J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

Contents lists available at ScienceDirect

J Clin Tuberc Other Mycobact Dis

journal homepage: www.elsevier.com/locate/jctube

Quality of life with tuberculosis T

Ashutosh N. Aggarwal
Department of Pulmonary Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

A R T I C LE I N FO A B S T R A C T

Keywords: Tuberculosis diagnosis and treatment currently revolves around clinical features and microbiology. The disease
Quality of life however adversely affects patients’ psychological, economic, and social well-being as well, and therefore our
Questionnaire focus also additionally needs to shift towards quality of life (QOL). The disease influences all QOL domains and
Stigma substantially adds to patient morbidity, and these complex and multidimensional interactions pose challenges in
Tuberculosis
accurately quantifying impairment in QOL. For this review, PubMed database was queried using keywords like
quality of life, health status and tuberculosis, and additional publications identified by a bibliographic review of
shortlisted articles. Both generic and specific QOL scales show a wide variety of derangements in scores, and
results vary across countries and patient groups. In particular, diminished capacity to work, social stigmatiza-
tion, and psychological issues worsen QOL in patients with tuberculosis. Although QOL has been consistently
shown to improve during standard anti-tubercular therapy, many patients continue to show residual impair-
ment. It is also not clear if specific situations like presence of comorbid illnesses, drug resistance, or co-infection
with human immunodeficiency virus additionally worsen QOL in these patients. There is a definite need to
incorporate QOL assessment as adjunct outcome measures in tuberculosis control programs. Governments and
program managers need to step up socio-cultural reforms and health education, and provide additional in-
centives to patients, to counter impairment in QOL.

1. Background (QOL). Despite this, patient perceptions about disease and their health
have remained largely unknown.
Worldwide, tuberculosis (TB) continues to be an important public QOL is a broad and complex multidimensional concept that in-
health issue, and a major cause of morbidity and mortality. Despite corporates physical, social, psychological, economic, spiritual and other
advances in diagnosis and therapy nearly ten million incident TB cases domains. It is therefore difficult to define and measure, but may be
were reported, and an estimated 1.6 million deaths occurred due to TB, broadly described as individuals’ perceptions of their position in life in
globally in 2017 [1]. Almost a quarter of the world's population is la- the context of the culture and value systems in which they live and in
tently infected with TB, and therefore at risk of progressing to active relation to their goals, expectations, standards and concerns [3]. QOL
disease sometime during their lifetime [1]. therefore is an expression of patient preferences and values rather than
According to the World Health Organization, health is defined as a clinician's assessment. For the latter, one simply needs to ask the patient
state of complete physical, mental, and social well-being and not a mere “How high is your fever?”, while for the former, patient response to the
absence of disease or infirmity. The impact of any disease, especially a question “How much are you bothered by your fever?” or “To what
chronic illness like tuberculosis, on an individual patient is therefore extent do you feel that fever prevents you from doing what you need to
often all-encompassing, affecting not only his physical health but also do?” can be recorded. Self-reported health-related QOL is therefore an
his psychological, economic, and social well-being. important adjunct measure in understanding and quantifying the actual
At present, the TB control services are geared towards optimizing impact of TB on patients.
microbiological cure, and using this parameter as an indicator for This review was conducted to summarize the various issues related
successful treatment. Although this is extremely important from a to QOL among patients with all forms of TB. A broad search was con-
public health perspective, such an approach does not adequately ad- ducted through the PubMed platform using keywords like quality of
dress the physical, mental and social suffering of patients due to TB [2]. life, health status and tuberculosis. Relevant publications for detailed
Patients suffer not only because of the symptoms of the disease, but also evaluation were identified through an abstract review of the search
because of the resultant general deterioration in their quality of life results. Additional key references were identified from bibliography of

E-mail address: aggarwal.ashutosh@outlook.com.

https://doi.org/10.1016/j.jctube.2019.100121

2405-5794/ © 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/BY-NC-ND/4.0/).
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

shortlisted publications during their full-text review. Data from large

and well-conducted studies was preferentially used to summarize and
tabulate important findings.

2. Instruments for describing and quantifying QOL in TB

An objective assessment of patient's QOL attempts to quantify the

functional effects of an illness and its consequent therapy on a patient,
as perceived by that patient. A wide variety of questionnaires and scales
have been employed to evaluate self-rated QOL in patients with active
TB [4–7]. Some of these evaluate QOL holistically, whereas others focus
on specific domains like physical health or psychological morbidity.
The simplest approach to QOL assessment is using only one sum-
mary item as a global descriptor of QOL. This can take the form of a
single question, a visual analogue scale (VAS), or a standard gamble
approach [8–13]. However, this is likely to miss important information
on several important facets of QOL that may be important to TB pa-
tients. More and more investigators therefore rely on standardized
multidimensional scales to obtain a more comprehensive picture of the
relevant facets and domains. Several of these instruments are generic,
which means that they can be used across a wide spectrum of disorders
(and even among healthy individuals). A commonly used scale in TB
research is Short Form 36 (SF-36) [13–31]. This gives scaled scores
across eight domains – Physical Functioning, Role Physical, Bodily Pain,
General Health, Vitality, Social Functioning, Role Emotional, and
Mental Health, and two summary scores – Physical Component Score Fig. 1. Important determinants of quality of life with tuberculosis.
and Mental Component Score. The EQ-5D, developed by the European
QOL Group, is another commonly used instrument [10,30–34]. It has of a pulmonary TB scale. The resultant QLICD-PT instrument has three
two components – health state description and evaluation. In the de- domains (with 28 items) for general QOL and one pulmonary TB spe-
scription part, health status is measured through five dimensions (5D) – cific domain (with 12 items) [56]. The scale has been shown to have
mobility, self-care, usual activities, pain/discomfort, and anxiety/de- acceptable degree of validity, reliability and responsiveness. To the best
pression. VAS is used to assess overall health status in the evaluation of our knowledge, both these new QOL instruments have not been used
part. The abbreviated World Health Organization Quality of Life scale by other independent researchers.
(WHOQOL-Bref) is another popular generic instrument [35–42]. This In addition, more specific instruments have been used to explore
26-item instrument evaluates QOL across four domains – Physical, individual QOL domains in TB. This is most evident in evaluation of
Psychological, Social relationships, and Environment. Some other psychological morbidity, where several tools such as General Health
generic scales used include Medical Outcome Survey (MOS) [9] Social Questionnaire 12 (GHQ12) [57], Patient Health Questionnaire (PHQ-9)
Functioning 12 (SF-12) [32,43], variants of the WHOQOL scale family [12,58–60], Centre for Epidemiologic Studies Depression Scale (CES-D)
[19,44,45], and other uncommon or in-house instruments [46–48]. [31], State-trait Anxiety Short-Form (STAI-6) [31], Kessler-10 item
Although generic measures permit comparisons across interventions scale (K-10) [45,61], Hospital Anxiety and Depression Scale (HADS)
and diagnostic categories, they fail to adequately capture facets parti- [25,32], and others have been used.
cularly important to a particular disease. More specific instruments may
prove better in this regard, and these can be either system-specific or
disease-specific. Since lungs are the predominant organ involved in TB, 3. QOL evaluation in TB patients
it is intuitive that respiratory-system specific questionnaires may be
appropriate in pulmonary TB. The St. George's Respiratory ques- QOL can be influenced by several patient, disease, and treatment-
tionnaire (SGRQ) has been used in some studies [32,49,50]. It has 76 related factors in TB patients (Fig. 1). Few investigators have evaluated
items, whose responses can be aggregated into an overall score and QOL in adult patients through cross-sectional studies (Table 1). In
three domain scores for Symptoms, Activity and Impact. Another ap- general, QOL of TB patients is poorer as compared to healthy in-
proach is to use disease specific instruments. Unfortunately, TB-specific dividuals across most domains, with physical functioning domain af-
QOL instruments have not been widely used. Dhingra and Rajpal pro- fected more severely than others [5,14,19,25,31,35–38,62]. Patients
posed a disease-specific QOL instrument (DR-12) from data on TB pa- with active TB generally also perceive their health status to be worse as
tients treated under programmatic conditions in India [51]. This scale compared to people with latent TB or previously cured TB
has 12 items over two domains – Symptoms, and Sociopsychological/ [5,8,13,16,17,21]. However, the relative contribution of TB towards
exercise adaptation. However, scale development was not scientifically impairment of QOL can sometimes be problematic as several patients
rigorous, and phrasing of items suggests it to be more of a health status have other comorbid illnesses or socio-economic problems [63].
rather than QOL instrument. It has been sparsely used [52,53]. Another Overall, QOL seems largely independent of age and gender [48,64].
disease specific instrument FACIT-TB (Functional Assessment of However, some studies report advancing age to be negatively correlated
Chronic Illness Therapy – Tuberculosis) has been developed, and psy- with QOL [10,13,38]. Others report worse QOL among women
chometrically validated in Arabic, for quantifying QOL in TB patients in [17,36,38]. One Indian study has shown higher QOL scores for physical
Iraq [54,55]. This questionnaire, which is a part of the FACIT mea- and psychological domains among women, probably suggestive of
surement system, consists of 45 items across five domains – Physical better coping strength [36]. Also, lower education level and poor socio-
well-being, Social and economic well-being, Emotional well-being/ economic status may be associated with greater impairment of QOL
Stigma of having TB, Functional well-being, and Spiritual well-being. [17,48]. Patients with relapse or retreatment tend to show the greatest
More recently, the generic module of the Chinese Quality of Life In- impairment in QOL [36].
struments for Chronic Diseases (QLICD) has been modified by addition

