Tropical Medicine and International Health doi:10.1111/j.1365-3156.2009.02364.

volume 14 no 10 pp 1173–1189 october 2009

Systematic Review

Pneumonia in severely malnourished children in developing

countries – mortality risk, aetiology and validity
of WHO clinical signs: a systematic review
Mohammod Jobayer Chisti1,2,*, Marc Tebruegge3,4,5,*, Sophie La Vincente2,5, Stephen M. Graham2,5
and Trevor Duke2,5,6

1 Clinical Science Division, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh
2 Centre for International Child Health, Department of Paediatrics, University of Melbourne, Royal Children’s Hospital,
Melbourne, Australia
3 Infectious Diseases Unit, Department of General Medicine, Royal Children’s Hospital, Melbourne, Australia
4 Department of Paediatrics, University of Melbourne, Australia
5 Murdoch Children’s Research Institute (MCRI), Melbourne, Australia
6 Discipline of Child Health, School of Medicine, University of Papua New Guinea, Port Moresby, Papua New Guinea

Summary objectives To quantify the degree by which moderate and severe degrees of malnutrition increase the
mortality risk in pneumonia, to identify potential differences in the aetiology of pneumonia between
children with and without severe malnutrition, and to evaluate the validity of WHO-recommended
clinical signs (age-specific fast breathing and chest wall indrawing) for the diagnosis of pneumonia in
severely malnourished children.
methods Systematic search of the existing literature using a variety of databases (Medline, EMBASE,
the Web of Science, Scopus and CINAHL).
results Mortality risk: Sixteen relevant studies were identified, which universally showed that
children with pneumonia and moderate or severe malnutrition are at higher risk of death. For severe
malnutrition, reported relative risks ranged from 2.9 to 121.2; odds ratios ranged from 2.5 to 15.1.
For moderate malnutrition, relative risks ranged from 1.2 to 36.5. Aetiology: Eleven studies evaluated
the aetiology of pneumonia in severely malnourished children. Commonly isolated bacterial pathogens
were Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and
Haemophilus influenzae. The spectrum and frequency of organisms differed from those reported in
children without severe malnutrition. There are very few data on the role of respiratory viruses and
tuberculosis. Clinical signs: Four studies investigating the validity of clinical signs showed that
WHO-recommended clinical signs were less sensitive as predictors of radiographic pneumonia in
severely malnourished children.
conclusions Pneumonia and malnutrition are two of the biggest killers in childhood. Guidelines for
the care of children with pneumonia and malnutrition need to take into account this strong and often
lethal association if they are to contribute to the UN Millennium Development Goal 4, aiming for
substantial reductions in childhood mortality. Additional data regarding the optimal diagnostic
approach to and management of pneumonia and malnutrition are required from regions where death
from these two diseases is common.

keywords aetiology, chest indrawing, fast breathing, malnutrition, mortality, pneumonia, sensitivity,
specificity

*Both authors considered joint first authors.

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Tropical Medicine and International Health
M. J. Chisti et al. Pneumonia in severely malnourished children
Introduction
Pneumonia is the biggest single cause of childhood deaths
under the age of five years in developing countries
(UNICEF ⁄ WHO 2006; Graham et al. 2008). Globally
there are more than nine million deaths among the under-
five population each year, of which about three million are
due to pneumonia (Black et al. 2003; Bryce et al. 2005).
Of these deaths, 90–95% occur in developing countries
(Williams et al. 2002; Mulholland 2003). The success of
the fourth United Nations Millennium Development Goal
4 (MDG 4), which aims to reduce child mortality by
two-thirds by 2015, will therefore depend in no small part
on a reduction of this enormous burden of child deaths
from acute respiratory infection.
Several interventions that aim to reduce the global
burden of deaths from pneumonia have been identified as
priorities. These include improving nutrition and rates of
breast-feeding, reducing indoor air-pollution, reducing
housing overcrowding, improving access to antibiotics,
care-seeking behaviour and referral practices, and
improving the quality of case management (Sazawal &
Black 1992; Mulholland 2007; Dherani et al. 2008; Roth
et al. 2008). If pneumonia case management is to have a
significant impact on global child mortality it is pertinent
that it is appropriate for those groups of children at highest
risk of death – neonates, HIV-infected and malnourished
children (Graham et al. 2008). Among these, malnourished
children represent the largest group. More than half of all
child deaths are associated with malnutrition. Pneumonia
is common in malnourished children and frequently
associated with fatal outcome (Rice et al. 2000; Bryce et al.
2005; Loeb & High 2005; Nannan et al. 2007). Of
children with malnutrition requiring hospital admission,
up to two-thirds are diagnosed with pneumonia (Shimeles
& Lulseged 1994; Ahmed et al. 1999).
With this review, we sought to explore the interaction
between pneumonia and malnutrition. Specifically, we
aimed to quantify the degree by which moderate and severe
malnutrition increases the mortality risk in pneumonia, to
identify differences in pneumonia aetiology between
severely and not severely malnourished children, and to
evaluate the validity of clinical signs recommended for the
diagnosis of pneumonia by the World Health Organization
(WHO) in severely malnourished children.
Methods
We conducted a search of the existing literature to identify
reports focusing on severe malnutrition and pneumonia.
Severe malnutrition was defined as follows: <-3 z score of
weight for age (W ⁄ A) or weight for height (W ⁄ H) of the
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median of the National Centre for Health Statistics
(NCHS) or <60% W ⁄ A of the median of the NCHS or
according to Wellcome classification (Jelliffe 1966; Well-
come Trust International Working Party 1970). Moderate
malnutrition was defined as <-2 to ‡-3 Z score of W ⁄ A or
W ⁄ H of the median of the NCHS or 60–74% W ⁄ A of the
median of the NCHS. The following databases were
searched: PubMed (1955–2008), EMBASE (1980–2008),
ISI Web of Science (1955–2008), Scopus (1950–2008)
and CINAHL (1981–2008). No limits were set, except
for the search of EMBASE, which was limited by age
(details below). The search strategies and outcomes are
summarised in Table 1. The searches were conducted in
January 2009. All abstracts retrieved by the individual
searches were reviewed. Full-text articles were retrieved
and evaluated if the abstract suggested potential relevance.
In addition to the publications identified by the electronic
database search (Table 1) a further two relevant publica-
tions were identified from the bibliographies (Tupasi 1985;
Post et al. 1992). In some instances where the original
publication contained insufficient information the authors
were contacted and asked to provide further details.
Inclusion criteria were (a) mortality risk: studies inves-
tigating fatal outcomes in children with pneumonia and
moderate and ⁄ or severe malnutrition, (b) aetiology: studies
reporting on bacteriological or virological investigations in
children with pneumonia and severe malnutrition, and
(c) clinical signs: studies in severely malnourished children
which compared, as a minimum, the sensitivity and
specificity of age-specific fast breathing and ⁄ or lower chest
wall indrawing with chest radiograph as the gold standard
for the diagnosis of pneumonia. Excluded were (i) reports
that included fewer than 10 malnourished children,
(ii) reports which did not use standard definitions for
malnutrition or provided no definition and (iii) reports in
which the respective data could not be clearly separated on
the basis of nutritional status.
Results
Pneumonia-related mortality risk in moderate and severe
malnutrition
Fifteen published studies evaluating mortality risk were
identified (Tupasi 1985; Tupasi et al. 1988, 1990c;
Deivanayagam et al. 1992; Post et al. 1992; Nathoo et al.
1993; Agrawal et al. 1995; Banajeh et al. 1997; Sehgal
et al. 1997; Yoon et al. 1997; Man et al. 1998; Bahwere
et al. 2004; Johnson et al. 2008; Nantanda et al. 2008;
Naheed et al. 2009); additionally, the results of a currently
unpublished study from Bangladesh (M.J. Chisti, unpub-
lished data) were included (Table 2). Nine publications
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M. J. Chisti et al. Pneumonia in severely malnourished children

