Systematic Review

Effectiveness of nutritional support to improve treatment

adherence in patients with tuberculosis: a systematic review

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Fasil Wagnew 1,2,*, Darren Gray3, Tsheten Tsheten 1
, Matthew Kelly1, Archie C. A. Clements4, and
Kefyalew Addis Alene5,6
1
National Centre for Epidemiology and Population Health, College of Health and Medicine, The Australian National University, Canberra,
Australian Capital Territory, Australia
2
College of Health Sciences, Debre Markos University, Debre Markos, Ethiopia
3
Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
4
Penninsula Medical School, University of Plymouth, Plymouth, United Kingdom
5
Geospatial and Tuberculosis Research Team, Telethon Kids Institute, Nedlands, Western Australia, Australia
6
Faculty of Health Sciences, School of Population Health, Curtin University, Bentley, Western Australia, Australia
*Correspondence: F. Wagnew. E-mail: fasilw.n@gmail.com; FasilWagnew.Shiferaw@anu.edu.au.

Context: Nutritional interventions substantially improve tuberculosis (TB) treatment

outcomes and prevent complications. However, there is limited evidence about the
connections between having nutritional support and TB treatment adherence.
Objective: The aim of this study was to determine the effectiveness of nutritional
support in improving treatment adherence among patients with TB. Data
Sources: Databases, including PubMed, Embase (Ovid), Web of Science, and
Scopus, were comprehensively reviewed to identify relevant studies reporting the
impacts of nutritional support on TB treatment adherence. Data Extraction: Two
authors independently screened the title, abstracts, and full article texts to identify
eligible studies and assess the risk of bias. Observational and interventional studies
were included. Data Analysis: A narrative synthesis approach was used to sum-
marize the findings qualitatively. Results: From the search, 3059 publications were
identified; of these, 8 studies were included in this systematic review. Three types of
nutritional interventions were identified: food baskets (eg, energy, micronutrient- or
macronutrient-enriched food support), nutritional advice and guidance, and incen-
tives for buying foods. Although 5 studies reported that nutritional support signifi-
cantly improved treatment adherence in patients with TB, 3 studies showed that
nutritional support had no effect on TB treatment adherence. Conclusions:
Providing nutritional support may improve adherence to TB treatment. However,
more well-powered, high-quality trials are warranted to demonstrate the effect of
nutrition support on cost-effectively improving adherence to TB treatment.
Systematic Review Registration: PROSPERO registration no. CRD42023392162.
Key words: nutritional support, treatment adherence, TB, systematic review.

INTRODUCTION of morbidity, mortality, and cost burden.1 According to

reports from the United States, poor adherence to treat-
Poor adherence to tuberculosis (TB) treatment is 1 of ment is responsible for 125 000 deaths, 10% of hospital
the major public health concerns that increases the risk admissions, and $100 billion in healthcare costs every

C The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.
V
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/
licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly
cited.

https://doi.org/10.1093/nutrit/nuad120
1216 Nutrition ReviewsV Vol. 82(9):1216–1225
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year.2,3 Although research has been conducted over the effectiveness of these strategies in improving adherence
past few years to improve medication adherence rates, to TB treatment merits special consideration.
there has not been much change in treatment adher- Previous studies have provided evidence that
ence.4,5 In particular, drug nonadherence is markedly nutritional intervention can improve treatment out-
higher among patients with chronic diseases as com- comes and its prognostic markers among patients with
pared with those with acute diseases.6,7 TB.30–32 However, evidence about the potential of nutri-

