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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, Bangladesh2 Centre for International Child Health, Department of Paediatrics, University of Melbourne, Royal Children’s Hospital,
Melbourne, Australia3 Infectious Diseases Unit, Department of General Medicine, Royal Children’s Hospital, Melbourne, Australia4 Department of Paediatrics, University of Melbourne, Australia5 Murdoch Children’s Research Institute (MCRI), Melbourne, Australia6 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.
Tropical Medicine and International Health doi:10.1111/j.1365-3156.2009.02364.x
volume 14 no 10 pp 1173–1189 october 2009
ª 2009 Blackwell Publishing Ltd 1173
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
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
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1174 ª 2009 Blackwell Publishing Ltd
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
Table 1 Search strategy used to identify relevant publications and outcome
Database Strategy and keywords used
Initial search
results (matches)
Relevant publications
Mortality risk Aetiology Clinical signs
Medline
(keyword)
Pneumonia AND (malnutrition OR
malnourished OR undernutrition ORmarasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)
557 Thirteen papers Ten papers Four papers
Medline
(MeSH)
((‘Malnutrition’[Mesh] OR ‘Protein-
Energy Malnutrition’[Mesh]) AND
‘Pneumonia’[Mesh] AND (‘Child, Pre
school’[Mesh] OR ‘Infant’[Mesh]))
142 Eight papers* Two papers* One paper*
EMBASE (exp pneumonia.mp) AND
(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>)
207 Seven papers* Three papers* Two papers*
Web of Science Pneumonia AND (malnutrition OR
malnourished OR undernutrition OR
marasmus OR kwashiorkor) AND(infant OR child* OR pediatric OR
paediatric)
241 Seven papers* Five papers* Three papers*
Scopus Pneumonia AND (malnutrition OR
malnourished OR undernutrition ORmarasmus OR kwashiorkor) AND
(infant OR child* OR pediatric OR
paediatric)
655 Eleven papers* Six papers* Four papers*
CINAHL Pneumonia AND (malnutrition ORmalnourished OR undernutrition OR
marasmus OR kwashiorkor) AND
(infant OR child* OR pediatric ORpaediatric)
23 One paper* No papers No papers
*No new publications identified.
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
ª 2009 Blackwell Publishing Ltd 1175
Tab
le2
Impact
of
sever
em
aln
utr
itio
non
mort
alit
yri
skass
oci
ate
dw
ith
pneu
monia
Ref
eren
ceC
ountr
y
Age
gro
up
(month
s)
Tota
lno.
of
pati
ents
⁄no.
of
dea
ths
Tota
lno.
of
seve
rely
maln
ouri
shed
pati
ents
⁄no.
of
dea
ths
RR
*or
OR
(CI)
Adju
sted
�⁄n
on-a
dju
sted
Sev
erit
yof
maln
utr
itio
n
Nahee
det
al.
(2009)
Bangla
des
h2–59
4155
⁄150
208
⁄27
4.6
(2.9
–7.4
)N
on-a
dju
sted
<-3
zsc
ore
of
W⁄A
Nanta
nda
etal
.(2
008)
Uganda
2–59
157
⁄24
40
⁄18
15.1
(5.4
–42.4
)A
dju
sted
for
cyanosi
s,
gru
nti
ng,
hypoxaem
ia,
pneu
monia
sever
ity,
HIV
infe
ctio
n
<-3
zsc
ore
of
W⁄A
Johnso
net
al.
(2008)
Nig
eria
0.5
–60
321
⁄34
36
⁄12
4.3
(2.3
–8.0
)N
on-a
dju
sted
Wel
lcom
ecl
ass
ifica
tion
Bahw
ere
etal
.(2
004)
Congo
0–60
793
⁄95
174
⁄42
2.8
*(2
.0–4.1
)N
on-a
dju
sted
<-3
zsc
ore
of
W⁄H
Man
etal
.(1
998)
Gam
bia
0–60
2193
⁄153
405
⁄62
3.0
*(2
.2–4.1
)�N
on-a
dju
sted
<-3
zsc
ore
of
W⁄A
Yoon
etal
.(1
998)
Phil
ippin
es0–5
9942
⁄39
–6.6
*A
dju
sted
for
co-v
aria
tes
<-3
zsc
ore
of
W⁄A
6–11
–5.1
*A
dju
sted
for
co-v
aria
tes
12–22
–121.2
Adju
sted
for
co-v
aria
tes
Banaje
het
al.
