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,  )
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
Justification

4. Objectives General Objective Specific objectives
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:
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
we looked at the number of TB patients received per day for treatment (N), and based on the number of controls needed from that health facility (n), calculate the interval (K). K = N/n.
Then each Kth patients who met control definition was selected.
The first was selected randomly between 1 and K using Ms Excel formula for simple random sampling

9. Data Collection and Analysis
We collected data from March ̶ May 2018 with 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
Exposure variables
Cases (N=50)
Controls (N=100)
cOR* (95% CI**)
P-value
n (%)
Contact with MDR-TB patient
Yes
11 (22)
2 (2)
13.82 (2.93 – 65.22)
0.003 No
39 (78)
98 (98)
Ref.
Sex
Female
20 (40)
21 (21)
2.51 (1.19 – 5.27)
0.014
Male
30 (60)
79 (79)
Living with MDR-TB person in the family within same house
38 (76)
58 (58)
2.29 (1.07 – 4.91)
0.033
12 (24)
42 (42)
Ref
Duration of window open per day
≤6 hours
12 (31.6)
35 (57.4)
2.9 (1.24 – 6.83)
>6 hours
26 (68.4)
26 (42.6)
Open window in the house
38 (82.6)
61 (67.0)
1.89 (0.97 – 5.63)
0.058
8 ((17.4)
30 (30.0)

13. Clinical and Medical TB history factors associated with MDR-TB, Bujumbura City, Burundi, 2018
Exposure variables
Cases (N=50)
Controls (N=100)
cOR* (95% CI**)
P-value
n (%)
Previously treated for TB
Yes
29 (58)
20 (20)
5.52 (2.62 – 11.64)
<0.001 No
21 (42)
80 (80)
Ref.
Previous TB treatment outcome
Relapse
17 (17)
4.50 (2.02 – 9.94)
0.005
Treatment failure
6 (12)
1 (1)
21.82 (2.49 – )
Lost to follow up
1 (2)
2 (2)
1.82 (0.16 – 20.99)
0.632
New case
22 (44)
Treatment interruption
45 (90)
70 (70)
0.25 (0.09 – 0.72)
0.009
5 (10)
30 (30)
HIV status
Positive
14 (28)
8 (8)
4.47 (1.73 – 11.57)
0.002
Negative
36 (72)
92 (92)
Treatment change before
44 (88)
98 (98)
0.15 (0.02 – 0.77)
0.023
Ref

14. Independent factors associated with MDR-TB, Bujumbura City, Burundi, 2018
Cases (n=50)
Controls (n=100)
cOR* (95% CI**)
aOR*** (95% CI)
P-value
Previously treated for tuberculosis
29 (58)
20 (20)
5.52 (2.62 – 11.64)
5.37 (3.34 – 12.30
<0.001
Contact MDR-TB patient
11 (22)
2 (2)
13.82 (2.93 – 65.22)
12.32 (2.93 – 65.22)
0.003
Treatment change
44 (88)
98 (98)
0.15 (0.02 – 0.77)
0.13 (0.02 – 0.75)
0.023
HIV Positive
14 (28)
8 (8)
4.47 (1.73 – 11.57)
2.50 (0.77 – 8.15)
0.129
Living with MDR-TB person in family
38 (76)
58 (58)
2.29 (1.07 – 4.91)
2.51 (1.03 – 6.11)
0.042
*cOR= crude Odds Ratio, **CI= Confidence Interval, ***aOR= adjusted Odds Ratio

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 Limitations
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 Marahatta et al., 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
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
The longer the treatment, the more the subject to some interruption, poor adherence of the patient, improper drug regimen
A population-based review of international drug resistance surveillance network over 11 countries showed that an association between the length of treatment and drug resistance could be the reflection of longer treatment (Espinal et al., 2001)
This was a positive change towards a new regimen that was approved to have more advantages (old regimen of twelve months of treatment to the new regimen of nine months)

17. Conclusion and Recommendations
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