Article

Burden of Seasonal and Pandemic Influenza-Associated Hospitalization during and after 2009 A(H1N1)pdm09 Pandemic in a Rural Community in India

University of Hong Kong, Hong Kong
PLoS ONE (Impact Factor: 3.23). 05/2013; 8(5):e55918. DOI: 10.1371/journal.pone.0055918
Source: PubMed

ABSTRACT

Influenza is vaccine-preventable; however, the burden of severe influenza in India remains unknown. We conducted a population-based study to estimate the incidence of laboratory confirmed influenza-associated hospitalizations in a rural community in western India.
We conducted active surveillance for hospitalized patients with acute medical illnesses or acute chronic disease exacerbations in Pune during pandemic and post pandemic periods (May 2009-April 2011). Nasal and throat swabs were tested for influenza viruses. A community health utilization survey estimated the proportion of residents hospitalized with respiratory illness at non-study facilities and was used to adjust incidence estimates from facility-based surveillance.
Among 9,426 hospitalizations, 3,391 (36%) patients were enrolled; 665 of 3,179 (20.9%) tested positive for influenza. Of 665 influenza positives, 340 (51%) were pandemic A(H1N1)pdm09 and 327 (49%) were seasonal, including A/H3 (16%), A/H1 (3%) and influenza B (30%). The proportion of patients with influenza peaked during August 2009 (39%) and 2010 (42%). The adjusted annual incidence of influenza hospitalizations was 46.8/10,000 during pandemic and 40.5/10,000 during post-pandemic period with comparable incidence of A(H1N1)pdm09 during both periods (18.8 and 20.3, respectively). The incidence of both pH1N1 and seasonal hospitalized influenza disease was highest in the 5-29 year olds.
We document the previously unrecognized burden of influenza hospitalization in a rural community following the emergence of influenza A(H1N1)pdm09 viruses in India. During peak periods of influenza activity circulation i.e during the monsoon period, 20% of all hospital admissions in the community had influenza positivity. These findings can inform development of influenza prevention and control strategies in India.

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Available from: Joshua A Mott
Burden of Seasonal and Pandemic Influenza-Associated
Hospitalization during and after 2009 A(H1N1)pdm09
Pandemic in a Rural Community in India
Mandeep S. Chadha
1
*
.
, Siddhivinayak Hirve
2.
, Fatimah S. Dawood
3
, Pallavi Lele
2
,
Avinash Deoshatwar
1,2
, Somnath Sambhudas
2
, Sanjay Juvekar
2
, Kathryn E. LaFond
3
, Joshua A. Mott
3
,
Renu B. Lal
3
, Akhilesh C. Mishra
1
*
1 National Institute of Virology, Indian Council of Medical Research, Pune, India, 2 Vadu Rural Health Program, King Edward Memorial Hospital Research Center, Pune,
India, 3 Influenza Division, National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
America
Abstract
Background:
Influenza is vaccine-preventable; however, the burden of severe influenza in India remains unknown. We
conducted a population-based study to estimate the incidence of laboratory confirmed influenza-associated
hospitalizations in a rural community in western India.
Methods:
We conducted active surveillance for hospitalized patients with acute medical illnesses or acute chronic disease
exacerbations in Pune during pandemic and post pandemic periods (May 2009–April 2011). Nasal and throat swabs were
tested for influenza viruses. A community health utilization survey estimated the proportion of residents hospitalized with
respiratory illness at non-study facilities and was used to adjust incidence estimates from facility-based surveillance.
Results:
Among 9,426 hospitalizations, 3,391 (36%) patients were enrolled; 665 of 3,179 (20.9%) tested positive for influenza.
Of 665 influenza positives, 340 (51%) were pandemic A(H1N1)pdm09 and 327 (49%) were seasonal, including A/H3 (16%), A/
H1 (3%) and influenza B (30%). The proportion of patients with influenza peaked during August 2009 (39%) and 2010 (42%).
The adjusted annual incidence of influenza hospitalizations was 46.8/10,000 during pandemic and 40.5/10,000 during post-
pandemic period with comparable incidence of A(H1N1)pdm09 during both periods (18.8 and 20.3, respectively). The
incidence of both pH1N1 and seasonal hospitalized influenza disease was highest in the 5–29 year olds.
