Child deaths from ARI
Review
Estimates of world-wide distribution
of child deaths from acute respiratory
infections
Brian G Williams, Eleanor Gouws, Cynthia Boschi-Pinto, Jennifer Bryce, and Christopher Dye
Acute respiratory infections (ARI) are among the
leading causes of childhood mortality. Estimates of the
number of children worldwide who die from ARI are
needed in setting priorities for health care. To
establish a relation between deaths due to ARI and all-
cause deaths in children under 5 years we show that
the proportion of deaths directly attributable to ARI
declines from 23% to 18% and then 15% (95% con-
fidence limits range from ±2% to ±3%) as under-5
mortality declines from 50 to 20 and then to 10/1000
per year. Much of the variability in estimates of ARI in
children is shown to be inherent in the use of verbal
autopsies. This analysis suggests that throughout the
world 1·9 million (95% CI 1·6–2·2 million) children
died from ARI in 2000, 70% of them in Africa and
southeast Asia.
Lancet Infectious Diseases 2002; 2: 25–32
Although mortality in all children worldwide under 5 years
old has diminished steadily over the past 50 years,1 it is now
increasing in some countries and remains unacceptably high
in others. Acute lower respiratory infections (ARI) are among
the leading causes of death in children under 5 years but
diagnosis and attribution of deaths to ARI is difficult and
uncertain. Mulholland2 argues that better estimates of the
burden of childhood pneumonia are needed and should be
given a high priority. Case definitions for pneumonia range
from those that are highly sensitive but unspecific to those
that are more specific but insensitive. When other diseases
such as malaria or measles are present, it might be difficult or
even impossible to decide on the primary cause of death. Even
when radiograph facilities are available there is little
agreement on what constitutes significant consolidation on a
paediatric chest radiograph. A further complication is that
community studies of childhood mortality depend largely on
verbal autopsies, which can be very unreliable for the
diagnosis of ARI.3 It is important, therefore, to quantify the
extent to which the variability in estimates of the number of
children that die from ARI reflects the variability inherent in
the use of verbal autopsies.
Leowski4 was one of the first to estimate the burden of
ARI mortality in children across the world. He selected 39
countries in the Americas, Asia, the Middle East, and Europe
for which data on ARI mortality in children were available,
grouped them according to their rates of total infant
mortality, and applied the ARI mortality rates in these groups
of countries to 111 other countries for which total infant
mortality, but not ARI mortality, was available. Garenne et al5
THE LANCET Infectious Diseases Vol 2 January 2002
For personal use. Only reproduce with permission from The Lancet Publishing Group.
developed a relation between ARI mortality and overall
mortality in children. Using historical data compiled by
Preston6 for several countries in the 19th and 20th centuries,
most of which are now industrialised, Garenne et al5 derived a
log-linear association between the proportion of childhood
deaths due to ARI and all-cause mortality. However, a log-
linear fit to the data assembled by Garenne et al5 is not
statistically different from a horizontal line because of the
substantial variability in the estimated values of ARI mortality
that still demands an explanation.
We comprehensively review data on ARI in developing
countries and use this analysis to estimate the number of
children that die from ARI in different regions of the world.
Methods
Age range
Mortality declines substantially with age over the first 5 years
of life and the age-dependent pattern of mortality varies
substantially for different diseases.6 Perinatal and neonatal
mortality are conventionally judged to extend to the age of
7 days and 1 month, respectively; infant mortality extends
up to the age of 1 year, and childhood mortality extends up
to the age of 5 years. We are concerned with under-5
mortality expressed as 5m0, the number of children that die
each year as a proportion of those currently alive.
Preston’s study
In an extensive study of patterns of mortality, Preston6
assembled data for 180 populations covering 44 countries
between 1861 (in England and Wales) and 1964. These data
are mainly from Europe and the Americas, but include
Hong Kong, Israel, Iceland, Jamaica, Japan, South Africa,
Taiwan, and Trinidad and Tobago. Preston6 used these data
to investigate and develop associations between mortality
from various causes and historical time, age, sex, and
economic development. Garenne et al5 later used Preston’s
data to develop a relation between the proportion of
childhood mortality due to ARI and all-cause mortality in
children.
BGW and CD are epidemiologists in communicable diseases at the
World Health Organization; and EG, CB-P, and JB are at the
Department of Child and Adolescent Health and Development of the
World Health Organization. All authors are at the World Health
Organization, Geneva, Switzerland.
Correspondence: Dr Brian Williams, Communicable Diseases, World
Health Organization, 20 Avenue Appia, Geneva 27, CH 1211,
Switzerland. Tel +41 22 791 4680; fax +41 22 791 4268;
email williamsbg@who.int
25
 Review Child deaths from ARI