(1997)
Yem
en0–59
529
⁄52
121
⁄26
4.0
2(2
.1–7.6
)N
on-a
dju
sted
<60%
W⁄A
Seh
gal
etal
.(1
997)
India
0.5
–60
201
⁄21
–3.9
(1.0
1–9.7
)A
dju
sted
for
age,
inabilit
y
tofe
ed,
bandem
ia,
dia
rrhoea
<-3
zsc
ore
of
W⁄A
Agra
wal
etal
.(1
995)
India
2–60
127
⁄15
10
⁄35
7.0
(2.1
–22.8
)N
on-a
dju
sted
<60%
W⁄A
Nath
oo
etal
.(1
993)
Zim
babw
e1–60
704
⁄104
82
⁄–3.8
*(2
.7–5.4
)A
dju
sted
for
pneu
monia
sever
ity,
age,
dura
tion
of
cough,
pre
vio
us
hosp
ital
adm
issi
on
<60%
W⁄A
Dei
vanaya
gam
etal
.(1
992)
India
1–132
210
⁄70
–5.8
(2.2
–15.6
)A
dju
sted
for
pneu
monia
sever
ity,
gast
roen
teri
tis
and
men
ingit
is<60%
W⁄A
Post
etal
.(1
992)
Bra
zil
0–11
253
⁄127
60
⁄47
11.7
(4.2
–32.6
)A
dju
sted
for
bre
ast
feed
ing,
soci
o-e
conom
icst
atu
s
<-3
zsc
ore
of
W⁄A
Tupasi
etal
.(1
990)
Phil
ippin
es0–59
528
⁄88
246
⁄45
2.5
(1.3
–4.8
)A
dju
sted
for
concu
rren
tm
easl
es,
clin
ical
com
pli
cati
on,
sever
eil
lnes
s,gen
der
<-3
zsc
ore
of
W⁄A
Tupasi
etal
.(1
988)§
Phil
ippin
es0–59
729
⁄34
83
⁄12
27.0
*(1
3.1
–55.7
)A
dju
sted
for
AL
RI
sever
ity,
bact
erea
mia
<60%
W⁄A
Tupasi
etal
.(1
985)
Phil
ippin
es0–59
810
⁄34
321
⁄25
12.8
*A
dju
sted
for
co-v
aria
tes
<60%
W⁄A
M.J
.C
his
ti,
unpubli
shed
data
)
Bangla
des
h0–59
198
⁄24
80
⁄18
5.2
(1.2
–22.0
)A
dju
sted
for
sever
ese
psi
s,
hypoxae
mia
,lo
bar
conso
lidati
on,
met
abolic
aci
dosi
s
<-3
zsc
ore
of
W⁄A
*R
elati
veri
sk.
�Acc
ord
ing
toanaly
sis
per
form
edby
the
ori
gin
al
auth
ors
.D
iffe
rent
studie
suse
ddif
fere
nt
class
ifica
tions
for
the
sever
ity
of
pneu
monia
⁄AL
RI.
�Calc
ula
ted
from
data
pro
vid
edin
the
ori
gin
alm
anusc
ript.
§Stu
dy
use
dnati
onal
refe
rence
valu
esfo
rth
edefi
nit
ion
of
maln
utr
itio
n.
Abbre
via
tions
use
d:
AL
RI,
acu
telo
wer
resp
irato
rytr
act
infe
ctio
n;
CI,
confiden
cein
terv
al;
no.,
num
ber
;O
R,
odds
rati
o.