2
 A.N. Aggarwal

Table 1
Characteristics of selected recent studies in tuberculosis patients reporting cross-sectional data from multi-dimensional quality of life scales.
Investigator Study setting Study subjects HIV+ Comorbid Non-TB comparator groups QOL measures Timing of QOL assessment
disorders

Dion et al. [30] Public hospital in 17 culture confirmed pulmonary TB patients None Excluded 25 latent TB, 8 previously SF-36, EQ-5D, VAS, Before or during treatment
Canada treated TB Standard gamble
Duyan et al. [48] Hospital in Turkey 120 inpatients with pulmonary TB None Excluded None In-house instrument At least one month after
hospitalization
Dhuria et al. [35] DOT centres in India 90 patients with pulmonary TB (20% retreatment cases) NR Excluded 90 age and gender matched WHOQOL-Bref Within 3 days of initiating TB
healthy persons treatment
Guo et al. [13] TB clinic in Canada 84 patients on TB treatment NR 45% 78 persons on treatment for SF-36, VAS, Health Within 2 months of diagnosis of
latent TB Utilities Index active/latent TB
Unalan et al. [17] TB dispensary in Turkey 196 patients with TB NR 26.5% 196 healthy persons, and 108 SF-36 During treatment
with latent/healed TB
Deribew et al. [44] Hospitals in Ethiopia 124TB/HIV co-infected patients 100% Excluded 467 HIV+ patients WHOQOL-HIV During intensive phase of TB
treatment
Babikako et al. [9] TB clinics in Uganda 133TB patients 50% NR None Medical Outcome Survey, Variable – before, during, or end
VAS of treatment
Chung et al. [37] Hospitals in Taiwan 140 patients with pulmonary TB NR NR 130 age and gender matched WHOQOL-Bref Within 2 weeks of initiating

3
healthy persons treatment
Kittikraisak et al. [10] Hospitals in Thailand 92TB patients 53.3% NR 49 HIV+ patients, 81 patients EQ-5D Variable
with treated TB
Louw et al. [46] Primary care clinics in 4900TB patients 59.9% NR None Social functioning 12 Within one month of treatment
South Africa initiation
Unalan et al. [19] TB sanitorium in Turkey 92TB patients NR NR None SF-36, WHOQOL-100 Early during treatment
Sharma et al. [39] TB clinic in India 60 MDR TB and 60 retreatment TB patients None Excluded 60 persons (details NR) WHOQOL-Bref Variable during treatment
Kisaka et al. [24] Hospital in Uganda 210 smear positive pulmonary TB patients (one third each 59% NR None SF-36 Variable during treatment
at diagnosis, end of intensive phase, and treatment
completion)
Dos Santos et al. [25] Hospital in Brazil 86 inpatients with pulmonary TB 37.2% 3.5% None SF-36 NR
Roba et al. [27] Hospitals, health centres 300TB, and 100 MDR TB, patients 13.8% NR None SF-36 At least one month after
in Ethiopia treatment initiation
Shahdadi et al. [28] Diabetes clinic in Iran 62 diabetic patients with pulmonary TB NR 100% None SF-36 NR
Laxmeshwar et al. TB clinics in India 95 MDR TB patients 4.2% NR None WHOQOL-Bref Variable during treatment
[42]
Sineke et al. [29] TB treatment site in 149 patients with drug-resistant TB 77.9% 4.4% None SF-36 NR
South Africa

DOT Directly observed treatment, EQ European Quality of Life, HIV Human immunodeficiency virus, MDR Multi-drug resistant, NR Not reported, QOL Quality of life, SF-36 Short Form 36, TB Tuberculosis, VAS Visual
analogue scale, WHOQOL World Health Organization Quality of Life.
J Clin Tuberc Other Mycobact Dis 17 (2019) 100121
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

