Assessment of treatment outcome and analysis of factors responsible for unsuccessful treatment outcome in DOTS programs is of paramount importance particularly in smear-positive PTB patients as they harbor a highly contagious form of M. tuberculosis
that can be monitored for speed of bacteriologic conversion on chemotherapy [19
In this study, treatment success in smear-positive PTB patients was 89.0%, slightly higher than the WHO international target of 87% (updated target 2011–2015) but remarkably higher than previous studies conducted in some parts of Ethiopia including 74.8% in Southern region [14
] and 29.5% in Gondar area of Ethiopia [15
]. A recent community-randomized trial intervention in Southern Ethiopia has also reported a similarly high proportion of successful outcome (89.3%) using health extension workers (HEWs) to follow-up the patients [22
]. Our finding of higher successful outcome in Tigray region as compared to other areas in Ethiopia could be the result of the decentralization of DOTS to health posts in Tigray region that has substantially reduced treatment default from 32% in 1996 to 15% in 2003 [9
]. According to the report, this was attributed to two main factors: health posts nearer to patients' residence and the use of volunteer community health workers (CHWs) in tracing patients who default from treatment [9
]. This is also consistent with a finding in Tanzania where community based DOTS had higher successful outcome rate (81%) as compared to facility based DOTS (70%) [23
]. Another likely reason for the higher successful outcome could be the 100% physical access to a treatment centre in the Region [10
]. A study conducted in Addis Ababa reported that patients’ attitude and behavior towards the disease are major factors influencing treatment adherence [24
]. This higher successful treatment outcome rate in Tigray region implies that DOTS performance is encouraging and the region is on the right track in achieving the WHO targets and the millennium development goals (MDG) in TB control.
The 10.8% unsuccessful outcome found in this study is comparatively lower than the 16.7% report from Southern Ethiopia [14
] and the 11.3% default rate in Arsi Zone of Oromia [17
]. The 3.2% default and 3.9% death rate recorded in this study is also lower when compared with the corresponding outcomes from Gondar area, Northwest Ethiopia, where 18.3% patients had defaulted and 10.1% had died [15
]. Studies conducted in other parts of Ethiopia recorded higher proportion of poor outcome [14
] compared to our data. This difference could be due to variation in DOTS performance in the various study areas. This could be attributed to the use of community health workers in tracing and follow-up of TB patients in Tigray region [9
] and Southern Ethiopia [22
] that has resulted in an improved performance of DOTS as compared to other areas that do not use this strategy. Other reasons for this variation could be the difference in duration of study period, sample size and study setting. For example, the study in Southern Ethiopia was conducted over a longer period (2002–2007) and involved more than 6547 patients. Unlike our study, the study in Gondar area, Northwest Ethiopia, was conducted in a hospital setting.
Elsewhere in Africa, different outcomes had been reported in different countries. A study conducted in Nigeria recorded 76.6% cured, 8.1% failed, 6.6% defaulted, 2% treatment interruption, 4.8% transferred out, and 1.9% died [25
]. Another study in Tanzania reported treatment success rates of 81% and 70% in patients under community vs. facility-based DOTS, respectively [23
]. Among the 4003 smear-positive PTB patients evaluated on DOTS in Malawi, 72% had completed treatment, 20% had died, 4% defaulted, 2% were transferred out and 1% had still positive smears at the end of treatment [26
In a multivariate regression model, this study showed that unsuccessful treatment outcome was significantly higher among patients older than 40 years of age, family size greater than 5 persons, among those unemployed and amongst re-treatment patients, as compared to their counterparts.
