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Influenza A(H1N1)pdm09-Associated Pneumonia Deaths
in Thailand
Charatdao Bunthi
1
*, Somsak Thamthitiwat
1
, Henry C. Baggett
1
, Pasakorn Akarasewi
2
,
Ruchira Ruangchira-urai
3
, Susan A. Maloney
1
, Kumnuan Ungchusak
2
1International Emerging Infections Program, Global Disease Detection Regional Center, Thailand Ministry of Public Health- US Centers for Disease Control and Prevention
Collaboration, Nonthaburi, Thailand, 2Bureau of Epidemiology, Thailand Ministry of Public Health, Nonthaburi, Thailand, 3Department of Pathology, Siriraj Hospital,
Mahidol University, Bangkok, Thailand
Abstract
Background:
The first human infections with influenza A(H1N1)pdm09 virus were confirmed in April 2009. We describe the
clinical and epidemiological characteristics of influenza A(H1N1)pdm09-associated pneumonia deaths in Thailand from May
2009-January 2010.
Methods:
We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance
system and performed detailed reviews of a subset.
Results:
Of 198 deaths reported, 49% were male and the median age was 37 years; 146 (73%) were 20–60 years. Among 90
deaths with records available for review, 46% had no identified risk factors for severe influenza. Eighty-eight patients (98%)
received antiviral treatment, but only 16 (18%) initiated therapy within 48 hours of symptom onset.
Conclusions:
Most influenza A(H1N1)pdm09 pneumonia fatalities in Thailand occurred in adults aged 20–60 years. Nearly
half lacked high-risk conditions. Antiviral treatment recommendations may be especially important early in a pandemic
before vaccine is available. Treatment should be considered as soon as influenza is suspected.
Citation: Bunthi C, Thamthitiwat S, Baggett HC, Akarasewi P, Ruangchira-urai R, et al. (2013) Influenza A(H1N1)pdm09-Associated Pneumonia Deaths in
Thailand. PLoS ONE 8(2): e54946. doi:10.1371/journal.pone.0054946
Editor: Yi Guan, The University of Hong Kong, China
Received July 21, 2012; Accepted December 20, 2012; Published February 4, 2013
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for
any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Funding: This work was funded primarily by the Thailand Ministry Of Public Health with additional support from the U.S. Centers for Disease Control and
Prevention (CDC). 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: charatdaob@th.cdc.gov
Introduction
The 2009 influenza pandemic virus, influenza A(H1N1)pdm09
was first confirmed in the United States by the Centers for Disease
Control and Prevention (CDC) in April 2009 and rapidly spread
worldwide [1,2,3,4]. Clinical manifestations of influenza
A(H1N1)pdm09 infection ranged from mild symptoms to severe
illness and death. Most patients with severe or fatal disease were
reported to have underlying medical conditions, including chronic
lung disease, diabetes, cardiovascular disease, neurological disease,
and pregnancy [5,6,7,8].
The first two cases of laboratory-confirmed influenza
A(H1N1)pdm09 infection in Thailand were reported on May
10, 2009, in exchange students who returned from Mexico.
Although the epidemiology of influenza A(H1N1)pdm09 deaths
has been well-described in the United States, Mexico, and Europe
[1,9,10], less is known about fatal cases in Thailand or other
countries in Asia [11,12,13].
We present epidemiological and clinical data on influenza
A(H1N1)pdm09-associated deaths among persons hospitalized
with pneumonia in Thailand, collected through retrospective
review of medical records.
Ethical Considerations
The medical records reviews were considered by the MOPH to
be part of the public health response to the 2009 influenza
pandemic in Thailand and therefore did not require review by the
human subjects Ethical Review Committee.
Methods
In 2004, Thailand’s Ministry of Public Health (MOPH)
established the National Avian Influenza Surveillance (NAIS)
system in response to human cases of avian influenza A(H5N1).
Under NAIS, hospitals were required to report all cases of severe
and fatal human influenza infection to the Bureau of Epidemiol-
ogy (BOE) [14]. In May 2009, at the start of the influenza
A(H1N1)pdm09 outbreak in Thailand, the MOPH encouraged
reporting of all suspected influenza A(H1N1)pdm09 cases through
the NAIS system along with submission of respiratory specimens
(nasopharyngeal swabs, throat swabs, or endotracheal tube
aspirates) to be tested at Thailand’s National Institute of Health
(NIH) for influenza viruses by real-time reverse transcription
polymerase chain reaction (rRT-PCR). Reports to NAIS were
submitted by hospital epidemiologists (or clinicians) electronically
through a web-based system or using paper forms and included
PLOS ONE | www.plosone.org 1 February 2013 | Volume 8 | Issue 2 | e54946
information on patient demographics, underlying medical condi-
tions, clinical characteristics, and outcome.