Table 1. The number of deaths per thousand children under 5 per year (5m0), the percentage of deaths attributed to ARI from the data and
the fitted curve, and the significance levels, for different sites and years. Down arrows: observed values less than fitted values; up arrows:
observed values greater than fitted values. One arrow=p < 0·05; two arrows=p < 0·01; three arrows=p < 0·001.

Site Years Deaths 5m0 ARI Fit p Years Deaths 5m0 ARI Fit p
(%) (%) (%) (%)
Argentina, Chaco7 68–70 1701 22·1 16·4 19·1 0·0287 ↓ Jamaica, Kingston7 68–70 1903 10·4 8·7 14·7 0·0000↓↓↓
Argentina, San Juan7 68–70 2156 20·6 20·0 18·7 0·2678 Kenya19 75–78 557 16·0 19·5 17·2 0·2243
Bangladesh, Matlab*11 93–94 292 26·5 21·2 20·1 0·6754 Mexico, Monterrey7 68–70 3953 18·1 16·3 17·9 0·1025
Bangladesh, Teknaf†12 82–85 1349 22·5 22·3 19·2 0·0275 ↑ Nepal, Jumla 84 74 38·9 18·9 22·3 0·4638
Bolivia, La Paz7 68–70 4276 27·1 32·0 20·3 0·0000 ↑↑↑ (intervention)20

Brazil, Centre-West 91 ·· 14·2 14·0 16·5 0·0030 ↓↓ Nepal, Jumla 84 64 64·8 31·3 25·3 0·3157
Region‡8 (surveillance)20

Brazil, Northeast 91 ·· 27·6 18·1 20·4 0·0142 ↓ Nepal, Kathmandu21 86–89 2101 94·0 22·4 27·4 0·0187↓
Region‡8 Pakistan, Abbottabad 85–87 378 21·7 20·8 19·0 0·4180
Brazil, Northern 91 ·· 16·6 16·5 17·4 0·2514 (control)22
Region‡8 Pakistan, Abbottabad 85–87 130 30·7 33·1 21·0 0·0043↑↑
Brazil, Recife7 68–70 3635 29·3 12·3 20·7 0·0000 ↓↓↓ (intervention)22

Brazil, Ribeirão 68–70 1126 13·7 10·7 16·3 0·0000 ↓↓↓ Philippines, Manila㛳16 85–87 29 14·3 24·1 16·6 0·3465
Preto7 PNG, Goroka9 80–89 170 20·8 34·7 18·7 0·0000↑↑↑
Brazil, São Paulo7 68–70 4312 17·7 16·4 17·8 0·1546 South Africa, Asians23 68–73 1063 11·8 19·9 15·5 0·0041↑↑
Brazil, South Region‡8 91 ·· 9·0 15·9 13·9 0·0744 South Africa, Asians23 74–79 728 7·4 15·0 12·8 0·2274
Brazil, Southeast 91 ·· 12·4 17·7 15·8 0·0336 ↑ South Africa, Asians23 80–85 491 5·2 8·1 10·8 0·1824
Region‡8 South Africa, 68–73 13810 40·0 19·7 22·5 0·0211↓
Canada, Sherbrooke7 70–71 371 4·1 8·6 9·4 0·7309 blacks23
Chile, Santiago7 68–70 2714 13·1 19·9 16·1 0·0011 ↑↑ South Africa, 74–79 9714 28·8 21·9 20·6 0·1719
Columbia, Cali7 68-70 1627 16·1 12·5 17·3 0·0000 ↓↓↓ blacks23

