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Hurwitz ES, Haber M, Chang A, et al. Effectiveness of Influenza Vaccination of Day Care Children in Reducing Influenza-Related Morbidity Among Household Contacts. JAMA. 2000;284(13):1677–1682. doi:10.1001/jama.284.13.1677
Author Affiliations: Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Ga (Drs Hurwitz and Cox); Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Ga (Dr Haber); Graduate School of Public Health, San Diego State University (Dr Chang), Department of Pediatrics, Naval Medical Center (Drs Shope and Waecker), and San Diego County Health Department (Dr Ginsberg and Ms Teo), San Diego, Calif.
Context A growing proportion of young children in the United States participate
in day care, and these children are considered to be at high risk for influenza
infection. Whether vaccinating day care children reduces household transmission
of influenza is not known.
Objective To evaluate the effect of vaccinating day care children on reducing
influenza-related morbidity among their household contacts.
Design Single-blind, randomized controlled trial conducted during the 1996-1997
Setting Ten day care centers for children of US Navy personnel in San Diego,
Participants A total of 149 day care attendees (aged 24-60 months) and their families
were randomized; 127 children and their 328 household contacts received 2
vaccine doses and were included in the analysis.
Interventions Inactivated influenza vaccine was administered to 60 children with 162
household contacts, and hepatitis A vaccine as a control was administered
to 67 age-matched children with 166 household contacts.
Main Outcome Measures Information regarding febrile respiratory illnesses and related morbidity
for household contacts of influenza-vaccinated vs control children (subgrouped
by influenza-vaccinated and unvaccinated contacts), obtained by telephone
interviews with parents every 2 weeks from November 1996 through April 1997.
Results Influenza-unvaccinated household contacts (n = 120) of influenza-vaccinated
day care children had 42% fewer febrile respiratory illnesses (P = .04) compared with unvaccinated household contacts of control children.
Among school-aged household contacts (aged 5-17 years), there was an 80% reduction
among contacts of vaccinated children (n = 28) vs contacts of unvaccinated
children (n = 31) in febrile respiratory illnesses (P
= .01), as well as reductions of more than 70% in school days missed (P = .02), reported earaches (P
= .02), physician visits (P = .007), physician-prescribed
antibiotics (P = .02), and adults who missed work
to take care of ill children (P = .04).
Conclusions These results indicate that vaccinating day care children against influenza
helps reduce influenza-related morbidity among their household contacts, particularly
among school-aged contacts. Future studies should be conducted in civilian
populations to assess the full effect of vaccinating day care children against
In the past decade, the proportion of US children younger than 5 years
in day care has increased substantially. Currently, as many as 70% of children
younger than 5 years spend 10 or more hours per week in some form of out-of-home
child care.1 Numerous studies2-7
have suggested that children in larger day care facilities are at greater
risk for respiratory infections than are children cared for at home or in
smaller child care settings (ie, ≤6 children). The increased risk of these
illnesses is associated with excess morbidity and related medical costs for
these children and may extend to their household contacts as well.
One important respiratory illness affecting day care children is influenza.
Day care children are considered to be at high risk for influenza infections;
in a recent study,8 50% of children attending
day care centers were infected in a single season. Influenza-related illnesses
may be associated with considerable economic impact, including medical costs,
workdays lost, school absences, physician visits, antibiotic use, and the
costs of arrangements for sick child care.
A previous study9 suggested that day
care children are more likely than school-aged children or adults to transmit
respiratory illnesses to their household contacts. Consequently, measures
to re duce or prevent transmission of such illnesses to household contacts
would be useful. In view of the high rate of influenza illnesses among day
care children, 1 possible benefit of influenza vaccination of day care children
would be to reduce transmission of influenza to household members.
Although recent studies10,11
have assessed the effectiveness of influenza vaccine in preventing otitis
media among day care children, few studies have examined whether vaccinating
day care children can reduce household transmission of influenza. This article
describes the impact of administering influenza vaccine to children attending
day care centers in reducing respiratory illnesses among their household contacts.
Detailed methods for this study, which was conducted during the 1996-1997
influenza period, have been described elsewhere.12
Briefly, children 24 to 60 months of age (matched for 2 age groups, 24 to
36 months and 37 to 60 months) attending 10 US Navy–affiliated day care
centers in the San Diego, Calif, area were invited to participate. Children
were randomized and received either influenza vaccine or hepatitis A vaccine
as a placebo control. Parents were blinded to the treatment assignment of
their children. Commercially available subunit influenza (FluShield purified
subviron, Wyeth Lederle Vaccines, Philadelphia, Pa) and hepatitis A (SmithKline
Beecham, Philadelphia, Pa) vaccines were administered in the standard recommended
doses and schedules for age; for both vaccines, this regimen was 2 doses administered
1 month apart. Children with prior influenza vaccination were excluded.
