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Influenza-like Illness in Households with Children of Preschool Age

Mughini-Gras, Lapo DVM, PhD; Pijnacker, Roan MSc; Enserink, Remko PhD; Heusinkveld, Moniek MD, PhD; van der Hoek, Wim MD, PhD; van Pelt, Wilfrid PhD

Author Information
The Pediatric Infectious Disease Journal: March 2016 - Volume 35 - Issue 3 - p 242-248
doi: 10.1097/INF.0000000000000988

Abstract

Influenza-like illness (ILI) is the leading cause of pediatric medical consultation. It mainly affects preschool children during the winter epidemics.1–3 Besides influenza virus, other viruses and to a lesser extent bacteria can cause ILI. ILI-causing viruses include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza viruses, human coronaviruses and human metapneumovirus, which are indistinguishable on clinical grounds.4 The increased proneness of preschool children to ILI is a reflection of their immunological naivety and expenditure of a great deal of time in day-care centers (DCCs), playgroups, etc., where there are numerous opportunities for pathogen transmission. Accordingly, children attending out-of-home child care are about twice as likely to suffer from ILI as those who are home-cared.5–9

With the rise of women’s labor force participation and increasing number of single-parent households, children are increasingly more likely to attend DCCs, which may in turn affect other household members, as preschool children may contribute to spreading ILI-causing agents to their siblings and parents.1,10–13 For instance, a US study involving 185 mothers has estimated that the risk for upper respiratory infections is twice as high in those mothers whose children attend DCCs than in those caring for their children at home.12 Furthermore, a Canadian study involving 374 households with DCC-attending children aged 5 years or younger has estimated that child-to-parent ILI transmission occurs about once every 3 ILI episodes in children.10 In a French study involving 543 household contacts of 279 ILI index cases visiting the general practitioner (GP) during the 1999–2000 winter season, the overall secondary attack rate was 24%, with contacts 5-year-old or younger being at about twice the risk for secondary ILI as those of older age groups. Moreover, the risk for secondary transmission was higher in contacts of index cases 5-year-old or younger than in those of adult index cases.1

It has been suggested that the excess of ILI in households with preschool children may have a significant socioeconomic impact because of increased recourse to medical care, “outsourced” care (eg, babysitting) and absenteeism from work,5,14 which may all eventually contribute to the community burden of ILI. Quantifying the societal burden of ILI in households with preschool children and characterizing the infection risks within these households are, therefore, a public health priority. Moreover, the evidence base for disease control policies like home isolation, treatment and vaccination, as well as recommendations for child-rearing standards and practices, builds upon the understanding of infection risks within the household. The aim of this study was to determine the societal burden (ie, incidence, health-care consumption and productivity loss) and determinants of ILI in households with preschool children.

PATIENTS AND METHODS

Data Collection

From October 2012 to October 2014 (25 months), we conducted a monthly repeated cross-sectional survey in households with preschool children. These households were randomly selected from population registries of 335 (out of 415) municipalities in the Netherlands that granted the research team access to their population registries. These municipalities accounted for 78% of the Dutch general population (~16.8 million inhabitants). Only households with children younger than 4 years were included, as this is the age after which children are eligible to enroll in primary school in the Netherlands. Monthly, a sample of 2000 children younger than 4 years living in different households (ie, 1 child per household) was drawn at random, and their parents were invited by regular mail to complete a web-based questionnaire for the sampled child and for 1 parent chosen freely within the household. Only 1 child–parent pair per household participated in the study. The following subjects were addressed in the questionnaire: demographic and household characteristics, occupation, contact with animals, recreational activities, eating habits, DCC attendance, chronic conditions, medication use, acute symptoms and related medical care and absenteeism from work and from DCC. Questions referred to the previous 4 weeks. The questionnaire was developed based on previous population-based studies in the Netherlands.15–18 The degree of urbanization and the socioeconomic status (SES) at the postcode level were obtained from Statistics Netherlands.