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1176 ª 2009 Blackwell Publishing Ltd
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
Bahwere 2004
Banajeh 1997
Sehgal 1997
Agrawal 1995
Deivanayagam 1992
Post 1992
Tupasi 1990
Chisti (unpublished)
0 10 20 3040 50 60
Odd
s ra
tioR
elat
ive
risk
Man 1998
Nathoo 1993
Tupasi 1988
Naheed 2009
Nantanda 2008
Figure 1 Summary of studies reporting
the mortality risk associated with severe
malnutrition among children with
pneumonia. Graphical representation ofstudies identified in the literature search.
Studies not providing confidence intervals
were not included in the figure. The dotted
line indicates a mortality risk [relative risk(RR) or odds ratio (OR)] equalling one.
The boxes represent RRs and ORs reported
by individual studies; the horizontal linesindicate the corresponding confidence
intervals.
Table 3 Impact of moderate malnutrition on mortality risk associated with pneumonia
Reference Country
Age group
(months)
Total no. of
patients ⁄no. of deaths
Total no. of
moderatelymalnourished
patients ⁄no. of deaths RR (CI)
Adjusted* ⁄ non-
adjusted
Severity of
moderate
malnutrition
Johnson et al. (2008) Nigeria 0.5–60 321 ⁄ 34 144 ⁄ 17 3.6 (1.2–11.7)� Non-adjusted 60–74% W ⁄ ABahwere 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 ⁄ HMan 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 ⁄ AYoon et al. (1998) Philippines 0–5 9942 ⁄ 39 – 4.1 Adjusted for co-variates <-2 to ‡-3 z
score of W ⁄ A6–11 – 3.4 Adjusted for co-variates
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 zscore of W ⁄ A
Tupasi et al. (1988)� Philippines 0–59 729 ⁄ 34 220 ⁄ – 11.3 (5.7–22.4) Adjusted for ALRI
severity, bacteraemia
60–74% W ⁄ A
Chisti et al. (2009,
unpublished data)
Bangladesh 0–59 198 ⁄ 24 44 ⁄ 4 3.2 (0.6–16.9)� Non-adjusted <-2 to ‡-3 zscore of W ⁄ A
*According to analysis performed by the original authors. Different studies used different classifications for the severity ofpneumonia ⁄ ALRI.
�Calculated from data provided in the original manuscript comparing children with moderate malnutrition with those without moderate or
severe malnutrition.�Study 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.
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
ª 2009 Blackwell Publishing Ltd 1177
Tab
le4
Bact
eria
lis
ola
tes
inse
ver
ely
maln
ouri
shed
childre
nw
ith
pneu
monia
Ref
eren
ceC
ountr
yA
ge
gro
up
Num
ber
of
pati
ents
wit
h
pneu
monia
Nutr
itio
nal
statu
s
Aet
iolo
gic
alagen
t,
num
ber
of
isola
tes
(per
centa
ge�
)
Sourc
eof
sam
ple
(s)
Shim
eles
&L
uls
eged
(1994)
Eth
iopia
4–60
month
s57
Kw
ashio
rkor,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
Kle
bsi
ella
pneu
monia
e10
(18%
)
Salm
onel
la(n
on-t
yphi)
3(4
%)
Stap
hyl
oco
ccus
aure
us
2(3
%)
Esc
her
ichia
coli
1(2
%)
Pse
udom
onas
spp.
1(2
%)
Blo
od
cult
ure
s
Adeg
bola
etal
.(1
994)
The
Gam
bia
3–60
month
s159*
Under
nutr
itio
n,
Kw
ashio
rkor,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
Stre
pto
cocc
us
pneu
monia
e11
(7%
)Sa
lmonel
lasp
p.
4(3
%)
Myc
obac
teri
um
tuber
culo
sis
4(3
%)
Hae
mophil
us
influen
zae
(type
b)
3(2
%)
H.
influen
zae
(non-t
ypable
)3
(2%
)S.
aure
us
1(1
%)
E.
coli
1(1
%)
K.
pneu
monia
e1
(1%
)M
ora
xel
lasp
p.
1(1
%)
Lung
asp
irat
es,
blo
od
cult
ure
s
Johnso
net
al.
