s12890 024 03350 W
s12890 024 03350 W
https://doi.org/10.1186/s12890-024-03350-w
Abstract
Background The spread of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to TB control
efforts. This study evaluated the treatment outcomes and associated factors among patients receiving treatment
for MDR-TB in southern Ethiopia.
Methods A retrospective follow-up study covering ten years, from 2014 to 2023, analyzed the records of confirmed
cases of pulmonary TB admitted to Yirgalem General Hospital, an MDR-TB treatment initiation center in the Sidama
Region. To compare the successful treatment outcomes across the years, a chi-square test of independence was con-
ducted. Bivariate and multivariable logistic regression models were used to identify factors associated with treatment
outcomes for MDR-TB.
Results Out of 276 confirmed MDR-TB cases, 4(1.4%) were diagnosed with resistance to second-line drugs (SLDs).
Overall, 138 patients achieved favourable treatment outcomes, resulting in a treatment success rate of 50.0% [95%
CI 44.1–55.9%]. Among these 138 patients, 105(76.1%, 95 CI 68.7–83.5%) were cured, while 33(23.9%, 95 CI 16.5–
31.3%) completed their treatment. The successful treatment outcomes varied significantly across the years, ranging
from 3.6% in 2020 to 90% in 2021. The analysis indicated a statistically significant difference in treatment outcomes
when considering data from 2014 to 2023 (χ2 = 44.539, p = 0.001). The proportion of patients with deaths, lost-to-
follow-up (LTFU), treatment failures and not evaluated were 7.9% [95% CI 4.8–11.2%], 10.9% [95% CI 7.2–14.6%), 2.2%
[95% CI 1.1–3.3%), and 28.9% [95% CI 23.7–34.2%] respectively. Individuals with a positive HIV status had signifi-
cantly lower odds of a favorable treatment outcome [AOR = 0.628, 95% CI (0.479–0.824), p = 0.018]. Similarly, patients
with a BMI of less than 18 are more likely to have unfavorable treatment outcomes compared to those with a BMI
of 18 or higher [AOR = 2.353, 95% CI 1.404–3.942, p < 0.001].
Conclusion The study revealed a concerning 1.4% prevalence of additional resistance to SLDs. The 50% rate of unfa-
vorable treatment among MDR-TB cases exceeds the target set by the WHO. A significant number of patients (10.9%)
were LTFU, and the 28.9% categorized as ‘not evaluated’ is also concerning. Enhanced strategic interventions are
needed to reduce such cases, and factors associated with poor treatment outcomes should receive greater attention.
Future prospective studies can further explore the factors influencing improved treatment success.
*Correspondence:
Hassen Mamo
binmamo@yahoo.com
Full list of author information is available at the end of the article
© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
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Kebede and Mamo BMC Pulmonary Medicine (2024) 24:527 Page 2 of 10
Additionally, the center is responsible for monitoring or the mycobacterial growth indicator tube (MGIT) sys-
several treatment follow-up centers (TFCs) for patients tem, which can take several weeks to obtain results [35].
undergoing ambulatory outpatient treatment care Chest X-rays and, in some cases, chest computed tomog-
through the DOT program. raphy (CT) scans are used to assess the extent and sever-
ity of pulmonary involvement, which can guide treatment
Study population and data collection decisions [36]. Due to the high co-occurrence of TB and
From January 2014 up to December 2023, a total of 308 HIV in Ethiopia, all TB patients, including those with
cases of MDR-TB were enrolled at the YGH MDR-TB MDR-TB, are tested for HIV [37]. HIV infection can
TIC. For this study, we included 276 cases of pulmonary impact the clinical presentation, treatment response, and
MDR-TB from the registry and medical records. Struc- management of MDR-TB. Finally, comprehensive clini-
tured data collection tools were developed based on the cal, social, and psychosocial assessments are conducted
national MDR-TB registration book and existing litera- to evaluate the patient’s overall health status, comorbidi-
ture to gather demographic and medical information. ties, and potential barriers to treatment adherence. This
Two trained nurses were employed to collect the data information is used to develop a personalized treatment
under supervision. The collected characteristics included plan and to identify any necessary support or interven-
sex, age, residence, year of enrollment, baseline informa- tions to ensure successful treatment outcomes.
