C Viboud, P Boëlle, S Cauchemez, et alRisk factors of influenza transmission in households
Cécile Viboud, Pierre-Yves Boëlle, Simon Cauchemez, Audrey Lavenu, Alain-Jacques Valleron,
Introduction Background: Influenza transmission in households is a subject of renewed interest, as the vaccination of children is currently under debate and antiviral treatments have been approved for prophylactic use.
THE epidemiology of influenza transmission in households
has been the subject of great interest and investigation in
Aims: To quantify the risk factors of influenza transmission in
the past, with the rationale that a better understanding of
influenza transmission mechanisms could aid in the design
Design of study: A prospective study conducted during the 1999 to 2000
of efficient control strategies.1 Several follow-up studies of
families during one or several consecutive influenza seasons
Setting: Nine hundred and forty-six households where a member, the
have described the occurrence and spread of infection in
index patient, had visited their general practitioner (GP) because of an
households in relation to age, family composition, crowding,
influenza-like illness were enrolled in the study. Five hundred and ten of
circulating viral strains, exposure in the community, and
the index patients tested positive for influenza A (subtype H3N2). Astandardised daily questionnaire allowed for identification of secondarycases of influenza among their household contacts, who were followed-up
The current thinking regarding influenza transmission is
for 15 days. Of the 395 (77%) households that completed the
that children play a major role in the early stages of the
questionnaire, we selected 279 where no additional cases had occurred on
epidemic, with the assumption that they are more suscepti-
the day of the index patient’s visit to the GP.
ble than older age groups, and that they contribute more
Methods: Secondary cases of influenza were those household contacts
extensively to the spreading of the virus in the population.3
who had developed clinical influenza within 5 days of the disease onset
Furthermore, children spend a great deal of time in com-
in the index patient. Hazard ratios for individual clinical anddemographic characteristics of the contact and their index patient were
munities where daily contact with other people is extensive;
derived from a Cox regression model.
for example, in schools, play groups, and daycare centres,
Results: Overall in the 279 households, 131 (24.1%) secondary cases
and it is assumed that close contact favours transmission.3
occurred among the 543 household contacts. There was an increased risk
However, the extent to which these mechanisms contribute
of influenza transmission in preschool contacts (hazard ratio [HR] =
to transmission has not been quantified. 1.85, 95% confidence interval [CI] = 1.09 to 3.26) as compared with
Recently, there has been renewed interest in the study of
school-age and adult contacts. There was also an increased risk in
influenza transmission in families, especially in light of the
contacts exposed to preschool index patients (HR = 1.93, 95% CI = 1.09to 3.42) and school-age index patients (HR = 1.68, 95% CI = 1.07 to
recent debates about whether large-scale vaccination of
2.65), compared with those exposed to adult index cases. No other factor
healthy children in daycare would be beneficial to other age
was associated with transmission of the disease.
groups,4,5 and whether contact prophylaxis with neu-
Conclusion: Our results support the major role of children in the
raminidase inhibitors could effectively prevent transmis-
dissemination of influenza in households. Vaccination of children or
sion.6-8 However, no data are available on the quantitative
prophylaxis with neuraminidase inhibitors would prevent, respectively,
evaluation of the predictors of influenza transmission in
32–38% and 21–41% of secondary cases caused by exposure to a sickchild in the household. Keywords: antivirals; children; epidemiology; influenza; prospective
In this work, we analyse a prospective study of influenza
studies; risk factors; vaccination.
transmission in families conducted in France during the1999 to 2000 influenza season, where influenza-positiveindex patients were identified by virological tests.9 From this
C Viboud, PhD, research fellow, Epidemiology and Information Sciences,
study we assess the risk factors for influenza transmission
Université Pierre et Marie Curie, Paris; Fogarty International Center,
associated with the individual characteristics of index
National Institute of Health, Bethesda; WHO Collaborating Center for
Electronic Diseases Surveillance (WHO CCEDS), Paris.
patients and their household contacts.