(1993)
Nig
eria
0–23
month
s11
Kw
ashio
rkor,
Mara
smic
-
kw
ash
iork
or
S.pneu
monia
e2
(18%
)
S.au
reus
2(1
8%
)
K.
pneu
monia
e1
(9%
)Sa
lmonel
lasp
p.
1(9
%)
Blo
od
cult
ure
s
Fagbule
etal
.(1
993)
Nig
eria
9m
onth
s–
5yea
rs
99
Kw
ashio
rkor,
Mara
smus,
Mara
smic
-kw
ash
iork
or
Kle
bsi
ella
spp.
39
(39%
)
S.au
reus
30
(30%
)
E.
coli
9(9
%)
Lung
asp
irat
es
Fri
edla
nd
(1992)
South
Afr
ica
2–84
month
s–
§K
was
hio
rkor,
Mara
smus,
Mara
smic
-kw
ash
iork
or
S.pneu
monia
e12
H.
influen
zae
4
E.
coli
2
Blo
od
cult
ure
s
Johnso
net
al.
(1992)
Nig
eria
0.5
–59
month
s50
Kw
ashio
rkor,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
S.au
reus
10
(20%
)
K.
pneu
monia
e2
(4%
)Sa
lmonel
lasp
p.
1(2
%)
Blo
od
cult
ure
s
Ber
kow
itz
(1983)
South
Afr
ica
4–53
month
s18
Kw
ashio
rkor,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
E.
coli
2(1
1%
)
K.
pneu
monia
e2
(11%
)Sa
lmonel
lasp
p.
1(6
%)
S.pneu
monia
e1
(6%
)
Blo
od
cult
ure
s
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1178 ª 2009 Blackwell Publishing Ltd
Tab
le4
(Conti
nued
)
Ref
eren
ceC
ountr
yA
ge
gro
up
Num
ber
of
pati
ents
wit
h
pneu
monia
Nutr
itio
nal
statu
s
Aet
iolo
gic
alagen
t,
num
ber
of
isola
tes
(per
centa
ge
�)Sourc
eof
sam
ple
(s)
Dia
llo
etal
.(1
979)
Nig
eria
0–8
month
s56
Kw
ash
iork
or,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
S.pneu
monia
e10
(18%
)
S.au
reus
8(1
4%
)A
lpha-
haem
oly
tic
Stre
pto
cocc
us
6(1
1%
)
E.
coli
2(4
%)
Gro
up
ASt
repto
cocc
us
1(2
%)
Gro
up
FSt
repto
cocc
us
1(2
%)
Salm
onel
lasp
p.
1(2
%)
Lung
asp
irate
s
More
hea
det
al.
(1974)
Thail
and
10–50
month
s12
Kw
ash
iork
or,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
S.pneu
monia
e1
(8%
)H
.in
fluen
zae
1(8
%)
M.
tuber
culo
sis
1(8
%)
Lung
asp
irate
s
Hughes
etal
.(1
969)
India
0.8
–33
month
s16
Bel
ow
3rd
per
centi
lefo
r
wei
ght
and
length
H.
influen
zae
6(3
8%
)S.
pneu
monia
e2
(13%
)L
ung
asp
irate
s
Chis
tiet
al.
(2009)
Bangla
des
h0–59
month
s31
Kw
ash
iork
or,
Mara
smus,
Mara
smic
-
kw
ash
iork
or
Pse
udom
onas
spp.
2(6
%)
Aci
net
obac
ter
spp.
2(6
%)
K.
pneu
monia
e1
(3%
)
E.
coli
1(3
%)
Ente
robac
ter
spp.
1(3
%)
Stre
pto
cocc
us
spp.
1(3
%)
Blo
od
cult
ure
s
Tota
l509
Tota
lis
ola
tes:
215
Num
ber
of
isola
tes
(per
centa
ge�
):
Kle
bsi
ella
spp.
56
(26.0
%)
S.au
reus
53
(24.6
%)
S.pneu
monia
e39
(18.1
%)
E.
coli
18
(8.4
%)
H.
influen
zae
17
(7.9
%)
Salm
onel
lasp
p.