Case Definition

Based on the symptoms reported in the questionnaire, a case of ILI was defined as a person with sudden onset of at least 1 of the following 5 systemic symptoms:

  • fever (≥38°C)
  • feverishness
  • malaise
  • headache
  • myalgia

and sudden onset of at least 1 of the following 4 respiratory symptoms:

  • cough
  • sore throat
  • runny nose
  • shortness of breath

A similar case definition has been adopted by the European Centre for Disease Prevention and Control (http://ecdc.europa.eu/en/activities/surveillance/eisn/surveillance/pages/influenza_case_definitions.aspx) and used in previous Dutch studies.2,5 Multiple episodes of ILI during the 4-week recall period were not differentiated, meaning that the participants were asked to report any of the above-listed symptoms as experienced during the previous 4 weeks; each participant could, therefore, be classified as a case or not by applying the aforementioned case definition.

Statistical Analysis

Monthly incidence, episodes/person-year (calculated as [365/28] × [4-week incidence proportion]5,15), medical care received (GP visits, hospitalizations and medication use) and days of absence from work or from DCC were used to describe the societal burden of ILI.

In total, 69 and 78 variables (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/C317) were assessed for association with ILI in children and parents, respectively. This was done using “univariate” logistic regression models that also included the following control variables: child age group (infants, 12 months old or younger; toddlers, 13–36 months; preschooler, 37–48 months) or parent age group (≤30, 31–34, 35–37, ≥38 years), gender, urbanization degree (<500, 500–999, 1000–1449, 1500–2500, >2500 addresses/km2), SES (a normalized score ranging from –4 to 4, based on income, employment and educational level per postcode), season (autumn, September–November; winter, December–February; spring, March–May; summer, June–August), influenza season year (October 2012–October 2013 and November 2013–October 2013) and presence/absence of any chronic respiratory condition (asthma, chronic obstructive pulmonary disease and other chronic lung diseases, respiratory allergies, lung cancer and pulmonary hypertension). A backward stepwise multivariable logistic regression model was built using variables showing a “univariate” P value ≤0.10. Variables were dropped one by one until all variables retained in the multivariable model had a P value <0.05. The effect of removing variables on the other covariates was monitored. The above control covariates were always kept into the models. Selection between collinear variables was made based on improved model fit as revealed by the Akaike information criterion. Biologically plausible interactions between independent variables were also assessed. A complete record analysis was performed. For simplicity, only the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) from the final multivariable models were presented.

The variable “presence/absence of ILI in the child” was then added as explanatory variable in the final multivariable model predicting parental ILI to test whether parents of ILI-affected children had a concurrent increased ILI risk. However, risk factors for parental ILI were reported independently of childhood ILI because we had no information on the ILI status of the other household members, and therefore, it would not have been entirely correct to explain parental ILI with the ILI child cases. All models presented here showed an overall statistical significance (likelihood-ratio χ2 test, P < 0.05) and goodness-of-fit (Hosmer–Lemeshow test, P > 0.05). Statistical analyses were performed using STATA 13 (StataCorp, College Station, TX).

RESULTS

Sample Description

General characteristics of the study participants are summarized in Table 1. In total, 49,732 child–parent pairs were invited (268 were unreachable because of incomplete/changed address) and 10,109 (20.3%) returned the questionnaire. Five hundred and eighty-one (5.8%) questionnaires were discarded because the parent reported information for a different child than the one sampled/invited, 395 (3.9%) because questionnaires were incomplete and 365 (3.61%) because were inconsistently filled in. The remaining 8768 child–parent pairs represented the aimed sample regarding the variables for which we had information for both participants and nonparticipants: child’s age, gender, urbanization degree, season and SES (Table 1).