Conclusions:
We document the previously unrecognized burden of influenza hospitalization in a rural community following
the emergence of influenza A(H1N1)pdm09 viruses in India. During peak periods of influenza activity circulation i.e during
the monsoon period, 20% of all hospital admissions in the community had influenza positivity. These findings can inform
development of influenza prevention and control strategies in India.
Citation: Chadha MS, Hirve S, Dawood FS, Lele P, Deoshatwar A, et al. (2013) Burden of Seasonal and Pandemic Influenza-Associated Hospitalization during and
after 2009 A(H1N1)pdm09 Pandemic in a Rural Community in India. PLoS ONE 8(5): e55918. doi:10.1371/journal.pone.0055918
Editor: Benjamin J. Cowling, University of Hong Kong, Hong Kong
Received October 3, 2012; Accepted January 3, 2013; Published May 15, 2013
Copyright: ß 2013 Chadha 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: The Influenza Disease Burden, India Study was supported by a Centers for Disease Control and Prevention co-operative agreement # 1U01IP000206.
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: acm1750@rediffmail.com (MSC); mscniv@hotmail.com (ACM)
. These authors contributed equally to this work
Introduction
Though virologic surveillance for human influenza is well
established globally [1], limited epidemiologic studies have been
carried out in tropical and sub-tropical developing countries [2]
and few estimates of influenza disease burden exist for these
countries. Excess mortality due to pneumonia and influenza has
been used to identify and measure the impact of influenza
epidemics in developed countries [3,4]. Estimates of the incidence
of severe non-fatal influenza or influenza-associated hospitalization
are another critical measure of influenza disease burden useful for
influenza prevention and treatment strategies.
Globally, influenza is a common in children with respiratory
infection resulting in substantial burden on the health care system
[5]. In India, acute respiratory infections (ARI) are a leading cause
of morbidity and mortality, particularly in children less than five
years of age in whom the incidence of hospitalized pneumonia is
estimated to be 0.37 episodes per child year [5]. An estimated 43
million episodes of ARI occur in India annually. Although several
studies have documented that 4–12% of respiratory illnesses in the
community are due to influenza [6–9] the contribution of
influenza to acute medical hospitalizations remains unknown.
Data on severe influenza, such as influenza-associated hospital-
ization is critical to measuring public health impact of influenza.
Understanding this burden in rural communities is particularly
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important in India where 69% of the population lives in rural
areas [10]. Reliable disease burden estimates will assist health care
planners in prioritizing investments in health, and evaluating
intervention strategies. We conducted a population-based surveil-
lance for patients hospitalized with acute medical illness in a rural
community in India to estimate the annual cumulative incidence
of influenza-associated hospitalizations during a two year period
coinciding with the emergence of the 2009 pandemic. Our data
highlights the impact of the 2009 H1N1 pandemic and seasonal
influenza and provides the first estimates of influenza-associated
hospitalization rates in India.
Results
Influenza surveillance among hospitalized patients
From May 2009 to April 2011, 9,426 patients who were
hospitalized in the participating hospitals were screened; 3,391
(36%) met eligibility criteria A total of 212 (6%) patients were
excluded due to specimen quality, of the remaining 3,179 patients,
influenza virus infection was confirmed in 665 (21%) (Table 1),with
highest positivity (52%) among persons 15–29 years of age.
The proportion of influenza positive hospitalized patients with
acute medical illness was significantly higher during year 1 than
year 2 (330/1435 vs. 331/1744 patients, p = 0.007). Pandemic
A(H1N1)pdm09 virus predominantly circulated in both years
(46% in year 1 and 56% in year 2), followed by influenza B (19%
and 40% in year 1 and 2, respectively) and Influenza A (6%
A(H1N1) and 29% A(H3N2) in year 1 and 12% A(H3N2) in year
2).
The most common diagnosis at discharge was Viral fever (77%),
enteric fever (6%), malaria (7%), pneumonia (2%), dengue fever
(1.5%) and fever of unknown origin (6.5%),Of the 665 inpatients
positive for influenza, 10 (1.5%) had known underlying chronic
illness; 8 had chronic obstuctive pulmonary disease/asthma and 2
had CVD. Influenza was associated with $10% of hospitalizations
for acute medical illness each month during May2009 through
September2010 (Figure 1).