Table 1 Search strategy used to identify relevant publications and outcome

Relevant publications
Initial search
Database Strategy and keywords used results (matches) Mortality risk Aetiology Clinical signs

Medline Pneumonia AND (malnutrition OR 557 Thirteen papers Ten papers Four papers
(keyword) malnourished OR undernutrition OR
marasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)
Medline ((‘Malnutrition’[Mesh] OR ‘Protein- 142 Eight papers* Two papers* One paper*
(MeSH) Energy Malnutrition’[Mesh]) AND
‘Pneumonia’[Mesh] AND (‘Child, Pre
school’[Mesh] OR ‘Infant’[Mesh]))
EMBASE (exp pneumonia.mp) AND 207 Seven papers* Three papers* Two papers*
(malnutrition ⁄ OR malnourished ⁄ OR
undernutrition ⁄ OR marasmus ⁄ OR
kwashiorkor.mp)
Limited to (infant <to one year> OR child
<unspecified age> OR preschool child
<1–6 years> OR school child
<7–12 years>)
Web of Science Pneumonia AND (malnutrition OR 241 Seven papers* Five papers* Three papers*
malnourished OR undernutrition OR
marasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)
Scopus Pneumonia AND (malnutrition OR 655 Eleven papers* Six papers* Four papers*
malnourished OR undernutrition OR
marasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)
CINAHL Pneumonia AND (malnutrition OR 23 One paper* No papers No papers
malnourished OR undernutrition OR
marasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)

*No new publications identified.

include data from Asia, six present data from Africa, while
one paper originates from South-America. All but one
report (Deivanayagam et al. 1992) exclusively included
children younger than 6 years of age.
In all studies identified in our literature search there was
a significant association between severe malnutrition and
mortality among children with pneumonia (Figure 1).
Among the seven studies reporting the relative risk (RR) of
mortality in children with severe malnutrition in compar-
ison to those without, the RR ranged from 2.9 to 121.2.
Notably, in the study reporting the latter RR (Yoon et al.
1997) confidence intervals were not provided and this
value appears high compared to the findings of other
studies. In the remaining studies 95% confidence intervals
(CIs) ranged between 2.0 and 13.1 (lower limit) and
4.1–55.7 (upper limit) (Tupasi 1985, 1988; Nathoo et al.
1993; Yoon et al. 1997; Man et al. 1998; Bahwere et al.
2004; Johnson et al. 2008). Among the nine studies
reporting the odds ratio (OR), OR ranged from 2.5 to 15.1,
with 95% CIs ranging between 1.01 and 5.4 (lower limit)
and 4.8–42.4 (upper limit) (Tupasi et al. 1990c;
Deivanayagam et al. 1992; Post et al. 1992; Agrawal et al.
1995; Banajeh et al. 1997; Sehgal et al. 1997; Nantanda
et al. 2008; Naheed et al. 2009).
Mortality in children with moderate malnutrition could
be determined in seven of the 16 studies above (Table 3). In
this group the RR of death ranged from 1.2 to 36.5. The
latter figure was reported without corresponding CI (Yoon
et al. 1997). In the remaining studies 95% CIs ranged
between 0.6 and 5.7 (lower limit) and 2.0–22.4 (upper

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Table 2 Impact of severe malnutrition on mortality risk associated with pneumonia

Total no. of
severely
Total no. of malnourished
Age group patients ⁄ patients ⁄
Reference Country (months) no. of deaths no. of deaths RR* or OR (CI) Adjusted  ⁄ non-adjusted Severity of malnutrition

Naheed et al. (2009) Bangladesh 2–59 4155 ⁄ 150 208 ⁄ 27 4.6 (2.9–7.4) Non-adjusted <-3 z score of W ⁄ A
Nantanda et al. (2008) Uganda 2–59 157 ⁄ 24 40 ⁄ 18 15.1 (5.4–42.4) Adjusted for cyanosis, <-3 z score of W ⁄ A
grunting, hypoxaemia,
pneumonia severity,
HIV infection
Johnson et al. (2008) Nigeria 0.5–60 321 ⁄ 34 36 ⁄ 12 4.3 (2.3–8.0) Non-adjusted Wellcome classification
Tropical Medicine and International Health

