Global, regional, and national burden of upper respiratory infections and otitis media, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021

Abstract

Background Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021.

Full text

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Articles
Lancet Infect Dis 2025;
25: 36–51
Published Online
September 9, 2024
https://doi.org/10.1016/
S1473-3099(24)00430-4
This online publication has
been corrected. The corrected
version first appeared at
thelancet.com/infection on
December 27, 2024
See Comment page 3
*Collaborators listed at the end
of the Article
Correspondence to:
Dr Hmwe H Kyu, Department of
Health Metrics Sciences, School
of Medicine, Institute for Health
Metrics and Evaluation,
University of Washington,
Seattle, WA 98195, USA
hmwekyu@uw.edu
Global, regional, and national burden of upper respiratory
infections and otitis media, 1990–2021: a systematic
analysis from the Global Burden of Disease Study 2021
GBD 2021 Upper Respiratory Infections and Otitis Media Collaborators*
Summary
Background Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and
contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the
combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the
Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of
the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries
and territories from 1990 to 2021.
Methods Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital
registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis
media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from
published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis
media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs
and examined the collective burden and contributing risk factors of both diseases.
Findings The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all
ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (–12·0 to –8·1)
from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (–0·8 to –0·1). Globally, the
incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5%
(–12·4 to –8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7).
The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of
episodes was in children aged 5–9 years. The number of new episodes of otitis media globally for all ages was
391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6)
in 2021, a decrease of 16·3% (–18·1 to –14·0) from 1990, when the incidence rate was 5925·5 per 100 000
(4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the
largest number of episodes was in children aged 2–4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000
(0·1 to 0·5), a decrease of 64·2% (–84·6 to –43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1).
In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden
accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and
8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the
all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1–5 months
had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0–6 days;
582 per 100 000 [176 to 1297]) and late neonates (aged 7–24 days; 482 per 100 000 [161 to 1052]).
Interpretation The findings of this study highlight the widespread burden posed by URIs and otitis media across all
age groups and both sexes. There is a continued need for surveillance, prevention, and management to better
understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their
impacts on individuals, communities, economies, and health-care systems worldwide.
Funding Bill & Melinda Gates Foundation.
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0
license.
Introduction
Upper respiratory infections (URIs) are the leading cause
of acute disease incidence worldwide.1 Despite their
relatively low risk of severe illness and mortality, URIs
pose a substantial economic and health-care burden due
to medical expenses, lost productivity, and increased
health-system strain.2–4 This burden is particularly
relevant for primary care providers when considering the
impact of concurrent or subsequent otitis media, a
common cause of care seeking for children younger than

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5 years.5 Additionally, the mismanagement of URIs and
otitis media contributes considerably to increased
antimicrobial resistance globally, with URIs being a
major contributor to antibiotic prescriptions.6–9
URIs can be acquired through various respiratory
routes, ranging from the transmission of pathogens onto
mucous membranes via contaminated hands to the
inhalation of aerosols from an infected individual.10,11
These transmission methods are influenced by factors
such as ambient temperature, humidity, and crowding.11
URIs are caused by numerous pathogens, including
rhino viruses, coronaviruses, influenza, respiratory
syncytial virus (RSV), Streptococcus pyogenes, Streptococcus
pneumoniae, Haemophilus influenzae, and Mycoplasma
pneumoniae. The potential risk of URIs progressing into
more severe disease is substantial given the sheer
magnitude of URI cases each year. This potential risk is
particularly important in the wake of the COVID-19
pandemic, which often saw infection beginning in the
upper respiratory tract before progressing to more life-
threatening illness.12,13
Acute otitis media, an infection of the middle ear that
can be caused by bacteria, viruses, or a combination of
both, is the second most common paediatric illness
following URIs.14,15 Acute otitis media is characterised by
the presence of fluid within the middle ear alongside the
signs of acute infection and ear pain.16 Acute otitis media
is often a complication following a URI when the
eustachian tube is colonised by URI-associated pathogens
through congestion of the nasal and nasopharyngeal
mucosa, allowing pathogens to enter the middle ear and
trigger inflammation.17 In previous research, more than
60% of URI episodes in children younger than 35 months
were complicated by a simultaneous case of otitis media.18
Infants who frequently have URIs are more likely to
contract a concurrent or subsequent instance of otitis
media.19
Although the link between URIs and acute otitis media
is well established, a comprehensive assessment of their
combined burden across age groups and diverse
geographical contexts has been lacking, particularly in
children younger than 5 years, thereby limiting informed
Research in context
Evidence before this study
Previous research using data from the Global Burden of
Diseases, Injuries, and Risk Factors Study (GBD) 2019 outlined
the burden of upper respiratory infections (URIs) on an
aggregate of children younger than 5 years, the age group in
which URI burden is the highest. Studies have previously
established a strong link between URIs and otitis media in
adults and children, indicating that URIs can adversely affect the
eustachian tube by facilitating pathogen colonisation of the
middle ear. We searched PubMed for the terms (“upper
respiratory infection*” OR “URI” OR “respiratory tract
infections”) AND (“otitis media”) AND (“burden” OR
“estimates” OR “prevalence” OR “incidence”) AND (“risk
factor*”), with no language restrictions, for publications from
Jan 1, 1980, to Oct 8, 2023. This search yielded 41 articles.
Of these studies, 20 reported on URI incidence, ten reported on
otitis media incidence, and 11 dealt with both URIs and otitis
media. Of the 11 studies reporting on URIs and otitis media,
all measured incidence in children younger than 8 years, with
no granular age breakdowns. None of the 11 studies reported
years lived with disability (YLDs), disability-adjusted life-years
(DALYs), years of life lost, or mortality. We also did not find
studies that reported the combined burden of URIs and otitis
media. Of the 11 studies, nine reported on subnational trends
and two were reviews that did not report global estimates.
Added value of this study
For the first time, this study assessed the incidence, mortality,
YLDs, and DALYs from URIs in more granular age groups of
children aged 1–5 months, 6–11 months, 12–23 months, and
2–4 years. We also integrated many new data sources on the
morbidity and mortality of URIs since GBD 2019. Until now,
the comprehensive burden of otitis media, a disease closely
related to URIs, has not been assessed. This study shows the
similarities in trends between these two conditions and
provides new insights into the burden of otitis media, as well as
the combined burden of both URIs and otitis media, by
providing the incidence, mortality, YLDs, and DALYs of otitis
media for 204 countries across all age groups, by sex.
Implications of all the available evidence
URIs result in substantial morbidity and economic burden
worldwide. Although they rarely cause death or severe disease,
URIs can lead to more serious infections such as otitis media
and lower respiratory infections, as seen for SARS-CoV-2, and
contribute to antimicrobial resistance through the
inappropriate prescription of antibiotic medicines as a
treatment for otitis media, URIs, or both. Understanding the
interconnected nature of URIs and otitis media is crucial to
addressing both the individual and combined burden of these
diseases effectively through the design of strategies and public
health interventions to address their impact. Strategies could
include promoting better hygiene practices, implementing
antimicrobial stewardship programmes, emphasising the
importance of as well as ensuring equal access to vaccinations,
and conducting further research to elucidate the underlying
causes and contributing factors. Implementing targeted
preventive interventions could help to reduce the burden of
URIs and otitis media in children younger than 2 years, who
account for the highest rate of episodes across all age groups.
By comprehensively addressing the impact of URIs and otitis
media, we can advance global public health efforts and
enhance the quality of life of affected individuals and
communities.

