TUBERCULOSIS TREATMENT OUTCOMES: A FIFTEEN YEAR COHORT STUDY IN JOS NORTH AND MANGU, PLATEAU STATE, NORTH - CENTRAL NIGERIA

Tuberculosis (TB) is an infectious disease with a major global health problem; being the tenth leading cause of death worldwide, and the leading cause of death from a single infectious agent. Nigeria is among the countries with high burden of tuberculosis and the highest global mortality rate. Medication adherence has been shown to have profound effect on other treatment outcomes. Objective To examine a fifteen-year cohort of tuberculosis treatment outcomes in Jos North and Mangu Local Government Areas of Plateau State. The study was done in five treatment centers which account for more than half of data for tuberculosis patients in Plateau State, North-Central Nigeria. The retrospective study was done from 2001 to 2015, where TB patient records who had completed treatment were evaluated. Treatment outcomes were classified as successful (cured, treatment completed) or unsuccessful (non-adherent, treatment failure or death) and analyzed using binomial logistic regression. Abstract Background Tuberculosis (TB) is an infectious disease with a major global health problem; being the tenth leading cause of death worldwide, and the leading cause of death from a single infectious agent. Nigeria is among the countries with high burden of tuberculosis and the highest global mortality rate. Medication adherence has been shown to have profound effect on other treatment outcomes. Objective To examine a fifteen-year cohort of tuberculosis treatment outcomes in Jos North and Mangu Local Government Areas of Plateau State. Methods The study was done in five treatment centers which account for more than half of data for tuberculosis patients in Plateau State, North-Central Nigeria. The retrospective study was done from 2001 to 2015, where TB patient records who had completed treatment were evaluated. Treatment outcomes were classified as successful (cured, treatment completed) or unsuccessful (non-adherent, treatment failure or death) and analyzed using binomial logistic regression. voluntary counseling and testing of HIV among TB patients is advocated, particularly among the male population.

3 voluntary counseling and testing of HIV among TB patients is advocated, particularly among the male population.
Abstract Background Tuberculosis (TB) is an infectious disease with a major global health problem; being the tenth leading cause of death worldwide, and the leading cause of death from a single infectious agent. Nigeria is among the countries with high burden of tuberculosis and the highest global mortality rate.
Medication adherence has been shown to have profound effect on other treatment outcomes.

Objective
To examine a fifteen-year cohort of tuberculosis treatment outcomes in Jos North and Mangu Local Government Areas of Plateau State.

Methods
The study was done in five treatment centers which account for more than half of data for tuberculosis patients in Plateau State, North-Central Nigeria. The retrospective study was done from 2001 to 2015, where TB patient records who had completed treatment were evaluated. Treatment outcomes were classified as successful (cured, treatment completed) or unsuccessful (non-adherent, treatment failure or death) and analyzed using binomial logistic regression.

Results
Males composed 58.1% of the population (10,156). Mean age ±SD was 35.5±15.5 years. The overall treatment success rate was 67.4%; non-adherence/defaulting rate was 18.5%, with majority of patients defaulting at the end of intensive phase of treatment; sputum conversion rate was 72.8% and mortality rate was 7.5%. A decrease in successful treatment outcomes from 83.8% to 64.4%, with a corresponding increase in unsuccessful treatment outcomes was observed.

Conclusion
Underlying reasons for medication non-adherence and treatment failure identified should be resolved by the patient, treatment supporter and health worker. Increased awareness and education on Mycobacterium tuberculosis is an intracellular microorganism that replicates very slowly, therefore prolonged multi-drug treatment regimen (6 months) is the recommended treatment strategy implemented through the Directly Observed Therapy (DOT). 2 Because of this treatment regimen, medication non-adherence remains a potential and actual challenge. Efforts have been made to identify factors influencing medication adherence, [3][4][5][6][7][8][9] from which interventions [9][10][11][12][13] have been developed to improve adherence. This is because adherence has been shown to have profound effect on other treatment outcomes. 14 Another way of identifying areas for intervention is the study of the pattern of treatment outcomes over the years to identify specific areas in TB management that require intervention in order to improve these outcomes and health services. Treatment outcomes of 5 TB patients in this study were classified as successful (cure or treatment completed) or unsuccessful (default, treatment failure or death), as defined from the World Health Organization (WHO) and National TB and Leprosy Control Program (NTBLCP) guidelines. 1,2 In Nigeria, studies have reported trends in tuberculosis treatment outcomes for the country, 1 and in different states within the country. 15,16 However assessment of treatment outcomes in individual DOT centers is lacking. 17 This will enable treatment centre-specific interventions to be implemented. This study was done to evaluate TB treatment outcomes and determine their predictors in five DOT centers in Jos-North and Mangu Local government areas of Plateau state, North-Central Nigeria through a fifteen year cohort study. Ethical approval and permission to collect data was obtained form the various hospital's Institutional review boards/ Ethical Committes before data collection. All information obtained were treated with confidentiality. De-identified patient data were collected and used for analyses, so that anonymity of the patients was maintained throughout the study.

