. The Médecins Sans Frontières independent clinic in Mumbai, India implemented ambulatory and home based management of patients receiving Imipenem through the use of port-a-cath. OBJECTIVE: We aimed to describe the adverse events and treatment outcomes of ambulatory pre- and XDR-TB patients initiated on imipenem through port-a-cath between January 2015 and June 2018 and to explore the challenges with this regimen as perceived by healthcare providers and patients. METHODS: A convergent mixed methods study with quantitative (longitudinal descriptive study using the routine data) and qualitative (descriptive study) part conducted concurrently. For the quantitative component, all XDR-TB and pre-XDR-TB initiated on imipenem containing regimen during January 2015-June 2018 were included. For qualitative component, interviews were carried out including patients who initiated on imipenem (n = 5) and healthcare providers (n = 7) involved in providing treatment. Treatment outcomes, culture conversion and adverse events during treatment were described. Thematic analysis was carried out for qualitative component. RESULTS: Of the 70 patients included, the mean age was 28.1 (standard deviation: 11.2) years and 36 (51.4%) were females. Fifty one (72.9%) had XDR-TB. All patients were resistant to fluoroquinilone, levofloxacin. Vomiting was reported by 55 (78.6%) patients and at least one episode of QTC prolongation (more than 500 msec by Fredrecia method) was detected in 25 (35.7%). Port-a-cath block and infection was seen in 11 (15.7%) and 20 (28.6%) patients respectively. Favourable outcomes were seen in 43 (61.4%) patients. Mortality was seen in 22 (31.4%) patients, 2 (2.9%) were lost-to-follow-up and 3 (4.3%) were declared as treatment failure. The overarching theme of the qualitative analysis was: Challenges in delivering Imipenem via port-a-cath device in ambulatory care. Major challenges identified were difficulties in adhering to drug dose timelines, vomiting, restricted mobility due to port-a-cath, paucity of infection control and space constraints at patients' home for optimal care. CONCLUSION: Administration of imipenem was feasible through port-a-cath. Though outcomes with ambulatory based imipenem containing regimens were promising, there were several challenges in providing care. The feasibility of infusion at day care facilities needs to explored to overcome challenges in infusion at patients home.

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.

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.

GeneXpert and Community Health Workers Supported Patient Tracing for Tuberculosis Diagnosis in Conflict-Affected Border Areas in India.

Médecins Sans Frontières (MSF) has been providing diagnosis and treatment for patients with tuberculosis (TB) via mobile clinics in conflict-affected border areas of Chhattisgarh, India since 2009. The study objectives were to determine the proportion of patients diagnosed with TB and those who were lost-to-follow-up (LTFU) prior to treatment initiation among patients with presumptive TB between April 2015 and August 2018. The study also compared bacteriological confirmation and pretreatment LTFU during two time periods: a) April 2015-August 2016 and b) April 2017-August 2018 (before and after the introduction of GeneXpert as a first diagnostic test). Community health workers (CHW) supported patient tracing. This study was a retrospective analysis of routine program data. Among 1042 patients with presumptive TB, 376 (36%) were diagnosed with TB. Of presumptive TB patients, the pretreatment LTFU was 7%. Upon comparing the two time-periods, bacteriological confirmation increased from 20% to 33%, while pretreatment LTFU decreased from 11% to 4%. TB diagnosis with GeneXpert as the first diagnostic test and CHW-supported patient tracing in a mobile-clinic model of care shows feasibility for replication in similar conflict-affected, hard to reach areas.

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.

'Working to stay healthy', health-seeking behaviour in Bangladesh's urban slums: a qualitative study.