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decision making on interventions and policies to address
the burden of these two associated diseases. Using the
estimates produced by the Global Burden of Diseases,
Injuries, and Risk Factors Study (GBD) 2021, we aimed
to assess the incidence, mortality, years lived with
disability (YLDs), and disability-adjusted life-years
(DALYs) of URIs and otitis media across age groups and
204 countries and territories. Compared with the
previous iteration, GBD 2019, we assessed the burden in
more granular age groups of children younger than
5 years (1–5 months, 6–11 months, 12–23 months, and
2–4 years) to better understand the burden in children,
who have the highest incidence rates of URIs and otitis
media. We also aimed to analyse the combined burden of
URIs and otitis media through YLDs, reflecting their
interconnected nature.
Methods
GBD modelling overview
GBD 2021 produced estimates of deaths, incidence, years
of life lost (YLLs), YLDs, and DALYs for URIs and otitis
media by age and sex for 204 countries and territories
from 1990 to 2021. Modelling was done using 1000 draws,
and 95% uncertainty intervals (UIs) were calculated as
the 25th and 975th ranked values of the 1000 draws.
Percentage changes were calculated as the dierence
between the final value (for the year 2021) and the initial
value (for the year 1990), then divided by the initial value
and multiplied by 100. Age-standardised rates were
computed using the GBD 2021 global population age
standard. Socio-demographic Index (SDI) for each
country was computed as the geometric mean of each
country’s lag-distributed income per capita, average years
of schooling, and the total fertility rate in females
younger than 25 years.20 Full descriptions of the GBD
studies and methodology have been previously
published.21
The GBD Sources tool, found on the Global Health
Data Exchange (GHDx), provides all metadata for input
sources described below. It allows readers to identify
which sources were used for estimating an outcome in
any given location. Statistical code used for GBD
estimation is also publicly available on the GHDx. This
research complies with the GATHER statement
(appendix 1 p 77).
Estimating incidence, prevalence, and mortality for
URIs and otitis media
Incidence and prevalence of non-COVID-19 URIs were
modelled using a Bayesian meta-regression tool,
DisMod-MR 2.1.21 The inputs into the URI model
consisted of data from published studies identified
through systematic reviews and nationally representative
surveys, including the US National Health Interview
Surveys and Demographic and Health Surveys (DHS).
Excluded from DisMod-MR 2.1 were data that were not
population-based and studies that did not provide
primary data, had a sample size of less than 150, or were
reviews or case series. A more comprehensive description
of the input data and the associated search string from
the systematic review is provided in appendix 1 (pp 4–11).
In the GBD framework, acute and chronic otitis media
are modelled as separate non-fatal health outcomes
using DisMod-MR 2.1. The inputs into the otitis media
models consisted of data from published studies
identified via systematic reviews, population-based
surveys, and health insurance claims data (more details
can be found in appendix 1 p 11). For the purposes of this
Article, we present the combination of acute and chronic
non-fatal otitis media as one disease category, non-fatal
otitis media, for consistency with fatal otitis media,
which is modelled as a single entity.
The Cause of Death Ensemble model (CODEm)
framework was used to estimate mortality due to non-
COVID-19 URIs and otitis media separately in the GBD
2021 study, using data from vital registration, sample-
based vital registration, and minimally invasive tissue
sample diagnoses as the inputs.21 CODEm creates a
diverse array of submodels with dierent functional
forms (linear mixed-eects models with random
intercepts at the super-region, region, and country levels,
assuming these random eects are normally distributed,
and spatiotemporal Gaussian process regression models)
for the outcome variable, either the mortality rate or
cause fraction, using various combinations of predictive
covariates. Appendix 1 provides the complete list of
covariates for URIs (p 4) and otitis media (p 11). The
selection of the ensemble of models was based on the
best performance in out-of-sample predictive validity
tests.
Estimating YLLs, YLDs, and DALYs
GBD calculates YLLs as the sum of each death multiplied
by the standard life expectancy at each age. URIs have
two severity levels: mild and moderate–severe URIs.
YLDs from URIs were calculated by multiplying a dis-
ability weight for each of the URI severity levels and the
percentage of episodes that fall into each level. Otitis
media has ten severity levels: acute otitis media, severe
infectious complications due to chronic otitis media,
mild hearing loss due to chronic otitis media, moderate
hearing loss due to chronic otitis media, mild hearing
loss with ringing due to chronic otitis media, moderate
hearing loss with ringing due to chronic otitis media,
vertigo with mild hearing loss due to chronic otitis
media, vertigo with mild hearing loss and ringing due to
chronic otitis media, vertigo with moderate hearing loss
due to chronic otitis media, and vertigo with moderate
hearing loss and ringing due to chronic otitis media.
YLDs from otitis media were calculated in the same
manner as URIs by multiplying each severity level’s
corresponding disability weight with the percentage of
episodes that are attributed to each severity level. The
disability weights for severity levels of URIs and otitis
For the GHDx GBD 2021 website
see https://ghdx.healthdata.org/
gbd-2021/
See Online for appendix 1

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media were derived from the GBD disability weights
study22 and can be found in appendix 1 (pp 15–16). DALYs
were calculated as the sum of YLLs and YLDs for all
locations, years, and age groups, by sex. More detailed
information on the calculation of YLLs, YLDs, and DALYs
has been published elsewhere.21
Risk attribution estimation for DALYs and YLDs
Detailed methods for GBD risk factor estimation have
been published elsewhere.23 To summarise, we selected
risk–outcome pairs that held a convincing or probable
causal relationship between the risk factor and the
outcome (URIs and household air pollution, as an
example). Relative risks for the associations between the
risk factors and URIs and otitis media were estimated on
the basis of published systematic reviews. The level
of exposure to risk factors was estimated using
spatiotemporal Gaussian process regression, a Bayesian
meta-regression method (DisMod-MR 2.1), or alternative
methodology (appendix 1 pp 16–79). Using available data
sources, exposure levels equating to minimum risk
(theoretical minimum risk) were determined (appendix 1
pp 16–79). YLDs and DALYs attributed to each risk factor
were computed by multiplying population attributable
fractions by the relevant outcome quantity for year, age
group, and sex.
Figure 1: URI and otitis media incidence rates (A) and DALY rates (B) per 100 000 population, by super-region, in 1990 and 2021
Shaded areas are 95% uncertainty intervals. DALY=disability-adjusted life-year. URI=upper respiratory infection.
Global Central Europe,
eastern Europe,
and central Asia
High income Latin America
and
Caribbean
North Africa and
Middle East
South Asia Southeast Asia,
east Asia,
and Oceania
Sub-Saharan
Africa
URIs
Otitis media
100
0
200
300
400
500
A
URIs
Otitis media
B
25
50
0
75
100
DALY rate per
100000 population
DALY rate per
100000 population
1990
2000
2010
2019
2021
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
2019
2021
1990
2000
2010
120000
160000
200000
240000
280000
0
2500
0
5000
7500
10000
12500
Year Year Year Year YearYearYearYear
Incidence rate per
100000 population
Incidence rate per
100000 population

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More detailed URI and otitis media burden results by
age and sex across locations and years are available in the
GBD Results Tool.
Role of the funding source
The funders of the study had no role in study design,
data collection, data analysis, data interpretation, or
writing of the report.
Results
Non-fatal and fatal burden of URIs
In 2021, there were 12·8 billion (95% UI 11·4–14·5)
episodes of URI globally for all ages across males and
females (appendix 2 p 5). In 1990, this value was
9·68 billion (8·58–11·0). The all-age incidence rate of
URI in 2021 was 162 484·8 per 100 000 population
(144 834·0–183 289·4; appendix 2 p 5; figure 1). The
highest incidence rate of URIs was seen in
children aged 12–23 months (328 644·6 per 100 000
[249 094·0–420 845·1]), followed by those aged
6–11 months
(313 772·9 per 100 000 [241 920·5–400 104·3])
and 1–5 months (295 690·7 [237 157·2–359 466·6];
appendix 2 p 5; figure 2). The largest count of URI
episodes was seen in children aged 5–9 years
(1·50 billion [1·02–2·06]), followed by those aged
2–4 years (1·18 billion [0·857–1·54]) and 10–14 years
(1·14 billion [0·793–1·57]; appendix 2 p 5; figure 2).
Among people aged 15 years and older, the age group
with the largest incidence rate per 100 000 in 2021
was age 15–19 years (160 574·2 [111 176·9–216 450·9]),
followed by 20–24 years (157 525·4 [112 631·9–214 581·1]),
and 25–29 years (152 689·1 [110 765·7–207 683·7]). The
same pattern was observed for URI episodes (appendix 2
p 5; figure 2).
Between 1990 and 2019, the global all-age incidence
rate of URIs decreased by 10·1% (95% UI –12·0 to –8·1),
from 181 552·5 per 100 000 (160 827·4 to 206 214·7) to
163 255·1 per 100 000 (145 630·6 to 183 924·0; figure 1;
appendix 2 p 5). From 2019 to 2021, the global all-age
incidence rate decreased by 0·5% (–0·8 to –0·1), to
162 484·8 per 100 000 (144 834·0 to 183 289·4), with
substantial variation across regions, showing increasing,
decreasing, or no changes in URI incidence rates
(appendix 2 p 5).
The highest all-age incidence rates per 100 000 popu-
lation in 2021 were seen in high-income North America
(269 253·0 [95% UI 241 387·5–297 109·8]), Oceania
(236 110·1 [208 105·9–267 109·9]), and Tropical Latin
America (227 863·0 [201 295·0–259 060·5]; appendix 2
p 5; figure 1). When classified by SDI, the largest number
of episodes in 2021 was seen in middle SDI regions at
3·85 billion (3·42–4·37) episodes, although the highest
rate of URIs was held by high SDI regions (203 538·2 per
100 000 [183 388·8–225 459·6]; appendix 2 p 5).
Globally, URIs accounted for 19 600 deaths (95% UI
7040–41 600) in 2021 (appendix 2 p 6), with a mortality
For the GBD Results Tool see
https://vizhub.healthdata.org/
gbd-results/
See Online for appendix 2
Figure 2: Global URI episodes in millions (A) and incidence rates per 100 000 population (B), by age, in 1990 and 2021
URI=upper respiratory infection.
0
100
000
200
000
300
000
400
000
URI incidence rate per 100
000 population
0
500
1000
1500
0–6 days
7–24 days
1–5 months
6–11 months
12–23 months
2–4 years
5–9 years
10–14 years
15–19 years
20–24 years
25–29 years
30–34 years
35–39 years
40–44 years
45–49 years
50–54 years
55–59 years
60–64 years
65–69 years
70–74 years
75–79 years
80–84 years
85–89 years
90–94 years
≥95 years
Age group
URI episodes (millions)
Year
1990
2021
A
B