Columbia, Cartegena7 68–70 1255 14·6 9·8 16·7 0·0000 ↓↓↓ South Africa, 80–85 5799 17·3 15·6 17·7 0·0108↓
blacks23
Columbia, Medellin 7
68-70 1348 14·4 11·5 16·6 0·0000 ↓↓↓
South Africa, whites23 68–73 2299 5·6 10·0 11·2 0·4296
El Salvador, 68-70 3820 30·5 11·6 20·9 0·0000 ↓↓↓
San Salvador7 South Africa, whites23 74–79 1787 4·5 12·0 9·9 0·2249

Ethiopia, Butajira 10
86 492 47·9 18·5 23·5 0·0213 ↓ South Africa, whites23 80–85 1285 3·2 7·8 8·0 0·9338

Ethiopia, North 94-95 229 51·8 19·7 24·0 0·1487 Tanzania, Bagamoyo 84–85 325 40·1 35·7 22·5 0·0000↑↑↑
Gondar§17 (control)24

Gambia, Upper 83 915 35·3 21·2 21·8 0·7372 Tanzania, Bagamoyo 84–85 260 29·2 34·2 20·7 0·0000↑↑↑
River13 (intervention)24

India, Gadchiroli 89 161 36·6 26·2 22·0 0·2465 Tanzania, Bagamoyo15 86–87 610 30·8 25·2 21·0 0·0368↑

(control)18 The Gambia, 82–83 120 63·0 20·0 25·1 0·1976

Farafenni¶25
India, Gadchiroli 89 176 26·2 18·8 20·1 0·6814
(intervention)18 USA, California7 69–70 898 4·4 9·2 9·8 0·7613
Zaire, Bwamanda14 89–91 246 47·6 19·5 23·5 0·1596

*Data given for recall over 5 years and 3 years; data for the shorter recall period used. †Excluding 12 deaths associated with acute diarrhoea, 11 with dysentery, five with chronic
diarrhoea, and 61 with sepsis. 301/1349 directly attributable to ARI. ‡Data based on provincial estimates; sample sizes not given.
§Data given for recall over 5 years and 1 year; data for the shorter recall period used.㛳Excluding deaths that were associated with measles.
¶Data given for children from 1 to 7 years of age; corrected for children under 5 assuming a constant death rate between the ages of 1 and 4 years.

The study of Garenne et al
5
Garenne et al searched the Medline database entries for
January 1980 to December 1991 for estimates of all-cause
mortality and mortality attributable to ARI in children
under 5 years in developing countries. Eight community
studies gave 11 estimates of the proportion of deaths due to
ARI and of all-cause mortality; vital registration data for
South Africa gave three estimates; and a study by PAHO7
gave a further 15 estimates from eight countries.
Additional data identified in this study
To supplement the data assembled by Garenne et al5 we
drew on a review by the Department of Child Health of the
World Health Organization, a search of Medline up to April
2001, and a report by Victora.8 Comparison of studies was
complicated by several inconsistencies in the way the studies
were done and reported. The studies varied in their
definitions of ARI, in the methods used to investigate the
cause of death, and in the procedures used to decide on the
primary cause of death when competing causes were
present. Some studies were designed to investigate ARI,
some to investigate other diseases, and others to establish
the general pattern of mortality. There were also differences
in age ranges of the children in the studies, access to health-
care facilities, and the duration and time of the studies.
To ensure consistency in the studies that were analysed we
proceeded as follows. (1)Most of the studies were based on
verbal autopsies, which involved questioning people, usually

26 THE LANCET Infectious Diseases Vol 2 January 2002

For personal use. Only reproduce with permission from The Lancet Publishing Group.
 Child deaths from ARI
Review

