Dr. Alexis Niyomwungere National Institute for Public Health Bujumbura, Burundi

1. The 7th East African Health and Scientific Conference Use of Electronic devices in Establishing the Risk factors for Multidrug-Resistant Tuberculosis in Bujumbura City, Burundi, 2018 Dr. Alexis Niyomwungere National Institute for Public Health Bujumbura, Burundi

2. Background • Tuberculosis (TB) is the leading cause of death infectious disease and the 9th leading cause of death worldwide (WHO Global Report 2018) • Among challenges of controlling TB is development of drug-resistance • Multidrug resistant Tuberculosis (MDR-TB); type of TB transmitted by M. tuberculosis strains that resist to Rifampicin and Isoniazid the two most powerful anti-TB drugs • MDR-TB is becoming a global threat ; affect both new persons and previously TB treated persons (WHO Global Report 2018) • Prevention measures (CDC TB Prevention, 2017) • Early diagnosis & immediate initiation of treatment • Treatment adherence • Avoid exposure to known MDR-TB patients • In 2017, there were an estimated 10.4 million new tuberculosis (TB) cases (WHO Global Report 2018) • Around 600,000 TB cases developed first-line drug resistance or MDR/RR-TB with MDR-TB accounting for 82% (WHO global TB report,2018) • In 2016, Burundi reported 2.6% of new cases of MDR-TB and 13% of cases previously treated (WHO Global TB report , 2017) • Burundi is not among top 30 countries with highest MDR-TB burden

3. Problem Statement Justification • Compared to 2016 and 2017, Burundi reported a reduction of MDR/RR-TB incidence in 2018, however the MDR-TB rate did not decrease (Global TB report 2016, 2017, 2018) • There are still deaths (average CFR of 7.5% per year for the last 7 years) due to MDR/RR-TB in Burundi (NTLCP annual report 2017) • On average, 52.7% (SD=12.8%) of reported MDR-TB cases for the last 7 years were from Bujumbura City (MDR-TB surveillance report,  2011-2017) • Despite the active surveillance of MDR-TB cases and strict follow up of confirmed MDR-TB patient and contact in Burundi; • Bujumbura continue having an increased number of MDR-TB patients although overall national incidence has decreased (MDR-TB surveillance report,  2017 and WHO Global report 2018) • Very few studies performed looking for determinants of MDR-TB in Bujumbura • To reduce this MDR-TB incidence, identification of MDR-TB determinants will facilitate the implementation of evidence based interventions strategies that are best suited for local situation

4. Objectives • General Objective • To establish factors associated with Multi-Drug Resistant Tuberculosis in Bujumbura City, Burundi • Specific objectives • To determine Socio-demographic factors associated with MDR-TB in Bujumbura City • To determine behavioral factors associated with MDR-TB in Bujumbura City. • To determine clinical and previous TB history factors associated with MDR-TB in Bujumbura City.

5. Methods • Study Site: • Bujumbura City is Burundi’s capital city • Largest city with a population of 692,331 (ISTEEBU, 2016) • Urban and peri-urban setups with informal settlements • The poverty index of the city is 28.7% • Three health districts and National Anti-TB center • Thirteen Centers for TB Diagnosis and Treatment (CDTs) • All MDR-TB patients are referred to the National center for MDR-TB care: admission for the first 4 months • Study Design: • Unmatched case control study • Hospital cases and controls • Study population: • Patients from Bujumbura City diagnosed with MDR-TB

6. Inclusion and Exclusion criteria Inclusion criteria • Cases: • Living in Bujumbura City, • Confirmed by GeneXpert to be MTB-rifampicin resistant and with culture and drug susceptibility testing confirmed to have MTB strain resistant to Isoniazid, • Patient must be on treatment and signed the consent form • Controls: • Living in Bujumbura City, • Laboratory confirmed to have pulmonary TB • On sixth month of treatment of pulmonary TB with first line anti-TB drugs and accept to sign the consent form Exclusion criteria • Controls: Presence of MTB organism after 5th month of treatment • Cases and Controls: • A Patient with extra pulmonary TB • A Patient diagnosed and/or treated in Bujumbura City but not resident

7. Sample Size • The sample size was calculated using Fleiss formula(2013) • Assumptions: • alpha level of significance (Zα/2) of 5%, • power (Z1-β) or percentage of detection of 80%, • ratio (r) of one case to two controls, • An odds ratio (OR) of 3 • An estimated proportion (p2) of controls not vaccinated of 17.4% • (n1 = number of cases and n2 = number of controls • Sample size= 150 (50 cases and 100 controls)