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rate of 0·2 per 100 000 (0·1–0·5), a 64·2% (43·4–84·6)
decrease in mortality rate from 1990 (appendix 2 p 6).
The age distribution of URI deaths and mortality rates is
illustrated in appendix 2 (p 2). The regions with the
highest mortality rate per 100 000 in 2021 were eastern
sub-Saharan Africa (1·4 per 100 000 [0·1–3·7]), western
sub-Saharan Africa (1·3 per 100 000 [0·2–3·7]), and
central sub-Saharan Africa (1·0 per 100 000 [0·1–3·3];
appendix 2 p 6). The highest number of deaths came
from the low SDI regions in 2021 (12 100 [1100–31 500]),
and the highest mortality rate was also from low SDI
regions (1·1 per 100 000 [0·1–2·8]; appendix 2 p 6).
The number of YLDs from URIs in 2021 was
4·41 million (95% UI 2·68 to 6·73) globally (appendix 2
p 7). In 1990, the number of YLDs from URIs was
3·34 million (2·01 to 5·10), representing a 31·8%
(29·1 to 34·9) increase from 1990 to 2021. In 2021, global
YLLs from URIs reached 1·27 million (0·299 to 2·98),
representing a decrease of 43·7% (–77·1 to –10·0) from
1990 (2·26 million [0·727 to 3·95]; appendix 2 p 7). In
2021, the number of global DALYs from URIs was
5·68 million (3·26 to 8·38), an increase of 1·3%
(–15·4 to 19·3) from 1990, when DALYs totalled
5·60 million (3·45 to 7·91; appendix 2 p 7). The rate of
DALYs per 100 000 has been decreasing across all super-
regions (figure 1; appendix 2 p 9), with a global decline
from 105·1 (64·6 to 148·3) in 1990, to 78·8 (45·2 to 116·0)
in 2010, to 73·8 (42·3 to 109·3) in 2019, and to 72·0
(41·3 to 106·2) in 2021.
Non-fatal and fatal burden of otitis media
The number of episodes of otitis media globally for all
ages across males and females reached 391 million
(95% UI 292 to 525) in 2021, an increase from 316 million
(233 to 432) in 1990 (appendix 2 p 10). The incidence rate
of otitis media in 2021 was 4958·9 per 100 000
(3705·4 to 6658·6), a decrease of 16·3% (–18·1 to –14·0)
since 1990 (5925·5 per 100 000 [4371·8 to 8097·9];
figure 1). The highest incidence rate was seen in
children aged 12–23 months (30 404·7 per 100 000
[16 470·1 to 50 221·0]), followed by those aged 6–11 months
(29 600·1 per 100 000 [17 571·3 to 45 019·3]) and
1–5 months (25 668·4 per 100 000 [15 768·7 to 38 629·4];
appendix 2 p 10; figure 3). The largest count of otitis
media episodes was seen in children aged 2–4 years
(98·6 million [55·2 to 155·0]), followed by those aged
5–9 years (90·6 million [45·5 to 159·0]) and 12–23 months
(39·0 million [21·1 to 64·5]; figure 3). Among people aged
15 years and older, the largest number of episodes in 2021
was seen in those aged 15–19 years (18·6 million
[11·4 to 29·1]), followed by those aged 20–24 years
(10·5 million [4·84 to 18·5]), and 35–39 years (9·68 million
[5·58 to 16·1]; appendix 2 p 10). The same pattern was
observed for the incidence rate (appendix 2 p 10; figure 3).
The highest incidence rate of otitis media in 2021 was
seen in western sub-Saharan Africa (8665·1 per 100 000
[95% UI 6267·5–12 058·9]; appendix 2 p 10; figure 1). The
largest number of episodes came from low-middle SDI
regions in 2021 (119 million [86·9–162]; appendix 2 p 10).
Figure 3: Global otitis media episodes in millions (A) and incidence rates per 100 000 population (B), by age, in 1990 and 2021
0
10
000
20
000
30
000
Otitis media incidence rate per
100
000
population
0
25
50
75
100
0–6 days
7–24 days
1–5 months
6–11 months
12–23 months
2–4 years
5–9 years
10–14 years
15–19 years
20–24 years
25–29 years
30–34 years
35–39 years
40–44 years
45–49 years
50–54 years
55–59 years
60–64 years
65–69 years
70–74 years
75–79 years
80–84 years
85–89 years
90–94 years
≥95 years
Age group
Otitis media episodes (millions)
Year
1990
2021
A
B