In addition, MOPH established a parallel surveillance system in
early 2009 to support the investigation of severe and fatal
pneumonia cases. Due to the natural overlap with NAIS, cases
from this severe and fatal pneumonia surveillance system were
reported through NAIS, but additional data and specimens were
requested. Under the severe and fatal pneumonia surveillance
system, clinicians were encouraged to submit respiratory speci-
mens and blood (serum or whole blood) for testing from patients
with community-acquired pneumonia that required intubation
and did not respond to treatment within 48 hours or resulted in
death. Clinicians were also encouraged to collect post-mortem
tissue specimens from fatal cases through consented autopsy or
necropsy. Respiratory, blood, and fresh frozen tissue specimens in
sterile containers were kept and shipped to the NIH for virology
and bacteriology testing within 48 hours. Formalin-fixed tissue
specimens were sent to the Department of Pathology at Siriraj
Hospital in Bangkok, where they were embedded in paraffin, cut
into 3 mm-thick sections, deparaffinized in xylene, and rehydrated
in graded alcohol. Each section was stained with hematoxylin and
eosin. During the influenza A(H1N1)pdm09 pandemic, under the
auspices of this surveillance system, MOPH also requested that
hospitals make medical records of fatal influenza A(H1N1)pdm09-
associated pneumonia cases available for review by public health
officials.
For this investigation, efforts were made to acquire medical
records from hospitals for all cases of influenza A(H1N1)pdm09-
associated pneumonia deaths that occurred during the first wave
and the beginning of second wave of the pandemic in Thailand
(May 2009 through January 2010), but records for only 90 cases
were available. Data on demographics, medical history, clinical
course, laboratory testing, and treatment were abstracted by
trained clinicians, nurses, and epidemiologists using a standardized
form. All chest radiographs (CXR) for which hospital radiology
reports were not available were reviewed by a radiologist from the
MOPH Chest Disease Institute.
Data Analysis
We first present descriptive statistics for all fatal cases of
influenza A(H1N1)pdm09-associated pneumonia reported to
Thailand’s NAIS system from May 2009 through January 2010,
defined as any death in a patient hospitalized with clinician-
diagnosed pneumonia and at least one respiratory specimen
positive for influenza A(H1N1)pdm09 by rRT-PCR. More
detailed descriptions of clinical characteristics, treatment, and
outcomes are presented for the subset of cases for which medical
record reviews were performed.
Descriptive data are presented as frequencies for discrete
variables and as means or medians for continuous variables. SPSS
version 17.0 (SPSS Inc, Chicago, Illinois) was used for all analyses.
Underlying medical conditions considered high-risk for severe
influenza infection were based on the World Health Organiza-
tion’s document, ‘‘Clinical Management of Human Infection with
Pandemic (H1N1) 2009 Virus’’: chronic pulmonary disease
(including asthma and chronic obstructive pulmonary disease
(COPD)), cardiovascular disease (except hypertension alone),
metabolic disorders (including diabetes mellitus), chronic renal
disease, certain neurological conditions, immunosuppression (e.g.,
HIV, cancer), pregnancy and obesity. Body mass index (BMI) was
calculated as weight in kilograms divided by a square of height in
meters (kg/m2) when measurements were available in the medical
records; obese and morbidly obese were defined as a BMI of 30–
39 kg/m
2
and a BMI of $40 kg/m
2
, respectively [15].
Results
From May 2009 through January 2010, 27,254 cases and 198
fatal cases of laboratory-confirmed influenza A(H1N1)pdm09-
associated pneumonia were reported to the MOPH-NAIS system
(0.7% case fatality proportion) (Figure 1). The median age for all
reported cases was 37 years (range, 0 to 91) and 49% were male
(Table 1, Figure 2). Data on underlying medical conditions were
available for 130 (66%) patients, and 68% were reported to have
at least one known high-risk condition for severe influenza
infection. Although obesity was noted as a co-morbid condition
in 22 (17%) cases, weight and height data to confirm the diagnosis
were available for only 14 cases, 9 (64%) of whom had BMI
$30 kg/m
2
.
Medical records were available for review for 90 (45%) of 198
reported influenza A(H1N1)pdm09-associated pneumonia deaths.
