|Year : 2020 | Volume
| Issue : 16 | Page : 86-90
Predictors of treatment outcome among adult patients with multi-drug resistant tuberculosis in Kano, Nigeria
Adamu Muhktar Mubarak1, Fatimah Isma'il Tsiga-Ahmed2, Rabiu Ibrahim Jalo2, Aminatu Kwaku Ayaba3, Usman Muhammad Ibrahim3, Rabi Adamu Sufi3, Ibrahim Aliyu Umar4, Imam Wada Bello4, Nura Musa Shuaib5, Yusuf Ahmed Mustafa6, Isa Muhammad Daneji6, Aliyu Aminu6
1 Department of Community Medicine, Faculty of Clinical Sciences, Bayero University, Kano, Nigeria
2 Department of Community Medicine, Aminu Kano Teaching Hospital, Bayero University, Kano, Nigeria
3 Department of Community Medicine, Aminu Kano Teaching Hospital, Kano, Nigeria
4 Department of Public Health, Kano State Ministry of Health, Kano, Nigeria
5 Communicable and Non-Communicable Disease Cluster, World Health Organisation Kano Field Office, Kano, Nigeria
6 Department of Medical Microbiology and Parasitology, Bayero University, Kano, Nigeria
|Date of Submission||02-Dec-2019|
|Date of Decision||21-May-2020|
|Date of Acceptance||08-Jun-2020|
|Date of Web Publication||26-Nov-2020|
Dr. Rabiu Ibrahim Jalo
Department of Community Medicine, Aminu Kano Teaching Hospital, Bayero University, Kano
Source of Support: None, Conflict of Interest: None
Background: Emergence of multidrug-resistant tuberculosis (MDR-TB) continues to threaten global tuberculosis (TB) treatment, care, and prevention, and it remains a major global health problem in many low- and middle-income countries with high morbidity and mortality. Objectives: The present study assessed MDR-TB treatment outcome and its predictors among adult patients in Kano, Nigeria. Methods: We conducted a secondary data analysis involving 283 adult patients treated for MDR-TB using routine data for MDR-TB programme in Kano State between August 2014 and September 2018. Results: The mean age (±standard deviation) of the respondents was 33.4 ± 11.6 years and up to 40% of them were within the age group of 25–34 years. About three-quarters of the participants 72.4% (205) were males; up to 63.6% (180) of the patients live in the urban areas, and mean duration of treatment initiation was 21 days after the diagnosis. Up to 66.8% (95% confidence interval [CI] = 61.1–72.4), patients had successful treatment, (cured) while 33.2% (95% CI = 27.6–38.9) died. After adjusting for confounding, gender and HIV status were found to be independent predictors of MDR-TB treatment outcome among MDR-TB patients in Kano. Male patients (adjusted odds ratio aOR = 0.38, 95% CI = 0.22–0.66, P = 0.001) and HIV-negative patients (aOR = 0.49, 95% CI = 0.28–0.87, P = 0.015) were less likely to die from MDR-TB. Conclusion: The study found a moderate treatment success rate for MDR-TB in Kano. Early initiation of treatment, control of HIV epidemic, and enhanced treatment supervision would likely improve treatment outcome.
Keywords: Kano, multi-drug resistance, outcome, predictors, treatment, tuberculosis
|How to cite this article:|
Mubarak AM, Tsiga-Ahmed FI, Jalo RI, Ayaba AK, Ibrahim UM, Sufi RA, Umar IA, Bello IW, Shuaib NM, Mustafa YA, Daneji IM, Aminu A. Predictors of treatment outcome among adult patients with multi-drug resistant tuberculosis in Kano, Nigeria. N Niger J Clin Res 2020;9:86-90
|How to cite this URL:|
Mubarak AM, Tsiga-Ahmed FI, Jalo RI, Ayaba AK, Ibrahim UM, Sufi RA, Umar IA, Bello IW, Shuaib NM, Mustafa YA, Daneji IM, Aminu A. Predictors of treatment outcome among adult patients with multi-drug resistant tuberculosis in Kano, Nigeria. N Niger J Clin Res [serial online] 2020 [cited 2021 Jan 19];9:86-90. Available from: https://www.mdcan-uath.org/text.asp?2020/9/16/86/301648
| Introduction|| |
Emergence of multidrug-resistant tuberculosis (MDR-TB) continues to threaten global tuberculosis (TB) treatment, care, and prevention, and it remains a major global health problem in many low- and middle-income countries with high morbidity and mortality., MDR-TB is a form of TB which is resistant to key first-line anti-TB drugs, rifampicin, and isoniazid, whereas extensively drug resistant (XDR)-TB includes MDR-TB and additional resistance to any of the fluoroquinolones and at least 1 second line injectable medications.