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Low SDI regions also had the highest rate of otitis media
in 2021 (8244·0 per 100 000 [5944·4–11 412·5]; appendix 2
p 10).
Globally, the number of deaths caused by otitis media
was 536 (95% UI 217 to 1240) in 2021 (appendix 2 p 11). In
both 1990 and 2021, the mortality rate of otitis media was
less than 0·1 per 100 000, with a decrease of 75·4%
(–83·8 to –57·1) in this period (appendix 2 p 11). The age
distribution of otitis media deaths and mortality rates is
illustrated in appendix 2 (p 3).
The number of YLDs from otitis media in 2021 was
2·45 million (95% UI 1·43 to 3·94) globally (appendix 2
p 7). In 1990, otitis media YLDs reached 2·03 million
(1·18 to 3·28), representing an increase of 20·7%
(16·8 to 24·5) from 1990 to 2021 (appendix 2 p 7). In 2021,
global all-age YLLs from otitis media reached 28 200
(9000 to 76 400), representing a decrease of 69·9%
(–84·2 to –39·3) since 1990 (93 600 [52 000 to 168 000];
appendix 2 p 7). In 2021, the global number of otitis
media DALYs was 2·48 million (1·46 to 3·97; appendix 2
p 7). The rate of DALYs per 100 000 has been decreasing
across all super-regions, with a global decline from 39·8
(23·9 to 63·2) in 1990, to 34·0 (20·1 to 54·3) in 2010, to
31·7 (18·7 to 50·6) in 2019, and to 31·4 (18·5 to 50·4) in
2021 (figure 1; appendix 2 p 9).
Combined burden of URIs and otitis media
The number of YLDs accounted for by URIs and otitis
media together in 2021 was 6·86 million (95% UI
4·24–10·4) for all ages across males and females (appendix
2 p 13). The age group with the largest combined count of
YLDs was age 5–9 years (925 000 [553 000–1 470 000]),
followed by 10–14 years (697 000 [396 000–1 110 000]) and
2–4 years (661 000 [380 000–1 040 000]; appendix 2 p 13).
Among people aged 15 years and older, the largest number
of combined YLDs was seen in those aged 15–19 years
(603 000 [351 000–973 000]), followed by those aged
20–24 years (521 000 [304 000–837 000]), and 25–29 years
(459 000 [263 000–733 000]; appendix 2 p 13).
The total combined rate of YLDs for all ages across
males and females was 87 per 100 000 (54–132; figure 4;
appendix 2 p 13). The age group with the largest
combined rate of YLDs was age 2–4 years (164 per
100 000 [94–259]), followed by 12–23 months (160 per
100 000 [92–250]) and 6–11 months (142 per 100 000
[82–221]; figure 4; appendix 2 p 13). Among people aged
15 years or older, the largest combined rate was seen in
those aged 15–19 years (97 per 100 000 [56–156]),
followed by those aged 20–24 years (87 per 100 000
[51–140]), and 25–29 years (78 per 100 000 [45–125];
appendix 2 p 13).
The number of DALYs in 2021 from the combined
burden of URIs and otitis media was 8·16 million
(95% UI 4·99–12·0) for all ages across males and females
(appendix 2 p 13). The age group with the largest count of
DALYs was age 5–9 years (998 000 [596 000–1 570 000]),
followed by 2–4 years (827 000 [474 000–1 240 000]) and
10–14 years (728 000 [421 000–1 130 000]; appendix 2 p 13).
Among people aged 15 years and older, the largest count
of DALYs was seen in those aged 15–19 years (622 000
[359 000–990 000]), followed by those aged 20–24 years
Figure 4: Combined YLD rates of URIs and otitis media globally, by age, in 2021
URIs=upper respiratory infections. YLD=years lived with disability.
0
50
100
150
200
YLD rate per 100
000 population
Disease
URIs
Otitis media
0–6 days
All ages
7–24 days
1–5 months
6–11 months
12–23 months
2–4 years
5–9 years
10–14 years
15–19 years
20–24 years
25–29 years
30–34 years
35–39 years
40–44 years
45–49 years
50–54 years
55–59 years
60–64 years
65–69 years
70–74 years
75–79 years
80–84 years
85–89 years
90–94 years
≥95 years
Age group
Figure 5: Maps of combined YLD rates (A) and DALY rates (B) for upper
respiratory infections and otitis media in 2021
DALY=disability-adjusted life-year. YLD=years lived with disability.

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43
Caribbean and central America Persian Gulf West Africa
Balkan Peninsula
Eastern
Mediterranean
Southeast Asia
A
Caribbean and central America Persian Gulf West Africa
Balkan Peninsula
Eastern
Mediterranean
Southeast Asia
B
DALY rate per 100
000 population
<60
60 to <75
75 to <100
100 to <125
125 to <150
150 to <175
175 to <200
200 to <225
225 to <250
250 to <275
275 to <300
≥300
YLD rate per 100
000 population
<60
60 to <70
70 to <80
80 to <90
90 to <100
100 to <110
110 to <120
120 to <130
130 to <140
≥140
Northern Europe
Northern Europe

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(538 000 [318 000–853 000]), and 25–29 years (473 000
[278 000–750 000]; appendix 2 p 13).
The all-age combined DALY rate in 2021 was 103 per
100 000 (63–152; appendix 2 p 13). Infants in the
1–5 months age group had the highest DALY rate per
100 000 in 2021 (647 [189–1412]), followed by early
neonates (aged 0–6 days; 582 per 100 000 [176–1297]) and
late neonates (aged 7–24 days; 482 per 100 000 [161–1052];
appendix 2 p 13). Among people aged 15 years and older,
the largest rate of DALYs was seen in those aged
15–19 years (100 per 100 000 [58–159]), followed by those
aged 20–24 years (90 per 100 000 [53–143]), and 95 years
and older (82 per 100 000 [57–127]; appendix 2 p 13).
The region with the largest combined DALY rate in
2021 was eastern sub-Saharan Africa (214·8 per 100 000
[95% UI 86·5–401·6]), followed by western sub-Saharan
Africa (198·5 per 100 000 [86·8–395·7]) and central sub-
Saharan Africa (178·4 per 100 000 [89·0–348·5]; appendix
2 p 14). The country with the highest combined DALY
rate in 2021 was Somalia (364·3 per 100 000
[103·0–1108·1]), followed by Central African Republic
(309·1 per 100 000 [119·3–684·1]) and Burkina Faso
(286·4 per 100 000 [96·0–816·8]; figure 5B; appendix 2
p 14).
Risk factor attribution of DALYs for URIs and otitis
media
The total number of DALYs attributable to the evaluated
risk factors of URIs in 2021 was 32 600 (95% UI
7690 to 79 100), a decrease of 54·6% (–79·7 to –29·0)
since 1990, when the total was 71 800 (21 100 to 141 000;
appendix 2 p 15). For otitis media, the total number of
DALYs attributable to evaluated risk factors in 2021 was
80 200 (35 100 to 144 000), a decrease of 23·7%
(–31·8 to –19·0) since 1990, when DALYs attributable to
the evaluated risk factors reached 105 000 (48 600 to
183 000; appendix 2 p 15).
In the GBD framework, URI burden is attributable to
four risk factors. The largest risk factor contributing to
URI DALYs in 1990 was low birthweight (57 600 DALYs
[95% UI 16 000 to 115 000]; appendix 2 p 15). Low
birthweight continued to be the largest risk factor for
URI DALYs in 2021 at 26 500 (5200 to 65 800), which was
a decrease of 54·0% (–80·0 to –26·8) since 1990
(appendix 2 p 15). The second largest risk factor for URI
DALYs in 2021 was short gestation (11 600 [1840 to 29 600]),
followed by household air pollution (9200 [1620 to 22 800])
and ambient particulate matter (2510 [983 to 5800];
appendix 2 p 15).
Otitis media is attributable to five risk factors in the
GBD framework. The greatest risk factor contributing to
the DALYs of otitis media in 1990 was second-hand
smoke (101 000 DALYs [95% UI 46 000 to 178 000];
appendix 2 p 15). In 2021, second-hand smoke remained
the greatest risk contributing to otitis media DALYs at
79 600 DALYs (34 600 to 143 000), a decrease of 21·6%
(–26·5 to –17·9) from 1990 (appendix 2 p 15). The second
largest risk factor of otitis media DALYs in 2021 was low
birthweight (444 [164 to 1070]), followed by household
air pollution (250 [110 to 521]), short gestation (202
[69 to 486]), and ambient particulate matter (78 [36 to 144];
appendix 2 p 15).
Discussion
To our knowledge, this study represents the first
comprehensive assessment of the global burden of
two interconnected infectious diseases, URIs and otitis
media, highlighting the magnitude of these conditions
and their impact on public health. The study also is the
first to explore the burden of these diseases at more
granular age and geographical levels. In 2021, there were
an estimated 12·8 billion episodes of URIs and
19 600 deaths due to URIs, while otitis media accounted
for 391 million episodes and 536 deaths. In both URIs
and otitis media, the highest burden was seen in neonatal
and paediatric age groups.
Our results show that URIs are widespread and
associated with substantial morbidity. The incidence rate
alone makes URIs the highest-ranking communicable
disease across the infections studied in the GBD
framework. Diarrhoea, the second highest-ranking
communicable disease in 2021, accounted for
approximately 59 000 episodes per 100 000 population,
while the third highest-ranking communicable disease
for all ages was COVID-19, estimated at 29 000 episodes
per 100 000 population; both occurred at substantially
lower rates than URIs (162 000 episodes per 100 000). In
children younger than 5 years, the incidence rate of URIs
was over three times greater than that of diarrhoea, and
over 15 times greater than that of COVID-19.24
Although URIs rarely result in death, with 19 600 deaths
globally in 2021, they contribute to nearly half of incident
episodes of all diseases globally and impose a substantial
burden on individuals, health-care systems, and
economies.2–5,21 Of deaths from URIs, the highest
mortality rates occurred among adults aged 95 years and
older and newborn babies, showing the disproportionate
impact of URIs among the more vulnerable members of
the population. Mortality rates due to URIs were highest
in sub-Saharan Africa, and the combined DALY rate
followed the same trend, with highest rates in Somalia,
Central African Republic, and Burkina Faso. This trend
might be explained in part by lower access to quality
health care in those regions. In 2019, universal health-
care coverage in Somalia and Central African Republic
largely lagged behind that in other countries.25 By
improving universal health-care coverage, the mortality
rates of URIs and other communicable diseases might
be alleviated.
Despite the relatively low mortality rate, it is important
to note that URIs can lead to more severe lower
respiratory infections (LRIs), which are associated with
much higher mortality rates.26 For example, SARS-CoV-2
often infected the upper respiratory tract before

