Predictors of tuberculosis infection among adults visiting anti-retroviral treatment center at east and west Gojjam, northwest, Ethiopia, 2017

Tuberculosis (TB) is often the commonest infection to develop among people living with human immunodeficiency virus (PLWHIV). Among the world’s 22 high-burden tuberculosis countries, Ethiopia ranks the seventh in worldwide and third in Africa [1]. HIV pandemic presents a massive challenge to the control of TB at all levels. In high HIV prevalence population, TB is a principal cause of morbidity and death, and HIV is driving the tuberculosis epidemic in many countries, especially in sub-Saharan Africa [2]. TB is leading cause of death among PLWHIV, which known as “fatal duo” as HIV reduces the body’s defense system and makes them more horizontal to TB infection. On the other hand, TB increases the development of HIV to acquired immune deficiency syndrome (AIDS) stages [3]. The association between HIV and TB often described as a co-epidemic; they are far harsher together than either disease alone in developing countries many people infected with HIV catch TB as the first sign of AIDS [4]. TB is the most common opportunistic infection in PLWHIV worldwide [5]. It is the first presenting sign in the majority of AIDS patients, including those who are taking antiretroviral treatment (ART). Despite major reductions with ART, however, risk of TB remains high in Africa [6, 7]. Globally, an estimated 13% of TB cases co-infected with HIV, and the bacteria accelerate the progression of HIV to AIDS [7]. Without proper treatment, 90% of PLWHIV die within months of contracting TB. The current challenge is to find ways of preventing both TB and HIV, and to improve diagnosis and management of co-infection, so the HIV/AIDS and Mycobacterium tuberculosis co-infection is one of the major global challenges in the prevention of TB and accounts for 33% HIV related deaths [6, 8]. Progress against HIV has far outstripped global efforts to tackle TB. In 2014, for the first time in decades, TB killed more people than any other infectious disease in the world. HIV infection is the strongest known risk factor for TB and estimated that there were 1.4 million TB deaths in 2015, and an additional 0.4 million co-morbid deaths [8‐10]. HIV-infected people have an annual risk of 5–15% of developing active TB once infected, and have a much higher risk of developing active TB than HIV-negative individuals [10‐13]. In resource-limited settings, the healthcare systems flurry under by the preventive, therapeutic and diagnostic challenges of the HIV–TB syndemic. However, HIV is not the only determinant for developing TB, various other factors: socio-demographic, clinical, life style and environmental are determinant for TB in HIV positives [14, 15]. In Ethiopia, the ministry of health attempt to improve community level access to care by decentralizing TB/HIV service from hospital to health centers and build up referral systems as well as step up standard operating procedures and standards of care to improve the quality [16, 17], but the burden of TB/HIV infection is still high. This unexpected scale of the outbreak of HIV related tuberculosis demands intensive and urgent action, but also there is no such study in the study area conducted before. Therefore, the aim of this study is to identify predictors of tuberculosis infection among HIV infected adults’ visiting anti-retroviral treatment center in public health institutions in East and West Gojjam Zone, Northwest Ethiopia, 2017.

Among 556 selected study participants, 552 study subjects (139 cases (25.2%) and 413 controls (72%) were responded and the overall response rate were 99.2% (96.5% for cases and 99% for controls). A higher percentage of women observed in the study participants 301(54.5%). Sixty-six (47.5%) of the cases and 235 (57%) of the controls were females. The median age of the participants was 32.5 years and IQR of 25–41.75. Seventy-six (54.7%) of the cases and 249 (60.3%) of the controls were rural residents. More than 2/3 of the study participants were completed primary school and above; 66.9% in the cases and 71.67% in the controls (Table 1).

This study showed that HIV infected adults taking CPT and early WHO clinical stage I/ II were less likely to the incidence of TB infection. Although, drinking alcohol, TB history in the family, CD₄ cell count of ≤200cells/μl and between 201 and 499 cells/μl, functional status of bedridden and ambulatory and having BMI of < 18.5 kg/^m2 were predictors of expansion of TB infection among HIV infected adults.

