Mental Health: Global Challenges Journal
ISSN 2612-2138
Syndemic Burden: Bridging the gap between
Tuberculosis and Mental Health Care for Integrated
Patient-Centered Solutions – a comprehensive
Sofia Sousa, Ana Aguiar
University of Porto, Porto, Portugal
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.
: 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.
Tuberculosis; Mental Health; Syndemic
Address for correspondence:
Sofia Sousa, MD, University of Porto, Porto, Portugal
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)
Submitted for publication: 19
October 2023
Revised: 24 January 2024
Accepted for publication: 31
January 2024
Mental Health: Global Challenges Journal
ISSN 2612-2138
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,
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,
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).
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
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
Mental Health: Global Challenges Journal
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.
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
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).
Mental Health: Global Challenges Journal
ISSN 2612-2138
Table 1: included studies, year of publication, title, number of articles, and main objective.
Author Year
Main objective(s)
Doherty et
al 2013 -
A review of the interplay
between tuberculosis and
mental health.
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 -
Issues Challenging Multidrug
Resistant Tuberculosis
Patients: A Systematic
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
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
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
Discuss the hypotheses on the association
between depression and TB, highlighting the
response and lipid
metabolism as potential mechanisms.
et al 2019 -
Tuberculosis - Depression
syndemic: A public health
3 To study the evidence base for Depression-
Tuberculosis Syndemic.
Kane et al 2019
low- and
A scoping review of health-
related stigma outcomes
for high-burden diseases in
low- and middle-income
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.
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
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
Lee et al 2020 -
Impact of mental disorders
on active TB treatment
outcomes: a systematic
review and meta-analysis.
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
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-
interventions for treatment
of common mental
disorders associated with
Tuberculosis: A systematic
Review the literature on interventions for treating
Common Mental Disorders (CMD) in people with
2021 -
Increased rates of
respiratory disease in
Establish the prevalence and association of
respiratory diseases in people with schizophrenia
Mental Health: Global Challenges Journal
ISSN 2612-2138
schizophrenia: A systematic
review and meta-analysis
including 619,214
individuals with
schizophrenia and
52,159,551 controls
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
et al 2022 -
The relationship between
mental health and risk of
active tuberculosis: a
systematic review
Examine the association between mental health
and TB disease risk to inform clinical and public
health measures.
Njie et al 2022 United
Prevalence of Tuberculosis
and Mental Disorders
Comorbidity: A Systematic
Review and Meta-analysis
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.
Assess the prevalence of suicidality and identify
the factors associated with suicidality in patients
with TB.
Alemu et
al 2023 East
Prevalence of depression in
people with tuberculosis in
East Africa: a systematic
review and meta-analysis
Examine evidence concerning the prevalence of
depression among tuberculosis patients in East
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
Mental Health: Global Challenges Journal
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
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
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.