Burden of Disease Caused by Otitis Media: Systematic

Review and Global Estimates

Lorenzo Monasta
1
*, Luca Ronfani
1
, Federico Marchetti
2
, Marcella Montico
1
, Liza Vecchi Brumatti
3
,
Alessandro Bavcar
4
, Domenico Grasso
5
, Chiara Barbiero
1
, Giorgio Tamburlini
3
1Epidemiology and Biostatistics Unit, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy, 2Department of Paediatrics, Institute for Maternal and
Child Health - IRCCS Burlo Garofolo, Trieste, Italy, 3Research Direction, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy, 4Unit for Health
Services Research and International Health, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy, 5Ear, Nose and Throat Unit, Department of
Paediatric Surgery, Institute for Maternal and Child Health - IRCCS Burlo Garofolo, Trieste, Italy
Abstract
Background: Otitis media (OM) is a leading cause of health care visits and drugs prescription. Its complications and sequelae
are important causes of preventable hearing loss, particularly in developing countries. Within the Global Burden of Diseases,
Injuries, and Risk Factors Study, for the year 2005 we estimated the incidence of acute OM, chronic suppurative OM, and
related hearing loss and mortality for all ages and the 21 WHO regional areas.
Methods: We identified risk factors, complications and sequelae of OM. We carried out an extensive literature review
(Medline, Embase, Lilacs and Wholis) which lead to the selection of 114 papers comprising relevant data. Data were
available from 15 of the 21 WHO regions. To estimate incidence and prevalence for all countries we adopted a two stage
approach based on risk factors formulas and regression modelling.
Results: Acute OM incidence rate is 10.85% i.e. 709million cases each year with 51% of these occurring in under-fives.
Chronic suppurative OM incidence rate is 4.76%i.e. 31million cases, with 22.6% of cases occurring annually in under-fives.
OM-related hearing impairment has a prevalence of 30.82 per ten-thousand. Each year 21thousand people die due to
complications of OM.
Conclusions: Our study is the first attempt to systematically review the available information and provide global estimates
for OM and related conditions. The overall burden deriving from AOM, CSOM and their sequelae is considerable, particularly
in the first five years of life and in the poorest countries. The findings call for incorporating OM-focused action within
preventive and case management strategies, with emphasis on the more affected.
Citation: Monasta L, Ronfani L, Marchetti F, Montico M, Vecchi Brumatti L, et al. (2012) Burden of Disease Caused by Otitis Media: Systematic Review and Global
Estimates. PLoS ONE 7(4): e36226. doi:10.1371/journal.pone.0036226
Editor: Ann M. Moormann, University of Massachusetts Medical School, United States of America
Received January 24, 2012; Accepted March 28, 2012; Published April 30, 2012
Copyright: 2012 Monasta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: For this work, financial support was received by the University of Edinburgh and by the Institute for Maternal and Child Health - Istituto Di Ricovero e
Cura a Carattere Scientifico Burlo Garofolo (n.31/09). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of
the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: monasta@burlo.trieste.it
Introduction
Acute otitis media (AOM) is a very common condition and a
leading cause of health care visits and antibiotic prescription [1].
Studies carried out in developed countries show that by their third
birthday 80% of children will have experienced at least one
episode of AOM [2,3] and 40% will have six or more recurrences
by the age of seven years [4]. As with most infectious diseases, the
burden of AOM varies substantially across countries, the main
differences residing in the frequency of suppurative complications
such as mastoiditis and meningitis and of sequelae such as hearing
loss due to chronic suppurative otitis media (CSOM) [1,3]. CSOM
is an important cause of preventable hearing loss, particularly in
the developing world [5], and a reason of serious concern,
particularly in children, because it may have long-term effects on
early communication, language development, auditory processing,
psychosocial and cognitive development, and educational progress
and achievement [6].
Based on prevalence surveys, which vary widely in disease
definition, sampling methods, and methodological quality, WHO
estimated that 28 thousand deaths every year are attributable to
complications of OM [6]. OM and CSOM can lead to death
mainly through meningitis and brain abscess. In addition WHO
estimated that between 65 and 330 million individuals suffer from
CSOM (show signs of CSOM), 50% of whom suffer from hearing
impairment [6].
In industrialised countries, hearing loss (both conductive and
sensorineural) is known to be the third most prevalent chronic
condition in older adults after hypertension and arthropathy with
considerable implications on physical and mental health [7,8].
Information on the adult population of less industrialised countries
is scanty [5]. A better knowledge of the incidence and prevalence
of AOM and its complications across ages and geographical
PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e36226
regions is necessary to adequately assess the need for interventions
aimed at reducing its health, social and economic burden.
As members of the Expert Group on pneumonia, meningitis,
sepsis, otitis media, pertussis and influenza of the Global Burden of
Diseases, Injuries, and Risk Factors Study, we estimated the global
burden of otitis media for all ages for all of the 21 WHO regional
areas [9], for the year 2005, through a systematic, transparent and
comprehensive literature review.
Methods
All aspects of the methods are described in more detail in Text
S1.
Identification of risk factors, complications and sequelae of OM
was the starting point (Figure 1, Table 1). Given the complexity of
the causal pathways, the frequent overlapping of conditions, the
lack of clear and consistent definitions and the fact that conditions
included may have a mild and temporary nature or be rare, we
focused in our review on AOM, CSOM, and on permanent
Hearing Impairment (HI, both conductive and sensorineural)
caused by OM (Figure S1). This simplification is consistent with
that adopted in previous estimates of the OM GBD [10].
We searched for all articles presenting original data on
incidence or prevalence of AOM or CSOM, and linking HI data
with CSOM (proportion of HI caused by CSOM, or proportion of
CSOM cases causing HI), published from 1980 to 2008. We did
not formally define nor register a review protocol. The systematic
review covering AOM, CSOM, HI and related risk factors was
carried out on Medline (PubMed, last search 11/08/2008),
Embase (last search 23/07/2008), Lilacs (last search 11/08/
2008), Wholis (last search 11/08/2008), without any language
restriction (details in Table S1). We retrieved 9356 records that
became 7168 after duplication removal (Figure 2 for the complete
flow diagram). We carried out a two-step evaluation to identify
relevant papers:
1) by titles, abstract and keywords, aimed at identifying papers
on epidemiology and risk factors of OM and reviews on OM
(Figure S2). Papers on risk factors were used to review and
complete the risk factors diagram (Figure S3).