mothers, about the deaths of their children over some The “true” prevalence, T, (based on the hospital
previous time. Although a longer recall time increases the diagnoses) is given in terms of the “observed” prevalence, O,
number of deaths that are recorded it also increases the (based on the verbal autopsies) by
recall bias. Where numbers were given for more than one O⫹P⫺1
recall period (usually 1, 3, or 5 years), only the data for the T=
N⫹P⫺1
shortest recall period were used. (2) We only counted deaths
as being due to ARI when ARI was given as the primary where the sensitivity, N, gives the probability that a true
cause of death and, in particular, we excluded deaths known positive is recorded as such, and the specificity, P, gives the
to be associated with both measles and ARI. (3) Where probability that a true negative is recorded as such. Then,
separate estimates of mortality were given for infants and since 0 < T < 1 we have
children, these were combined to obtain total under-5 O<N
mortality. 4) Studies had to include children up to at least 5 and
years old. Where the age range exceeded 5 years the data O < 1⫺P
were corrected to give an estimate of under-5 mortality.
Estimates of 5q0 (the probability of dying between age 0 and (with the inequalities reversed if N+P<1).
exact age 5 years per 1000 live births) were converted to The sensitivity and specificity can be seen to statistically
estimates of 5m0 (the number of children less than 5 years bias the estimates of prevalence, because if we knew both
old who die each year as a proportion of those alive). (5) of these figures we could correct the observed values to
Because ARI is likely to vary seasonally, especially in get a best, unbiased, estimate of the true value. In the
temperate climates, studies were only included if they were
done over at least 1 year. Table 2. Number of people positive or negative on verbal autopsy
In the additional studies included in this analysis eight (first letter P or N), positive or negative on clinical diagnosis
were intended to establish causes and patterns of mortality (second letter P or N), the corresponding “observed” and “true”
in children. Of these studies, four were done as part of estimates of prevalence, and of corresponding sensitivity and
demographic surveillance systems,9−12 one study was in specificity, expressed as percentages.
preparation for a conjugate polysaccharide vaccine trial,13
Reference Observed/true Prevalence
one in relation to nutritional status,14 and one was to assess
risk factors associated with childhood mortality.15 One PP PN NP NN Obs True Sens Spec
study16 was designed to assess ARI in children under 5 years. 3 17 15 8 71 22·5 28·8 53·1 89·9
Five estimates were obtained from a review of childhood 3 20 9 12 52 34·4 31·2 69·0 81·3
mortality in each of the regions of Brazil.8 3 20 8 16 48 39·1 30·4 71·4 75·0
28 18 19 9 81 21·3 29·1 48·6 90·0
Corrections to previous estimates 28 86 45 19 34 57·1 71·2 65·6 64·2
Some minor numerical corrections were made to the data 28 107 24 33 20 76·1 71·2 81·7 37·7
published by Garenne et al and revised numbers are given in 29 7 17 18 175 11·1 11·5 28·0 91·1
table 1. In addition, we added the data published by von 30 66 12 34 18 60·0 76·9 66·0 60·0
Schirnding et al23 for white and Indian people in South 30 59 7 41 23 50·8 76·9 59·0 76·7
Africa to obtain a further six data points, and recalculated
30 86 14 16 14 78·5 76·9 86·0 46·7
the data for coloured people. A study in Bangladesh26 did not
31 26 75 10 132 41·6 14·8 72·2 63·8
use a standardised coding for ARI deaths and was excluded.
31 25 11 33 66 43·0 26·7 69·4 66·7
31 26 10 36 63 45·9 26·7 72·2 63·6
Curve fitting
The estimates of the proportion of deaths due to ARI in the 31 24 12 35 64 43·7 26·7 66·7 64·6
various studies range from 8% to 36%, and the number of 31 22 14 29 70 37·8 26·7 61·1 70·7
deaths from 29 to 13 810. Fitted functions are, therefore, 32 20 7 7 45 34·2 33·8 74·1 86·5
sensitive to the weighting scheme used. Since the data are 32 24 6 26 38 31·9 53·4 48·0 86·4
overdispersed and the residual variation is significantly 32 160 53 21 105 62·8 53·4 88·4 66·5
greater than can be explained on the basis of the errors due 32 202 33 44 92 63·3 66·2 82·1 73·6
to the finite sample sizes, we adopted a weighting scheme 32 60 44 17 78 52·3 38·9 77·9 63·9
that allows for both the sample-size errors and a residual 32 83 24 74 32 50·2 74·0 52·9 57·1
variability that we assume to have a constant variance as 32 328 103 42 82 77·7 66·6 88·6 44·3
described in the panel.
32 386 53 78 52 77·2 81·6 83·2 49·5
32 111 39 68 46 56·8 68·0 62·0 54·1
Variability in verbal autopsies
32 115 34 74 43 56·0 70·8 60·8 55·8
In most of the studies included here verbal autopsies were
used to determine the cause of death. We therefore used 32 156 88 23 123 45·9 62·6 63·9 84·2

data from seven separate studies (table 2) that were designed 32 78 74 38 80 43·0 56·3 51·3 67·8
to compare verbal autopsies with hospital-based diagnoses 33 8 25 24 238 10·8 11·2 24·2 90·8
to investigate the reliability of verbal autopsies in the 33 19 20 10 45 30·9 41·5 48·7 81·8
diagnosis of ARI as the cause of death.

