Treatment outcomes and factors associated with “successful treatment” among tuberculosis patients at peripheral health settings of Northern Ethiopia: a registry-based retrospective case-series analysis.

Objective: Evidence on treatment outcomes and identifying factors facilitating treatment success through a register based retrospective study have significant contribution in the improvement of a national tuberculosis program. This study was aimed at determining treatment outcomes and factors associated with “successful treatment” outcomes. Results: A total of 3445 patient records were included. More than half, (58%) were males and the mean age was 33.88 ± 16.91 years (range: 0-90). From the total TB patients, 18.8% were HIV co infected. The treatment outcome of TB patients were 371 (10.8%) cured, 2234 (64.8) treatment completed, died 119 (3.5%) died, 9 (0.3%) failed, 178 (5.1%) defaulted and 534 (15.5%) were transferred out. The overall treatment success rate was 89.5%. The overall treatment success rate was 87% in year 2009-2010 to 92.8% in 2013-2014 with 6.67% change in the outcome indicator over the five years period. Among pulmonary TB, pulmonary negative TB and extra pulmonary TB the rate of successful treatment outcome was 83.1% to 89%, 85.1% to 89.4%, and 87.4% to 92%, respectively in the year 2009-2010 to 2013-2014. The percentage of the overall successful treatment outcomes were significantly associated with the year of treatment (p- =0.014).


Introduction
Tuberculosis (TB) is placed as one of the top ten and third cause of morbidity from all diseases and infectious disease, respectively. Every day, around 5,000 TB related deaths are recorded, of which, 95% occur in low-and middle-income countries (LMICs) [1]. Moreover, multidrug/rifampicin-resistant TB (MDR/RR-TB) is becoming a public health crisis and health security threat [2]. The main strategy to control TB relies on early diagnosis and prompt treatment initiation [3]. WHO has implemented the standardized directly observed treatment, short-course (DOTS)/Stop TB Strategy to scale up TB prevention and control. Despite the efforts made under the global End TB strategy, a significant number of people are unknown to the health system or are not receiving proper treatment. Majority of these belongs to peripheral health settings of LMICs [4,5]. For example TB treatment saved about 54 million lives globally between 2000 and 2017, but important diagnostic and treatment gaps persist. TB treatment success rate for people with TB was 83% in 2016. Most of the gaps in detection and treatment were in WHO African region, where the burden of HIV associated TB is highest [6]. Studies have indicated that access to treatment, poor socioeconomic status, health service access and use, treatment seeking behavior and poor knowledge about the disease affects treatment outcomes [7]. Ethiopia is among the 22 high TB and 30 MDR-TB burden countries [1]. In Ethiopia, the incidence of TB and MDR/RR-TB in 2018 was 164 and 5.2 per 100,000 populations, respectively [8]. The TB control program in Ethiopia introduced health facility-based DOTS as a pilot program in 1992. Since then a number of patients were enrolled to the national TB program. Though Ethiopia national TB program is working under the global strategy, there are challenges in the success of the national TB program [9]. WHO recommends that treatment outcome analysis should be carried out every year at national and district levels [10]. Hence, determining treatment outcome and factors affecting treatment outcome will in turn contribute to the improvement of TB control programs and to decrease TB morbidity and mortality. In Ethiopia considerable number of studies has been conducted, showing different TB treatment outcomes [11][12][13][14][15][16][17][18][19]. However, further information is required on the outcomes of TB treatment in all forms of TB and all age groups and on factors responsible for facilitating treatment outcome. Therefore, this study was aimed at assessing tuberculosis treatment outcomes and factors associated with treatment success in all forms of TB patients that have been treated for TB in the health settings.