P-Y Boëlle, PhD, lecturer; A-J Valleron, DRSC, director; F Carrat, MD, PhD, lec-
turer, Epidemiology and Information Sciences, Université Pierre et Marie
Curie, Paris; Assistance Publique des Hopitaux de Paris, Paris. S
Cauchemez, MPH, research fellow; A Lavenu, MPH, research fellow,
Epidemiology and Information Sciences, Université Pierre et Marie Curie,
Paris. A Flahault, MD, PHD, professor; Epidemiology and Information
This study, which is described in detail elsewhere,9 was
Sciences, Université Pierre et Marie Curie, WHO CCEDS, Paris Assistance
Publique des Hopitaux de Paris, Paris.
conducted within the framework of the French Sentinel network. The Sentinel network is a computerised public
health surveillance system compiled with the voluntary and
Cécile Viboud, Fogarty International Center, National Institutes of
Health, 16 Center Drive Bethesda, MD 20892, USA.
unpaid participation of 1790 general practitioners (GPs)
located all over France. Since November 1984 it has been
Submitted: 15 August 2003; Editor’s response: 18 December 2003;
collecting weekly reports on 10 communicable diseases,
including influenza-like illness. In addition to the continuous
British Journal of General Practice, 2004, 54, 684-689.
surveillance of disease activity, the network is a setting for
British Journal of General Practice, September 2004 HOW THIS FITS IN
influenza viruses is the transmission between
household members. Children are more susceptible than older
age groups, and they contribute more extensively to the
spreading of the virus in the population.
This study quantifies the risk factors of influenza transmission
in households and investigates the impact of two interventionstrategies for controlling epidemics within them. Vaccination of
children or prophylaxis with neuraminidase inhibitors would
prevent, respectively, 32–38% and 21–41% of secondary casescaused by exposure to a sick child.
thorough investigations conducted over limited time peri-
ods.10,11 One hundred and sixty-one of the GPs from the
network volunteered to participate in this specific study of
influenza transmission in households. They received train-ing on the study protocol and virology sampling during a
A household was enrolled when a member visited the GP
and met the following inclusion criteria: the patient had hada fever >38°C within 48 hours of the visit, together with res-piratory signs; there was at least one other member in thehousehold; the consulting patient was the first case in thehousehold; the patient was not hospitalised as a result of
this visit. If the inclusion criteria were met, the patient wasconsidered to be the index case of the household. Following
discussion of this observational follow-up by the study sci-
entific committee and jurists from the institutional sponsor,
oral consent was obtained from the index patient (or the
index patient’s parents if the index patient was a child). All
studies conducted within the framework of the Sentinel net-
work are approved by the French Commission Nationale del’Informatique et des Libertés (approval no. 471 393).
Information concerning social and demographic charac-
teristics of the household was collected upon enrollment in
the study. Daily details about 13 symptoms (fever >38°C;
feverishness; cough; sore throat; nasal congestion, rhinor-
rhea or sneezing; dysphonia; fatigue; headache; stiffness ormyalgias; otalgias; ocular symptoms; loss of appetite; sleep
Figure 1. Flow diagram of the study. Dotted boxes denote subjects
disturbances), medication, visits to physicians, and missed
days of work of each household member, were reported in astandardised questionnaire for the 15 days following the
Respiratory syncytial virus, parainfluenzae virus and aden-
initial visit of the index patient to their GP. The initial visit was
ovirus infections were diagnosed with the immunofluores-
counted as day 0 of the follow-up. A daily severity score was
cence test.9 Influenza was diagnosed where one or more
calculated as the proportion of the 13 symptoms reported
results with the immunofluorescence test, viral culture and
on a given day (ranging from 0 to 1) as described else-
the polymerase chain reaction (PCR) test were positive. Of
where.9 All participants who completed the questionnaire
the 946 index patients, 510 were influenza A (subtype
H3N2)-positive and, of these, 395 (77%) completed the fol-low-up with their household contacts (Figure 1). The 510
influenza A-positive patients were located in 21 of the 21
Between January 2000 and March 2000, 946 index patients
administrative regions of France. The median number of
and their household contacts were enrolled in the study.
index cases per region was 16, with a range of 2–61. At
Nasal swabs were obtained from all index patients.
