Open access Original research

Malnutrition assessment methods in

adult patients with tuberculosis: a
systematic review
Lies ter Beek ‍ ‍,1,2,3 Mathieu S Bolhuis,4 Harriët Jager-­Wittenaar,5,6
René X D Brijan,3 Marieke G G Sturkenboom,4 Huib A M Kerstjens,1
Wiel C M de Lange,1,2 Simon Tiberi,7,8 Tjip S van der Werf ‍ ‍,1,9
Jan-­Willem C Alffenaar,10,11,12 Onno W Akkerman ‍ ‍1,2

To cite: ter Beek L, Bolhuis MS, ABSTRACT

Jager-­Wittenaar H, et al. Strengths and limitations of this study
Objectives Malnutrition is associated with a twofold
Malnutrition assessment higher risk of dying in patients with tuberculosis (TB) and
methods in adult patients ► PubMed, CINAHL and EMBASE were systematically
considered an important potentially reversible risk factor
with tuberculosis: a searched for studies in the last decade, to prevent
systematic review. BMJ Open for failure of TB treatment. The construct of malnutrition older studies describing outdated supportive care
2021;11:e049777. doi:10.1136/ has three domains: intake or uptake of nutrition; body strategies to be eligible for inclusion.
bmjopen-2021-049777 composition and physical and cognitive function. The ► As there is no instrument for ‘risk of bias assess-
objectives of this systematic review are to identify ment’ of studies on diagnosis (eg, malnutrition
► Prepublication history and
malnutrition assessment methods, and to quantify how assessment), we evaluated risk of bias by scoring
additional supplemental material
for this paper are available malnutrition assessment methods capture the international the presence of essential components required for
online. To view these files, consensus definition for malnutrition, in patients with TB. adequate assessment and reporting of malnutrition.
please visit the journal online Design Different assessment methods were identified. We ► To report on how malnutrition was assessed in
(http://​dx.​doi.​org/​10.​1136/​ determined the extent of capturing of the three domains studies on tuberculosis (TB), we quantified how
bmjopen-​2021-​049777). of malnutrition, that is, intake or uptake of nutrition, body malnutrition assessment methods capture the in-
composition and physical and cognitive function. ternational consensus definition for malnutrition, in
LtB and MSB contributed
Results Seventeen malnutrition assessment methods patients with TB.
equally.
were identified in 69 included studies. In 53/69 (77%) ► Implementation of new criteria in study protocols
Received 04 February 2021 of studies, body mass index was used as the only takes time. This implementation might take longer
Accepted 19 November 2021 malnutrition assessment method. Three out of 69 studies than the time period used in this review.
(4%) used a method that captured all three domains of
malnutrition.
Conclusions Our study focused on published articles. As hunger-­ related malnutrition caused by
Implementation of new criteria takes time, which may food-­insecurity impacts the immune system,1 10 11
take longer than the period covered by this review. malnutrition is an important risk factor for re-­ac-
Most patients with TB are assessed for only one aspect tivation of TB, with a reported 27% attributable
of the conceptual definition of malnutrition. The use risk.1 12 Malnutrition is considered an important,
of international consensus criteria is recommended potentially reversible risk factor for treatment
to establish uniform diagnostics and treatment of failure.13 Therefore, a better understanding
malnutrition.
in assessing malnutrition in patients with TB is
PROSPERO registration number CRD42019122832.
urgently needed.14
The European Society for Clinical Nutrition
and Metabolism (ESPEN) defines malnutri-
BACKGROUND tion as ‘a state resulting from lack of intake or
In 2019, tuberculosis (TB) was the worldwide uptake of nutrition that leads to altered body
© Author(s) (or their leading cause of death from a single infec- composition (decreased fat-­ free mass) and
employer(s)) 2021. Re-­use tious agent, with 10 million new patients, and body cell mass leading to diminished physical
permitted under CC BY-­NC. No
commercial re-­use. See rights
1.2 million deaths.1 TB prevalence is up to and mental function and impaired clinical
and permissions. Published by 20 times higher among people living in low-­ outcome from disease’.10 In patients with TB,
BMJ. income countries compared with high-­income two types of malnutrition may coexist: malnu-
For numbered affiliations see countries.2 TB, poverty and malnutrition are trition without disease10; and disease-­related
end of article. closely linked. Prevalence of malnutrition in malnutrition once active disease has devel-
Correspondence to
patients with TB is studied to be 50% to 57%, oped. The latter is often driven by a combina-
Dr Onno W Akkerman; and malnutrition is associated with a twofold tion of loss of appetite, malabsorption and/
​o.​w.​akkerman@​umcg.​nl risk of dying.3–9 or inflammation-­driven catabolism.10 11 A low