TABLE 1
TABLE 1:
General Characteristics of the Study Participants

In total, 7268 mothers [median age 34 years, interquartile range (IQR), 31–37] and 1500 fathers (37 years; IQR, 33–41) were enrolled in the study. These matched with 4210 female (median age, 27 months; IQR. 16–37) and 4558 male (26 months; IQR, 16–38) children, half of which (50.4%) attended DCCs. Median DCC attendance frequency was 2 days/week (IQR, 1–2), and the median duration of DCC attendance was 24 months (IQR, 9–24). Most (98.0%) households had 2 parents and had 2 children (47.2%), followed by those with 1 child (35.0%) and ≥3 children (17.8%).

Societal Burden

In total, 1307 (14.9%) parents and 1893 (21.6%) children met the case definition, resulting in 1.94 ILI episodes/parent-year (95% CI: 1.85–2.04) and 2.81 ILI episodes/child-year (95% CI: 2.70–2.93). For 631 (7.2%) child–parent pairs, ILI was concurrently experienced in children and parents. Adjusting for overrepresentation of mothers, sex-standardized parental monthly incidence was 13.2%, that is, 1.72 ILI episodes/parent-year (95% CI: 1.61–1.84). ILI incidence showed a clear seasonality in both children and parents, peaking during the winter and decreasing during the summer (Fig. 1).

FIGURE 1
FIGURE 1:
Incidence of ILI in children younger than 4 years and in their parents (n = 8768 child–parent pairs) by study month. An optimized cubic smoothing P-spline function is fitted to the observed data. Autumn, September–November; winter, December–February; spring, March–May; summer, June–August.

Of the 1307 ILI-affected parents, 23.0% had fever, 59.3% feverishness, 13.0% malaise, 67.3% headache and 22.2% myalgia. Of the 1893 ILI-affected children, 86.4% had fever, 51.2% feverishness, 6.9% malaise, 6.2% headache and 1.3% myalgia. Symptom frequencies are reported in Table 2. Amongst ILI cases, median duration of symptoms was 6 days (IQR, 4–10) in parents and 5 days (IQR, 3–10) in children; 231 parents (17.7%) and 676 (35.7%) children with ILI visited the GP, but none was hospitalized, and 386 (29.5%) parents and 729 (38.5%) children with ILI took medicines. Antimicrobials were taken by 158 (8.3%) children and 67 (5.1%) parents with ILI. Two-hundred and eighty-two (21.6%) and 309 (16.3%) parents were absent from work because of their own illness (median work absenteeism, 2 days; IQR, 1–3) and their child’s illness (1 day; IQR, 1–2), respectively. For 51 (3.9%) parents and 73 (3.9%) children with ILI, someone else had to miss work. Child DCC absenteeism was 22.8% (median, 1 day missed; IQR, 1–2).

TABLE 2
TABLE 2:
Symptoms Reported by the Participating Child–parent Matching Pairs (n = 8768).

Risk Factors

Table 3 shows the factors significantly associated with ILI in the final multivariable model for children comprising 1887 ILI-affected and 6842 ILI-free children. An increased ILI risk was found for children with chronic respiratory conditions, with developmental disabilities attending DCCs, living in households with 2 children and with the participating parents employed in health care or in child care. ILI was more likely to occur in children attending DCCs for ≤12 months compared with home-cared children. Attending DCCs for 13–24 months was not significant, but having attended DCCs for >24 months was associated with decreased ILI risk. Other protective factors were summertime camping and breastfeeding in infants 6-month-old or younger.

TABLE 3
TABLE 3:
Factors Significantly Associated with ILI in Children Aged 4 Years or Younger

Table 4 shows the factors significantly associated with ILI in the final multivariable model for parents comprising 1298 ILI-affected and 7431 ILI-free parents. An increased risk for ILI was found in parents with chronic respiratory conditions and with a DCC-attending child having developmental disabilities. ILI was more likely to occur in mothers than in fathers, especially in unemployed mothers having multiple DCC-attending children. The risk for ILI was lower in pregnant mothers than in fathers/nonpregnant mothers. A decreased ILI risk was found in parents working in health care, camping during the summer, being older than 35 years and having ≥2 children.