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Many patients with TB do not complete the full tional support to improve adherence to TB treatment
regimen necessary to recover from the disease. Previous remains limited and inconclusive.23 Therefore, in this
studies estimated that the prevalence of poor adherence systematic review, we aimed to examine the effective-
to TB treatment ranged from 33% to 50%.8,9 This is a ness of nutritional support to improve treatment adher-
significant contributor to prolonged transmission of ence in patients with TB.
TB, amplification of drug resistance, hampered treat-
ment success, and catastrophic economic effects, espe-
cially in the presence of comorbidities.10,11 A recent METHODS
meta-analysis also reported that missing more than 10%
of doses of the prescribed TB drugs causes a 6-fold This systematic review was developed on the basis of
higher risk of poor treatment outcomes.12 the Preferred Reporting Items for Systematic Reviews
There are multiple factors that can be associated and Meta-analysis (PRISMA) recommendations33 and
with poor adherence to TB treatment, of which3 are was registered with the International Prospective
major factors: patient status, healthcare delivery sys- Register of Systematic Reviews (PROSPERO; identifier
tems, and healthcare providers.13–16 Nutrition-related
CRD42023392162). The PRISMA checklist is provided
factors such as malnutrition and a weakened immune
in Table S1 in the Supporting Information online.
system are reported as major contributors of poor treat-
ment adherence.17,18 In addition, household food inse-
curity is a significant contributor to TB treatment
Study selection and eligibility criteria
nonadherence in low- and middle-income coun-
tries.19,20 It can be challenging for people with food Observational and interventional studies were included
insecurity to complete their TB treatment for an according to the research questions developed using the
extended time (ie, a minimum of 6 months). A qualita-
PICOS (Population, Intervention, Comparator,
tive study in Swaziland showed that most patients with
Outcomes, and Studies) format34 (Table 1). Conference
food insecurity discontinued their treatment because it
and meeting abstracts without adequate information,
increased their appetite and they already had insuffi-
articles in languages other than English, animal studies,
cient access to food.21 The presence of food insecurity
systematic reviews, and those with insufficient informa-
leading to undernutrition is also associated with ampli-
fied disease severity, compromised treatment outcomes, tion on the primary outcomes of interest were
and heightened mortality rates.17,22 Thus, interventions excluded.
focusing on food security could improve adherence to
TB treatment.23,24 Providing nutritional support to
Search strategy
patients and their families is a vital motivator that
enhances adherence to treatment plans and serves as a
A comprehensive search was undertaken in the
safeguard against the potentially overwhelming finan-
PubMed, Embase (via Ovid), Web of Science, and
cial burden caused by TB.25
A comprehensive intervention aiming to maximize Scopus databases for relevant studies published between
adherence to TB treatment is needed to prevent treat- January 1, 2000, and January 1, 2023. Grey literature
ment interruption and the transmission of the disease and reference lists of identified articles were hand-
in the community.26 Directly observed treatment, searched for additional relevant studies missed in the
short-course (DOTS), has been 1 of the most commonly initial search strategy.
used interventions since 199327 to increase adherence The search strategy combined key terms such as
to TB treatment, despite that it requires further enablers “tuberculosis,” “nutritional intervention,” “food
such as financial and food support.28 Accordingly, a support,” “treatment adherence,” and “treatment com-
variety of public health program strategies, including pliance.” The full search strategies for each database are
financial incentives, nutrition support, and digital tech- provided in the Table S2 in the Supporting Information
nologies, have also been implemented to improve online. Searches were conducted between December 2,
adherence to TB drugs.29 Understanding the 2022 to January 30, 2023.

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 Table 1 PICOS criteria for inclusion of studies
Parameter Inclusion criteria
Population Patients with pulmonary tuberculosis aged 15 y, based on the World Health Organization classification of
adults,61 with acid-fast bacilli sputum smear-positive or smear-negative, with or without comorbidities,
were considered.
Intervention Additional food support, macronutrient or micronutrient supplementation, incentives for groceries, and

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nutritional guidance or advice, which seeks to improve or assist treatment adherence
Comparator Patients with tuberculosis who did not receive nutritional support
Outcomes Studies on nutritional support targeted at the improvement of adherence to tuberculosis treatment
Study design Randomized controlled trials, quasi-experimental, cohort, case–control, and cross-sectional studies