THE LANCET Infectious Diseases Vol 2 January 2002 27

For personal use. Only reproduce with permission from The Lancet Publishing Group.
 Review Child deaths from ARI

2
Data from Garenne
Data from Preston

Ln(Odds true prevalence ARI)

40 Log-linear fit
Percentage of deaths due to ARI

Log transformed to Preston's data 1

95% CI 95% CI

30 0

20 –1

–2
10

–3
0
–3 –2 –1 0 1 2
0 20 40 60 80 100 Ln(Odds observed prevalence ARI)
Mortality per 1000 children per year
Figure 3. Natural logarithm of the odds of true prevalence plotted against
Figure 1. Percentage of deaths due to ARI plotted against the total natural logarithm of the odds of observed prevalence of ARI with 95%
mortality in children under 5 years of age. Data from references 5,6. confidence ellipses for the data points.

data presented below, the best estimates of the observed Results

prevalence are all less than 30% so that from equation In figure 1 the percentage of deaths attributable to ARI is
3 the specificities in the studies designed to determine plotted against the total mortality in children for the data
the proportion of deaths in children attributable to assembled by Garenne et al.5 The line, which is a log-linear
ARI must be greater than 70%. However, the specificities fit to Preston’s data,6 is consistent with the data of Garenne
in 16 out of the 29 studies designed to test the accuracy et al5 but only explains 4% of the variance. The data
of verbal autopsies for the diagnosis of ARI, presented assembled for this study are given in table 1 and plotted in
in table 2, are less than 70%, which indicates that figure 2 with a log-linear curve fitted to the data and
these studies represent a biased selection of patients and weighted as described in the panel. The fitted curve then
must be treated with caution. We did a linear regression explains 61% of the variance. The decline in the proportion
on the logistically transformed proportions of children of deaths due to ARI when the general mortality falls below
whose deaths were attributed to ARI on verbal autopsy about 20/1000 children at risk per year is clearly significant.
and in the hospital, and calculated confidence bands The curve fitted to Preston’s data6 in figure 1 does not differ
for the fitted curve. To separate the variability owing significantly (p > 0·05) from the curve fitted to the data
to the finite sample sizes from the variability inherent presented here in figure 2.
in the use of verbal autopsies we calculated bootstrap There is, however, much variability in the data as
estimates34 of the sampling errors in the log-transformed indicated by the fact that many of the error bars, which only
data. Subtraction of the sampling variance from the include the sampling errors, do not cover the confidence
variance of the observed points about the fitted line band for the fitted curve. Only 15% of the residual-sum-of-
gives the variability inherent in the verbal autopsy squares in figure 2 is explained by the stochastic variability
diagnoses. The resulting confidence bands and the fitted due to the sample sizes. The last column in table 1 indicates
line are then back-transformed to give the confidence which points are significantly above the fitted line (up
bands for the original data. arrows) or significantly below the fitted line (down arrows),

1·0
40 Expected value of true prevalence
95% CI
Percentage of deaths due to ARI

95% CI, adjusting for errors

0·8 in print estimates
30
True prevalence ARI

0·6
20
0·4

10 Data from Puffer and Serano

Data from Preston 0·2
Weighted log-linear curve (see figure 1)
0 95% CI
0·0
0 20 40 60 80 100
Mortality per 1000 children per year 0·0 0·2 0·4 0·6 0·8 1·0
Observed prevalence ARI
Figure 2. Percentage of deaths due to ARI plotted against total mortality
in children under 5 years of age. Data are for the studies in table 1. Figure 4. “True” and “observed” prevalence of ARI for data in table 2.