TABLE 4
TABLE 4:
Factors Associated with ILI in Parents of Children Aged 4 Years or Younger

In both parents and children, ILI risk was higher in spring, autumn and winter than in summer. A decreased ILI risk was observed in the 2013–2014 versus the 2012–2013 influenza season. Parents whose children had ILI were significantly more likely to experience ILI in the same 4-week period (OR: 4.13; 95% CI: 3.63–4.70).

DISCUSSION

This study was performed to determine the societal burden and correlates of ILI in households with preschool children in a high-income country. Monthly ILI incidence was estimated at 13.2% in parents and 21.6% in children, resulting in an overall rate of 1.72 ILI episodes/parent-year and 2.81 ILI episodes/child-year, respectively. These estimates are higher than those of 7.4–11.8% obtained via an internet-based monitoring system in the Dutch general population during the 2003–2008 winter seasons,3 suggesting that ILI occurs more often in households with preschool children than in the community. The impact of ILI on the health-care system and on the society as a whole also appears relevant, with 35.7% of children and 17.7% of parents with ILI seeking medical care, and 45.7% and 22.8% of ILI-affected parents and children reporting, respectively, a loss of working and DCC days and about one third of those with ILI taking medications, which often represent out-of-pocket costs.

The low response rate may have represented a potential source of bias, as people experiencing ILI might have been more motivated to complete the questionnaire. However, response rates were not higher in winter (when ILI incidence was highest) than in the other seasons (Table 1). Although recall bias may have underestimated ILI incidence because people might have forgotten (mild) ILI episodes, an overestimation of ILI incidence might have also occurred as a result of “telescoping,” that is, when people remember episodes as being more recent than they actually are.19 Moreover, we cannot exclude that some ILI cases might have been due to noninfectious causes.

No marked differences were observed between the seasonal patterns of childhood and parental ILI incidence. Moreover, parents of ILI-affected children were at increased risk of ILI during the same 4-week period as their children. This is suggestive of substantial household transmission, in agreement with previous research showing that secondary transmission of ILI-causing agents occurs often within the household.11,20–24 Additionally, mothers were more likely to experience ILI than fathers were, possibly reflecting different gender-related responses to pathogens and/or traditionally female-oriented tasks like caring for the children. This is further supported by the somewhat higher risks amongst unemployed mothers, as they are likely to devote more time to child caregiving. Moreover, such risks seemed to increase with multiple DCC-attending children in the household, indicating that attending DCCs does not only increase ILI risk in children, but also in (their) parents, possibly via increased chance for secondary transmission.10,12 Although this study could not determine whether household transmission had any specific directionality, previous research showed that parents frequently acquire ILI in secondary transmission from their children.10,24

Attending DCCs was confirmed to be a risk factor for childhood ILI until 12 months of attendance, but not afterwards, even becoming protective after 24 months of attendance. Because we adjusted for child’s age, this may well be the effect of immunological maturation resulting from the (excess of) infections experienced during the first year of attendance, as evidenced for gastroenteritis in a recent Danish study.25

Children with developmental disabilities attending DCCs had an increased ILI risk. This agrees with previous research showing that these children, by reason of their commonly displayed at-risk behaviors, impaired health and functioning have a higher prevalence of a range of medical conditions, including respiratory illness.26 Our study showed that also the parents of (DCC-attending) developmentally disabled children are at increased risk for ILI, possibly reflecting a higher chance for secondary transmission from this particularly vulnerable population.