inclusion, the only difference between households that com-
British Journal of General Practice, September 2004
C Viboud, P Boëlle, S Cauchemez, et al
pleted the study (n = 395) and those lost to follow-up
(n = 115) was in the sex of the index patient: 19% of the
Although occurrence of secondary transmission is the ult-
households with a female index patient and 26% of those
imate outcome of interest in this work, time to transmission
with a male index patient were lost to follow-up (P = 0.04).
is important as well, because the level of exposure to
In particular, there was no difference regarding variables
influenza in the household is not constant over time.
such as the age of the index patient, severity of the disease
Household members became sick and recovered during
on the first day of illness, body temperature, and inclusion
the study follow-up. Adjustment for factors that varied
between households; for example, exposure to influenza
We used a clinical definition of influenza, without labo-
and household structure, was needed to assess the true
ratory testing, to identify secondary patients. Clinical
role of individual predictors of transmission. The Cox model
influenza was defined as the presence of a fever >38°C, or
is a popular regression model used to assess the relation of
feverishness when the temperature was not taken, or at
explanatory covariates to the time of occurrence of events,
least two of the following symptoms: cough; sore throat;
which in this study is the onset of clinical influenza in con-
nasal congestion, rhinorrhoea, or sneezing; fatigue;
tacts. This model allows adjustment for time-dependent
headache; stiffness; myalgias. This definition is based on
covariates; for example, the level of exposure to influenza in
the criteria that define influenza-like illness in clinical trials
of neuraminidase inhibitors.7,8,13 Household contacts who
Extensions to the Cox model exist that deal with the
developed clinical influenza within 5 days of the initial visit
dependence between observations, in particular for correlat-
of the index patient were classified as secondary patients.
ed household members. In this study, dependence between
To avoid ambiguity about the true introducer of infection in
household contacts is due to shared household structure
the household, we excluded households in which one or
and exposure to the same index patient.17 Household con-
more contacts had developed clinical influenza on the day
tacts who had not developed clinical influenza within 5 days
of the initial GP visit of the index patient (day 0) from the
(412/543 [75.9%]) were considered as censored (for these
main analysis. The incubation period of influenza is
contacts, transmission events had not occurred within
around 1–1.5 days,14,15 therefore this procedure minimises
the probability that the household members (index patient
Similarly to previous studies of influenza transmission in
and contacts) were infected from a common source from
families,18 we distinguished between preschool children
outside the household and not by transmission within the
(0–5 years old), school-age children (6–15 years old), and
household. Among the 395 households that completed
adults (>15 years) to quantify the effect of age. Size limita-
the study, 116 reported potential co-existing primary
tion did not allow for more refined subcategories, such as
patients and were excluded from the main analysis. We
infants or adolescents. We included the following covariates
subsequently performed sensitivity analyses with an
separately in the model: age of the household contact (0–5,
extended dataset that included those households where
6–15, >15 years); influenza vaccination of the contact;
co-existing primary cases were reported on the day of the
influenza-like illness of the contact in the previous year; his-
initial visit, and also a more specific definition of clinical
tory of chronic disease and tobacco consumption of the
influenza based on the combined presence of fever >38°C
contact; duration of illness of the index patient (above or
below the median); and severity of disease of the index
In the remaining 279 of households, the mean number of
patient on the first day of symptoms (above or below the
children per household under 15 years of age was 0.71. This
median). We also adjusted for three household-specific
is in line with the national figure of 0.68 for French house-
parameters that could confound individual characteristics:
holds of two or more members.12 The mean age of index
the number of children ≤15 years in the household, the num-
patients was 38.4 years (standard deviation [SD] = 19.4),
ber of adults, and the level of exposure to influenza infection
241 (86.4%) of them were adults (mean age = 43.1 years,
in the household. We used a daily index, calculated as the
SD = 16.6) and 38 (13.6%) were children aged ≤15 years
sum of the severity scores of the household members (the
(mean age = 9.1 years, SD = 4.7) of whom 10 (3.6%) were
daily severity score was the proportion of symptoms report-
<5 years of age. Ten per cent of the index patients were
ed on a given day among the 13 listed in the questionnaire
vaccinated against influenza, and 14% had experienced
and ranged from 0 to 1) as a proxy for the level of exposure
clinical influenza in the preceding year.