The median age of these 90 patients was 38.5 years (range, 0–91)
and 56% were male (Table 1, Figure 2). Of the 90 fatal cases with
records reviewed, 49 (54%) patients had evidence of at least one
known high-risk condition for severe influenza, most commonly
diabetes mellitus (18%); 42 (47%) patients had no identified risk
factors. Of the 13 non-pregnant patients with height and weight
available for BMI calculation, three (23%) were obese (BMI of 30–
39 kg/m
2
) and 4 (31%) were morbidly obese (BMI $40 kg/m
2
).
Among the 90 fatal cases with medical record reviews
completed, none had received the monovalent influenza pandemic
strain vaccine but one (1%) had received seasonal influenza
vaccine. Five cases (6%) occurred among pregnant women and all
five were treated with oseltamivir. Three were in the second
trimester of pregnancy, and all three experienced fetal demise.
Two patients were in the third trimester and both delivered their
babies by caesarian section. One of the two neonates, delivered
after 31 weeks gestation weighing 1,560 grams, was diagnosed with
laboratory-confirmed influenza A(H1N1)pdm09 infection on the
first day of life. This baby was treated with oseltamivir, recovered
and was discharged at 28 days of age [13]. The other baby, who
was delivered at 28 weeks gestation weighing 1,230 grams,
developed respiratory distress syndrome (rRT-PCR of respiratory
specimen was negative for influenza A(H1N1)pdm09), and died
after 12 days.
Sixty-one patients (68%) had sought medical care at least once
as an initial visit at local health care facilities (local health center,
private clinic, private or public hospital) before being hospitalized.
This includes 57 patients who were hospitalized at another facility
before the hospitalization during which death occurred, hereafter
referred to as the final hospitalization.
At the final hospitalization, 17% had influenza-like illness
(documented fever $38uC with cough or sore-throat). Forty-six
percent of patients did not have documented fever at admission.
Based on patient histories, 73% had report of fever with cough or
sore throat. Of 88 patients with documentation of a CXR, 62
(69%) had either CXR reports or films available for radiologist
review. All 62 patients had abnormal CXR; 53 (85%) patients
showed diffuse pulmonary infiltration and 9 (15%) patients had
localized pulmonary infiltration. Seventy-seven (86%) patients
were managed in an intensive care unit, 89 (99%) received
mechanical ventilation, and 54 (60%) were diagnosed with acute
respiratory distress syndrome. Antibiotic therapy was prescribed to
all patients except one during the first five days of the final
hospitalization, and 37 (42%) patients received steroids. Eight (9%)
patients had chronic renal failure requiring dialysis (Table 2).
Antiviral treatment was administered to 88 (98%) patients, all of
whom received oseltamivir. Zanamivir was used in combination
with oseltamivir for nine patients. Oseltamivir was initiated during
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 2 February 2013 | Volume 8 | Issue 2 | e54946
Figure 1. Laboratory-confirmed influenza A (H1N1)pdm09 cases and deaths. Detailed legend: Laboratory-confirmed influenza A
(H1N1)pdm09 cases and deaths reported to Bureau of Epidemiology, Ministry of Public Health Thailand from May 2009-March 2010. Bars represent
number of deaths. Line represents number of cases.
doi:10.1371/journal.pone.0054946.g001
Table 1. Demographic characteristics and underlying medical conditions of influenza A (H1N1)pdm09 virus-associated pneumonia
fatalities in Thailand, May 2009-January 2010.
Characteristic
No. (%)
Total cases = 198
No. (%)
Medical records reviewed= 90
Male 97 (49) 50 (56)
Age group (years)
Age ,5 11 (6) 4 (4)
5–9 7 (4) 4 (4)
10–19 12 (6) 0 (0)
20–39 80 (40) 38 (42)
40–60 66 (33) 32 (36)
.60 22 (11) 12 (13)
High risk condition for severe influenza* N = 130 N = 90
Diabetes Mellitus 25 (19) 16 (18)
Cardiovascular diseases 13 (10) 10 (11)
Kidney disease{11 (8) 8 (9)
Pregnancy 11 (8) 5 (6)
Obesity{9/14 (64) 6/13 (46)
Asthma 8 (6) 5 (6)
Chronic lung disease110 (8) 5 (6)
Cancer 6 (5) 5 (6)
HIV 2 (2) 2 (2)
Neuromuscular diseases 9 (7) 1 (1)
Thalassemia 2 (2) 1 (1)
At least one of the above conditions 89 (68) 49 (54)
Not report for the above conditions 41 (32) 41 (46)
*According to WHO on Clinical Management of Human Infection with influenza A(H1N1)pdm09 [15].