To define the period of influenza activity, surveillance of influenza
and other respiratory viruses was conducted by obtaining pharyngeal specimens
from 5 to 10 children with new-onset respiratory illness twice weekly in pediatric
clinics where day care children were most likely to seek care. Viral identification
used monoclonal antibodies in an indirect fluorescent assay.
Information concerning respiratory illnesses and related morbidity among
children attending these day care centers and all other household members
was obtained through telephone interviews conducted every 2 weeks between
November 1996 and April 1997 by trained interviewers using standardized questionnaires.
The overall completion rate for the questionnaires was more than 90%.
The definitions of respiratory illnesses used for the analysis included
any respiratory illness reported by the care provider, a respiratory illness
associated with a fever, and a respiratory illness associated with a temperature
of 38°C (101°F) or higher. Symptoms of a respiratory illness included
at least 1 of the following: cough, sore throat, and/or runny nose. Respiratory
illnesses had to be preceded by at least 3 symptomatic days, and only 1 new-onset
illness could be included in a 2-week period.
To assess vaccine response and serologic evidence of infection, blood
specimens were obtained from the children attending day care 3 times during
the study: before vaccination, 1 month after the second vaccination, and at
the end of the study. Hemagglutination inhibition antibody titers to influenza
A(H1N1), A(H3N2), and B were obtained; a 4-fold or greater rise defined infection.
Human subjects approval for this study was obtained from the institutional
review boards of the Naval Medical Center, San Diego, Calif, the Centers for
Disease Control and Prevention, and the San Diego State University School
of Public Health. Written informed consent for participation was obtained
from parents or legal guardians.
Estimates of the effectiveness of vaccination of day care children in
reducing influenza-related morbidity among household contacts were based on
rates of respiratory illnesses and febrile respiratory illnesses among household
contacts of vaccinated and control children during the influenza period. Because
a large proportion of adult household contacts had also received influenza
vaccine (as a result of military requirements), analyses of effectiveness
among household contacts were completed for contacts who had and had not received
influenza vaccine. The influenza period was defined as the weeks during which
influenza isolates were detected with active surveillance. Respiratory-related
morbidity was assessed among household contacts of vaccinated and unvaccinated
day care children by comparing several factors, including missed school, adults
who missed work to care for ill children, physician visits, earache, antibiotics
prescribed, and over-the-counter medicines used.
To estimate vaccine effectiveness in preventing respiratory illnesses
in household contacts, a logistic model was fitted with the illness status
of the household contact as the dependent variable and the vaccination status
of the day care child as the predictor variable. We tested the hypothesis
that there was no difference in the rate of respiratory illnesses and related
morbidity between the household contacts of vaccinated and unvaccinated day
care children. One-sided P values were used to evaluate
the protective effect of influenza vaccine. The generalized estimation equations
method was used to account for correlations among members of the same household.13
A description of the number of subjects enrolled and available for analysis
has been provided elsewhere.12 Of 748 children
attending the day care centers, 149 (20%) were randomized. Excluding children
lost to follow-up and those who did not receive 2 vaccine doses, there were
127 day care children and their household contacts (60 influenza vaccinated
and 67 control children) included in the analysis. The racial distribution
among vaccinated and control children was not significantly different; overall,
42% were white, 27% were black, and 31% were Hispanic. The mean age in both
groups was 3.7 years.
The age distribution and influenza vaccination status of the 328 household
contacts of study children are shown in Table 1. The mean family size was 3.8 for vaccinated children and
3.7 for control children. For both vaccinated and control children, the mean
age of household contacts younger than 18 years was 7 years. Less than 10%
of household contacts younger than 18 years received influenza vaccines during
the study period. Forty percent of the adults had been vaccinated, because
at least 1 of the adults in each household was a member of the military, for
whom influenza vaccination is routinely required.
Of the 143 isolates obtained, the most frequently detected were influenza
B (31%) and A(H3N2) (29%). No influenza A(H1N1) isolates were identified.
