Treatment outcomes of patients with tuberculosis in war affected region of Khyber Paktunkhwa, Pakistan


 Background: Globally, tuberculosis (TB) remains the leading cause of death from a single infectious disease. TB treatment outcome is an indicator for the effectiveness of a national TB control program. This study aimed to assess treatment outcomes of TB patients and its determinants in Batkhela, Khyber Pakhtunkhwa, Pakistan.
Methods: A retrospective cohort study was designed using all TB patients who were enrolled at District Head Quarter (DHQ) Hospital Batkhela, Pakistan, from January 2011 to December 2014. A multivariable logistic regression models were used to identify factors associated with successful TB treatment outcomes defined as the sum of cure and completed treatment. 
Results: A total of 515 TB patients were registered, of which 237 (46%) were males and 278 (53.98%) females. Of all patients, 234 (45.44%) were cured and 210 (40.77%) completed treatment. The overall treatment success rate was 444 (86.21%). Age 0-20 years (adjusted odds ratio, AOR= 3.47; 95% confidence interval, CI)= 1.54-7.81; P= 0.003), smear-positive pulmonary TB (AOR)= 3.58; 95% CI= 1.89-6.78; P= <0.001), treatment category (AOR= 4.71; 95% CI= 1.17-18.97; P= 0.029), and year of enrollment 2012 (AOR= 6.26; 95% CI= 2.52-15.59; P= <0.001) were significantly associated with successful treatment outcome.
Conclusions: The overall treatment success rate is satisfactory but still need to be improved to achieve the international targeted treatment outcome. Type of TB, age, treatment category, and year of enrollment were significantly associated with successful treatment outcomes.


Abstract
Background: Globally, tuberculosis (TB) remains the leading cause of death from a single infectious disease. TB treatment outcome is an indicator for the effectiveness of a national TB control program. This study aimed to assess treatment outcomes of TB patients and its determinants in Batkhela, Khyber Pakhtunkhwa, Pakistan.
Methods: A retrospective cohort study was designed using all TB patients who were (AOR= 6.26; 95% CI= 2.52-15.59; P= <0.001) were significantly associated with successful treatment outcome. Conclusions: The overall treatment success rate is satisfactory but still need to be improved to achieve the international targeted treatment outcome. Type of TB, age, treatment category, and year of enrollment were significantly associated with successful treatment outcomes.
Increasing the rate of successful treatment outcome is one of the strategies for effective control of TB in the community. The End TB Strategy defines targets for 2030; to decrease the incidence rate by 80% (new cases per 100,000 population per year) and 90% reduction in the number of TB deaths compared with levels in 2015 [3]. However, successful treatment outcome has increased in several countries following the implementation of Directly Observed Treatment Short-Course (DOTS) program [4]. TB is still a major health problem in Pakistan, with an estimated 510,000 new TB cases and approximately 15,000 drug resistant TB cases reported every year [5]. Recently, a standardized TB prevention and control program that regularly monitors the incidence of TB and as well as drug susceptibility testing in the population has been launched at Hayatabad Medical Complex Peshawar, Khyber Pakhtunkhwa province [6]. In Khyber Pakhtunkhwa province of Pakistan several studies have been conducted on the prevalence of TB [7][8][9][10][11][12], however, there are limited studies on the treatment outcome of TB [13]. Therefore, this study was undertaken to assess TB treatment outcome and its determinants in Batkhela, Khyber Pakhtunkhwa, Pakistan.

Study setting
Batkhela is the capital city of Malakand district and it is one of the popular business city in Khyber Pakhtunkhwa province. Malakand district is situated in Khyber Pakhtunkhwa province. The total population of the district is 720,295 (2017 census) [14]. The area is surrounded by district Dir (Lower) in the north, Swat district in the east, Mardan and Charsadda districts in the south east and south west respectively, Mohmand and Bajaur agencies are in the west (Fig. 1). The DHQ Hospital Batkhela, providing health care facilities to the local residence of Batkhela and district Malakand. The area has been providing humanitarian protection and shelter for a large number of refugees from different districts of Malakand division during flood and war.

Study population
All TB patients who were enrolled at DHQ Hospital between 1 st January 2011 and 31 st December 2014 were included.

Study design and data collection
A hospital based retrospective cohort study was conducted. Data were collected from patient medical records and TB registration books. The registration books contained basic information such as socio-demography and clinical profile of the patients, date of TB diagnosis and treatment outcome. The data was collected by trained unit healthcare personnel under supervision of principal investigator by using self-designed performa and entered into Excel sheet.

