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Influenza A(H1N1)pdm09-Associated Pneumonia Deaths in Thailand


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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. We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance system and performed detailed reviews of a subset. 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. 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.
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Influenza A(H1N1)pdm09-Associated Pneumonia Deaths
in Thailand
Charatdao Bunthi
*, Somsak Thamthitiwat
, Henry C. Baggett
, Pasakorn Akarasewi
Ruchira Ruangchira-urai
, Susan A. Maloney
, Kumnuan Ungchusak
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
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.
We identified influenza A(H1N1)pdm09-associated pneumonia deaths from a national influenza surveillance
system and performed detailed reviews of a subset.
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.
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:
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.
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 | 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
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
and a BMI of $40 kg/m
, respectively [15].
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
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
) and 4 (31%) were morbidly obese (BMI $40 kg/m
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
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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.
Table 1. Demographic characteristics and underlying medical conditions of influenza A (H1N1)pdm09 virus-associated pneumonia
fatalities in Thailand, May 2009-January 2010.
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
. 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.
Chronic lung disease includes obstructive pulmonary disease, chronic bronchitis, and pulmonary tuberculosis.
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
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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.
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).
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
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).
A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
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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.
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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.
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.
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A(H1N1)pdm09-Associated Pneumonia Deaths, Thailand
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... Influenza caused by virus (A and B) can cause varying severity from asymptomatic to complicated illness or death. 1,2 After WHO declared that Influenza A/pdm 09 (H1N1) is post pandemics(2010), the level of concern has decreased but it is not clear if post pandemic influenza differ substantially with pandemic influenza in terms of clinical manifestation and outcomes. 3,4 There have been several studies which explain that the morbidity and mortality caused after influenza pandemics on later years are high every year in other parts of world but not a single study has been carried out in our country Nepal. ...
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Background: It is important to monitor the cases affected by Influenza A/pdm09 as it is difficult to predict the behavior of Influenza A/pdm09 virus as a seasonal influenza. This study aimed to measure the clinical outcomes of patients with Influenza A/pdm 09 in a tertiary care hospital of Nepal in post pandemic period. Methods: A retrospective study was conducted in a tertiary care hospital of central Nepal to record the confirmed cases of Influenza A/pdm 09 from April 2018 to March 2019.The medical records of those patients whose throat sample had been sent to laboratory for testing Influenza A/pdm 09 were referred. The outcomes were then abstracted from the hospital system/medical record department. Results: Among 141 influenza suspected cases, 35.5%(N=50) were Influenza A/Pdm 09 positive. Both male and female were equal in distribution (N=25). Most positive cases were from the age group of 15-64 yrs. Out of total,72 %( N=36) with Influenza A/pdm 09 were discharged after treatment whereas case fatality rate was 22 %( N=11). Twenty-one positive cases were admitted in intensive care unit in which 52.4% expired. The average length of stay in I.C.U and mechanical ventilation were 6.4 days and 5.8 days respectively. Conclusions: This study in post pandemic period in Nepal shows the outcomes of patients with confirmed influenza A/pdm 09 in a year time period with comparably high case fatality rate.
... The serial interval also varies by influenza type. In the Thailand household study, influenza B (mean SI 3.8 days) [35], Freitas et al. [25], Echevarria-Zuno et al. [20], Charu et al. [26], Homaria et al. [36], Cerbino Neto et al. [37], Fowlkes et al. [38], Wu et al. [27], Perez-Flores et al. [39], Comas-Garcia et al. [24], Fajardo-Dolci et al. [40], Saborio et al. [19], Yang et al. [33], Bunthi et al. [41]) had a longer SI than both seasonal influenza A(H1N1) (mean SI 3.1 days) and pandemic influenza A(H1N1)pdm09 (mean SI 3.1 days). A similar study in Hong Kong found that the SI for A(H1N1)pdm09 (SI 3.2 days; s.d. ...