ter Beek L, et al. BMJ Open 2021;11:e049777. doi:10.1136/bmjopen-2021-049777 1

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body mass index (BMI) is a characteristic for chronic confirmed or clinically diagnosed TB, published
malnutrition.15 However, since malnutrition leads to loss between 1 January 2009 and 18 September 2020 were
of fat-­free mass in all individuals, including those who considered eligible for inclusion. Since the aim of the
are overweight or obese, patients with either a normal or review is to identify how malnutrition is assessed in
high BMI may be malnourished as well.10 In 2015, ESPEN current research, 2009 was chosen as a starting point.
published their first consensus on diagnostic criteria for Restricting the search to the last decade will prevent
malnutrition,15 followed by the Global Leadership Initia- older studies describing outdated supportive care strat-
tive on Malnutrition (GLIM) criteria in 2018, which egies to be eligible for inclusion.
were established by ESPEN, the American Society for Only studies that focused on adult patients with TB
Parenteral and Enteral Nutrition, la Federación Latino were included, because the assessment of malnutrition
Americano de Terapia Nutriconal, Nutricion Clinica y in children requires different methods than in adults as
Metabolismo and the Parenteral and Enteral Nutrition children are growing, and the criteria for measuring their
Society of Asia.16 nutritional status differ per by age.20
It was not until 2013 that the WHO presented their Reviews and study protocols were excluded since they
first guideline on nutritional care and support for do not present original data. Case reports and abstracts/
patients with TB. In this guideline, the WHO stressed posters were also excluded since the information provided
that all patients with active TB receive individualised on methods used in this type of publication is considered
nutritional assessment and management, including too limited.
dietary counselling and nutritional interventions, to
improve nutritional status and consequently, prevent Study selection
TB treatment failure.17 Nutritional assessment is Screening of title and abstract was done independently
a necessary step in the ‘nutritional care process’, by two authors using the Rayyan web application.21 Eval-
enabling the professional to design a treatment plan uation of the screening of the first 10 articles was used
together with the patient.18 However, the 2013 WHO to define the criteria that determine which studies were
guideline only refers to BMI as a method of assessing eligible for final inclusion. Final inclusion was based
malnutrition for adults. The important issue of lack on an independent judgement of the full text of both
of consistency and understanding of how malnutri- authors. Disagreements about inclusion were resolved
tion can be assessed in patients with TB results from, through discussion and if consensus was not reached, a
the complexity of TB being on the one hand strongly third author was consulted, which resulted in consensus
associated with malnutrition and on the other by the in all cases.
vertical and siloed nature of TB programmes.
Patient and public involvement
The primary aim of this review is to identify malnu-
No patient involved
trition assessment methods that are used in adult
patients with TB. The secondary aim is to quantify how Data collection
malnutrition assessment methods capture the inter- Data collection was performed by two authors inde-
national consensus definition for malnutrition in this pendently. The following characteristics were extracted
population. from each study: citation, first author, country, years of
publication and data collection, aim of the malnutrition
assessment, number of included patients, number of HIV
METHODS coinfected patients, disease location, drug susceptibility
The protocol for this review was registered at PROSPERO of the Mycobacterium tuberculosis isolate.
with number CRD42019122832. The Preferred Reporting
Items for Systematic Reviews and Meta-­Analyses (PRISMA) Data analysis
statement was used.19 To report on how malnutrition was assessed in studies on
TB, we determined the extent of capturing of the three
Search strategy domains of malnutrition, malnutrition included in the
In September 2020, PubMed, CINAHL and EMBASE ESPEN conceptual definition of malnutrition, that is,
were systematically searched for studies in any language. intake or uptake of nutrition (Domain A), body compo-
The search term consisted of a domain describing sition (Domain B), and physical and cognitive function
‘malnutrition’ and a domain describing ‘tuberculosis’, (Domain C).10 22 23
while excluding in vitro, animal and paediatric studies. Domain A was considered to be covered to some extent
Details of the search strategy can be found in online (+) if the method addressed nutritional intake or uptake
supplemental material 1. at all. It was considered to be covered extensively (++)
if the method addressed nutritional intake or uptake in
Inclusion and exclusion criteria depth. For domain B, weight change, BMI and anthro-
Studies in the English language that aimed to assess pometric measurements, such as skinfold measurements
malnutrition and described a method for assessment were considered covering domain B to some extent (+). It
of malnutrition in patients with microbiologically was considered extensively addressed (++) if the method