Bahwere et al. (2004) Congo 0–60 793 ⁄ 95 174 ⁄ 42 2.8* (2.0–4.1) Non-adjusted <-3 z score of W ⁄ H
Man et al. (1998) Gambia 0–60 2193 ⁄ 153 405 ⁄ 62 3.0* (2.2–4.1)à Non-adjusted <-3 z score of W ⁄ A
Yoon et al. (1998) Philippines 0–5 9942 ⁄ 39 – 6.6* Adjusted for co-variates <-3 z score of W ⁄ A
6–11 – 5.1* Adjusted for co-variates
12–22 – 121.2 Adjusted for co-variates
Banajeh et al. (1997) Yemen 0–59 529 ⁄ 52 121 ⁄ 26 4.02 (2.1–7.6) Non-adjusted <60% W ⁄ A
Sehgal et al. (1997) India 0.5–60 201 ⁄ 21 – 3.9 (1.01–9.7) Adjusted for age, inability <-3 z score of W ⁄ A
to feed, bandemia, diarrhoea
Agrawal et al. (1995) India 2–60 127 ⁄ 15 10 ⁄ 35 7.0 (2.1–22.8) Non-adjusted <60% W ⁄ A
M. J. Chisti et al. Pneumonia in severely malnourished children

Nathoo et al. (1993) Zimbabwe 1–60 704 ⁄ 104 82 ⁄ – 3.8* (2.7–5.4) Adjusted for pneumonia <60% W ⁄ A
severity, age, duration of cough,
previous hospital admission
Deivanayagam et al. (1992) India 1–132 210 ⁄ 70 – 5.8 (2.2–15.6) Adjusted for pneumonia severity, <60% W ⁄ A
gastroenteritis and meningitis
Post et al. (1992) Brazil 0–11 253 ⁄ 127 60 ⁄ 47 11.7 (4.2–32.6) Adjusted for breast feeding, <-3 z score of W ⁄ A
socio-economic status
Tupasi et al. (1990) Philippines 0–59 528 ⁄ 88 246 ⁄ 45 2.5 (1.3–4.8) Adjusted for concurrent measles, <-3 z score of W ⁄ A
clinical complication,
severe illness, gender
Tupasi et al. (1988)§ Philippines 0–59 729 ⁄ 34 83 ⁄ 12 27.0* (13.1–55.7) Adjusted for ALRI <60% W ⁄ A
severity, bactereamia
Tupasi et al. (1985) Philippines 0–59 810 ⁄ 34 321 ⁄ 25 12.8* Adjusted for co-variates <60% W ⁄ A
M.J. Chisti, unpublished Bangladesh 0–59 198 ⁄ 24 80 ⁄ 18 5.2 (1.2–22.0) Adjusted for severe sepsis, <-3 z score of W ⁄ A
data) hypoxaemia, lobar consolidation,
metabolic acidosis

*Relative risk.
 According to analysis performed by the original authors. Different studies used different classifications for the severity of pneumonia ⁄ ALRI.
àCalculated from data provided in the original manuscript.
§Study used national reference values for the definition of malnutrition.
Abbreviations used: ALRI, acute lower respiratory tract infection; CI, confidence interval; no., number; OR, odds ratio.

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M. J. Chisti et al. Pneumonia in severely malnourished children

Bahwere 2004

Relative risk
Man 1998
Nathoo 1993
Tupasi 1988

Figure 1 Summary of studies reporting Naheed 2009

the mortality risk associated with severe Nantanda 2008
malnutrition among children with
Banajeh 1997
pneumonia. Graphical representation of
Sehgal 1997

Odds ratio
studies identified in the literature search.
Studies not providing confidence intervals Agrawal 1995
were not included in the figure. The dotted
Deivanayagam 1992
line indicates a mortality risk [relative risk
(RR) or odds ratio (OR)] equalling one. Post 1992
The boxes represent RRs and ORs reported Tupasi 1990
by individual studies; the horizontal lines
Chisti (unpublished)
indicate the corresponding confidence
intervals. 0 10 20 3040 50 60

Table 3 Impact of moderate malnutrition on mortality risk associated with pneumonia

Total no. of
moderately
Total no. of malnourished Severity of
Age group patients ⁄ patients ⁄ Adjusted* ⁄ non- moderate
Reference Country (months) no. of deaths no. of deaths RR (CI) adjusted malnutrition

Johnson et al. (2008) Nigeria 0.5–60 321 ⁄ 34 144 ⁄ 17 3.6 (1.2–11.7)  Non-adjusted 60–74% W ⁄ A
Bahwere et al. (2004) Congo 0–60 793 ⁄ 95 99 ⁄ 10 1.2 (0.6–2.4)  Non-adjusted <-2 to ‡-3 z
score of W ⁄ H
Man et al. (1998) Gambia 0–60 2193 ⁄ 153 507 ⁄ 35 1.6 (1.1–2.6)  Non-adjusted <-2 to ‡-3 z
score of W ⁄ A
Yoon et al. (1998) Philippines 0–5 9942 ⁄ 39 – 4.1 Adjusted for co-variates <-2 to ‡-3 z
6–11 – 3.4 Adjusted for co-variates score of W ⁄ A
12–22 – 36.5 Adjusted for co-variates
Post et al. (1992) Brazil 0–11 253 ⁄ 127 48 ⁄ 26 1.5 (1.04–2.0)  Non-adjusted <-2 to ‡-3 z
score of W ⁄ A
Tupasi et al. (1988)à Philippines 0–59 729 ⁄ 34 220 ⁄ – 11.3 (5.7–22.4) Adjusted for ALRI 60–74% W ⁄ A
severity, bacteraemia
Chisti et al. (2009, Bangladesh 0–59 198 ⁄ 24 44 ⁄ 4 3.2 (0.6–16.9)  Non-adjusted <-2 to ‡-3 z
unpublished data) score of W ⁄ A

*According to analysis performed by the original authors. Different studies used different classifications for the severity of
pneumonia ⁄ ALRI.
 Calculated from data provided in the original manuscript comparing children with moderate malnutrition with those without moderate or
severe malnutrition.
àStudy used national reference values for the definition of malnutrition.
ALRI, acute lower respiratory tract infection; CI, confidence interval; no., number; OR, odds ratio; RR, relative risk.

limit) (Tupasi et al. 1988; Post et al. 1992; Yoon et al.
1997; Man et al. 1998; Bahwere et al. 2004; Johnson et al.
2008; M.J. Chisti, unpublished data).
In addition to these original studies we identified one
review by Caulfield et al. (2004) on the causes of mortality
in malnourished children. In this paper the authors
summarised the observations from 10 studies conducted in
sub-Saharan Africa and Asia. They also present estimates
of the mortality risks based on additional information
provided by the authors of these studies and further
statistical analysis. The original reports contained
insufficient data for us to specifically calculate the

