Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar.

Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%-6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%-24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.

Improving detection of tuberculosis among household contacts of index tuberculosis patients by an integrated approach in Myanmar: a cross-sectional study.

BACKGROUND: Contact tracing for tuberculosis (TB) is a recommended measure to improve the case detection rate; however, actual implementation in Myanmar is limited and low detection rates have been reported. Household contacts of a known index TB case are at high risk of infection, thus a more strategic action for contact tracing is required to achieve the goal of the World Health Organization End TB Strategy. This study aimed to assess TB case detection rates among household contacts by an integrated approach and identify risk factors for TB. METHODS: A cross-sectional study was conducted in Mandalay City, Myanmar. Household contacts of index TB cases who had been receiving treatment for at least 3 months were prospectively investigated by an integrated approach which included modification of screening methods and active facilitation of screening investigations as follows. Initial chest x-ray (CXR) was performed for all contacts at the responsible facilities followed by sputum specimen collection for those aged ≥15 years and gene Xpert MTB/RIF examination. Transportation of all household contacts to health facilities and transportation of sputum samples for smear and gene Xpert MTB/RIF examination at centers were arranged by the research team to ensure that all household contacts received all investigations. Risk factors for TB among household contacts were identified by multiple logistic regression models. RESULTS: Of 174 household contacts, 115 were ≥ 15 years and 59 were < 15 years. The percentage of TB cases detected among the household contacts was 13.8%. There were 14 (12.2%) positive TB cases among the 115 contacts aged ≥15 years while 10 (16.9%) of those aged < 15 years had clinical signs and symptoms of TB with an abnormal CXR. Risk factors among household contacts for TB were being a caretaker of an index case, active and passive smoking, and drinking alcohol. CONCLUSIONS: The integrated approach of TB contact tracing by special arrangement for CXR, sputum and gene Xpert MTB/RIF examination yielded a high TB detection rate in a high TB prevalence area. Logistic and financial administration is needed to strengthen contact tracing. Further research on high-risk household contacts should be considered for increasing TB detection rates.

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar.

BACKGROUND: The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. OBJECTIVES: To assess whether CBMDR-TBC project's support improved treatment initiation. METHODS: In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. RESULTS: Of 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. CONCLUSION: Receiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also reduced time to treatment initiation. We also recommend improved tracking of all diagnosed patients as early as possible.

Evaluation of a tuberculosis active case finding project in peri-urban areas, Myanmar: 2014-2016.

OBJECTIVES: We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). DESIGN: Cross-sectional analysis of project records, township TB registers and annual TB reports. RESULTS: In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. CONCLUSIONS: The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB.

Patients with MDR-TB on domiciliary care in programmatic settings in Myanmar: Effect of a support package on preventing early deaths.

BACKGROUND: The community-based MDR-TB care (CBMDR-TBC) project was implemented in 2015 by The Union in collaboration with national TB programme (NTP) in 33 townships of upper Myanmar to improve treatment outcomes among patients with MDR-TB registered under NTP. They received community-based support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each project township had a project nurse exclusively for MDR-TB and a community volunteer who provided evening directly observed therapy (in addition to morning directly observed therapy by NTP). OBJECTIVES: To determine the effect of CBMDR-TBC project on death and unfavourable outcomes during the intensive phase of MDR-TB treatment. METHODS: In this cohort study involving record review, all patients diagnosed with MDR-TB between January 2015 and June 2016 in project townships and initiated on treatment till 31 Dec 2016 were included. CBMDR-TBC status was categorized as "receiving support" if project initiation in patient's township was before treatment initiation, "receiving partial support" if project initiation was after treatment initiation, and "not receiving support" if project initiation was after intensive phase treatment outcome declaration. Time to event analysis (censored on 10 April 2017) and cox regression was done. RESULTS: Of 261 patients initiated on treatment, death and unfavourable outcomes were accounted for 13% and 21% among "receiving support (n = 163)", 3% and 24% among "receiving partial support (n = 75)" and 13% and 26% among "not receiving support (n = 23)" respectively. After adjusting for other potential confounders, the association between CBMDR-TBC and unfavourable outcomes was not statistically significant. However, when compared to "not receiving support", those "receiving support" and "receiving partial support" had 20% [aHR (0.95 CI: 0.8 (0.2-3.1)] and 90% lower hazard [aHR (0.95 CI: 0.1 (0.02-0.9)] of death, respectively. This was intriguing. Implementation of CBMDR-TBC coincided with implementation of decentralized MDR-TB centers at district level. Hence, patients that would have generally not accessed MDR-TB treatment before decentralization also started receiving treatment and were also included under CBMDR-TBC "received support" group. These patients could possibly be expected to sicker at treatment initiation than patients in other CBMDR-TBC groups. This could be the possible reason for nullifying the effect of CBMDR-TBC in "receiving support" group and therefore similar survival was found when compared to "not receiving support". CONCLUSION: CBMDR-TBC may prevent early deaths and has a scope for expansion to other townships of Myanmar and implications for NTPs globally. However, future studies should consider including data on extent of sickness at treatment initiation and patient level support received under CBMDR-TBC.

