Influenza A (H1N1) in Victoria, Australia: a community case series and analysis of household transmission.

Abstract

We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in community cases from Victoria, Australia in 2009.
Questionnaires were used to collect information on epidemiological characteristics, illness features and co-morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.
The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in those who did not (p = 0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness (ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop influenza-like symptoms.
Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within households.

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Influenza A (H1N1) in Victoria, Australia: A Community
Case Series and Analysis of Household Transmission
Clare Looker, Kylie Carville, Kristina Grant, Heath Kelly*
Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
Abstract
Background: We characterise the clinical features and household transmission of pandemic influenza A (pH1N1) in
community cases from Victoria, Australia in 2009.
Methods: Questionnaires were used to collect information on epidemiological characteristics, illness features and co-
morbidities of cases identified in the 2009 Victorian Influenza Sentinel Surveillance program.
Results: The median age of 132 index cases was 21 years, of whom 54 (41%) were under 18 years old and 28 (21%) had
medical co-morbidities. The median symptom duration was significantly shorter for children who received antivirals than in
those who did not (p=0.03). Assumed influenza transmission was observed in 63 (51%) households. Influenza-like illness
(ILI) developed in 115 of 351 household contacts, a crude secondary attack rate of 33%. Increased ILI rates were seen in
households with larger numbers of children but not larger numbers of adults. Multivariate analysis indicated contacts of
cases with cough and diarrhoea, and contacts in quarantined households were significantly more likely to develop
influenza-like symptoms.
Conclusion: Most cases of pH1N1 in our study were mild with similar clinical characteristics to seasonal influenza. Illness and
case features relating to virus excretion, age and household quarantine may have influenced secondary ILI rates within
households.
Citation: Looker C, Carville K, Grant K, Kelly H (2010) Influenza A (H1N1) in Victoria, Australia: A Community Case Series and Analysis of Household
Transmission. PLoS ONE 5(10): e13702. doi:10.1371/journal.pone.0013702
Editor: Justin Brown, University of Georgia, United States of America
Received May 14, 2010; Accepted September 13, 2010; Published October 28, 2010
Copyright: ? 2010 Looker 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: This study was supported by the Australian National Health and Medical Research Council Strategic Awards, Urgent Research - H1N1 Influenza grant
number 604982. The funder 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: heath.kelly@mh.org.au
Introduction
The experience of pandemic influenza A (pH1N1) amongst
hospitalised patients in Victoria [1] and overseas [2,3,4,5,6,7] has
been widely reported. Less information is available for community
cases, despite it now being clear that the vast majority of cases
were mild and occurred in non-hospitalised patients. [8,9]
On 20thMay 2009, the Victorian Department of Health
confirmed the first case of 2009 pH1N1 in the state, the second
case in Australia. In total 3,089 cases and 26 deaths from pH1N1
were notified in Victoria in 2009. [10] Concern about clinical
severity and community vulnerability during the initial phases of
the H1N1 pandemic led to the implementation of a number of
mitigation measures and significant social disruption. Confirmed
cases were isolated, close contacts quarantined, and schools or
classrooms in which there were confirmed cases closed. Such
public health measures received widespread media coverage and
caused significant community concern. [11,12,13,14]
Quarantine measures also potentially altered the risk of
infection to household contacts of a case. Recent work by
Cauchemez found lower transmissibility of the 2009 pH1N1 virus
in US households than in previous pandemics. [15] Previous
studies of seasonal influenza have found the transmission of
influenza in households can be influenced by age, family structure,
circulating virus and exposure in the community. [16,17] The
patterns of transmission of pH1N1 in Australian households
remains largely unexamined to date.
In this case series, we aimed to describe the epidemiological
characteristics, clinical features and treatment of Victorian sentinel
surveillance patients with laboratory-confirmed pH1N1. We also
aimed to identify case and contact factors that may have impacted
on the incidence of influenza-like illness (ILI) amongst household
contacts of cases with confirmed pandemic influenza infection.
Methods
Victorian general practice sentinel surveillance network
Cases were identified through the Victorian General Practice
Sentinel Surveillance scheme. [18] In 2009 this scheme comprised
87 metropolitan and rural general practitioners (GPs). Patients
presenting to participating GPs with ILI were asked to consent to a
combined nose and throat swab. The formal definition of ILI used
in the surveillance program is based on the symptom triad of fever,
cough and fatigue. This case definition has been found to have a
positive predictive value for laboratory-confirmed influenza of
between 23.3 and 59.7%. [19] On occasion participating GPs may
swabpatients inwhom they suspectinfluenzadespite the patient not
having all three symptoms, for example, perhaps having rhinor-
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rhoea instead of cough. We encouraged GPs to apply the same
criteria for ILI in 2009 as they used in previous influenza seasons.