The number of influenza-associated hospitalizations peaked in
the monsoon season during August of each year. Although
pandemic A(H1N1)pdm09 virus was detected in May 2009, the
overall monthly peak in influenza-associated hospitalizations
during year 1 was associated with A(H3N2) but was lower than
the monthly peak of A(H1N1)pdm09-associated hospitalizations
during year 2.
Incidence of all-cause, respiratory, and influenza-
associated hospitalizations
Acute medical hospitalizations and respiratory illness hospital-
izations were comparable during year 1 and 2 (acute medical
hospitalization: 223.6 vs. 229.1 per 10,000 persons; respiratory
illness hospitalizations: 149.1 vs. 160.9 per 10,000 persons)
(Table 2). Children ,5 years had the highest incidences of all-
cause acute medical illness and respiratory illness hospitalizations
during both years. Duration of hospitalization was upto two days
33.6% patients,3–7 days in 62.6% and more than 7days in 3.7%
patients. During year 1 and 2, influenza-associated hospitalizations
accounted for 21% and 18% of all acute medical hospitalizations
and 25% and 31% of all respiratory hospitalizations, respectively.
Among children 5–14 years, influenza-associated hospitalizations
accounted for 30–35% of all acute medical hospitalizations and
38–48% of all respiratory hospitalizations.
Influenza-associated hospitalization was significantly higher
(46.8; 95% CI, 42.6–51.2 per10,000 persons) in year 1 than year
2 (40.5; 95% CI, 36.9–44.3 per 10,000 persons) (Table 2). During
both years, rates were highest among persons aged 15–29,
followed by children aged 5–14 years, and lowest among ,1 year
olds and persons .60 years (Figure 2).
Influenza-associated hospitalization incidence by type
and sub-type
Influenza A(H1N1)pdm09-associated hospitalization rates were
highest (21.5/10,000 persons), followed by seasonal influenza A
(16.4/10,000 persons) and influenza B (8.8/10,000 persons) in
year 1 (Table 3). During year 2, influenza A(H1N1)pdm09-
associated hospitalization rates remained highest (23/10,000
persons), followed by influenza B (16/10,000 persons). Compared
with year 1, influenza B-associated hospitalization rates during
year 2 were almost two-fold higher (8.8 vs. 16.4/10,000 persons)
and seasonal influenza A hospitalization rates were .10 fold lower
(16.4 vs. 1.5 per 10,000 persons). Among infants aged ,1 year,
influenza-associated hospitalizations were exclusively due to
influenza B during year 1 and A(H1N1)pdm09 during year 2. In
the age groups (1–4, 5–14, 15–29 and 30–44 years)a drop in
incidence of influenza A and rise in type B in year2 was observed.
In the older age groups of 45–49 and 60 years and above also a fall
in influenza A and rise in influenza B as well in influenza
A(H1N1)pdm09.
Estimates of influenza-associated hospitalization
incidence by enrollment screening definition
The estimated average annual influenza-associated hospitaliza-
tion incidence during the study period was 44.1/10,000 persons.
Using ILI screening definition for enrollment, the estimated
influenza-associated hospitalization incidence is 30.1/10,000
persons, (68% of the burden estimate resulting from enrolling
patients with all acute medical illness) (Table 4) and using SARI
screening definition it is 1.3/10,000 persons which are significant
underestimates.
Discussion
Our study is the first attempt to estimate burden of influenza
among acute medical hospitalized patients in a large population
based study in rural India. Adopting a broad surveillance case
definition ensured that influenza cases presenting as acute
Table 1. Characteristics of the study population and
influenza positivity, by age group, Vadu, District Pune, India,
May 2009–April 2011.
Under surveillance Enrolled
Influenza
positive
Age, years No. % No. % No. %
,1r 1,281 1 86 3 5 1
1–4 9,307 8 251 8 39 6
5–14 19,262 16 404 13 143 22
15–29 43,868 38 1426 45 348 52
30–44 24,816 21 554 17 83 12
45–59 10,921 9 279 9 33 5
60+ 7,434 6 179 6 14 2
All ages 116,889 100 3179 665
doi:10.1371/journal.pone.0055918.t001
Influenza Burden in a Rural Community in India
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exacerbations of chronic disease or having atypical presentations
were not missed. However, the numbers of patients with
underlying chronic disease is low; there is a possibility that
chronic diseases go undiagnosed in the community. Population-
based surveillance in a well-enumerated population and health
utilization surveys enabling adjustment for patients admitted to
non-participating hospitals allowed us to better estimate the
annual incidence of all acute medical illness hospitalizations,
respiratory hospitalizations, as well as influenza-associated hospi-
talizations. I Influenza accounted for a substantial proportion of all
acute medical and respiratory illness hospitalizations during and
after the emergence of the A(H1N1)pdm09 virus. Use of ILI or
SARI case definitions, to estimate the burden of influenza-
associated hospitalizations would have substantially underestimat-
ed the impact of influenza in the study population.