4. Physical functioning and role limitation anxiety, and 23.3% suffered from low self-esteem [25]. Patients with
depression or anxiety also had lower overall QOL scores as compared to
Physical functioning is a reflection of an individual patient's capa- patients without. In a study from Ethiopia, 53.9% patients were cate-
city to carry out basic day-to-day activities, and role functioning en- gorized as having probable depression at start of treatment, and QOL
compasses a person's ability to function in designated roles at work, impairment, loss to follow-up, and mortality were significantly higher
society, and home. The physical effects of TB are highly variable, and among this subset [12]. A study from southern India reported depres-
depend on patient's premorbid health status, severity of symptoms, and sion in 40.8% TB patients receiving anti-tubercular therapy (ATT) [60].
duration of illness. Debilitating somatic symptoms are often the hall- Most patients had mild or moderate depression, with a higher pre-
mark of active TB, and patients are often specially concerned about valence in pulmonary as compared to extrapulmonary disease (80.4%
generalized weakness and weight loss [63]. Poor performance status vs. 19.6%).
has been shown to be a strong predictor of mortality in Japanese pa- Adequate treatment can ameliorate some of these psychological is-
tients with active pulmonary TB [65]. The diagnosis of tuberculosis in sues. A South African study using HADS showed that both anxiety and
the family increases the workload on the family primary caregivers depression domains changed by +95% from a state of ‘moderate pro-
(wives and mothers), and diminishes the caregiver's ability to generate blems’ to a state of reporting ‘no problems’ [32].
income and care for the remainder of the family [66].
7. Economic well-being
5. Social functioning
Patients of TB are most commonly in the economically productive
One of the most important facets affecting QOL is the stigma asso- age group, and hence the resultant economic cost is rather substantial.
ciated with TB, both at the family and the community level [63,67]. In a Several patients and families feel the financial burden of disease, re-
study from urban Zambia, 82% TB patients reported stigma [68]. In sulting both from cost of treatment as well as indirectly from loss of
another study from southern India, 51.2% TB patients felt stigmatized, wages [79,82]. A study in Thailand noted that adult TB patients spent
and stigma was greater among sputum smear positive patients [69]. In more than 15% of their income on out-of-pocket expenses for diagnosis
a study using an improvised scale to quantify stigma, mean TB-related and therapy of TB, and often needed to take loans or sell property [66].
stigma score in Chinese patients was 9.33 (maximum scale score of 27) Another study on southern India reported expenditure up to 40% of
[70]. patients’ income, with non-medical expenses (such as travel costs), and
TB is most commonly stigmatized due to the perceived risk of diagnosis/treatment in the private sector, also imposing a dispropor-
transmission from patients to other susceptible community members tionate burden on poor households [82].
[71]. In other instances, the reasons could relate to the association of
TB with HIV infection or low socio-economic status, and traditional 8. Effect of treatment
myths about TB [68]. Patients often report issues such as loss of friends,
lack of respect among colleagues, and social isolation at workplace Few investigators have longitudinally evaluated QOL in cohorts of
[72,73]. The stigma associated with disease may be greater among adult patients on ATT, mostly from endemic or high-burden countries
women and inability to get married, and divorce, have both been (Table 2). The greatest improvement in QOL seems to occur within the
commonly reported in developing countries [74–76]. Contrary to initial 2–3 months of therapy [5]. A study from South India reported
popular belief, stigmatization of TB patients is not just confined to improvement in patient perceptions about physical and mental well-
developing countries, but may be also be widely prevalent in low-TB being after treatment [15]. In a study from northern India, QOL im-
burden countries as well [77]. proved significantly at end of intensive phase, and further at end of
treatment [41]. Similar results were reported from another north Indian
6. Emotional and psychological health study, where overall QOL, and all domains except social, improved after
treatment for three months, and all domains improved further at
A wide range of psychological reactions are observed once TB is treatment completion at six months [36]. Another study from north
diagnosed. Worry is a common feeling after disclosure of diagnosis India showed that QOL improved across all domains among patients
[15,78]. The diagnosis may come as a shock to the patient, and there showing microbiological conversion on sputum examination, but not
are instances of denial of diagnosis [63,78,79]. Another common among those with persistent sputum positivity at end of intensive phase
feeling at diagnosis is fear of seclusion and social boycott, and some- of treatment [38]. In a study from Pakistan, mean QOL scores more
times even death [63,75]. In particular, hospitalization and isolation of than doubled in TB patients after completing ATT [34]. A study from
patients (a common practice in several low-burden countries) can have China reported gradual improvement in QOL with TB treatment, with
important emotional and psychological ramifications [63,80]. physical function, role-motional, bodily pain, and general health do-
Depressive symptoms such as low mood, tiredness, reduced sexual main scores comparable to healthy individuals after treatment [14]. In
desire, sleep disturbances, anorexia, loss of weight, etc. are commonly one study from Iraq that longitudinally used a TB-specific QOL ques-
seen [57]. Cross-sectional, community-based data from the World tionnaire, physical well-being, functional well-being, and the total QOL
Health Survey on nearly 250,000 adults from low- and middle-income scores were significantly increased after two months of ATT [55]. All
countries has shown a much higher prevalence of depressive episodes in QOL subscales, except social and economic well-being and spiritual
patients with TB (23.7% vs. 6.8% among those without TB) [81]. The well-being, improved at end of treatment, and the total QOL score had a
odds for subsyndromal depression and brief depressive episodes were statistically significant contribution towards predicting likelihood of
also higher among TB patients. Interaction analysis showed that de- favourable response to ATT. In a study from Yemen, both physical and
pression amplified difficulties in self-care in TB patients but did not mental summary scores improved at end of intensive phase of treatment
affect other health status domains. Using PHQ as a screening tool, a [23]. While the former improved further at treatment completion, the
Nigerian study identified 27.7% patients with depression [58]. In an- latter remained largely static, with mean scores still below population
other study on patients attending public primary care clinics in South norms. In a study from Indonesia, 94% patients showed a clinically
Africa, 32.9% showed psychological distress and 8.3% were receiving significant improvement in SGRQ scores after two months of treatment,
anti-depressant therapy [61]. On multivariable analysis older age, and 80% achieved additional significant improvement by end of
lower formal education, and poverty were independently associated treatment at six months [50]. Progressive improvement across all QOL
with psychological distress. A cross-sectional study in Brazil on hospi- domains was also reported among Malaysian patients receiving ATT
talized TB patients found that 31.4% had depression, 38.4% had [20]. This suggests that QOL correlates with other objectives measures

4
 A.N. Aggarwal

Table 2
Characteristics of selected recent longitudinal studies reporting data from multi-dimensional quality of life scales among patients receiving treatment for tuberculosis.
Investigator Study setting Study subjects HIV+ Comorbid disorders Non-TB comparator groups QOL measures Timing of serial QOL assessment

Chamla, 2004 [14] TB center in China 102 patients with pulmonary TB NR NR 103 age and gender matched healthy SF-36 ST, EIP, ET
persons
Rajeswari et al. [15] TB units in India 610 patients with TB NR NR None SF-36 ST, EIP, ET
Marra et al. [16] TB clinic in Canada 7.7% 10.6% 102 persons with latent TB SF-36 Baseline, 3 months, 6 months
Dhuria et al. [36] DOT centres in India 90 patients with pulmonary TB NR Excluded 90 persons (details NR) WHOQOL-Bref Baseline, 3 months, 6 months
Maguire et al. [50] TB clinic in Indonesia 115 patients with pulmonary TB 4.5% NR None SGRQ Baseline, 2 months, 6 months
Guo et al. [18] TB control clinics in Canada 89 patients with TB NR 46% None SF-36 Baseline, 3 months, 6 months
Kruijshaar et al. [31] Clinics in UK 61 patients with TB (20 had extrapulmonary NR NR None SF-36, EQ-5D Baseline, 2 months
disease)
Aggarwal et al. [38] DOT centres in India 1034 patients with pulmonary TB NR NR None WHOQOL-Bref ST, EIP, ET
Deribew et al. [45] Hospitals in Ethiopia 124TB/HIV coinfected patients 100% Excluded 465 HIV+ patients WHOQOL HIV-Bref During intensive phase, 6 months
later
Atif et al. [20] Chest clinic in Malaysia 216 patients with pulmonary TB None Excluded None SF-36 ST, EIP, ET
Bauer et al. [21] Hospitals in Canada 48 patients with pulmonary TB (8 had NR Excluded 105 persons with latent TB, 110 SF-36 1, 2, 4, 6, 9 and 12 months
extrapulmonary disease) healthy persons
Dujaili et al. [55] Specialist Respiratory Centre 305 patients with pulmonary TB None Excluded None FACIT-TB ST, EIP, ET
in Iraq

5
Ahmad et al. [22] Hospital in Pakistan 81 patients with MDR TB NR 12.3% None SF-36 Baseline, 12 months, ET (>20
months)
Jaber et al. [23] TB centres in Yemen 243 patients with TB NR 16.5% None SF-36 ST, EIP, ET
Louw et al. [43] Primary care clinics in South 1196 patients with TB NR 36.8% None SF-12 Baseline, 6 months
Africa
Mthiyane et al. [47] Hospitals in South Africa 62TB/HIV coinfected patients 100% Excluded 20 HIV+ patients FAHI Baseline, 3 months, 6 months, 12
months
Kastien-Hilka et al. [32] Primary care clinics in South 131 patients with pulmonary TB None 20.6% None SF-12, EQ-5D, SGRQ ST, 4, 8, 16 weeks, ET
Africa
Ramkumar et al. [26] DOT centres in India 92 patients with TB NR NR 83 age and gender matched healthy SF-36 ST, 3 months, ET
persons
Siddiqui et al. [53] DOT centres in India 316 patients with TB (50 had diabetes) NR 15.8% None DR..−12 ST, EIP, ET
Singh et al. [40] Hospital in India 50 patients with pulmonary TB NR NR 50 age and gender matched healthy WHOQOL-Bref Baseline, 2 months, 6 months
persons
Jorstad et al. [33] Hospital in Tanzania 69 patients with extrapulmonary TB 23.2% NR 63 patients without TB EQ-5D ST, 2–3 months, ET
Saleem et al. [34] TB clinic in Pakistan 226 patients with pulmonary TB NR Excluded None EQ-5D ST, EIP, ET
Dar et al. [41] Hospital in India 198 patients with pulmonary TB NR NR None WHOQOL-Bref ST, EIP
Jaber and Ibrahim [89] TB centres in Yemen 80 patients with MDR TB NR 28.8% None SF-36 Baseline, ET, 12 months after ET

