Factors associated with tuberculosis treatment completion by Gender during 2014 - 2016 in Kampala, Uganda: A retrospective descriptive study

A retrospective cohort study using routine data of all eligible individuals who were initiated on first-line TB therapy between 2014 and 2016. De-identified data was obtained from all the Kampala divisions electronic TB registers, cleaned and analysed using STATA version 13. females, males more from TB care and die compared to females.


Abstract Background
To date, limited number of studies have explored the effect of gender in treatment outcomes in Uganda. No data on disaggregated treatment outcomes and influential factors by gender has been comprehensive compiled by the existing studies.

Objective
To determine the gender differences in TB patients treatment outcomes between 2014 and 2016 in Kampala in order to inform national policy and provide targeted interventions.

Methods
A retrospective cohort study using routine data of all eligible individuals who were initiated on first-line TB therapy between 2014 and 2016. De-identified data was obtained from all the Kampala divisions electronic TB registers, cleaned and analysed using STATA version 13.

Results
Of the 18,855 patients started on treatment during the study period, only 17,461 were included in the final analysis. Males were more likely to be 35 years or older, received DOT at facility yet females were more likely to be new patients. In addition, males were more likely to be pulmonary bacteriologically confirmed than females (OR 1.08 95% CI 1.00 -1.17). Successful treatment completion and ART uptake were similar by gender. Of all outcomes, 83% were treatment successfully, 11% died, 1% treatment failed treatment and 5% got lost to follow-up. Compared to females, males were more likely to be lost from TB care and die compared to females.

Conclusion
Among TB patients in Kampala from 2014 to 2016, we found evidence that successful treatment completion is not influenced by gender. However other factors that may be associated with successful TB treatment completion include age, disease classification, HIV status and type of patient. Background Tuberculosis (TB) is an airborne-transmitted infectious disease with high morbidity and mortality around the world. According to the 2017 global TB report, an estimated 10.4 million people fell ill with TB in the previous year (Global TB report 2017). TB burden is more pronounced in African countries probably due to high HIV prevalence and so the continent accounts for about 25% of TB cases (Global TB report, 2017). In the above report, approximately 1.9 times males aged 15 years and old were diagnosed with TB worldwide compared to females in 2016.
While previous studies have reported gender disparities in health seeking behavior and treatment outcomes (Chandrashekhar T Sreeramareddy et al, 2014), late access to TB treatment and adherence coupled with health system challenges often lead to poor treatment outcomes and high mortality as well (Abhijit . Differences in health literacy, sociocultural factors, provider or system-level barriers, low degree TB suspicion index by health provider, the number and types of providers seen before TB diagnosis have been reported as contributing to the differences in TB clinical status at presentation, notification rates and TB treatment outcomes by gender (Dodor et al, 2005). These factors can be summarized into three broad themes: TB-related knowledge, education gender roles and status in the family. Surprisingly, despite facing more socioeconomic and cultural adversities women are less likely to die, fail or default from TB treatment compared to men (Jimenez-Corona ME et al, 2006).
To date, a limited number of investigators have explored the factors associated with treatment completion by gender especially within a single cohort in Uganda. In addition, most studies of gender and TB have been conducted in high resource settings, and the extent to which differences in management by gender persist in low-resource contexts is not clear. Pearson's chi-square and two sample t-test was used for categorical variables to evaluate associations between dependent and independent variables. All variables with a p-value less or equal to 0.20 at the bi-variable analysis stage were included in a logistic regression to identify factors associated with treatment completion by gender.
In addition, collinearity and confounding elements among factors were checked and removed from the final model. The association was considered significant between predictor variables with the dependent variable if the p-value was < 0.05. Odds ratios and their corresponding 95% confidence interval (CI) were reported as the measures of association.

Ethical considerations
Prior to data collection, ethical approval was obtained from the School of Medicine The study will inform national policy and provide targeted gender based interventions aimed at reducing disproportionate TB burden in the country.

1.
To Providing ART to TB/HIV co-infected immediately during TB treatment reduces the risk of dying or getting lost to follow up. These findings disclose the differences between male and female TB patients with regards to clinical characteristics and possible impact on treatment outcomes. We did not divide deaths as being TB related or non-TB related due to the difficulties in evaluating the impact of TB on mortality. All-cause mortality is more objective and applicable in clinical practice.

Conclusions
Furthermore the study was performed in an under developed country with a high HIV prevalence, and ART initiation may have not been prompt and routine among all TB/HIV co-infected patients. This may limit the ability of our findings to be applied to high to middle-income countries or low HIV endemic areas.
Since getting lost to follow up during TB treatment was influenced by male gender and patient type, instituting gender-specific strategies in TB management like getting family or community support for male patients could reduce unfavourable treatment outcomes. Integration of TB and HIV services especially for counselling may also allow for efficient delivery of important information to patients. Further studies focusing on immunological characteristics are also warranted to elucidate gender related factors other than socio-cultural and clinical factors.
There are several limitations to this study. The duration of presenting symptoms or extent of disease before diagnosis was not recorded in our patients, yet this may influence outcomes. Study hospitals included a national referral hospital where patients with a higher severity or co-morbidities may have been included.
We also acknowledge that interpretation of the strength of our findings should be considered in the context of multiple statistical comparisons, and that the potential for type-1 errors exists. The differences that we reported were generally small-tomoderate in magnitude, and caution should be taken in ascribing too much importance to any single finding. Ethics approval was obtained from the Makerere University College of Health sciences research ethics review board. As secondary data were used, the need for informed patient consent was waived.