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Table 4 Bacterial isolates in severely malnourished children with pneumonia

Number of Aetiological agent,

patients with Nutritional number of isolates Source of
Reference Country Age group pneumonia status (percentage ) sample(s)

Shimeles Ethiopia 4–60 months 57 Kwashiorkor, Klebsiella pneumoniae 10 (18%) Blood cultures
& Lulseged Marasmus, Salmonella (non-typhi) 3 (4%)
(1994) Marasmic- Staphylococcus aureus 2 (3%)
kwashiorkor Escherichia coli 1 (2%)
Pseudomonas spp. 1 (2%)
Adegbola et al. (1994) The Gambia 3–60 months 159* Undernutrition, Streptococcus pneumoniae 11 (7%) Lung aspirates,
Tropical Medicine and International Health

Kwashiorkor, Salmonella spp. 4 (3%) blood cultures

Marasmus, Mycobacterium tuberculosis 4 (3%)
Marasmic- Haemophilus influenzae (type b) 3 (2%)
kwashiorkor H. influenzae (non-typable) 3 (2%)
S. aureus 1 (1%)
E. coli 1 (1%)
K. pneumoniae 1 (1%)
Moraxella spp. 1 (1%)
Johnson et al. (1993) Nigeria 0–23 months 11 Kwashiorkor, S. pneumoniae 2 (18%) Blood cultures
M. J. Chisti et al. Pneumonia in severely malnourished children

Marasmic- S. aureus 2 (18%)

kwashiorkor K. pneumoniae 1 (9%)
Salmonella spp. 1 (9%)
Fagbule et al. (1993) Nigeria 9 months– 99 Kwashiorkor, Klebsiella spp. 39 (39%) Lung aspirates
5 years Marasmus, S. aureus 30 (30%)
Marasmic- E. coli 9 (9%)
kwashiorkor
Friedland (1992) South Africa 2–84 months –§ Kwashiorkor, S. pneumoniae 12 Blood cultures
Marasmus, H. influenzae 4
Marasmic- E. coli 2
kwashiorkor
Johnson et al. (1992) Nigeria 0.5–59 months 50 Kwashiorkor, S. aureus 10 (20%) Blood cultures
Marasmus, K. pneumoniae 2 (4%)
Marasmic- Salmonella spp. 1 (2%)
kwashiorkor
Berkowitz (1983) South Africa 4–53 months 18 Kwashiorkor, E. coli 2 (11%) Blood cultures
Marasmus, K. pneumoniae 2 (11%)
Marasmic- Salmonella spp. 1 (6%)
kwashiorkor S. pneumoniae 1 (6%)

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 Table 4 (Continued)

Number of Aetiological agent,

patients with Nutritional number of isolates Source of
Reference Country Age group pneumonia status (percentage  ) sample(s)

Diallo et al. (1979) Nigeria 0–8 months 56 Kwashiorkor, S. pneumoniae 10 (18%) Lung aspirates
Marasmus, S. aureus 8 (14%)
Marasmic- Alpha-haemolytic

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kwashiorkor Streptococcus 6 (11%)
E. coli 2 (4%)
Group A Streptococcus 1 (2%)
Group F Streptococcus 1 (2%)
Salmonella spp. 1 (2%)
Morehead et al. (1974) Thailand 10–50 months 12 Kwashiorkor, S. pneumoniae 1 (8%) Lung aspirates
Tropical Medicine and International Health

Marasmus, H. influenzae 1 (8%)

Marasmic- M. tuberculosis 1 (8%)
kwashiorkor
Hughes et al. (1969) India 0.8–33 months 16 Below 3rd H. influenzae 6 (38%) Lung aspirates
percentile for S. pneumoniae 2 (13%)
weight and
length
Chisti et al. (2009) Bangladesh 0–59 months 31 Kwashiorkor, Pseudomonas spp. 2 (6%) Blood cultures
Marasmus, Acinetobacter spp. 2 (6%)
M. J. Chisti et al. Pneumonia in severely malnourished children

Marasmic- K. pneumoniae 1 (3%)

kwashiorkor E. coli 1 (3%)
Enterobacter spp. 1 (3%)
Streptococcus spp. 1 (3%)

Total 509 Total isolates: 215

Number of isolates (percentageà):
Klebsiella spp. 56 (26.0%)
S. aureus 53 (24.6%)
S. pneumoniae 39 (18.1%)
E. coli 18 (8.4%)
H. influenzae 17 (7.9%)
Salmonella spp. 11 (5.1%)
Streptococci (other) 9 (4.2%)
M. tuberculosis 5 (2.3%)
Pseudomonas spp. 3 (1.4%)
Acinetobacter spp. 2 (0.9%)
Moraxella spp. 1 (0.5%)
Enterobacter spp. 1 (0.5%)

*Study population comprised of 51% of children with oedematous malnutrition ⁄ marasmus and 40% with severe undernutrition.
 Percentage refers to the proportion of children in whom the respective organism was isolated (out of the total study population).
§Total number of patients not mentioned; percentages were therefore not calculated.
àPercentage refers to the proportion each bacterial organism has contributed to the total number of isolates (n = 215).