Engagement of public and private medical facilities in tuberculosis care in Myanmar: contributions and trends over an eight-year period.

BACKGROUND: As part of the WHO End TB strategy, national tuberculosis (TB) programs increasingly aim to engage all private and public TB care providers. Engagement of communities, civil society organizations and public and private care provider is the second pillar of the End TB strategy. In Myanmar, this entails the public-public and public-private mix (PPM) approach. The public-public mix refers to public hospital TB services, with reporting to the national TB program (NTP). The public-private mix refers to private general practitioners providing TB services including TB diagnosis, treatment and reporting to NTP. The aim of this study was to assess whether PPM activities can be scaled-up nationally and can be sustained over time. METHODS: Using 2007-2014 aggregated program data, we collected information from NTP and non-NTP actors on 1) the number of TB cases detected and their relative contribution to the national case load; 2) the type of TB cases detected; 3) their treatment outcomes. RESULTS: The total number of TB cases detected per year nationally increased from 133,547 in 2007 to 142,587 in 2014. The contribution of private practitioners increased from 11% in 2007 to 18% in 2014, and from 1.8% to 4.6% for public hospitals. The NTP contribution decreased from 87% in 2007 to 77% in 2014. A similar pattern was seen in the number of new smear (+) TB cases (31% of all TB cases) and retreatment cases, which represented 7.8% of all TB cases. For new smear (+) TB cases, adverse outcomes were more common in public hospitals, with more patients dying, lost to follow up or not having their treatment outcome evaluated. Patients treated by private practitioners were more frequently lost to follow up (8%). Adverse treatment outcomes in retreatment cases were particularly common (59%) in public hospitals for various reasons, predominantly due to patients dying (26%) or not being evaluated (10%). In private clinics, treatment failure tended to be more common (8%). CONCLUSIONS: The contribution of non-NTP actors to TB detection at the national level increased over time, with the largest contribution by private practitioners involved in PPM. Treatment outcomes were fair. Our findings confirm the role of PPM in national TB programs. To achieve the End TB targets, further expansion of PPM to engage all public and private medical facilities should be targeted.

The contribution of a non-governmental organisation's Community Based Tuberculosis Care Programme to case finding in Myanmar: trend over time.

BACKGROUND: It is estimated that the standard, passive case finding (PCF) strategy for detecting cases of tuberculosis (TB) in Myanmar has not been successful: 26% of cases are missing. Therefore, alternative strategies, such as active case finding (ACF) by community volunteers, have been initiated since 2011. This study aimed to assess the contribution of a Community Based TB Care Programme (CBTC) by local non-government organizations (NGOs) to TB case finding in Myanmar over 4 years. METHODS: This was a descriptive study using routine, monitoring data. Original data from the NGOs were sent to a central registry within the National TB Programme and data for this study were extracted from that database. Data from all 84 project townships in five regions and three states in Myanmar were used. The project was launched in 2011. RESULTS: Over time, the number of presumptive TB cases that were referred decreased, except in the Yangon Region, although in some areas, the numbers fluctuated. At the same time, there was a trend for the proportion of cases treated, compared to those referred, that decreased over time (P = 0.051). Overall, among 84 townships, the contribution of CBTC to total case detection deceased from 6% to 4% over time (P < 0.001). CONCLUSIONS: Contrary to expectations and evidence from previous studies in other countries, a concerning reduction in TB case finding by local NGO volunteer networks in several areas in Myanmar was recorded over 4 years. This suggests that measures to support the volunteer network and improve its performance are needed. They may include discussion with local NGOs human resources personnel, incentives for the volunteers, closer supervision of volunteers and improved monitoring and evaluation tools.

High treatment success rate among multidrug-resistant tuberculosis patients in Myanmar, 2012-2014: a retrospective cohort study.