28 THE LANCET Infectious Diseases Vol 2 January 2002

For personal use. Only reproduce with permission from The Lancet Publishing Group.
 Child deaths from ARI
40
Percentage of deaths due to ARI
30
20
10
Expected value
95% CI
Fitted line
0
0 20 40 60 80
Mortality per 1000 children per year
Figure 5. Percentage of deaths due to ARI, adjusting for bias in verbal
autopsies.
allowing for the errors in the fit as well as the sampling
errors. Because, as noted above, verbal autopsies are known
to be unreliable for the diagnosis of ARI as a cause of death,
we consider next the extent to which the variability in the
data could be a consequence of using verbal autopsies.
Figure 3 gives the log-transformed odds of the true
(hospital) versus the observed (verbal autopsy) prevalences.
The 95% confidence ellipses for each data point give the
errors due to the finite sample sizes. Although these errors
contribute significantly to the general variability in the data,
they do not account for all of the variability. Fitting a
straight line to the log-transformed odds (figure 3) and
detransforming the fitted line gives the association between
the true and observed prevalence (figure 4). The narrow
band in figure 4 gives 95% confidence limits for the fitted
Figure 6. Estimates of the percentage of children that die from lower ARI, by country in 2000. The last category includes values up to 26·0%.
THE LANCET Infectious Diseases Vol 2 January 2002
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Review
line, the outer band in figure 4 gives 95% confidence limits
for the point estimates, including the error in the estimate
of the fitted line but excluding the error due to the finite
sample sizes.
In figure 5 we replot the data in figure 2 with the fitted
line giving the estimate of the proportion of deaths due to
ARI. Figure 5 also shows the corresponding line allowing
for the bias estimated from fitting the hospital diagnoses to
the verbal autopsy diagnoses with a 95% confidence band
(figure 4). Figure 5 shows that the use of verbal autopsies
could bias the estimates of the percentage of children who
100 die of ARI downwards by about 4%. Because the
confidence limits implied by the analysis of verbal autopsies
include 80% (39 of 49) of the data points, it is likely that the
variability inherent in verbal autopsies accounts for most of
the remaining 85% of the variability in figure 2 that is not
accounted for by the variability arising from the finite
sample sizes.
Finally, we combine the fits derived here (figure 2) with
estimates of total mortality in children for 171 of the 191
member states of the WHO,1 which includes 99% of the
world’s children to estimate the number of children who die
from ARI. We extrapolated the estimates of total childhood
mortality up to 1999 as reported by Ahmad et al,1 assuming
an exponential trend, to obtain the best estimate of the
country specific under-5 mortality in the year 2000. The
proportional mortality derived from the fit given in figure 2,
with population estimates for each country,35 was then used
to estimate the number of deaths in children under 5 due to
ARI in each country of the world. The results are displayed
in figure 6. The proportion of children who die from ARI is
<5%
5% to 10%
10% to 15%
15% to 20%
20% to 25%
>25%
Countries in which
surveys were done
29
 Review
Table 3. Total number of children dying each year, estimated
number that die of ARI followed by 95% confidence limits, and
percentage of deaths due to ARI in each WHO region.
Region Deaths ARI deaths Range
AFR 3608 794 677–911
AMR 436 60 47–73
EMR 1345 261 221–302
EUR 217 24 17–32
SEAR 3274 606 519–694
WPR 979 132 102–162
Total 9901 1880 1582–2178
All numbers in thousands. AFR=Africa, AMR=Americas, EMR=Eastern Mediterranean,
EUR=Europe, SEAR=South East Asia, WPR=Western Pacific.
very low in the established market economies and somewhat
higher in the countries of the former Soviet Union. In most
of Asia, and Central and South America, the proportions are
towards the middle of the worldwide range, whereas in some
countries, mainly in Africa and in parts of the Far East, the
proportion of children dying from ARI is still very high.
The errors associated with the fitted line in figure 2 were
combined with the errors in the estimates of total childhood
mortality1 to determine the errors in the estimates of the
number of children dying of ARI. Aggregating these data by
WHO regions36 gives the results in table 3 and we estimate
that between 1·6 and 2·2 million children (95% confidence
interval) die of ARI each year throughout the world with
about 40% of these deaths happening in Africa and about
30% in southeast Asia.
Discussion
The analysis presented here confirms the association put
forward by Garenne et al5 on the basis of their analysis of
Preston’s data6 in which the proportion of deaths
attributable to ARI diminshes as general mortality
diminshes. As under-5 mortality diminshes from 50 to 20,
10 and then 5/1000 children at risk per year, the proportion