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progressing to more severe and fatal disease in the lower
respiratory tract.27 URIs can be caused by a variety of
dierent viruses, including rhinoviruses, coronaviruses,
adenoviruses, enteroviruses, influenza viruses, para-
influenza viruses, and RSV. Of these, rhinoviruses are
among the predominant viral pathogens responsible for
URIs.28 During the COVID-19 pandemic, rhinoviruses
continued to propagate despite the use of face masks,
physical distancing, and lockdown measures.29
In terms of URI-related morbidity, YLDs due to URIs
are higher than those for many more prominent
infectious diseases, such as tuberculosis, HIV, and LRIs.21
When considered in combination with otitis media,
the impact of URIs in terms of healthy life lost
due to disability grows, emphasising the long-term
consequences and potential impact on quality of life
caused by these infections. Similar to URIs, the incidence
of otitis media has been increasing since 1990. Previous
studies have consistently reported the highest incidence
rates of otitis media in children aged 1–4 years, with a
peak incidence in children aged 6–18 months.18,21,30 In this
study, the highest incidence rates of otitis media were
estimated for children aged 12–23 months, followed by
those aged 6–11 months, showing considerable overlap
with age groups most aected by URIs. Together, URIs
and otitis media accounted for 6·86 million YLDs in
2021, with children aged 5–9 years contributing the
largest proportion of this burden, followed by those aged
10–14 years. These infections spread quickly among
school-aged children,11,16,18,19 underscoring the need for
targeted prevention and intervention strategies, which
could include promoting appropriate hygiene practices,
implementing antimicrobial stewardship programmes,
and emphasising the importance of vaccinations.7,16,31–35
The rise in antimicrobial resistance (AMR) is
particularly notable when considering the widespread
occurrence of URIs and otitis media, as URIs account for
a large proportion of antibiotic prescriptions in primary
care settings.36 The inappropriate prescription of
antibiotics in some cases of URI facilitates an
environment conducive to the emergence of AMR,
especially as most URIs are self-limiting and require only
symptomatic relief.36 Further understanding of the
causes of URIs and their associated pathogens is needed
to enable better preparedness for outbreaks and the
development of eective prevention and control
strategies that do not include the use of antibiotic
treatments.37
Recent advancements in our understanding of AMR
underscore the evolving challenges in treating otitis
media globally.38 These findings are particularly relevant
given the high dependency of otitis media treatment on
eective antibiotics. Pneumococcal conjugate vaccines in
particular have been shown to have a positive impact on
decreasing otitis media,39 but recent studies have reported
a shift in the bacteria causing otitis media towards
pneumococcal types not included in vaccines and other
bacteria.40 This shift, coupled with regional variations in
AMR, suggest the need for ongoing surveillance, tailored
treatment and prevention strategies, and stewardship
interventions to reduce unnecessary antibiotic use.
In addition to the significant potential for antibiotic
overuse, URIs and otitis media are associated with
increased health expenses and substantial health-related
productivity losses, particularly due to their high
prevalence among children, which contributes to work
absenteeism among parents and guardians. Parents or
guardians are often faced with the dicult decision of
sending sick children to school or missing work,41 a
choice that is disproportionately dicult for low-income
families and that potentially has a broader impact on
children and communities than could be examined in
the scope of this study.
The heavy burden of URIs and otitis media presents
opportunities for the development of vaccines and
medications that can reduce the burden of these diseases
and their impact on society. Such development is
particularly important when considering the ineective-
ness of common over-the-counter cold medicines.42 Some
preventive options for otitis media include published
guidelines for prevention and intervention such as those
from the Centers for Disease Control and Prevention,43
continued medical education to both medical
practitioners and the general public on the patho-
physiology of otitis media as well as its linkage to URIs,
and the introduction of relevant vaccines, such as the
higher-valency pneumococcal conjugate vaccines that are
currently becoming available, into national immunisation
programmes.44,45 Additionally, develop ments in mucosal
immunology and genetics are facilitating more targeted
treatment strategies, potentially transforming the
management of URIs and otitis media in the near
future.46–48
Ultimately, a multifaceted approach might be needed
to help prevent and manage the combined impact of
URIs and otitis media, given the varied eectiveness of
public health interventions.49,50 Unlike diseases such as
measles, for which vaccination is a straightforward
solution, strategies for URIs and otitis media must be
more diverse and specific. Tailoring public health
initiatives to local needs and resources is essential, and it
is important to understand local URI and otitis media
burdens and corresponding risk factors. For instance,
low birthweight, a leading risk factor for URIs and otitis
media in our study, can be reduced through improved
maternal health programmes and comprehensive care
during childhood, especially in low-income areas.51,52
While the prevalence of low birthweight has slightly
declined globally since the 2000s,53 it remains a
considerable risk factor for both diseases. Similarly,
exposure to household air pollution from solid fuels—
another leading risk factor for both URIs and otitis media
in our study—has decreased in some regions since the
1990s but continues to be a major problem, particularly

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in low-income and middle-income countries, with
2·3 billion people globally still having no access to clean
cooking as of 2021.54 Addressing the leading risk factors
for URIs and otitis media, including low birthweight and
exposure to household air pollution, as well as exposure
to second-hand smoke,55 the leading risk factor for otitis
media, could help reduce the burden of these diseases
and other respiratory conditions.
This study has several limitations, including the
availability of URI and otitis media data. In data-scarce
locations, estimates were generated on the basis of
regional patterns, covariates, and out-of-sample
predictive validity assessment. Locations with few or no
data produce wide uncertainty intervals during the
estimation process. Even in situations where data were
abundant, measurements might not have been based on
the same case definitions across studies. To combat these
limitations, methods of standardising case definitions
have provided more robust analyses.21 With the delays
that occur in data reporting, the recency of included data
varies across the two diseases. For example, URIs had
non-fatal data up to 2021, but the most recent non-fatal
data for otitis media included in the modelling were
from 2018. Data can also be problematic in situations
where one disease can progress into another more severe
disease; the survey and literature data used in this study
do not specify when a case of URI has progressed into a
case of LRI. Additionally, population attributable fraction
assumptions imply that there is a causal link between
exposure and outcome without confounding, that
removing the exposure would not aect the distribution
of unrelated risk factors, and that a practical intervention
to eliminate the exposure is possible.56 However, these
assumptions might not always hold true in real-world
scenarios. Furthermore, we attempted to account for
potential biases when quantifying the relationship
between risk factors and outcomes by incorporating bias
covariates; however, these might not fully identify and
correct bias if the input studies have inherent biases.
Finally, the risk factors evaluated for both URIs and otitis
media in our study might not encompass all possible risk
factors, as our inclusion criteria were limited to risk–
outcome pairs with convincing or probable evidence of a
causal relationship, in line with GBD standards.
While SARS-CoV-2 and other pathogens probably
contribute to the global burden of URIs, the exact
proportion remains unclear due to the infrequent and
variable use of comprehensive diagnostic testing and
lack of robust surveillance for URIs at the pathogen
level.57,58 This limits our understanding of the distribution
and frequency of URI pathogens and hinders the
potential for more targeted, early interventions. The
evolving landscape of respiratory pathogens necessitates
further research and more widespread pathogen
surveillance to clarify the relative contributions of various
pathogens to the global burden of URIs and inform
targeted public health interventions.59,60 Currently, GBD
does not quantify pathogens for URIs and otitis media.
Pathogen burden is crucial in understanding the
connection between URIs and more severe disease
progression, as well as in the creation of targeted disease-
mitigating protocols, including vaccines. To address this
limitation, we aim to include detailed results on pathogen
burden in future rounds of GBD. Additionally, we will be
able to quantify the indirect impact of the COVID-19
pandemic on the burden of URIs and otitis media in
subsequent rounds of the GBD as more data become
available. At present, assessing the available data, which
are limited, the impact of COVID-19 on URI episodes is
unclear. DHS data from five countries with at least
three timepoints including 2020 or 2021 (available as of
June, 2024) do not show a clear pattern of eect from the
COVID-19 pandemic on URIs. Some countries have
shown an increase in URI prevalence from prepandemic
years to postpandemic years, while others have shown a
decrease. In Madagascar, for example, there was an
increase in period prevalence from 2009 (5·74%
[5·14–6·33]) to 2021 (12·5% [11·7–13·4]), whereas Côte
d’Ivoire showed a decrease in period prevalence from
2012 (10·7% [9·61871–11·82528]) to 2021 (9·48%
[8·52–10·4]; appendix 2 p 4). In those countries that
showed a decrease, the trend of declining URI prevalence
was already evident before the pandemic. Therefore, it
remains unclear whether the decrease can be attributed
to non-pharmaceutical interventions or is merely a
continuation of previous trends. For DHS countries that
showed an increase between 2019 and 2021, it is possible
that changes in DHS data are due to misclassified
COVID-19 cases, as the DHS collect data on URI
symptoms but not on COVID-19 testing. This is an
important limitation, indicating the need for caution
when interpreting these results and future research that
could help to clarify these uncertainties. Existing
literature suggests that the non-pharmaceutical
interventions implemented during the COVID-19
pandemic have not substantially aected pathogens that
commonly cause URIs, such as rhinoviruses.61,62 Another
limitation is the potential underdiagnosis of COVID-19,
which could aect URI incidence and mortality. Recent
studies indicate that COVID-19 deaths might have been
misclassified as non-COVID-19 respiratory conditions,63–65
highlighting the need for comprehensive investigations
to understand the extent of such misclassification
involving URIs.
The results of this study show the substantial burden
imposed by URIs and otitis media. Although URIs and
otitis media do not often result in severe illness or death,
their high incidence rates and substantial morbidity
should not be ignored. Furthermore, given the close
association between URIs and otitis media, there is need
for comprehensive strategies that address the prevention,
early diagnosis, and eective management of these
conditions together, particularly in young children, who
are most aected. The potential for URIs to progress to