Risk of bias in the hand-search of reference lists of the included

studies. After the removal of duplicates, a total of 2926
Risk of bias was evaluated using 2 published quality- records were screened for title and abstract, which
rating scales: the Cochrane risk of bias 2 (RoB 2)35 for resulted in 68 articles for full-text reviewing. Finally, in
randomized controlled trials (RCTs) and the Risk of the full-text review, 5 interventional studies37–41 and
Bias in Nonrandomized Studies of Interventions 342–44 retrospective comparative studies met the inclu-
(ROBINS-I) tool36 for non-RCTs. Two authors (F.W. sion criteria, comprising 1467 participants. A flowchart
and T.T.) independently evaluated the risk of bias for showing the selection process of articles is provided in
each included article. When there was any disagree- Figure 1.
ment, the 2 authors reached a decision by consensus.
Studies were categorized as at low risk of bias when all Characteristics of the included studies
important contents were evaluated and found to be at
low risk. A risk of bias was assessed what the authors The characteristics of the 8 included studies are provided
reported having done for each domain in each study in Table 2.37–44 All included studies were conducted in
and then made a decision as to whether the study as low- and middle-income countries; 4 studies were con-
“low,” “high,” or “unclear” risk of bias. The risk of bias ducted in the upper-middle-income countries of
assessment tools are listed in Table S3 in the Supporting China,38 Russia,44 Georgia,42 and Brazil43; and 4 were
Information online. conducted in the lower-middle-income countries of
Senegal,37 Tanzania,39 India,41 and Timor-Leste (East
Data extraction and summarization Timor).40 The included studies focused on the most vul-
nerable groups of population. For instance, 3 stud-
After removing duplicate articles from the Endnote 20 ies37,39,41 were conducted with patients with TB and
software library, 2 authors (F.W. and T.T.) independently human immunodeficiency virus (HIV) coinfection, and
screened the title, abstract, and full text of each article to 340,42,44 were conducted with a high proportion of home-
identify eligible studies and extracted the required infor- less or malnourished adults. Only 2 studies38,43 involved
mation from the included articles using a standardized members of the general adult population with TB.
Joanna Briggs Institute data extraction form. All included studies were published between 2001 and
Discrepancies were resolved through discussion. Data on 2021. Studies varied in sample size from 26 participants in
primary author, year of publication, country of study, Senegal37 to 518 participants in Russia.44 Five37–39,41,43 of
study period, study design, sample size, types of nutri- the 8 studies (62.5%) were underpowered; they included
tional interventions, duration of follow-up, and out- fewer than 75 participants per arm (Table 2).
comes were extracted by the reviewers using a
standardized data extraction format. Because of the pres- Intervention types and compositions
ence of a high degree of heterogeneity across the
included studies, a meta-analysis was not performed. The included studies used a variety of nutritional inter-
Instead, a narrative synthesis was used to qualitatively ventions. Six studies used interventions combining
summarize the effect of nutritional support on TB treat- high-energy food baskets and micronutrient supple-
ment adherence. mentations,37,39–41,43,44 comprising varieties of meals,
including meat, powdered milk, red kidney beans, rice,
RESULTS locally prepared cereals, and vitamin- or mineral-
enriched biscuits.
Initially, 3048 articles were obtained from the electronic A study in China38 used interventions combining
databases search and 11 additional articles were found dietary guidance, which advised patients to consume

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Figure 1 Flow diagram of the literature search process.

high-protein foods and vitamin B–enriched foods, and intervention group was significantly higher than that of
avoid smoking and alcoholic drinks. Last, Bock et al42 the comparator group. In addition, 3 studies reported
used incentives for groceries to improve TB treatment that the proportion of poor adherence was lower in the
adherence. intervention group than in the comparator group:
Of the 8 included studies, 5 used clinic-based 12.9% vs 30.3% in Brazil,43 27% v 67% in Russia,44 and
DOTS to assess treatment adherence,40–44 and 2 studies 3.9% vs 12.3% in Tanzania.39
relied on patient self-reporting.37,38 Only 1 study did However, 3 other studies37,40,41 concluded that treat-
not provide details on the methods used for measuring ment adherence was not significantly associated with the
treatment adherence.39 nutritional support compared with those who did not
receive the nutritional support. Of those, 2 studies37,40 did
Effectiveness of nutritional support on tuberculosis not have clear control and intervention groups. Both
treatment adherence groups received nutritional interventions: the intervention
group received food baskets, and the control group
Two studies38,42 concluded that the proportion of received nutritional advice. Studies in Senegal37 and India41
patients with good treatment adherence in the included only patients with TB and HIV coinfection.