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Tropical Medicine and International Health
M. J. Chisti et al. Pneumonia in severely malnourished children
mortality risk associated with pneumonia. However, in all
studies combined, the RR of fatal outcome associated with
moderate and severe malnutrition and pneumonia was
estimated to be 4.03 (95% CI: 2.67–6.08) and 8.09 (95%
CI: 4.36–15.01), respectively, compared to well nourished
children.
Aetiology of pneumonia in children with severe
malnutrition
Eleven studies that evaluated the aetiology of pneumonia in
severely malnourished children and fulfilled the inclusion
criteria were identified, comprising a total of 509 children
(Table 4). A further 18 publications (Mimica et al. 1971;
Escobar et al. 1976; Silverman et al. 1977; Shann et al.
1984a; Christie et al. 1988; Gonzaga et al. 1990; Rahman
et al. 1990; Tupasi et al. 1990a,b; Johnson et al. 1993;
Aderele et al. 1995; Garcia 1996; Falade et al. 1997; Scott
& Hall 1999; Vuori-Holopainen & Peltola 2001; Bahwere
et al. 2004; Johnson et al. 2008; Nantanda et al. 2008)
reporting on mixed study populations comprised of
malnourished and well-nourished children were excluded,
as these reports did not specify which organisms were
isolated in each of the two groups. We excluded one
further study that exclusively focused on Staphylococcus
aureus infections in malnourished children (Aderele et al.
1994).
All reports included originated from Africa or Asia, and
all but one focused on children younger than 5 years of
age. The majority of studies included a relatively small
number of severely malnourished children with only five of
the studies including more than 50 patients. Six studies
used blood cultures alone to identify the causative organ-
ism (Berkowitz 1983; Friedland 1992; Johnson et al. 1992,
1993; Shimeles & Lulseged 1994; M.J. Chisti, unpublished
data), four used lung aspirates alone (Hughes et al. 1969;
Morehead et al. 1974; Diallo et al. 1979; Fagbule 1993),
and one study used a combination of blood cultures and
lung aspirates (Adegbola et al. 1994).
The findings varied considerably between individual
studies (Table 4). In all four studies originating from
Nigeria (Diallo et al. 1979; Johnson et al. 1992, 1993;
Fagbule 1993) S. aureus was a relatively common isolate,
accounting for 14–30% of the cases. In one of these studies
(Fagbule 1993) Klebsiella species were isolated in 39% of
the cases, while these organisms were significantly less
frequent in the other three studies from the same country
(Diallo et al. 1979; Johnson et al. 1992, 1993). However,
similar findings were reported by studies from Ethiopia
(Shimeles & Lulseged 1994) and South Africa (Berkowitz
1983), in which Klebsiella species were identified as the
causative agent in 18% and 11% of the cases, respectively.
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volume 14 no 10 pp 1173–1189 october 2009
Other
Salmonella spp.
5% Klebsiella spp.
26%
H. influenzae
8%
E. coli
8%
S. aureus
S. pneumoniae 25%
18%
Figure 2 Bacterial isolated (n = 215) from all published reports.
Escherichia coli was another relatively common isolate in
some studies. In one South African study (Berkowitz 1983)
this organism accounted for 11% of the isolates. However,
the total number of isolates in this study was small, and
solid conclusions can therefore not be made. Strikingly,
Streptococcus pneumoniae was not isolated from any case
in three studies including a total of 206 patients (Johnson
et al. 1992; Fagbule 1993; Shimeles & Lulseged 1994) and
only accounted for a small proportion of cases in a further
four studies (Hughes et al. 1969; Morehead et al. 1974;
Berkowitz 1983; Johnson et al. 1993). Streptococcus
pneumoniae was a common isolate in only three reports,
being responsible for 7–18% of the cases (Diallo et al.
1979; Friedland 1992; Adegbola et al. 1994). Similarly,
only four of the eleven studies reported cases in whom
Haemophilus influenzae was identified as the causative
agent (Hughes et al. 1969; Morehead et al. 1974; Friedland
1992; Adegbola et al. 1994). Haemophilus influenzae
isolates were not typed in most studies.
The total number of isolates in all reports combined was
215. Overall, the most commonly isolated organisms in
severely malnourished children with pneumonia were,
in descending order: Klebsiella species, S. aureus,
S. pneumoniae, E. coli, H. influenzae and Salmonella
species (Figure 2). Other organisms, including
Acinetobacter species, Pseudomonas species, Moraxella
species and Enterobacter species were rare.
Three of the studies also investigated viral aetiology
(Hughes et al. 1969; Berkowitz 1983; Johnson et al. 1993).
However, only one detailed study of viral agents in
malnourished children with pneumonia was identified
(Adegbola et al. 1994). The authors reported that in 55 of
158 (35%) children a viral agent was identified, comprising
adenovirus (17%), respiratory syncytial virus (6%),
parainfluenza virus (6%), herpes simplex virus (6%),
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 Table 5 Sensitivity and specificity of clinical features of pneumonia in children without severe malnutrition

Number
Author, year, country Inclusion criteria Age range of patients Clinical parameter Sensitivity (%) Specificity (%) Nutritional status

Fast breathing
Shamo‘on et al., 2004, Cough or breathing 0–6 years 147 WHO-defined fast 99 98 Well nourished
Jordan difficulties breathing*
Cherian et al., 1997, Cough 0–6 years 42 WHO-defined fast 76 – Well nourished

ª 2009 Blackwell Publishing Ltd

India breathing*
Falade et al., 1995, Cough or breathing 3 months–5 years 255 WHO-defined fast 79 65 Well nourished
The Gambia difficulties breathing*
Campbell et al., 1988, Cough or breathing 0–5 years 154 ‡50 ⁄ min 71 98 Well nourished
The Gambia difficulties
Singhi et al., 1994, Cough or breathing 2–6 months 138 ‡50 ⁄ min 87 95 Well nourished
Tropical Medicine and International Health

India difficulties 7–11 months 66 ‡50 ⁄ min 83 96

12–35 months 142 ‡40 ⁄ min 94 99
36–60 months 76 ‡40 ⁄ min 72 97
Mulholland et al., 1992, Cough or breathing 0–5 years 730 ‡40 ⁄ min 83 (in Manila) 68 (in Manila) Well nourished
Philippines & Swaziland difficulties 77 (in Swaziland) 69 (in Swaziland)
‡50 ⁄ min 62 (in Manila) 92 (in Manila)
77 (in Swaziland) 69 (in Swaziland)
Palafox et al., 2000, Cough or rhinorrhoea 0–5 years 110 *WHO-defined fast 74 67 Well nourished
Mexico breathing
M. J. Chisti et al. Pneumonia in severely malnourished children

Gupta et al., 1996, Cough or breathing 0–5 years 222  Fast breathing 83 98 *Well nourished
India difficulties
Chest indrawing ⁄ retractions
Shamo‘on et al., 2004, Cough or breathing 0–6 years 147 Chest indrawing 88 77 Well nourished
Jordan difficulties
Cherian et al., 1997, Cough 0–6 years 42 Subcostal retraction 76 – Well nourished
India
Singhi et al., 1994, Cough or breathing 2–6 months 138 Chest indrawing 95 91 Well nourished
India difficulties 7–11 months 66 Chest indrawing 89 92
12–35 months 142 Chest indrawing 94 96
36–60 months 76 Chest indrawing 76 95
Palafox et al., 2000, Cough or rhinorrhoea 0–5 years 110 Chest indrawing 71 59 Well nourished
Mexico
Gupta et al., 1996, Cough or breathing 0–5 years 222 Chest indrawing 62 98 àWell nourished
India difficulties