The World Health Organization (WHO) has estimated that in 2015, approximately 580,000 people developed MDR-TB of whom 55,000 had XDR-TB. Resistance arises from both service- and patient-related factors in the management of the disease ranging from poor compliance, poor drug quality, inadequate supervision, insufficient dosing, inappropriate drug combinations, duration of treatment, and poor training of health-care providers on MDR-TB management. The treatment of MDR-TB is complicated, takes long duration, is associated with several adverse events and is very expensive with median average cost of treatment estimated at $7114 per patient. MDR-TB treatment is also associated with unsuccessful treatment outcome compared to non-MDR-TB treatment.
The WHO classified the treatment outcomes for MDR-TB into five types: cure, treatment completed, died, failed treatment, and loss to follow-up. Successful treatment includes being cured and completing treatment, while unsuccessful treatment includes dying, treatment failure, and loss to follow-up., Globally, treatment success rate for MDR-TB is 55% according to the 2018 global TB report which is below the WHO target. Various studies have been conducted around the globe to determine the predictors of treatment outcome for MDR-TB and factors such as unilateral disease, HIV seronegativity, and standardized treatment regimen have been associated with successful treatment outcome, whereas factors such as substance abuse, homelessness, previous TB treatment, resistance to ofloxacin, alcohol dependence, and gender were found to be associated with poor treatment outcomes.,, These factors are, therefore, useful in programme planning for both drug susceptible TB and MDR-TB to successfully end the global TB epidemic.
Globally, the proportion of MDR-TB patients in the 2015 cohort who successfully completed treatment (i.e., cured or completed treatment) was 55% with 8% treatment failure, 15% deaths, and 14% were lost to follow-up; and for 7%, there was no outcome information. The treatment success rate was the highest in the WHO Eastern Mediterranean Region (62%) and was the lowest in the WHO South-east Asia Region (50%). In contrast, treatment failure was the highest in the WHO European Region (12%), and the death rate was highest in the WHO African Region (20%); loss to follow-up was highest in the WHO Region of the Americas (26%), whereas WHO Western Pacific Region had the highest percentage of cases without outcome data (17%). A systematic review in Canada found a pooled treatment success rate of 60% for MDR-TB. The study also found the pooled treatment success for MDR-TB patients that received individualized regimen was significantly higher when compared with patients who received standardized regimen (64% vs. 52%). Similarly, a retrospective cohort study in Brazil which included 1972 patients found an overall treatment success of 60%. The survey reported that success was more likely in non-HIV patients, sputum-negative at baseline, unilateral disease, and first episode of MDR-TB. Furthermore, patients receiving standardized regimen had 2.7-fold odds of success compared to those receiving individualized treatment when failure/relapse were considered, and 1.4-fold odds of success when death was included as an unsuccessful outcome while a similar study in Japan reported overall treatment completion rate to be 57%., In Pakistan, the treatment success rate for MDR-TB was found to be 39.2%. This is quite low compared to a study conducted in Taiwan among 692 MDR-TB patients: 570 (82.4%) were successfully treated, 84 (12.1%) died, 18 (2.6%) had treatment failure, and 20 (2.9%) were lost to follow-up. According to the global TB report, treatment success for MDR-TB was <50% in China, India, Indonesia, Mozambique, the Republic of Moldova, and Zimbabwe. A retrospective cohort study from 1992 to 2002 in South Africa revealed 239 (49%) were cured or completed treatment, 68 (14%) died, 144 (29%) defaulted from treatment, 27 (5%) failed, 10 (2%) transferred out, and 3 (<1%) remained on treatment. Another prospective cohort study in South Africa reported that 348 (46.0%) patients were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died, and 158 (20.9%) defaulted. Thus, treatment success among the high-HIV prevalence cohort was poor compared to the other study, this is likely due to the burden of HIV and HIV/MDR-TB co-infection while another study in Tanzania from 2009 to 2014 found MDR-TB treatment success of 75.7%.