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Table 2 Characteristics and summary description of included studies in assessing the effectiveness of nutritional support to improve treatment adherence in patients with
tuberculosis
Reference Country Study design Participants, Intervention group Comparator Follow-up Outcomes of interest and main
and period N group period findings
Martins et al, Timor-Leste RCT 270 Patients received additional Patients 8 mo Primary outcome included the
200940 (East Timor) November– food every time they attended received completion of treatment.
July 2006 the clinic. In the intensive nutritional Secondary outcomes included
phase, each day they were advice. adherence to treatment,
provided at the clinic 1 bowl weight gain, and clearance of
of feijuada, meat, red kidney sputum smears.
beans, and vegetable stew Findings: In this setting food
with rice. supplementation did not sig-
In the continued phase, patients nificantly improve treatment
received unprepared food to adherence or treatment
take home (red kidney beans, outcome.
rice, and oil) (1 meal/d per
adult).
Benzekri Senegal RCT 26 Patients received a monthly Patients 6 mo Primary outcome included the
et al, June–August food basket consisting of 5 kg received treatment adherence.
201937 2017 of cowpeas (Vigna unguicu- RUTF. No significant effect has been
lata) and 3 kg of rice grown found; medication adherence
in Senegal, 1.5 L of vegetable for 7 d RUTF (96.8%; food bas-
oil, and 1.6 kg of powdered ket, 95.1%) and week 4 of
milk. RUTF (98%; food basket,
98.4%).
Hu et al, China Interventional 123 Patients received health educa- Patients in the 6 mo Findings: The treatment
202138 studies tion and dietary guidance comparator adherence rate of patients
October 2019– about nutritious foods, vita- arm with TB in the intervention
October mins, and avoiding alcohol received group (96.83%) was signifi-
2020 use. regular care cantly higher compared
and food with the control group
advice. (75%).
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Filho et al, Brazil Historical com- 142 Patients received baskets of Patients At the end of TB treatment outcome was a
200943 parative nonperishable food, distrib- received TB primary outcome of interest.
study uted monthly. only the treatment Findings: The statistical compar-
September standard TB ison between the 2 groups
2001–July treatment revealed that the rate of poor
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2006 care. adherence was markedly

lower in the intervention
group (12.9% vs 30.3%).
(continued)
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Nutrition ReviewsV Vol. 82(9):1216–1225

Table 2 Continued
Reference Country Study design Participants, Intervention group Comparator Follow-up Outcomes of interest and main
and period N group period findings
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Sudarsanam India RCT 103 Patients received a locally pre- Patients in the After TB treat- The primary outcome of interest
et al, January– pared cereal–lentil mixture comparator ment end was TB treatment outcomes.
201141 November providing 930 kcal and a mul- arm Secondary outcomes were body
2005 tivitamin micronutrient received composition, adherence and
supplement. only stand- condition on follow-up 1 y
ard TB after cessation of TB therapy
drugs. and supplementation.
Findings: The overall adherence
to TB treatment was not statis-
tically significance between
the 2 groups(P ¼ 0.197).
G€arden et al, Russia Historical com- Intervention: 142 Patients received food packages Patients 6 mo The primary outcome of interest
201344 parative Control: 376 once a day 5 d/wk, which received was adherence to TB
study comprised canned meat, only stand- treatment.
December bread, butter, egg, soup with ard TB drugs Findings: Patients receiving
2001– cream, juice, tea, and yogurt. food supports had a good
January 2004 treatment adherence
Jeremiah Tanzania RCT 100 Patients received a nutritional Patients After 2 mo Primary outcome was rifampicin
et al, September supplement in the form of received exposure. Adherence to TB
201439 2010–August high-energy and vitamin/min- only stand- treatment was also reported.
2011 eral-enriched biscuits for 2 ard TB Poor treatment adherence was
mo. treatments. higher among patients who
were not receiving nutritional
supports (3.9% vs 12.3%).
Bock et al, Georgia Historical com- 185 Patients received a $5 grocery Patients At the end of There was a strong association
200142 parative coupon for each DOT received TB between the use of incen-
study appointment. only stand- treatment tives and increased
November ard TB adherence.
1996– treatments.
October
1997
Abbreviations: DOT, directly observed treatment; RCT, randomized, controlled trial; RUTF, ready-to-use therapeutic food; TB, tuberculosis.
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 There were substantive heterogeneities in study set- spread and preventing drug-resistant TB. This is war-
tings, types of interventions, and adherence measures ranted for successful treatment outcomes and a key ele-
among the included studies, and the data were not simi- ment to achieving the World Health Organization’s
lar enough to combine different studies. Therefore, End TB targets.45 However, evidence indicates that
there was insufficient common ground for estimating many patients with TB discontinue treatment during
pooled effect sizes using meta-analysis. the follow-up period. Adherence is a complicated phe-