Fast breathing and indrawing combined

Cherian et al., 1997, Cough 0–6 years 42 *WHO-defined fast 87 – Well nourished
India breathing plus subcostal
retraction
Mulholland et al. 1992, Cough or breathing 0–5 years 730 ‡50 ⁄ min plus indrawing 65 (in Manila) 91 (in Manila) Well nourished
Philipines & Swaziland difficulties 69 (in Swaziland) 89 (in Swaziland)

1181
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Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009

M. J. Chisti et al. Pneumonia in severely malnourished children

influenza A virus (5%), measles virus (3%) and influenza B

Nutritional status

Well nourished
virus (1%).

Clinical features in the diagnosis of pneumonia in

malnourished children
In the early 1990s the WHO introduced guidelines for the
Specificity (%)

diagnosis of pneumonia based primarily on clinical fea-

tures. Age-specific fast breathing and chest wall indrawing
are the two main features used to diagnose pneumonia and
categorise severity in resource-limited settings.
97

Studies of the validity of these clinical features have been

Sensitivity (%)

published before (Shann et al. 1984b; Campbell et al.

1988; Cherian et al. 1988; Harari et al. 1991) and since
(Mulholland et al. 1992; Redd et al. 1994; Singhi et al.
1994; Dai et al. 1995; Taylor et al. 1995; Gupta et al.
93

1996; Palafox et al. 2000; Shamo’on et al. 2004; March

Mde & Sant’Anna 2005) the formulation of the WHO
‡50 ⁄ min plus indrawing

case-management strategy. Some studies were conducted

specifically on children without malnutrition (Campbell
Clinical parameter

et al. 1988; Mulholland et al. 1992; Singhi et al. 1994;

*Less than 2 months of age: ‡60 ⁄ min, 2–12 months of age: ‡50 ⁄ min, 12–60 months of age: ‡40 ⁄ min.

Falade et al. 1995; Gupta et al. 1996; Cherian et al. 1997;

Palafox et al. 2000; Shamo’on et al. 2004); others did not
 Infants: ‡50 breaths ⁄ min, 12 to 35 months: ‡40 breaths ⁄ min, 36–60 months: ‡30 breaths ⁄ min.

specify nutritional status of the study population (Shann

et al. 1984b; Cherian et al. 1988; Harari et al. 1991; Redd
et al. 1994; Dai et al. 1995; March Mde & Sant’Anna
2005). Only four published studies have specifically eval-
of patients
Number

uated the validity of the WHO-recommended clinical signs

for the diagnosis of pneumonia in severely malnourished
154

children (Aref et al. 1992; Falade et al. 1995; Cherian et al.

1997; Wafula et al. 1998). The results are summarized in
Age range

0–5 years

Tables 5 and 6.
In the majority of studies in children without severe
malnutrition, both fast breathing and chest indrawing were
reported to perform well as clinical predictors of pneu-
Cough or breathing difficulties

monia. The sensitivity of both parameters was generally

à Study included 3% severely malnourished children.

close to or above 80%; the specificity was above 90% in

the majority of studies.
In children with severe malnutrition, the sensitivity of
Inclusion criteria

fast breathing as a predictor of radiographically proven

pneumonia ranged from 14% to 76%, and specificity from
WHO: World Health Organization.

66% to 100%. Wafula et al. (1998) reported that the

sensitivity of fast breathing was only 37% in severely
malnourished children below the age of five years, even
with a cut-off set as low as 40 breaths per min. Falade et al.
Campbell et al., 1988,

(1995) found that lowering the WHO-recommended cut-

Author, year, country
Table 5 (Continued)

offs by five breaths per minute increased sensitivity slightly

from 61% to 76%, while simultaneously decreasing
The Gambia

specificity from 79% to 66%. For chest indrawing alone,

sensitivity was overall poor and widely variable (range:
17–71%), while specificity was high (range: 95–98%).
Only two studies reported on the specificity and sensitivity

1182 ª 2009 Blackwell Publishing Ltd

 Table 6 Sensitivity and specificity of clinical features of pneumonia in severely malnourished children

Total study
population Malnourished Sensitivity Specificity
Author, year, country Inclusion criteria (no.) children (no.) Age range Clinical parameter (%) (%) Nutritional status

Fast breathing

ª 2009 Blackwell Publishing Ltd

Wafula et al., 1998, Hospitalised severely 107 103 0–5 years ‡40 ⁄ min 37 85 Kwashiorkor,
Kenya malnourished children ‡50 ⁄ min 25 96 marasmus, and
‡60 ⁄ min 14 100 marasmic-kwashiorkor
Cherian et al., 1997, Runny nose or cough of 312 16 0–6 years WHO-defined 75 – Marasmus
India recent onset, with or fast breathing
without fever
Tropical Medicine and International Health

Falade et al., 1995, Cough, breathing 742 487 3 months– WHO-defined 61 79 W ⁄ A <70% and ⁄ or
The Gambia difficulties or chest pain 5 years fast breathing kwashiorkor, and
<5 breaths ⁄ min below 76 66 marasmic-kwashiorkor
WHO definitions
Aref et al., 1992, Hospitalised severely 100 100 4 months– ‡40 ⁄ min 73 89 Kwashiorkor,
Egypt malnourished children 3 years ‡50 ⁄ min 42 95 marasmus, and
marasmic-kwashiorkor
Chest indrawing
Wafula et al., 1998, Hospitalised severely 107 103 0–5 years Chest indrawing 35 96 Kwashiorkor,
M. J. Chisti et al. Pneumonia in severely malnourished children

Kenya malnourished children marasmus, and

marasmic-kwashiorkor
Cherian et al., 1997, Runny nose or cough of 312 16 0–6 years Subcostal retraction 87 – Marasmus
India recent onset, with or
without fever
Falade et al., 1995, Cough, breathing 742 487 3 months– Chest indrawing 17 98 W ⁄ A <70% and ⁄ or
The Gambia difficulties or 5 years Kwashiorkor, and
chest pain marasmic-kwashiorkor
Aref et al., 1992, Hospitalised severely 100 100 4 months– Chest indrawing 71 95 Kwashiorkor,
Egypt malnourished children 3 years marasmus, and
marasmic-kwashiorkor
Fast breathing and indrawing combined
Cherian et al., 1997, Runny nose or cough of 312 16 0–6 years WHO-defined 87 – Marasmus
India recent onset, with or fast breathing
without fever plus subcostal
retraction
Aref et al., 1992, Hospitalised severely 100 100 4 months– ‡40 ⁄ min plus 60 97 Kwashiorkor,
Egypt malnourished 3 years chest indrawing marasmus, and
children ‡50 ⁄ min plus 39 100 marasmic-kwashiorkor
chest indrawing

ALRI, acute lower respiratory tract infection; CXR, chest X-ray; WHO, World Health Organisation.