{
Kidney disease includes chronic renal failure, polycystic kidney disease.
{
Obesity defined as body mass index (BMI) $30 kg/m
2
. BMI calculated as weight in kilograms divided by height in meters squared among non-pregnant patients; 14
patients overall and 13 patients with medical records reviewed had height and weight available BMI calculation.
1
Chronic lung disease includes obstructive pulmonary disease, chronic bronchitis, and pulmonary tuberculosis.
doi:10.1371/journal.pone.0054946.t001
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 3 February 2013 | Volume 8 | Issue 2 | e54946
the final hospitalization for 87 patients, while only one patient had
received treatment at a previous medical facility (3 days before the
final hospitalization). The median time from symptom onset to the
first dose of oseltamivir was 4.5 days (range, 0 to 20 days). The
median time from symptom onset to death was 9 days (range, 1 to
46 days). The median time from admission to death and from first
dose of oseltamivir to death was 4.5 days and 4 days (range, 0 to 32
days for both), respectively (Table 3). The timing between each
step in the clinical course between symptom onset, hospitalization,
oseltamivir administration, and death was similar for patients aged
,18 years and those $18 years, except the time from symptom
onset to the first dose of oseltamivir was significantly shorter
among patients aged 18 years and older (p = 0.01).
Nine patients (10%) had blood culture results available; all
blood cultures were done on the first day of the final
hospitalization. Three (33%) were positive for possible pathogens:
Acinetobacter baumannii (1), Salmonella group D and Pseudomonas spp.
(1), and Staphylococcus aureus (1). All three patients with positive
cultures had been previously admitted to another hospital and
were transferred within 24 hours of the original admission.
Pulmonary tissue was submitted for 12 patients, but only five
specimens were adequate for histopathological examination.
Diffuse alveolar damage was found in two patients; the other
three were found to have focal lymphocytic interstitial infiltrates,
pulmonary congestion and pulmonary edema, respectively. Six of
the 12 patients with pulmonary tissue collected had fresh frozen
specimens submitted for bacterial PCR testing at the Thailand
NIH using in-house assays, all of which were negative for
Chlamydophila pneumoniae,Mycoplasma pneumoniae,Legionella species,
Streptococcus pneumoniae,Haemophilus influenzae,Moraxella catarrhalis,
Burkholderia pseudomallei,Escherichia coli,Klebsiella pneumoniae,Pseudo-
monas aeruginosa,Stenotrophomonas maltophilia and Acinetobacter species.
Discussion
We found that the majority of influenza A(H1N1)pdm09-
associated pneumonia deaths in Thailand occurred in adults aged
20 to 60 years, which is similar to previous studies [16,17], but
differed from the older age predominance of seasonal influenza
deaths [18,19]. Only 53% of fatal cases with medical records
reviewed had evidence of high-risk conditions for severe influenza
infection, although the proportion was higher (67%) among all 198
fatal cases reported to NAIS. Regardless, the proportion of fatal
cases with no reported high-risk condition was substantial and was
on the lower end of what has been reported in other countries.
Figure 2. Age distribution of influenza A (H1N1)pdm09 deaths. Detailed legend: Age distribution of influenza A (H1N1)pdm09 deaths
reported to the National Avian Influenza Surveillance (NAIS) system, Bureau of Epidemiology, Ministry of Public Health, Thailand and those for whom
medical charts were available for review - May 2009-January 2010. Bars represent number of deaths for each age group (Figures are in a separate file).
doi:10.1371/journal.pone.0054946.g002
Table 2. Hospital course of 90 influenza A (H1N1)pdm09
virus-associated pneumonia deaths in Thailand for whom
medical record reviews were conducted, May 2009-January
2010.
Hospital Course No. (%)
Admission to intensive care unit 77 (86)
Mechanical ventilation 89 (99)
Positive blood culture* 3 (3)
Shock requiring vasopressor therapy 80 (89)
Acute Respiratory Distress Syndrome 54 (60)
Renal failure with dialysis 8 (9)
Antiviral treatment 88 (98)
Oseltamivir 88 (98)
Zanamivir 9 (10)
Antibiotic treatment within first 5 days of admission 89 (99)
Received steroid treatment during hospitalization 37 (42)
Leukopenia (WBC ,5,000) 28 (31)
Leukocytosis (WBC .15,000) 21 (23)
Hemoglobin ,10 12 (13)
Platelet count ,100,000{11 (12)
Serum creatinine .1.5125 (29)
AST .2xUNL (70)"29 (57)
ALT .2xUNL (80)"17 (33)
*Blood culture positive for Acinetobacter baumannii (1), Salmonella group D and
pseudomonas spp. (1) and Staphylococcus aureus (1).