DOT Directly observed treatment, DR−12 Dhingra and Rajpal scale, EIP End of intensive phase, EQ European Quality of Life, ET End of treatment, FACIT Functional Assessment of Chronic Illness Therapy, FAHI
Functional Assessment of HIV Infection, HIV Human immunodeficiency virus, MDR Multi-drug resistant, NR Not reported, QOL Quality of life, SF-12 Social Functioning 12, SF-36 Short Form 36, SGRQ St George's
Respiratory Questionnaire, St Start of treatment, TB Tuberculosis, WHOQOL World Health Organization Quality of Life.
J Clin Tuberc Other Mycobact Dis 17 (2019) 100121
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

of response to therapy. In a study from Uganda, QOL progressively patients with pulmonary TB at time of diagnosis [31]. Another pro-
improved as the patients’ duration of TB treatment increased [9]. In a spective study in Zanzibar followed up patients with presumptive EPTB,
study from Uganda, both physical and mental component summary and reduction in working capacity was reported in a lower proportion
scores significantly improved at end of intensive phase, and further by of patients with lymphadenitis as compared to other patients [33].
end of treatment completion [24]. In two studies from South Africa, These patients had better self-rated QOL at baseline as compared to
QOL improved significantly during treatment and at treatment com- EPTB at other sites. Overall, QOL improved in all patients with ade-
pletion, with biggest gains in the physical health scores [32,43]. No quate treatment, but residual impairment was not reported for any site.
socio-demographic traits were significantly associated with this im-
provement, suggesting that TB treatment was the principal determinant 10. Drug resistance
of change in QOL. Maximum improvements were seen in physical,
followed by psychological domain. In general, patients with multi-drug resistant (MDR) TB have en-
Relatively little information is available from low TB burden dured disease and treatment in the past as well, and hence face addi-
countries. In a study from Canada, QOL was better in most domains tional difficulties related to family life, social stigmatization, and fi-
after TB treatment, with most significant improvements observed in nancial hardships. Treatment for MDR TB is also longer, more complex,
vitality, physical functioning, role physical, social functioning, and role associated with frequent adverse effects, and associated with sub-
emotional domains [16]. In contrast, another study on Canadian pa- optimal outcomes. It is therefore not hard to imagine that QOL among
tients showed that while mental component summary scores improved patients with MDR TB is likely to be much more impaired [87,88]. A
throughout treatment, the physical component summary score im- study from north India showed that patients with MDR TB had worse
proved only slightly during the 2–4 month period and then slightly QOL as compared to drug-susceptible patients receiving retreatment
declined again [21]. with ATT [39]. In contrast, an Ethiopian study found that QOL was
On the other hand, adverse effects from ATT may sometimes para- similarly reduced among MDR and gender-matched drug-susceptible
doxically worsen QOL. For instance, gastrointestinal disturbances, vi- patients with TB [27]. However, MDR patients reported worse general
sual impairment or peripheral neuropathy may hamper physical func- health scores and extensive stigmatization. In a retrospective study on
tioning [63]. A Canadian study reported that major, but not minor, 61 HIV/MDR-TB patients in India, 16% had depression at baseline, and
adverse drug reactions were associated with significant reductions in a all except one improved with ATT and psychological support [59]. In a
few mental and physical subscales of SF-36 [18]. This study also follow-up study of MDR TB patients programmatically managed in
showed that patients with low pre-treatment QOL scores were more Pakistan, QOL was severely impaired across all domains before starting
likely to experience adverse drug reactions. A study from UK suggested treatment [22]. At one year of treatment, there was minimal and
that while the psychological burden from depression improved with clinically insignificant improvement in QOL scores. At completion of
treatment, that with anxiety did not [31]. treatment, there was significant improvement in QOL domain scores
Although most patients report normal or near-normal QOL after and summary component measures, but the scores still remained below
successful TB treatment, a small proportion can still show residual standard population norms, suggesting significant residual impairment
impairment of QOL [15,16,20,23,31,38,49,83]. In particular, a recent of QOL. A study from western India found that psychological and
systematic review suggests that psychological well-being and social physical health domains were the most affected among patients re-
functioning continue to remained impaired even after successful mi- ceiving treatment for MDR TB, and that loss of work adversely affected
crobiological cure with treatment [62]. In addition to persistent phy- the social relationships and environmental domains [42]. However,
sical changes, patients also report continued emotional distress or im- QOL in this study was not as low as reported in some other studies, and
paired mental health even after completion of ATT [20,84]. was not influenced by drug-resistance pattern. Qualitatively, pill
The long term impact of successful TB treatment on QOL is not burden significantly affected QOL. A study from Yemen showed clini-
clear. Few studies show that the overall QOL in patients previously cally important improvement in QOL scores at end of treatment for
treated 1–2 years back was largely similar to that in the general po- MDR TB, but there was no further improvement over next one year.
pulation [21,30,83,85]. Other investigators report substantial impair- Duration of illness before diagnosis of MDR TB was an important pre-
ment in QOL, even several years after completing treatment, although it dictor of improvement in both physical and mental domain scores [89].
was still better when compared to other chronic respiratory disorders A cross-sectional study in Namibia attempted to correlate adverse
[86]. Apart from the global assessment, individual QOL facets may be drug events with QOL around the time of completion of MDR TB
important for patients. For instance, overcoming stigma and resuming treatment [90]. QOL ratings were moderately low in these patients and
normal social life (including joining work, resuming interactions with were not correlated with adverse reactions (which were most com-
friends and colleagues, etc.) may be difficult for some patients. Others monly mild). In another study from South Africa, patients on drug-re-
may have significant organ damage (such as extensive lung fibrosis or sistant TB treatment who reported an adverse event had poorer QOL
destruction) that can result in persistent symptoms and inability to (principally mental health and well-being) as compared to patients who
resume normal daily activities. Other events (such as loss of job or di- did not, especially those on intensive phase treatment for six months or
vorce) due to TB diagnosis may also have long-lasting social, psycho- less [29]. However, in both studies, most adverse events had already
logical and financial implications. occurred much before quantification of QOL, while some were persis-
tent for variable length of time.
9. Extrapulmonary disease A recent systematic review and meta-analysis obtained a summary
prevalence of 25% for depression across 15 studies, and 24% for anxiety
There is only sparse data on how extrapulmonary TB (EPTB) in- across three studies [87].
fluences QOL. A study from China reported similar QOL scores between
pulmonary and extrapulmonary TB, though site distribution or numbers 11. TB and human immunodeficiency virus (HIV) co-infection
for the latter were not provided [14]. In general, QOL is likely to be
related to the anatomic location of disease, and some forms are more Nearly 9% of TB patients are co-infected with HIV, and TB/HIV co-
likely to be associated with substantial morbidity and long-term dis- infection seems to be driving the resurgence of TB in the developed
ability. Therefore, the impact of skeletal tuberculosis or tuberculous world [1]. In a study from Ethiopia, TB/HIV co-infected patients were
meningitis is likely to be much different in comparison to tuberculous documented to have poorer QOL across all domains when compared to
lymphadenitis or pleural tuberculosis. A study from UK found that HIV seronegative TB patients, even after adjusting for potential con-
patients with lymph node disease appeared to report better QOL than founders like age, gender, occupation, social support, WHO staging, and

6
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

CD4 lymphocyte count [44]. Similarly, another study from Ethiopia related measures can therefore be used more frequently as an adjunct to
showed that QOL in TB/HIV co-infected patients was more impaired as routine disease outcome indices, and perhaps included into forth-
compared to that in HIV seropositive patients without TB, and treat- coming guidelines. This can assist health care providers to target spe-
ment led to greater improvement in QOL in the former group [45]. cific mental and physical health components that are adversely affected
Similar observations were also reported from a cross-sectional study by the disease or treatment [98]. For this, there is also a need for de-
from India [91]. In contrast, a study from Brazil found that QOL was veloping psychometrically robust and ethnically appropriate TB-spe-
similarly impaired among patients receiving treatment for HIV infec- cific QOL measures in different countries. We were unable to locate any
tion, active TB, and TB/HIV con-infection, with the maximal decrease quality data that described QOL in children with TB, and this is one area
being observed in the physical domain in the last group [11]. Sub- where information needs to be generated. Given that the interaction
stantial impairment of physical and mental health was documented in a between healthcare providers and patients, as well as the services
study on HIV-infected TB patients treated in Thailand [92]. Physical rendered by the clinical team, can heavily impact a patient's QOL, there
symptoms were largely relieved with treatment, but mental health re- is urgent need improve the overall quality of TB care [99]. TB control
mained unchanged or worsened in nearly two-third patients. In con- programs should also try and implement patient friendly regimens that
trast, a study from South Africa reported greater impairment in physical reduce pill burden, and keep hospitalization and isolation at a
functioning, but better mental health, among TB/HIV co-infected pa- minimum. Metrics such as quality-adjusted life years (QALYs) can be
tients [46]. Another study from South Africa showed overall improve- used for economic assessment of interventions, and choosing those that
ment in QOL with therapy in TB/HIV coinfected patients [47]. This provide the greatest health effects [100].
improvement appeared similar among those receiving, and not re- The other major target should be to promote awareness and try and
ceiving concomitant anti-retroviral therapy. However, patients with bring about relevant social reforms. There is a need to understand the
CD4 counts below 200/µL had a poorer QOL, both pre-treatment and roots of misconceptions about TB and to address the lack of knowledge
during and after completion of treatment. about disease. Good communication, especially at time of diagnosis and
initiating treatment, is necessary, and psychological counseling should
12. Impact of other comorbidities be an integral part of TB management [101]. TB patients receiving
adequate social support from family, friends and community are likely
Several TB patients have other concurrent comorbid illnesses that to have better QOL [102]. Hence, there may be a case of implementing
can themselves influence QOL. In particular, diabetes is a common wellness interventions at family and/or community level to improve
association [1]. It is possible that QOL in such patients may be worse. QOL. There is also a potential role for targeted, culturally relevant
However, most QOL studies conducted in specific disease states tend to psychosocial support interventions for persons treated for TB disease,
either exclude patients with comorbid illnesses that can confound especially during the early months of treatment that integrate patients
quantification of QOL, or ignore the associated clinical conditions while back into their communities as quickly as possible. At a higher level,
describing QOL (Tables 1 and 2). Hence data in this area is rather policymakers should promote social protection and livelihood-
sparse. In one study from northern India, TB patients having diabetes strengthening interventions, such as poverty alleviation, food security,
shower poorer QOL at start of treatment, as compared to patients cash transfers, etc. [103]. Another major set of interventions are re-
without diabetes [53]. In another study on diabetic patients in Iran, a quired to reduce TB stigma. Education and support programs aimed at
significant inverse association was noted between QOL and hemoglobin healthcare providers, TB patients, and at-risk community members may
A1c levels, suggesting that poor glycemic control may worsen QOL in prove useful [71]. Other important measures to combat stigmatization
TB patients [28]. include advocacy, communication, social mobilization, and personal
empowerment of marginalized groups and women who dis-
13. Quality of TB care proportionally bear the burden of TB stigma. TB clubs or social net-
works could be created for patients to improve patient interaction with
As per the International Standards of Tuberculosis Care, a patient- other stakeholders [104].
centered approach to therapy needs to be developed for all patients in
order to promote adherence, improve QOL, and relieve suffering [93]. Funding
Unfortunately, quality of TB care is still far from optimal, especially in
high burden countries [94]. There are still considerable delays in TB None.
diagnosis and, and several patients are lost even before treatment can
be initiated; this contributes to prolonged patient suffering [95,96]. Declaration of Competing Interest
Several patients find the current mechanisms of directly observed ATT
to be inflexible and intrusive, and prefer the less effective unsupervised None.
treatment [97]. The quality of drugs supplied through TB programs,
and their guaranteed availability, are also important issues. Most TB References
programs still do not address the non-medical aspects of tuberculosis
with enough seriousness. All these factors directly influence QOL in TB [1] World Health Organization. Global tuberculosis report 2018. Geneva: World
patients. These issues may adversely affect speed of recovery as well as Health Organization; 2018.
[2] Aggarwal AN. Health-related quality of life: a neglected aspect of pulmonary tu-
treatment outcomes, and thereby indirectly contribute to impairment of berculosis. Lung India 2010;27(1):1–3. https://doi.org/10.4103/0970-2113.
QOL. 59259.
[3] The world health organization quality of life assessment (WHOQOL): position
paper from the World Health Organization. Soc Sci Med 1995;41(10):1403–9.
14. What can be done to improve QOL in TB patients [4] Guo N, Marra F, Marra CA. Measuring health-related quality of life in tuberculosis:
a systematic review. Health Qual Life Outcomes 2009;7:14. https://doi.org/10.
From a programmatic perspective, one must deviate from the tra- 1186/1477-7525-7-14.
[5] Bauer M, Leavens A, Schwartzman K. A systematic review and meta-analysis of the
ditional indicators of disease severity and treatment response to capture impact of tuberculosis on health-related quality of life. Qual Life Res
the overall health status, with a greater emphasis on patient's, rather 2013;22(8):2213–35. https://doi.org/10.1007/s11136-012-0329-x.
than clinician's, perspective of disease [2]. TB control programs need to [6] Brown J, Capocci S, Smith C, Morris S, Abubakar I, Lipman M. Health status and
quality of life in tuberculosis. Int J Infect Dis 2015;32:68–75. https://doi.org/10.
look beyond clinical and microbiological aspects, and try and include
1016/j.ijid.2014.12.045.
socio-cultural and psychological dimensions that impact the disease and [7] Khan S, Tangiisuran B, Imtiaz A, Zainal H. Health status and quality of life in
its treatment as part of evaluation and monitoring tools. QOL and tuberculosis: systematic review of study design, instruments, measuring properties

7
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

and outcomes. Health Sci J 2017;11(1):1–10. https://doi.org/10.21767/1791- [32] Kastien-Hilka T, Rosenkranz B, Sinanovic E, Bennett B, Schwenkglenks M. Health-
809X.1000484. related quality of life in South African patients with pulmonary tuberculosis. PLoS
[8] Dion MJ, Tousignant P, Bourbeau J, Menzies D, Schwartzman K. Measurement of One 2017;12(4):e0174605https://doi.org/10.1371/journal.pone.0174605.
health preferences among patients with tuberculous infection and disease. Med [33] Jorstad MD, Amus J, Marijani M, Sviland L, Mustafa T. Diagnostic delay in ex-
Decis Making 2002;22(5 Suppl):S102–14. trapulmonary tuberculosis and impact on patient morbidity: a study from
[9] Babikako HM, Neuhauser D, Katamba A, Mupere E. Feasibility, reliability and Zanzibar. PLoS One 2018;13(9):e0203593https://doi.org/10.1371/journal.pone.
validity of health-related quality of life questionnaire among adult pulmonary 0203593.
tuberculosis patients in urban Uganda: cross-sectional study. Health Qual Life [34] Saleem S, Malik A, Ghulam A, Ahmed J, Hussain H. Health-related quality of life
Outcomes 2010;8:93. https://doi.org/10.1186/1477-7525-8-93. among pulmonary tuberculosis patients in Pakistan. Qual Life Res
[10] Kittikraisak W, Kingkaew P, Teerawattananon Y, Yothasamut J, Natesuwan S, 2018;27(12):3137–43. https://doi.org/10.1007/s11136-018-1954-9.
Manosuthi W, et al. Health related quality of life among patients with tuberculosis [35] Dhuria M, Sharma N, Ingle G. Impact of tuberculosis on the quality of life. Indian J
and HIV in Thailand. PLoS One 2012;7(1):e29775. https://doi.org/10.1371/ Community Med 2008;33(1):58–9. https://doi.org/10.4103/0970-0218.39249.
journal.pone.0029775. [36] Dhuria M, Sharma N, Narender Pal S, Ram Chander J, Saha R, Gopal Krishan I. A
[11] Dowdy DW, Israel G, Vellozo V, Saraceni V, Cohn S, Cavalcante S, et al. Quality of study of the impact of tuberculosis on the quality of life and the effect after
life among people treated for tuberculosis and human immunodeficiency virus in treatment with dots. Asia Pac J Public Health 2009;21(3):312–20. https://doi.org/
Rio de Janeiro, Brazil. Int J Tuberc Lung Dis 2013;17(3):345–7. https://doi.org/ 10.1177/1010539509336242.
10.5588/ijtld.12.0123. [37] Chung WS, Lan YL, Yang MC. Psychometric testing of the short version of the
[12] Ambaw F, Mayston R, Hanlon C, Medhin G, Alem A. Untreated depression and world health organization quality of life (WHOQOL-BREF) questionnaire among
tuberculosis treatment outcomes, quality of life and disability, Ethiopia. Bull pulmonary tuberculosis patients in Taiwan. BMC Public Health 2012;12:630.
World Health Organ 2018;96(4):243–55. https://doi.org/10.2471/blt.17.192658. https://doi.org/10.1186/1471-2458-12-630.
[13] Guo N, Marra CA, Marra F, Moadebi S, Elwood RK, Fitzgerald JM. Health state [38] Aggarwal AN, Gupta D, Janmeja AK, Jindal SK. Assessment of health-related
utilities in latent and active tuberculosis. Value Health 2008;11(7):1154–61. quality of life in patients with pulmonary tuberculosis under programme condi-
https://doi.org/10.1111/j.1524-4733.2008.00355.x. tions. Int J Tuberc Lung Dis 2013;17(7):947–53. https://doi.org/10.5588/ijtld.12.
[14] Chamla D. The assessment of patients' health-related quality of life during tu- 0299.
berculosis treatment in Wuhan, China. Int J Tuberc Lung Dis 2004;8(9):1100–6. [39] Sharma R, Yadav R, Sharma M, Saini V, Koushal V. Quality of life of multi drug
[15] Rajeswari R, Muniyandi M, Balasubramanian R, Narayanan PR. Perceptions of resistant tuberculosis patients: a study of north India. Acta Med Iran
tuberculosis patients about their physical, mental and social well-being: a field 2014;52(6):448–53.
report from south India. Soc Sci Med 2005;60(8):1845–53. https://doi.org/10. [40] Singh SK, Agrawal A, Tiwari KK. Improvement in quality of life in pulmonary
1016/j.socscimed.2004.08.024. tuberculosis patients: a prospective study. Trop Doct 2017;47(2):97–100. https://
[16] Marra CA, Marra F, Colley L, Moadebi S, Elwood RK, Fitzgerald JM. Health-related doi.org/10.1177/0049475516643256.
quality of life trajectories among adults with tuberculosis: differences between [41] Dar SA, Shah NN, Wani ZA, Nazir D. A prospective study on quality of life in
latent and active infection. Chest 2008;133(2):396–403. https://doi.org/10.1378/ patients with pulmonary tuberculosis at a tertiary care hospital in Kashmir,
chest.07-1494. Northern India. Indian J Tuberc 2019;66(1):118–22. https://doi.org/10.1016/j.
[17] Unalan D, Soyuer F, Ceyhan O, Basturk M, Ozturk A. Is the quality of life different ijtb.2018.07.002.
in patients with active and inactive tuberculosis? Indian J Tuberc [42] Laxmeshwar C, Stewart AG, Dalal A, Kumar AMV, Kalaiselvi S, Das M, et al.
2008;55(3):127–37. Beyond 'cure' and 'treatment success': quality of life of patients with multidrug-
[18] Guo N, Marra F, Fitzgerald JM, Elwood RK, Marra CA. Impact of adverse drug resistant tuberculosis. Int J Tuberc Lung Dis 2019;23(1):73–81. https://doi.org/
reaction and predictivity of quality of life status in tuberculosis. Eur Respir J 10.5588/ijtld.18.0149.
2010;36(1):206–8. https://doi.org/10.1183/09031936.00159409. [43] Louw JS, Mabaso M, Peltzer K. Change in health-related quality of life among
[19] Unalan D, Soyuer F, Ozturk A. Comparison of SF-36 and WHOQOL-100 life quality pulmonary tuberculosis patients at primary health care settings in south africa: a
scales in early period tuberculosis subjects. J Pak Med Assoc 2012;62(11):1161–7. prospective cohort study. PLoS One 2016;11(5):e0151892https://doi.org/10.
[20] Atif M, Sulaiman SA, Shafie AA, Asif M, Sarfraz MK, Low HC, et al. Impact of 1371/journal.pone.0151892.
tuberculosis treatment on health-related quality of life of pulmonary tuberculosis [44] Deribew A, Tesfaye M, Hailmichael Y, Negussu N, Daba S, Wogi A, et al.
patients: a follow-up study. Health Qual Life Outcomes 2014;12:19. https://doi. Tuberculosis and HIV co-infection: its impact on quality of life. Health Qual Life
org/10.1186/1477-7525-12-19. Outcomes 2009;7:105. https://doi.org/10.1186/1477-7525-7-105.
[21] Bauer M, Ahmed S, Benedetti A, Greenaway C, Lalli M, Leavens A, et al. Health- [45] Deribew A, Deribe K, Reda AA, Tesfaye M, Hailmichael Y, Maja T, et al. Change in
related quality of life and tuberculosis: a longitudinal cohort study. Health Qual quality of life: a follow up study among patients with HIV infection with and
Life Outcomes 2015;13:65. https://doi.org/10.1186/s12955-015-0250-4. without TB in Ethiopia. BMC Public Health 2013;13:408. https://doi.org/10.
[22] Ahmad N, Javaid A, Syed Sulaiman SA, Basit A, Afridi AK, Jaber AA, et al. Effects 1186/1471-2458-13-408.
of multidrug resistant tuberculosis treatment on patients' health related quality of [46] Louw J, Peltzer K, Naidoo P, Matseke G, McHunu G, Tutshana B. Quality of life
life: results from a follow up study. PLoS One 2016;11(7):e0159560https://doi. among tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary
org/10.1371/journal.pone.0159560. public health care patients in three districts in South Africa. Health Qual Life
[23] Jaber AA, Khan AH, Syed Sulaiman SA, Ahmad N, Anaam MS. Evaluation of Outcomes 2012;10:77. https://doi.org/10.1186/1477-7525-10-77.
health-related quality of life among tuberculosis patients in two cities in yemen. [47] Mthiyane T, Pym A, Dheda K, Rustomjee R, Reddy T, Manie S. Longitudinal as-
PLoS One 2016;11(6):e0156258https://doi.org/10.1371/journal.pone.0156258. sessment of health related quality of life of HIV infected patients treated for tu-
[24] Kisaka SM, Rutebemberwa E, Kasasa S, Ocen F, Nankya-Mutyoba J. Does health- berculosis and HIV in a high burden setting. Qual Life Res 2016;25(12):3067–76.
related quality of life among adults with pulmonary tuberculosis improve across https://doi.org/10.1007/s11136-016-1332-4.
the treatment period? a hospital-based cross sectional study in Mbale Region, [48] Duyan V, Kurt B, Aktas Z, Duyan GC, Kulkul DO. Relationship between quality of
Eastern Uganda. BMC Res Notes 2016;9(1):467. https://doi.org/10.1186/s13104- life and characteristics of patients hospitalised with tuberculosis. Int J Tuberc Lung
016-2277-y. Dis 2005;9(12):1361–6.
[25] Dos Santos AP, Lazzari TK, Silva DR. Health-Related quality of life, depression and [49] Pasipanodya JG, Miller TL, Vecino M, Munguia G, Bae S, Drewyer G, et al. Using
anxiety in hospitalized patients with tuberculosis. Tuberc Respir Dis (Seoul) the St. George respiratory questionnaire to ascertain health quality in persons with
2017;80(1):69–76. https://doi.org/10.4046/trd.2017.80.1.69. treated pulmonary tuberculosis. Chest 2007;132(5):1591–8. https://doi.org/10.
[26] Ramkumar S, Vijayalakshmi S, Seetharaman N, Pajanivel R, Lokeshmaran A. 1378/chest.07-0755.
Health-related quality of life among tuberculosis patients under revised National [50] Maguire GP, Anstey NM, Ardian M, Waramori G, Tjitra E, Kenangalem E, et al.
Tuberculosis Control Programme in rural and urban Puducherry. Indian J Tuberc Pulmonary tuberculosis, impaired lung function, disability and quality of life in a
2017;64(1):14–9. https://doi.org/10.1016/j.ijtb.2016.11.004. high-burden setting. Int J Tuberc Lung Dis 2009;13(12):1500–6.
[27] Roba AA, Dasa TT, Weldegebreal F, Asfaw A, Mitiku H, Teklemariam Z, et al. [51] Dhingra VK, Rajpal S. Health related quality of life (HRQL) scoring in tuberculosis.
Tuberculosis patients are physically challenged and socially isolated: a mixed Indian J Tuberc 2003;50:99–104.
methods case-control study of health related quality of life in Eastern Ethiopia. [52] Dhingra VK, Rajpal S. Health related quality of life (HRQL) scoring (DR-12 score)
PLoS One 2018;13(10):e0204697https://doi.org/10.1371/journal.pone.0204697. in tuberculosis – additional evaluative tool under dots. J Commun Dis
[28] Shahdadi H, Salarzaee M, Balouchi A. Quality of life of diabetic patients with 2005;37(4):261–8.
smear positive PTB in southeastern Iran: a cross-sectional study in a poor region of [53] Siddiqui AN, Khayyam KU, Siddiqui N, Sarin R, Sharma M. Diabetes prevalence
Iran. Indian J Tuberc 2018;65(2):159–63. https://doi.org/10.1016/j.ijtb.2017.08. and its impact on health-related quality of life in tuberculosis patients. Trop Med
035. Int Health 2017;22(11):1394–404. https://doi.org/10.1111/tmi.12968.
[29] Sineke T, Evans D, Schnippel K, van Aswegen H, Berhanu R, Musakwa N, et al. The [54] Abdulelah J, Sulaiman SAS, Hassali MA, Blebil AQ, Awaisu A, Bredle JM.
impact of adverse events on health-related quality of life among patients receiving Development and psychometric properties of a tuberculosis-specific multi-
treatment for drug-resistant tuberculosis in Johannesburg, South Africa. Health dimensional health-related quality-of-life measure for patients with pulmonary
Qual Life Outcomes 2019;17(1):94. https://doi.org/10.1186/s12955-019-1155-4. tuberculosis. Value Health Reg Issues 2015;6:53–9. https://doi.org/10.1016/j.
[30] Dion MJ, Tousignant P, Bourbeau J, Menzies D, Schwartzman K. Feasibility and vhri.2015.03.006.
reliability of health-related quality of life measurements among tuberculosis pa- [55] Dujaili JA, Sulaiman SA, Hassali MA, Awaisu A, Blebil AQ, Bredle JM. Health-
tients. Qual Life Res 2004;13(3):653–65. https://doi.org/10.1023/b:Qure. related quality of life as a predictor of tuberculosis treatment outcomes in iraq. Int
0000021320.89524.64. J Infect Dis 2015;31:4–8. https://doi.org/10.1016/j.ijid.2014.12.004.
[31] Kruijshaar ME, Lipman M, Essink-Bot ML, Lozewicz S, Creer D, Dart S, et al. Health [56] Sun Y, Yang Z, Wan C, Xu C, Chen L, Xu L, et al. Development and validation of the
status of UK patients with active tuberculosis. Int J Tuberc Lung Dis pulmonary tuberculosis scale of the system of quality of life instruments for
2010;14(3):296–302. chronic diseases (QLICD-PT). Health Qual Life Outcomes 2018;16(1):137. https://

8
A.N. Aggarwal J Clin Tuberc Other Mycobact Dis 17 (2019) 100121

doi.org/10.1186/s12955-018-0960-5. countries. BMC Med 2017;15(1):209. https://doi.org/10.1186/s12916-017-

[57] Aydin IO, Ulusahin A. Depression, anxiety comorbidity, and disability in tu- 0975-5.
berculosis and chronic obstructive pulmonary disease patients: applicability of [82] Rajeswari R, Balasubramanian R, Muniyandi M, Geetharamani S, Thresa X,
GHQ-12. Gen Hosp Psychiatry 2001;23(2):77–83. Venkatesan P. Socio-economic impact of tuberculosis on patients and family in
[58] Issa BA, Yussuf AD, Kuranga SI. Depression comorbidity among patients with tu- India. Int J Tuberc Lung Dis 1999;3(10):869–77.
berculosis in a university teaching hospital outpatient clinic in Nigeria. Ment [83] Muniyandi M, Rajeswari R, Balasubramanian R, Nirupa C, Gopi PG, Jaggarajamma
Health Fam Med 2009;6(3):133–8. K, et al. Evaluation of post-treatment health-related quality of life (HRQoL) among
[59] Das M, Isaakidis P, Van den Bergh R, Kumar AM, Nagaraja SB, Valikayath A, et al. tuberculosis patients. Int J Tuberc Lung Dis 2007;11(8):887–92.
HIV, multidrug-resistant TB and depressive symptoms: when three conditions [84] Dias AA, de Oliveira DM, Turato ER, de Figueiredo RM. Life experiences of patients
collide. Glob Health Action 2014;7:24912. https://doi.org/10.3402/gha.v7. who have completed tuberculosis treatment: a qualitative investigation in south-
24912. east Brazil. BMC Public Health 2013;13:595. https://doi.org/10.1186/1471-2458-
[60] Shyamala KK, Naveen RS, Khatri B. Depression: a neglected comorbidity in pa- 13-595.
tients with tuberculosis. J Assoc Physicians India 2018;66(12):18–21. [85] Li CT, Chu KH, Reiher B, Kienene T, Chien LY. Evaluation of health-related quality
[61] Peltzer K, Naidoo P, Matseke G, Louw J, McHunu G, Tutshana B. Prevalence of of life in patients with tuberculosis who completed treatment in Kiribati. J Int Med
psychological distress and associated factors in tuberculosis patients in public Res 2017;45(2):610–20. https://doi.org/10.1177/0300060517694491.
primary care clinics in South Africa. BMC Psychiatry 2012;12:89. https://doi.org/ [86] Banu Rekha VV, Ramachandran R, Kuppu Rao KV, Rahman F, Adhilakshmi AR,
10.1186/1471-244x-12-89. Kalaiselvi D, et al. Assessment of long term status of sputum positive pulmonary TB
[62] Kastien-Hilka T, Abulfathi A, Rosenkranz B, Bennett B, Schwenkglenks M, patients successfully treated with short course chemotherapy. Indian J Tuberc
Sinanovic E. Health-related quality of life and its association with medication 2009;56(3):132–40.
adherence in active pulmonary tuberculosis- a systematic review of global litera- [87] Alene KA, Clements ACA, McBryde ES, Jaramillo E, Lonnroth K, Shaweno D, et al.
ture with focus on South Africa. Health Qual Life Outcomes 2016;14:42. https:// Mental health disorders, social stressors, and health-related quality of life in pa-
doi.org/10.1186/s12955-016-0442-6. tients with multidrug-resistant tuberculosis: a systematic review and meta-ana-
[63] Hansel NN, Wu AW, Chang B, Diette GB. Quality of life in tuberculosis: patient and lysis. J Infect 2018;77(5):357–67. https://doi.org/10.1016/j.jinf.2018.07.007.
provider perspectives. Qual Life Res 2004;13(3):639–52. https://doi.org/10.1023/ [88] Vo NX, Xuan Doan TB, Kha Vo DN, Tran TK, Vo TQ. Assessing quality of life for
B:QURE.0000021317.12945.f0. multidrug-resistant and extensively drug-resistant tuberculosis patients. J Pak Med
[64] Jankowska-Polanska BK, Kaminska M, Uchmanowicz I, Rycombel A. Quality of life Assoc 2019;69:S137–57. (Suppl 2)(6).
and health behaviours of patients with tuberculosis - sex differences. Pneumonol [89] Jaber AAS, Ibrahim B. Health-related quality of life of patients with multidrug-
Alergol Pol 2015;83(4):256–65. https://doi.org/10.5603/PiAP.2015.0046. resistant tuberculosis in Yemen: prospective study. Health Qual Life Outcomes
[65] Horita N, Miyazawa N, Yoshiyama T, Kojima R, Omori N, Kaneko T, et al. Poor 2019;17(1):142. https://doi.org/10.1186/s12955-019-1211-0.
performance status is a strong predictor for death in patients with smear-positive [90] Sagwa EL, Ruswa N, Mavhunga F, Rennie T, Leufkens HG, Mantel-Teeuwisse AK.
pulmonary TB admitted to two Japanese hospitals. Trans R Soc Trop Med Hyg Adverse events and patients' perceived health-related quality of life at the end of
2013;107(7):451–6. https://doi.org/10.1093/trstmh/trt037. multidrug-resistant tuberculosis treatment in Namibia. Patient Prefer Adherence
[66] Kamolratanakul P, Sawert H, Kongsin S, Lertmaharit S, Sriwongsa J, Na-Songkhla 2016;10:2369–77. https://doi.org/10.2147/ppa.S116860.
S, et al. Economic impact of tuberculosis at the household level. Int J Tuberc Lung [91] Jha DK, Jha J, Jha AK, Achappa B, Holla R. Quality of life among HIV-tuberculosis
Dis 1999;3(7):596–602. co-infected patients. Perspect Clin Res 2019;10(3):125–9. https://doi.org/10.
[67] Kelly P. Isolation and stigma: the experience of patients with active tuberculosis. J 4103/picr.PICR_99_18.
Community Health Nurs 1999;16(4):233–41. https://doi.org/10.1207/ [92] Kittikraisak W, Burapat C, Nateniyom S, Akksilp S, Mankatittham W, Sirinak C,
S15327655JCHN1604_3. et al. Improvements in physical and mental health among HIV-infected patients
[68] Cremers AL, de Laat MM, Kapata N, Gerrets R, Klipstein-Grobusch K, Grobusch treated for TB in Thailand. Southeast Asian J Trop Med Public Health
MP. Assessing the consequences of stigma for tuberculosis patients in urban 2008;39(6):1061–71.
Zambia. PLoS One 2015;10(3):e0119861https://doi.org/10.1371/journal.pone. [93] TB CARE I. International standards for tuberculosis care. 3rd ed. The Hague: TB
0119861. CARE I; 2014.
[69] Shivapujimath R, Rao AP, Nilima AR, Shilpa DM. A cross-sectional study to assess [94] Daniels B, Kwan A, Pai M, Das J. Lessons on the quality of tuberculosis diagnosis
the stigma associated with tuberculosis among tuberculosis patients in Udupi from standardized patients in China, India, Kenya, and South Africa. J Clin Tuberc
district, Karnataka. Indian J Tuberc 2017;64(4):323–6. https://doi.org/10.1016/j. Other Mycobacterial Dis 2019;16:100109https://doi.org/10.1016/j.jctube.2019.
ijtb.2016.10.002. 100109.
[70] Yin X, Yan S, Tong Y, Peng X, Yang T, Lu Z, et al. Status of tuberculosis-related [95] Naidoo P, Theron G, Rangaka MX, Chihota VN, Vaughan L, Brey ZO, et al. The
stigma and associated factors: a cross-sectional study in central China. Trop Med south african tuberculosis care cascade: estimated losses and methodological
Int Health 2018;23(2):199–205. https://doi.org/10.1111/tmi.13017. challenges. J Infect Dis 2017;216(suppl_7):S702–13. https://doi.org/10.1093/
[71] Courtwright A, Turner AN. Tuberculosis and stigmatization: pathways and inter- infdis/jix335.
ventions. Public Health Rep 2010;125(Suppl 4):34–42. https://doi.org/10.1177/ [96] Subbaraman R, Nathavitharana RR, Satyanarayana S, Pai M, Thomas BE, Chadha
00333549101250s407. VK, et al. The tuberculosis cascade of care in india's public sector: a systematic
[72] Johansson E, Diwan VK, Huong ND, Ahlberg BM. Staff and patient attitudes to review and meta-analysis. PLoS Med 2016;13(10):e1002149https://doi.org/10.
tuberculosis and compliance with treatment: an exploratory study in a district in 1371/journal.pmed.1002149.
Vietnam. Tuber Lung Dis 1996;77(2):178–83. [97] Pinto LM, Udwadia ZF. Private patient perceptions about a public programme;
[73] Johansson E, Long NH, Diwan VK, Winkvist A. Attitudes to compliance with tu- what do private indian tuberculosis patients really feel about directly observed
berculosis treatment among women and men in Vietnam. Int J Tuberc Lung Dis treatment? BMC Public Health 2010;10:357. https://doi.org/10.1186/1471-2458-
1999;3(10):862–8. 10-357.
[74] Hudelson P. Gender differentials in tuberculosis: the role of socio-economic and [98] Atif M, Sulaiman SA, Shafie AA, Ali I, Hassali MA, Saleem F. WHO guidelines for
cultural factors. Tuber Lung Dis 1996;77(5):391–400. treatment of tuberculosis: the missing links. Int J Clin Pharm 2012;34(4):506–9.
[75] Khan A, Walley J, Newell J, Imdad N. Tuberculosis in Pakistan: socio-cultural https://doi.org/10.1007/s11096-012-9657-8.
constraints and opportunities in treatment. Soc Sci Med 2000;50(2):247–54. [99] Reid MJA, Arinaminpathy N, Bloom A, Bloom BR, Boehme C, Chaisson R, et al.
[76] Long NH, Johansson E, Diwan VK, Winkvist A. Fear and social isolation as con- Building a tuberculosis-free world: the lancet commission on tuberculosis. Lancet
sequences of tuberculosis in Vietnam: a gender analysis. Health Policy (New York) 2019;393(10178):1331–84. https://doi.org/10.1016/s0140-6736(19)30024-8.
2001;58(1):69–81. [100] Miller TL, McNabb SJ, Hilsenrath P, Pasipanodya J, Weis SE. Personal and societal
[77] Craig GM, Daftary A, Engel N, O'Driscoll S, Ioannaki A. Tuberculosis stigma as a health quality lost to tuberculosis. PLoS One 2009;4(4):e5080. https://doi.org/10.
social determinant of health: a systematic mapping review of research in low in- 1371/journal.pone.0005080.
cidence countries. Int J Infect Dis 2017;56:90–100. https://doi.org/10.1016/j.ijid. [101] Peddireddy V. Quality of life, psychological interventions and treatment outcome
2016.10.011. in tuberculosis patients: the Indian scenario. Front Psychol 2016;7:1664. https://
[78] Venkatraju B, Prasad S. Psychosocial trauma of diagnosis: a qualitative study on doi.org/10.3389/fpsyg.2016.01664.
rural TB patients' experiences in Nalgonda district, Andhra Pradesh. Indian J [102] Zarova C, Chiwaridzo M, Tadyanemhandu C, Machando D, Dambi JM. The impact
Tuberc 2013;60(3):162–7. of social support on the health-related quality of life of adult patients with tu-
[79] Liefooghe R, Michiels N, Habib S, Moran MB, De Muynck A. Perception and social berculosis in Harare, Zimbabwe: a cross-sectional survey. BMC Res Notes
consequences of tuberculosis: a focus group study of tuberculosis patients in 2018;11(1):795. https://doi.org/10.1186/s13104-018-3904-6.
Sialkot, Pakistan. Soc Sci Med 1995;41(12):1685–92. [103] Hargreaves JR, Boccia D, Evans CA, Adato M, Petticrew M, Porter JD. The social
[80] Marra CA, Marra F, Cox VC, Palepu A, Fitzgerald JM. Factors influencing quality of determinants of tuberculosis: from evidence to action. Am J Public Health
life in patients with active tuberculosis. Health Qual Life Outcomes 2004;2:58. 2011;101(4):654–62. https://doi.org/10.2105/ajph.2010.199505.
https://doi.org/10.1186/1477-7525-2-58. [104] Macq J, Solis A, Martinez G, Martiny P, Dujardin B. An exploration of the social
[81] Koyanagi A, Vancampfort D, Carvalho AF, DeVylder JE, Haro JM, Pizzol D, et al. stigma of tuberculosis in five "municipios" of Nicaragua to reflect on local inter-
Depression comorbid with tuberculosis and its impact on health status: cross- ventions. Health Policy (New York) 2005;74(2):205–17. https://doi.org/10.1016/
sectional analysis of community-based data from 48 low- and middle-income j.healthpol.2005.01.003.