Our observation of poor outcome in patients older than 40 years of age as compared to those aged 15–40 years is in agreement with the findings of previous studies in which older age increases the risk for unfavorable treatment outcome [13
]. One study stated that an age in excess of 46 years was found to be a significant risk factor for non-successful treatment outcome [27
]. Another study in Thailand showed that an age of above 60 years was significantly correlated with treatment interruption and treatment failure [29
]. Higher age has been previously reported to be a risk factor for death [15
]. It was documented that individuals at the extremes of age had the poorest outcomes [14
]. Older individuals often have concomitant diseases and general physiological deterioration with age, less able to reach health facilities and are also poorer than the younger population [14
Data from this study revealed that retreatment cases have an increased risk of unsuccessful outcome compared to new cases. This is consistent with other published reports, in which history of prior TB treatment was significantly associated with unsuccessful treatment outcome [14
]. It is also reported that prior sub-optimal therapy is known to be a major contributor to the development of multidrug resistance (MDR) TB [37
]. Thus, the high proportion of unsuccessful outcome in retreatment cases in our study could be related to a higher frequency of drug resistance. The prevalence of MDR TB in Ethiopia is estimated to be 1.6% among new cases and 12% among retreatment cases [5
]. According to a previous study, risk factors for unsuccessful outcome were associated with patient behavior and attitudes, as patients registered as defaulters tend to default again [14
]. Other risk factors include selection of drug-resistant strains and the development of severe and complicated forms of the disease, all of which contribute to poor outcome among previously treated patients [14
The higher proportion of unsuccessful treatment outcome in patients with family size greater than 5 persons or those unemployed could be due to the relation of unemployment and larger family sizes to low income. Patients with low income often suffer from malnutrition which may result in more drug side effects and low stamina among patients and may possibly lead to poor adherence, death or discontinuation of anti-TB chemotherapy. A study in Estonia [38
] and Brazil [39
] suggested that one of the main risk factors for TB was poverty. In our study, the majority of the TB patients (62.4%) had very low family income (<300 Birr per month). In agreement with this study, another study reported that unemployment was highly associated with unfavorable treatment outcome [40
Unlike the results of other studies, factors such as sex of patients, educational status, HIV status, and distance from treatment center did not show any statistically significant association with unsuccessful treatment outcome. According to many reports, urban residents [15
] and women [13
] had higher probabilities of successful treatment outcome.
The lack of any appreciable link between HIV status of patients and distance from treatment centre with TB treatment outcome was somewhat unexpected. Other studies had also indicated that most of the factors associated with treatment non-completion, apart from the patient’s age and level of education, are those related to physical access to health-care services [16
]. These differences between this study and other study results could be explained by differences in sample size among the studies, difference in disease burden, and socio-demographic factors. Variations in environmental factors or true biological effects, or even a combination of all factors could also explain the differences in the study results. In Tigray region, access to health care services was facilitated by the community health workers and this may have contributed to improved outcome, including for the HIV co-infected patients.
Previous studies established that HIV is associated with unsuccessful treatment outcomes which include treatment interruption [29
] and death [35
]. As previously reported, smear-negative PTB patients had the lowest rate of successful treatment outcome [42
]. These patients have a higher frequency of HIV co-infection; in addition, they may be less able to develop an adequate immune response to control the infection; furthermore their diagnosis is difficult, often resulting in treatment delay and poor outcome [44
]. Another study conducted in Ethiopia has shown that HIV-positive patients are more likely to default than HIV-negatives [45
]. This study also reported default rates of nearly 19% in extra-pulmonary TB (EPTB) and approximately 28% in smear-negative PTB (including EPTB). This and other related studies have indicated a background of HIV infection in these types of TB [45
]. Thus, on the other hand, the lack of association between HIV status and unsuccessful treatment outcome observed in this study may be due to the exclusion of these forms of TB associated with HIV infection.
The strength of this study lies in its ability to collect verified data from TB patients to determine treatment outcomes. Studying 15 randomly selected districts has enabled us to generalize our findings to the Region. Otherwise, the study was partly based on retrospective design; therefore, selection bias could occur as we were unable to trace the whereabouts of some patients. Other important variables including patient-health worker communication, delay in health care seeking and provider and health system related factors were not assessed. Furthermore, treatment outcome and associated risk factors for patients with extra-pulmonary TB, those with smear-negative PTB and patients younger than 15 years of age were also not evaluated in this study.