Each year, influenza causes substantial mortality and morbidity worldwide. It is important to understand influenza in the tropics because of the significant burden in the region and its relevance to global influenza circulation. In this review, influenza burden, transmission dynamics, and their determinants in the tropics are discussed. Environmental, cultural , and social conditions in the tropics are very diverse and often differ from those of temperate regions. Theories that account for and predict influenza dynamics in temperate regions do not fully explain influenza epidemic patterns observed in the tropics. Routine surveillance and household studies have been useful in understanding influenza dynamics in the tropics, but these studies have been limited to only some regions; there is still a lack of information regarding influenza burden and transmission dynamics in many tropical countries. Further studies in the tropics will provide useful insight on many questions that remain.
In Thailand, during the A(H1N1)pdm2009 pandemic, 82% of fatal cases did not received the specific treatment within 48 hours of the onset of symptoms. Specific diagnostic tests, especially RT-PCR, were not available throughout the country. To assist early clinical diagnosis and treatment, this study compared the clinical features and treatment outcomes of children presenting with influenza-like illness (ILIs). These included confirmed cases of A(H1N1)pdm2009, as well as seasonal influenza and cases for which no cause could be specified. The medical records of patients aged less than 15 years with ILIs, who had RT-PCR performed for influenza virus between May 2009 and December 2011 at Srinagarind Hospital, were reviewed. Clinical features, chest radiographs and treatment outcomes were compared between those positive for A(H1N1)pdm2009, and those with seasonal influenza and/or the unspecified causes group. In 179 complete medical records, 27.4% were positive for A(H1N1)pdm2009, 13.4% for seasonal influenza and the cause of illness in the remainder was unspecified. Both A(H1N1)pdm2009 and seasonal influenza viruses infected older children more than did the unspecified group (group median ages 96, 48 and 24 months, respectively). Sore throat, heada­che and myalgia were significantly more frequent in the A(H1N1)pdm2009 group than in the other two groups (p <0.001). Half of all children had pneumonia but there were no significant differences among groups. There was no mortality in this study. In conclusion, sore throat, headache and myalgia were the significant clinical features suggestive of A(H1N1)pdm2009 infection in children and might be helpful indicators prompting early administration of specific treatments in the settings where definitive laboratory tests are not available.
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In April 2009, in response to the WHO's alert due to the existence of human infection cases with a new AH1N1 influenza virus, known as swine flu, Andalusian Health Authorities trigger an specific action plan. The surveillance actions developped provided us with appropriate clinical, epidemiological and virological characteristics of the disease. During the first few days, contingency plans were set up based on epidemiological surveillance and outbreak control measures were adopted through early alert and rapid response systems. After phase 6 was declared, influenza sentinel and severe cases surveillance were used in order to plan healthcare services, to reduce transmission and to identify and protect the most vulnerable population groups. Behaviour of pandemic influenza in Andalusia was similar to that observed in the rest of the world. Atack rate was similar to a seasonal flu and the peak was reached at the 46th/2009 week. Most of them were mild cases and affected particularly to young people. The average age of hospitalised patients was 32. Prior pulmonary disease, smoking and morbid obesity (BMI>40) were the most common pathologies and risk factors in severe cases. An impact scenario of pandemic wave in Andalusia, with an expected attack rate from 2 to 5%, was prepared considering watt observed in the southern hemisphere. Characteristics of the epidemic concerning its extent, severity and mortality rate were adjusted to this scenario.
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Background: On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identified from the rapidly evolving U.S. outbreak. Methods: Enhanced surveillance was implemented in the United States for human infection with influenza A viruses that could not be subtyped. Specimens were sent to the Centers for Disease Control and Prevention for real-time reverse-transcriptase-polymerase-chain-reaction confirmatory testing for S-OIV. Results: From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. Of patients with available data, 18% had recently traveled to Mexico, and 16% were identified from school outbreaks of S-OIV infection. The most common presenting symptoms were fever (94% of patients), cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9%) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously. Conclusions: A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.