GPs collected data on age, sex, symptoms and vaccination status of
the patient. Recruitment for testing was at the discretion of the GP.
Laboratory testing
Nose and throat swabs were sent to the Victorian Infectious
Diseases Reference Laboratory (VIDRL), a World Health
Organization National Influenza Centre. Testing for influenza A
viruses involved extraction of RNA from nose/throat swabs.
cDNA was derived by reverse transcription using random
hexamers and amplified using fast real-time PCR incorporating
primers and probes targeting the matrix gene of influenza A.
Samples testing positive in the screening assay were confirmed as
positive or negative for the pandemic virus in a second real-time
PCR assay incorporating primers and probes specific for the
haemagglutinin gene of that virus.
Study recruitment
Eligiblestudyparticipantsweredefined asallsurveillancepatients
who had tested positive to pH1N1 between 1stMay (the start of the
surveillance season) and 31stAugust 2009 (when we commenced
recruitment for this study) and for whom address details were
available. Almost all (97%, 353/363) of the sentinel cases with
pH1N1 infection identified in 2009 surveillance were identified
during this period. These individuals were contacted by mail. Each
potential participant was sent patient information, a consent form
and study questionnaire. Participants were asked to return the
consentformandquestionnairebymail.Non-respondentsweresent
a second letter four weeks after the initial mailing. Questionnaire
data were only used if the relevant consent form was received.
Data collection
The questionnaire content was informed by early findings on
the clinical spectrum of pH1N1, potential risk factors and known
characteristics of seasonal influenza. The questionnaire collected
demographic details, height and weight, illness characteristics,
household contact details, exposure history, vaccination history,
and co-morbidities (including pregnancy). Duration of symptoms
was defined as the number of days between the index case’s first
and last symptoms. These symptoms could be any reported during
the illness (not only fever, cough and fatigue). We recorded the age
of the index case (in years) but the age of contacts was only
categorised as child (less than 18 years old) or adult. Information
on household contacts was provided by the index case (or parent/
guardian if the index case was a child) and ILI in a contact was
defined as ‘fever, cough, tiredness’.
The government’s response to the pandemic was based on
phases recommended in the Australian Health Management Plan
for Pandemic Influenza. [20] The first Delay phase was
implemented throughout Australia on 28thApril 2009. During
the Delay, Contain and Modified Sustain phases, antiviral
treatment with oseltamivir or zanamivir was recommended for
all confirmed cases of pH1N1. [21] During these phases antiviral
therapy was also recommended for all suspected cases and the
close contacts of suspected and confirmed cases. A suspected case
was defined as an individual with fever and a recent onset of
rhinorrhoea, nasal congestion, sore throat or cough, and either
close contact with a confirmed case within the last seven days or
recent travel to a country with known local transmission. From the
23rdJune 2009, when Victoria moved to the Protect phase,
antiviral medication was no longer recommended for cases with
mild infection or for household contacts. Rates of antiviral
treatment were compared across pandemic phases to examine
the impact of phase recommendations on treatment patterns.
Key aspects of the Victorian Government’s Pandemic Plan
included isolation of confirmed and suspected cases and voluntary
home quarantine for household contacts of suspected and
confirmed cases. During the Delay and Contain phase confirmed
and suspected cases were advised by the state Department of
Health to isolate themselves for seven days following the
commencement of antiviral treatment. During these phases the
household contacts of both confirmed and suspected cases were
also requested by the Department of Health, and through advice
delivered by treating doctors, to remain in voluntary home
quarantine for seven days, although there was no mechanism to
enforce this advice or determine whether it had been followed.
The requirement for household contact quarantine was lifted
during the Modified sustain phase. In this phase confirmed cases
were only asked to isolate themselves for three days following
commencement of antiviral treatment. The study questionnaire
asked if the index case or any member of the household was
voluntarily isolated or quarantined. Participants were not asked to
specify whether the household contacts who undertook voluntary
quarantine were also contacts who developed influenza-like
symptoms. We did not gather information on whether the entire
household complied with the voluntary quarantine and from
whom advice about voluntary quarantine had been received.
For household contact data, the index case was defined as the
participant who had been identified through sentinel surveillance
and who was the focus of the questionnaire. Household contacts
were any other people living in the household. The index case was
asked to record the number of household contacts above and
below 18 years of age, the number who developed influenza-like
symptoms within one week of the index case becoming ill, the age
of unwell contacts, their relationship to the index case, and
whether the contact received antiviral treatment. No laboratory
testing was done for household contacts.
Statistical analysis
Categorical variables were compared using Pearson’s x2and
Fisher’s exact tests. Nonparametric data were compared using
Wilcoxon rank sum tests, with p values ,0.05 considered statistically
significant. Crude secondary attack rates were calculated according
to household size by dividing the number of contacts who became
unwell by the total number of contacts in households of that size.
To determine whether there were associations between
particular index case characteristics and ILI in a contact,
univariate and multivariate logistic regression was conducted.
Generalised estimating equations (GEE) were used to account for
household clustering in the logistic regression model. Factors
significant at P=0.10 in univariate analysis were included in
multivariate analysis. Possible risk factors included whether the
index case was a child or adult, the number of children and adults
in the household, whether contacts voluntarily quarantined
themselves, whether the index case received antiviral treatment,
the index case symptoms (e.g. cough) and symptom duration. The
number of children in the household was included in the model as
children have previously been found to be more infectious and
susceptible to influenza infection than adults. [17,22,23] Statistical
analysis was performed using Stata/IC 10.0 for Windows.
Results
Patient and illness characteristics
In total, 953 patients had nose and throat swabs taken at a
sentinel GP practice between 1stMay and 31stAugust 2009, when
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this study commenced. Of these, 353 (37%) tested positive for
pH1N1 and were sent a study questionnaire. Completed
questionnaires were returned by 132 patients and eleven letters
were ‘returned to sender’ due to incorrect address details. The
response rate was 132/342 (39%) of potential participants who
received a letter.
Study participants were similar to all positive surveillance cases
in terms of gender and median age (Table 1). However there were
some differences in important age categories, with a greater
proportion of study participants aged 10–17 years old (23%; 31/
132) compared to all surveillance patients (15%; 54/353)
(p=0.04). The study included fewer participants who were 18–
49 years old (46%; 61/132) compared with all surveillance patients
(62%, 219/353) (p=0.002). Thirty-seven cases did not provide
information about Aboriginal or Torres Strait Islander status while
all other cases reported no Indigenous background. Indigenous
status was not considered in our analysis.
Of the 132 cases, 28 (21%) had underlying medical conditions,
including 11% of children (younger than 18 years) and 28% of
adults (Table 2). Of 75 adults, seven (9%) were obese and five (7%)
were morbidly obese. Two (4%) of 47 children were obese. Two of
the obese adults and one of the obese children had an underlying
medical condition. Two (40%) morbidly obese adults had
underlying medical conditions. A total of 28 cases (21%) reported
receiving the 2009 seasonal influenza vaccine, 15% of children
and 26% of adults. Eight study participants reported working as
health care workers while 76 (57%) were school or university
students.
The most common self-reported symptoms were fever (93%),
fatigue (92%) and ‘body aches’ (79%); 71% (94/132) of cases
reported all three symptoms while 58% (76/132) reported the
triad of fever, cough and fatigue. Despite fever forming part of
the ILI case definition, review of symptom details provided by
GPs with the surveillance swabs showed that some GPs tested
patients who did not present with fever but in whom they
nonetheless suspected influenza. Significantly more adults than
children reported myalgia and ‘body aches’. Fourteen (11%)
cases reported diarrhoea and 23 (17%) reported vomiting. The
median duration of symptoms reported by adults was signifi-
cantly longer (9 days) than that reported for children (7 days,
p=0.003).
Treatment
About half the index cases (48%; 63/130), both adults and
children, received antiviral treatment. Almost all index cases (95%;
59/62) who received antivirals reported completing the full
treatment course. The median duration of symptoms in children
who received antivirals was five days (interquartile range (IQR) 4,
7) compared with seven days (IQR 5.5, 10) in those who did not
(p=0.03). However no difference was seen among adults; those
who received antivirals reported a median symptom duration of
ten days (IQR 5, 14) compared with nine days (IQR 7, 12) in those
who did not (p=0.68).
There was no significant reduction in the proportion of index
cases receiving antiviral treatment in the Protect phase, with 42/
89 (47%) of the cases diagnosed during this phase receiving
antivirals compared with 21/41 (51%) of those diagnosed in earlier
pandemic phases (p=0.67). However, 18/77 (23%) of the contacts
of cases diagnosed during the Protect phase compared with 17/38
(45%) of contacts of cases diagnosed prior to the Protect phase
reported receiving antivirals (p=0.02).
Five participants, two children and three adults, reported
hospitalisation. A hospitalised child reported a one day admission,
and two adult cases reported a one day and six day admission.
Duration was not reported for the other two cases.