tion such as sputum smear, treatment category (new or
re-treatment), prior drug exposure, HIV status, other Operational definitions
co-morbid diseases, confirmed method of diagnosis, All terms used in the study are operationally defined and
resistance type, body-mass-index (BMI), and treatment classified according to recommended guidelines [38]. Pre-
outcomes. sumptive TB refers to a patient who presents with symp-
toms or signs suggestive of TB (previously known as a
TB suspect). Rifampicin-resistant TB was defined as the
MDR‑TB diagnosis in Ethiopia detection of resistance to RIF using either phenotypic or
The diagnosis of MDR-TB in Ethiopia, as it is elsewhere, genotypic methods, with or without co-resistance to other
involves a multi-step process [29–32]. The initial step is anti-TB drugs. Multidrug-drug resistant TB (MDR-TB)
a clinical diagnosis. Patients with a history of previous was defined as caused by MTB strains that are resistant
TB treatment, especially those who have relapsed, failed to at least both and RIF and INH. The term cured was
treatment, or defaulted, are at an increased risk of devel- used to indicate patients with no evidence of treatment
oping MDR-TB and are considered presumptive cases of failure, where three or more consecutive cultures taken
the condition. Additionally, patients presenting with per- at least 30 days apart showed negative results after the
sistent symptoms of TB, such as cough, fever, weight loss, intensive phase. Treatment completed referred to patients
and night sweats, despite receiving appropriate first-line who showed no evidence of failure but did not have a
TB treatment, are also considered presumptive cases of record of three or more consecutive cultures taken at least
MDR-TB. 30 days apart showing negative results after the intensive
The presumptive TB cases then undergo bacteriological phase. Treatment failure was defined as a patient whose
confirmation, during which sputum samples are collected treatment was terminated or required a permanent regi-
and examined microscopically for the presence of acid- men change of at least two anti-TB drugs. The term died
fast bacilli (AFB). If AFB are detected, the samples are referred to a confirmed TB patients who passed away for
further tested using rapid molecular diagnostics, such as any reason before or during the course of treatment. Lost-
the Xpert MTB/RIF assay [33], to detect the presence of to-follow-up (LTFU) included patients whose treatment
MTB and determine resistance to RIF, a key first-line TB was interrupted for two consecutive months or more. Not
drug. Samples with RIF resistance are considered highly evaluated referred to a TB patient for whom no treatment
suggestive of MDR-TB and require further testing. outcome is assigned. This includes cases “transferred out”
Confirmed MDR-TB cases undergo comprehensive to another treatment unit as well as cases for whom the
drug susceptibility testing (DST) to determine resistance treatment outcome is unknown to the reporting unit.
patterns to a wider range of anti-TB drugs, including Treatment success or favorable treatment outcome was
INH, ethambutol, and injectable agents (e.g., kanamycin, used to describe patients who met the definitions of cure
amikacin, capreomycin) [34]. This information is cru- or treatment completion. Poor or unfavorable treatment
cial for designing an appropriate and effective treatment outcome was used to describe patients who died, were
regimen for the patient. DST is typically performed using LTFU, and/or experienced treatment failure during the
culture-based methods, such as the proportion method course of treatment.
Kebede and Mamo BMC Pulmonary Medicine (2024) 24:527 Page 4 of 10
centage proportions. Descriptive and regression models Other (district towns) 246 89.1
were utilized to identify factors associated with favora- Occupation
ble and unfavourable treatment outcomes. To determine Govermental employees 96 34.8
factors independently associated with unfavorable treat- Non-employees 180 65.2
ment outcomes, stepwise backward logistic regression Enrollment year
analysis was employed. A statistical significance level of 2014 33 12
p < 0.05 was deemed to be significant. 2015 10 3.6
2016 18 6.5
2017 30 10.9
Results
2018 50 18.1
Socio‑demographic characteristics
2019 28 10.1
Between 2014 and 2023, a total of 308 cases were enrolled
2020 28 10.1
in the MDR-TB center at YGH for treatment initiation.
2021 10 3.6
However, 32 of these were excluded as they were referred
2022 33 12
from outside the SNRS. Therefore, only 276 cases were
2023 36 13
considered. Among these 276 cases, 175(63.4%) were
male patients and 101(36.4%) were female patients,
resulting in a male-to-female ratio of approximately 2:1.
