Treatment success and mortality among adults with tuberculosis in rural eastern Uganda: a retrospective cohort study

Although tuberculosis is treatable and curable with a standard course of antibiotics, the disease continues to claim millions of lives globally. The 2019 World Health Organization (WHO) Global Tuberculosis report indicates that 10 million people developed tuberculosis disease in 2018 and 1.5 million of them died [1]. The WHO recommends that a good performing tuberculosis program should achieve at least 90% treatment success rate and 85% cure rate [2]. These targets contribute to the effective reduction of tuberculosis transmission at household and community levels, and in reducing tuberculosis related complications and mortality [3]. Nonetheless, tuberculosis control programs all over the world have challenges in meeting the recommended treatment success rate particularly for persons with new bacteriologically confirmed pulmonary tuberculosis (BC-PTB) diagnosis. According to current data, global treatment success rate for persons with new BC-PTB diagnosis improved from 82% in 2016 [4] to 85% in 2017 [1], which is still lower than the desired target of at least 90%.

Sub Saharan Africa has the highest burden of tuberculosis and the slowest decline in the number of tuberculosis incident cases [5], and suboptimal tuberculosis treatment success rate. Recent systematic review and meta-analysis show a treatment success rate of 76.2% among persons with BC-PTB in sub Saharan Africa over the past 10 years [6], far below the global treatment success rate of 85% [1] and the WHO recommended rate of at least 90% [2]. This meta-analysis also shows that sub Saharan Africa may be experiencing a gradual but steady decline in tuberculosis treatment success rate [6]. There is therefore a need to conduct research that can inform interventions to improve treatment success rate particularly in sub Saharan Africa where the burden of tuberculosis and HIV are both very high. The burden of tuberculosis is higher among people living with Human Immunodeficiency Virus (PLHIV) where it is the number one cause of mortality [7]. Accordingly, more data are needed especially from rural or remote areas on treatment outcomes among persons with tuberculosis to inform interventions.

Therefore, the purpose of this study was to measure treatment outcomes, namely treatment success and mortality rates, among persons with BC-PTB in rural eastern Uganda, determine whether HIV infection is associated with these treatment outcomes, and identify other factors amenable to interventions that can contribute to treatment success rate.

Our data from rural eastern Uganda shows that treatment success rate for persons with BC-PTB is suboptimal and mortality rate is high. Our data also shows that HIV infection and older age are associated with reduced treatment success rate and increased mortality rate while CB-DOTS is associated with reduced mortality compared to facility-based DOTS. The treatment success rate reported here is no different from that reported in a recent meta-analysis of tuberculosis treatment success rate for sub Saharan Africa, which was 76.2% [6]. Since the treatment success rate in eastern Uganda falls below the desired target of at least 90%, site-specific measures are needed to address barriers to achieving high treatment success rate.

Mortality rate was high in this cohort of adult persons with BC-PTB. We were not able to ascertain the exact date of death from the records, therefore it is not clear whether mortality occurred early or later during treatment. The mortality rate in this study is comparable to that observed in other cohorts of persons with tuberculosis in sub Saharan Africa such as Ethiopia [11]. However, some cohorts from sub Saharan Africa have reported significantly lower mortality rates of less than 5% [12, 13]. It is clear that a wide variation in mortality rates in the treatment cohorts in sub Saharan Africa exists. These differences may be explained by the prevalence of HIV in the different countries across the continent, especially given the relationship between HIV and mortality [14] and that we found in our cohort.

Our study shows HIV infected persons with BC-PTB have reduced treatment success rate and increased mortality rate. These findings are not unique because the relationship between HIV and tuberculosis is well-established [15]. HIV is a known strong risk factor for tuberculosis disease, alters the clinical presentation, progression, and prognosis of tuberculosis as well as response to treatment [14]. In addition, tuberculosis disease is the commonest opportunistic infection among PLHIV, and the leading cause of mortality [7]. Dual treatment of tuberculosis and HIV is associated with increased pill burden and this may lead to medication fatigue and potentially non-adherence [16, 17]. Non-adherence to anti-tuberculosis medications in turn reduce treatment success rate [18] and increase mortality rate [19]. In general, several pathways could explain the observed relationship. Our finding is consistent with several studies in sub Saharan Africa [20‐28] where HIV infected persons have been documented to have reduced treatment success rate compared to HIV uninfected persons. HIV infected persons with BC-PTB might hence benefit from closer clinical and laboratory monitoring and treatment adherence support so as to improve treatment success rate and reduce mortality rate.