In the 279 households there were 615 contact members.
Upon completion of the study and data entry by trained
We disregarded 72 contacts with insufficient information on
personnel, less than 4% of the information was missing.
clinical follow-up, and in the final analysis included 543 con-
Because of the low rate of missing values, these values
tacts, with a mean age of 32.1 years (SD = 19.9), compris-
were not replaced. All statistical analyses were carried out
ing 401 (73.8%) adults (mean age = 40.4 years, SD = 16.3)
and 142 (26.2%) children (mean age = 8.7 years,SD = 4.1) of whom 36 (6.6%) were below 5 years of age.
The proportion of children among the 72 contacts who didnot fully complete the questionnaire was 26%. Seven per
cent of the household contacts were vaccinated against
Overall, 131 (24.1%) of the 543 contacts developed symp-
influenza, and 9% had experienced clinical influenza in the
toms of influenza within 5 days of the onset of disease in the
index patient, and hence were considered as secondary
British Journal of General Practice, September 2004 Table 1. Comparison of demographic data for household contacts(n = 543), grouped by secondary cases and non-case contacts.
Chronic diseases (n [%]) 45 (10.9)
aP for trend = 0.06. SD = standard deviation. Table 2. Hazard ratios for individual predictors of influenza Figure 2. Number of secondary cases of influenza by day ofhousehold transmission, adjusted on a daily score for exposure tohousehold outbreak. Overall there were 131 secondary cases. Dayinfluenza infection, the number of children under 15 years old and0 is the day of onset of influenza A (H3N2) illness in the index casethe number of adults in the household.= day of the visit to the general practitioner.
cases. Influenza transmission was observed in 97 (35%)
households. Of the 97 households, 67 (69.1%) reported one
secondary case, 26 (26.8%) reported two, and four (4.1%)
reported three. The median time lag between the onset of
influenza in the index patient and the onset of symptoms in
the secondary patient was 2 days (range = 1–5 days)
(Figure 2). The demographic and medical data for the
secondary patients and non-case household contacts are
presented in Table 1. We found no significant differences in
the individual characteristics of these two groups of contacts
with regard to age, sex, smoking status, history of chronic
disease, influenza vaccination, or previous influenza-like ill-
ness. However, clinical influenza was reported in 38.5%
(10/26) of contacts in households where the index patient
belonged to the 0–5 years age group, in 33.7% (28/83) of the
6–15 years age group and in 21.4% (93/434) of adults,
(Cochran-Armitage trend test, P = 0.004). Note that these
estimates are not adjusted on household structure.
Households in which the index patient was a child had more
children than those where the index patient was an adult
The median severity of disease on day 0 (proportion of 13 clinical
symptoms reported on the day of the visit to the general practitioner) was
(respective median number of children = 2 versus 1,
0.65 for index cases (range = 0–1). bThe median duration of disease was
8 days in index cases (range = 0–15). CI = confidence interval. Risk factors of influenza transmission in
1.68, 95% CI = 1.07 to 2.65), compared with those exposed
The Cox statistical analysis showed that transmission of
to adult index patients. No other factor related either to the
influenza was clearly associated with the age of both the
contact or to the index patient was associated with influenza
index patient and the contact. We found an increased risk of
clinical influenza in preschool contacts compared with
We tested the effect of discarding the households where
adults, with a hazard ratio (HR) of 1.85, 95% confidence
co-existing primary cases were reported on the day of the
interval (CI) = 1.09 to 3.26. There was no increased risk in
initial visit to the GP from the analysis. We repeated the ini-
school-age contacts (HR = 1.12, 95% CI = 0.73 to 1.71).
tial statistical analysis with an extended dataset comprising
There was also an increased risk of clinical influenza in con-
all households (n = 395), in which 313 secondary cases
tacts exposed to preschool index patients (HR = 1.93, 95%
were reported (secondary attack rate in contacts = 38.3%).