The mean age was 28.95 ± 12.882 years, with a median age Additionally, 16(5.8%) patients had comorbid diseases
of 26 (interquartile range [IQR] = 20–35) years. Among other than HIV co-infections, with diabetes mellitus
the cases, 160(57.97%) patients were between 20 and being the most common. The average BMI was 17.1736,
35 years of age, with the minimum and maximum ages with a median IQR of 17.000 (15.2000–18.9000), and
being 1 and 80 years, respectively. The majority (89.1%) 79.3% of the patients had a baseline BMI value ≥ 18 kg/
of the patients were from rural areas of the region, and m2 (Table 2). All bacteriologically confirmed MDR-TB
the highest number of cases were from Aroresa, Chire, cases were also screened and treated based on confirma-
Arbegona, and Hula districts, which are located more tory drug susceptibility test (DST) results before and after
than 100 km away from the treatment initiation center, treatment initiated. Based on DST result, 14(5.1%) were
as well as Hawassa city. Moreover, 180(65.2%) of the par- resistant to both INH and RIF (13 retreatment and 1 new
ticipants were non-employees. In terms of the year of cases). Four (1.5%) MDR-TB cases were diagnosed with
treatment initiation, 50(18.1%) patients were enrolled in additional resistance to SLDs at enrollment, with levo-
2018, representing the highest proportion, followed by floxacin being the dominant drug resistance observed in
36(13.0%) patients enrolled in 2023 (Table 1). 3 MDR-TB female patients who had previous exposure to
ant-TB drugs.
Medical and anthropometric characteristics
Among the 276 cases, 210(76.1%) had previously received Treatment outcomes
anti-TB drugs (retreatment cases) the rest were new at The final treatment outcomes of 80 patients (29.1%,
enrollment. At enrollment, all patients were tested for 95% CI 23.74–34.24%) had no recorded treatment out-
HIV co-infection, and 21(7.6%) patients tested positive. comes in the treatment center. This includes 1 patient in
Kebede and Mamo BMC Pulmonary Medicine (2024) 24:527 Page 5 of 10
Table 2 Clinical and anthropometric characteristics of MDR-TB (cured + complete) among male participants was approx-
patients at Yirgalem General Hospital MDR-TB treatment initiation imately 1.6(84/54) times compared to females. Treatment
center, Sidama Region, South Ethiopia, 2014–2023, N = 276 outcomes varied significantly from year to year, with
Variable History of previous drug Overall, no(%) the lowest success rates observed in 2020 (3.6%), 2023
use, no(%) (11.1%), and 2022 (36.4%). Slight changes were noted
Yes (N = 210) No (N = 66) between 2016, 2017, and 2018, while the highest success
rate (90%) was recorded in 2021. The difference in suc-
HIV status cessful treatment outcomes between the years were sta-
Reactive 13(61.9) 8(38.1) 21(7.6) tistically significant (χ2 = 44.539, p = 0.001).
Non-reactive 197(77.3) 58(22.7) 255(92.4)
Co-morbid disease other than HIV
Yes 16(100) 0(0) 16(5.8) Factors affecting treatment outcomes
No 194(74.6) 66(25.4) 260(94.2) Out of variables tested in the bivariate and multivariable
Resistance profile logistic regression (Table 4), individuals with a positive
RIF only 197(76.4) 61(23.6) 258(93.5) HIV status had significantly lower odds of a favorable
RIF + INH 13(92.9) 1(7.1) 14(5.1) treatment outcome compared to those with a negative
Any resistance to SLD 3(75) 1(25) 4(1.4) HIV status (adjusted odds ratio (AOR) = 0.628, 95% CI
(Fluoroquinolone) 0.479–0.824, p = 0.018]. Individuals having a BMI < 18
Diagnostic method had significantly higher risk of having unfavourable treat-
GeneXpert 187(75) 60(33.1) 247(89.4) ment outcome compared to those having BMI of ≥ 18
Line probe Assay 14(82.4) 3(16.6) 17(6.1) (AOR = 2.353, 95% CI 1.404–3.942, p < 0.001). The AOR
Confirmed culture 5(55.6) 4(44.4) 9(3.3) of 0.628 suggests that being HIV positive is linked to a
Other (clinical) 3(100) 0(0) 3(1.1) higher risk of unfavorable outcomes compared to being
Baseline sputum smear test result HIV negative. The lower odds ratio indicates a significant
Positive 123(69.5) 54(30.5) 177(64.1) negative impact on treatment success among those who
Negative 85(89.5) 10(10.5) 95(34.9) are HIV reactive. The AOR of 2.353 indicates that having
Not done 2(50) 2(50) 4(1.4) a low BMI is associated with a significantly higher risk
BMI (kg/m2) of unfavorable outcomes. This means that underweight
< 18 37(64.9) 20(35.1) 57(20.7) patients are more likely to experience negative treatment
≥ 18 173(79) 46(21) 219(79.3) results. Overall, the analysis identifies HIV positivity and
Have drug adverse 120(43.5) low BMI as significant factors negatively impacting treat-
effects ment outcomes for MDR-TB patients.