Influenza activity began in mid November, peaked in mid January, and continued
through early February. Both influenza A(H3N2) and influenza B isolates were
obtained during this period; there was no apparent period when 1 isolate was
more prevalent. During the influenza period, 75% of all isolates were influenza
The influenza vaccine efficacy and clinical effectiveness among these
children have been described elsewhere.12 Vaccine
efficacy in preventing serologically proven influenza virus infection was
45% (95% confidence interval [CI], −2% to 69%) for influenza B and 31%
(95% CI, −95% to 73%) for influenza A(H3N2). For both influenza A(H3N2)
and B, children without pre-existing hemagglutination inhibition antibody
to these antigens had lower antibody responses to vaccine, were less likely
to develop a serologic response that was protective against infection, and
were more likely to develop serologic evidence of influenza infection. Although
there were no statistically significant reductions in respiratory or febrile
respiratory illnesses among all vaccinated children, there was a trend for
reductions in such illnesses among vaccinated children with preexisting hemagglutination
inhibition antibodies to influenza A(H3N2) and B. Among children with prevaccination
hemagglutination inhibition titers of 5 or lower to influenza A(H3N2) or B,
the vaccine effectiveness for respiratory illnesses was −23% (95% CI, −56%
to 3%) compared with 11% (95% CI, −9% to 26%) for those with prevaccination
titers of 10 or higher (P = .04).
Among unvaccinated household contacts, influenza vaccination of day
care children resulted in a 16% reduction in respiratory illnesses (P = .10), a 42% reduction in respiratory illnesses associated
with fever (P = .04), and a 47% reduction in respiratory
illnesses with a temperature of 38°C (101°F) or higher (P = .04) (Table 2). Among
vaccinated household contacts, there was a 28% reduction in respiratory illnesses
(P = .04) and a 22% reduction in respiratory illnesses
with a temperature of 101°F or higher (P = .38),
both not significant.
Assessment of vaccine effectiveness among unvaccinated household contacts
by age group demonstrated that the greatest impact of vaccinating day care
children was among school-aged household contacts (Table 3). Among household contacts 5 to 17 years of age, respiratory
illnesses were reduced 50% (P = .007); febrile respiratory
illnesses, including those with a temperature of 38°C (101°F) or higher,
were reduced 80% (P = .01). No significant reductions
in respiratory illnesses with or without fevers were observed among household
contacts who were younger than 5 years. Among adults, there was a 40% reduction
in febrile respiratory illnesses and a 31% reduction in illnesses associated
with a temperature of 38°C (101°F) or higher, but these differences
were not statistically significant.
In addition to reductions in respiratory and febrile respiratory illnesses,
analysis of the illnesses with the highest reported temperature among 5- to
17-year-old household contacts of vaccinated children demonstrated reductions
of more than 70% in the following respiratory-related morbidity events: missed
school, adults who missed work to care for ill children, physician visits,
earache, and antibiotics prescribed. Over-the-counter medicine use decreased
45% (Table 4). No similar reductions
were observed for adults or children younger than 5 years who were household
Among day care children who had serologic specimens available for testing,
influenza A(H3N2) infections were confirmed in 8 (16%) of 51 controls compared
with 5 (11%) of 46 vaccinated day care children, and influenza B infections
were confirmed in 22 (43%) of 51 controls and 11 (24%) of 46 vaccinated children.
For household contacts of these children with serologic evidence of influenza
A(H3N2) or B infection, there was more than a 60% reduction in febrile respiratory
illnesses, including those associated with a temperature of 38°C (101°F)
or higher, among the contacts of vaccinated, infected children when compared
with the contacts of infected control children (Table 5). These reductions were not statistically significant, but
the number of household contacts available for this analysis was small. Assessment
of 5- to 17-year-old household contacts of influenza-infected study children
demonstrated that the contacts of vaccinated children had a 60% or greater
incidence of fewer respiratory and febrile respiratory illnesses than contacts
of infected control subjects. These reductions were statistically significant
for all respiratory illnesses of the contacts of influenza B–infected
Analyses were also completed of the effectiveness of influenza vaccination
of household contacts, although the study was not designed for this purpose,
and these subjects were aware of their vaccination status. Among vaccinated
household contacts of control children, there was a 61% reduction in febrile
respiratory illnesses (P = .04) and a 57% reduction
in respiratory illnesses (P = .06) associated with
a temperature of 38°C (101°F) or higher (Table 6). In contrast, for vaccinated household contacts of vaccinated
day care children, there was a 29% reduction in febrile respiratory illnesses
and a 37% reduction in respiratory illnesses associated with a temperature
of 38°C (101°F) or higher. These differences, however, were not statistically
These findings show that the benefits of influenza vaccination of children
attending day care centers extend to their family members, particularly school-aged
children 5 to 17 years of age, even in military families, among which a large
proportion of adults have also received influenza vaccine. In addition to
reductions in respiratory illnesses, 5- to 17-year-old household contacts
of vaccinated day care children had significant reductions in respiratory-related
morbidity, such as missed school days, physician visits, antibiotics, and
lost parental work to care for the children during their respiratory illness
with the highest temperature. Thus, prevention of spread of influenza-related
illnesses from day care children to their household contacts may have an important
economic impact on the households in which these children live.