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more severe diseases, their contribution to AMR, and the
pandemic potential of some URI pathogens necessitate
comprehensive research and evidence-based strategies.
Future studies are needed to better understand where
stra tegies such as strengthening vaccination programmes,
enhancing antibiotic stewardship, and promo ting public
health campaigns focused on hygiene and prevention are
most needed.
GBD 2021 Upper Respiratory Infections and Otitis Media Collaborators
Sarah Brooke Sirota,* Matthew C Doxey,*
Regina-Mae Villanueva Dominguez, Rose Grace Bender,
Avi na Vongpradith, Samuel B Albertson, Amanda Novotney,
Katrin Burkart, Austin Carter, Parsa Abdi, Meriem Abdoun,
Ayele Mamo Abebe, Kedir Hussein Abegaz, Richard Gyan Aboagye,
Hassan Abolhassani, Lucas Guimarães Abreu, Hasan Abualruz,
Eman Abu-Gharbieh, Salahdein Aburuz, Mesafint Molla Adane,
Isaac Yeboah Addo, Victor Adekanmbi,
Qorinah Estiningtyas Sakilah Adnani, Leticia Akua Adzigbli,
Muhammad Sohail Afzal, Saira Afzal, Bright Opoku Ahinkorah,
Sajjad Ahmad, Ayman Ahmed, Haroon Ahmed, Syed Anees Ahmed,
Karolina Akinosoglou, Mohammed Ahmed Akkaif, Salah Al Awaidy,
Samer O Alalalmeh, Mohammed Albashtawy, Mohammad T AlBataineh,
Adel Ali Saeed Al-Gheethi, Fadwa Naji Alhalaiqa, Robert Kaba Alhassan,
Abid Ali, Liaqat Ali, Mohammed Usman Ali, Syed Shujait Ali, Waad Ali,
Joseph Uy Almazan, Jaber S Alqahtani, Ahmad Alrawashdeh,
Rami H Al-Rifai, Najim Z Alshahrani, Khaled Altartoor,
Jaar A Al-Tawfiq, Nelson Alvis-Guzman, Yaser Mohammed Al-Worafi,
Hany Aly, Safwat Aly, Karem H Alzoubi, Walid Adnan Al-Zyoud,
Abebe Feyissa Amhare, Hubert Amu, Ganiyu Adeniyi Amusa,
Abhishek Anil, Saeid Anvari, Ekenedilichukwu Emmanuel Anyabolo,
Jalal Arabloo, Mosab Arafat, Demelash Areda, Brhane Berhe Aregawi,
Abdulfatai Aremu, Seyyed Shamsadin Athari, Avinash Aujayeb,
Zewdu Bishaw Aynalem, Sina Azadnajafabad, Ahmed Y Azzam,
Muhammad Badar, Pegah Bahrami Taghanaki, Saeed Bahramian,
Atif Amin Baig, Milica Bajcetic, Senthilkumar Balakrishnan,
Maciej Banach, Mainak Bardhan, Hiba Jawdat Barqawi,
Mohammad-Mahdi Bastan, Kavita Batra, Ravi Batra,
Amir Hossein Behnoush, Maryam Beiranvand, Alemu Gedefie Belete,
Melaku Ashagrie Belete, Apostolos Beloukas, Azizullah Beran,
Pankaj Bhardwaj, Ashish Bhargava, Ajay Nagesh Bhat,
Mohiuddin Ahmed Bhuiyan, Veera R Bitra, Aadam Olalekan Bodunrin,
Eyob Ketema Bogale, Sri Harsha Boppana, Hamed Borhany,
Souad Bouaoud, Colin Stewart Brown, Danilo Buonsenso,
Yas ser Bustanji, Luis Alberto Cámera, Carlos A Castañeda-Orjuela,
Luca Cegolon, Muthia Cenderadewi, Sandip Chakraborty,
Vijay Kumar Chattu, Esther T W Cheng, Fatemeh Chichagi,
Patrick R Ching, Hitesh Chopra, Sonali Gajanan Choudhari,
Devasahayam J Christopher, Dinh-Toi Chu, Isaac Sunday Chukwu,
Erin Chung, Alexandru Corlateanu, Natalia Cruz-Martins,
Sriharsha Dadana, Omid Dadras, Tukur Dahiru, Xiaochen Dai,
Jai K Das, Nihar Ranjan Dash, Mohsen Dashti, Mohadese Dashtkoohi,
Fernando Pio De la Hoz, Shayom Debopadhaya,
Berecha Hundessa Demessa, Asmamaw Bizuneh Demis,
Vinoth Gnana Chellaiyan Devanbu, Devananda Devegowda,
Kuldeep Dhama, Vishal R Dhulipala, Daniel Diaz, Michael J Diaz,
Thanh Chi Do, Thao Huynh Phuong Do, Masoud Dodangeh,
Fariba Dorostkar, Ashel Chelsea Dsouza, Haneil Larson Dsouza,
Senbagam Duraisamy, Oyewole Christopher Durojaiye,
Arkadiusz Marian Dziedzic, Abdelaziz Ed-Dra, Michael Ekholuenetale,
Temitope Cyrus Ekundayo, Iman El Sayed, Faris El-Dahiyat,
Muhammed Elhadi, Mohammed Elshaer, Majid Eslami,
Ugochukwu Anthony Eze, Adeniyi Francis Fagbamigbe, Ali Faramarzi,
Folorunso Oludayo Fasina, Nuno Ferreira, Florian Fischer, Ida Fitriana,
Luisa S Flor, Santosh Gaihre, Márió Gajdács, Nasrin Galehdar,
Mohammad Arfat Ganiyani, Miglas Welay Gebregergis,
Mesfin Gebrehiwot, Teferi Gebru Gebremeskel, Genanew K Getahun,
Molla Getie, Keyghobad Ghadiri, Afsaneh Ghasemzadeh,
Mahsa Ghorbani, Mohamad Goldust, Mahaveer Golechha, Pouya Goleij,
Giuseppe Gorini, Anmol Goyal, Shi-Yang Guan, Giovanni Guarducci,
Mesay Dechasa Gudeta, Renu Gupta, Sapna Gupta, Veer Bala Gupta,
Vivek Kumar Gupta, Mostafa Hadei, Najah R Hadi, Arvin Haj-Mirzaian,
Rabih Halwani, Samer Hamidi, Ahmad Hammoud, Nasrin Hanifi,
Fahad Hanna, Zaim Anan Haq, Md Rabiul Haque,
S M Mahmudul Hasan, Hamidreza Hasani, Md Saquib Hasnain,
Hadi Hassankhani, Johannes Haubold, Khezar Hayat, Omar E Hegazi,
Kamal Hezam, Ramesh Holla, Praveen Hoogar, Nobuyuki Horita,
Mihaela Hostiuc, Hong-Han Huynh, Segun Emmanuel Ibitoye,
Olayinka Stephen Ilesanmi, Irena M Ilic, Milena D Ilic,
Mohammad Tarique Imam, Mustafa Alhaji Isa, Md Rabiul Islam,
Sheikh Mohammed Shariful Islam, Nahlah Elkudssiah Ismail,
Masao Iwagami, Vinothini J, Abdollah Jafarzadeh, Khushleen Jaggi,
Ammar Abdulrahman Jairoun, Mihajlo Jakovljevic, Elham Jamshidi,
Shubha Jayaram, Bijay Mukesh Jeswani, Ravi Prakash Jha, Jobinse Jose,
Nitin Joseph, Charity Ehimwenma Joshua, Jacek Jerzy Jozwiak,
Vai shali K, Zubair Kabir, Himal Kandel, Kehinde Kazeem Kanmodi,
Surya Kant, Rami S Kantar, Ibraheem M Karaye,
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Min Seo Kim, Ruth W Kimokoti, Sonali Kochhar,
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Hare Krishna, Vijay Krishnamoorthy, Barthelemy Kuate Defo,
Md Abdul Kuddus, Mohammed Kuddus, Ilari Kuitunen,
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L V Simhachalam Kutikuppala, Chandrakant Lahariya,
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Mohammad Sadeq Najafi, Soroush Najdaghi,
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Mohammad-Mahdi Rashidi, Devarajan Rathish, Nakul Ravikumar,
Salman Rawaf, Elrashdy Moustafa Mohamed Redwan,
Luis Felipe Felipe Reyes, Nazila Rezaei, Nima Rezaei,
Omid Rezahosseini, Syed Mohd Danish Rizvi,
Jeerson Antonio Buendia Rodriguez, Luca Ronfani,
Shekoufeh Roudashti, Priyanka Roy, Guilherme de Andrade Ruela,
Basema Ahmad Saddik, Mohammad Reza Saeb, Umar Saeed,
Pooya Saeedi, Mehdi Safari, Fatemeh Saheb Sharif-Askari,
Narjes Saheb Sharif-Askari, Amirhossein Sahebkar, Monalisha Sahu,
Joseph W Sakshaug, Nasir Salam, Afeez Abolarinwa Salami,
Mohamed A Saleh, Malik Sallam, Yoseph Leonardo Samodra,
Rama Krishna Sanjeev, Milena M Santric-Milicevic, Aswini Saravanan,
Benn Sartorius, Anudeep Sathyanarayan, Jennifer Saulam, Sonia Saxena,
Ganesh Kumar Saya, Benedikt Michael Schaarschmidt,
Austin E Schumacher, Mansour Sedighi, Ashenafi Kibret Sendekie,
Subramanian Senthilkumaran, Yashendra Sethi,
SeyedAhmad SeyedAlinaghi, Mahan Shafie, Samiah Shahid,
Masood Ali Shaikh, Sunder Sham, Mohammad Ali Shamshirgaran,
Mohd Shanawaz, Mohammed Shannawaz, Amin Sharifan,
Javad Sharifi-Rad, Rajesh P Shastry, Aziz Sheikh, Mika Shigematsu,
Rahman Shiri, Aminu Shittu, Ivy Shiue, Seyed Afshin Shorofi,
Emmanuel Edwar Siddig, Colin R Simpson, Jasvinder A Singh,
Paramdeep Singh, Surjit Singh, Robert Sinto, Ranjan Solanki,
Sameh S M Soliman, Muhammad Suleman,
Rizwan Suliankatchi Abdulkader, Chandan Kumar Swain,
Lukasz Szarpak, Seyyed Mohammad Tabatabaei, Mohammad Tabish,
Zanan Mohammed-Ameen Taha, Jabeen Taiba, Iman M Talaat,
Jacques Lukenze Tamuzi, Birhan Tsegaw Taye, Yibekal Manaye Tefera,