BMI Body Mass Index, INH Isoniazid, RIF Rifampicin
Discussion
2017 (N = 30), 3 patients in 2018 (N = 50), 3 patients in The management of MDR-TB necessitates increased
2019 (N = 28), 26 patients in 2020 (N = 28), 18 patients resources for detection, successful treatment, and effec-
in 2022 (N = 33), and 29 patients in 2023 (N = 36). The tive reduction of its burden. In 2015, Ethiopia successfully
overall treatment success rate was 50%(138/276) [95% achieved the millennium development goals established
CI 44.1–55.9%]. Of these 138 favorable treatment cases, for TB and expressed its commitment to expedite the
105(76.1%, 95% CI 68.7–83.5%) patients were declared eradication of TB by 2035 as part of a national strategic
cured, while 33(23.9, 95% CI 16.5–31.3%) completed plan [39]. This plan emphasizes the implementation of
their treatment. In the ten-year retrospective follow-up robust TB case-finding strategies and the utilization of
study, 22 patients (7.9%, 95% CI 4.8–11.2%) died during rapid diagnostic technologies to address the gap in iden-
treatment, 30(10.9%, 95% CI 7.2–14.6%) were LTFU, 6 tifying missed TB cases and combat MDR-TB threat.
patients (2.2%, 95% CI 1.1–3.3%) experienced treatment Our study indicated that 76.1% of MDR-TB patients
failure, and 80 (28.9%, 95% CI 23.7–34.2%) fell into the had previously undergone treatment for TB, and 5.1%
‘not evaluated’ category (Table 3). exhibited resistance to both INH and RIF (for new/pre-
Regarding the adverse effects of the drugs, 120 out of vious exposure), while 1.4% of MDR-TB cases demon-
276(43.5%) developed drug side effects following the strated additional resistance to SLDs (pre-XDR/TB) at
initiation of treatment. The proportion of male patients the baseline and treated within the cohort of MDR-TB. A
with favourable treatment outcomes was 48.0% (84/175) study that analyzed an aggregated and individual patient
and that of female participants in the cohort was 53.5% data [40] using six eligible studies reporting treatment
54/101. However, the relative ratio of treatment success outcome on 1993 MDR-TB patients in Ethiopia found a
Table 3 Trends of treatment outcomes of MDR-TB patients at Yirgalem General Hospital MDR-TB treatment initiation center, Sidama Region, South Ethiopia, 2014–2023 (N = 276)
Enrollment year
Treatment outcome 2014 N = 33 2015 N = 10 2016 N = 18 2017 N = 30 2018 N = 50 2019 N = 28 2020 N = 28 2021 N = 10 2022 N = 33 2023 N = 36 Total
N = 276
Kebede and Mamo BMC Pulmonary Medicine
Favorable, no(%) 27(81.8) 7(70.0) 11(61.1) 18(60.0) 30(60.0) 19(67.9) 1(3.6) 9(90.0) 12(36.4) 4(11.1) 138(50.0)
Cured 21 6 10 12 20 16 1 8 7 4 105(76.1)
Female 7 2 2 3 7 7 0 6 3 1 38(36.2)
Male 14 4 8 9 13 9 1 2 4 3 67(63.8)
(2024) 24:527
Complete 6 1 1 6 10 3 0 1 5 0 33(23.9)
Female 2 1 0 3 5 0 0 1 4 0 16(48.5)
Male 4 0 1 3 5 3 0 0 1 0 17(51.5)
Unfavorable, no(%) 6(18.2) 3(30.0) 7(38.9) 12(40.0) 20(40.0) 9(32.1) 27(96.4) 1(10.0) 21(63.6) 32(88.9) 138(50.0)
Died 3 1 4 1 5 3 1 1 2 1 22(7.9)
Female 1 0 1 0 3 0 0 0 0 0 5(1.8)
Male 2 1 3 1 2 3 1 1 2 1 17(6.2)
LTFU 2 1 2 8 12 2 0 0 1 2 30(10.9)
Female 0 1 0 3 1 0 0 0 1 1 7(2.5)
Male 2 0 2 5 11 2 0 0 0 1 23(8.3)
Failure 1 1 1 2 0 1 0 0 0 0 6(2.2)
Female 0 0 1 2 0 1 0 0 0 0 4(1.4)
Male 1 1 0 0 0 0 0 0 0 0 2(0.7)
Not evaluated 0 0 0 1 3 3 26 0 18 29 80(28.9)
Female 0 0 0 0 3 1 8 0 10 9 31(38.8)
Male 0 0 0 1 0 2 18 0 8 20 49(61.2)
Page 6 of 10
Kebede and Mamo BMC Pulmonary Medicine (2024) 24:527 Page 7 of 10
Table 4 Bivariate and multivariable analysis of factors associated with treatment outcomes of MDR-TB treatment at YGH MDR-TB
treatment initiation center, Sidama Region, South Ethiopia, 2014–2023 (N = 276)
Variable Treatment outcome COR (95% CI) AOR (95% CI) p-value
Unfavorable no(%) Favorable no(%)
Age in years
