Analysis of tuberculosis treatment outcomes among pulmonary tuberculosis patients in Bahawalpur, Pakistan
Atif et al. BMC Res Notes
Analysis of tuberculosis treatment outcomes among pulmonary tuberculosis patients in Bahawalpur, Pakistan
Muhammad Atif 0
Zainab Anwar 0
Razia Kaneez Fatima 2
Iram Malik 0
Saima Asghar 0
Shane Scahill 1
0 Department of Pharmacy, The Islamia University of Bahawalpur , Bahawalpur , Pakistan
1 Massey University , Auckland , New Zealand
2 National Tuberculosis Control Program of Pakistan , Islamabad , Pakistan
Objective: Monitoring tuberculosis treatment outcomes and understanding the reasons for unsuccessful treatment are important indicators for evaluating the performance of the national tuberculosis control program. The aim of this study was to evaluate the treatment outcomes among pulmonary TB (PTB) patients and identify the predictors of unsuccessful treatment outcome. Results: Treatment success rate of 67.8% among new and retreatment PTB patients and 69% in new smear positive PTB patients was observed. Close to 21% (20.9%) and 15.7% PTB and new smear positive PTB patients had loss to follow-up during treatment. Overall, older patients (AOR 1.02; 95% CI 1.01-1.0), smokers (AOR 1.65; 95% CI 1.02-2.67) and retreatment cases of TB (AOR 2.34; 95% CI 1.43-3.84) were at greater risk of having unsuccessful treatment outcomes. Moreover, sputum positivity at 2 months (AOR 13.78; 95% CI 5.09-37.26) was a significant predictor of poor treatment outcomes in new smear positive PTB patients. The treatment success rate among PTB patients was lower than the recommended 85% success rate. TB patients at higher risk of unsuccessful treatment outcomes should be provided with enhanced supervision and treatment monitoring to improve the success rate of TB management in Pakistan.
Pulmonary tuberculosis; New smear positive pulmonary tuberculosis; Treatment outcomes; Unsuccessful treatment outcome; Pakistan; High TB burden countries
Despite the fact that tuberculosis (TB) is a preventable
disease, it still ranks among the top ten causes of death
]. According to a recent report by the World
Health Organization (WHO) in 2016, around 10. million
people were infected with Mycobacterium tuberculosis
and 1.7 million people died (including .4 million deaths
among human immunodeficiency virus (HIV)-positive
people) due to TB [
]. According to 2016 estimates, 56%
of people suffering from TB were living in five
countries (in descending order); India, Indonesia, China, the
Philippines and Pakistan [
]. Pakistan shares 61% of the
TB burden in the WHO Eastern Mediterranean Region
]. In 2016, 356,390 new and relapsed cases of TB were
notified in Pakistan, showing an increase in the number
of notified cases compared with 2015 (323,856 cases) [
]. Among all notified cases in 2016, 80% were
pulmonary tuberculosis (PTB) cases, and 4% cases had known
HIV infection . Although trends in TB mortality rates
in Pakistan from 2012 to 2016 demonstrate a substantial
decline in associated deaths ranging from 34 to 23 cases
per 100,000 population [
], TB remains a significant
killer in this country.
To control the global burden of TB, in 2006 the WHO
developed the Stop TB Strategy (2006–2015) that was
built on the Stop TB Partnership’s first global plan (2001–
]. The main targets outlined in the strategy linked
to the Millennium Development Goals (MDGs) were
reduction in TB prevalence and mortality rate due to TB
by 50% by 2015 as compared to 1990 [
]. Pakistan has
met this Stop TB target of 50% reduction in TB
mortality rates over the specified time and has made enormous
progress regarding successful treatment of
drug-susceptible TB. However, the country still faces a burdensome
prevalence rate of 341 cases per 100,000 population and
an incidence rate of 270 cases per 100,000 [
Moreover, in recent years, Pakistan is estimated to stand fourth
among countries of the world with the highest
proportion of multidrug-resistant TB (MDR-TB) .
The WHO recommends that treatment outcome
analysis among PTB patients be carried out every year
at national and district levels [
]. Considering the
recommendations of the WHO and taking into account the
steady surge in burden of TB in Pakistan, this study aims
to assess treatment outcomes of PTB patients including
newly diagnosed smear positive PTB cases at the Bahawal
Victoria Hospital (BVH) in southern Punjab, Pakistan.
This study was undertaken at the TB DOTS (directly
observed treatment, short course) clinic in the
Respiratory Department of the BVH. The BVH, a 1600 bedded
health facility, serves as a tertiary care referral hospital in
the southern region of Punjab, Pakistan. The Chest
Disease Unit (CDU) of the BVH has 8–10 physicians, 5–6
chest specialists and two pharmacists who provide
routine care to patients with chest-related diseases [
TB outdoor clinic is visited by 35–40 TB patients daily.