In practice, strengthening the collaboration between tuberculosis and HIV control programs would improve the management of HIV infected persons with tuberculosis. This might enhance treatment success rate and reduced mortality rate.

We found that persons with BC-PTB who were more than 50 years of age had reduced treatment success rate and increased mortality rate. Studies in several parts of sub Saharan [20, 22, 23, 25, 27, 29‐33], indicate that older or increasing age is associated with reduced treatment success rate among persons with tuberculosis. This could be because older persons interrupt treatment adherence more often than younger persons, are challenged by several health determinants such as low socio-economic status as well as low immunity that cannot effectively fight infections [25], and medical complications that comes along with ageing. Comparable to our findings, a systematic review [34] found that persons who are 30 years of age and beyond tend to be non-adherent to anti-tuberculosis medications. Older persons with tuberculosis might therefore benefit from close monitoring for response to tuberculosis treatment [35].

Our study indicates that male sex is associated with lower treatment success rate compared to female sex. This finding is consistent with several studies in Africa [22, 25, 27]. In particular, the study in Nigeria [27], reports gender disparities in treatment outcomes where male sex was associated with reduced sputum smear conversion at 2 and 5 months of treatment, increased treatment failure and reduced treatment success rate. Another study in Benin reports male sex is associated with increased treatment failure [36], and treatment failure translates into unsuccessful treatment of tuberculosis.

The observed difference could be attributed to men’s poor healthcare seeking behavior compared to women [37], which translates to delayed diagnosis of tuberculosis and missing of clinic visits for drug refills hence treatment non-adherence and ultimately unsuccessful treatment of tuberculosis. Our finding implies that the need to design gender-specific interventions across tuberculosis programs might be beneficial.

Our data shows lower mortality rate in recent years, between 2016 and 2018, compared to later year. This improvement may be attributable to improvements in healthcare system over time: better staffing and improved healthcare provider competence and confidence to manage persons with BC-PTB through mentorships and coaching, and better counseling among others. Elsewhere [38], healthcare providers indicated that tuberculosis clinics have been established across most health facilities to provide more time to understand and solve the challenges of persons with tuberculosis. This approach has led to better management of persons with tuberculosis. In addition, continuous quality improvement interventions have been introduced to tackle operational challenges in tuberculosis programing. It was stated that these initiatives have strengthened the healthcare system.

Our study indicates that community-based DOTS is associated with reduced mortality rate compared to facility-based DOTS. This finding is consistent with the results of previous systematic reviews and meta-analyses where community-based DOTS is reported to improve treatment completion and cure, and to reduce mortality rate [39‐42]. One of the plausible reasons is that in community-based DOTS, persons with tuberculosis take medications under the direct supervision of a treatment supporter at home or in their community [43], and this is likely to result into better treatment adherence [44] and completion hence better cure rate and reduced mortality rate.

Our result is also consistent with findings of another meta-analysis which reports community-based DOTS is associated with lower mortality rate compared to facility-based DOTS [45]. Although there is sufficient evidence that community-based DOTS has better treatment outcomes compared to facility-based DOTS [39, 40], our result may suffer confounding due to indication, especially since we did not have data on disease severity. We recommend that in future, studies should measure disease severity when comparing mortality between facility and community-based DOTS.

In conclusion, we have shown that adult persons with BC-PTB in rural eastern Uganda have suboptimal treatment success rate and high mortality rate. Tuberculosis and HIV co-infection and older age were associated with reduced treatment success and increased mortality rates.

Integration of tuberculosis and HIV prevention and management should be enhanced; particularly early screening and prophylaxis for tuberculosis among HIV infected persons, especially those who are older as they have poorer prognosis with TB disease. Community-based DOTS should be implemented widely and more research should be done to examine successful ways for implementation of Community-based DOTS especially in rural areas such as those where our study was conducted.