**Records available for 89 of 90 patients.
***Records available for 85 of 90 patients.
****Records available for 51 of 90 patients, AST (aspatate aminotransferase),
ALT (alanine transaminase); UNL (upper normal limit).
doi:10.1371/journal.pone.0054946.t002
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 4 February 2013 | Volume 8 | Issue 2 | e54946
The prevalence of high-risk conditions among fatal influenza
A(H1N1)pdm09 cases in the U.S. ranged from 68% [20] to 73%
[5] and in Brazil was 55% (excluding obesity) [21]. Similar to
previous studies [5,22,23,24,25,26,27,28,29,30], diabetes mellitus,
cardiovascular disease and chronic lung disease were common
underlying medical conditions among influenza A(H1N1)pdm09
virus-associated deaths in Thailand.
Oseltamivir was administered to nearly all patients in our
report, which was likely facilitated by domestic production in
Thailand and by efforts to preposition antiviral medication in
hospitals around the country. The antiviral treatment stockpile in
Thailand was sufficient to treat 0.5% of the population at the
beginning of the pandemic, with one million treatment courses
added during the first wave of the pandemic [31]. However,
treatment was initiated within 48 hours of symptom onset in only
16 (18%) patients. Further, antiviral treatment was almost never
prescribed to patients on their initial visit to a health care facility.
Studies have shown that early oseltamivir treatment (,48 hours
after symptom onset) is associated with decreased risk of ICU
admission and death [5,14,32]. The median duration from illness
onset to initiation of antiviral therapy was 4.5 days, well beyond
the 48 hour time period recommended by WHO and the U.S.
CDC [15,33]. Our finding of delayed antiviral initiation among
fatal influenza A(H1N1)pdm09 cases was similar to findings
reported from the U.S., Mexico and China [5,8,25] and may have
been related to insufficient information disseminated to clinicians
early in the outbreak, resulting in lack of clinical recognition of
influenza, lack of familiarity with recommendations for empiric
antiviral therapy [15], or concern over the potential development
of drug resistance. Anecdotal reports also indicated that clinicians
may have been reluctant to prescribe antiviral drugs without
laboratory confirmation of influenza virus infection; laboratory
testing for influenza viruses is not frequently available in the
outpatient setting in Thailand.
Our report is subject to several limitations. Although 198
hospitalized influenza A(H1N1)pdm09-associated pneumonia fa-
talities were identified, medical records were only available for
review for 90 (45%). Additionally, some influenza A(H1N1)pdm09
deaths likely occurred outside of the hospital [34]. Therefore, our
findings may not be representative of all hospitalized influenza
A(H1N1)pdm09 pneumonia deaths or of fatal influenza
A(H1N1)pdm09 cases in Thailand overall. However, the age
and sex distribution, as well as the prevalence of most high-risk
conditions, for the 90 cases in our series was similar to that of all
198 fatal influenza A(H1N1)pdm09 pneumonia cases reported to
the NAIS system. Data were extracted solely from chart review,
limiting results to recorded data and prohibiting verification by
interview with relatives or clinicians. As a result, we may have
underestimated the number of patients with underlying medical
conditions, despite efforts made to review both inpatient and
outpatient records from all health facilities where the patient
received treatment. Height and weight were available for very few
patients, preventing a robust assessment of obesity prevalence,
a putative risk factor for severe influenza infection [6,15,21,25].
Finally, we lacked a comparison group of hospitalized non-fatal
influenza A(H1N1)pdm09 pneumonia cases so were unable to
determine the proportion of hospitalized patients who died or
assess risk factors for death. Although we were not able to assess
risk factors, other studies conducted during the pandemic
confirmed that many of the WHO-defined risk factors [15] did
increase the risk of severe disease and death among persons
infected with influenza A(H1N1)pdm09 [6,20,24,35].