2) by full text, when available, aimed at identifying papers on
epidemiology of AOM, CSOM and HI. All articles with
original data on AOM, CSOM or HI incidence or prevalence
were included.
Information on mortality was collected through WHO vital
registration databases, when available and reliable, or estimated
for countries and areas where data were unavailable or unreliable.
Both the selection of relevant papers and data extraction were
carried out independently by two of the authors (respectively by
Figure 1. Sequelae of OM (complete scheme) with ICD-10-CM diagnosis codes.
doi:10.1371/journal.pone.0036226.g001
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 2 April 2012 | Volume 7 | Issue 4 | e36226
LM and AB or CB, and by LM and MM, LVB or CB). Any
disagreement were resolved through discussion involving a third
author (LR).
Estimation process: incidence of AOM and CSOM
When only prevalence data were available, prevalence was
transformed into incidence based on the average duration of
AOM and CSOM. Although studies show that clinically
symptomatic AOM usually has a shorter duration [11,12] we
assumed a duration of 21 days because when both prevalence and
incidence data were available the actual duration, including the
effusion was shown to be around 21 days [13]. This was the only
real evidence on duration of AOM we could rely on. The average
duration of CSOM in adults is 10 years [1419].
The estimation process was divided into two phases. In the first
and second phase all estimations were done by country within a
specific area, the only exception being Oceania, for which we
extrapolated country specific data to the whole region. As
described below, while phase one estimations were carried out
using a formula based on risk factors, the second phase was based
on exponential regression models. Phase one, in fact, generated
estimates for countries in regions in which we had original data.
Phase two allowed us to expand the estimates to regions with no
data and in general to fine tune all previously elaborated estimates.
Estimates were done by all age groups [9]. We did not calculate
estimates by gender, since evidence on gender differences is scanty
and conflicting.
AOM and CSOM estimates: first phase. The first phase
was carried out by the following formula based on risk factors:
N
N
e=cy
~ Pop
new
| Inc
Ref
| 1z
P
i~1?n

Prev
RF:new:i
{Prev
RF:Ref:i
|RR
RF:i
{1 g
Were N
e/cy
is the number of cases, Pop
new
is the population,
Inc
Ref
is the incidence in the reference population, Prev
RF.new.i
is
the prevalence of a specific risk factor i in the new population,
Prev
RF.Ref.i
is the prevalence of the i risk factor in the reference
population, RR
RF.i
is the risk ratio for risk factor i.
Incidence in the reference population refers to the incidence for
those countries for which data were available from the literature.
Risk estimates were extracted from the literature review [2022]
and in particular from day care center attendance (RR 2.45),
exclusive bottle-feeding vs. exclusive breastfeeding up to six
months (RR 2.00), parental smoking (RR 1.66), and malnutrition
(RR 3.48).
The choice of limiting the list of risk factors to the ones above
was determined, among the more relevant, by two fundamental
reasons. The first being that we needed good quality data on risk
ratios and, thus, we focused on data from meta-analyses.
Malnutrition was an exception but we considered it to be a key
factor in developing countries. The second reason is that we
needed risk factors for which we could have reliable information
for each country. Malnutrition was included only for developing
countries (no data on malnutrition is available for developed
countries and malnutrition is certainly more important in
developing countries), while day-care centre attendance was only
included for developed countries (no data on day-care centre is
available for developing countries and is certainly more important
in developed countries).
We used two different sets of risk factors. For Western Europe,
North America High Income, Asia Pacific High Income and
Australasia we used the following risk factors and associated
Relative Risks (RRs): adults smoking (RR 1.66), exclusive
breastfeeding at six months (RR 2.00), day-care attendance (RR
2.45). Data for these risk factors, for the year 2005, were taken
from WHO, UNICEF and OSCE reports and databases [2327]
(www.oecd.org/els/social/family/database). For all other areas,
day-care was substituted with under five children underweight
(RR 3.48).
AOM and CSOM estimates: second phase. Areas for
which we did not have any data were: Europe Central, Europe
Eastern, Oceania, Asia East, Asia Central, Latin America
Southern and Latin America Andean. To be able to cover these
areas and to fine tune the estimates elaborated in phase one, we
adopted a more robust strategy.
Phase two was based on exponential regression models. A model
for AOM and a model for CSOM incidence rates were built for
less industrialised areas. These models were based on the following
factors: [2325] prevalence of Acute Respiratory Infections (ARI)
in children under five (ARI-U5), underweight prevalence in under
five children (U-U5), under five mortality rate (MR-U5),
proportion of children under six months exclusively breastfed
(EBF), prevalence of adults smoking (AS). These models were
based on data and phase one estimates from 45 countries and
helped estimate AOM and CSOM incidence for the age group 1
4 years and validate the estimates of all countries. These models
had an R
2
of 0.83 for AOM and 0.85 for CSOM:
N
AOM=35.1859 * (1.0235
ARI-U5
) * (1.0060
U-U5
) * (0.9979
AS
) *
(1.0079
MR-U5
) * (0.9846
EBF
)
Table 1. Definitions of main conditions involved in the sequelae of otitis media.
Otitis media is the generic term for all types of inflammation of the middle ear [60,61].
Acute otitis media (AOM) is usually a short-term inflammation of the middle ear, characterised by the rapid onset of one or more signs or symptoms of acute
inflammation in the middle ear such as earache, tugging at the ear, fever, or irritability in the presence of a middle-ear effusion. It is often preceded by upper respiratory
symptoms, including a cough and rhinorrhoea [39,60,61].
Chronic suppurative otitis media (CSOM) is defined as a persistent inflammatory process associated with a perforated tympanic membrane draining exudate for
more than 6 weeks [62]. It is often associated with a cholesteatoma.
Hearing impairment (HI): is the total or partial inability to hear sound in one or both ears [63]. WHO defines disabling hearing impairment as having permanent
unaided hearing threshold in the better ear of more than 30 dB in children aged up to 15 years, or more than 40 dB in adults at frequencies of 0.5, 1, 2, and 4 kHz [64].
- Conductive hearing loss (CHL) is the total or partial inability to hear sound in one or both ears because of some mechanical problem in the external or middle ear.
The three tiny bones of the ear (ossicles) may fail to conduct sound to the cochlea, or the eardrum may fail to vibrate in response to sound. Fluid in the middle ear can
cause CHL [63].