Mohamad-Hani Temsah, Dufera Rikitu Terefa, Ramna Thakur,
Rekha Thapar, Sathish Thirunavukkarasu, Ales Tichopad,
Jansje Henny Vera Ticoalu, Marcos Roberto Tovani-Palone,
Nghia Minh Tran, Ngoc Ha Tran, Nguyen Tran Minh Duc,
Guesh Mebrahtom Tsegay, Munkhtuya Tumurkhuu,
Aniefiok John Udoakang, Era Upadhyay, Seyed Mohammad Vahabi,
Asokan Govindaraj Vaithinathan, Rohollah Valizadeh,
Tommi Juhani Vasankari, Manish Vinayak, Muhammad Waqas,
Haftom Legese Weldetinsaa, Nuwan Darshana Wickramasinghe,
Ali Yadollahpour, Sajad Yaghoubi, Saber Yezli, Dehui Yin,
Dong Keon Yon, Naohiro Yonemoto, Yong Yu, Fathiah Zakham,
Ghazal G Z Zandieh, Iman Zare, Fatemeh Zarimeidani,
Michael Zastrozhin, Chunxia Zhai, Haijun Zhang, Zhi-Jiang Zhang,
Yang Zhao, Juexiao Zhou, Hafsa Zia, Magdalena Zielińska,
Mohammad Zoladl, Samer H Zyoud, Aleksandr Y Aravkin,
Nicholas J Kassebaum, Mohsen Naghavi, Theo Vos, Simon I Hay,
Christopher J L Murray, and Hmwe H Kyu.
*Co-first author.
Affiliations
Aliations are provided in appendix 3 (pp 4–18).
Contributors
See appendix 3 (pp 18–23) for more detailed information about
individual author contributions to the research, divided into the
following categories: managing the overall research enterprise; writing
the first draft of the manuscript; primary responsibility for applying
analytical methods to produce estimates; primary responsibility for
seeking, cataloguing, extracting, or cleaning data; designing or coding
figures and tables; providing data or critical feedback on data sources;
developing methods or computational machinery; providing critical
feedback on methods or results; drafting the manuscript or revising it
critically for important intellectual content; and managing the
estimation or publications process.
Declaration of interests
S Afzal reports payment for educational events and webinars from
King Edward Medical University and collaborative partners including
Johns Hopkins University, University of California, University of
Massachusetts, University of Nebraska, Imperial College London,
KEMCA-UK, KEMCAANA, and APPNA; participation on a data safety
monitoring board or advisory board with National Bioethics Committee
Pakistan, the King Edward Medical University Institutional Ethical
Review Board, and the Fatima Jinnah Medical University and
Sir Ganga Ram Hospital Ethical Review Board; leadership or fiduciary
roles in other board, society, committee or advocacy groups (paid or
unpaid) with the Pakistan Association of Medical Editors, Faculty of
Public Health Royal Colleges UK (fellow), Society of Prevention,
Advocacy and Research at King Edward Medical University, and Pakistan
Society of Infectious Diseases (member); and other financial or non-
financial interests with the Corona Experts Advisory Group (member),
Dengue Advisory Group (member), Technical Working Group or
guidelines development for COVID-19 (member), National Command
and Operation Committee of the Government of Pakistan (expert
opinion), Pakistan Medical & Dental Council Research and Journals
Committee (member), HEC Research and Publications Committee
(member), Quality Assurance Agency HEC (member), Public Health
and Preventive Medicine at King Edward Medical University (Dean),
Quality Enhancement Cell at King Edward Medical University (director),
Annals of King Edward Medical University (chief editor), and History Book
of King Edward Medical University (chief editor), all outside the
submitted work. S A Meo reports grants or contracts from the
Deputyship for Research and Innovation, Ministry of Education in Saudi
Arabia (IFKSUOR3-4-9), outside the submitted work. A Beloukas reports
grants or contracts from Gilead (research grant and sponsorship to the
University of West Attica) and GSK (research sponsorship to the
University of West Attica); participation on a data safety monitoring
board or advisory board with Gilead and GSK, paid to the University of
West Attica; supports for attending meetings or travel from Gilead and
GSK, paid to the University of West Attica; and receipt of equipment,
materials, drugs, medical writing, gifts, or other services from Cepheid
in the form of free-of-charge reagents for a research project; all outside
the submitted work. C S Brown reports other financial support from
market research companies via ad-hoc, one-o market research
advisories on a variety of infection topics, all anonymous, conducted
with no direct communication nor any knowledge of any pharmaceutical
companies or products, outside the submitted work. I M Ilic and
M D Ilic report support for the present manuscript from the Ministry of
Science, Technological Development and Innovation of the Republic of
Serbia (project numbers 175042, 2011-2023, 451-03-47/2023-01/200111).
N E Ismail reports leadership or fiduciary roles in other board, society,
committee, or advocacy groups (unpaid) as the Bursar and Council
Member of the Malaysian Academy of Pharmacy and is a member of the
Committee of the Malaysian Pharmacists Society Education Chapter,
outside the submitted work. J J Jozwiak reports payment or honoraria
for lectures, presentations, speakers bureaus, manuscript writing,
or educational events from Novartis, Adamed, and Amgen, outside the
submitted work. K Krishan reports non-financial support from the UGC
Centre of Advanced Study, CAS II, awarded to the Department of
Anthropology, Panjab University (Chandigarh, India), outside the
submitted work. M-C Li reports grants or contracts from the National
Science and Technology Council, Taiwan (NSTC 112-2410-H-003-031);
and leadership or fiduciary roles in board, society, committee,
or advocacy groups (paid or unpaid) as Technical Editor with the
Journal of the American Heart Association, all outside the submitted work.
L Monasta reports support from the Italian Ministry of Health (Ricerca
Corrente 34/2017) and payments made to the Institute for Maternal and
Child Health IRCCS Burlo Garofolo, outside the submitted work.
C E Moore reports participation on an advisory board for an MRC grant
with Gwen Knight (unpaid), WHO Advisory Group for the WHO
Medically Important Antimicrobial List, and REVIVE Advisory Group as
member of the steering group; and leadership or fiduciary roles in
board, society, committee, or advocacy groups (unpaid) with the
Microbiology Society as Co-chair of Impact and Influence Group,
all outside the submitted work. A P Okekunle reports support for the
present manuscript from the National Research Foundation of Korea
funded by the Ministry of Science and ICT (2020H1D3A1A04081265)
and support for attending meetings or travel from the National Research
Foundation of Korea (funded by the Ministry of Science and ICT;
2020H1D3A1A04081265), outside the submitted work. E Ortiz-Prado
reports grants or contracts from Universidad de las Americas, outside
the submitted work. L F Reyes reports grants or contracts from MSD;
consulting fees from GSK, MSD, and Pfizer; payment or honoraria for
lectures, presentations, speakers bureaus, manuscript writing,
or educational events from GSK, MSD, and Pfizer; payment for expert
testimony from GSK and MSD; and support for attending meetings or
See Online for appendix 3

