Fully and Partially Integrated Services for Tuberculosis / Human Immunodeficiency Virus in Myanmar : A Health Services Review, Cohort and Molecular Study

Abstract

The overall goal of this thesis is to provide adequate services for TB/HIV co-infected patients, in order to reduce the burden of TB/HIV. To achieve the goal, we need to identify which model of care services for those patients is better. Thus, we conducted a study in Myanmar with the objective to assess the different integrated services for TB/HIV in three parts. The first part reviewed the TB/HIV services which had been implemented in Myanmar. The second part looked at the comparison of the outcomes between the fully and partially integrated services. The last part identified the molecular epidemiology of tuberculosis treatment failure patients co-infected with human immunodeficiency virus. Part 1 Title: Evolution of TB/HIV services among different integrated models in Myanmar: a health services review Background: Myanmar is one of the countries highly affected by tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection. We aimed to review the coverage of TB/HIV integrated services as well as to document the performance of integrated services. Methods: A retrospective program review was conducted using aggregated data of the National TB Programme (NTP) of Myanmar from 2005 to 2016. Results: TB/HIV services were initiated in seven townships in 2005. Townships were slowly expanded until 2013 at which time the momentum was increased due to an increase in the government budget allocation for NTP. The relationship is evident from the joinpoint regression showing two clear periods with vastly differing slopes with a breakpoint at 2013. During the first period (before 2013), the relationship was not significant. Since 2013, there was an average of 1.4 townships established for every 10 million kyats allocated from the budget. In 2016, the whole country was eventually covered by TB/HIV services in different types of integration. The trends of all services varied across the years. As a whole, ART coverage among HIV positive TB patients remained low and it was the only significant difference among the three types of integration, which was observed the highest in the partially integrated townships with both vertical teams. The proportions of all three services were highly correlated with each other, with the Pearson product-moment correlation coefficient, between HIV testing and CPT of 0.62, between HIV testing and ART of 0.53, and between CPT and ART of 0.65. Low rates of services were observed consistently in Rakhine State while high rates were observed in Yangon, Mandalay and Nay Pyi Taw Regions. Conclusions: Myanmar could expand well TB/HIV services. The performance of HIV testing and CPT provision was adequate. However, ART coverage among HIV-positive TB patients remained low across all types of integration. Barriers of low ART coverage need to be investigated to reduce the burden of TB/HIV. Part 2 Title: Fully vs. partially integrated services for TB/HIV in Myanmar: A health services review and a cohort study Background: In Myanmar, integrated TB/HIV services are operated either fully (as one single unit) or partially (each vertical program provides both services). We aimed to review the fully and partially integrated services for TB/HIV co-infected patients and to assess their TB treatment outcomes. Methods: We analyzed the compiled service data base and conducted a cohort study on newly registered TB/HIV patients in 12 townships in Myanmar. Results: No significant association between region/state and types of integration was detected. Townships with partially integrated services had significantly larger population size, higher percentage of urban population and higher TB and TB/HIV case notification rates. Coverage of ART, CPT and financial, social and dietary supports were all low, especially dietary and financial supports that were below 10% to 15% respectively. Taking ART and CPT were aware by patients for less than 65% and 30%. The only different coverage between the two groups was Xpert MTB/RIF testing which was less common in the partially integrated model (OR = 0.55, 95% CI: 0.34- 0.87; P=0.006). Treatment complete rate and unfavorable outcome were not significantly different between the two although fully integrated services reported higher cured rate (RRR= 3.51, 95% CI: 1.24 - 9.98). Younger age group has positive effect on both cure and complete rate. Being married and good education enhances only complete rate. The effect of occupation, monthly family income, population size and percentage of urban population became non-significant. Conclusions: These mixed results suggest that during expansion of fully integrated services, the progress of treatment outcome should be carefully monitored. Part 3 Title: Infection of multiple Mycobacterium tuberculosis strains amongTB/HIV co-infected patients: A molecular study in Myanmar Background: Appearance of Mycobacterium tuberculosis in the sputum of a TB/HIV co-infected patient under treatment may indicate either failure or new infection. This study aims to evaluate whether TB treatment failure among TB/HIV co-infected patients is real failure. Methods: A prospective cohort study was conducted among 566 TB/HIV co-infected patients who started TB treatment in 12 townships in the upper Myanmar. Among 566 participants, 16 (2.8%) resulted treatment failure. We performed a molecular study using Mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) genotyping for them. The MIRU-VNTR profiles were analyzed using the web server, MIRU-VNTRplus. All data were entered into EpiData version 3.1 and analyzed using R version 3.4.3. Results: Among 16 failure patients, seven had incomplete laboratory results. Of nine remaining patients, nobody had exactly the same MIRU-VNTR pattern between the initial and final isolates. Their paired isolates were different in 2 to 17 loci (median = 8). Four subjects had persistent EAI lineages and one each had persistent Beijing lineage, changing from EAI to Beijing, from Beijing to EAI, NEW-1 to Beijing and NEW-1 to X strains. The only statistically significant variable associated with numbers of un-identical loci was gender. In male patients, the initial and final isolates had an average of 5.6 un-identical loci compared to the average of 12.5 loci in the female (t-test P value = 0.04). Conclusion: Thus in our study subjects, infection of multiple Mycobacterium tuberculosis strains is a possible cause of TB treatment failure. Explanation for the association between gender and distance of genotypes from the initial to subsequent Mycobacterium tuberculosis infection needs further studies. This study concluded that so far, fully integration had covered only less than a half of all townships in Myanmar. To speed up the coverage, more support in policy and financial aspects is needed. The fully integrated services for TB/HIV did not show better TB treatment outcome. During expansion of fully integrated services, the progress of treatment outcome should be carefully monitored. Barriers of low ART coverage need to be investigated to reduce the burden of TB/HIV. Infection of multiple Mycobacterium tuberculosis strains is a possible cause of TB treatment failure among TB/HIV co-infected patients. It suggests that infection control measures at the health care settings for TB and HIV patients are crucial in order to reduce TB transmission to each other. Keywords: TB/HIV co-infection, integrated services, TB treatment outcomes, Infection of multiple Mycobacterium tuberculosis strains