1183
volume 14 no 10 pp 1173–1189 october 2009
Tropical Medicine and International Health
M. J. Chisti et al. Pneumonia in severely malnourished children
of both indicators combined. The study by Cherian et al.
(1997) reported a sensitivity of 87% for the combination of
WHO-defined fast breathing and subcostal retractions
(specificity not reported). Aref et al. (1992) assessed the
performance of a combination of fast breathing and chest
wall indrawing, reporting a sensitivity of 60% and 39%
when fast breathing was defined as ‡40, or alternatively
‡50 breaths ⁄ min, respectively. The specificity was reported
to be 97% and 100%, respectively.
Discussion
This review has shown that both severe and moderate
degrees of malnutrition substantially increase the risk of
death among children with pneumonia. This is important
information for clinicians. In many health facilities in
developing countries, a moderate degree of malnutrition is
so commonplace it is often not recorded as an admission
diagnosis, the increased risk of death is not appreciated,
and no additional intervention is provided. The studies
evaluating the impact of moderate malnutrition are
relatively few, and in two of seven studies the confidence
intervals included one. However, the number and
proportion of moderately malnourished children included
in the studies that provided the relevant information (six of
seven studies) was substantial (n = 1062; 23.7% of a
total of 4487 patients). Similarly, in those studies in which
the relevant patient numbers were available (13 of 16
studies), severely malnourished children represented a
considerable group (n = 1866; 16.2% of a total of 11 497
patients).
Importantly, there is evidence that there is a gradation of
mortality risk, with a significantly increased risk associated
with severe malnutrition in all studies (Figure 1). However,
the magnitude of this increase varied between studies. This
might be due to the heterogeneity between study popula-
tions and methodologies, including differences in the
proportion of children with severe malnutrition, geo-
graphical variations, and the prevalence of other important
co-morbidities such as human immunodeficiency virus
(HIV) infection. Factors contributing to the increased
mortality risk include immunodeficiency associated with
malnutrition, high rates of co-morbidities, delayed health-
seeking behaviour among families of children with mal-
nutrition, and potentially delays in diagnosis due to the
insensitivity of clinical signs. Few of the studies listed in
Tables 2 and 3 were conducted in settings with high HIV
prevalence. Notably, the study by Nathoo et al. (1993)
from Zimbabwe found that HIV-infected children pre-
senting with pneumonia were more severely malnourished
than HIV-uninfected children, and had an increased risk of
death.
1184
volume 14 no 10 pp 1173–1189 october 2009
A bacterial cause of pneumonia was identified in 42% of
the 509 children with severe malnutrition included in this
review. Diagnostic procedures for bacterial pneumonia
such as those used in these studies have recognised
limitations for detecting all cases of bacterial pneumonia
and therefore the actual proportion of children with
bacterial pneumonia is likely to be considerably higher
(Scott & Hall 1999). Five studies in this review used lung
aspirates and reported isolation rates ranging from 25% to
79% (Morehead et al. 1974; Fagbule 1993). Blood cultures
– used in eight of the studies – are a safer alternative.
However, in most of the reports included in this review the
yield of blood cultures was below 40% (Berkowitz 1983;
Johnson et al. 1992, 1993; Shimeles & Lulseged 1994).
The data summarised in this review suggest that the
spectrum and frequency of causative organisms may be
different in severely malnourished children. Klebsiella
species and S. aureus were the most common causative
organisms in severely malnourished children in all reports
combined. In contrast, studies of community-acquired
pneumonia in children in industrialised countries have
shown S. pneumoniae to be the most common causative
bacterial organism (McCracken 2000; Sinaniotis &
Sinaniotis 2005; Hale & Isaacs 2006). Studies of
bacterial pneumonia in developing countries predomi-
nately including children without severe malnutrition also
reported S. pneumoniae and H. influenzae as the most
common pathogens (Shann et al. 1984a; Berman 1991).
However, with the increased uptake of pneumococcal and
H. influenzae type b vaccines in developing countries, it
appears likely that these pathogens will become relatively
less important as causative agents of pneumonia (Martin
et al. 2004; Adegbola et al. 2005; CDC 2008; Morris et al.
2008; Scott & English 2008). Escherichia coli and
Salmonella species were other Gram-negative organisms
that were relatively common in severely malnourished
children with pneumonia, while infrequent in children
without severe malnutrition.
Other authors have previously expressed their concern
regarding the microbiological techniques used in some
studies of pneumonia aetiology, potentially leading to an
underestimation of more fastidious organisms such as
H. influenzae (Shann et al. 1984a). In addition, the use of
antibiotics prior to culture will also introduce a potential
bias against isolation of sensitive organisms. Antibiotics are
commonly prescribed for acute respiratory infection at
peripheral health facilities prior to referral and presenta-
tion to central hospitals and nutritional rehabilitation
units. None of the studies in this review reported testing for
antibacterial activity in the urine, the only modality to
objectively ascertain whether antibiotics had been given
previously. Further, severely malnourished children who
ª 2009 Blackwell Publishing Ltd
Tropical Medicine and International Health
M. J. Chisti et al. Pneumonia in severely malnourished children
develop pneumonia after admission will usually be receiv-
ing a broad-spectrum antibiotic such as cotrimoxazole as
routine prophylaxis. Such practices are likely to substan-
tially reduce the likelihood of isolating pathogens sensitive
to these commonly used antibiotics, especially S. pneu-
moniae and H. influenzae (Shann et al. 1984a; Berman
1991). Furthermore, most studies included in this review
did not describe the timing of investigations and interven-
tions in detail. Often it was unclear what proportion of
cases were potentially hospital-rather than community-
acquired. It is therefore possible that in combination these
factors have considerably distorted the microbiological
data reported.
The currently recommended first-line treatment of
pneumonia in severely malnourished children is chloram-