Drug-resistant TB is considered to be a man-made problem, resulting from the consequences of individual or combined factors related to the management of drug supply, patient management, patient adherence, behavioral factors, enabling environment, economic status, and poor infection control practices have all been identified as major contributing factors to the occurrence and spread of MDR-TB. High mortality associated with MDR-TB in African countries coupled with weak health system and dearth of local information prompts the need to determine MDR-TB treatment outcome and its predictors in Kano (Northern Nigeria).
| Methods|| |
The health structure in Kano State is in line with the Nigerian National Health Policy which is based on the concept and practice of primary health care. Eighty-two percent of all the health facilities in the State are public. There are total of 1403 public health facilities, of which 3 are tertiary, 40 secondary, and 1360 are primary. The state has 541 directly observed therapy short course (DOTS) clinics, 252 acid-fast bacilli (AFB) laboratories, and 18 GeneXpert sites and one MDR-TB treatment center located at infectious disease hospital. The DOTS, AFB, and GeneXpert services cut across both public and private sector, including faith-based institutions. A number of development partners and nongovernmental organizations are supporting the state TB programme. Outcome data for each patient was recorded either as cured or died on the MDR-TB database.
Diagnosis and treatment of multidrug-resistant tuberculosis
Within the Kano State TB program, GeneXpert is being used for the diagnosis of MDR-TB while line probe assay is used to identify the resistance to second-line anti-TB drugs before commencement of treatment.
Previously, patients diagnosed with MDR-TB are placed on levofloxacin, moxifloxacin with injectable kapreomycin, amikacin, streptomycin, or kanamycin (old regimen). However, since January 2018, an 11-month short treatment regimen (new regimen) using moxifloxacin or levofloxacin with bedaquiline and linezolid for HIV-negative patients (delamanid and bedaquiline for HIV positive patients) was introduced in Kano.
We conducted a secondary data analysis of the routine data for MDR-TB programme in Kano State.
The study population included all 283 adult MDR-TB patients with information on MDR-TB treatment outcome between August 2014 and September 2018.
All adult MDR-TB patients (aged 15 years and above) who had complete information about treatment outcome on the state MDR-TB database.
- MDR-TB patients on treatment
- MDR-TB patients with incomplete information (missing data).
A pro forma was used to extract the data (age, sex, treatment initiation, place of residence, regimen, initiation of treatment, HIV status, treatment site, and treatment outcome) from the MDR-TB database of Kano State.
Data extracted were entered into Microsoft Excel Spreadsheet, cleaned, and analyzed using IBM SPSS version 20.0 (Armonk, New York, USA). Age and treatment initiation (duration between diagnosis and start of treatment) were summarized and presented using mean, standard deviation (SD), median, and range, whereas frequencies and percentages were used to summarize the qualitative variables: Sex, age group, place of residence, regimen, initiation of treatment, HIV status, treatment site, and treatment outcome.
Treatment outcome (cured or died) was the dependent variable while the independent variables included age, sex, place of residence, regimen, treatment initiation, HIV status, and treatment site. The Chi-square test was used to analyze the factors associated with treatment outcome. In all tests of significance, P < 0.05 was considered statistically significant. At multivariate level, all variables found to have P < 0.05 and another factor found to be predictor of MDR-TB treatment outcome from the literature review were entered into the regression model. Binary logistic regression analysis was used to obtain the adjusted odds ratio (aOR) with 95% confidence intervals (CIs) for the predictors of MDR-TB treatment outcome.