CI = 1.09 to 3.42) and school-age index patients (HR =
We retrieved similar results, but all hazard ratio estimates
British Journal of General Practice, September 2004
C Viboud, P Boëlle, S Cauchemez, et al
were somewhat closer to one than those of the main analy-
combination of cough and fever as case definition,16 we
sis. There was an increased risk of clinical influenza in
found risk estimates consistent with those derived from our
preschool contacts (HR = 1.90, 95% CI = 1.35 to 2.67) but
original broader definition, although some of our risk est-
not in school-age contacts (HR = 0.94, 95% CI = 0.71 to
imates were no longer significant due to lack of statistical
1.26). There was also an increased risk of clinical influenza
in contacts exposed to young index patients, with a hazard
The choice of a time period of 1–5 days from the inclusion
ratio of 1.62, 95% CI = 1.31 to 2.00 for preschool index
of index patients to the onset of symptoms in secondary
patients and a hazard ratio of 1.27, 95% CI = 1.03 to 1.57 for
patients (mean delay = 2.4 days) minimised the risk of
infections from non-influenza pathogens and from extra-
The additional sensitivity analysis using a more specific
household sources. Indeed, in the present study, we found
definition of clinical influenza (based on fever and cough)
influenza transmission in 24.1% of the household contacts
gave results in line with those from the main analysis. The
and in 34.8% of the households. These figures are within the
secondary attack rate in contacts was 18.1%. There was an
range of previously published estimates in comparable
increased risk of clinical influenza in preschool contacts (HR
= 2.28, 95% CI = 1.46 to 3.59) but not in school-age con-
Overall, although we do not know the exact proportion of
tacts (HR = 0.61, 95% CI = 0.37 to 1.01). Although no more
patients with influenza among the contacts showing symp-
significant, the magnitude of risk and confidence intervals
toms of clinical influenza, we can provide an estimate. It has
associated with the age of the index patient was consistent
been reported that 75–80% of household transmissions
with the previous estimates (HR = 1.03, 95% CI = 0.42 to
occur directly from the influenza-positive index patient or
2.54) for preschool index patients and HR = 1.44, 95% CI =
from the same source of infection as the index patient.7,8 In
0.83 to 2.51 for school-age index patients.
this group, all of the clinical secondary cases have aninfluenza aetiology. The remaining 20–25% are due to trans-
Discussion
mission from the community at large.7,8 In this second
The present study identifies age of index patients and age of
group, the probability of infection by influenza equals the
contacts as the main predictors of influenza transmission in
prevalence of influenza in the community. From the propor-
families. These factors appear to be more important than
tion of influenza infections in index patients at inclusion we
other individual variables, whether they are related to the
estimate the prevalence of influenza in the community at
contact person or to the index patient. Based on our risk
54% in this study. A plausible range estimate of the propor-
estimates, 40–48% of the secondary cases exposed to a
tion of influenza infection among secondary patients is
child sick with influenza in the household are attributable to
Reasons for increased transmission from children
The role of children in the dissemination of influenza is com-
Two factors may have harmed the validity of our results. The
monly accepted,2,3 and can be explained by three different
first is that the household contacts were not tested for
and possibly complementary mechanisms. First, children are
influenza infection to limit intervention bias.9 It is therefore
believed to experience a large number of extra-household
possible that some of the clinical infections detected here
contacts with their peers in schools or daycare centres,
may be due to respiratory viruses other than influenza.
although very little quantitative information is available on the
However, there was little circulation of other respiratory
subject. Our study was not designed to test this mechanism.
viruses in the community during the study period: only 25 of
Second, children are assumed to be more susceptible to
the 946 (2.6%) index patients tested positive for respiratory
influenza infection because of lower immunity, although it
syncytial virus and none were found to be positive for
depends on virus (sub)types and setting.3,21 Accordingly, we
parainfluenzae virus or adenovirus. Furthermore, a recent
found evidence of increased susceptibility to clinical influen-
investigation of the genetic sequences of influenza viruses
za in preschool children. We have no clear explanation as to
recovered in families suggested that transmission from com-
why there was no increased susceptibility in school-age chil-
munity sources was rare in families where an index patient
dren, but influenza A (H3N2) infections usually have a wider
distribution of age-specific attack rates than influenza A
Instead of laboratory tests, we used a broad clinical defin-
(H1N1) or influenza B infections.18 It is also possible that few
ition based on fever or respiratory signs to identify sec-
differences in susceptibility between adults and school-age
ondary cases. Indeed, 38% of contacts classified as sec-
children occurred in this particular year, due to the circulation
ondary patients did not report a fever. In patients consulting
of the same influenza viruses (A/Sydney/5/97-like viruses,
physicians for a respiratory illness during an influenza epi-
A/H3N2 subtype) for the third consecutive winter. Third, chil-
demic period, the relative risk that fever >37.8°C is associ-
dren could also be more infectious both because of an
ated with an influenza diagnosis was 2.5 in one study (4.6 for
increased amount of virus shedding and an increased dura-
influenza A [H3N2] specifically),20 and 3.3 in another.16
tion of the infectious period, as reported in recent clinical
However, syndromes associated with true influenza infection
studies.22,7 Our results are in line with these findings.