2 ter Beek L, et al. BMJ Open 2021;11:e049777. doi:10.1136/bmjopen-2021-049777

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included identification of muscle mass, lean mass or fat-­ included studies was assessed by rating the following four
free mass. Domain C was considered to be covered to characteristics:
some extent (+) if functionality was addressed. Domain ► Rationale for the assessment of malnutrition.
C was considered extensively covered (++) if physical (eg, ► Malnutrition was assessed and clear cut-­ off points
handgrip strength), mental and cognitive function tests were described in the method section. For example:
were performed, or questions about activities of daily 'malnutrition was assessed as BMI <18.5 kg/m2.
living were addressed. ► Malnutrition was reported in the results section.
As micronutrient or trace elements in serum are not ► The results with regard to malnutrition were reflected
representative for intake or uptake of protein or energy,10 on in the discussion section.
laboratory tests were not considered to attribute to any The characteristics were graded for quality of the study.
of the malnutrition domains. Serum albumin and C reac- Risk of bias was rated by - (meaning high risk of bias), +
tive protein are parameters for inflammation but are not (medium risk of bias), or ++ (low risk of bias). The scores
related to parameters of protein/energy intake or func- were added and the total was translated into very low (≥7
tionality, nor do they represent body composition and plusses), low (5–6 plusses), medium (3–4 plusses) or high
were therefore not taken into consideration. In addi- risk of bias (≤2 plusses).
tion, while prealbumin (ie, transthyretin) is sensitive for
changes in protein and energy intake, this marker is influ-
enced by inflammation activity.10 RESULTS
As there is no instrument for ‘risk of bias assessment’ The search resulted in 2175 studies after removal of dupli-
of studies on diagnosis (eg, malnutrition assessment), cates. After screening by title and abstract, 272 studies
we evaluated risk of bias by scoring the presence of were selected for a full text eligibility check. Review of the
essential components required for adequate assess- full text resulted in inclusion of 69 studies.3 24–91 A flow
ment and reporting of malnutrition. The risk of bias in diagram of the selection process is visualised in figure 1.

Figure 1 Flow diagram of the selection process of studies describing assessment in the context of malnutrition.

ter Beek L, et al. BMJ Open 2021;11:e049777. doi:10.1136/bmjopen-2021-049777 3

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used, 34/53 studies (64%) used BMI <18.5 kg/m2. In

Table 1 Cut-­off values BMI exclusively used
seven studies, no cut-­off values for BMI were described.
Studies using only BMI for Table 1 shows all the cut-­off values of BMI used as single
Cut-­off value assessment of malnutrition n=53
method.
≤20.0 kg/m2 1
<20.0 kg/m2 2 Capturing of the domains of malnutrition
<18.5 kg/m2 34 Table 2 presents the capturing of the domains of malnutri-
≤18.5 kg/m2 3 tion per assessment method.3 24–91 Uptake or intake of nutri-
<18.49 kg/m2 1
tion (A) was addressed to some extent by four methods that
2
were used in five of the 69 studies. Body composition (B)
<18.4 kg/m 1
was addressed to some extent by all but two studies, 67/69
<17.0 kg/m2 2 (97%). Two methods did not address domain B, as these
2
<16.0 kg/m 2 were methods that used self-­reporting of diet quality and
No clear cut-­off value 7 a food frequency questionnaire as assessment methods.
described in study Physical and/or cognitive functionality (C) was addressed
to some extent by only 3/69 studies (4%).
BMI, body mass index.
Only 2 of the 17 different assessment methods that were
used in the 69 studies captured all three domains of the
In total, among 69 studies, 17 different methods were definition, that is, the Subjective Global Assessment was
used to assess malnutrition. Four studies used multiple (ie, used in two studies and the Mini Nutritional Assessment
two to four) methods to assess malnutrition. Four studies was used in one study. Forty-­one studies (59%) assessed
used multiple criteria but integrated these together into malnutrition for the purpose of their primary aim. The
one method to perform an assessment. In 53/69 (77%) three studies that used a method that captured all three
of the studies, BMI was used as single assessment method. domains of the definition, had a primary aim related to
Among these studies eight different cut-­off points were malnutrition.