11
(5.1
%)
Str
epto
cocc
i(o
ther
)9
(4.2
%)
M.
tuber
culo
sis
5(2
.3%
)
Pse
udom
onas
spp.
3(1
.4%
)A
cinet
obac
ter
spp.
2(0
.9%
)
Mora
xel
lasp
p.
1(0
.5%
)
Ente
robac
ter
spp.
1(0
.5%
)
*Stu
dy
popula
tion
com
pri
sed
of
51%
of
chil
dre
nw
ith
oed
emato
us
maln
utr
itio
n⁄m
ara
smus
and
40%
wit
hse
ver
eunder
nutr
itio
n.
�Per
centa
ge
refe
rsto
the
pro
port
ion
of
childre
nin
whom
the
resp
ecti
ve
org
anis
mw
as
isola
ted
(out
of
the
tota
lst
udy
popula
tion).
§T
ota
lnum
ber
of
pati
ents
not
men
tioned
;per
centa
ges
wer
eth
eref
ore
not
calc
ula
ted.
�Per
centa
ge
refe
rsto
the
pro
port
ion
each
bact
eria
lorg
anis
mhas
contr
ibute
dto
the
tota
lnum
ber
of
isola
tes
(n=
215).
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
ª 2009 Blackwell Publishing Ltd 1179
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.
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%),
Other
Salmonella spp.5% Klebsiella spp.
26%
S. pneumoniae18%
S. aureus25%
H. influenzae8%
E. coli8%
Figure 2 Bacterial isolated (n = 215) from all published reports.
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1180 ª 2009 Blackwell Publishing Ltd
Tab
le5
Sen
siti
vit
yand
spec
ifici
tyof
clin
ical
featu
res
of
pneu
monia
inch
ildre
nw
ithout
sever
em
aln
utr
itio
n
Auth
or,
yea
r,co
untr
yIn
clusi
on
crit
eria
Age
range
Num
ber
of
pati
ents
Cli
nic
al
para
met
erSen
siti
vit
y(%
)Spec
ifici
ty(%
)N
utr
itio
nal
statu
s
Fas
tbre
athin
gSham
o‘o
net
al.,
2004,
Jord
an
Cough
or
bre
athin
gdif
ficu
ltie
s0–6
yea
rs147
WH
O-d
efined
fast
bre
ath
ing*
99
98
Wel
lnouri
shed
Cher
ian
etal
.,1997,
India
Cough
0–6
yea
rs42
WH
O-d
efined
fast
bre
ath
ing*
76
–W
ell
nouri
shed
Fala
de
etal
.,1995,
The
Gam
bia
Cough
or
bre
athin
gdif
ficu
ltie
s3
month
s–5
yea
rs255
WH
O-d
efined
fast
bre
ath
ing*
79
65
Wel
lnouri
shed
Cam
pbel
let
al.,
1988,
The
Gam
bia
Cough
or
bre
athin
g
dif
ficu
ltie
s
0–5
yea
rs154
‡50
⁄min
71
98
Wel
lnouri
shed
Sin
ghi
etal
.,1994,
India
Cough
or
bre
athin
g
dif
ficu
ltie
s
2–6
month
s138
‡50
⁄min
87
95
Wel
lnouri
shed
7–11
month
s66
‡50
⁄min
83
96
12–35
month
s142
‡40
⁄min
94
99
36–60
month
s76
‡40
⁄min
72
97
Mulh
oll
and
etal
.,1992,
Phil
ippin
es&
Sw
azi
land
Cough
or
bre
athin
g
dif
ficu
ltie
s
0–5
yea
rs730
‡40
⁄min
83
(in
Manil
a)
77
(in
Sw
azi
land)
68
(in
Manil
a)
69
(in
Sw
azi
land)
Wel
lnouri
shed
‡50
⁄min
62
(in
Manil
a)
77
(in
Sw
azi
land)
92
(in
Manil
a)
69
(in
Sw
azi
land)
Pala
fox
etal
.,2000,
Mex
ico
Cough
or
rhin
orr
hoea
0–5
yea
rs110
*W
HO
-defi
ned
fast
bre
ath
ing
74
67
Wel
lnouri
shed
Gupta
etal
.,1996,
India
Cough
or
bre
athin
g
dif
ficu
ltie
s
0–5
yea
rs222
�Fast
bre
athin
g83
98
*W
ell
nouri