Our findings show that alcohol drinkers were predictors of TB infection among HIV positive patients in this study. This was consistent with previous studies conducted in South India [18], West Africa [19] and Amhara Region [20]. Nevertheless, in contrast to the study conducted in Gambia [21] alcohol use is not associated with TB infection, this is because of socio-demography, sampling technique difference and sample size. Smoking was not associated with increased TB infection in this study; this is in agreement with previous study conducted in Addis Ababa [22]. However, in other study conducted in West Africa [19], which identified smoking as predictors for increased TB infection among HIV infected adults, this difference was probably due to sample size difference, social desirability bias where smokers deprived of their smoking status in this study. Previous TB history in the family found to be predictors for increased TB occurrence in the study; this is in line with the study conducted in Croatia, West Africa and southwest Ethiopia [19, 23, 24].

Low body mass index (LBMI< 18.5 kg/ m²) was associated with increased TB infection in this study; this is parallel to a study done in South India [18], Croatia [23], South Africa [25] and south central Ethiopia [26]. This might be due to the fact that under nutrition deteriorates the immunity level that increases the reactivation of latent tuberculosis infection. On the other hand, malnutrition can aggravate the immune deficiency and increase the risk of active TB. Building on the existing knowledge this study also found out that low body mass index increased the likelihood of tuberculosis infection [22, 27]. The CD₄ count ≤200 cells/μl and between 201 and 499 cells/μl were about 2.34 and 2.63 times more likely to develop TB as compared to CD₄ count ≥500 cells/μl respectively. This is comparable with previous reports conducted [14, 20, 24, 26, 28‐33]. The most important predictors for the development of TB in HIV patients as it frequently reported in literatures are the immunological state of the person. Maintaining the CD4 positive cell level as high as possible in patients with advanced disease helps the person to have low risk of re-activation of tubercle bacilli [34]. This study confirm that patients with functional status bedridden and ambulatory were 3.3 and 8 times more likely predictors for the expansion of TB infection, this is related to other findings conducted in Hawassa, Addis Ababa, Northwest Ethiopia and Amhara Region [11, 20, 26, 32, 34]. This is because of the low immunity behavior of the participant during the study period.

In addition, our findings indicating that cotrimoxazole preventive therapy had protective effect against TB infection were also consistent with previous research reports [11, 14, 35, 36]. Cotrimoxazole preventive therapy has advantageous effect in increasing CD4 cell count as well falling viral load and CPT is reasonably priced and is generally well tolerated, this endorse TB/HIV associations should give priority high level coverage to the achievement of cotrimoxazole preventive therapy as they have proven usefulness in improving patients condition [27]. Different studies have shown that isonized preventive therapy reduces the risk of infection in people living with HIV however, differently in this study IPT has not associated with risk of TB, because of low coverage of IPT [31] and confounding factors in the study participants. WHO clinical staging and TB infection among HIV positive adults were significantly associated in the study. Those patients in WHO clinical stage I/ II were about 0.340 times less likely to develop TB as compared to those WHO clinical stages III/IV. This is consistent with the study conducted in Amhara Region [20]. Nevertheless, this result was not in line with study done in Tanzania [30] and south central Ethiopia [26]. The possible reason for the difference might be source population, sample size and socio demographic difference. This could make clear when the patients get early WHO stage that the immunity protective capacity will be highest which would make them protect to tuberculosis infection, as well as TB is one of the AIDS defining criteria to categorize the patients into the late WHO clinical staging which again was not addressed with this study. This study indicated determinants of TB infection among HIV positive adults visiting ant-retroviral treatment centers that would be significant for prioritizing TB screening, diagnosis, treatment and prevention. In addition, the study showed that cotrimoxazole preventive therapy and early WHO clinical stage I or II are protective effect for reducing TB infection among HIV positive adults in resources-limited settings [32, 33, 37, 38]. The study has the following limitations; case control study design could not set up temporal relationship and can only shows associations; it could not proof causations. Recall bias might have also affected the occurrence of information related to substance use such as cigarette smoking, chat chewing and alcohol consumption; also social desirability bias is unavoidable during data collection period.

This study indicated that drinking alcohol, previous TB history in the family, functional status being bedridden and ambulatory, CD₄ cell count <500cells/μl, BMI < 18.5 k g/^m2 were predictors of increased tuberculosis infection among HIV infected adults visiting ant-retroviral treatment centers in East and West Gojjam Zone and attention is given for these predictors for TB diagnosis. However, this imitated that in early WHO clinical stag I or II and using cotrimoxazole preventive therapy is necessary to reduce the overall risk of TB infection among HIV positive individuals. Hence, these findings supply momentum to strengthen tracing of TB household and member contacts screening.