BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from Determinants for tuberculosis in HIV infected adults in Northwest Ethiopia: a multicenter case control study ForJournal: peerBMJ Open review only Manuscript ID: bmjopen-2015-009058 Article Type: Research Date Submitted by the Author: 11-Jun-2015 Complete List of Authors: Alemu, Yihun Mulugeta; University , Epidemiology Aweke, Werku; University, Epidemiology wilder-smith, Annelies; Heidelberg University,Institute of Public Health, International Health <b>Primary Subject Global health Heading</b>: Secondary Subject Heading: Epidemiology Keywords: EPIDEMIOLOGY, PUBLIC HEALTH, Tuberculosis < INFECTIOUS DISEASES http://bmjopen.bmj.com/ http://bmjopen.bmj.com/ on September 24, 2021 by guest. Protected copyright. on September 24, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 21 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from 1 2 3 4 5 Determinants for tuberculosis in HIV infected adults in Northwest Ethiopia: a 6 7 multicenter case control study 8 9 Correspondence author; Name: Yihun Mulugeta, Alemu E: mail: [email protected] 10 11 Yihun Mulugeta Alemu 1, 2*, Worku Awoke2, Wilder-Smith Annelies1 12 13 14 1Institute of Public Health, Heidelberg University, Germany 15 For peer review only 16 2School of Public Health, College of Medicine and Health Science, Bahir Dar University, 17 18 Ethiopia 19 20 21 3Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 22 23 Determinants of tuberculosis in HIV infected adults 24 25 Key words: Determinants, tuberculosis, HIV, adults, multi-center 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 24, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 1 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 21 BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from 1 2 3 4 Summary Boxes 5 6 What is already known in this subject? 7 8 9 Previous studies to investigate the link have identified independent determinants for TB as 10 clinical (highly activated antiretroviral therapy, lower level of CD4 cell count, cotrimoxazole 11 12 preventive therapy and isoniazid preventive therapy) and life style (alcohol consumption). 13 14 However, determinants for TB among HIV infected adults are not well described in resource 15 For peer review only 16 limited settings. 17 What this study adds? 18 19 This study identified independent determinants for tuberculosis (highly activated antiretroviral 20 21 22 therapy, lower level of CD4 cell count, cotrimoxazole preventive therapy, isoniazid preventive 23 24 therapy and alcohol consumption) in HIV infected adults at resource limited settings. In addition 25 26 the study identified independent life style determinants for tuberculosis (Khat chewing and 27 28 29 tobacco smoking) in HIV infected adults. The independent association of life style variables 30 31 (Khat chewing and tobacco smoking) have never been identified by any published study in this 32 33 types of source population (HIV infected adults). Determinants for TB among HV infected adult http://bmjopen.bmj.com/ 34 35 36 are complex and encompass a wide range of factors. This study will contribute to a more 37 38 comprehensive & multidisciplinary approach for prevention and control of TB among HIV- 39 40 infected adults in resource limited settings. 41 on September 24, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 2 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 21 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from 1 2 3 4 Abstract 5 6 Background: 7 8 Tuberculosis presents a major infectious diseases burden in resource-limited settings. HIV is 9 10 driving the tuberculosis epidemic in many countries. Determinants for tuberculosis among HIV 11 12 13 infected patients is not well described in resource limited settings. 14 15 Objective: For peer review only 16 17 The objective of this study was to identify determinants for tuberculosis among HIV infected 18 19 adults in Northwest Ethiopia. 