Table 2 Comparison of 17 different assessment methods by malnutrition domain capturing

Domains A B C
Intake or uptake of Body Physical and
Description of domain nutrition composition cognitive function Total
PIBW, BMI, albumin, TLC, cholesterol, Hb – + – +
Weight change – + – +
BMI & MUAC – + – +
Self-­report of diet quality + – – +
MNA ++ + ++ +++++
MUST + + – ++
AMA – ++ – ++
BMI/albumin – + – +
BMI, MUAC, TSF, MAMC, Hb, Ht, albumin, – + – +
total protein, globulin, iron fixation capacity,
retinol, tocopherol Zn, SE, Fe
MAMC – ++ – ++
Underweight – + – +
TSF/TST – + – +
SGA ++ ++ ++ ++++++
BMI – + – +
BIA: (body fat%) – + – +
MUAC – + – +
FFQ ++ – – ++
AMA, arm muscle area; BIA, bio-­electrical impedance analysis; BMI, body mass index; Fe, iron; FFQ, Food Frequency Questionnaire;
Hb, haemoglobin; Ht, haematocrit; MAMC, mid arm muscle circumference; MNA, mini nutritional assessment; MUAC, mid upper arm
circumference; PIBW, percent ideal body weight; SE, selenium; SGA, subjective global assessment; TLC, total lymphocyte count; TSF, triceps
skin fold ; TST, triceps skinfold thickness; Zn, zinc.

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the predominant type of malnutrition. Disease-­ related