Data Collection
Data were collected from TB treatment cards from January 2001 to December 2015 by the researcher and a trained research assistant manually, using a pre-designed proforma before tranferring to a 6 personal computer. Incomplete data, especially those without treatment outcomes were excluded from the study therefore data from 10,156 TB patients were collected.

Data Analysis
Data checking and cleaning was done in Microsoft Excel before exporting to STATA® version 11.0 (College Station Texas, USA) for analysis. Binomial logistic regression analysis was done to determine the predictors of medication non-adherence.

Results
The mean age ± SD was 35.5±15.5. The males were slightly more (58 %) than the females (table 1

Discussion
This study examined treatment outcomes among a cohort of TB patients retrospectively from patient records over a 15-year period. An overall treatment success rate of 67.4%, less than the Nigerian and global success rate of 86% 1 was observed. A drop in the overall treatment success rate from 83.8% to 64.4% was also observed. The predictors of unsuccessful treatment outcomes were being male, having a history of non-adherence, treatment failure and unknown HIV status.
Tuberculosis disease was distributed slightly more in males than females as similarly observed in other studies. 19,20 The possible reasons given were; women experiencing barriers to service access, longer clinical delays in diagnosis or producing sputum of poor quality than men. 21 A community based intervention study however reported significantly more women diagnosed with TB at community level than in the health facilities because the interventions reduced barriers to services with poor women who had previously faced difficulties travelling to health centres particularly benefitting. 21 TB was found more in the productive age group as was similarly observed in other studies and consistent with global epidemiological findings. 15 The non-adherence/defaulting rate pattern observed a sharp increase (from 30.6% to 54.2%) in 2002, which was the highest defaulting rate observed over the years. This could be as a result of the strict compliance of DOT, where TB patients came everyday for 2-3 months (initial phase of treatment) with the DOT officers observing them take their medicines. This resulted to the high defaulting rate as the patients became tired of coming everday (most being very sick) and most patients could not afford transportation cost to the DOT centers. Recommendations were made to modify the DOT system of accessing TB treatment. 27,28 This probably led to the susequent decrease in defaulting rate as contact tracing, community DOT and decrease in number of visits to the DOT center from daily to weekly is being practiced.

Factors Associated with Treatment Outcomes
Males were 1.15 times more likely to default from taking their anti TB medicines than females as similarly observed in other studies. 17,29 A study further attributed the more likelihood of default and poor treatment outcomes in men to high risk behaviour (alcohol, substance and tobacco abuse). 29 Females were more likely to have successful treatment outcomes because of a greater immune response due to oestrogen, which increases interferon alpha gamma and potentiates the macrophage activation while testosterone in males inhibits immune response. However this effect is reversed in HIV positive TB patients where males tend to have a better immune response than females. 30 9 TB patients were 4 times likely to default if they did not know their HIV status in the course of their TB treatment. This finding was not consistent with that of Central Ethiopia and Abuja-Nigeria, where TB/HIV co-infected patients had less likelihood of having successful treatment outcomes. 22,26 One plausible explanation for our finding is that HIV infected patients who have TB co-infection were likely to have received more/reinforced adherence counseling from trained adherence counselors prior to commencement of therapy thus, may be more aware of the consequences of non-adherence in TB/HIV co-infection.
TB patients with a history of defaulting/ non-adherence had a 2.3 times higher likelihood to default again from taking their anti-TB medicines, consistent with findings from other studies. 22,25 A strengthening of adherence counseling is encouraged so that factors responsible can be identified and resolved. This is important because non-adherence and regular treatment interruptions can lead to development of resistant TB, treatment failure, relapse, longer infections or even death as similarly reported. 22 Once a patient defaults from TB treatment, the likelihood of treatment failure increases most likely from the development of drug resistance, leading to poor/unsuccessful treatment outcomes. Some of the data was limited by some missing variables in patients' medical record charts and were eliminated in the course of data checking and cleaning.
In conclusion, findings from this research have revealed an increase in the number of enrolments of TB patients in Plateau State. TB treatment outcomes from five DOT facilities were evaluated to show a decrease in tuberculosis treatment success rates in Plateau State from a fifteen year cohort study.
Therefore, appropriate interventions that would detect underlying reasons for non-adherence among males, those with a history of defaulting, especially at the end of the intensive phase is advocated.

Declarations
Ethics approval and consent to participate Ethical approval and permission to collect data was obtained form the institutional review boards/ Ethical Committe before data collection: Jos University Teaching Hospital: Institutional Health Research Ethical Committee Reference Number: JUTH/DCS/ADM/127/XIX/6058, All information obtained were treated with confidentiality. De-identified patient data were used for analyses, so that anonymity of the patients was maintained.

Consent for Publication
Not Applicable

Availability of Data and Materials
The datasets generated and analyzed during the current study are available from the corresonding author on reasonable request.

Competing Interest
The authors declare that they have no competing interests.