The TB unit within the chest clinic works under the
National Tuberculosis Control Program (NTP) [
As suggested by the NTP guidelines, ‘presumptive TB
cases’ are identified at the TB outdoor clinic based on
their symptoms and follow-up microscopy [
]. The TB
DOTS clinic has a separate diagnostic laboratory and an
X-ray room. Smear positive patients are referred for
registration, and TB treatment is provided free of charge to
Study design and data collection
This was a retrospective study including all new and
retreatment smear negative and smear positive PTB
patients (1 year cohort) diagnosed and registered at BVH
between January 1 and December 31, 2014. Medical
registers and TB treatment cards were reviewed to collect
socio-demographic, clinical and treatment-related data
]. Individual treatment files were also reviewed
to obtain biochemical and hematological data of PTB
Reporting of treatment outcomes
The outcomes of treatment were reported in
accordance with six outcome categories developed and
recommended by the WHO and the International Union
Against Tuberculosis and Lung Disease (IUATLD). This
allows standardized reporting of treatment outcomes
among all new and retreatment PTB patients [
Descriptions for outcome categories are provided in
Additional file 1: Table S1.
Data were analyzed using the Statistical Package for
Social Sciences (IBM, SPSS Statistics for Windows,
version 21.0. Armonk, NY: IBM Corp.). Categorical
variables were analyzed using counts and proportions (%).
Continuous variables were described in terms of mean
and standard deviations (SD). Simple logistic regression
analysis was applied to evaluate the relationship between
the dependent variable (i.e., unsuccessful treatment
outcome) and the selected socio-demographic and clinical
variables. Statistically significant variables in univariate
analysis were analyzed using multiple logistic regression
analysis to determine the final predictors of
unsuccessful treatment outcome. The beta, standard error, adjusted
odd ratios (AOR), 95% CI and p value were documented
for each predictor [
A total of 969 TB patients were registered at the study
site. Out of these, 690 (71.2%) PTB patients were
included in the study. Over one quarter of patients (279,
28.8%) were excluded with 270 (27.8%) patients having
EPTB, 8 (.8%) having incomplete records of TB treatment
and 1 (.1%) being diagnosed with MDR-TB. In terms of
microscopic findings, 283 (41%) patients were smear
positive while the remaining 407 (59%) were smear negative.
Among the 283 smear positive cases, the large majority
(242, 85.5%) were new cases of PTB. For details, please
refer to Table 1.
Out of 690 PTB patients, only 468 (67.8%) patients
were found to be successfully treated. Among the
unsuccessfully treated patients, 14 (2.0%) failed the treatment,
144 (20.9%) were lost to follow-up and 35 (5.1%) died
during the treatment course (Additional file 2: Table S2).
Of all new smear positive PTB patients, 163 (67.3%) were
reported as cured and 4 (1.7%) completed the treatment
Through multiple logistic regression analysis, factors
that remained significantly associated with the
unsuccessful treatment outcome among new and retreatment
PTB patients were; age 45 years and above (OR 1.02;
95% CI 1.01, 1.03, p < .0005), being a retreatment case of
PTB (OR 2.34, 95% CI 1.43, 3.84, p = .001) and being a
smoker (OR 1.65, 95% CI 1.02, 2.67, p = .04). For the new
smear positive PTB patients, the only determinant in the
multiple logistic regression analysis which was
significantly related to the unsuccessful treatment outcome was
In this study, the overall treatment success rate among
PTB patients was low. In addition, treatment
success in new smear positive PTB patients was less than
the WHO successful target rate of 85%. Along similar
lines, other high TB burden countries such as Somalia
], Nigeria [
] India (74%) and Brazil (71%)
have reported suboptimal treatment success rates [
Interestingly, in contrast to our findings, the overall
treatment success rate in the Eastern Mediterranean
Region of the WHO including Pakistan was above 90%
for the 2014 cohort [
]. This variation in TB treatment
outcomes around the world might be explained by
different factors such as the study design and sample size
of study population, complexity of the disease among
the patients, quality of facilities provided at the
treatment center, HIV status of patients and local beliefs
among TB patients about the DOTS strategy.
In the current study the major reasons for the lower
treatment success rate were firstly, higher loss to
follow-up and secondly, the death rate. Studies from
Libya and Ethiopia also documented consistent
findings regarding loss to follow-up among smear positive
PTB patients [
]. At the local level, patient loss to
follow-up might also be compounded by the need to
purchase medicines to alleviate the side effects of TB
medicines in those who already have poor financial
status. As reported in the literature , patients’ time
constraints, long distances from TB clinics and
stigmatizing attitudes towards their illness might contributed
towards treatment non-compliance. The second major
factor responsible for lower treatment success rates was
the higher death rate amongst our Pakistani patients.
This is in agreement with previously conducted studies
in Singapore and the United States [
]. A higher
death rate in our study could be attributed to the study
setting. BVH is a tertiary care referral hospital in the
southern region of Punjab, Pakistan and it is likely that
a relatively higher number of complex TB patients are
registered or referred to the BVH, thereby contributing
towards the high mortality rate. Moreover, the higher
loss to follow-up rate might have contributed to the
development of a more complex and drug resistant M.
TB strain among the TB patients. This would result in
an increase in the risk of death.