- Sensorineural hearing loss (SNHL) is the total or partial inability to hear sound in one or both ears resulting from a dysfunction of the inner ear. It most often
occurs when the tiny hair cells (called cilia) that transmit sound through the ear are injured. This type of hearing loss is sometimes called nerve damage, although this
is not accurate [63].
doi:10.1371/journal.pone.0036226.t001
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 3 April 2012 | Volume 7 | Issue 4 | e36226
Figure 2. Screening process of articles on epidemiology of AOM, CSOM and HI, according to the PRISMA 2009 Flow Diagram. AOM:
Acute Otitis Media; CSOM: Chronic Suppurative Otitis Media; HI: Hearing Impairment.
doi:10.1371/journal.pone.0036226.g002
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 4 April 2012 | Volume 7 | Issue 4 | e36226
N
CSOM=4.8451 * (1.0152
ARI-U5
) * (1.0298
U-U5
) * (1.0055
AS
) *
(1.0021
MR-U5
) * (0.9872
EBF
)
We should not be surprised to see that single risk factors have
coefficients that vary from .1 to ,1 in different models (i.e. AS in
the models above and EBF in the ones below), if we take into
account the possibility of different interrelations between risk
factors considered simultaneously.
For more industrialised areas (Europe Western, North America
High Income and Australasia) we built exponential models to
estimate AOM and CSOM for 14 years old children based on
breastfeeding, adults smoking, day-care attendance (DCA) and
under five mortality rate. The models were based on 22 countries
Europe Western countries and helped re-estimate the other
countries and validate the estimates of all countries. The R
2
for
these models were 0.61 for AOM and 0.79 for CSOM:
N
AOM
14
=20.9264 * (0.9882
EBF
) * (1.0124
DCA
) * (1.0008
AS
) *
(0.9998
MR-U5

3
)
N
CSOM
14
=0.8572 * (1.0010
EBF
) * (1.0110
DCA
) * (1.0123
AS
) *
(1.0022
MR-U5

3
)
The estimates of AOM and CSOM for Australia, Greenland
and New Zealand were calculated as a weighted average of the
estimates for aboriginals and non-aboriginals, with weight based
on proportion of aboriginals to non-aboriginals by age group. For
Asia Pacific High Income we kept the estimates based on the first
phase model.
Estimation process: prevalence of Hearing Impairment
According to the WHO definitions [28,29] (Table S2), we
estimated the prevalence of HI for all four degrees (slight,
moderate, severe and profound). We used the following assump-
tion to extend the estimates to the four degrees of HI or to estimate
the WHO thresholds from other thresholds used (pg.6): Where
non-WHO thresholds used, the prevalence of hearing impairment
at the WHO thresholds was interpolated assuming the log of the
cumulative prevalence is linear with threshold. This relationship
holds reasonably well in most studies [29].
Again, a two phases estimation process was adopted in order to
elaborate robust estimates. Details on the assumptions made and
on both estimation phases are described in the Text S1.
HI estimates: first phase. We estimated cases of HI due to
otitis media on the basis of the Oman age distribution of HI [30].
The Oman study was the only one reporting a complete age
distribution of HI due to OM. The Oman distribution included
HI caused by presbyacusis and accidents, thus we corrected this
distribution to only include HI due to CSOM, and on the basis of
the 0.19% of the population affected by HI due to CSOM
calculated from Oman but adjusted to Europe, using Finland
(0.001232%).
N
Prevalence of HI.35 dB in best ear was extrapolated to
countries on the basis of cases of CSOM per age group.
N
Prevalence was cumulated to calculate cumulated cases and
then cases by age group.
N
Total for Western Europe were then calculated adding all
cases per country and age group.
This was done for all regions for which we had countries with
data: Brazil [19], China [31], India [32,33], Malaysia [34],
Nigeria [35], Oman [30] and South Africa [36].
HI estimates: second phase. Two regression models were
used in the second phase: one model was used to estimate the
prevalence of slight HI (25 dB to 40 dB), and another to estimate
moderate HI (40 dB to 60 dB), using estimates from respectively
11 and 10 countries (China, India, Japan, Malaysia, Australia,
Oman, Finland, Brazil, United States of America, South Africa,
Nigeria) for which we had more reliable data and/or estimates. In
the 40 dB model we used estimates from the same countries but
excluding Malaysia, which did not have a good fit in the model
compared with the other countries. The models, with regressors
and coefficients, are reported in Text S1.
Mortality estimates
We selected a number of countries for which we had reliable
WHO 2005 Vital Registration data. Using these data and
regressors such as incidence of AOM, CSOM, AOM in 14,
CSOM in 14 and under five mortality rate, we developed and
evaluated three different regression models. Models and reasons
for choosing different models for different areas are described in
detail in Text S1.
The 1
st
model was based on overall otitis mortality rate
610million from 12 countries and four regressors (U5 mortality,
overall CSOMx1000, CSOM 14, AOM 14) had a R
2
of 0.954
and a Standard Error (SE) of 8.09:
N
MORT
1
=2107.3699+0.0804*U5-MR+34.0711*CSOM2
0.3516*CSOM1420.4326*AOM14
The 2
nd
was based on nine countries and two regressors (U5
Mortality rate and adult mortality): had a R
2
of 0.996 and an SE
of 2.60:
N
MORT
2
=8.4023+0.5101*U5-MR20.1222*Adult-MR+0.0168*
(U5-MR)
2
The 3
rd
model was based on seven countries and the same four
regressors as model one: had a R
2
of 0.997 and an SE of 0.32:
N
MORT
3
=27.8715+0.5709*U5-MR+2.3664*CSOM+0.0776*
CSOM1420.0382*AOM14
For all areas but five we selected the average of two models (1
st
and 3
rd
). For Asia Pacific High Income we selected an average
between the 2
nd
and the 3
rd
models. For Latin America Andean
we used the 3
rd
model. Australasia used the 2
nd
model. The choice
of the models to adopt for each area were made on the basis of
models fitting vital registration data when available even if less
reliable than the ones used for the generation of the models or on
the basis of unreliable or negative estimates generated by the other
models.