< 24 56(53.3) 49(46.7) 1.000 1.000 0.132
24–44 68(51.1) 65(48.9) 0.510 (0.238–1.094) -
≥ 45 14(36.8) 24(63.2) 0.558(0.266–1.171)
HIV status
Non-reactive 122(47.8) 133(52.2) 1.000 1.000
Reactive 16(76.2) 5(23.8) 0.287 (0.2–0.70) 0.628 (0.479—0.824) 0.018
Non-HIV comorbidity
No 134(51.5) 126(48.5) 1.000 1.000
Yes 4(25.0) 12(75.5) 3.190 (1.003–10.152) 1.063(1.003–1.128) 0.077
History of TB drug use
No 36(54.5) 40(45.5) 1.000 1.000 0.257
Yes 102(48.6) 108(51.4) 0.787(0.452–1.371) 0.944(0.827–1.078)
BMI
≥ 18 98(44.7) 121(55.3) 1.000 1.000
< 18 40(70.2) 17(29.8) 2.905(1.552–5.438) 2.353(1.404–3.942) < 0.001
pooled treatment success of 59.2% highlighting treatment factor for MDR-TB. However, it is worth noting that pos-
success among MDR-TB patient was below acceptable sible mismanagement of anti-TB drug-sensitive cases at
range. In a study in the northwestern part of Ethiopia various levels can be a contributing factor to the emer-
which analyzed retrospective data from 2011 to 2021 gence of drug resistance. The finding of 1.4% of cases
[41], the treatment success rate was 77.1%. diagnosed with additional resistance to core SLDs in
A systematic review published in 2014 [42] reported our study is alarming and poses a threat to the national
high prevalence of MDR-TB in the range of 3.3–46.3%, TB end strategy, as the majority of cases remain undiag-
and two studies reported XDR-TB in the range of 1–4.4% nosed, putting the community at risk and increasing the
in Ethiopia. The review concluded that ‘most power- likelihood of disease progression towards another form
ful’ predictor of the emergence of MDR-TB reported in of MDR-TB, such as XDR-TB. Notably, the findings from
Ethiopia was previous exposure to anti-TB drug treat- our study recommend future community-based studies
ment. This review indicated that MDR-TB in Ethiopia is a to obtain updated a nationwide figure.
serious public health problem that needs to be addressed In the current cohort study, 50.0% of patients
urgently. A subsequent similar systematic review and achieved successful treatment outcomes is lower than
meta-analysis study published in 2017 [43] reported the rates reported in hospital-based studies conducted
an overall prevalence of MDR-TB among newly diag- in northwest and northeast Ethiopia [41]. Our study
nosed and previously treated TB patients to be 2% (95% notably reports an 7.9% [95% CI 4.8–11.2%] death rate
CI 1–2%) and 15% (95% CI 12–17%), respectively for among patients during the treatment course, which is
16 eligible studies assessed. This study also found that comparable with a hospital-based study by Belachew
previously treated TB patients were at a higher risk of et al. 9.3% [41]. Furthermore, all patients diagnosed
developing a MDR-MTB infection compared to newly with additional resistance to SLDs died after enroll-
diagnosed cases. The study concluded that the burden of ment, which may reflect the level of patient-centered
MDR-TB remains high in Ethiopian settings, especially in services in the treatment center. The fact that all
previously treated TB cases although for the past 10 years patients with additional resistance died highlights the
(2006 to 2014) the overall MDR-TB prevalence showed a need for improved patient-centered services and treat-
stable time trend. ment outcomes. Furthermore, our study found that
Later studies conducted in the eastern [44], central 50.0% of MDR-TB cases had unsuccessful treatment
[45], and southern Ethiopia [46, 47] have implicated pre- outcomes in the entire cohort. This figure is fivefold
vious exposure to anti-TB treatment as a common risk higher than the expected estimate by the WHO, which
Kebede and Mamo BMC Pulmonary Medicine (2024) 24:527 Page 8 of 10
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