BACKGROUND: Kamrangirchar and Hazaribagh are the largest slum areas in Dhaka, Bangladesh. In 2013, Médecins Sans Frontières initiated an urban healthcare programme in these areas providing services for factory workers and responding to the sexual and reproductive health needs of young women. Little in-depth information is available on perceptions of health and health seeking behaviour in this population. We aimed to provide a better understanding of community perceptions toward health and health care in order to inform programme strategies. METHODS: In-depth interviews were conducted with women (n = 13); factory workers (n = 14); and key informants (n = 13). Participants were selected using purposive maximum variation sampling and voluntarily consented to take part. Topic guides steered participant-led interviews, which were audio-recorded, translated and transcribed from Bangla into English. By comparing cases, we identified emerging themes, patterns and relationships in the data. NVivo11© was used to sort and code the data. RESULTS: Emerging themes indicated that in Kamrangirchar and Hazaribagh, health is seen as an asset necessary for work and, thus, for survival. Residents navigate a highly fragmented health system looking for 'quick fixes' to avoid time off work, with the local pharmacy deemed 'good enough' for 'common' health issues. Health care seeking for 'serious' conditions is characterised by uncertainty, confusion, and unsatisfactory results. Decisions are made communally and shaped by collective perceptions of quality care. People with limited socio-economic capital have few options for care. 'Quality care' is perceived as comprehensive care 'under one roof,' including predictive biomedical diagnostics and effective medication, delivered through a trusting relationship with the care provider. CONCLUSIONS: Health seeking behaviour of slum dwellers of Kamrangirchar and Hazaribagh is based on competing priorities, where quick and effective care is key, focussed on the ability to work and generate income. This takes place in a fragmented healthcare system characterised by mistrust of providers, and where navigation is informed by word-of-mouth experiences of peers. Improving health in this context demands a comprehensive and integrated approach to health care delivery, with an emphasis on rapid diagnosis, effective treatment and referral, and improved trust in care providers. Health education must be developed in collaboration with the community to identify knowledge gaps, support decision-making, and be channelled through existing networks. Further research should consider the effectiveness of interventions aiming to improve the practice of pharmacists.

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).

High burden of malaria and anemia among tribal pregnant women in a chronic conflict corridor in India.

BACKGROUND: With more than 200 million cases a year, malaria is an important global health concern, especially among pregnant women. The forested tribal areas of Andhra Pradesh, Telangana and Chhattisgarh in India are affected by malaria and by an on-going chronic conflict which seriously limits access to health care. The burden of malaria and anemia among pregnant women in these areas is unknown; moreover there are no specific recommendations for pregnant women in the Indian national malaria policy. The aim of this study is to measure the burden of malaria and anemia among pregnant women presenting in mobile clinics for antenatal care in a conflict-affected corridor in India. METHODS: This is a descriptive study of routine programme data of women presenting at first visit for antenatal care in Médecins sans Frontières mobile clinics during 1 year (2015). Burden of malaria and anemia were estimated using rapid diagnostic tests (SD BIOLINE® and HemoCue® respectively). RESULTS: Among 575 pregnant women (median age: 26 years, interquartile range: 25-30) 29% and 22% were in their first and second pregnancies respectively. Mid-Upper Arm Circumference (MUAC) was below 230 mm in 74% of them. The prevalence of anemia was 92.4% (95% Confidence Intervals (CI): 89.9-94.3), while severe anemia was identified in 6.9% of the patients. The prevalence of malaria was 29.3% (95%CI: 25.7-33.2) with 64% caused by isolated P. falciparum, 35% by either P. falciparum or mixed malaria and 1% by either P. vivax, or P.malariae or P. ovale. Malaria test was positive in 20.8% of asymptomatic cases. Malaria was associated with severe anemia (prevalence ratio: 2.56, 95%CI: 1.40-4.66, p < 0.01). CONCLUSIONS: Systematic screening for malaria and anemia should be integrated into maternal and child health services for conflict affected populations in highly endemic tribal areas. Interventions should include the use of rapid diagnostic test for all pregnant women at every visit, regardless of symptoms. Further studies should evaluate the impact of this intervention alone or in combination with intermittent malaria preventive treatment.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Tuberculosis ethambutol resistance: concordance between phenotypic and genotypic test results.

embB306 mutations are potential markers for detecting ethambutol resistance in clinical Mycobacterium tuberculosis isolates. However, more recently, embB306 mutations have been found in ethambutol susceptible isolates and an association with broad drug resistance rather than ethambutol resistance has been reported. To further investigate this question, we analyzed the association between embB306 mutations and phenotypic ethambutol resistance among 197 isolates from a drug resistance survey performed in Karakalpakstan, Uzbekistan. 39 strains had an embB306 mutation, out of which seven were ethambutol susceptible, thus, displaying discrepant test results. After re-analysis, the seven isolates were tested ethambutol resistant. All of these strains had an increased ethambutol MIC, however, three strains showed no or weak growth on the critical concentration of 2 microg/ml on Löwenstein-Jensen. In three strains we confirmed the presence of heteroresistant mixed populations which might influence conventional ethambutol testing. Final concordance between molecular and phenotypic EMB testing was high with a sensitivity of 78% and a specificity of 100%. Our results confirm that embB306 mutations are useful markers for predicting ethambutol resistance. Discrepancies between molecular and phenotypic ethambutol resistance test results are most likely caused by problems with conventional susceptibility testing.

Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures.

BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment.