Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
Syndemic Burden: Bridging the gap between
Tuberculosis and Mental Health Care for Integrated
Patient-Centered Solutions – a comprehensive
review
Sofia Sousa, Ana Aguiar
University of Porto, Porto, Portugal
Abstract
Introduction: Mental health issues are prev
alent, yet their treatment remains inadequate.
Tuberculosis presents substantial mental health challenges. Their co-
occurrence is a frequent
phenomenon. However, the integration of mental health professionals or services is not a
common practice.
Purpose
: To review the evidence about the relation between tuberculosis and mental health,
and its consequences concerning the implementation of policies and services.
Methodology: We conducted a comprehensive review using the MeSH terms "Tuberculosis" and
"Mental Health" on PubMed
. We identified and assessed systematic reviews, regular reviews,
scoping review and meta-analyses for their appropriateness and relevance.
Results: A total of 341 studies were accessed for eligibility and 17 studies were included. Mental
disorders and tuberculosis are frequent comorbidities. Their relation is commonly described as
“syndemic”. Shared risk factors, social vulnerabilities, and upstream social determinants are
prevalent in both conditions. There is a potential for the integration of both conditions into policy
and service organization.
Conclusions: Mental disorders treatment gap could be shortened by addressing mental health
problems among TB patients. The WHO Global End TB Strategy prioritizes integrated patient-
centered car
e, and fostering collaborative partnerships between tuberculosis and mental
health services could enhance its implementation.
Keywords
Tuberculosis; Mental Health; Syndemic
Address for correspondence:
Sofia Sousa, MD, University of Porto, Porto, Portugal
E-mail: assousa@icbas.up.pt
This work is licensed under a Creative Commons Attribution-Non-Commercial 4.0 International
License (CC BY-NC 4.0).
©Copyright: Sousa, 2024
Publisher: Sciendo (De Gruyter)
DOI: https://doi.org/10.56508/mhgcj.v7i1.180
Submitted for publication: 19
October 2023
Revised: 24 January 2024
Accepted for publication: 31
January 2024
2
14
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
Introduction
Mental health (MH) constitutes an integral
component of human flourishing. Mental
disorders not only stand as prominent contributors
to disability but also pose substantial risks for
premature mortality (Charlson et al., 2015; Rehm
and Shield, 2019). This burden associated with
mental disorders is on the rise across all levels of
sociodemographic development (Patel, Saxena,
Lund, Thornicroft, Baingana, Bolton, Chisholm,
Pamela Y Collins, et al., 2018). Beyond the strain
placed on healthcare budgets, MH disorders
exert a substantial burden on societies. This
impact extends to individuals, families,
workplaces, and the overall economy, leading to
reduced labor engagement, earlier retirements,
and increased welfare dependency, as
evidenced by Doran in 2017 (Doran and Kinchin,
2019).
While the high burden of disease attributable
to MH is primarily due to high prevalence
conditions such as depression and anxiety, in
most low and middle income countries (LMIC), by
far, the majority of expenditure is on
treatment/care of severe conditions such as
schizophrenia and bipolar mood disorder
(Freeman, 2022). Budgets for prevention and
promotion are usually minimal or even non-
existent in most LMIC (Freeman, 2022). According
to Global Burden of Disease 2017, mental
disorders have consistently formed more than
14% of Disability-Adjusted Life Years for nearly
three decades, and have greater than 10%
prevalence in all regions (James et al., 2018). The
burden of mental disorders affects individuals of
all sexes and spans across age groups. It begins
in childhood, with conditions like idiopathic
intellectual disability and autism spectrum
disorders, and persists into later life,
encompassing depressive disorders, anxiety
disorders, and schizophrenia (James et al., 2018).
Moreover, stands as a prominent cause of
disability on a global scale and plays a significant
role in contributing to the overall burden of
disease worldwide (World Health Organization,
2020).
The connection between Tuberculosis (TB) and
mental disorders is widely acknowledged, even
though it has received relatively less research
attention (Janse Van Rensburg et al., 2020).
Research has indicated that mental disorders are
frequently observed as comorbidities among TB
patients, but they are not always readily
recognized by healthcare workers and physicians
(Doherty et al., 2013; Koyanagi et al., 2017;
Plana-Ripoll et al., 2019; Janse Van Rensburg et
al., 2020).
Depression affected more than 264 million
people of all ages in 2019 (Sweetland et al.,
2014). Depression and TB often coexist in
individuals and share common risk factors (Duko,
Bedaso and Ayano, 2020). TB patients who are
depressed are less likely to seek medical advice
and adhere to prescribed treatment regime,
which results in: prolong infectiousness,
emergence of drug resistance, increased
morbidity and mortality. Thus, depression may be
a silent driver of global TB epidemic (Ruiz-Grosso
et al., 2020) and the emergence of Multidrug
resistant TB (MDR-TB) (Sweetland et al., 2014).
Undiagnosed depression can threaten the
robustness of directly observed treatment (DOT)
model despite large public health investment
(Chandra et al., 2019). There is compelling
evidence indicating that depressive symptoms
are linked to reduced adherence to treatment
regimens for chronic conditions, particularly those
with therapeutic requirements similar to TB, such
as HIV (Wagner et al., 2011; Blashill, Gordon and
Safren, 2014).
Purpose
A clear understanding of the specific types of
MH disorders and social stressors that may be
common to TB patients is needed to design,
evaluate and monitor effective interventions
(Alene et al., 2018). In this sense, we aim to
comprehensively review the relation between
tuberculosis and mental health, in order to
answer to the following specific objectives:
1. To review the evidence about the relation
between tuberculosis and mental health,
considering social determinants of health;
2. To assess the effects of mental health
disease in the treatment and clinical outcomes
of patients with TB;
3. To analyze the effects of TB on patients’
mental health outcomes;
4. To analyze potential consequences to
the implementation of policies and services
Methodology
Search of studies
A comprehensive review of systematic reviews
was conducted in PubMed, Cochrane library and
PsycINFO, according to PRISMA guidelines. A
search using the MeSH terms “Tuberculosis” and
“Mental Health” was conducted on referred
databases in December 2023, being our final
search expression (for Pubmed and PsycINFO) as
follow: (("tuberculosi"[All Fields] OR
"tuberculosis"[MeSH Terms] OR "tuberculosis"[All
Fields] OR "tuberculoses"[All Fields] OR
15
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
"tuberculosis"[All Fields]) AND ("mental
health"[MeSH Terms] OR ("mental"[All Fields] AND
"health"[All Fields]) OR "mental health"[All Fields])).
In order to address the objectives mentioned, in
an exploratory way, we filtered the article type to
include only systematic reviews, reviews and
meta-analysis. In the case of Cochrane libray, we
only use the term “Tuberculosis” in the search
expression, since the joint of "Tuberculosis" and
"mental health" only delivered 4 reviews, not
related with any of the terms.
We opted to utilize the term "mental health"
because its definition encompasses all
psychological disorders. This choice allows us to
include a greater number of articles related to
tuberculosis. Additionally, prior evidence
emphasized the role of depression more
prominently than other mental health illnesses. As
a result, we chose to adopt a broader term for
the current review.
For the definition of the construct of “mental
health” we considered the definition proposed by
the WHO as “a state of well-being in which an
individual realizes his or her own abilities, can
cope with the normal stresses of life, can work
productively and is able to make a contribution
to his or her community” (World Health
Organization, 2022).
Selection of studies
We considered all the studies found from
inception until December 2023 to this
comprehensive review.
Title and abstracts were screened for
appropriateness and relevance in the first step of
the review. Articles were excluded if: did not
include the terms “Tuberculosis” or “Mental health”
in the title and abstract; studies that only focused
on “tuberculosis” or only on “mental health”;
studies that were not systematic reviews, reviews
or meta-analysis; studies related with drug
secondary effects, alcohol or drug addiction or
latent TB infection.
Data extraction and analysis
Following the conclusion of the search
process, the two authors independently carried
out the selection of articles for inclusion and the
extraction of key findings from the studies. The
research team evaluated the ultimate collection
of manuscripts, and subsequently, they extracted
thematic information regarding the study's
objectives, the employed methodology the
study's setting, and noteworthy findings.
Moreover, since we included systematic
reviews, reviews, scoping reviews and meta-
analysis, we summarized the information of the
studies using a narrative approach. We extracted
qualitative evidences using the 'thematic
synthesis' method and methodically organized
them into broader descriptive themes (Barnett-
Page and Thomas, 2009), which were then
compared for interrelationships and categorized
into four final themes. Furthermore, considering
the type of articles included for revision and the
full nature of the present comprehensive review,
we did not assess the quality of the included
studies since, by default, among epidemiological
studies, the systematic reviews and meta-analysis
articles are on the top of the pyramid considering
higher quality of reported evidence and lower risk
of bias.
Ethical considerations
Our data was already published in peer-review
journals that demand ethically approved
research, so ethical approval or personal consent
have not been necessary.
Results
A total of 341 results were found (Figure 1). Of
these, 320 were excluded because they did not
include “tuberculosis” or “mental health” in the
title or abstract or were not systematic reviews,
reviews, scoping reviews or meta-analysis (Figure
1). A total of 17 studies were included in our final
revision (Table 1). The time-frame between the
included studies ranged from 2013 and 2023.
Concerning the number of articles referred in
each included review, the smallest review was
from Chandra et al., 2019 (Chandra et al., 2019),
with 3 articles included and, the largest, was
published by Doherty et al., (2013), had a total of
189 articles revised.
Epidemiology of Mental Health and
Tuberculosis
The epidemiology of mental health in
tuberculosis (TB) patients reveals a significant
burden of mental health (MH) disorders, social
stressors, and diminished health-related quality of
life, particularly among multidrug-resistant TB
(MDR-TB) patients. Compared to the general
population, TB patients exhibit a higher
prevalence of MH disorders (Doherty et al., 2013).
Depression, for instance, is three to six times more
common among TB patients than in healthy
controls, while anxiety rates are almost twice as
high. Alarmingly, one in ten MDR-TB patients
experiences psychosis (Alene et al., 2018).
Respiratory diseases such as TB are significantly
more prevalent in people with schizophrenia
compared with the general population (Suetani
et al., 2021). Suicide was reported in 0.92% of TB
patients at the end of 2 years, whereas 2.2% to
8.4% of all TB deaths were reported due to
suicide (Patwal et al., 2023).
16
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
Table 1: included studies, year of publication, title, number of articles, and main objective.
Author Year
Country/
countries
Title
N
articles
Main objective(s)
Doherty et
al 2013 -
A review of the interplay
between tuberculosis and
mental health.
189
Examine the interplay between tuberculosis and
mental health;
Identify the key issues which are likely to be of
clinical importance in treating patients with
psychiatric comorbidity in tuberculosis.
Thomas et
al 2016 -
Psycho-Socio-Economic
Issues Challenging Multidrug
Resistant Tuberculosis
Patients: A Systematic
Review.
15
Review the psychosocial challenges faced by
Multidrug Resistant Tuberculosis (MDR-TB) patients
which complicates the MDR-TB treatment.
Magee et
al 2017 -
Integrated Public Health
and Health Service Delivery
for Noncommunicable
Diseases and Comorbid
Infectious Diseases and
Mental Health.
-
Explore the epidemiology of joint burdens, risk
factors, and prognoses of these co-occurring
conditions.
Alene et al 2018 -
Mental health disorders,
social stressors, and health-
related quality of life in
patients with multidrug-
resistant tuberculosis: A
systematic review and
meta-analysis
40
Quantify mental health disorders, social stressors,
and health-related quality of life in patients with
multidrug-resistant tuberculosis.
Zhang et
al 2019 -
The interplay between
depression and
tuberculosis.
-
Discuss the hypotheses on the association
between depression and TB, highlighting the
immuno-inflammatory
response and lipid
metabolism as potential mechanisms.
Chandra
et al 2019 -
Tuberculosis - Depression
syndemic: A public health
challenge.
3 To study the evidence base for Depression-
Tuberculosis Syndemic.
Kane et al 2019
low- and
middle-
income
countries
A scoping review of health-
related stigma outcomes
for high-burden diseases in
low- and middle-income
countries.
186
Provide a critical overview of the breadth of
research on stigma for each of five conditions
(HIV, tuberculosis, mental health problems,
epilepsy and substance use disorders) in low-
and middle-income countries.
Rensburg
et al 2020
Low-to-
middle
income
countries
Comorbidities between
tuberculosis and common
mental disorders: a scoping
review of epidemiological
patterns and person-
centred care interventions
from low-to-middle income
and BRICS countries
100
Review the nature and extent of tuberculosis and
common mental disorder comorbidity and
person-centred tuberculosis care in low-to-
middle income countries and emerging
economies.
Lee et al 2020 -
Impact of mental disorders
on active TB treatment
outcomes: a systematic
review and meta-analysis.
10
Determine whether TB patients with concurrent
mental disorders have poorer treatment
outcomes than patients without mental disorders.
Duko et al 2020 -
The prevalence of
depression among patients
with tuberculosis: a
systematic review and
meta-analysis.
25
Quantitatively summarize epidemiologic
evidence on the prevalence of depression
among patients
with TB and formulate a
recommendation for future clinical practice as
well as research.
Farooq et
al 2021 -
Pharmacological or non-
pharmacological
interventions for treatment
of common mental
disorders associated with
Tuberculosis: A systematic
review.
26
Review the literature on interventions for treating
Common Mental Disorders (CMD) in people with
TB.
Suetani et
al
2021 -
Increased rates of
respiratory disease in
21
Establish the prevalence and association of
respiratory diseases in people with schizophrenia
17
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
schizophrenia: A systematic
review and meta-analysis
including 619,214
individuals with
schizophrenia and
52,159,551 controls
Janusz
Rybakowski 2022 -
Infections and mental
diseases: from tuberculosis
to COVID-19
-
Conduct a narrative review on the relationship
between mental diseases and infectious factors
such as tuberculosis
Hayward
et al 2022 -
The relationship between
mental health and risk of
active tuberculosis: a
systematic review
10
Examine the association between mental health
and TB disease risk to inform clinical and public
health measures.
Njie et al 2022 United
States
Prevalence of Tuberculosis
and Mental Disorders
Comorbidity: A Systematic
Review and Meta-analysis
9
E
xamine Tuberculosis and mental disorder
comorbidity prevalence and its impact on TB
treatment outcomes.
Patwal et
al 2023 -
Prevalence of suicidal
ideations and suicide
attempts in patients with
tuberculosis: A systematic
review and meta-analysis.
9
Assess the prevalence of suicidality and identify
the factors associated with suicidality in patients
with TB.
Alemu et
al 2023 East
Africa
Prevalence of depression in
people with tuberculosis in
East Africa: a systematic
review and meta-analysis
9
Examine evidence concerning the prevalence of
depression among tuberculosis patients in East
Africa.
Figure 1. Flowchart with the included studies
Records identified from:
Pubmed (n = 218)
Cochrane Library (n=104)
PsycINFO (n=19)
Records screened
(n = 341)
Records excluded based in title and abstract:
Studies that did not include “tuberculosis” or “mental
health” (n = 319)
Not systematic reviews, reviews, scoping reviews or
meta-analysis (n = 1)
Reports sought for retrieval
(n = 21)
Reports excluded based on full-text:
Studies that focused on drug secondary effects (n=1)
Studies related with drug or alcohol abuse (n=1)
Studies that focused on latent TB infection (n=1)
Full text not available (n=1)
Reports assessed for eligibility
(n = 17)
Studies included in comprehensive review
(n = 17)
Identification of studies via databases and registers
Identification
Screening
Included
18
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
Research consistently demonstrates that
individuals undergoing TB treatment are at an
elevated risk of mental illness (Alene et al., 2018;
Plana-Ripoll et al., 2019). A 2020 review involving
25 studies reported a prevalence of depression
among TB patients, using the Hamilton
Depression Rating Scale, at 45.19% (Duko,
Bedaso and Ayano, 2020; Njie and Khan, 2022).
Furthermore, the prevalence is even higher
among MDR-TB patients at 52.34% (Duko, Bedaso
and Ayano, 2020). In another review in East Africa
countries, the pooled prevalence estimate of
depression amongst tuberculosis patients was
43.03% (Alemu and Zeleke, 2023).
MDR-TB patients, who undergo prolonged
treatment with anti-TB drugs and face severe side
effects, are particularly vulnerable to MH issues
(Thomas et al., 2016). Reviews have indicated
varying prevalence rates of anxiety among TB
patients, ranging from 2% to 27% (Janse Van
Rensburg et al., 2020). Depression, in particular,
independently contributes to higher morbidity,
mortality, drug resistance, TB reactivation, and
community TB transmission (Chandra et al.,
2019). Depressed individuals with TB often delay
seeking care and exhibit inconsistent medication
adherence, increasing the risks of drug
resistance, morbidity, and mortality (Sweetland et
al., 2014).
Compounding these challenges, mental
illness often emerges during the TB disease
trajectory, with detrimental consequences,
particularly in low and middle income countries
grappling with complex issues like poverty,
gender disparities, limited education, and
inadequate healthcare systems (Janse Van
Rensburg et al., 2020). Furthermore, TB, especially
MDR-TB, is associated with long-term physical
complications, sparking interest in how these
sequelae affect mental health and social
functioning (Chakaya, Kirenga and Getahun,
2016; Alene et al., 2018).
The interconnection between mental illness
and TB is claimed to be bidirectional and
influenced by biological, psychological, social,
and healthcare system factors (Zhang et al.,
2019; Janse Van Rensburg et al., 2020). TB and
MH are both influenced by common social
determinants, such as poverty, inadequate
access to healthcare, and housing conditions
(Whiting, Unwin and Roglic, 2010). These factors
can increase the risk of both TB and mental
illness.
MH disorders may develop following TB
infection, but patients with such disorders also
appear to have an increased risk of TB. In fact,
most mental disorders are associated with an
elevated risk of subsequent medical conditions
(Oh et al., 2017; Momen et al., 2020). TB is
relatively common among patients with
psychiatric disorders, with rates of major
depression being even higher than in the general
population, particularly in individuals diagnosed
with TB (Doherty et al., 2013).
Recognizing and addressing the MH needs of
TB patients is crucial for improving overall
outcomes and reducing the burden of both
conditions.
TB is a chronic illness that can cause
significant psychological distress (Pachi et al.,
2013). The physical symptoms, social isolation,
and fear of transmission can lead to anxiety and
depression among TB patients.
Stigma detrimentally affects the support
networks and the quality of services provided to
individuals with stigmatized conditions.
Mistreatment TB patients can lead to adverse MH
outcomes, maladaptive coping behaviors, and
the emergence of other comorbid conditions.
Furthermore, TB-related stigma has the potential
to erode the resilience of affected patients (Kane
et al., 2019; Alfaiate et al., 2023).
The stigma associated with TB can exacerbate
psychological distress. People with TB may be
ostracized, discriminated against, or excluded
from their communities, leading to feelings of
shame and social isolation.
Psychological factors and patient perception
about illness are important factors for adherence
to a long term therapy required in chronic illness
like TB (Pachi et al., 2013). In order to maximize
the rate of adherence, health workers involved in
the management of these patients should
develop a higher index of suspicion for possible
psychopathology and utilize the available
consultation/liaison psychiatric services (Pachi et
al., 2013).
Moreover, depression alone serves as a risk
factor for TB. Cohort studies have demonstrated
that patients with depression are more likely to
develop TB, with a dose-response relationship
observed between the severity of depression and
the subsequent risk of TB (Oh et al., 2017). There is
robust evidence from cohort studies in Asia
demonstrating that depression and schizophrenia
can increase risk of active TB, with effect
estimates ranging from Hazard Rate (HR)=1.15
(95% CI 1.03 to 1.28) to 2.63 (95% CI 1.74 to
3.96) for depression and HR=1.52 (95% CI 1.29
to 1.79) to Relative Risk (RR)=3.04 for
schizophrenia (Hayward et al., 2022).
TB and mental illness frequently co-occur due
to shared risk factors such as homelessness, HIV
positivity, substance abuse, and migrant status
(Doherty et al., 2013). Patients with mental illness
face an increased risk of TB infection due to
factors like higher rates of homelessness, shelter
19
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
or group home residence, and potential
contributors to disease progression such as
smoking, poor nutrition, diabetes, and HIV
infection (Doherty et al., 2013). Social stressors like
discrimination, reduced income, divorce, and
stigma are prevalent among individuals with TB,
significantly affecting their quality of life and
treatment outcomes (Alene et al., 2018).
The relationship between TB and
socioeconomic conditions is intricate, with social
vulnerability and mental disorders acting as
intertwined factors. Both conditions are influenced
by upstream health determinants, often
coexisting in a substantial portion of the
population. Poverty emerges as a formidable
determinant of TB, shaping its various stages, from
exposure risk to susceptibility, diagnosis, treatment
compliance, and successful treatment (Knut
Lönnroth, Ernesto Jaramillo, Brian Williams, 2010;
Hargreaves et al., 2011; World Health
Organisation, 2013; Duarte et al., 2018; Janse
Van Rensburg et al., 2020). Overcrowded and
poorly ventilated living and working environments
directly increase TB transmission risk, while
undernutrition contributes significantly to the
development of active disease (World Health
Organisation, 2013). Poverty is also associated
with limited health knowledge and a lack of
empowerment to address health-related risks
(World Health Organisation, 2013).
Moreover, research consistently underscores
the robust connection between social
disadvantage and poor MH (Patel, Saxena, Lund,
Thornicroft, Baingana, Bolton, Chisholm, Pamela
Y. Collins, et al., 2018). Factors such as poverty,
childhood adversity, and violence emerge as
critical risk factors for the onset and persistence of
mental disorders. These MH challenges, in turn,
often result in income loss due to limited
educational attainment and reduced
employment opportunities and productivity. This
intricate interplay between social determinants,
mental disorders, and economic disadvantage
creates a vicious cycle that perpetuates poverty
across generations (Patel, Saxena, Lund,
Thornicroft, Baingana, Bolton, Chisholm, Pamela
Y. Collins, et al., 2018).
Possible causal mechanisms
Psychiatric disorders may be connected with
an infection in various periods of life (Rybakowski,
2022). Depression appears to be the
predominant mental illness associated with TB
patients in existing studies. However, the exact
nature of the relationship between depression
and TB remains unclear, and it seems to have
bidirectional association. Understanding this
mechanism is crucial for directing research efforts
to enhance TB therapy effectiveness and reduce
comorbidity with depression (Zhang et al., 2019).
The causal pathways connecting TB and
depression are complex and multidirectional,
encompassing biological, social, behavioral,
pharmaceutical, and psychosocial factors
(Ugarte-Gil et al., 2013; Janse Van Rensburg et
al., 2020).
Biological factors likely contribute to this
bidirectional relationship. TB infection or
reactivation may trigger depression, possibly due
to the host's inflammatory response and
alterations in the hypothalamic-pituitary-adrenal
axis. TB infection can induce chronic
inflammation, releasing pro-inflammatory
cytokines that affect central nervous system
enzymes. Additionally, certain anti-TB medications
might contribute to mental health issues like
depression (Duko, Bedaso and Ayano, 2020).
Conversely, depression may raise the risk of TB
through immuno-inflammatory responses and
lipid metabolism. Increased pro-inflammatory
cytokines seen in depression can dampen
cellular and humoral immune system activation,
potentially aiding TB progression (Zhang et al.,
2019).
Social determinants also play a significant
role. Poverty, as mentioned earlier, is a shared risk
factor for both TB and depression. Overcrowded
and poorly ventilated conditions facilitate TB
transmission, while exposure to violence, social
exclusion, drug abuse, and malnutrition may
contribute to both diseases (Janse Van Rensburg
et al., 2020). Moreover, depression can mimic TB
symptoms and exacerbate them. When
combined with negative coping behaviors,
depression can lead to non-adherence to TB
treatment, posing a considerable challenge
(Sweetland et al., 2018).
Psychosocial factors, including perceived
stigma and treatment nonadherence, are vital in
this relationship. Stigma associated with TB
diagnosis can heighten the risk of depression due
to the fear it engenders (Chandra et al., 2019).
Multidrug-resistant TB patients often experience
stigma, discrimination, isolation, and a lack of
social support, which can lead to negative
emotions, social rejection, low self-esteem, and
impaired psychosocial well-being (C. et al., 2014;
Alene et al., 2018).
The discussion surrounding the link between
stigma and health outcomes is often
compartmentalized within specific disease
categories, hindering the identification of
common moderators or mechanisms. This
separation limits our understanding of stigma's
overall impact on individual well-being and
global disease burden (Kane et al., 2019).
Additionally, pharmacological issues must be
considered. Psychiatric side effects of anti-TB
20
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
agents and potential interactions between TB
treatment medications and drugs used to
manage psychiatric or addiction disorders are
important factors to be mindful of. Managing TB
in the presence of depression can be particularly
challenging due to these interactions (Doherty et
al., 2013).
Policy and Services
In an 2023 Operational handbook on
tuberculosis and comorbidities dedicated to
mental health conditions, World Health
Organization (WHO) refers that mental health care
is one of the health services to be integrated with
TB services as outlined in the End TB Strategy and
the WHO Framework for collaborative action on
tuberculosis and comorbidities (World Health
Organization, 2023).
WHO’s strategy for achieving the elimination of
TB underscores the importance of addressing the
social-economic determinants of TB. To achieve
this, countries must strengthen their health and
social sectors by implementing universal health
coverage and social protection measures (World
Health Organisation, 2013; WHO, 2015; Santos,
Duarte and Nunes, 2020). Moreover, actions to
reduce the risk of mental disorders across the
lifespan, both at the community and country
levels, are imperative. Recognizing that
addressing social determinants of health is a
shared responsibility across health programs and
sectors is vital for comprehensive care (Carod-
Artal, 2017).
Integrating MH care into all levels of the
general health system is essential to improve the
quality of care and reduce the stigma
associated with mental disorders (Levav and Rutz,
2002). Health system barriers, such as
fragmented health information systems, limited
patient management, and communication gaps
between levels of care, exacerbate challenges
during the TB disease episode (Janse Van
Rensburg et al., 2020).
During anti-TB treatment, nonadherence and
adverse treatment effects are common,
potentially leading to delayed recovery or
exacerbation of comorbid depression-like
symptoms. Combining antidepressant drugs with
effective nursing measures that promote good
mental health may help alleviate depressive
symptoms in TB patients (Oh et al., 2017).
Screening and managing depression among TB
patients have been identified as crucial strategies
to alleviate their suffering, and integrating TB
programs with regular psychiatric services can
substantially reduce this burden (Duko, Bedaso
and Ayano, 2020).
A pilot experience in Pakistan studied
integrating units for TB and mental health within
existing TB treatment facilities. Screening and
offering mental health interventions to
symptomatic patients resulted in higher rates of
TB treatment completion (Pasha et al., 2021).
Given the high prevalence of depression among
TB patients, routine social support and counseling
should be integral components of TB care and
management programs, with the integration of
psychiatric services further reducing the burden of
depression (Duko, Bedaso and Ayano, 2020).
WHO's Global End TB Strategy emphasizes
integrated, patient-centered care linked to social
protection and innovative research. Achieving
these goals necessitates more person-centered
TB care models and collaborative partnerships
between TB and mental health professionals
(Chandra et al., 2019; Janse Van Rensburg et al.,
2020). Improving the environment, society, and
family support for TB patients can enhance their
mental health outcomes (Liu et al., 2021).
Addressing the co-occurrence of
noncommunicable and communicable diseases
presents challenges that require integrated public
health and care delivery efforts (Magee et al.,
2017). Integrating TB and mental health services,
particularly when dealing with multidrug-resistant
TB patients, is essential to screen for and manage
comorbid psychopathology and promote
therapy adherence (Magee et al., 2017;
Sweetland et al., 2019).
Surveys indicate receptivity to integrating TB
and mental health care services into TB care and
prevention, despite challenges such as low
awareness, limited resources, and training gaps
(Sweetland et al., 2019). A 2021 review suggests
the feasibility of interventions to improve mental
health outcomes and treatment adherence in TB
patients, including psychosocial interventions,
stigma reduction, socioeconomic support, and
various psychological therapies, education, or
pharmacological interventions (Farooq, Tunmore
and Comber, 2021). These interventions can
address common mental disorders and barriers
to TB control worldwide, focusing on factors like
stigma, socioeconomic disadvantages, health
belief models, and support for family members
(Farooq, Tunmore and Comber, 2021).
Discussion
The co-occurrence of tuberculosis (TB) and
mental health (MH) disorders is a complicated
and diverse issue with significant public health
implications (Janse Van Rensburg et al., 2020).
The findings from this study highlight the
importance of a comprehensive strategy to
addressing this dual burden since we found a
positive and independent association between
common mental disorders and TB.
21
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
The epidemiological data clearly show a
considerable link between TB and MH disorders,
with depression being the most commonly
implicated mental illness among TB patients
(Chandra et al., 2019). Individuals with TB have a
significantly greater frequency of MH issues,
particularly depression and anxiety, than the
overall population. Notably, patients with
multidrug-resistant tuberculosis (MDR-TB) endure
an even larger burden of mental health
concerns. This epidemiological link underscores
the importance of a more comprehensive
strategy to TB care, one that includes
comprehensive MH support (World Health
Organisation, 2013; WHO, 2015; Magee et al.,
2017). In light of the observed comorbidity
between TB and mental illness, regardless of the
direction of causality, this work carries significant
implications for the delivery of care for both
mental disorders and TB. There is an urgent need
for the development of practical and innovative
psychosocial and economic interventions
tailored to assist TB patients in managing their
illness, enhancing treatment adherence,
improving treatment outcomes, and ultimately
enhancing their overall quality of life.
Understanding the risk factors and social
determinants common to both TB and MH is
essential. Poverty, homelessness, substance
abuse, and social stressors emerge as shared risk
factors. Overcrowded living conditions and
inadequate access to healthcare further
exacerbate these risks. Addressing these
upstream determinants is imperative for effective
prevention and management of both diseases.
Poverty alleviation, improved living conditions,
and social support systems are crucial
components of such efforts. Efforts to alleviate
poverty not only reduce the risk of TB transmission
but also lower the chances of infection
progressing to disease. Poverty alleviation
measures improve access to healthcare services
and promote adherence to recommended
treatments. Addressing the determinants of ill
health through holistic approaches, like "health-in-
all-policies," can significantly enhance TB care
and prevention.
A complex combination of biological, social,
behavioral, pharmacological, and psychosocial
processes underpins the bidirectional link
between TB and MH issues. Both disorders are
caused by biological factors such as
inflammatory reactions and hypothalamic-
pituitary-adrenal axis dysfunction. Poverty and
violence are two social variables that further
complicate this link. Furthermore, the overlap in
symptoms between TB and depression, together
with depression's detrimental impact on
adherence to TB therapy, produces a loop of
increased disease burden.
Non-compliance as a major difficulty in the
treatment of TB and mental illness. Many
challenges faced by patients lie outside the
formal health system sphere – transport
problems, occupational issues, medication
reactions and food assistance. Building a strong
emotional and psychological support system for
TB and mental health patients is crucial for
increasing chances of their survival.
To address the co-occurrence of TB and MH
issues, a comprehensive policy framework and
coordinated care delivery are required. The END
TB strategy of the World Health Organization
highlights the importance of addressing social
determinants and establishing universal health
coverage. Integrating MH care into general
health systems is critical for reducing stigma and
improving care quality. However, bottlenecks in
the health care system, fragmented information
systems, and communication gaps offer
substantial challenges.
Efforts to integrate psychological and TB care
have showed promise in terms of enhancing
treatment results and lowering depressive and
anxiety symptoms. There is still a lack of thorough
integration at both the policy and ground levels,
particularly in diagnosing and treating depression
in TB patients. The absence or scarcity of
integration between TB and MH at both policy
and operational levels prompts a critical
question. It is prudent to explore a more holistic
approach, encompassing both communicable
and non-communicable diseases, to foster the
integration of healthcare services within a person-
centered perspective. Such an approach holds
the potential to alleviate the dual burden of TB
and mental health disorders, thereby improving
the overall well-being of individuals affected by
these intertwined conditions.
Efforts to address MH and social stressors can
profoundly impact patient care. A systematic
review commissioned by WHO found that TB
patients who received social support during
treatment were significantly more likely to adhere
to their treatment regimens (Yamazaki, 2017).
Integrating psychological and TB services has the
potential to improve TB outcomes and progress
toward TB elimination (Lee et al., 2020). However,
there is a notable lack of published experiences
regarding policy or ground-level integration,
including the identification and appropriate
management of depression in TB patients,
despite repeated contact with healthcare
providers in directly observed treatment (DOT)
centers.
The link between TB and MH disorders is
epidemiologically significant and intricately
22
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
entwined due to similar risk factors, complex
pathophysiologic mechanisms, and policy
implications (Doherty et al., 2013). Addressing this
twofold burden requires a multifaceted approach
spanning social, biological, and healthcare
dimensions. Integrating MH treatments into TB
care, addressing social determinants, and
enacting policies that prioritize universal health
coverage are all critical steps toward relieving the
suffering of people suffering from both issues.
Understanding this relationship is critical for
improving individual health outcomes and for the
worldwide endeavor to manage and eliminate
TB.
To increase understanding of the possible
mechanisms responsible for this association,
further studies are needed. The most described
relation in the literature was between TB and
depression, described as ‘TB-depression
syndemic’(Chandra et al., 2019), which poses
significant risk to the Global End TB Strategy. The
bidirectional relationship between the TB and
depression needs to be recognized to control the
global TB epidemic (Sweetland et al., 2018). As
mentioned before, depression is associated with
a range of adverse outcomes in TB such as poor
functional impairment, poor adherence to
medication and self-care regimens, increased
medical symptom burden and increased
mortality. Depression may also increase risk of TB
reactivation, antibiotic drug resistance, contribute
to disease progression, and/or inhibit the
physiological response to anti-tuberculosis
treatment. Conversely, TB may precipitate
depression. This results in worse prognoses for TB,
treatment with drugs that have significant
neuropsychiatric side effects, enhanced stigma
and social isolation. These factors then lead to
further depression and anxiety (Farooq, Tunmore
and Comber, 2021).
Concluions
In conclusion, the link between TB and MH
disorders is both epidemiologically substantial
and intricately intertwined due to shared risk
factors, complex pathophysiology, and
significant policy implications. To address this
dual burden effectively, a multidimensional
approach is necessary, involving social,
biological, and healthcare aspects. Integrating
MH into TB care, addressing socioeconomic
factors, and prioritizing universal health coverage
in policies are crucial steps to alleviate suffering in
individuals with both TB and MH concerns.
Understanding this complex link is critical for
global TB control efforts. The scarcity or absence
of integration between TB and MH at policy or
ground levels prompts reasonable questioning. A
more comprehensive approach, encompassing
both communicable and non-communicable
diseases, could facilitate the integration of
healthcare services from a person-centered
perspective.
Funding
This work received financial support from the
Portuguese Funds through FCT - Foundation for
Science and Technology, I.P., under the projects
UIDB/04750/2020 and LA/P/0064/2020. Ana
Aguiar, was supported by her PhD Grant
(Reference: 2020.09390.BD), co-funded by the
Fundação para a Ciência e a Tecnologia (FCT)
and the Fundo Social Europeu (FSE) Program. It's
important to note that the funders played no role
in the study's conception, data collection and
analysis, decision to publish, or the preparation of
the manuscript.
Conflict of interest
The authors declare that they have not
conflicts of interest.
References
Alemu, W. G. and Zeleke, T. A. (2023) ‘Prevalence
of depression in people with tuberculosis
in East Africa: a systematic review and
meta-analysis’, African Health Sciences,
23(1), pp. 231–240. doi:
10.4314/ahs.v23i1.25.
Alene, K. A. et al. (2018) ‘Mental health disorders,
social stressors, and health-related quality
of life in patients with multidrug-resistant
tuberculosis: A systematic review and
meta-analysis’, Journal of Infection, 77(5),
pp. 357–367. doi:
10.1016/j.jinf.2018.07.007.
Alfaiate, A. et al. (2023) ‘Tuberculosis and COVID-
19 Related Stigma: Portuguese Patients
Experiences’, Tuberculosis and
Respiratory Diseases, 86(3), pp. 216–225.
doi: 10.4046/trd.2022.0062.
Blashill, A. J., Gordon, J. R. and Safren, S. A.
(2014) ‘Depression longitudinally mediates
the association of appearance concerns
to ART non-adherence in HIV-infected
individuals with a history of injection drug
use.’, Journal of behavioral medicine,
37(1), pp. 166–172. doi: 10.1007/s10865-
012-9476-3.
C., S. et al. (2014) ‘Health-related quality of life,
23
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
depression, and anxiety in patients with
autoimmune hepatitis’, Journal of
Hepatology, 60(3), pp. 618–624.
Available at:
http://ovidsp.ovid.com/ovidweb.cgi?T=JS
&PAGE=reference&D=emed12&NEWS=
N&AN=2014123616.
Carod-Artal, F. J. (2017) ‘Social determinants of
mental health’, Global Mental Health:
Prevention and Promotion, pp. 33–46.
doi: 10.1007/978-3-319-59123-0_4.
Chakaya, J., Kirenga, B. and Getahun, H. (2016)
‘Long term complications after
completion of pulmonary tuberculosis
treatment: A quest for a public health
approach’, Journal of Clinical
Tuberculosis and Other Mycobacterial
Diseases, 3, pp. 10–12. doi:
10.1016/j.jctube.2016.03.001.
Chandra, M. et al. (2019) ‘Tuberculosis -
Depression syndemic: A public health
challenge’, Indian Journal of Tuberculosis,
66(1), pp. 197–202. doi:
10.1016/j.ijtb.2019.02.007.
Charlson, F. J. et al. (2015) ‘Excess mortality from
mental, neurological and substance use
disorders in the Global Burden of Disease
Study 2010’, Epidemiology and
Psychiatric Sciences, 24(2), pp. 121–140.
doi: 10.1017/S2045796014000687.
Doherty, A. M. et al. (2013) ‘A review of the
interplay between tuberculosis and
mental health’, General Hospital
Psychiatry, 35(4), pp. 398–406. doi:
10.1016/j.genhosppsych.2013.03.018.
Doran, C. M. and Kinchin, I. (2019) ‘A review of
the economic impact of mental illness.’,
Australian health review : a publication of
the Australian Hospital Association, 43(1),
pp. 43–48. doi: 10.1071/AH16115.
Duarte, R. et al. (2018) ‘Tuberculosis, social
determinants and co-morbidities
(including HIV)’, Pulmonology, 24(2), pp.
115–119. doi:
10.1016/j.rppnen.2017.11.003.
Duko, B., Bedaso, A. and Ayano, G. (2020) ‘The
prevalence of depression among
patients with tuberculosis: A systematic
review and meta-analysis’, Annals of
General Psychiatry, 19(1), pp. 1–11. doi:
10.1186/s12991-020-00281-8.
Farooq, S., Tunmore, J. and Comber, R. (2021)
‘Pharmacological or non-
pharmacological interventions for
treatment of common mental disorders
associated with Tuberculosis: A systematic
review’, Chronic Respiratory Disease, 18.
doi: 10.1177/14799731211003937.
Freeman, M. (2022) ‘Investing for population
mental health in low and middle income
countries—where and why?’, International
Journal of Mental Health Systems, 16(1),
pp. 1–9. doi: 10.1186/s13033-022-00547-
6.
Hargreaves, J. R. et al. (2011) ‘The social
determinants of tuberculosis: from
evidence to action.’, American journal of
public health, 101(4), pp. 654–662. doi:
10.2105/AJPH.2010.199505.
Hayward, S. E. et al. (2022) ‘The relationship
between mental health and risk of active
tuberculosis: A systematic review’, BMJ
Open, 12(1). doi: 10.1136/bmjopen-
2021-048945.
James, S. L. et al. (2018) ‘Global, regional, and
national incidence, prevalence, and
years lived with disability for 354 Diseases
and Injuries for 195 countries and
territories, 1990-2017: A systematic
analysis for the Global Burden of Disease
Study 2017’, The Lancet, 392(10159), pp.
1789–1858. doi: 10.1016/S0140-
6736(18)32279-7.
Janse Van Rensburg, A. et al. (2020)
‘Comorbidities between tuberculosis and
common mental disorders: A scoping
review of epidemiological patterns and
person-centred care interventions from
low-to-middle income and BRICS
countries’, Infectious Diseases of Poverty,
9(1). doi: 10.1186/s40249-019-0619-4.
Kane, J. C. et al. (2019) ‘A scoping review of
health-related stigma outcomes for high-
burden diseases in low- and middle-
income countries’, BMC Medicine, 17(1).
doi: 10.1186/s12916-019-1250-8.
Knut Lönnroth, Ernesto Jaramillo, Brian Williams, C.
D. and M. R. (2010) ‘Tuberculosis: the role
of risk factors and social determinants’, in
Equity, social determinants and public
health programmes, pp. 220–237.
Koyanagi, A. et al. (2017) ‘Depression comorbid
with tuberculosis and its impact on health
status: Cross-sectional analysis of
community-based data from 48 low- and
middle-income countries’, BMC
Medicine, 15(1), pp. 1–10. doi:
24
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
10.1186/s12916-017-0975-5.
Lee, G. E. et al. (2020) ‘Impact of mental
disorders on active tuberculosis treatment
outcomes: a systematic review and
meta-analysis’, INT J TUBERC LUNG DIS,
24(12), pp. 1279–1284. doi:
10.5588/ijtld.20.0458.Impact.
Levav, I. and Rutz, W. (2002) ‘The WHO World
Health Report 2001: New understanding -
New hope’, Israel Journal of Psychiatry
and Related Sciences, 39(1), pp. 50–56.
Liu, K. et al. (2021) ‘Prevalence and Correlates of
Anxiety and Depressive Symptoms in
Patients With and Without Multi-Drug
Resistant Pulmonary Tuberculosis in China
’, Frontiers in Psychiatry , p. 1542.
Available at:
https://www.frontiersin.org/article/10.3389/f
psyt.2021.674891.
Magee, M. et al. (2017) ‘Integrated Public Health
and Health Service Delivery for
Noncommunicable Diseases and
Comorbid Infectious Diseases and Mental
Health.’, in Prabhakaran, D. et al. (eds).
Washington (DC). doi: 10.1596/978-1-
4648-0518-9_ch16.
Momen, N. C. et al. (2020) ‘Association between
Mental Disorders and Subsequent
Medical Conditions’, New England
Journal of Medicine, 382(18), pp. 1721–
1731. doi: 10.1056/nejmoa1915784.
Njie, G. J. and Khan, A. (2022) ‘Prevalence of
Tuberculosis and Mental Disorders
Comorbidity: A Systematic Review and
Meta-analysis’, Journal of Immigrant and
Minority Health, 24(6), pp. 1550–1556.
doi: 10.1007/s10903-021-01312-6.
Oh, K. H. et al. (2017) ‘Depression & risk of
tuberculosis: A nationwide population
based cohort study’, International Journal
of Tuberculosis and Lung Disease, 21(7),
pp. 804–809. doi: 10.5588/ijtld.17.0038.
Pachi, A. et al. (2013) ‘Psychiatric Morbidity and
Other Factors Affecting Treatment
Adherence in Pulmonary Tuberculosis
Patients’, Tuberculosis Research and
Treatment, 2013, pp. 1–37. doi:
10.1155/2013/489865.