Table 3 Subanalysis of malnutrition assessment methods
malnutrition is a (sub)acute condition, in which loss
Use of an of weight and muscle/fat-­free mass does not automat-
BMI as assessment
ically result in a low BMI, while loss of weight and fat-­
the only method that
Year of No of assessment attributes to free mass are related to poor clinical outcomes including
start data studies method three domains increased morbidity and mortality.15 92 With the current
collection (n=69) N% % global overweight and obesity epidemic, patients with
catabolic diseases such as TB may lose more than 20%
2000–2004 9 9 89 –
of their weight and muscle mass within 3–6 months, and
2005–2009 12 7 58 – still show BMI values at or above normal range.93 When
2010–2014 14 13 93 – assessing malnutrition in patients with TB solely based on
2015–2019 19 15 79 – BMI, these patients will not be identified when they are
No available 15 10 67 3 20 malnourished, despite the therapeutic and prognostic
data on implications of malnutrition.94
year of data This review indicates that the international criteria
collection for the assessment of malnutrition have not yet found
Total 69 53 77 34 their way into studies with patients with TB. The 2013
WHO guideline on nutritional care only refers to BMI
as a method of assessing malnutrition for adults, which
may contribute to the status quo. BMI is by far the most
A descriptive subanalysis, as shown in table 3, was
frequently used assessment method for malnutrition
performed to compare studies regarding their use
(77%) in studies with patients with TB. Only a few (4%)
of assessment tools, by their period of data collec-
of the studies that reported on the assessment methods
tion.3 24–91 No differences were found between 5-­ year
addressed all domains of the conceptual definition of
periods regarding the use of BMI as the only assessment
malnutrition. For the studies performed after the ESPEN
method. The studies that used methods that capture all
criteria of 201595 and the GLIM criteria of 2018,16 this
three domains of the ESPEN definition of malnutrition
may be explained by the fact that the WHO does not
did not describe when their data was collected Of the 69
yet refer to these criteria in their communications. The
included studies, 18 studies (26%) were on inpatients, 26
GLIM criteria have been developed for global use and is
studies (38%) on outpatients, 7 (10%) on both type of
therefore recommended to be used in any setting for all
patients and in 18 studies (26%) the type of patients was
patients with TB. The GLIM framework does not include
not described.
the domain of functionality as criterion.
Risk of bias assessment There are some limitations in our study. First, our study
Online supplemental material 2 shows the risk of bias focused on published articles and not on the underlying
assessment and details of the 69 included studies.3 24–91 study protocol. In some cases, detailed information on
Twenty-­one of the 69 studies (30%) did not describe the the assessment and operationalisation of malnutrition
rationale for the assessment of malnutrition. Fifteen of might be available in the study protocol, however, it was
the 69 studies (22%) described their assessment method not addressed in the article making it unavailable to the
without clear cut-­off values. Risk of bias was very low in public domain. Second, implementation of new criteria
24 studies (35%), low in 20 studies (29%), medium in 20 in study protocols takes time. This implementation might
studies (29%) and high in five studies (7%). take longer than the time period used in this review.
Third: research and clinical practice are different settings
and the results from our review are not a reflection of
DISCUSSION clinical practice. Nevertheless, we postulate that BMI is
This review showed that most patients with TB are used the most commonly used method in clinical practice
assessed for only one aspects of the construct of malnutri- since the WHO recommends that BMI is the method to
tion. BMI is often used assessment method for malnutri- assess undernutrition/malnutrition.
tion in studies with patients with TB, even though it only Awareness of the presence of malnutrition and concept
partly covers just one malnutrition domain (domain B). of malnutrition assessment in healthcare professionals
In addition, while some studies did not report a cut-­off working with patients with TB needs improvement.
value for BMI, in other studies different cut-­off values for Future studies regarding malnutrition assessment in
BMI were used, therefore making it difficult to compare patients with TB should aim at implementation of inter-
these studies. The use of BMI could be justified from a national consensus criteria regarding malnutrition assess-
public health perspective, since a low BMI is a charac- ment. Using the same terminology for malnutrition may
teristic of chronic malnutrition that involves loss of both make a difference to our patients, improve outcomes as
fat and muscle tissue.15 However, the use of BMI alone well as reduce chronic sequelae and help to end TB.
for assessing malnutrition in this population is debat- It should be stressed that we need to agree on using
able. In clinical settings, disease-­related malnutrition is standardised methods for malnutrition assessment and

ter Beek L, et al. BMJ Open 2021;11:e049777. doi:10.1136/bmjopen-2021-049777 5

 Open access

interventions. However, malnutrition assessment should Supplemental material This content has been supplied by the author(s). It has
always be preceded by malnutrition screening with a vali- not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been
peer-­reviewed. Any opinions or recommendations discussed are solely those
dated tool (online supplemental material 3).16 of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and
In conclusion, most studies in adult patients with TB responsibility arising from any reliance placed on the content. Where the content
did not describe their assessment method for malnutri- includes any translated material, BMJ does not warrant the accuracy and reliability
of the translations (including but not limited to local regulations, clinical guidelines,
tion. Most patients with TB are assessed for only one or
terminology, drug names and drug dosages), and is not responsible for any error
two aspects of the conceptual definition of malnutrition. and/or omissions arising from translation and adaptation or otherwise.
Various methods for assessing of malnutrition have been Open access This is an open access article distributed in accordance with the
used, and only a very small proportion of the published Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which
studies on TB used an assessment method that fully permits others to distribute, remix, adapt, build upon this work non-­commercially,
reflects the definition of malnutrition. The use of inter- and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the use
national consensus criteria is recommended to establish is non-­commercial. See: http://​creativecommons.​org/​licenses/​by-​nc/​4.​0/.
systematic and uniform diagnostics and treatment of
malnutrition. ORCID iDs
Lies ter Beek http://​orcid.​org/​0000-​0002-​5058-​920X
Tjip S van der Werf http://​orcid.​org/​0000-​0002-​4824-​1642
Author affiliations Onno W Akkerman http://​orcid.​org/​0000-​0001-​5638-​9260
1
Department of Pulmonary Diseases and Tuberculosis, University of Groningen,
University Medical Center Groningen, Groningen, The Netherlands
2
Tuberculosis Center Beatrixoord, University of Groningen, University Medical Center
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