The average annualized incidence of influenza-associated
hospitalizations in current study was 44.1 per 10,000 persons,
which is substantially higher than 3.6–11.5/10,000 persons
reported in the United States [11]. We undertook this burden
study when a pandemic virus was emerging, thus our estimated
incidence rates of influenza-associated hospitalizations are higher
than what has been observed for seasonal influenza elsewhere. We
found the highest influenza-associated hospitalization incidences
occurred among persons aged 5–29 years which differs markedly
from findings for seasonal influenza in other countries. In the US
and Canada, influenza-associated hospitalization incidences are
highest among those .65 years with underlying medical
conditions (40–56 per 10,000), infants aged ,6 months (18–104
per 10,000) and adults .65 years without underlying conditions
(9–23 per 10,000) [12–18]. Similarly, in Thailand and Hong
Kong, hospitalization incidences are highest among older adults,
and incidences among children exceed those in the United States
[19–23].In contrast, we found the lowest hospitalization incidences
in persons aged .60 years, followed by infants aged ,1 year. The
difference in the relative age distribution of influenza-associated
hospitalization incidence between our study and others might be
due to the A(H1N1)pdm09 virus which resulted in increased
morbidity and mortality among younger persons compared to
seasonal influenza. However, persons aged 1–29 years had the
highest hospitalization incidence for acute medical illness,
respiratory illness, and influenza suggesting that our population
is likely to have differed from populations in other studies in
propensity to seek care. Despite these differences, the incidence
estimates for infants aged ,1 year and children aged 1 to 5 years
in our study are similar to the estimates from the US for similar
age groups [24,25], suggesting that these age groups be targeted
for influenza prevention strategies.
In our population, 46–57% of the burden of influenza-
associated hospitalizations was accounted for by A(H1N1)pdm09
influenza virus with seasonal influenza A virus accounting for 35%
of the burden in 2009–10 and 4% in 2010–11. Children and
young adults bore a disproportionate burden of A(H1N1)pdm09-
associated hospitalizations, possibly due to lack of prior exposure
to similar viruses. In a study carried out in Pune, high rates of
influenza-associated hospitalizations and deaths among persons
aged ,35 were observed during the peak of A(H1N1)pdm09
activity in August-September 2009 [26]. Influenza B virus
infection accounted for 19–39% of all influenza-associated
hospitalizations in our study, despite conceptions that influenza
B is typically associated with milder disease [27].
The seasonality of influenza virus circulation and seasonal
patterns for excess hospitalizations for pneumonia and influenza
during the winter are known for temperate countries [28]. Some
tropical and sub-tropical countries have documented significant
transmission throughout the year while others have documented a
biannual pattern [28]. Although the A(H1N1)pdm09 virus resulted
in influenza-associated hospitalizations continuously during Ju-
ly2009–April2011, we documented a clear seasonality to influen-
za-associated hospitalizations in our study with peaks during the
monsoon season each year. In year 1, Influenza A(H3N2)
Figure 1. Laboratory confirmed influenza-associated hospitalizations by month of disease onset and influenza type/sub-type,
Vadu, District Pune, India, May 2009–April 2011 (n = 665).
doi:10.1371/journal.pone.0055918.g001
Influenza Burden in a Rural Community in India
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Table 2. Adjusted annual cumulative incidence{ per 10,000 persons by age, Vadu, District Pune, India, May 2009–April 2011.