Ethical approval for the study was obtained from the Kano State Ministry of Health Research-Ethics Committee, Kano (Nigeria).
| Results|| |
The mean age (±SD) of the patients was 33.4 ± 11.6 years and up to 40% of the participants fall within age group of 25–34 years. About three-quarter of the participants 72.4% (205) were males and two-third 63.6% (180) live in the urban areas of the state; median duration of treatment initiation was 21 days (range: 1–175 days). Other sociodemographic characteristics of patients are shown in [Table 1].
|Table 1: Socio-demographic characteristics of adult patients with multidrug-resistant tuberculosis in Kano|
Click here to view
Up to 66.8% (95% CI = 61.1–72.4) patients had successful treatment (cured), whereas 33.2% (95% CI = 27.6–38.9) died within the period under review [Table 2]. At bivariate level of analysis, treatment outcome was found to be significantly associated (P < 0.05) with patient's gender and HIV status [Table 3]. Two factors with P < 0.05 (gender and HIV status) and another factor found to be predictor of MDR-TB treatment from the literature review (treatment regimen) were entered into logistic regression model to adjust for confounding. After adjusting for confounding, gender and HIV status were found to be independent predictors of MDR-TB treatment outcome. Male patients (aOR = 0.38, 95% CI = 0.22–0.66, P = 0.001) and HIV-negative patients (aOR = 0.49, 95% CI = 0.28–0.87, P = 0.015) were less likely to die from MDR-TB [Table 4].
|Table 2: Treatment outcome among adult patients with multidrug-resistant tuberculosis in Kano|
Click here to view
|Table 3: Factors associated with multidrug-resistant tuberculosis treatment outcome in Kano|
Click here to view
|Table 4: Predictors of multidrug-resistant tuberculosis treatment outcome in Kano|
Click here to view
| Discussion|| |
The study found treatment success rate for MDR-TB in Kano to be 66.8%; this is considered a modest cure rate for Africa sub-region, where treatment for MDR-TB remains a huge challenge. Similar findings were reported in Tanzania (75.7%), Taiwan (82.4%), Japan (57%,) Brazil (60%), and Canada (60%).,,, Studies from across Africa reported a low treatment success rate in South Africa of about 49%, and even lower among HIV-positive cohorts (46%). The poor treatment success seen in HIV cohort is likely due to the fact that HIV/MDR-TB co-infected patients showed consistently low immunity and response to treatment. This moderate level of treatment success may be attributed to the use of newer short course regimen, introduction of treatment support, and use of community-based health facilities to administer and supervise treatment for majority MDR-TB patients in Kano. More so, majority (63.6%) of the patients lived in the urban areas where there is access to treatment and healthcare services. High-treatment success rate reported from countries such as Taiwan is largely attributed to the development of additional treatment centers for MDR-TB with strict directly observed therapy treatment supervision, video supervision of some patients, psychosocial as well as financial support to MDR-TB patients.
Countries such as Pakistan reported the success rate as low as 39.2%, which was very similar to the findings from India, Indonesia, Mozambique, the Republic of Moldova, and Zimbabwe., This is in agreement with the 2015 global TB report which found the treatment success rate to be highest in the WHO Eastern Mediterranean Region (62%) and was lowest in the WHO South-East Asia Region (50%)., Loss to follow-up, overcrowding, poor socioeconomic status, and treatment interruptions due to drug stock outs were some of the factors responsible for poor treatment outcome among the studied population.
After adjusting for confounding, gender, and HIV status were found to be independent predictors of MDR-TB treatment outcome. Male patients and HIV-negative patients were less likely to die from MDR-TB. Conversely, a study in Netherlands found the predictors of treatment outcome to include gender, substance abuse, homelessness, and alcohol dependence. This is similar to our study finding where gender was found to be an independent predictor of treatment outcome as nearly half (48.7%) of the female patients died during MDR-TB treatment. This is likely due to additional demand of childbirth, child rearing, high parity, poor nutrition, and sub-standard living conditions among the women of reproductive age group in Northern Nigeria. Studies from Brazil and Portugal reported HIV positivity as an independent predictor of treatment outcome., This is similar to our finding as HIV was found to be an independent predictor of treatment outcome with 45.1% mortality among HIV patients. Both HIV and MDR-TB suppress the immune system, which ultimately affects the treatment outcome when compared to patients with MDR-TB infection only. HIV infection remains a significant driver of MDR-TB and the end TB strategy cannot be effective unless HIV infection is also controlled. Early treatment initiation and enhanced supervision should be adopted by the healthcare providers so as to improve treatment outcome. Other studies reported MDR-TB treatment outcome predictors to include the presence of cavitary lesions on X-rays, low body mass index, and resistance to streptomycin and ethambutol.