In the multiple logistic regression analysis, being a
retreatment case, older age, and being a smoker were the
independent predictors of unsuccessful treatment
outcomes among PTB patients. In line with our findings,
studies conducted elsewhere have reported poor
treatment outcomes among retreatment TB cases [
14, 17, 22
Similarly, the current study revealed that there is
relatively higher treatment failure rates amongst retreatment
cases (Additional file 3: Table S3) and that could be a
consequence of possible MDR-TB in this subgroup.
Unfortunately, at the time the study was conducted the WHO
] culture and drug susceptibility testing
(DST) that were not accessible for complex TB cases at
BVH (now these services are available).
This study highlighted that older patients were at greater
risk of having poor treatment outcomes for TB. Similar to
our findings, a previous Pakistani study [
] and an
Ethiopian study [
] reported increased age to be associated
with unsuccessful treatment outcome. As older patients are
reasonably fragile, non-ambulatory and reliant on family
members for transport to health centers for their ongoing
treatment there are more likely to be treatment
interruptions in this cohort. Smoking was another independent risk
factor associated with the unsuccessful treatment outcome
among PTB patients. In line with our findings, a recently
conducted study in Pakistani TB patients found
smoking to be significantly associated with unsuccessful
treatment outcomes [
]. Similarly, other studies showed higher
unsuccessful treatment outcomes possibly due to
treatment failure among TB patients who smoke [
Analysis of treatment outcomes among new smear
positive PTB patients is important to conduct, as they are
major indicators of NTP performance. In this study, along
with the assessment of treatment outcomes in new smear
positive PTB patients, risk factors for unsuccessful
treatment outcomes were also determined. Our study revealed
sputum positivity at 2 months to be an independent
predictor of unsuccessful treatment outcome among new smear
positive PTB patients. All 10 patients in our study with a
positive sputum smear result at 2 months failed
treatment, indicating direct association of sputum positivity
at 2 months with treatment failure among smear positive
PTB patients. Similar to our findings, studies from India
and South Africa have reported significant associations
between sputum non-conversion and poor treatment
In conclusion, the treatment success rate among PTB
patients in this Pakistani study were lower than the
expected success target of 85%. Similarly, treatment success
rates in new smear positive PTB cases were also less than
targets set by the WHO. A large proportion of patients
were lost to follow-up and died during treatment, which
causes serious concern and warrants urgent action.
Effective tracing methods for patients lost to follow-up should
be developed and implemented to minimize treatment
interruptions. Moreover, patients with an increased risk
of having unsuccessful treatment outcomes should be
provided with enhanced supervision and treatment
monitoring to improve outcomes.
Our study as a few limitations. First, the findings cannot
be generalized to indicate TB treatment success rate in the
whole of Pakistan. This is because, BVH serves a complex
population of TB patients from distant and rural areas.
Indeed, the higher proportion of loss to follow-up and the
death rate support this notion. Second, the retrospective
design of this study is another limitation. It was not possible
to prospectively access all of the patients’ clinical variables,
information regarding major side effects of anti-TB drugs
and factors that might have affected loss to follow-up and
death rates (these were not written in patient charts).
Additional file 1: Table S1. Definition of treatment outcomes.
Additional file 2: Table S2. Treatment outcomes of all smear negative
and smear positive pulmonary tuberculosis patients as per the Standard*
Criteria (n = 690).
Additional file 3: Table S3. Number of new and retreatment smear
negative and smear positive pulmonary tuberculosis patients by treatment
outcomes category (n = 690).
AOR: adjusted odds ratios; BVH: Bahawal Victoria Hospital; CDU: Chest Disease
Unit; DOTS: directly observed treatment, short course; DST: drug sensitivity
testing; HIV: human immunodeficiency virus; IUATLD: International Union
Against Tuberculosis and Lung Disease; MDR-TB: multidrug resistant
tuberculosis; MGDs: Millennium Development Goals; NTP: National Tuberculosis
Control Program; PTB: pulmonary tuberculosis; SD: standard deviation; TB:
tuberculosis; WHO: World Health Organization.
MAT and ZA made substantial contributions to the conception and design of
the study. SS, IM, SA and RKF also made contributions to the conception and
design of the manuscript. ZA collected data. All authors were involved in data
interpretation. ZA, MAT, IM, SA and RKF drafted the manuscript. SS and MAT
critically revised the manuscript. MAT is the research supervisor of ZA, IM and
SA. All authors read and approved the final manuscript.
We would like to thank the Medical Superintendent and Assistant Medical
Superintendent of the Bahawal Victoria Hospital for their help in facilitating
this research work.
The authors declare that they have no competing interests.
Availability of data and materials
The raw data on which conclusions of this manuscript rely is available upon
request. Please contact Zainab Anwar at .
Consent to publish
Ethics approval and consent to participate
The study was approved by the Pharmacy Research Ethics Committee (PREC)
at the Islamia University of Bahawalpur (Ref. No. 13 − 2015/PREC). The study
design and conduct was also approved by the Medical Superintendent (Diary
No. 14849, date: 19-9-15) and the Head of the CDU Department, BVH.
No funding was involved in the preparation of this article or in the decision to
submit it for publication.
Springer Nature remains neutral with regard to jurisdictional claims in
published maps and institutional affiliations.
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