Laboratory procedure
According to the standard protocol the sputum was collected from the suspected patients having symptom of TB in 5ml sterile bottle, after collection of sputum the bottle were kept in 15 ml sterile bottle to avoid the leakage of the infectious samples. The samples were labeled and further process by the laboratory technician of the hospitals. Smear microscopy with Ziehl-Neelsen staining and fluorescence microscopy are used in the Hospital for both the diagnosis and monitoring of TB [15].

Standard definition
TB treatment outcomes and clinical cases were defined according to the standard World Health Organization (WHO) definitions (Table 1). In this study, treatment success was defined as a sum of cured and treatment completed; and poor treatment was defined as the sum of treatment failure, death or lost to follow up. A patient who was initially sputum smear-positive and who finished treatment with bacteriology result at the end of treatment or was sputum smear negative on two occa end of treatment Treatment completed A patient who completed treatment but did not meet the criteria for cure or failure; th applies to sputum smear-positive and sputum smear-negative patients with pulmonar patients with EPTB Treatment failure A patient who was initially sputum smear-positive and remained bacteriology or spu positive at month five or later during treatment Death A patient who died from any cause during the course of treatment.
Lost to follow-up a patient who has been on treatment for at least four weeks and whose treatment was for eight or more consecutive weeks Transfer out A patient who has been transferred to another recording and reporting unit and whose outcome is unknown Successful treatment outcome A patient who was cured or completed treatment Unsuccessful treatment outcome A patient who had treatment failure, lost to follow up, or death Smear-positive pulmonary TB A patient with at least two sputum specimens which were positive for acid fast baci microscopy, or a patient with only one sputum specimen which was positive for AFB by and chest radiographic abnormalities consistent with active pulmonary tuberculosis (PTB Smear-negative pulmonary tuberculosis A patient with symptoms suggestive of TB, with at least two sputum specimens negative for AFB by microscopy, and with chest radiographic abnormalities consistent PTB, or a patient with two sets of at least two sputum specimens taken at least two w and which were negative for AFB by microscopy and radiographic abnormalities con PTB and lack of clinical response to one week of broad spectrum antibiotic therapy.

Extra-pulmonary tuberculosis (EPTB)
This included TB of organs other than the lungs, such as lymph nodes, abdomen, ge tract, skin, joints and bones, the meninges and others.

Statistical analysis
The collected data were checked for completeness by principal investor. Data were entered, cleared and descriptive analyses were carried out using Statistical Package for Social Sciences (SPSS) version 20. Multivariable logistic regression model was used to analyze the association between treatment outcome and potential determinate variables at 95% confidence interval. P-value of less than 0.05 was considered as statistically significant.

Results
A total of 515 TB patients, registered and treated for TB at DHQ Hospital between January 2011 to December 2014, were included in this study. Of these, 278 (53.98%) were female and 185 (35.92%) were age less than 20 years (Table 2).

Clinical characteristics of the patients
Of the total patients, 252 (48.93%) were smear positive PTB, 82 (15.92%) were smear negative PTB and 181 (35.15%) were EPTB as shown in Table 2
In this study, patients with age less than 60 years were nearly three times more likely to get successful treatment outcome as compared to patients with age greater than 61 years. These results are consistent with previous studies conducted in Ethiopia [26]. This may be due to the fact that older age patients are at a higher risk of death due to ageing. Another reason for low treatment outcome in older age patients could be because older age patients might be at higher risk of having chronic comorbidities such as cardiovascular diseases, hypertensions, and cancers.
Low socio-economic status, poor adherence to treatment, and difficulty of traveling and arriving early at health facilities for DOTS could be also other reasons for low treatment outcomes in older age patients. These findings highlight the importance of providing close follow up for older age patients to increase their successful treatment outcome. Secondly, in this study those patients who had documented evidence of completion were counted as having a successful treatment outcome, whereas they may have undetected failure of therapy. This may lead to overestimation of the treatment outcome rate in our study. Third, as the study used data reported between 2011 and 2014, we have not assessed recent treatment outcomes, and a longer follow-up period will be required to assess longer-term trends in treatment outcomes.

Conclusions
The overall treatment success rate is satisfactory but still need to be improved to achieve the international targeted End TB Strategy milestones. Type of TB, age, treatment category, and year of enrollment were significantly associated with successful treatment outcomes. Successful treatment outcomes were decreased over time which is an alarming signal for MDR-TB.  Supplementary data.xlsx