May 2009–April 2010 (Year 1)
*
Acute Medical Respiratory*** Influenza Virus Positive
% of Acute Medical and Respiratory
Hospitalizations Associated with
Influenza
Age (years)
**
Adjusted Incidence{ 95% CI
Adjusted
Incidence{ 95% CI
Adjusted
Incidence{ 95% CI % of acute medical
%of
respiratory
,1 463.2 374.3 - 567.9 361.5 281.0 - 453.1 11.3 1.3 - 37.6 2% 3%
1–4 345.5 306.2 - 387.1 244.3 211.8 - 280.6 54.3 39.7 - 73.2 16% 22%
5–14 178.7 159.6 - 199.6 128.7 112.4 - 146.5 61.8 50.6 - 74.5 35% 48%
15–29 268.4 251.6 - 286.2 174.4 160.8 - 188.9 67.1 58.8 - 76.4 25% 38%
30–44 164.4 147.7 - 182.7 100.8 87.6 - 115.2 25.2 19.0 - 33.2 15% 25%
45–59 165.0 140.2 - 192.3 110.0 89.6 - 132.4 18.3 11.1 - 29.7 11% 17%
60+ 160.3 130.6 - 193.8 102.2 78.7 - 129.7 11.6 4.4 - 22.6 7% 11%
all ages 223.6 214.4 - 233.0 149.1 141.7 - 156.9 46.8 42.6 - 51.2 21% 31%
May 2010–April 2011 (Year 2)
Acute Medical Respiratory*** Influenza Virus Positive
% of Acute Medical and Respiratory
Hospitalizations Associated with
Influenza
Age (years)
**
Adjusted Incidence{ 95% CI
Adjusted
Incidence{ 95% CI
Adjusted
Incidence{ 95% CI % of acute medical
%of
respiratory
,1 578.1 480.2 - 692.9 455.8 368.3 - 559.0 44.5 21.1 - 87.5 8% 10%
1–4 278.3 246.1 - 314.4 187.7 160.9 - 217.5 36.7 25.6 - 51.5 13% 20%
5–14 126.4 111.1 - 142.9 100.3 86.7 - 115.1 38.4 30.2 - 48.0 30% 38%
15–29 270.3 255.1 - 286.1 190.1 177.2 - 203.4 58.3 51.3 - 66.0 22% 31%
30–44 179.0 162.5 - 196.3 124.2 110.7 - 139.1 23.3 17.5 - 30.0 13% 19%
45–59 249.9 221.5 - 281.7 156.5 133.9 - 182.0 28.8 19.8 - 41.2 12% 18%
60+ 244.6 210.2 - 283.3 167.9 139.4 - 200.4 18.7 9.7 - 31.1 8% 11%
all ages 229.1 220.5 - 237.9 160.9 153.7 - 168.3 40.5 36.9 - 44.3 18% 25%
{
Incidences were adjusted for health utilization at non-study facilities using the following formula: adjusted hospitalization incidence = (unadjusted incidence)/(% of acute medical hospitalizations reported on health utilization
survey that occurred at study facilities).
*From 2009 and 2010 mid-year population estimates from Vadu HDSS.
**Adjustment factor = proportion of acute medical hospitalizations reported on HUS that occurred at study facilities: 0.46 for persons aged ,1 year, 0.50 for 1–4 years, 0.78 for 5–14 years, 0.73 for 15–29 years, 0.76 for 30–44 years,
0.68 for 45–59 years, 0.67 for .60 years.
***Defined as one or more respiratory symptoms in persons $5 years: cough, runny nose, sore throat, breathing difficulty or ear ache.
Defined as one or more respiratory symptoms in persons ,5 years: cough, runny nose, fast breathing, or ear ache.
doi:10.1371/journal.pone.0055918.t002
Influenza Burden in a Rural Community in India
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predominantly contributed to the peak and A(H1N1)pdm09 in
year 2. A previous multisite study conducted from 2004 to 2008
identified similar seasonal patterns for influenza in western India,
similarly, influenza activity has been shown to peak in the
monsoon season in other parts of India [6,7].
Our study has certain limitations. 6% patients enrolled were not
included in the study due to poor quality of samples collected and
approximately 10% patients were sampled more than seven days
after onset of illness when virus shedding may have ceased by then,
this could have led to missing some cases.