shed
Ches
tin
dra
win
g⁄r
etra
ctio
ns
Sham
o‘o
net
al.,
2004,
Jord
an
Cough
or
bre
athin
g
dif
ficu
ltie
s
0–6
yea
rs147
Ches
tin
dra
win
g88
77
Wel
lnouri
shed
Cher
ian
etal
.,1997,
India
Cough
0–6
yea
rs42
Subco
stal
retr
act
ion
76
–W
ell
nouri
shed
Sin
ghi
etal
.,1994,
India
Cough
or
bre
athin
g
dif
ficu
ltie
s
2–6
month
s138
Ches
tin
dra
win
g95
91
Wel
lnouri
shed
7–11
month
s66
Ches
tin
dra
win
g89
92
12–35
month
s142
Ches
tin
dra
win
g94
96
36–60
month
s76
Ches
tin
dra
win
g76
95
Pala
fox
etal
.,2000,
Mex
ico
Cough
or
rhin
orr
hoea
0–5
yea
rs110
Ches
tin
dra
win
g71
59
Wel
lnouri
shed
Gupta
etal
.,1996,
India
Cough
or
bre
athin
gdif
ficu
ltie
s0–5
yea
rs222
Ches
tin
dra
win
g62
98
�Wel
lnouri
shed
Fas
tbre
athin
gan
din
dra
win
gco
mbin
edC
her
ian
etal
.,1997,
India
Cough
0–6
yea
rs42
*W
HO
-defi
ned
fast
bre
ath
ing
plu
ssu
bco
stal
retr
act
ion
87
–W
ell
nouri
shed
Mulh
oll
and
etal
.1992,
Phil
ipin
es&
Sw
azi
land
Cough
or
bre
athin
gdif
ficu
ltie
s0–5
yea
rs730
‡50
⁄min
plu
sin
dra
win
g65
(in
Manil
a)
69
(in
Sw
azi
land)
91
(in
Manil
a)
89
(in
Sw
azi
land)
Wel
lnouri
shed
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
ª 2009 Blackwell Publishing Ltd 1181
influenza A virus (5%), measles virus (3%) and influenza B
virus (1%).
Clinical features in the diagnosis of pneumonia in
malnourished children
In the early 1990s the WHO introduced guidelines for the
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.
Studies of the validity of these clinical features have been
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.
1996; Palafox et al. 2000; Shamo’on et al. 2004; March
Mde & Sant’Anna 2005) the formulation of the WHO
case-management strategy. Some studies were conducted
specifically on children without malnutrition (Campbell
et al. 1988; Mulholland et al. 1992; Singhi et al. 1994;
Falade et al. 1995; Gupta et al. 1996; Cherian et al. 1997;
Palafox et al. 2000; Shamo’on et al. 2004); others did not
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-
uated the validity of the WHO-recommended clinical signs
for the diagnosis of pneumonia in severely malnourished
children (Aref et al. 1992; Falade et al. 1995; Cherian et al.
1997; Wafula et al. 1998). The results are summarized in
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-
monia. The sensitivity of both parameters was generally
close to or above 80%; the specificity was above 90% in
the majority of studies.
In children with severe malnutrition, the sensitivity of
fast breathing as a predictor of radiographically proven
pneumonia ranged from 14% to 76%, and specificity from
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.