Of 131 cases who answered questions regarding isolation during
their illness, 67 (51%) reported isolating themselves. The median
duration of isolation was five (IQR 3, 7) days for adults and seven
(IQR 4, 7) days for children (p=0.10). Of the 123 cases who lived
with others, 23 (18%) reported other household members
undergoing voluntary home quarantine. The duration of volun-
tary household quarantine was longer if the index case was a child
(median 7 days; IQR 4, 7) than if the index case was an adult
(median 3 days; IQR 2.5, 5) (p,0.01).
Household Contacts
A total of 122 of 132 index cases lived in households with
between two and nine household members. One lived in a
university college with 250 ‘household’ members and was excluded
from the household analysis. Eight cases lived alone and one case
did not provide household details.
The 122 index cases had a total of 351 household contacts, of
whom 115 were reported as developing influenza-like symptoms
Table 1. Demographic characteristics of the 132 study respondents compared with sentinel surveillance cases and the Victorian
population.
Victorian Population
(%) (n=5,313,823)
Surveillance Cases
(%) (n=353)
Case Series Participants
(%) (n=132)
Gender
Female 50173 (49) 75 (57)
Median Age (range) 3722 (10 mths –78 yrs)21 (10 mths –64 yrs)
Age Group
0–23 months3 2 (1)1 (1)
2–4 years4 10 (3)3 (2)
5–9 years6 37 (10)19 (14)
10–17 years 10 54 (15)31 (23){
18–49 years 46219 (62)61 (46){
50–64 years1830 (8)17 (13)
$65 years 14 1 (0)0 (0)
{p,0.05 on univariate analysis of case series versus surveillance cases.
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within one week of the index case, a crude household secondary
attack rate of 33%. The median age of contacts with reported ILI
was 24 years (range 1 to 69 years). There was no significant
difference in the median ages of index cases and unwell contacts
(p=0.26).
Assumed influenza transmission was observed in 63 (51%)
households. Of these, index cases in 32 (51%) households reported
one secondary case, 19 (15%) reported two, five (8%) reported
three, and seven (11%) reported four or more secondary cases.
The crude secondary attack rate did not alter significantly
according to household size (Table 3).
We determined if an association existed between particular
index case characteristics and the occurrence of ILI in
household contacts (Table 4). After controlling for clustering
Table 2. Underlying medical conditions, body mass index and illness characteristics of index cases, according to age group.
Clinical Characteristics
All Participants
Total (%) (n=132)
Children , ,18 years
Total (%) (n=54)
Adults $ $18 years
Total (%) (n=78)
Underlying Medical Conditions
Any one condition 28 (21)6 (11) 22 (28)
Pregnancy 1 (1)0 (0)1 (1)
Hypertension 10 (8) 0 (0) 10 (13)*
Chronic respiratory disease 7 (5) 1 (2) 6 (8)
Immunocompromised 2 (2) 1 (2)1 (1)
Obstructive sleep apnoea 1 (1)0 (0)1 (1)
Cardiac disease 3 (2) 1 (2)2 (3)
Neurological disease1 (1)0 (0) 1 (1)
Type I Diabetes1 (1) 0 (0)1 (1)
Type II Diabetes1 (1) 0 (0)1 (1)
Haematological disease2 (2) 1 (2) 1 (1)
Renal disease 0 (0)0 (0)0 (0)
Other chronic disease7 (5) 3 (6)4 (5)
Obese (BMI 30–34.9 in adults $18 years or BMI
percentile 95–100 in children aged 2 to 18 years)1
9 (7)2 (4)7 (9)
Morbidly obese (BMI $35 in adults only)1
5 (4)-5 (7)
Illness Characteristics
Median days from symptom onset to swab (IQR)2
1 (IQR 0, 3)1 (IQR 0, 3) 1 (IQR 0, 3)
Median duration of symptoms (days)3
7 (IQR 5, 11)6.5 (IQR 4, 10)9 (IQR 5, 14)**
Self-reported clinical symptoms
Cough86 (65)33 (61) 53 (68)
Fever123 (93)52 (96) 71 (91)
Shakes/chills88 (67) 35 (65)53 (68)
Sore throat82 (62) 32 (59) 50 (64)
Shortness of breath 38 (29) 12 (22)26 (33)
Rhinorrhoea 53 (40)27 (50)26 (33)
Blocked nose 43 (33)14 (26) 29 (37)
Body aches104 (79)38 (69) 66 (86)*
Diarrhoea14 (11)6 (11)8 (10)
Vomiting23 (17)12 (22)11 (14)
Nausea37 (28) 13 (24)24 (31)
Sore, red eyes 17 (13)10 (19)7 (9)
Myalgia 78 (59)24 (44)54 (69) ***
Arthralgia 51 (39)22 (41)29 (37)
Fatigue122 (92) 52 (96)70 (90)
IQR = interquartile range.
*p,0.05 on univariate analysis of children versus adult cases.
**p,0.05 on Wilcoxon ranksum analysis.
***p,0.01 on univariate analysis of children versus adult cases.
1Body Mass Index (BMI, weight in kilograms divided by height squared in metres) Excludes one pregnant women, one child under two, and 8 patients (6 children and 2
adults) missing height or weight data.
2Excludes one child and 6 adults with missing data.
3Excludes eight adults with missing data.
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of contacts within households, contacts of index cases with
cough (odds ratio (OR) 2.25, 95% CI 1.08, 4.69) and diarrhoea
(OR 3.22, 95% CI 1.15, 9.03) were found to be significantly
more likely to become unwell than contacts of index cases
without these symptoms. Contacts of index cases with symptom
duration greater than one week were also significantly more
likely to become unwell (OR 3.06, 95% CI 1.57, 5.98).
Quarantining of the household was significantly associated with
an increased risk of household contacts developing ILI (OR
2.76, 95% CI 1.23, 6.21). Whether the index case was a child or
an adult did not affect the risk of a household contact
developing an ILI. The risk increased with the number of
children in the household (OR=1.37, 95% CI 1.11, 1.69) but
not the number of adults.
Discussion
We report a case series of community patients with pH1N1
during the peak of the 2009 Victorian influenza pandemic. The
response rate of 39% was lower than expected and may reflect
increasing community perceptions that the pandemic was not as
severe as initially reported. Compared to all sentinel general
practice patients with pandemic influenza, a higher proportion of
10–17 year olds and lower proportion of 18–49 year olds
responded. In 2009, with significant concern about the spread of
pH1N1 in schools and universities, 33% of sentinel surveillance
swabs were collected at one of two university health clinics,
suggesting that university students may have been over-represent-
ed amongst overall surveillance cases. A number of the ‘return to
Table 3. Number of unwell household contacts and crude secondary attack rate (%) by household size.
Number of household
members (including index
case) within household
Number of
households
(n=122)
Number of unwell household contacts (not including index
case)
0 (%)12345
Total number of
contacts with ILI
Crude
secondary
attack rate
22415 (63)9----9 38%
320 12 (60)53---1128%
4 42 20 (48)7105-- 4233%
5 259 (36)94-3- 29 29%
67 3 (43)-2--21440%
73 1 (33)-1-1-633%
80--------
910 (0)000104 50%
doi:10.1371/journal.pone.0013702.t003
Table 4. Risk factors for transmission of influenza A (H1N1) from index case to household contacts.
Contacts (n=351)
Characteristic of index case
Number (%) of homes
(n=122)
Well Contacts
(n=236)
Unwell Contacts
(n=115)
Univariate odds
ratio (95% CI)
Multivariate odds
ratio (95% CI)
Age of index case
Child (0–17 years)
Adult ($18 years)
53 (43)
69 (57)
138
98
59
56
0.83 (0.45, 1.51)
1
Index case symptom
Cough
Runny nose
Diarrhoea
Vomiting
82 (67)
50 (41)
14 (11)
22 (18)
141 (60)
95 (40)
19 (8)
45 (19)
90 (78)
49 (43)
21 (18)
28 (24)
2.60 (1.36, 4.98)
1.13 (0.62, 2.04)
2.47 (0.97, 6.28)
1.48 (0.72, 3.03)
2.25 (1.08, 4.69)*
3.22 (1.15, 9.03)*
Symptom length (n=337)
.1 week
#1 week
60(49)
62 (51)
152 (66)
79 (34)
49 (46)
57 (54)
2.34 (1.27, 4.32)
1
3.06 (1.57, 5.98)**
Antiviral treatment (n=345) 59 (48)106 (45) 59 (52) 1.45 (0.79, 2.67)
Isolation/quarantine
Index case
Whole family
61 (50)
25 (20)
112 (47)
31 (13)
58 (50)
29 (25)
1.16 (0.63, 2.11)
2.28 (1.01, 5.16)2.76 (1.23, 6.21)*
Household
Number of children
Number of adults
1.02 (0.82, 1.27)
1.09 (0.91, 1.30)
0.87 (0.55, 1.36)
1.37 (1.11, 1.69)**
CI = confidence interval.
*p,0.05 on univariate analysis of well and unwell contacts.
**p,0.01 on univariate analysis of well and unwell contacts.
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