At the onset of this study to assess the burden of seasonal
influenza-associated hospitalizations, the A(H1N1)pdm09 virus
emerged. Thus, our estimates may not reflect influenza-associated
hospitalization burden during typical seasonal influenza epidem-
ics. Nevertheless, our study does document both seasonal and
A(H1N1)pdm09-associated hospitalization burden during the 2
years following emergence of the A(H1N1)pdm09 virus. The study
is ongoing and will produce estimates of influenza-associated
hospitalization for more typical seasonal influenza epidemics in the
future. Rates of hospitalization were high in comparison to other
countries, it is possible that the media publicity, increased public
awareness, and panic amongst the public following deaths due to
the H1N1pdm influenza virus in 2009 could have unusually
altered population’s propensity to seek care so also heightened
provider awareness and responsiveness to the pandemic. However,
the rate of hospitalization continued to be high even in the 2
nd
year of our study when public and provider panic had subsided.
While we could have over-estimated the influenza burden in
first year of study, we observed comparable rates of influenza
burden in second year. India is a large country with diverse
geography, demography, and climate, and our estimates of
influenza-associated hospitalization do not necessarily reflect the
impact of influenza in all regions of the country. However, the
study area is representative of a phenomenon that is increasingly
seen across India viz. fast-growing communities situated not far
from urban area.
Rates of hospitalization, especially related to influenza-associ-
ated illness, are critical to measuring public health impact of
influenza in order to enable countries to make informed evidence-
based decisions while allocating scarce resources towards preven-
tion and control. Reliable disease burden estimates will assist
health care planners in prioritizing investments in health and
research, improving access to health care and evaluating
intervention strategies.
Methods
Study area and population characteristics
A rural population in 22 villages within a geographical area of
232 sq. km in Pune District, India has been under household
demographic surveillance (HDS) since 2001. A bi-annual census
enumerates birth, migration, and death events and ascertains
cause of death through verbal autopsy. In May 2010, the study site
included a population of 116,898 persons comprising 34,181
households. A health utilization survey was conducted six-monthly
to enumerate hospitalizations and determine cause and place of
hospitalization (within/outside the study area). The proportion of
ARI-associated hospitalizations occurring outside the area was
estimated for the population under demographic surveillance and
used to adjust the incidence of influenza-associated hospitalization
for the study area.
The study area Vadu, is located 30 km north-east of Pune City
in Western India and has a health structure typical of a rural area
in close proximity of a large city. The public sector services include
a rural hospital and primary health centers located in villages. The
private sector several small general hospitals where most residents
seek health care. The study population is served by 30 hospitals (a
35-bed rural hospital at Vadu, a 5-bed primary health center, and
28 private nursing homes having 2–30 (median 10) beds each).
The enrolled hospitals are small private hospitals which provide
medical care for patients through their out-patient clinics and are
not necessarily referral hospitals wherein serious patients are
referred by health care providers. The majority of admissions to
these hospitals occur for patients who seek medical care in their
outpatient clinic and are then advised admission. Unfortunately
we did not record whether the patient came directly to the hospital
in an emergency or was admitted after an outpatient consultation.
Figure 2. Adjusted annual cumulative incidence of influenza associated hospitalization per 10,000 population, by age, Vadu,
District Pune, India, May 2009–April 2011.
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Table 3. Adjusted annual cumulative incidence
1
of influenza associated hospitalization per 10,000 population by age, influenza type and subtype, Vadu, District Pune, India, May
2009–April 2011.