20 21 22 Methods: 23 24 A multicenter case control study was conducted in three hospitals and ten health centers. Cases 25 26 were HIV infected adults diagnosed with active tuberculosis and controls were HIV infected 27 adults without active tuberculosis. We recruited 150 cases and 296 controls. Interviewers 28 29 administered questionnaires and case report forms were used to systematically collect the data. 30 31 Results: 32 33 Being smokers (AOR (adjusted odds ratio) =5.47; 95%CI: 2.26, 13.22), presence of tuberculosis http://bmjopen.bmj.com/ 34 35 patient in the family (AOR=2.66; 95%CI: 1.25, 5.66), alcohol drinker (AOR=2.49; 95%CI: 1.29, 36 37 4.8) and chewing khat (AOR=2.22; 95%CI: 1.11, 4.41) were independent determinants for 38 tuberculosis. Highly active antiretroviral therapy (HAART) (AOR=0.25; 95%CI: 0.13, 0.51) had 39 40 a protective benefit against tuberculosis. 41 on September 24, 2021 by guest. Protected copyright. 42 Conclusion: 43 44 HIV infected adults who have substance use (tobacco smoking, khat chewing and alcohol) 45 46 should be prioritized for tuberculosis screening. This study reaffirmed that initiation of HAART 47 is one of the best strategies to reduce tuberculosis occurrence in HIV infected adults. Increased 48 49 coverage of isoniazid and cotrimoxazole preventive therapy have protective benefit against 50 51 active tuberculosis. Contact tracing of household contacts for tuberculosis should be intensified. 52 53 54 55 56 57 3 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 21 BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from 1 2 3 ARTICLE SUMMARY 4 5 Strength and limitation of the study 6 7 This is the first multicenter case control study in Northwest Ethiopia that identify determinants 8 9 for tuberculosis in HIV infected adults. 10 11 The study identified determinants for tuberculosis that will be important to prioritize TB 12 screening, treatment, prevention and control. 13 14 This study reaffirmed that initiation of HAART is one of the best strategies to reduce 15 For peer review only 16 tuberculosis among HIV infected adults in resource limited settings. 17 18 As we used a retrospective case control approach; temporal relationship could not be established; 19 the study design could not proof causation. 20 21 Ascertainment of tuberculosis patient among HIV infected adults might lack sensitivity and 22 23 specificity. 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 24, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 4 58 59 60 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 21 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2015-009058 on 15 April 2016. Downloaded from 1 2 3 INTRODUCTION 4 5 The advent of HIV was a massive setback for the prevention and control of tuberculosis (TB) 6 7 1.TB is the leading cause of morbidity and mortality among people living with HIV (PLWHIV) 8 2 9 .There is a strong synergy between TB and HIV infection in HIV high-burden countries 10 3 11 particularly in resource-limited settings where the impact of both diseases are more significant . 12 One-third of the world’s population is infected with TB 2. In 2013, an estimated 9.0 million 13 14 people developed TB; 1.1 million was HIV infected 4. Ethiopia ranks as the seventh TB burden 15 For5 peer review only 16 country in the world . 17 18 In resource-limited settings the health care systems are overwhelmed by preventive, therapeutic 19 and diagnostic challenges of "HIV-TB syndemic". In Ethiopia; the dual epidemics drained 20 21 resources and overburdened the already very limited health work-force1. HIV increases the 22 6 23 lifetime risk for developing TB . However, HIV is not the only factor determines TB; various 24 25 other determinants contribute to TB-HIV co-infection. Studies to investigate the link have 26 identified determinants for TB as socio-demographic7,8, clinical9,10, life style11,12 and 27 28 environmental13. However, determinants for TB among HIV infected adults are not well 29 30 described in resource limited settings. This study assessed determinants for TB among HIV 31 32 infected adults in Northwest Ethiopia. 33 http://bmjopen.bmj.com/ 34 METHODS 35 Study design 36 37 We conducted a multicenter case control study from May 12 to June 5, 2014 in Northwest 38 39 Ethiopia. All eligible governmental health institutions in ten provinces were included. Those 40 41 were Bahir Dar, Dangella, Kossober, Fnote Selam, Bure, Dur Betie, Deber Tabor, Wereta, Addis on September 24, 2021 by guest. Protected copyright. 42 Zemen and Nefas Mewcha. Three hospitals and ten health-centers were included. 43 44 Participants 45 46 Cases were HIV infected adults diagnosed with active TB and on TB treatment during the data 47 48 collection period.