do not necessarily always include fever. In the latter studies,30–40% of patients with respiratory syndromes caused by
Strategies for limiting secondary transmission of
influenza were afebrile. Furthermore, by applying a specific
British Journal of General Practice, September 2004
This work provides a quantification of the major role of chil-
symptoms predicting influenza infection.
dren, and particularly younger children, in the transmission
Extending the Cox model. New York: Springer-
of influenza in families. Based on attributable fractions of
exposure to sick children in the household of around
18. Monto AS, Sullivan KM. Acute respiratory illness in the community.
40–48% we can assess the potential impact of two interven-
Frequency of illness and the agents involved.
tion strategies. The first is the vaccination of children in
19. Gubareva LV, Novikov DV, Hayden FG. Assessment of
advance of the epidemic season. The efficacy of influenza
hemagglutinin sequence heterogeneity during influenza virus
vaccine has been estimated to be around 80% in preventing
20. Carrat F, Tachet A, Rouzioux C, et al. Evaluation of clinical case
the disease in children.23 Thus, 32–38% of the secondary
definitions of influenza: detailed investigation of patients during the
household cases from exposure to a sick child could be
21. Longini IM Jr, Koopman JS, Haber M, Cotsonis GA. Statistical
averted by vaccinating children. The second is the prophy-
inference for infectious diseases. Risk-specific household and
lactic treatment of household contacts with neuraminidase
inhibitors after exposure to a child sick with influenza.
22. Nicholson K, Webster RG, Hay A. Textbook on influenza. Oxford:
Parents usually consult a GP or a paediatrician if their child
has symptoms of influenza-like illness, so the diagnostic of
23. Nicholson KG, Wood JM, Zambon M. Influenza.
influenza needs to be established. Using rapid influenza
24. Uyeki TM, Fukuda K, Cox NJ. Influenza surveillance with rapid
tests during the visit would allow identification of 72–95% of
children truly sick with influenza.24 If the time since onset ofsymptoms in the child diagnosed with influenza is less than
Acknowledgments
48 hours, then prophylaxis of contacts can be initiated with
We thank the patients, their families and the 161 GPs of the French
an efficacy of around 74–89% in preventing the disease.23
Sentinelles network who participated in the study. This study was partly
This strategy would prevent 21–41% of cases in exposed
supported by a grant from GlaxoSmithKline, Marly-Le-Roi, France.
Cécile Viboud was supported by a grant from the French Ministry of
household contacts. These figures should help clinicians
Education and Research and the Fondation pour la Recherche
choose adequate strategies for controlling the size of
Médicale at the time of this study.
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British Journal of General Practice, September 2004
La crisis del maíz y la tortilla: crisis de la soberanía alimentaria en México . “Del lugar de las delicias de Paxil y Cayalá vinieron las mazorcas amarillas, y las zaquihal o mazorcas blancas.” “.Este maíz amarillo y blanco, fue lo que hallaron los creadores como lo apropiado para la comida del hombre y de esto se hizo su carne cuando fue formado, y asimismo de este alime
Conversion Technique - By Jack Carpenter I have never used anything other than Colchicine circulate air around the treated crowns are in my opinion (DMSO has sometimes been used) to effect conversion. The use of DMSO did not seem to cause greater amounts of conversions. I am simply not familiar with the CRITICAL importance as crown rot may occur. Always several other things I have heard