The major strength of this study was the availability of information on treatment outcome for all patients included in the analysis while its limitation includes missing information about time to event (to allow for survival analysis), and other comorbidities (diabetes, hypertension, etc.,), as they are not recorded on the programme database.
| Conclusion|| |
The study found a moderate treatment success rate for MDR-TB in Kano. Early initiation of treatment, control of HIV epidemic, and enhanced treatment supervision would likely improve treatment outcome.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Leveri TH, Lekule I, Mollel E, Lyamuya F, Kilonzo K. Predictors of treatment outcomes among multidrug resistant tuberculosis patients in Tanzania. Tuberc Res Treat 2019;10:10-5.
Bastos ML, Lan Z, Menzies D. An updated systematic review and meta-analysis for treatment of multidrug-resistant tuberculosis. Eur Respir J 2017;49:1-15.
National Tuberculosis and Leprosy Control Program; Workers Manual. Federal Ministry of Health, Nigeria; 2014.
Anderson L, Baddeley A, Dias HM, Floyd K, Baena I, Gilpin C, et al
. Global Tuberculosis Report. Geneva: Irwin Law; 2018.
Alene KA, Yi H, Viney K, McBryde ES, Yang K, Bai L, et al
. Treatment outcomes of patients with multidrug-resistant and extensively drug resistant tuberculosis in Hunan Province, China. BMC Infect Dis 2017;17:573.
Bastos ML, Cosme LB, Fregona G, do Prado TN, Bertolde AI, Zandonade E, et al
. Treatment outcomes of MDR-tuberculosis patients in Brazil: A retrospective cohort analysis. BMC Infect Dis 2017;17:718.
Kawatsu L, Uchimura K, Izumi K, Ohkado A, Yoshiyama T. Treatment outcome of multidrug-resistant tuberculosis in Japan - the first cross-sectional study of Japan tuberculosis surveillance data. BMC Infect Dis 2018;18:445.
Rao NA, Irfan M, Mahfooz Z. Treatment outcome of multi-drug resistant tuberculosis in a tertiary care hospital in Karachi. J Pak Med Assoc 2009;59:694-8.
Yu MC, Chiang CY, Lee JJ, Chien ST, Lin CJ, Lee SW, et al
. Treatment outcomes of multidrug-resistant tuberculosis in Taiwan: Tackling loss to follow-up. Clin Infect Dis 2018;67:202-10.
Shean KP, Willcox PA, Siwendu SN, Laserson KF, Gross L, Kammerer S, et al
. Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002. Int J Tuberc Lung Dis 2008;12:1182-9.
Farley JE, Ram M, Pan W, Waldman S, Cassell GH, Chaisson RE, et al
. Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence. PLoS One 2011;6:e20436.
Dessalegn M, Daniel E, Behailu S, Wagnew M, Nyagero J. Predictors of multidrug resistant tuberculosis among adult patients at Saint Peter Hospital Addis Ababa, Ethiopia. Pan Afr Med J 2016;25:5.
Kano State Ministry of Health. Strategic Health Development Plan II. Kano State Ministry of Health; 2017.
Samuels JP, Sood A, Campbell JR, Khan FA, Johnston JC. Comorbidities and treatment outcomes in multidrug resistant tuberculosis: A systematic review and meta-analysis. Sci Rep 2018;8:4980.
Pradipta IS, van't Boveneind-Vrubleuskaya N, Akkerman OW, Alffenaar JC, Hak E. Treatment outcomes of drug-resistant tuberculosis in the Netherlands, 2005-2015. Antimicrob Resist Infect Control 2019;8:115.
Oliveira O, Gaio R, Villar M, Duarte R. Predictors of treatment outcome in multidrug-resistant tuberculosis in Portugal. Eur Respir J 2013;42:1747-9.
[Table 1], [Table 2], [Table 3], [Table 4]