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In 2009, Thailand experienced rapid spread of the pandemic influenza A(H1N1)pdm09 virus. The national response came under intense public scrutiny as the number of confirmed cases and associated deaths increased. Thus, during July-December 2009, the Ministry of Public Health and the World Health Organization jointly reviewed the response efforts. The review found that the actions taken were largely appropriate and proportionate to need. However, areas needing improvement were surveillance, laboratory capacity, hospital infection control and surge capacity, coordination and monitoring of guidelines for clinical management and nonpharmaceutical interventions, risk communications, and addressing vulnerabilities of non-Thai displaced and migrant populations. The experience in Thailand may be applicable to other countries and settings, and the lessons learned may help strengthen responses to other pandemics or comparable prolonged public health emergencies.
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Seasonal influenza places a major burden on public health. Consequently, the World Health Organization (WHO) and over 40% of national governments recommend vaccination of at-risk groups. However, no systematic global data are available to assess vaccine provision nor the effect of immunization policies. To address this situation, IFPMA IVS surveyed global vaccine supply, covering 157 countries from 2004 to 2009. The study also used UN data and a novel vaccine provision “hurdle” rate (set at 15.9% of the population, based on WHO immunization recommendations for the elderly) to compare vaccine supply with development status. In a sub-group of 26 countries, the level of vaccine provision was also correlated to the presence/absence of specific vaccination policies.
Fundamento: El análisis de los casos graves de gripe pandémica es necesario para identificar grupos de población vulnerables y adecuar las políticas de prevención y control. Se analizan las características clínicas y epidemiológicas así como los factores asociados a riesgo de muerte en los casos de infección por virus pandémico (H1N1) 2009 hospitalizados en unidades de cuidados intensivos (UCI) en España y notificados entre el 24 de abril de 2009 y el 31 de enero de 2010. Métodos: En el marco de la estrategia nacional de vigilancia de casos hospitalizados por gripe pandémica se recogió, a nivel nacional, información clínica y epidemiológica individualizada de todos los casos hospitalizados en UCI por infección por virus pandémico (H1N1) 2009. Resultados: De los 1.231 casos ingresados en una UCI 271 fallecieron (letalidad: 22%). La mediana de edad fue 40 años (rango: 0-90). Un total de 838 (76,3%) pacientes presentaban alguna patología subyacente, siendo la respiratoria la más frecuente (34,1%), seguida en adultos de la obesidad mórbida (18,8%). Un 93,1% recibió tratamiento antiviral y un 25,6% (n=231) lo recibió en 48 horas desde el inicio de síntomas. En el análisis multivariante el cáncer (OR 2,71; IC95% 1,44-5,1), las inmunodeficiencias (OR 2,25; IC95% 1,29-3,92) y la obesidad mórbida (OR 1,79; IC95% 1,13- 2,85) estaban asociados significativamente a muerte en los adultos. Conclusiones: Las conclusiones deben estar relacionadas con los resultados: La mortalidad de los pacientes adultos ingresados en la UCI por gripe (H1N1) 2009 estuvo asociada a la coexistencia de cáncer, inmunodeficiencia y obesidad mórbida. En el caso de los niños estaban significativamente asociados al riesgo de fallecimiento la presencia de cáncer, las inmunodeficiencias y los trastornos convulsivos.
Pneumonia and seasonal influenza have major repercussions on mortality, morbidity and costs worldwide. At the end of March 2009, an outbreak of influenza A (H1N1) was reported in Mexico that rapidly spread throughout the world, including the United States, reaching pandemic proportions. The activity of influenza A (H1N1) has reached levels higher than those reported in previous years, mainly affecting the pediatric population aged less than 18 years old. In addition, a group of comorbid conditions were more frequently associated in patients with severe influenza A (H1N1), including chronic pulmonary disease, immunosuppression, heart disease, obesity and pregnancy.The current pandemic has had a substantial impact on public health in the United States and in many other countries worldwide. Therefore, the present review aims to examine the North American experience of the influenza A (H1N1) epidemic, focussing chronologically on the epidemiology of the virus, high risk groups, diagnosis, vaccination and management.