of deaths attributable to ARI decreases from 23% to 18%,
15%, and then 11% (with 95% confidence limits of about
±2% to ±3% at all levels). There is, however, a significant
amount of residual variation in the data.
Much of the residual variability in the estimates of the
proportion of childhood deaths attributed to ARI is due to
the use of verbal autopsies to determine the cause of death.
The classification of deaths by verbal autopsies is difficult,
especially in neonates, and the more so when trying to
distinguish respiratory infections from other conditions.12
Many studies have explored the problem of obtaining
reliable, repeatable, and consistent results when using verbal
autopsies to diagnose ARI.11,15,17,29,37
Unfortunately, it is difficult to quantify the effect of using
verbal autopsies on estimates of the proportion of deaths due
to ARI because the studies designed to measure this directly
differ from the community studies. The rate of false-positive
diagnoses is higher in the comparative studies than in the
community studies, and the prevalence of ARI is much
higher in the comparative studies than in the community
studies (47% vs 19%, respectively). Nevertheless, if we apply
30
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Child deaths from ARI
the results of the comparative studies to the community
studies, this suggests that the percentage of deaths due to
ARI (figure 5) could be underestimated by about 4%,
which would increase our estimate of the number of
%ARI childhood deaths due to ARI in the world from 1·9 million
22a
to about 2·3 million.
14
Attributing deaths to ARI is complicated further because
ARI is often associated with other illnesses such as measles
19
and malaria, as well as malnutrition. In two of the studies15,17
11
ARI deaths referred to deaths from pneumonia only, in two
19
others the definition of ARI included tachypnoea,13,14 and in
13 three other studies11,12,16 a death due to ARI was classified on
19 the basis of a combination of related signs and symptoms.
Most of the studies listed measles as a separate cause of
death, while ARI deaths following measles was addressed
separately in one study only.11 Tupasi et al16 attributed 62%
of all deaths to ARI but most of these were associated with
measles. When measles deaths are excluded the proportion
falls to 24% (table 2). Similarly, Spika et al12 estimated that
29% of deaths could be attributed to ARI but if deaths
associated with other causes are excluded the figure falls to
22% (table 2).
In seven of 15 studies done in the Americas under
PAHO7 the recorded percentage of children who die from
If we know the sample size and assume binomial errors
then we can calculate the stochastic variance for each data
point i in the usual way as ␴ i=piqi/ni. However, there is also
2
variability due to other factors including the inherent
uncertainty associated with the use of verbal autopsies. We
let this unknown, but constant, variance in each point
estimate be s2. The total variance is then
S2=∑ (␴ 2i+s2)
i
and we estimate s2 as
Ŝ ⫺∑i␴ i
2 2
2
Ŝ =
N
where Sˆ is the total sum of the squares of the deviations
2
about the fitted line and N is the total number of points.
The log-likelihood is then (apart from constant terms)
⫺∑ ␦ 2i ␻ i /2
i
where ␦i is the difference between the observed and fitted
values and ␻ i , the weight for point i is
1
␻
ˆ=
␴ i⫹Ŝ
2 2
so that
n␦ 2i
L⫽⫺ 2
∑
i N␴ ⫹Ŝ2⫺∑ ␴ 2i
2
i
i
When ␴ i →0 the log-likelihood is just the standard
expression for unweighted least squares; when S ⬇⌺␴i2 the
2
log-likelihood is given by the standard expression using the
variances estimated for binomial errors. The parameters of
the fitted curve were then varied to maximise the
likelihood and the confidence limits for the fitted
parameters calculated in the usual way.27
THE LANCET Infectious Diseases Vol 2 January 2002
 Child deaths from ARI
ARI falls significantly below the expected line, and only in
Bolivia is the recorded number significantly greater than the
expected number (table 1 and red dots in figure 2).
However, in these studies care was taken to distinguish
between ARI as an underlying cause and ARI as an
associated condition, and deaths were attributed to more
than 40 different possible causes. The proportion of deaths
for which ARI was an associated condition rather than the
underlying cause varied from 24% in Recife, Brazil, to 52%
in La Paz, Bolivia. If all of the deaths for which ARI is an
associated cause had been classified as ARI deaths, the
number of deaths due to ARI would have increased by two
to threefold. Puffer and Serano7 note that “as diagnostic and
recording procedures are improved the role of lower
respiratory conditions as underlying causes decreases
and they become more significant as associated conditions
(consequences) of other causes of death”. It seems likely
that the low proportion of deaths attributable to ARI in
this study is due to the extensive and detailed nature
of the diagnostic procedures and classifications that
were used.
Two studies gave estimates of the proportion of deaths