Consent for publication
Not applicable

Availability of data and material
The data collected and used for the study is available and there is no objection from Uganda Ministry of Health to share this data

Competing interests
Authors declare no competing interest   According to the standard definitions adopted from WHO, the following clinical case and treatment outcome operational terms will be used:

Pulmonary Bacteriologically Confirmed TB patient (P-BC)
A patient with Genexpert sputum test results MTB detected or at least one sputum specimen which with positive for acid fast bacilli (AFB) by microscopy.

Pulmonary Clinically Diagnosed TB patient (P-CD)
A patient who does not fulfil the criteria for bacteriological confirmation but has been diagnosed with active TB by a clinician or other medical practitioner who has decided to give the patient a full course of TB treatment. This includes cases diagnosed on the basis of X-ray abnormalities or suggestive histology and Extra Pulmonary cases without laboratory confirmation.

Extra Pulmonary TB patient (EPTB)
This is a patient with TB in the organs other than the lungs, such as lymph nodes, abdomen, genitourinary tract, skin, joints and bones, the meninges and others.  Mortality in TB patients is mainly affected by age, disease classification, ART uptake and health facility level of care. This means that younger, clinically diagnosed or extra-pulmonary who are treated from lower levels of care are prone to death. Providing ART to TB/HIV coinfected immediately during TB treatment reduces the risk of dying or getting lost to follow up. These findings disclose the differences between male and female TB patients with regards to clinical characteristics and possible impact on treatment outcomes. We did not divide deaths as being TB related or non-TB related due to the difficulties in evaluating the impact of TB on mortality. All-cause mortality is more objective and applicable in clinical practice.

Conclusions
Furthermore the study was performed in an under developed country with a high HIV prevalence, and ART initiation may have not been prompt and routine among all TB/HIV coinfected patients. This may limit the ability of our findings to be applied to high to middleincome countries or low HIV endemic areas.
Since getting lost to follow up during TB treatment was influenced by male gender and patient type, instituting gender-specific strategies in TB management like getting family or community support for male patients could reduce unfavourable treatment outcomes. Integration of TB and HIV services especially for counselling may also allow for efficient delivery of important information to patients. Further studies focusing on immunological characteristics are also warranted to elucidate gender related factors other than socio-cultural and clinical factors.
There are several limitations to this study. The duration of presenting symptoms or extent of disease before diagnosis was not recorded in our patients, yet this may influence outcomes.
Study hospitals included a national referral hospital where patients with a higher severity or co-morbidities may have been included.
We also acknowledge that interpretation of the strength of our findings should be considered in the context of multiple statistical comparisons, and that the potential for type-1 errors exists. The differences that we reported were generally small-to-moderate in magnitude, and caution should be taken in ascribing too much importance to any single finding. Ethics approval was obtained from the Makerere University College of Health sciences research ethics review board. As secondary data were used, the need for informed patient consent was waived.

Consent for publication
Not applicable

Availability of data and material
The data collected and used for the study is available and there is no objection from Uganda Ministry of Health to share this data

Competing interests
Authors declare no competing interest  According to the standard definitions adopted from WHO, the following clinical case and treatment outcome operational terms will be used:

Pulmonary Bacteriologically Confirmed TB patient (P-BC)
A patient with Genexpert sputum test results MTB detected or at least one sputum specimen which with positive for acid fast bacilli (AFB) by microscopy.

Pulmonary Clinically Diagnosed TB patient (P-CD)
A patient who does not fulfil the criteria for bacteriological confirmation but has been diagnosed with active TB by a clinician or other medical practitioner who has decided to give the patient a full course of TB treatment. This includes cases diagnosed on the basis of X-ray abnormalities or suggestive histology and Extra Pulmonary cases without laboratory confirmation.

Extra Pulmonary TB patient (EPTB)
This is a patient with TB in the organs other than the lungs, such as lymph nodes, abdomen, genitourinary tract, skin, joints and bones, the meninges and others.
According to WHO, treatment outcomes were categorized into, successful treatment completion is if TB patient cured (negative smear microscopy at the end of treatment and on at least one previous follow-up test) or completed treatment with resolution of symptoms.
Unsuccessful treatment completion on the other hand is if treatment resulted in treatment failure (remaining smear-positive after 5 months of treatment), getting lost to follow up (patients who interrupted their treatment for two consecutive months or more after registration), or died.