8. Sampling Procedures • From National MDR-TB register (Cases selection); • List all patients on treatment from Bujumbura City • Using Ms. Excel, randomly generated a list of 50 patients • Generated a list of CDTs from which they were referred • From the TB register in CDT (Controls selection), • Generated a list of TB patients on sixth month of treatment • Based on the number of cases per CDT, 2 controls per cases were recruited • Systematic random sampling method was used: calculated K = N/n (N: number of TB patients received per day for treatment and n: number of controls needed from that health facility) • Each Kth patient was recruited, the first randomly selected between 1 and K

9. Data Collection and Analysis • We collected data from March 2018 ̶ May 2018with Electronic tablets • Standardized structured questionnaire administered • Variables collected; • Socio-demographic characteristics: Demographics, distance and mean time to CDT, • Clinical characteristics including laboratory information • TB/VIH coinfection, diabetes, vaccination, bacillary load, TB type • Behavioral variables: Smoking and SHS, alcohol intake, drug abuse, imprisonment • Medical history of TB: TB in family, contact with MDR-TB, TB treatment history, treatment adherence • Analysis was performed with Epi InfoTM 7.0 and STATA version 12 • Descriptive analysis done and Crude odds ratios calculated at bivariate analysis; • Factors with P-value ≤0.25 used at multivariate • Unconditional forward selection logistic regression; • Independent factors associated with MDR-TB • Variables with p-values ≤0.05 considered statistically significant and reported in the final model

10. Ethical Approval • Scientific and ethical clearance obtained from Institutional Research and Ethics Committee (FAN: IREC 2054) • Authorization obtained from Burundi Ministry of Health to conduct the investigation and access to the patients records (Ref. 633/04/DGSSLS/2018) • Written consent to participants before interview • Questionnaires were kept in a locked cabinet • Data were stored in password protected computers

11. RESULTS

12. Socio-demographic and behavioral factors associated with MDR-TB, Bujumbura City, Burundi, 2018

13. Clinical and Medical TB history factors associated with MDR-TB, Bujumbura City, Burundi, 2018

14. Independent factors associated with MDR-TB, Bujumbura City, Burundi, 2018

15. Discussion 1/2 • Among socio demographic factors, Contact with a MDR-TB patient and living with an MDR-TB patient in the family had a higher odds for developing MDR-TB, • Continuous contact lead to continuous exposure to resistant strain. • Contrast to others where continuous contact with MDR-TB patient had a lower odds tending to be protective (Mulu et al., 2015) • The study had a small proportion of primary MDR-TB cases • In our study, no behavioral factor was independently associated with the MDR-TB although having a house window opened less than 6 hours per day had a strong association • Increased sensitization on TB and MDR-TB in the City • Similar findings by Weyenga et al., 2009, • As clinical factor, HIV positive had higher odds of getting MDR-TB compared to HIV negative although not statistically significant • Majority of case patients (75%) in our study had secondary MDR-TB • Similar to findings in Ethiopia and in a systematic review of published paper (Espinal et al., 2001; Suchindran et al., 2009; Wells et al., 2007; Workicho et al., 2017a) • Contrast with Weyenga et al., 2009 and Mulu et al., 2015

16. Discussion 2/2 • Previously treated for TB had a higher odds of developing MDR-TB compared to new cases of MDR • Development of strains resistant to drugs by the bacteria due to the length of the treatment • Compares to studies done in several part of the world and similar to findings from a population based surveillance network over 11 countries (Espinal et al., 2001) • However our findings, high proportion of new MDR-TB cases (42%) compared to Marahattaet al., 2012 findings (5.5%) • Change of treatment in the previous episodes showed a protective effect in our findings, • Shift from the old regimen to the new regimen in 2016-2017 • Similar findings with Demile et al., 2018 Limitations • Case control study- likelihood that participants did not recall the true information • Cases and controls on treatment • Professional and well-trained interviewers • Using a structured questionnaire • Link questions to events

17. Conclusion and Recommendations Conclusion • Tablets quickly collect data and make it easy and ready for analysis • Contact with an MDR-TB patient and living with MDR-TB patient in the family and history of previous treatment were the major sociodemographic and clinical and medical TB treatment history determinants for contracting multidrug-resistant tuberculosis • There was no behavioral factors associated with the development of the MDR-TB Recommendations • Encourage the use of tablets for data collection • The TB control program should trace and screen all contacts of MDR-TB patients; revisit the policy on tuberculosis treatment adherence and basic TB infection control practice within the MDR-TB patients. • Further study on MDR-TB patient pathway could show when the contact transmission happen

18. Acknowledgements • Burundi Ministry of Health • Moi university • Kenya FELTP, Ministry of Health • National Tuberculosis, leprosy and lung disease program, Burundi • Bujumbura City Health Department • Participants and interviewers

19. Thank you