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nomenon that can be associated with multiple factors at
Assessment of risk of bias the individual and institutional levels.46 Even achieving
the global End TB goal will be challenging if nonadher-
Assessment of methodological quality and risk of bias ence is left unaddressed. The DOTS strategy has long
in the RCTs reviewed is shown in Table S3 in the been helpfully implemented in many countries.
Supporting Information online. All trials reported suffi- However, additional measures might be required,
cient details of random sequence generation and a low including financial and food support.47,48
selection bias was found because all publications of In this review of the nutritional supports described
RCTs provided information about the processes of ran- in 8 studies, 6 studies focused on food baskets highly
dom sequence generation in the studies. Blinding to enriched with macro- or micronutrients, 1 on nutri-
participant’s performance bias was high for 2 trials,40,41 tional advice and guidance, and 1 on incentives for buy-
low for 1 trial,37 and unclear for the remaining trial.39 ing groceries. Accordingly, 5 studies reported
Overall, there was low attrition bias (incomplete out- significantly improved treatment adherence among
come data) across the trials because all trials reported a patients receiving support compared with patients with-
low proportion of dropout rates (see Table S3 in the out nutritional support, as evidenced by an increased
Supporting Information online). proportion of adherence or markedly decreased nonad-
Risk-of-bias assessment for non-RCTs is presented herence. This finding is consistent with a previous
in Table S3 in the Supporting Information online. Bias review of patients with TB and HIV coinfection, which
due to confounding was high across studies except that found improved adherence to treatment among those
of Hu et al.38 Measurement of outcome bias was high who received food support.23 Similar studies among
across the studies because the evaluators were aware of patients living with HIV found a positive relationship
interventions. Studies varied with respect to attrition between food support and adherence to antiretroviral
bias; risk of attrition bias was low in 2 studies,38,43 therapy.49,50 In addition, a systematic review of qualita-
whereas that of the remaining 2 studies42,44 was unclear. tive studies illustrated that a food shortage was identi-
The included studies were unclear regarding reporting fied as a common barrier to treatment adherence for
bias because the protocols were unavailable online (see patients living with TB.24 This could be because inad-
Table S3 in the Supporting Information online). equate nutrition support is likely to increase undernu-
Further details of the quality assessment for the RCTs trition and the adverse effects of TB treatment,19 which,
and non-RCTs are provided in the Table S3 in the in turn, hamper adherence to and completion of care
Supporting Information online. and treatment. Therefore, it is important to note that
food support has multiple roles: it is an enabler to ini-
DISCUSSION tiate and continue TB treatment, contributes to manag-
ing malnutrition,51 and mitigates the social and
Given the paucity of evidence of interventions improv- financial burdens of TB at the individual and household
ing treatment adherence, we aimed in this systematic levels.52
review to examine the recent literature focusing on In contrast, 337,40,41 of the 8 studies reported no
nutritional support strategies that have been determined significant association with improved adherence to TB
to enhance treatment adherence among patients with treatment when nutritional intervention was added to
TB. Eight studies comprising a total of 1467 participants the standard TB treatments. This nonsignificant thera-
were included. Five of the 8 studies showed that nutri- peutic effect might be due to various factors. For
tional support was associated with improved adherence instance, more than 60% of all included studies had
to TB treatment. However, the remaining 3 studies inadequate sample sizes, which may have resulted in
showed no significant effect on improving adherence to missing a meaningful difference in treatment adherence
TB treatment. between groups even when improving treatment adher-
Globally, enhancing adherence to TB treatment ence substantially. Most importantly, 2 of 3 studies37,40
and then getting a successful treatment outcome are did not have clear control and intervention groups,
vital public health goals. Accordingly, greater than 90% because both groups received nutritional interventions.
treatment adherence is a target for controlling the Also, the 2 included studies37,41 with a nonsignificant