Despite these limitations, our findings that the majority (78%) of
influenza A(H1N1)pdm09 virus-associated fatalities were in adults
aged 20–60 years and that one-third to one-half had no known
Table 3. Timing of antiviral therapy relative to clinical course of 90 influenza A (H1N1)pdm09 virus-associated pneumonia fatalities
in Thailand for whom medical record reviews were conducted, May 2009-January 2010.
Clinical course Median time in Days (Range) p-Value*
Symptom onset to hospital admission 4.0 (0–14)
Age ,18 years (n= 8) 5.0 (2–14) 0.31
Age $18 years (n= 82) 4.0 (0–14)
Symptom onset to 1st Oseltamivir dose 4.5 (0–20)
Age ,18 years (n= 7) 8.0 (3–14) 0.01
Age $18 years (n= 81) 4.0 (0–20)
Hospital admission to 1st Oseltamivir dose 0.0 (23–10)
Age ,18 years (n= 7) 1.0 (0–9) 0.09
Age $18 years (n= 81) 0.0 (23–10)
Symptom onset to death 9.0 (1–46)
Age ,18 years (n= 8) 13.5 (4–46) 0.43
Age $18 years (n= 82) 9.0 (1–25)
Hospital admission to death 4.5 (0–32)
Age ,18 years (n= 8) 6.5 (1–32) 0.31
Age $18 years (n= 82) 4.5 (0–18)
First Oseltamivir dose to death 4.0 (0–32)
Age ,18 years (n= 7) 1.0 (0–32) 0.94
Age $18 years (n= 81) 4.0 (0–18)
*Mann-Whitney U test comparing age ,18 to $18 years.
doi:10.1371/journal.pone.0054946.t003
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 5 February 2013 | Volume 8 | Issue 2 | e54946
high-risk medical conditions may have implications for public
health practice in Thailand. Consistent with early guidance from
the World Health Organization’s Strategic Advisory Group of
Experts in July 2009, pandemic vaccine recommendations in
Thailand initially included healthcare workers, pregnant women
and persons with high-risk medical conditions and were soon
expanded to include children aged 6 months to 2 years [36].
Although Thailand did not recommend vaccination for healthy
adults [37], the high proportion of deaths observed in this group
suggests that a wider vaccination strategy may have been
beneficial if resources had allowed. However, the monovalent
pandemic vaccine was not widely available in Thailand until
January 2010, after our review was completed. During the
pandemic, Thailand also had targeted recommendations in place
for seasonal influenza vaccine, which has been suggested in at least
one report to have provided some protection against influenza
A(H1N1)pdm09 [38], but uptake was generally low [39]. In
countries without early access to pandemic vaccines, antiviral
treatment recommendations may ultimately be more important.
Antiviral treatment should be considered as soon as influenza is
suspected, especially in patients with high-risk condition [33]. To
improve clinical outcomes, interventions to facilitate earlier
antiviral administration should be pursued. Further evaluation of
the entire spectrum of influenza A(H1N1)pdm09 virus-associated
illness would allow better estimation of the burden of the 2009
pandemic in Thailand and may help identify risk factors for severe
illness and guide prevention and control efforts during seasonal
epidemics and for future pandemics.
Acknowledgments
We thank Michael Jhung and Sonja Olsen from the Influenza Division,
U.S. CDC, for reviewing the manuscript; Mongkol Aueprasertkul from
Department of pathology, Siriraj Hospital, Mahidol University for data
from pathological examination; Puangtong Tungpruchayakul and Prasong
Srisaengchai from the Thailand MOPH- U.S. CDC Collaboration for
assistance with data entry and analysis; Nantaya Roenklin, Suthanun
Sutthachana from BOE; Sununta Henchaishon from IEIP; all personnel
from 51 Provincial Health Offices; all personnel from12 Offices of Disease
Prevention and Control for assistance with data collection; Ponglada
Subhanachart from Chest Disease Institute for consultation on chest x-ray
findings. Funding was provided by the Centers for Disease Control and
Prevention and the Thailand Ministry of Public Health.
Author Contributions
Reviewed and edited the manuscript: ST HB PA SM KU. Conceived and
designed the experiments: CB ST RR HB PA SM KU. Performed the
experiments: CB ST. Analyzed the data: CB. Wrote the paper: CB RR.
References
1. (2009) Swine influenza A (H1N1) infection in two children–Southern California,
March-April 2009. MMWR Morb Mortal Wkly Rep 58: 400–402.
2. (2009) Update: swine influenza A (H1N1) infections–California and Texas, April
2009. MMWR Morb Mortal Wkly Rep 58: 435–437.
3. (2009) Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico,
March-April 2009. MMWR Morb Mortal Wkly Rep 58: 467–470.
4. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, et al. (2009) Emergence
of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360:
2605–2615.
5. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, et al. (2009)
Hospitalized patients with 2009 H1N1 influenza in the United States, April-June
2009. N Engl J Med 361: 1935–1944.
6. Santa-Olalla Peralta P, Cortes-G arcia M, Vicente-Herr ero M, Castrillo-
Villamandos C, Arias-Bohigas P, et al. (2010) Risk factors for disease severity
among hospitalised patients with 2009 pandemic influenza A (H1N1) in Spain,
April - December 2009. Euro Surveill 15.
7. Pebody RG, McLean E, Zhao H, Cleary P, Bracebridge S, et al. (2010)
Pandemic Influenza A (H1N1) 2009 and mortality in the United Kingdom: risk
factors for death, April 2009 to March 2010. Euro Surveill 15.
8. Dominguez-Cherit G, Lapinsky SE, Macias AE, Pinto R, Espinosa-Perez L, et
al. (2009) Critically Ill patients with 2009 influenza A(H1N1) in Mexico. JAMA
302: 1880–1887.
9. (2009) Hospitalized patients with novel influenza A (H1N1) virus infection -
California, April-May, 2009. MMWR Morb Mortal Wkly Rep 58: 536–541.
10. Bassetti M, Parisini A, Calzi A, Pallavicini FM, Cassola G, et al. (2010) Risk
factors for severe complications of the novel influenza A (H1N1): analysis of
patients hospitalized in Italy. Clin Microbiol Infect.
11. Champunot R, Tanjatham S, Kerdsin A, Puangpatra P, Wangsai S, et al. (2010)
Impact of pandemic influenza (H1N1) virus-associated community-acquired
pneumonia among adults in a tertiary hospital in Thailand. Jpn J Infect Dis 63:
251–256.
12. de Silva UC, Warachit J, Waicharoen S, Chittaganpitch M (2009) A preliminary
analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand
from early outbreak data, June-July 2009. Euro Surveill 14.
13. Dulyachai W, Makkoch J, Rianthavorn P, Changpinyo M, Prayangprecha S, et
al. (2010) Perinatal pandemic (H1N1) 2009 infection, Thailand. Emerg Infect
Dis 16: 343–344.
14. Hanshaoworakul W, Simmerman JM, Narueponjirakul U, Sanasuttipun W,
Shinde V, et al. (2009) Severe human influenza infections in Thailand:
oseltamivir treatment and risk factors for fatal outcome. PLoS One 4: e6051.
15. WHO (2009) Clinical management of human infection with pandemic (H1N1)
2009, revised guidance. Available: http://www.who.int/csr/resources/
publications/swineflu/clinical_management_h1n1.pdf. Accessed 2011 Jan 10.
16. Vaillant L, La Ruche G, Tarantola A, Barboza P (2009) Epidemiology of fatal
cases associated with pandemic H1N1 influenza 2009. Euro Surveill 14.
17. Reichert T, Chowell G, Nishiura H, Christensen RA, McCullers JA (2010) Does
Glycosylation as a modifier of Original Antigenic Sin explain the case age
distribution and unusual toxicity in pandemic novel H1N1 influenza? BMC
Infect Dis 10: 5.
18. Simmerman JM, Chittaganpitch M, Levy J, Chantra S, Maloney S, et al. (2009)
Incidence, seasonality and mortality associated with influenza pneumonia in
Thailand: 2005–2008. PLoS One 4: e7776.
19. Lee CH, Avery C, Asherin Ryan, Rainbow, etal. (2011) Pandemic (H1N1) 2009-
associated Deaths Detected by Unexplained Deaths and Medical Examiner
Surveillance. Emerg Infect Dis 17: 1479–1483.
20. Louie JK, Acosta M, Winter K, Jean C, Gavali S, et al. (2009) Factors associated
with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection
in California. JAMA 302: 1896–1902.
21. Yokota RT, Skalinski LM, Igansi CN, de Souza LR, Iser BP, et al. (2011) Risk
factors for death from pandemic (H1N1) 2009, southern Brazil. Emerg Infect Dis
17: 1467–1471.
22. Tutuncu EE, Ozturk B, Gurbuz Y, Haykir A, Sencan I, et al. (2010) Clinical
characteristics of 74 pandemic H1N1 influenza patients from Turkey. Risk
factors for fatality. Saudi Med J 31: 993–998.