Pasha, A. et al. (2021) ‘Impact of integrating
mental health services within existing
tuberculosis treatment facilities’, Medicine
Access @ Point of Care, 5, p.
239920262110113. doi:
10.1177/23992026211011314.
Patel, V., Saxena, S., Lund, C., Thornicroft, G.,
Baingana, F., Bolton, P., Chisholm, D.,
Collins, Pamela Y, et al. (2018) ‘The
<em>Lancet</em> Commission on
global mental health and sustainable
development’, The Lancet, 392(10157),
pp. 1553–1598. doi: 10.1016/S0140-
6736(18)31612-X.
Patel, V., Saxena, S., Lund, C., Thornicroft, G.,
Baingana, F., Bolton, P., Chisholm, D.,
Collins, Pamela Y., et al. (2018) ‘The
Lancet Commission on global mental
health and sustainable development’,
The Lancet, 392(10157), pp. 1553–1598.
doi: 10.1016/S0140-6736(18)31612-X.
Patwal, R. et al. (2023) ‘Prevalence of suicidal
ideations and suicide attempts in patients
with tuberculosis: A systematic review and
meta-analysis’, Journal of Psychosomatic
Research, 167, p. 111171. doi:
https://doi.org/10.1016/j.jpsychores.2023.
111171.
Plana-Ripoll, O. et al. (2019) ‘Exploring
Comorbidity Within Mental Disorders
among a Danish National Population’,
JAMA Psychiatry, 76(3), pp. 259–270. doi:
10.1001/jamapsychiatry.2018.3658.
Rehm, J. and Shield, K. D. (2019) ‘Global Burden
of Disease and the Impact of Mental and
Addictive Disorders’, Current Psychiatry
Reports, 21(2), p. 10. doi:
10.1007/s11920-019-0997-0.
Ruiz-Grosso, P. et al. (2020) ‘Association between
tuberculosis and depression on negative
outcomes of tuberculosis treatment: A
systematic review and meta-analysis’,
PLoS ONE, 15(1), pp. 1–13. doi:
10.1371/journal.pone.0227472.
Rybakowski, J. (2022) ‘Infections and mental
diseases: from tuberculosis to COVID-19’,
Psychiatria Polska, 56(5), pp. 931–944.
doi: 10.12740/PP/152125.
Santos, J. A., Duarte, R. and Nunes, C. (2020)
‘Host factors associated to false negative
and indeterminate results in an
interferon‐γ release assay in patients with
active tuberculosis’, Pulmonology, 26(6),
pp. 353–362. doi:
10.1016/j.pulmoe.2019.11.001.
Suetani, S. et al. (2021) ‘Increased rates of
respiratory disease in schizophrenia: A
systematic review and meta-analysis
25
Mental Health: Global Challenges Journal
https://www.sciendo.com/journal/MHGCJ
ISSN 2612-2138
including 619,214 individuals with
schizophrenia and 52,159,551 controls’,
Schizophrenia Research, 237(October
2020), pp. 131–140. doi:
10.1016/j.schres.2021.08.022.
Sweetland, A. et al. (2014) ‘Depression: A silent
driver of the global tuberculosis
epidemic’, World Psychiatry, 13(3), pp.
325–326. doi: 10.1002/wps.20134.
Sweetland, A. C. et al. (2018) ‘Addressing the
tuberculosis–depression syndemic to end
the tuberculosis epidemic’, INT J TUBERC
LUNG DIS, 21(8), pp. 852–861. doi:
10.5588/ijtld.16.0584.Addressing.
Sweetland, A. C. et al. (2019) ‘Integrating
tuberculosis and mental health services:
Global receptivity of national tuberculosis
program directors’, International Journal
of Tuberculosis and Lung Disease, 23(5),
pp. 600–605. doi: 10.5588/ijtld.18.0530.
Thomas, B. E. et al. (2016) ‘Psycho-socio-
economic issues challenging multidrug
resistant tuberculosis patients: A
systematic review’, PLoS ONE, 11(1), pp.
1–15. doi:
10.1371/journal.pone.0147397.
Ugarte-Gil, C. et al. (2013) ‘Association of Major
Depressive Episode with Negative
Outcomes of Tuberculosis Treatment’,
PLoS ONE, 8(7), pp. 1–7. doi:
10.1371/journal.pone.0069514.
Wagner, G. J. et al. (2011) ‘A closer look at
depression and its relationship to HIV
antiretroviral adherence.’, Annals of
behavioral medicine : a publication of
the Society of Behavioral Medicine,
42(3), pp. 352–360. doi: 10.1007/s12160-
011-9295-8.
Whiting, D., Unwin, N. and Roglic, G. (2010)
‘Equity, social determinants and public
health’, Equity, social determinants and
public health programmes. Available at:
http://www.who.int/social_determinants/.
WHO (2015) ‘Implementing The End TB Strategy’,
Antimicrobial Agents and
Chemotherapy, 58(12), pp. 7250–7257.
Available at:
https://www.cambridge.org/core/product/
identifier/CBO9781107415324A009/type/
book_part%0Ahttp://arxiv.org/abs/1011.16
69%0Ahttp://dx.doi.org/10.1088/1751-
8113/44/8/085201%0Ahttp://www.ncbi.nl
m.nih.gov/pubmed/25246403%0Ahttp://
www.pubmedcentral.nih.gov/artic.
World Health Organisation (2013) ‘End TB Strategy’,
World Health Origanisation, 53(9), pp.
1689–1699.
World Health Organization (2020) Depression
report 2020. Available at:
https://www.who.int/news-room/fact-
sheets/detail/depression.
World Health Organization (2022) Mental Health,
Concepts in mental health. Available at:
https://www.who.int/news-room/fact-
sheets/detail/mental-health-
strengthening-our-response.
World Health Organization (2023) WHO
operational handbook on tuberculosis.
Module 6: tuberculosis and comorbidities
-mental health conditions, Module 5:
management of tuberculosis in children
and adolescents. Available at:
https://apps.who.int/iris/bitstream/handle/1
0665/340256/9789240022614-eng.pdf.
Yamazaki, M. (2017) Guidelines for treatment of
drug-susceptible tuberculosis and patient
care, Kekkaku.
Zhang, K. et al. (2019) ‘The interplay between
depression and tuberculosis’, Journal of
Leukocyte Biology, 106(3), pp. 749–757.
doi: 10.1002/JLB.MR0119-023R
26