Uncertainty bounds
For AOM and CSOM incidence and HI prevalence, uncer-
tainty bounds were calculated using the standard error (SE) of the
second phase regression models. Further sources of uncertainty for
AOM and CSOM estimates derive from the data selected from
original studies, from the adoption of estimates generated by the
model used in phase one, from the decision on how to estimate the
age distributions, and from the approach taken to convert
prevalence to incidence. For HI estimates, uncertainty also derives
from the use of previously estimated AOM and CSOM incidence,
the adoption of WHO formulas to estimate different degrees of
HI, the decisions on how to transpose original data on worst to
best year, the use of data selected from original studies (including
the heterogeneity in methods used to establish HI in different
studies and the uncertainty of survey data) and finally the adoption
of the Oman distribution in the estimation of HI by age. For
mortality estimates, uncertainty bounds were calculated using the
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 5 April 2012 | Volume 7 | Issue 4 | e36226
SE of the regression models. Further uncertainty derives from the
methodology used to estimate the age distribution, and from the
use of estimates of AOM and CSOM as regressors, which for their
nature are subject to imprecision. To account for all sources of
uncertainty, we increased the confidence level to 99%. It is,
however, important to emphasise that the increase from 95% to
99% should be considered as a way to include other sources of
uncertainty and that by no means these bounds should be
considered to express 99% confidence.
Results
Out of 584 papers on OM epidemiology, 307 were excluded
because they were clearly not providing information relevant to
our study. Out of the remaining 277, 29 were not available in full
text. We then evaluated the 248 papers available in full text and
excluded further 134 because not relevant for our study. Out of
the remaining 114 papers, 39 contained data on AOM, 65 on
CSOM and 43 on HI (Figure 2).
Data on AOM were available from six regions, the majority of
the studies (32 of 44) being carried out in Europe Western and
North America High Income (Table S3). Data on HI/CSOM
were available for a greater number of regions. We were able to
find data on CSOM from 15 regions, data on proportion of
CSOM causing HI from 10 regions and data on proportion of HI
caused by OM from 11 regions. Data covering all four classes of
indicators were available only for three regions, whilst for six
regions no data were found. Overall, our review was able to collect
some data on AOM, CSOM or HI from 15 out of 21 regions,
while only three areas had data on all three conditions: Europe
Western, North Africa/Middle East and North America High
Income.
In Tables 2 and 3 (Table S4) and Figures 3, 4, 5, 6 we report
global estimates for AOM, CSOM, HI and attributable mortality.
AOM
Global AOM incidence rate (new episodes per hundred people
per year) is, according to our estimates, 10.85% i.e. 709 million
cases each year with 51% of these occurring in children under five
years of age (U5) (Tables 2 and 3). Global incidence rate ranges
from 3.64 for Europe Central (40% of cases occurring in children
05) to 43.36 and 43.37 for Sub-Saharan Africa West (56% in U5)
and Central (58% in U5) respectively. Other areas with incidence
lower than 5 are Asia Pacific High Income (3.75), Asia East (3.93),
Europe Eastern (3.96) and Latin America Southern (4.25).
Global incidence rate is highest in the age group 14 (60.99%)
and in the first year of life (45.28%). Incidence lowers to a
minimum of 1.49 in the age group 3544 and raises again to 2.3%
after 75 years of age.
Areas with an incidence rate higher than 100% in the 14 age
group are Oceania (114.98%), Sub-Saharan Africa Central
(143.87%) and West (154.12%). An incidence rate of over 100%
means we expect children in this age group to have an average of
more than one episode of AOM in a one year time. In such age
group four areas have an incidence below 30%: Latin America
Andean (29.39%) and Southern (25.56%), Asia East (27.38%) and
Asia Pacific High Income (24.21%).
CSOM
Global estimated CSOM incidence rate is 4.76 per thousand
people for a total of 31 million cases, with 22.6% of these cases
occurring annually in U5 children. Latin America Andean is the
area with the lowest incidence (1.70 per thousand), followed by
Asia Pacific High Income (3.02) and North America High Income
(3.06). Oceania has the highest incidence with 9.37, while two
other areas have an incidence higher than 7: Sub-Saharan Africa
Central (7.56) and West (7.22).
Globally, CSOM incidence rate is highest is the first year of life
(15.40 per thousand) and reaches its lowest value after 65 years of
age (2.51).
In the first year of life, Asia Pacific High Income has the lowest
incidence rate (1.59 per thousand), while Oceania has the highest
(35.96). The proportion of cases occurring in U5 vary from 1.8%
in the Asia Pacific High Income, to 38.9% in Oceania and 41.0%
in Sub-Saharan Africa Central.
Hearing Impairment
HI caused by OM, defined as permanent hearing loss for best
ear .25 dB, has a prevalence of 30.82 per ten thousand, with
Europe Western, Australasia, North America High Income and
Asia Pacific High Income all having a prevalence below 2 per ten
thousand. Asia South has by far the highest prevalence (97.04),
followed by Oceania (51.23) and then by Sub Sahara Africa West,
East and Central all in the range of 30 to 35.
Prevalence increases with age, with 9.34 per ten thousand in the
first year of life and a highest prevalence of 45.05 in the age group
6574.
In Asia South, by the age of five, six out of one thousand
children (6.02 per thousand) have a HI of at least 25 dB in the best
ear caused by sequelae of OM. Oceania follows with 3.02 per
thousand, then Sub-Saharan Africa West, East and Central with
2.21, 1.95 and 1.92 respectively. On the opposite extreme, less
than one child per ten thousand suffers from HI by the age of five
in Europe Western (0.55 per ten thousand), Australasia (0.62)
North America High Income (0.64) and Asia Pacific High Income
(0.80).
Mortality
According to our estimates, globally, each year approximately
21 thousand people, i.e. 33 per 10 million people, die due to the
complications of OM. Mortality is higher in the first year of life
(85.4 per 10 million) and in the age group 14 years of age (90.5).
it lowers to 13.6 in the 2534 years age group and raises again to
the highest values after 75 years of age (160.5).
North America High Income shows the lowest mortality (1.6 per
10 million), followed by Asia Pacific High Income (1.7), Europe
Western (2.8) and Australasia (3.7). Oceania has the highest
mortality with 101.1 deaths each year per 10 million, followed by
Sub-Saharan Africa Central (96.2) and West (91.8). Other areas
with a mortality higher than 50 per 10 million are Sub-Saharan
Africa East (73.49) and Asia South (68.88).
Discussion
Our study is the first attempt to systematically review the
available information and provide global estimates for the
incidence of AOM and CSOM, the prevalence of OM-related
HI, and for OM-related mortality.
In our review we had to face a number of difficulties, the main
ones being the scarcity or absence of data from some geographical
areas and age groups and the heterogeneity of the available
information, due to heterogeneity in study design, measurements
and definitions. We provide estimates for 21 geographical sub-
regions and 13 age groups. Since we were able to collect data on
either AOM, CSOM or HI from 15 out of 21 regions, some of our
estimates are based on modelling. In other cases we extrapolated
to sub-regional level data that were collected in only a few
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 6 April 2012 | Volume 7 | Issue 4 | e36226
Table 2. AOM and CSOM incidence rate, HI prevalence and mortality estimates for the year 2005, by WHO areas.