(1995) found that lowering the WHO-recommended cut-
offs by five breaths per minute increased sensitivity slightly
from 61% to 76%, while simultaneously decreasing
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 sensitivityTab
le5
(Conti
nued
)
Auth
or,
yea
r,co
untr
yIn
clusi
on
crit
eria
Age
range
Num
ber
of
pati
ents
Clinic
al
para
met
erSen
siti
vit
y(%
)Spec
ifici
ty(%
)N
utr
itio
nal
statu
s
Cam
pbel
let
al.,
1988,
The
Gam
bia
Cough
or
bre
athin
gdif
ficu
ltie
s0–5
yea
rs154
‡50
⁄min
plu
sin
dra
win
g93
97
Wel
lnouri
shed
*L
ess
than
2m
onth
sof
age:
‡60
⁄min
,2–12
month
sof
age:
‡50
⁄min
,12–60
month
sof
age:
‡40
⁄min
.�I
nfa
nts
:‡5
0bre
ath
s⁄m
in,
12
to35
month
s:‡4
0bre
ath
s⁄m
in,
36–60
month
s:‡3
0bre
ath
s⁄m
in.
�Stu
dy
incl
uded
3%
sever
ely
maln
ouri
shed
chil
dre
n.
WH
O:
Worl
dH
ealt
hO
rganiz
ati
on.
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1182 ª 2009 Blackwell Publishing Ltd
Tab
le6
Sen
siti
vit
yand
spec
ifici
tyof
clin
ical
featu
res
of
pneu
monia
inse
ver
ely
maln
ouri
shed
chil
dre
n
Auth
or,
yea
r,co
untr
yIn
clusi
on
crit
eria
Tota
lst
udy
popula
tion
(no.)
Maln
ouri
shed
childre
n(n
o.)
Age
range
Cli
nic
al
para
met
er
Sen
siti
vit
y
(%)
Spec
ifici
ty
(%)
Nutr
itio
nal
statu
s
Fas
tbre
athin
gW
afu
laet
al.,
1998,
Ken
ya
Hosp
italise
dse
ver
ely
maln
ouri
shed
childre
n
107
103
0–5
yea
rs‡4
0⁄m
in37
85
Kw
ashio
rkor,
mara
smus,
and
mara
smic
-kw
ash
iork
or
‡50
⁄min
25
96
‡60
⁄min
14
100
Cher
ian
etal
.,1997,
India
Runny
nose
or
cough
of
rece
nt
onse
t,w
ith
or
wit
hout
feve
r
312
16
0–6
yea
rsW
HO
-defi
ned
fast
bre
athin
g
75
–M
ara
smus
Fala
de
etal
.,1995,
The
Gam
bia
Cough,
bre
athin
g
dif
ficu
ltie
sor
ches
tpain
742
487
3m
onth
s–
5yea
rs
WH
O-d
efined
fast
bre
athin
g
61
79
W⁄A
<70%
and
⁄or
kw
ash
iork
or,
and
mara
smic
-kw
ash
iork
or
<5
bre
aths
⁄min
bel
ow
WH
Odefi
nit
ions
76
66
Are
fet
al.,
1992,
Egypt
Hosp
italise
dse
ver
ely
maln
ouri
shed
childre
n
100
100
4m
onth
s–
3yea
rs
‡40
⁄min
73
89
Kw
ashio
rkor,
mara
smus,
and
mara
smic
-kw
ash
iork
or
‡50
⁄min
42
95
Ches
tin
dra
win
gW
afu
laet
al.,
1998,
Ken
ya
Hosp
italise
dse
ver
ely
maln
ouri
shed
childre
n
107
103
0–5
yea
rsC
hes
tin
dra
win
g35
96
Kw
ashio
rkor,
mara
smus,
and
mara
smic
-kw
ash
iork
or
Cher
ian
etal
.,1997,
India
Runny
nose
or
cough
of
rece
nt
onse
t,w
ith
or
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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
ª 2009 Blackwell Publishing Ltd 1183
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.
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
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
1184 ª 2009 Blackwell Publishing Ltd
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
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
Tropical Medicine and International Health volume 14 no 10 pp 1173–1189 october 2009
M. J. Chisti et al. Pneumonia in severely malnourished children
ª 2009 Blackwell Publishing Ltd 1185
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: [email protected]
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