The large number of household contacts of study children, primarily
adults, who received influenza vaccine as part of the military health care
program undoubtedly reduced the ability of this study to detect the full potential
impact of influenza vaccination of day care children. In most households in
this study, at least 1 adult had received influenza vaccine, which reduced
the number of household contacts at risk for influenza infections and further
reduced the potential for transmission of influenza among unvaccinated contacts.
It is possible that had this study been conducted in a nonmilitary population
with few vaccinated household contacts, the effect of reducing respiratory
illnesses among household contacts might have been even greater and might
have included adults and children younger than 5 years.
In addition to the large number of household contacts who had received
influenza vaccine, there are several other factors that may have contributed
to the inability to detect an impact on household contacts who were outside
the 5- to 17-year-old age range. A relatively small number of children younger
than 5 years were available for analysis when compared with the number of
school-aged children and adults. Moreover, younger children have high rates
of respiratory illnesses associated with many different respiratory pathogens,
and, in contrast to school-aged children and adults, these illnesses may be
difficult to distinguish from influenza-related infections. Furthermore, a
large proportion of the adult household contacts, in contrast to school-aged
children and children younger than 5 years, may have been more likely to have
natural immunity to the prevalent strains of influenza, which may have been
protective against infection.
The serologically determined vaccine efficacy in the day care children
in this study was 45%.12 As was observed for
household contacts younger than 5 years, there were no significant reductions
in respiratory or febrile respiratory illnesses among vaccinated day care
children. However, children with pre-existing titers to influenza A(H3N2)
and B were significantly less likely to have respiratory illnesses and influenza
infections, suggesting that preexisting immunity to influenza may have been
important for vaccine efficacy and effectiveness in this age group. The inability
to identify reductions in clinical illnesses among these children may have
occurred, as suggested for household contacts younger than 5 years, because
of the limited number of children available for analysis and the difficulty
in distinguishing influenza illnesses from the many other respiratory illnesses
that may occur in this age group.
This study demonstrated that even among influenza-vaccinated children
who subsequently became infected with influenza, there may be a reduction
in respiratory illnesses among household contacts. This finding suggests that
influenza vaccine may work not only by preventing infection, but also by reducing
the likelihood of virus being spread from vaccinated, infected individuals
to susceptible persons. One possible explanation is that the apparent reduction
in transmission was a result of IgA antibody in the respiratory tract of these
Although this study was not designed to assess vaccine effectiveness
among household contacts who had received influenza vaccine, our analysis
did demonstrate that influenza vaccination of household contacts (almost all
of whom were adults) led to a reduction in respiratory illnesses among those
contacts in households in which the day care child had not been vaccinated.
In contrast, in households in which the day care child had received influenza
vaccine, influenza vaccination of household contacts did not result in statistically
significant reductions in respiratory or febrile respiratory illnesses. This
difference probably occurred in large part because rates of respiratory illnesses
were already reduced in these households among unvaccinated contacts because
of vaccination of the day care child.
Recent concern has been raised about the emergence of drug-resistant
organisms, including Streptococcus pneumoniae, as
a result of increased antibiotic use, particularly among children attending
day care centers.14 Although the number of
subjects included in the study was small, the study suggests that influenza
vaccination of children attending day care centers might lead to major reductions
in respiratory illnesses and antibiotic use among their household contacts.
Additional larger studies are needed to further assess the potential effect
of influenza vaccination of day care children in reducing antibiotic use and
antimicrobial resistance among household contacts.
A previous study9 demonstrated that day
care children are at high risk for respiratory illnesses, including influenza
infections, and as a result may be more likely to be a primary source of such
illnesses in their households. Another study15
suggested that vaccination of children, primarily school-aged, may reduce
the prevalence of influenza-related illnesses in communities. Although similar
studies involving vaccination of day care children have not been conducted,
in view of the large proportion of children in day care, the high risks of
respiratory illnesses in these children, and their importance in transmission
of these illnesses within households, influenza vaccination of day care children
may have a similar impact on reducing related morbidity in households and
communities. Recently, there has been concern about the possibility of an
influenza pandemic and optimal measures to control such a pandemic, including
vaccination of target populations such as young children, to reduce spread
of influenza.16 Our results suggest that during
such pandemics, vaccination programs targeting day care children may be 1
effective strategy to reduce influenza transmission in households and perhaps
This study suggests that even in a military population in which a large
proportion of active-duty personnel have been vaccinated, influenza vaccination
of day care children may have additional benefits to families, including reduced
illness, family disruption, lost parental work to take care of ill children
and visit physicians, and antibiotic use among household contacts. Future
studies in military and civilian populations are needed to define the role
of such a targeted influenza vaccine program. These studies should further
elucidate the cost-effectiveness and potential benefits in preventing household
and community spread of influenza and the possible role of such programs in
reducing morbidity during influenza pandemics.