Areas
AOM% incidence CSOM% incidence
HI.25 dB best ear 6/666
prevalence Deaths 6/666666
AOM MIN MAX CSOM MIN MAX HI MIN MAX Deaths MIN MAX
Asia Central 7.90 7.21 8.59 4.05 3.53 4.56 8.60 7.96 9.24 18.88 12.24 30.98
Asia East 3.93 3.24 4.61 3.67 3.16 4.18 9.69 9.05 10.32 9.32 9.04 9.62
Asia Pacific High Income 3.75 3.31 4.19 3.02 2.17 3.88 1.91 1.28 2.54 1.72 1.00 2.49
Asia South 14.52 13.84 15.21 6.56 6.05 7.08 97.04 96.37 97.71 68.88 68.21 69.02
Asia South East 8.15 7.47 8.84 4.69 4.17 5.20 14.67 14.03 15.31 27.16 25.18 29.81
Australasia 7.25 6.81 7.69 3.41 2.56 4.26 1.36 0.75 1.99 3.69 0.00 9.83
Caribbean 9.08 8.40 9.77 4.18 3.67 4.70 7.32 6.68 7.96 18.60 12.57 78.84
Europe Central 3.64 2.95 4.32 3.69 3.17 4.20 5.02 4.39 5.65 4.97 2.61 16.08
Europe Eastern 3.96 3.28 4.65 3.75 3.24 4.26 5.30 4.67 5.93 5.72 4.73 9.31
Europe Western 5.91 5.88 5.99 3.39 3.24 3.57 1.34 0.72 1.96 2.82 2.53 3.11
Latin America Andean 5.39 5.02 6.07 1.70 1.19 2.21 5.30 4.64 5.96 12.72 12.32 12.72
Latin America Central 6.78 6.10 7.47 3.92 3.40 4.43 5.28 4.65 5.91 12.36 9.16 16.96
Latin America Southern 4.25 3.56 4.93 3.60 3.09 4.12 5.15 4.52 5.79 6.00 3.94 13.53
Latin America Tropical 5.90 5.21 6.59 3.74 3.23 4.25 4.95 4.32 5.58 9.60 8.82 10.58
North Africa Middle East 8.67 7.98 9.35 4.41 3.90 4.92 8.63 7.99 9.27 21.96 18.48 27.17
North America High Income 5.46 5.40 5.53 3.06 2.82 3.30 1.41 0.79 2.04 1.63 1.23 1.90
Oceania 28.56 27.87 29.24 9.37 8.86 9.88 51.23 50.57 51.88 101.07 86.63 112.17
Sub-Saharan Africa Central 43.37 42.69 44.06 7.56 7.04 8.07 30.20 29.57 30.84 96.20 90.27 102.71
Sub-Saharan Africa East 22.81 22.13 23.50 6.06 5.55 6.57 31.91 31.26 32.56 73.49 68.30 78.20
Sub-Saharan Africa Southern 14.71 14.02 15.40 4.79 4.27 5.30 9.37 8.73 10.00 33.96 29.11 43.66
Sub-Saharan Africa West 43.36 42.68 44.05 7.22 6.71 7.74 34.37 33.74 35.00 91.82 85.26 98.34
Total 10.85 10.25 11.46 4.76 4.27 5.24 30.82 30.18 31.47 32.78 31.07 35.30
doi:10.1371/journal.pone.0036226.t002
Table 3. Global AOM and CSOM incidence rate, HI prevalence and mortality estimates for the year 2005, by WHO age groups.
Age Groups
AOM% incidence CSOM% incidence
HI.25 dB best ear 6/666
prevalence Deaths 6/666666
AOM MIN MAX CSOM MIN MAX HI MIN MAX Deaths MIN MAX
011 m. 45.28 44.63 45.93 15.40 14.82 15.97 9.34 8.72 9.99 85.42 73.06 85.10
14 60.99 60.32 61.65 10.13 9.59 10.67 22.84 22.20 23.49 90.54 86.46 97.28
59 22.15 21.51 22.80 8.31 7.77 8.84 26.28 25.63 26.93 38.86 37.21 41.85
1014 18.50 17.86 19.15 3.89 3.35 4.43 26.95 26.30 27.59 32.50 31.00 34.75
1519 3.53 2.90 4.16 3.36 2.88 3.85 26.87 26.22 27.51 19.47 19.01 21.17
2024 3.14 2.52 3.77 4.80 4.25 5.38 29.68 29.04 30.32 13.72 12.86 14.84
2534 1.56 0.95 2.17 3.31 2.80 3.82 30.61 29.96 31.25 13.56 12.88 14.72
3544 1.49 0.90 2.08 3.17 2.71 3.64 32.85 32.21 33.49 19.12 18.02 20.91
4554 1.77 1.20 2.35 4.10 3.62 4.60 35.32 34.68 35.96 14.82 14.00 16.04
5564 1.92 1.37 2.47 3.74 3.34 4.14 39.58 38.94 40.22 23.36 22.14 25.28
6574 2.10 1.57 2.65 2.47 2.12 2.77 45.05 44.42 45.69 49.26 46.88 53.72
7584 2.34 1.86 2.83 2.55 2.28 2.77 43.24 42.60 43.88 156.19 149.09 168.15
85+ 2.27 1.86 2.68 2.73 2.56 2.83 37.73 37.10 38.37 179.01 167.26 200.77
Total 10.85 10.25 11.46 4.76 4.27 5.24 30.82 30.18 31.47 32.78 31.07 35.30
doi:10.1371/journal.pone.0036226.t003
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 7 April 2012 | Volume 7 | Issue 4 | e36226
countries. Data were particularly scarce on incidence/prevalence
of AOM and CSOM in adult and elderly age groups.