Articles
www.thelancet.com/infection Vol 25 January 2025
49
travel from GSK and Pfizer, outside the submitted work. O Rezahosseini
reports support for attending meetings or travel from the Research
Department of Nordsjælands Hospital and European Society of Clinical
Microbiology and Infectious Diseases 2024, outside the submitted work.
L Ronfani reports support for the present manuscript from the Italian
Ministry of Health (Ricerca Corrente 34/2017; payments made to the
Institute for Maternal and Child Health IRCCS Burlo Garofolo).
Y L Samodra reports a leadership or fiduciary role in a board, society,
committee, or advocacy group (paid or unpaid) as co-founder of Benang
Merah Research Center (bmrc.id), outside the submitted work. S Saxena
reports grants or contracts and support for attending meetings or travel
from the National Institute for Health and Care Research (NIHR) Senior
Investigator Award, NIHR School for Public Health Research (grant
number NIHR 204000), NIHR Northwest London Applied Research
Collaboration; participation on a data safety monitoring board or
advisory board with the BMJ International Editorial Board (advisory,
unpaid) and the NIHR (Academy Chair, £7500 per annum honorarium
paid to their institution); and leadership or fiduciary roles in board,
society, committee, or advocacy groups (paid or unpaid) with the
European Public Health Association as President of the Child and
Adolescent Health Section, all outside the submitted work.
B M Schaarschmidt reports research grants from Else Kröner-Fresenius
Foundation, Deutsche Forschungsgemeinschaft, and PharmaCept
GmbH; payment or honoraria for lectures, presentations, speakers
bureaus, manuscript writing, or educational events from AstraZeneca;
and support for travel from Bayer, all outside the submitted work.
A Sharifan reports leadership or fiduciary roles in other board, society,
committee, or advocacy groups (unpaid) as a steering committee
member of Cochrane; and receipt of equipment, materials, drugs,
medical writing, gifts, or other services from Elsevier, outside the
submitted work. C R Simpson reports grants from HRC (New Zealand),
Ministry of Health (New Zealand), MBIE (New Zealand), Chief Scientist
Oce (UK), and MRC (UK); and leadership or fiduciary roles in other
board, society, committee, or advocacy groups (paid or unpaid) as a
Chair of the New Zealand Government Data Ethics Advisory Group,
outside the submitted work. J A Singh reports consulting fees from
ROMTech, Atheneum, ClearView Healthcare Partners, American
College of Rheumatology, Yale, Hulio, Horizon Pharmaceuticals,
DINORA, Frictionless Solutions, Schipher, Crealta/Horizon, Medisys,
Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care Options,
Putnam Associates, Focus Forward, Navigant Consulting, Spherix,
MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD,
Practice Point Communications, and the National Institutes of Health;
payment or honoraria for lectures, presentations, speakers bureaus,
manuscript writing, or educational events on the speakers bureau of
Simply Speaking; support for attending meetings or travel from
OMERACT as a steering committee member; participation on a data
safety monitoring board or advisory board with the FDA Arthritis
Advisory Committee; leadership or fiduciary roles in other board, society,
committee, or advocacy groups as a past steering committee member of
the OMERACT (an international organisation that develops measures
for clinical trials and receives arm’s-length funding from
12 pharmaceutical companies; paid), as Chair of the Veterans Aairs
Rheumatology Field Advisory Committee (unpaid), and as the Editor and
Director of the UAB Cochrane Musculoskeletal Group Satellite Center
on Network Meta-analysis (unpaid); stock or stock options in Atai Life
Sciences, Kintara Therapeutics, Intelligent Biosolutions, Acumen
Pharmaceutical, TPT Global Tech, Vaxart Pharmaceuticals, Atyu
Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris
Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals,
Aebona Pharmaceuticals, and Charlotte’s Web, and previously owned
stock options in Amarin, Viking, and Moderna Pharmaceuticals, outside
the submitted work. J H V Ticoalu reports leadership or fiduciary roles
in board, society, committee, or advocacy groups (paid or unpaid) with
Benang Merah Research Center (bmrc.id) as a co-founder, outside the
submitted work. E Upadhyay reports the following published patents:
a system and method of reusable filters for anti-pollution mask; a system
and method for electricity generation through crop stubble by using
microbial fuel cells; a system for disposed personal protection
equipment into biofuel through pyrolysis and method; and a novel
herbal pharmaceutical aid for formulation of gel and method thereof.
E Upadhyay also reports patents filed: herbal drug formulation for
treating lung tissue degenerated by particulate matter exposure; and a
method to transform cow dung into the wall paint by using natural
materials and composition thereof. Additionally, E Upadhyay reports
leadership or fiduciary roles in other board, society, committee, or
advocacy groups (paid or unpaid) as Joint Secretary of Indian
Meteorological Society, Jaipur Chapter (India), and as Member-Secretary
of DSTPURSE Program, outside the submitted work. M Zielińska
reports other financial interests as an employee of AstraZeneca, outside
the submitted work.
Data sharing
To download the data used in these analyses, please visit the GHDx GBD
2021 website.
Acknowledgments
This study was funded by the Bill & Melinda Gates Foundation.
Editorial note: The Lancet Group takes a neutral position with respect to
territorial claims in published maps and institutional aliations.
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