due to ARI that were greater than expected. The first was
part of a control project using co-trimoxazole to treat acute
respiratory infections in Bagamoyo, Tanzania.24 Because the
focus was on identifying and treating ARI, it is possible that
some of the ARI deaths should have been regarded as being
associated with ARI rather than directly caused by ARI,
which could explain the unusually high estimate for the
proportion of deaths due to ARI.
The second study, by Coakley et al9 in Papua New
Guinea, was part of a pneumonia research programme that
used verbal autopsies in which families were visited 3
months after the death of the child. The high proportion of
deaths attributable to ARI (34·7%, table 1) could be because
the study focused on pneumonia rather than on other causes
of mortality.
Finally, we note that in recent years the impact of
HIV on under-5 mortality has become apparent in some
countries but especially those in east and southern Africa.
A study38 has shown that in Botswana, for example,
where the prevalence of HIV is high and childhood
mortality was previously low compared with other countries
in the region, up to 48% of childhood deaths might be
attributable to HIV. In those countries where HIV
prevalence is high in pregnant women, the patterns of
childhood mortality are likely to change considerably over
the next decade or so.
Conclusion
ARI is still one of the most important causes of childhood
mortality in poor countries. It is important to obtain reliable
estimates of the number of children who die from ARI and
to understand how and why this varies among communities.
We have been able to show that the proportion of deaths
due to ARI declines as general mortality declines following a
log-linear association of the form suggested by Garenne et
al5 on the basis of their analysis of historical data collected by
Preston.6 Several of the individual studies nevertheless
depart significantly from the fitted line and we have
THE LANCET Infectious Diseases Vol 2 January 2002
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Review
Search strategy and selection criteria
Articles referring to mortality in children were identified
from previous reviews, a searches of Medline and
unpublished work, as well as an extensive, unpublished
electronic and a paper-based search were done by the
Department of Child Health of the World Health
Organization. Keywords in the search of electronic
databases were “pneumonia”, “acute respiratory
infections”, “childhood mortality” and “deaths”, and
“verbal autopsies”.
examined the extent to which this may be due to the
variability inherent in the use of verbal autopsies.
Unfortunately, despite the large number of studies that have
explored the variability in the use of verbal autopsies, most
of these comparative studies are done under conditions
different from conditions in studies of the extent of ARI
mortality in children. Nevertheless, if we extrapolate the
data from these studies to the conditions of studies of the
extent of ARI as a cause of death in children, we find that the
variability inherent in the use of verbal autopsies could
explain most of the observed variability.
The variability can be reduced if care is taken only to
include deaths that are directly attributable to ARI. The
study of Puffer and Serano7 shows that for every death
directly attributable to ARI there could be two to three
further deaths for which ARI is an associated cause of death.
This in turn draws attention to the importance of dealing
with comorbidity and why interventions against
pneumonia, for example, could have a larger effect on all-
cause mortality than they have on the direct cause of death
at which the intervention is targeted.
The log-linear fit in figure 2 provides the best estimate of
the association between the proportion of deaths due to ARI
and general under-5 mortality. As general mortality
diminishes the mortality due to ARI diminishes faster and
based on this relationship we estimate that between 1·6 and
2·2 million children die each year from ARI.
Acknowledgments
We thank Claudia Stein, Michel Garenne, Kim Mulholland, and Robert
Black for reviewing this paper and for their comments and suggestions.
This work was supported by the World Health Organization
Departments of Child and Adolescent Health and Development, and
Vaccines and Biologicals. We have received no outside funding in
support of this project, and have no conflicts of interest involving
financial or personal relationships with other persons or organisations
that could inappropriately influence the work.
Figure 6: the designations employed and the presentation of material
on this map do not imply the expression of any opinion whatsoever on
the part of the WHO concerning the legal status of any country,
territory, city, or area or of its authorities, or concerning the
delimitation of its frontiers or boundaries. Dashed lines represent
approximate border lines for which there may not yet be full
agreement.
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