While there are no other global estimates of AOM, our findings
related to CSOM, HI and OM-related mortality can be compared
with the estimates released by the WHO in 2004 [6]. It is
noteworthy that our point estimate for CSOM prevalence (200.8
million cases) (Table S4) falls in between the range of estimates
provided by WHO (65.5 to 328.2 million cases). Since we had no
access to methods used by WHO to calculate previous estimates
and we avoided any comparison or adjustment with WHO data
while elaborating our methods and estimates, this may be
considered as a reciprocal validation of both estimates. Our HI
Figure 3. AOM incidence rate estimates for the year 2005 per hundred people, by the 21 WHO regions.
doi:10.1371/journal.pone.0036226.g003
Figure 4. CSOM incidence rate estimates for the year 2005 per thousand people, by the 21 WHO regions.
doi:10.1371/journal.pone.0036226.g004
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 8 April 2012 | Volume 7 | Issue 4 | e36226
prevalence estimates, on the contrary, are much lower than those
reported by WHO. Adding up the HI prevalent cases for all HI
degrees (25 dB, 40 dB, 60 dB and 80 dB for best ear) we
calculated a global estimate of 20.1 million cases. The WHO
report provides an estimate, of 164.1 million people with CSOM-
associated, but this was obtained by simply calculating 50% of
CSOM prevalence. Our estimates of HI are based on a more
complex and, in our opinion, more reliable model. In addition,
our definition of HI includes only permanent HI while the WHO
report does not explicitly exclude temporary HI. Finally, our
mortality estimate (21.4 thousand deaths due to AOM, CSOM
and related complications) is close to that reported by WHO (28
thousand) [6] which includes only mortality due to CSOM, but
Figure 5. OM-associated HI (.25 dB for best ear) prevalence rate estimates for the year 2005 per ten thousand people, by the 21
WHO regions.
doi:10.1371/journal.pone.0036226.g005
Figure 6. OM-associated mortality estimates for the year 2005 per ten million people, by the 21 WHO regions.
doi:10.1371/journal.pone.0036226.g006
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 9 April 2012 | Volume 7 | Issue 4 | e36226
much higher than the one reported in the GBD 2001 and 2004
update (4 and 5 thousand respectively) [10,37].
Not surprisingly, the incidence of AOM and, to a lesser extent,
of CSOM is particularly high in the first five years when its
incidence is more than double that of pneumonia [38] and in
Sub-Saharan Africa and South Asia. The prevalence of HI follows
a similar geographical distribution, but although it becomes
significant quite early, it increases gradually to reach its maximum
in the elderly population. Mortality attributable to OM is relatively
low as compared to other causes. However, the overall burden
deriving from the combination of AOM, CSOM and their
sequelae is considerable, particularly in the first five years of life
and in the poorest countries. AOM, CSOM and HI significantly
contribute to temporary disability, suffering, use of health services
and drug prescription and self-medication, particularly of non-
steroidal anti-inflammatory drugs and antibiotics [39]. The direct
and indirect costs of AOM, CSOM and related HI for health
systems and households, the consequences on learning and
working performances [40,41] and the cost and adverse effects
of drugs at both individual and population level represent an
important burden for societies.
The findings of our review represent a serious challenge for
health authorities. Early diagnosis and treatment of AOM,
including the rational use of antibiotics should be improved, by
incorporating clinical algorithms in current outpatient guidelines
and by supporting the use of otoscopy in primary care practice. By
doing this, prevention of complications and long term sequelae of
AOM will be greatly strengthened. This is especially important for
children under five, who bear 51% of all cases of AOM, and are
particularly affected by the consequences on language develop-
ment and school performance of early onset HI [4244]. It is also
particularly relevant for the poorest countries. We found that
AOM incidence in Sub-Saharan Africa, South Asia and Oceania
is two to eight times higher than in the remaining regions (Table 2,
Figure 3). Here, co-morbidity with malnutrition, HIV and
exposure to contaminated water greatly increases the risk of
developing CSOM and its complications [45].
Health policies and programmes should incorporate preventive
interventions as well as improved care seeking and access to
effective treatment for common conditions such as AOM and
CSOM.
Breastfeeding, smoking avoidance during and after pregnancy,
and reduction of exposure to indoor air pollution are the pillars of
prevention of AOM and its complications and sequelae [4648] as
well as of many other infant and child conditions. Vaccines against
Streptococcus pneumoniae and HiB have been introduced to
reduce the burden of child mortality consequent to meningitis and
pneumonia. Although Hib vaccines (anti-capsular) do not target
NTHi (non-capsular) which cause OM, a recent anti-Streptococ-
cus pneumoniae capsular vaccine conjugated to a NTHi protein
may be expected to reduce the incidence of AOM [49], and this
should be taken into account when estimating and comparing the
cost-effectiveness of vaccines [50] as well as of other preventive
strategies.
Early diagnosis and treatment based on prompt care-seeking
remain crucial particularly in the first years of life, also as a way to
prevent HI. In developing countries, there have been attempts to
standardize diagnosis and treatment of sick children through the
IMCI strategy [51,52]. Although IMCI does not focus explicitly on
AOM, it ensures, when effectively implemented, effective
treatment on a pragmatic basis to children with nonspecific signs
and symptoms that may be caused by AOM, but it does not call
for attention to the ear when examining the child to search for ear
discharge. The family and community component of IMCI is
supposed to improve care-seeking [52] for children with
nonspecific signs and symptoms. Improved care-seeking needs to
be combined with affordable access and effective care, which are
still an utopia in most of the poorest countries and for the most
disadvantaged groups [53]. There is the need to implement in
clinical practice what we know about indications to antibiotic
treatment of AOM in children, by adapting evidence from
research studies [5456] to local health system and risk factors.
However, appropriately designed studies are necessary in order to
assess to which extent strategies proven effective in developed
countries (i.e. the wait and see strategy) [57,58] are applicable in
totally different contexts. Uncertainties still existing about
treatment of CSOM in children should also be addressed [59].
In conclusion, our review calls for incorporating OM-focused
action within preventive and case management strategies, with
emphasis on high burden countries and for more research on
epidemiology of OM and related conditions, focusing on high
burden countries.
Supporting Information
Text S1 Expanded Methods Section.
(PDF)
Figure S1 Sequelae of OM, simplified scheme.
(PDF)
Figure S2 1
st
screening by titles, abstract and key-
words.
(PDF)
Figure S3 Risk factor diagram.
(PDF)
Table S1 Search strategies and results.
(PDF)
Table S2 WHO grades of hearing impairment.
(PDF)
Table S3 Data coverage.
(PDF)
Table S4 AOM and CSOM incidence and prevalence, HI
cases and prevalence estimates, and Mortality esti-
mates, by age groups and WHO region.
(PDF)
Acknowledgments
We thank Harry Campbell (University of Edinburgh Medical School, UK)
and Igor Rudan (Croatian Centre for Global Health, Split, Croatia),
leaders of the Global Burden of Disease Expert Group on pneumonia,
meningitis, sepsis, otitis media, pertussis and influenza, for their support,
guidance and advice. We carried out study as members of this Expert
Group and in the context of the new Global Burden of Diseases, Injuries, and
Risk Factors Study (GBD Study), led by a consortium including Harvard
University, the Institute for Health Metrics and Evaluation at the
University of Washington, Johns Hopkins University, the University of
Queensland, and the World Health Organization.