Year 1: May 2009–April 2010
Seasonal A H1N1pdm09 B
Age (years) Adjustment Factor
2
Adjusted Incidence (95% CI) Adjusted Incidence (95% CI) Adjusted Incidence (95% CI)
,1 0.46 0.0 0.0 - 19.2 0.0 - 11.3 1.3 - 37.6
1–4 0.50 14.8 7.7 - 26.0 29.6 19.1 - 44.3 9.9 4.3 - 19.6
5–14 0.78 19.1 13.1 - 26.7 30.1 22.4 - 39.3 12.5 8.0 - 19.2
15–29 0.73 21.3 16.7 - 26.8 31.7 26.2 - 38.4 14.1 10.3 - 18.6
30–44 0.76 13.9 9.3 - 20.0 9.4 5.9 - 14.8 1.9 0.5 - 4.9
45–59 0.68 10.7 5.0 - 19.2 6.1 2.3 - 13.6 1.5 0.0 - 5.8
60+ 0.67 7.0 1.7 - 16.0 2.3 0.0 - 8.7 2.3 0.0 - 8.7
all ages 16.4 14.0 - 19.2 21.5 18.8 - 24.7 8.8 7.1 - 10.9
Year 2: May 2010–April 2011
,1 0.46 0.0 0.0 - 18.9 44.5 21.1 - 87.5 0.0 -
1–4 0.50 4.3 1.2 - 11.1 21.6 13.3 - 33.5 10.8 5.2 - 19.9
5–14 0.78 0.0 0.0 - 1.9 18.2 12.9 - 25.5 20.2 14.6 - 27.8
15–29 0.73 1.6 0.7 - 3.4 32.5 27.4 - 38.4 24.2 19.7 - 29.3
30–44 0.76 1.6 0.5 - 4.2 14.6 10.1 - 20.1 7.1 4.1 - 11.2
45–59 0.68 2.7 0.6 - 8.2 17.9 10.7 - 27.8 8.2 3.9 - 16.0
60+ 0.67 0.0 0.0 - 5.2 10.4 3.9 - 20.2 8.3 3.1 - 18.3
all ages 1.5 0.9 - 2.5 23.0 20.3 - 25.9 16.0 13.7 - 18.4
1
Adjusted hospitalization incidence = (unadjusted incidence)/(% of acute medical hospitalizations reported on health utilization survey that occurred at study facilities).
2
Adjustment factor = proportion of acute medical hospitalizations reported on HUS that occurred at study facilities.
doi:10.1371/journal.pone.0055918.t003
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The area is well connected with Pune, a city, 30 kilometers
away. Winters (November–March) are mild, and the monsoon
season from June through September.
Surveillance for influenza-associated hospitalization
Hospital-based surveillance was initiated in May, 2009 in 29 of
30 hospitals (One private hospital did not consent to participate).
Field-based investigators screened all overnight hospital admis-
sions daily. Using a broad case definition, all patients presenting to
a hospital with a medical illness with acute onset of respiratory
symptoms, fever or history of fever within the past week, or acute
exacerbation of a pre-existing chronic medical condition (chronic
lung disease, asthma, cardio-vascular disease) were enrolled.
Patients residing outside HDS area, and patients hospitalized for
elective/emergency surgeries, trauma, orthopedic, ophthalmolog-
ical, psychiatric or obstetric care were excluded. Data on clinical
symptoms, signs, and treatment were collected on admission, at
time of interview and at discharge including patient outcome.
Written informed consent was obtained from each study
participant (or parent/legal guardian for persons ,18 years) prior
to enrolment. The study protocol was reviewed and approved by
the Institutional Review Boards of the National Institute of
Virology (NIV), Pune, King Edward Memorial Hospital, and the
USCDC, Atlanta.
Laboratory testing
Nasal and/or throat swabs were collected and combined into a
single vial of virus transport medium [29] and transported at 2–8C
to the NI V, Pune for virologic testing. Real time RT-PCR was
used to detect influenza viruses using the CDC protocol [30].
Data analysis
Year one was May2009–April2010 and year two May2010–
Apri2011. Annual cumulative incidence of influenza-associated
hospitalizations unadjusted for healthcare utilization outside the
surveillance area was the number of laboratory-confirmed
influenza-associated hospitalizations per year divided by 2009
and 2010 population. The annual cumulative incidence adjusted
for healthcare utilization patterns was calculated by dividing the
unadjusted annual cumulative incidence by the proportion of
acute respiratory illness hospitalizations among HDS area
residents recorded at facilities under surveillance.
Unadjusted and adjusted cumulative incidences of acute-
medical illness, all-cause respiratory illness and influenza-associat-
ed hospitalization were calculated by influenza type and subtype
and by age group.
To evaluate the effect of screening definitions on the estimate of
influenza-associated hospitalization incidence, incidence was also
calculated using patients with laboratory-confirmed influenza who
met commonly used screening definitions for influenza divided by
population denominators. These included influenza-like illness
(ILI) defined as measured fever .38
0
and cough or sore throat;
severe acute respiratory illness (SARI) defined as ILI plus shortness
of breath or difficulty in breathing for patients .5 years of age OR
the WHO IMCI definition of pneumonia for those ,5 years of
age; acute respiratory illness (ARI) defined as sudden onset and $1
of the respiratory symptoms: cough, sore throat, shortness of
breath, or nasal discharge; and febrile acute respiratory illness
(FARI) defined as ARI plus measured fever .38
0
.