phenicol [World Health Organization (WHO) 1991;
Ahmed et al. 1999; WHO 1999]. However, a recent, large
comparative multicentre study on very severe pneumonia,
which also included a considerable number of children
with severe malnutrition, suggests that the combination of
parenteral ampicillin and gentamicin may be superior to
chloramphenicol (Asghar et al. 2008). One potential
reason for the superiority of ampicillin and gentamicin is
that these antibiotics may be more effective against enteric
Gram-negative bacilli than chloramphenicol. Nevertheless,
it is likely that there are considerable differences between
regions regarding the extent and spectrum of antibiotic
resistance of bacterial organisms. Therefore, guidelines for
the empiric therapy of pneumonia should ideally be based
on the knowledge of local resistance patterns.
Three areas related to the aetiology of pneumonia in
severely malnourished children remain largely unexplored.
Firstly, the role of viral infections in this setting is unclear.
Few data exist on which viral agents predominate in these
children and whether the spectrum of viruses differs from
that observed in well-nourished children. Secondly, the role
of Mycobacterium tuberculosis presenting as acute lower
respiratory infection in severely malnourished children has
not been well studied, despite the likely importance in TB
endemic settings. Thirdly, the causes of pneumonia in HIV-
infected children with co-existing malnutrition have also not
been sufficiently studied (Robertson & Molyneux 2001;
Bachou et al. 2006), despite the great potential relevance to
public health in countries with high HIV prevalence.
The optimal diagnosis of pneumonia relies on a combi-
nation of history, clinical signs and chest X-ray. While
chest X-rays are generally considered to be a reliable
diagnostic tool in all forms of pneumonia, interobserver
variability in their interpretation can be substantial (Sarria
et al. 2003; Bada et al. 2007; Pauls et al. 2007).
Radiographic changes may be vague or inconclusive or
even absent despite the presence of clinical signs of
ª 2009 Blackwell Publishing Ltd
volume 14 no 10 pp 1173–1189 october 2009
pneumonia (Doherty 1991; Hamid et al. 1996; Wafula
et al. 1998). Conversely, clinical signs of pneumonia can be
absent in the presence of radiological signs of pneumonia
(Bachur et al. 1999; Murphy et al. 2007).
Adequate laboratory and radiological services are
frequently not available in primary health care facilities
where malnourished children present with pneumonia.
Auscultation performed by primary healthcare workers in
resource-poor settings has not been sufficiently validated as
a diagnostic tool in pneumonia. Given these limitations,
the WHO recommends that the diagnosis of pneumonia
should primarily be based on visible clinical parameters,
including respiratory rate and chest wall indrawing (WHO
1990, 1991; Cashat-Cruz et al. 2005).
Data from most studies in children without malnutrition
suggest that fast breathing and chest wall indrawing have
an acceptable sensitivity and specificity. In contrast, the
predictive value of these two clinical signs for pneumonia in
severely malnourished children was generally poor sug-
gesting that a large proportion of pneumonia cases would
be missed if fast-breathing and ⁄ or chest wall indrawing are
used as the only diagnostic tool. Therefore, the recom-
mendation to use a low threshold-strategy regarding the
initiation of broad spectrum antibiotics in severely mal-
nourished children appears justified (WHO 1991, 1999).
However, findings varied considerably between studies.
These differences may be due to heterogeneity of the study
populations, large variation in sample sizes and wide
confidence intervals, and bias related to the subjectivity in
the assessment of these clinical signs.
The previous research on clinical diagnostic tools of
pneumonia in severely malnourished children has been
narrowly focused. Potentially useful diagnostic tools, such
as pulse oximetry for the detection of hypoxaemia as an
indicator of severe pneumonia, have not been sufficiently
evaluated for the diagnosis of pneumonia in children with
severe malnutrition.
Potential Limitations
Limitations of this analysis relate to the quality of the data
reported in the studies reviewed, and heterogeneity of the
populations studied. It is likely that there were children
with some degree of malnutrition in the comparison groups
(i.e. children without severe or moderate malnutrition).
Also the lack of height data limits classification as it
underreports stunting and may overestimate wasting.
Conclusions
The combination of pneumonia and malnutrition has an
enormous impact on child mortality globally. Severe
1185
Tropical Medicine and International Health
M. J. Chisti et al. Pneumonia in severely malnourished children
malnutrition is associated with a significant increase in
mortality risk in children with pneumonia. The currently
available data suggest that the spectrum and frequency
of causative agents of bacterial pneumonia in severely
malnourished children may differ from that observed in
children without severe malnutrition, and that a reliance
on simple clinical signs will underestimate the burden of
disease and potentially delay diagnosis. Further research
is needed to more fully investigate pneumonia aetiology
in different geographical regions, and explore the
importance of viruses and M. tuberculosis in greater detail.
Also, additional research is needed to improve the
prevention, early detection, management and outcome
of pneumonia in severely malnourished children in
resource-poor settings.
Acknowledgements
We thank Prof. AWBR Johnson for providing further data
related to his manuscript and for his constructive sugges-
tions. M.J.C is supported by an Australian Development
Scholarship provided by the Australian Agency for Inter-
national Development (AusAID). M.T is supported by a
Fellowship award by the European Society for Paediatric
Infectious Diseases (ESPID) and an International Research
Scholarship by The University of Melbourne. The Centre
for International Child Health is a WHO Collaborating
Centre for Research & Training in Child & Neonatal
Health, is supported by the RE Ross Trust (Victoria), and
is part of the AusAID Knowledge Hub for Women’s and
Children’s Health.
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Corresponding Author Trevor Duke, Centre for International Child Health, Department of Paediatrics, University of Melbourne,
Royal Children’s Hospital Melbourne, Flemington Road, Parkville, Victoria 3052, Australia. Tel.: +61 3 9345 5968; Fax: +61 3 9345
6667; E-mail: trevor.duke@rch.org.au
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