Author Contributions
Conceived and designed the experiments: LM LR MM GT FM DG.
Performed the experiments: LM LR AB MM LVB CB. Analyzed the data:
LM LR MM AB LVB CB. Contributed reagents/materials/analysis tools:
LM LR AB. Wrote the paper: LM LR FM GT FM.
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 10 April 2012 | Volume 7 | Issue 4 | e36226
References
1. Klein JO (2000) The burden of otitis media. Vaccine 19 Suppl 1: S2S8.
2. Teele DW, Klein JO, Rosner B (1989) Epidemiology of otitis media during the
first seven years of life in children in greater Boston: a prospective, cohort study.
J Infect Dis 160: 8394.
3. Vergison A, Dagan R, Arguedas A, Bonhoeffer J, Cohen R, et al. (2010) Otitis
media and its consequences: beyond the earache. Lancet Infect Dis 10: 195203.
4. Casselbrant ML, Mandel EM (2003) Epidemiology. In: Rosenfeld RM,
Bluestone CD, eds. Evidence-based otitis media. Hamilton, (ON): BC Decker.
pp 147162.
5. Berman S (1995) Otitis media in developing countries. Pediatrics 96: 126131.
6. Acuin J (2004) Chronic suppurative otitis media - Burden of Illness and
Management Options. Geneva: World Health Organization.
7. Cruickshanks KJ, Wiley TL, Tweed TS, Klein BE, Klein R, et al. (1998)
Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The
Epidemiology of Hearing Loss Study. Am J Epidemiol 148: 879886.
8. Yueh B, Shapiro N, MacLean CH, Shekelle PG (2003) Screening and
management of adult hearing loss in primary care: scientific review. JAMA
289: 19761985.
9. Harvard University, Institute for Health Metrics and Evaluation at the
University of Washington, Johns Hopkins University, University of Queensland,
World Health Organization (2009) GBD Study Operations Manual Final
Draft Jan. 2009.
10. Mathers CD, Lopez AD, Murray CJL (2006) The burden of disease and
mortality by condition: data, methods and results for 2001. In: Lopez AD,
Mathers CD, Ezzati M, Jamison DT, Murray CJL, eds. Global Burden of
Disease and Risk Factors. Washington, (DC): World Bank. pp 45240.
11. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J (2001)
Pragmatic randomised controlled trial of two prescribing strategies for childhood
acute otitis media. BMJ 322: 336342.
12. NICE Short Clinical Guidelines Technical Team (2008) Respiratory tract
infections antibiotic prescribing. Prescribing of antibiotics for self-limiting
respiratory tract infections in adults and children in primary care. London:
National Institute for Health and Clinical Excellence.
13. Mandel EM, Doyle WJ, Winther B, Alper CM (2008) The incidence, prevalence
and burden of OM in unselected children aged 18 years followed by weekly
otoscopy through the common cold season. Int J Pediatr Otorhinolaryngol 72:
491499.
14. Osma U, Cureoglu S, Hosoglu S (2000) The complications of chronic otitis
media: report of 93 cases. J Laryngol Otol 114: 97100.
15. Cusimano F, Cocita VC, DAmico A (1989) Sensorineural hearing loss in
chronic otitis media. J Laryngol Otol 103: 158163.
16. Sade J, Halevy A (1976) The natural history of chronic otitis media. J Laryngol
Otol 90: 743751.
17. Papp Z, Rezes S, Jokay I, Sziklai I (2003) Sensorineural hearing loss in chronic
otitis media. Otol Neurotol 24: 141144.
18. Tuz M, Dogru H, Uygur K, Aynali G (2006) Sensorineural Hearing Loss
Associated with Chronic Otitis Media. S D U

Typ Fak Derg 13: 12.

19. Fernandes de Azevedo A, Pinto DC, de Souza NJ, Greco DB, Goncalves DU
(2007) Sensorineural hearing loss in chronic suppurative otitis media with and
without cholesteatoma. Braz J Otorhinolaryngol 73: 671674.
20. Uhari M, Mantysaari K, Niemela M (1996) A meta-analytic review of the risk
factors for acute otitis media. Clin Infect Dis 22: 10791083.
21. Ip S, Chung M, Raman G, Chew P, Magula N, et al. (2007) Breastfeeding and
maternal and infant health outcomes in developed countries. Evid Rep Technol
Assess (Full Rep). pp 1186.
22. Lasisi AO, Olaniyan FA, Muibi SA, Azeez IA, Abdulwasiu KG, et al. (2007)
Clinical and demographic risk factors associated with chronic suppurative otitis
media. Int J Pediatr Otorhinolaryngol 71: 15491554.
23. World Health Organization (2008) World Health Statistics 2008.
24. World Health Organization (2009) World Health Statistics 2009.
25. UNICEF (2006) The State of the Worlds Children 2007: The Double Dividend
of Gender Equality.
26. OECD (2008) OECD in Figures 2008. Available: http://www.oecd.org/
dataoecd/44/17/41733586.pdf. Accessed 2012 Mar 19.
27. OECD (2008) OECD Health Data 2008. Available: http://stats.oecd.org/
index.aspx?DataSetCode =HEALTH_STAT. Accessed 2012 Mar 19.
28. WHO-PDH (1991) Report of the Informal Working Group on Prevention of
Deafness and Hearing Impairment, Programme Planning. Geneva, 1821 June
1991. WHO/PDH/91.1.
29. Mathers CD, Smith A, Concha M Global Burden of hearing loss in the year
2000 - GBD 2000 Working Paper.
30. Al Khabori M, Khandekar R (2004) The prevalence and causes of hearing
impairment in Oman: a community-based cross-sectional study. Int J Audiol 43:
486492.
31. Liu C, Bu XK, Xing GQ, Zhou L, Xu X, et al. (2006) [Epidemiologic study on
hearing impairment and ear diseases in old people]. Zhonghua Er Bi Yan Hou
Tou Jing Wai Ke Za Zhi 41: 661664.
32. Bansal R, Raj A (1998) Hearing loss in rural population: The etiology. Indian
Journal of Otolaryngology and Head and Neck Surgery 50(2)()(pp 147155),
1998 Date of Publication: 1998 147155.
33. Jacob A, Rupa V, Job A, Joseph A (1997) Hearing impairment and otitis media
in a rural primary school in south India. Int J Pediatr Otorhinolaryngol 39:
133138.