Background: Since 2011, Myanmar has adopted domiciliary care for multidrug-resistant tuberculosis (MDR-TB) patients and implemented several patient-support measures such as community-based directly observed treatment, nutritional support and financial incentives for patients and providers. We assessed treatment outcomes among MDR-TB patients registered for treatment in the Yangon and Mandalay Regions of Myanmar during 2012-2014 and factors associated with unfavourable treatment outcomes. Methods: We performed a retrospective cohort study involving secondary analysis of routine programmatic data extracted from the electronic MDR-TB treatment registries. We calculated the adjusted risk ratio (aRR) and 95% confidence interval (CI). Results: Of 2185 MDR-TB patients (75% HIV tested, 14% HIV positive with 70% of them receiving antiretroviral therapy), 1746 (80%) were successfully treated (cured and treatment completed) and 20% had unfavourable outcomes (14% died, 3% lost to follow-up, 2% failure and 1% not evaluated). Compared with young patients (<25 y), patients 25-54 y of age (aRR 2.0 [95% CI 1.3 to 2.9]) and >55 y (aRR 3.2 [95% CI 2.1 to 4.8]) were more likely to have unfavourable outcomes. HIV-positive patients (especially not receiving ART; aRR 2.2 [95% CI 1.4 to 3.6]) and patients with 'unknown HIV status' (aRR 1.9 [95% CI 1.5-2.4]) had a higher risk of unfavourable outcomes compared with HIV-negative patients. Conclusions: Treatment success was high and deaths accounted for three-fourths of unfavourable outcomes. Joint care and management of MDR-TB and HIV co-infected patients should be strengthened.

National scale-up of tuberculosis-human immunodeficiency virus collaborative activities in Myanmar from 2005 to 2016 and tuberculosis treatment outcomes for patients with human immunodeficiency virus-positive tuberculosis in the Mandalay Region in 2015.

Background: HIV-associated TB is a serious public health problem in Myanmar. Study objectives were to describe national scale-up of collaborative activities to reduce the double burden of TB and HIV from 2005 to 2016 and to describe TB treatment outcomes of individuals registered with HIV-associated TB in 2015 in the Mandalay Region. Methods: Secondary analysis of national aggregate data and, for treatment outcomes, a cohort study of patients with HIV-associated TB in the Mandalay Region. Results: The number of townships implementing collaborative activities increased from 7 to 330 by 2016. The number of registered TB patients increased from 1577 to 139 625 in 2016, with the number of individuals tested for HIV increasing from 432 to 114 180 (82%) in 2016: 10 971 (10%) were diagnosed as HIV positive. Uptake of co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) nationally in 2016 was 77% and 52%, respectively. In the Mandalay Region, treatment success was 77% and mortality was 18% in 815 HIV-associated TB patients. Risk factors for unfavourable outcomes and death were older age (≥45 years) and not taking CPT and/or ART. Conclusion: Myanmar is making good progress with reducing the HIV burden in TB patients, but better implementation is needed to reach 100% HIV testing and 100% CPT and ART uptake in TB-HIV co-infected patients.

Reactogenicity and immunogenicity profiles of a novel pentavalent diphtheria-tetanus-whole cell pertussis-hepatitis B and Haemophilus influenzae type B vaccine: a randomized dose-ranging trial of the Hib tetanus-conjugate content.

BACKGROUND: Combined vaccines containing diphtheria-tetanus-pertussis whole-cell (DTPw), Haemophilus influenzae type b (Hib), and hepatitis-B vaccines are essential for the continuing success of vaccination programs in developing nations. This randomized, dose-ranging study assessed the immunogenicity and reactogenicity of primary and booster vaccination with pentavalent DTPw-HBV/Hib vaccines containing 10, 5 or 2.5 microg of polyribosylribitol phosphate (PRP) conjugated to tetanus toxoid (trials Hib-052/064). METHODS: Six hundred eighty infants were randomized to receive one of 5 vaccine combinations at 6, 10, and 14 weeks of age. Of these, 351 received the same vaccine at 15-24 months of age. The immune response was evaluated on blood samples collected 1 month after the 3-dose primary course and before and 6 weeks after the booster dose. Reactogenicity was assessed during a 4-day period after each vaccine dose using diary cards. RESULTS: After primary vaccination, all subjects had seroprotective anti-PRP antibody concentrations (> or = 0.15 microg/mL) and > 95% had concentrations > or = 1.0 microg/mL, irrespective of the PRP dose administered. Anti-PRP antibody avidity after primary vaccination and antibody persistence until the second year of life were similar among groups. The booster dose induced marked increases in anti-PRP antibody GMCs and antibody avidity, indicative of effective priming and the presence of immune memory. All vaccination regimens elicited good immune responses and comparable antibody persistence to the other vaccine antigens, with significant increases in all antibody concentrations observed after boosting. All vaccination regimens were safe, with similar overall reactogenicity profiles. CONCLUSION: Hib conjugate vaccines containing reduced amounts of PRP can be effectively combined with the licensed DTPw-HBV vaccine to provide protection against 5 major childhood pathogens in a single injection.