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effect on adherence were carried out among patients patients to successfully complete their TB treatment.
with TB and HIV coinfection that may need special Therefore, high-quality, well-powered, and multicentric
consideration. For instance, in previous trials examin- clinical trials of nutritional support on improving
ing the effect of nutritional interventions on TB treat- adherence to TB treatment are urgently warranted to
ment outcomes among patients with TB and HIV confirm this finding. Such trials should ideally stratify
coinfection, no significant effect was found.53–55 This by comorbid status (eg, HIV) to examine differential

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may indicate that the nutritional intervention in dose-response effects in these key, high-risk popula-
patients with TB and HIV coinfection may need an tions. Implementation research will also be relevant to
extra dose to be effective, owing to malabsorption and evaluate the feasibility, acceptability, and cost-
increased utilization of nutrients.56 Patients with TB effectiveness of the various form of nutritional support
and HIV coinfection may also need close follow-up in diverse communities and various geographical areas.
because they may have been sicker and less able to take
their prescribed medications and nutritional Limitations of the study
interventions.
Furthermore, marked heterogeneity in the compo- This systematic review has some important limitations
sition, form, and amount of nutritional interventions that must be kept in mind when interpreting the find-
across the countries also contributed to these observed ings. Despite an extensive search, we only found 8 rele-
variabilities. A meta-analysis was not performed, due to vant articles. The majority of the included studies had a
the presence of high heterogeneity between the studies. limited sample size, which could potentially compro-
Therefore, future clinical trials would be needed to con- mise the precision of these findings. As well, only
firm these findings. articles published in the English language were
Most recently, food support is mentioned in the
included, which may miss relevant articles not pub-
World Health Organization TB treatment guidelines,20
lished in English. In addition, some studies used patient
but it is not well explained in the context of improving
self-report to measure treatment adherence in the con-
adherence to TB treatment. In addition, material incen-
text of clinical care. However, this method may overes-
tives, in combination with other forms of social sup-
timate adherence score as compared with objective
port, are thought to improve adherence and treatment
adherence measures such as electronic drug prescrip-
outcomes for various diseases by directly influencing
tions and laboratory tools. Wide heterogeneities in the
patients’ health behaviours.57,58 This approach is also
description of interventions and outcome evaluations
essential for patients with TB because the disease mainly
affects poor people. Patient-centered support interven- were observed across the studies, so a meta-analysis and
tions such as enablers and food incentives should be a stratified analysis were not performed. Furthermore,
incorporated into the current TB control program to this systematic review did not provide a detailed review
help patients overcome some of the economic con- of studies that highlighted exclusively on cost, feasibil-
straints affecting their treatment adherence.8 For ity, and acceptability of the interventions.
instance, the World Health Organization developed a
post-2015 Global TB strategy that explicitly encom- CONCLUSION
passes the role of universal health coverage and social
protection, including food support.59 The Government Providing nutritional support may improve adherence
of India has also announced a monthly direct benefit to TB treatment. However, more research with adequate
transfer for patients with TB to enable the purchase of power is warranted to demonstrate the effect of nutri-
high-protein foods.60 Therefore, integrated interven- tional support on cost-effectively improving adherence
tional strategies have to be cost-effectively tailored to to TB treatment. The body of research supporting nutri-
the clinical practice; otherwise, benefits are substantially tional supports designed to increase TB treatment
reduced in usual clinical practice with low adherence adherence is incompletely understood, with 5 studies
rates. Accordingly, standardized nutritional supports reporting improved adherence to TB medications in the
may provide enormous benefits to improve TB treat- intervention group, and 3 reporting no association
ment adherence in areas with a high prevalence of food between the 2 groups.
insecurity and undernutrition.
Acknowledgments
Implications for future research
We thank the Australian National University library for
Considering the growing global risk of drug-resistant offering us with a wide range of available online
TB, it is crucial to prioritize efforts aimed at assisting databases.

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