34. Elango S, Purohit GN, Hashim M, Hilmi R (1991) Hearing loss and ear
disorders in Malaysian school children. Int J Pediatr Otorhinolaryngol 22:
7580.
35. Lasisi AO, Sulaiman OA, Afolabi OA (2007) Socio-economic status and hearing
loss in chronic suppurative otitis media in Nigeria. Ann Trop Paediatr 27:
291296.
36. Prescott CA, Kibel MA (1991) Ear and hearing disorders in rural grade 2 (Sub
B) schoolchildren in the Western Cape. S Afr Med J %19;79: 9093.
37. World Health Organization (2008) The global burden of disease. 2004 update p.
38. Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H (2004) Global estimate of
the incidence of clinical pneumonia among children under five years of age. Bull
World Health Organ 82: 895903.
39. Rovers MM, Schilder AG, Zielhuis GA, Rosenfeld RM (2004) Otitis media.
Lancet 363: 465473.
40. Teele DW, Klein JO, Chase C, Menyuk P, Rosner BA (1990) Otitis media in
infancy and intellectual ability, school achievement, speech, and language at age
7 years. Greater Boston Otitis Media Study Group. J Infect Dis 162: 685694.
41. Arlinger S, Lunner T, Lyxell B, Pichora-Fuller MK (2009) The emergence of
cognitive hearing science. Scand J Psychol 50: 371384.
42. Williams CJ, Jacobs AM (2009) The impact of otitis media on cognitive and
educational outcomes. Med J Aust 191: S69S72.
43. Roberts J, Hunter L, Gravel J, Rosenfeld R, Berman S, et al. (2004) Otitis
media, hearing loss, and language learning: controversies and current research.
J Dev Behav Pediatr 25: 110122.
44. Bennett KE, Haggard MP, Silva PA, Stewart IA (2001) Behaviour and
developmental effects of otitis media with effusion into the teens. Arch Dis Child
85: 9195.
45. Taipale A, Pelkonen T, Taipale M, Bernardino L, Peltola H, Pitkaranta A
(2011) Chronic suppurative otitis media in children of Luanda, Angola. Acta
Paediatr.
46. Paradise JL, Rockette HE, Colborn DK, Bernard BS, Smith CG, et al. (1997)
Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during
the first two years of life. Pediatrics 99: 318333.
47. Cook DG, Strachan DP (1999) Health effects of passive smoking-10: Summary
of effects of parental smoking on the respiratory health of children and
implications for research. Thorax 54: 357366.
48. Bruce N, Perez-Padilla R, Albalak R (2000) Indoor air pollution in developing
countries: a major environmental and public health challenge. Bull World
Health Organ 78: 10781092.
49. Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, et al. (2006)
Pneumococcal capsular polysaccharides conjugated to protein D for prevention
of acute otitis media caused by both Streptococcus pneumoniae and non-typable
Haemophilus influenzae: a randomised double-blind efficacy study. Lancet 367:
740748. S0140-6736(06)68304-9 [pii];10.1016/S0140-6736(06)68304-9 [doi].
50. Boonacker CW, Broos PH, Sanders EA, Schilder AG, Rovers MM (2011) Cost
effectiveness of pneumococcal conjugate vaccination against acute otitis media in
children: a review. Pharmacoeconomics 29: 199211.
51. Victora CG, Hanson K, Bryce J, Vaughan JP (2004) Achieving universal
coverage with health interventions. Lancet 364: 15411548.
52. Hill Z, Kendall C, Arthur P, Kirkwood B, Adjei E (2003) Recognizing childhood
illnesses and their traditional explanations: exploring options for care-seeking
interventions in the context of the IMCI strategy in rural Ghana. Trop Med Int
Health 8: 668676.
53. Gunasekera H, Morris PS, Daniels J, Couzos S, Craig JC (2009) Otitis media in
Aboriginal children: the discordance between burden of illness and access to
services in rural/remote and urban Australia. J Paediatr Child Health 45:
425430.
54. Damoiseaux RA, Rovers MM (2011) AOM in children. Clin Evid (Online)
2011. Available: http://bestpractice.bmj.com/best-practice/evidence/0301.
html. Accessed 2012 Mar 19.
55. Hoberman A, Paradise JL, Rockette HE, Shaikh N, Wald ER, et al. (2011)
Treatment of acute otitis media in children under 2 years of age. N Engl J Med
364: 105115. 10.1056/NEJMoa0912254 [doi].
56. Tahtinen PA, Laine MK, Huovinen P, Jalava J, Ruuskanen O, Ruohola A
(2011) A placebo-controlled trial of antimicrobial treatment for acute otitis
media. N Engl J Med 364: 116126. 10.1056/NEJMoa1007174 [doi].
57. Rovers MM, Glasziou P, Appelman CL, Burke P, McCormick DP, et al. (2006)
Antibiotics for acute otitis media: a meta-analysis with individual patient data.
Lancet 368: 14291435.
58. Marchetti F, Ronfani L, Nibali SC, Tamburlini G (2005) Delayed prescription
may reduce the use of antibiotics for acute otitis media: a prospective
observational study in primary care. Arch Pediatr Adolesc Med 159: 679684.
59. Acuin J (2007) Chronic suppurative otitis media. Clin Evid (Online) 2007.
Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943814/pdf/
2007-0507.pdf. Accessed 2012 Mar 19.
60. SIGN (2003) Diagnosis and management of childhood otitis media in primary
care - A national clinical guideline.
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 11 April 2012 | Volume 7 | Issue 4 | e36226
61. Gates GA, Klein JO, Lim DJ, Mogi G, Ogra PL, et al. (2002) Recent advances
in otitis media. 1. Definitions, terminology, and classification of otitis media. Ann
Otol Rhinol Laryngol Suppl 188: 818.
62. Alberta Clinical Practice Guidelines Working Group (2000) Diagnosis and
Treatment of Acute Otitis Media in Children - 2008 Update.
63. Medline plus enciclopedia (2011) Hearing loss. National Library of Medicine -
National Institutes of Health. Available: http://www.nlm.nih.gov/medlineplus/
ency/article/003044.htm. Accessed 2012 March 19.
64. World Health Organization (2001) International classification of functioning,
disability and health: ICF.
Burden of Disease Caused by Otitis Media
PLoS ONE | www.plosone.org 12 April 2012 | Volume 7 | Issue 4 | e36226