23. Santa-Olalla Peralta P, Cortes Garcia M, Limia Sanchez A, Andres Prado J,
Pachon Del Amo I, et al. (2010) [Critically ill patients with 2009 pandemic
influenza A (H1N1) infection in Spain: Factors associated with death, April
2009-January 2010.]. Rev Esp Salud Publica 84: 547–567.
24. Fowlkes AL, Arguin P, Biggerstaff MS, Gindler J, Blau D, et al. (2011)
Epidemiology of 2009 pandemic influenza A (H1N1) deaths in the United
States, April-July 2009. Clin Infect Dis 52 Suppl 1: S60–68.
25. Cui W, Zhao H, Lu X, Wen Y, Zhou Y, et al. (2010) Factors associated with
death in hospitalized pneumonia patients with 2009 H1N1 influenza in
Shenyang, China. BMC Infect Dis 10: 145.
26. Mayoral Cortes JM, Ruiz Fernandez J, Pachon Diaz J, Navarro Mari JM, Puell
Gomez L, et al. (2010) [Infection by the pandemic virus (H1N1) 2009 in
Andalusia.]. Rev Esp Salud Publica 84: 517–528.
27. Restrepo MI, Mazo M, Anzueto A (2010) [Influenza A (H1N1). Experience in
the United States]. Arch Bronconeumol 46 Suppl 2: 13–18.
28. Nguyen-Van-Tam JS, Openshaw PJ, Hashim A, Gadd EM, Lim WS, et al.
(2010) Risk factors for hospitalisation and poor outcome with pandemic A/
H1N1 influenza: United Kingdom first wave (May-September 2009). Thorax
65: 645–651.
29. Muhammad Ismail HI, Tan KK, Lee YL, Pau WS, Razali KA, et al. (2011)
Characteristics of children hospitalized for pandemic (H1N1) 2009, Malaysia.
Emerg Infect Dis 17: 708–710.
30. Cox CM, Blanton L, Dhara R, Brammer L, Finelli L (2011) 2009 Pandemic
influenza A (H1N1) deaths among children–United States, 2009–2010. Clin
Infect Dis 52 Suppl 1: S69–74.
31. Ungchusak K, Sawanpanyalert P, Hanchoworakul W, Sawanpanyalert N,
Maloney SA, et al. (2012) Lessons learned from influenza A(H1N1)pdm09
pandemic response in Thailand. Emerg Infect Dis 18: 1058–1064.
32. Yokoyama T, Tsushima K, Ushiki A, Kobayashi N, Urushihata K, et al. (2010)
Acute lung injury with alveolar hemorrhage due to a novel swine-origin
influenza A (H1N1) virus. Intern Med 49: 427–430.
33. Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, et al. (2011) Antiviral agents
for the treatment and chemoprophylaxis of influenza – recommendations of the
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 6 February 2013 | Volume 8 | Issue 2 | e54946
Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep
60: 1–24.
34. Lees CH, Avery C, Asherin R, Rainbow J, Danila R, et al. (2011) Pandemic
(H1N1) 2009-associated deaths detected by unexplained death and medical
examiner surveillance. Emerg Infect Dis 17: 1479–1483.
35. Bassetti M, Parisini A, Calzi A, Pallavicini FM, Cassola G, et al. (2011) Risk
factors for severe complications of the novel influenza A (H1N1): analysis of
patients hospitalized in Italy. Clin Microbiol Infect 17: 247–250.
36. WHO (2009) WHO recommendations on pandemic (H1N1) 2009 vaccines.
Available: http://www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_
20090713/en/index.html. Accessed 2012 October 15.
37. Iamsirithaworn S, Akarasewi P, Yingyong T, Suthachana S, Pittayawonganon
C, et al. (2011) Three Waves of the 2009 H1N1 Influenza Pandemic in
Thailand. Siriraj Med J 63: 64–67.
38. Garcia-Garcia L, Valdespino-Gomez JL, Lazcano-Ponce E, Jimenez-Corona A,
Higuera-Iglesias A, et al. (2009) Partial protection of seasonal trivalent
inactivated vaccine against novel pandemic influenza A/H1N1 2009: case-
control study in Mexico City. BMJ 339: b3928.
39. Palache A (2011) Seasonal influenza vaccine provision in 157 countries (2004–
2009) and the potential influence of national public health policies. Vaccine 29:
9459–9466.
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
PLOS ONE | www.plosone.org 7 February 2013 | Volume 8 | Issue 2 | e54946