Acknowledgments
Disclaimer: The findings and conclusions in this report are those of the
authors and do not necessarily represent the official position of the Centers
for Disease Control and Prevention.
Thanks are due to Anthony Mounts for his constructive critique, and to
Timothy Uyeki for his valuable input on study design. The authors are
grateful to all the private and public sector hospitals and their patients for
their willingness to participate in the study. Lastly the authors thank the
field staff of Vadu DSA and the laboratory staff of the National Institute of
Virology for their contribution to the study.
Author Contributions
Conceived and designed the experiments: MSC SH JAM RBL ACM.
Analyzed the data: MSC SH FSD PL AD SS KEL RBL. Contributed
reagents/materials/analysis tools: JAM. Wrote the paper: MSC SH FSD
AD KEL RBL. Data acquisition: MSC SH AD SJ KEL. Study
coordination and monitoring of the multi-centric study: MSC ACM.
Laboratory supervision: MSC. Monitoring of field studies: SH. Critical
review of article: FSD PL AD SJ KEL JAM RBL ACM. Protocol
development: AD KEL JAM RBL. Project and Director of National
Institute of Virology: ACM.
Table 4. Effect of screening case definitions on estimates of influenza-associated hospitalization annual incidence, Vadu, District
Pune, India, May 2009–April 2011.
Screending definition
# of patients
meeting screening
definition
# (%) patients with specimens
positive for influenza virus
Adjusted influenza-associated
hospitalization annual incidence
per 10,000 persons % underestimate*
Acute medical hospitalization 3179 665 (20,9%) 44.1
ILI** 1632 454 (27.8%) 30.1 32%
ARI*** 2183 566 (25.9%) 37.5 15%
FARI{ 1659 455 (27.4%) 30.1 32%
SARI` 87 20 (23.0%) 1.3 97%
*% underestimate defined as ((1-estimated hospitalization incidence based on use of the given screening definition)/estimated hospitalization incidence based on use
of all acute medical hospitalizations as a screening definition) expressed as a percentage).
**Influenza-like illness (ILI) was defined as fever and either cough or sore throat.
***Acute respiratory illness (ARI) was defined as .1 of the following: cough, nasal discharge, sore throat, or shortness of breath (based on history).
{
Febrile acute respiratory illness (FARI) was defined as the presence of ARI plus fever.
`
For persons .5 years, severe acute respiratory illness (SARI) was defined as the presence of ILI and either shortness of breath or difficulty breathing.
For children ,5 years, SARI was defined as pneumonia or severe pneumonia as defined by the Integrated Management of Childhood Illness guidelines as any of the
following: any general danger sign (i.e. unable to drink or breastfeed, vomiting, convulsions, lethargic, or unconscious), chest indrawing, stridor, or fast breathing on
examination.
doi:10.1371/journal.pone.0055918.t004
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    [Show abstract] [Hide abstract] ABSTRACT: Though respiratory viruses are thought to cause substantial morbidity globally in children aged <5 years, the burden of severe respiratory virus infections in children is unknown in India where 20% of the world's children live. During August 2009-July 2011, prospective population-based surveillance was conducted for hospitalizations of children aged <5 years in a rural community in Haryana State. Clinical data and respiratory specimens were collected. Swabs were tested by RT-PCR for influenza and parainfluenza viruses, respiratory syncytial virus (RSV), human metapneumovirus, coronaviruses, and adenovirus. Average annual hospitalization incidence was calculated using census data and adjusted for hospitalizations reported on a community healthcare utilization survey to occur at non-study hospitals. Of 245 hospitalized children, respiratory viruses were detected among 98 (40%), of whom 92 (94%) had fever or respiratory symptoms. RSV (34.6/10,000, 95% CI 26.6-44.7) accounted for the highest virus-associated hospitalization incidences and 20% of hospitalizations. There were 11.8/10,000 influenza-associated hospitalizations (7% of hospitalizations). RSV and influenza detection peaked in winter (November-February) and rainy seasons (July), respectively. Respiratory viruses were associated with a substantial proportion of hospitalizations among young children in a rural Indian community. Public health research and prevention in India should consider targeting RSV and influenza in young children.
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