Risk factors for tuberculosis treatment failure among pulmonary tuberculosis patients in four health regions of Burkina Faso, 2009: case control study

Introduction In Burkina Faso, the tuberculosis (TB) treatment failure rate increased from 2.5% in 2000 to 8.3% in 2006. The risk factors for TB treatment failure in the country are not well known. The study aims to determine the risk factors for treatment failure among pulmonary tuberculosis patients in four health region of Burkina Faso and to recommend appropriate interventions. Methods A case control study was conducted among pulmonary TB patients who began TB treatment in 2009. A case was any patient who remained smear-positive at fifth month of TB treatment and a control was a patient who tested smear-negative at fifth month of treatment. A structured questionnaire was administered to one hundred cases and one hundred controls to collect information on exposure factors. Odds ratio were calculated using bivariate and multivariate analysis to determine the association between exposures and outcome. Results Multivariate analysis showed that independent risk factors for TB treatment failure were fail to take TB drugs for more than 14 consecutive days (OR = 18.53; 95% CI:4.56 - 75.22), sputum smear-positive at two months of treatment (OR = 11.52; 95%CI:5.18-25.60), existence of comorbidity (OR = 5.74; 95%CI:1.69-19.44), and use of traditional medicines or herbs (OR = 2.97; 95%CI:1.12-7.85). Conclusion Early identification of patients with the above risk factors for intense case management will improve TB treatment outcome. Patient with smear positive at 2ndnd month of treatment require more intense follow-up, and involving traditional healers who provide traditional medicines or herbs in the educational programme on TB are required. The national referral laboratory capacity needs to be strengthened to do drug susceptibility testing and routine drug monitoring on cases of non conversion at 2nd month of treatment.


Introduction
In Burkina Faso, the incidence of TB, all forms, increased from 198/100 000 in 2000 to 241/100 000 population in 2004 before declining at 226/100 000 population in 2007 [1]. Of a total of 14 227 (96/100 000 population) new smear positive TB estimated by WHO [2] in 2007, only 2 614 (18%) were detected and notified. Of these new smear positive cases, 73% have been successfully treated. These are below the target of global TB control that is at least 70% case detection rate and 85% of treatment success rate in identifying the particular personal stressors that inhibit compliance with TB treatment, as well as provider-level impediments to achieving treatment completion. This study aims to identify these factors associated with TB treatment failure in four health regions where treatment failure is reported. It is anticipated that the findings of this investigation will be used to develop an intervention site that will pilot the use of innovative case management approaches to reduce TB treatment failure rate, ensure treatment completion among pulmonary TB patients and prevent TB multidrug resistance.
Possible reasons for treatment failure in patients receiving appropriate regimens include [4,5]: non adherence to the drug regimen, drug resistance, malabsorption of drugs, laboratory error, and extreme biological variation in response. In Finland a cohort study of risk factors for poor TB treatment outcome found that the significant risk factors included: male sex, older age, non-HIV related immunosuppression, previous history of TB, and pause in treatment [6]. In Brazil, researchers found that treatment delay, previous TB treatment, lifestyle factors, illiteracy and excessive alcohol consumption, and not having received family support were associated with treatment failure [7]. In Cameroon, a study report that age above or equal to 40 years and bacillary of 3+ or pretreatment sputum smear were significantly associated with non conversion of sputum smear at the end of two months of treatment.
Also persistent positive smear at the end of two months of treatment were significantly associated with unfavorable treatment outcomes [8]. An earlier case-control study in Egypt aiming at investigating predictors of treatment failure found that noncompliance to treatment, deficient health education to the patient, poor patient knowledge regarding the disease and diabetes mellitus as co-morbid condition were significant risk factors [9]. In Nigeria, a cohort of sputum smear-positive pulmonary tuberculosis patients at the initiation of therapy who were followed up to the end of treatment at eighth month reported that male gender and poor knowledge of tuberculosis predicted poor treatment outcome [10].
In Burkina Faso, a study conducted in the referral TB Centre

Results
The majority of patients (60%) were from North health region.
Median age was 39.5 years (ranged 18-77 years) for cases and 38.5 years (ranged 18-82 years) for controls. As show in Table 1, cases and controls were comparable for age except age group of less than 25 years. Cases had more male when controls had almost the same between male and female. Cases and controls were also comparable for marital status, education level and occupation.

Bivariate analysis
In Bivariate analysis, in Table 2, sex was significantly associated with TB treatment failure. Cases were two times more likely to be male (p=0.006) than controls. Being less than 45 years old is protective. However it is not statistically significant.

Stratify analysis
Factors associated with TB treatment failure were stratified by age group and sex to assess for possible confounding and effect modification (seeTable 5, Table 6). Cases less than 45 years old have three times more likely to fail to visit TB centre to get TB drug than cases more than 45 years. Age is not effect modifier to use of traditional medicine or herbs, history of TB drug side effects and received support from family. Table 6 shows that among TB treatment failure, males were three times more likely to have sputum smear-positive after 2 months of treatment than females. The sex appears to be effect modifier. Also, males were eight times more likely to fail to take TB drugs than

Sex as effect modifier
females. Age appears to interact with sputum smear result after 2 months of treatment, existence of underlying condition, history of previous TB treatment, failure to visit TB centre to get TB drug centre and the sex interacts with laboratory result positive after 2 month of treatment and fail to take TB drug.

Multivariable analysis
Multivariable logistic regression analysis was performed to study the factors associated with TB treatment failure while controlling other possible factor associated (  Our study has some limitations: the time-lag between the TB treatment failure and the interview was around one year and might result in a recall bias. Also the interviews were conducted by health workers in TB diagnosis and treatment centres who knows previously the patients and this will lead that participants respond to particular questions with the answers that they consider to be most socially desirable (or least stigmatizing), rather than answering with complete honesty. The factors related to health care services were not investigated and may play a role in TB treatment failure.

Conclusion
The independent risk factors for TB treatment failure identified are failing to take TB drugs for more than 14 days, having underlying diseases such as liver and kidney disease, usage of traditional medicines or herbs, and having sputum smear positive after 2 months of treatment. Factors related to health care services were not investigated and may also play a role in TB treatment failure.
There is thus need to study health centre-specific challenges to high

Competing interests
The author's declare no competing interests.