Study setting
The study was conducted in three peripheral health facilities; Mekelle, Semen and Kasech Health Centers of Mekelle, in Northern Ethiopia. The study area is located 783 kms to the North of the capital city of Ethiopia, Addis Ababa. The total population of Mekelle has been estimated to be around 216,000 in 2007 [20].
Selected health facilities were the biggest facilities in terms of TB care and treatment provision with highest patient flow and were located in the relatively high performer zone with regard to TB case detection [21]. Based on the TB clinics' registration log books, on average 230, 300 and 160 patients per year were estimated to be receiving TB treatments in Mekelle, Semen and Kassech Health Centers, respectively.

Study design and data collection procedure
The study design was a register based retrospective case series analyses on patients of all TB forms who received TB therapy between July 2009 and July 2014. A structured data extraction form was prepared and used to collect information on socio-demographic characteristics (such as age and sex) and clinical-related data (such as, TB history, TB type, date starting treatment, HIV status, date end of treatment and treatment outcome). The data source was the TB registers at the TB clinics of the health facilities, where all patients diagnosed for active TB disease are put on anti-TB treatment and monitored throughout the treatment course. The inclusion criteria were having a complete and readable record in the TB registration book and patients that were diagnosed as non TB after starting of treatment were excluded from the study.

Operational definition
Treatment outcome was defined according to the existing WHO definitions at the time of data collection [22]. Accordingly, components were defined as follows: cured-pulmonary TB patient with smear or culture negative in the last month of treatment and at least one previous occasion. Treatment completed -A TB patient who completed treatment without evidence of failure but with no record to show that sputum smear or culture results in the last month of treatment and on at least one previous occasion were negative, either because tests were not done or because results are unavailable. Treatment failed-is a TB patient whose sputum smear or culture is positive at month 5 or later during treatment. Died -is defined as TB patient who dies for any reason before starting or during the course of treatment. Lost to follow up-A TB patient who did not start treatment or whose treatment was interrupted for 2 consecutive months or more. Not evaluated-A TB patient for whom no treatment outcome is assigned. This includes cases "transferred out" to another treatment unit as well as cases for whom the treatment outcome is unknown to the reporting unit. Treatment success-was defined as the sum of cured and treatment completed. In this study the findings of transferred out patients were not included as one of the TB treatment outcomes.

Statistical analysis
SPSS version 22 for Windows was used for data analysis. Descriptive statistics were used to summarize patients, characteristics across the outcomes variables. Trend analysis was performed using the percentages of successful treatment outcomes.
Moreover, percentage changes in outcome indicators for five years period was analysed. Trend p-value less than 0.05 were considered as statistically significant. Report of the Ministry of Health which was shown to increase from 84% in 2010 to 92% in 2014 [26]. The possible reason might be due to improved adherence of patients to anti-tuberculosis treatment. The overall successful treatment outcome recorded in the present study was in agreement with previous studies conducted in Ethiopia and elsewhere [13,18,[27][28][29][30]]. Our result is higher the national pooled estimates (68.1%) calculated for six European countries [31]. In this report, a cure rate of 69.1% was found in pulmonary positive patients. Difference in outcome could be due to variation in DOTS performance. Other reasons could be difference in duration of study period, sample size and in the study setting.

Results
The proportion of HIV+/TB co-infection (18.8%) in the present study was higher than the national average (10.7%) [26], but was lower than (29. 4

Limitations
One of the major limitations of this study was the use of retrospective secondary data, which is limited to whatever documented in the TB registers of the TB clinic.
Variables such as treatment adherence and other disease conditions which might affect outcome were not captured in the patient's file. Furthermore, selected sites encompass small geographic region and hence patients from these facilities might have a different profile from patients residing in other parts of the country. Another limitation might emerge from the study design where we cannot make causal inferences regarding the efficacy of the investigated treatment and the internal validity might be low due to the lack of comparator group.

Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests

Authors' contribution
IA participated in all phases of the study including writing the proposal, data collection and writing the manuscript. MA participated in the study as advisor and monitoring and evaluation activities. MS participated in the study as advisor and helped with statistics. SN helped with writing the proposal and helped during data collection. All authors will read and approve the final manuscript before publishing.