The characteristics of Dutch DCCs have been presented in detail elsewhere.2,18,27 In brief, DCCs in the Netherlands provide government-regulated, paid, nonparental care for children younger than 4 years of age. There are approximately 6000 active DCCs caring for approximately 50% of the Dutch preschool population (~700,000 children).2,27 On average, a Dutch DCC enrolls 82 children, with a ratio of 5 children per caregiver.2,18,27 Small DCCs tend to be organized vertically (children of all ages grouped together), whereas larger DCCs tend to be organized horizontally (children of similar age grouped together).2 On average, children attend DCCs for 2.5 days a week, reflecting the high part-time employment of Dutch parents.2,18,27

Interestingly, children of parents employed in health care or child care were at increased risk for ILI, whereas occupation in health care showed a borderline significant protective effect for parental ILI. Although this may suggest pathogen spread from a parent’s work setting to the household, it is also possible that parents working in health care/child care are more knowledgeable of health-related and child-related topics and, therefore, reported more accurately. Similarly, parents employed in health care may be more knowledgeable of hygiene measures as to prevent contagion and may have acquired some immunity because of repeated (occupational) exposure to ILI-causing agents and/or regular influenza vaccination, which is recommended for health care workers. Although ILI can be caused by numerous pathogens, influenza viruses are likely to account for a substantial proportion of ILI cases, especially during the winter. A major limitation of this study was the lack of information about influenza vaccination, which might be relevant to disentangle the risk found for some of the groups with an indication for influenza vaccination, including those with underlying medical conditions. Moreover, SES, a well-known confounder of population health studies, was measured at the postcode level, so the adjustment made in the analysis only reflects this resolution.

Another difference between children and parents concerned the effect of the number of children in the household. Although the risk for childhood ILI increased with the presence of 2 children and was insignificant with ≥3 children, parental risk decreased with ≥3 children. Similar findings have been reported elsewhere11,24 and may be explained by increased opportunities for between-sibling transmission and by immunological maturation in parents (and perhaps in children, to a minor extent) because of repeated immune boosts with every additional child in the household. This becomes even more plausible because we adjusted for age (which also showed that older parents had less ILI) and for the youngest–oldest child age interval (Tables 3 and 4). Breastfeeding in 6-month-old infants 6-month-old or younger was protective for ILI. There is overwhelming evidence that, even in developed countries, breastfeeding protects against respiratory infections amongst others,28 particularly in the first 6 months of life,29,30 that is, the recommended period of exclusive breastfeeding.

Children and parents with chronic respiratory conditions were at increased ILI risk, which is in accordance with previous studies reporting that conditions like asthma may increase the susceptibility to clinically overt respiratory infections and their complications.31,32 Pregnancy was associated with decreased ILI risk. This might be explained by a general attitude of (and recommendation to) pregnant women to avoid direct contact with sick people because of increased risk of gestational problems caused by illness during pregnancy.33,34 Interestingly, summertime camping was protective against ILI in both children and parents. Camping is a popular accommodation for holiday trips among the Dutch, especially during the summer. According to 2013 Eurostat tourism statistics (http://ec.europa.eu/eurostat), residents in the Netherlands have the fifth highest preference for camping among the 28 European Union Member States, with approximately 16% of all holiday trips being indeed camping trips. Typically, Dutch families with young children would prefer camping in spacious, well-equipped campsites, including children’s playgrounds, recreational/sport facilities and bathing waters, and possibility of nature trails and excursions, although missing almost none of the “luxuries” of their homes (eg, gas cookers, refrigerators and washing machines). In this context, we speculated that summertime camping is a proxy for outdoor leisure activities in a season of generally low ILI-causing agent activity that may have significant health benefits because of, for instance, sunlight exposure/increased vitamin D production,35 as well as expenditure of a great deal of time in the open air under relatively less crowded conditions, thereby reducing the frequency of contacts with potentially contagious people. We also confirmed previous findings that the 2013–2014 influenza season was mild in the Netherlands when compared with the exceptionally long-lasting 2012–2013 influenza season.36

In conclusion, ILI in households with preschool children poses a high societal burden. Risk-mitigating initiatives seem justified for DCC attendees, (unemployed) mothers, people with chronic respiratory conditions and households with developmentally disabled children. Although improving hygiene in DCCs is generally desirable and may help reducing respiratory infections among the youngest,37,38 there was also reassuring evidence that children attending DCCs for >2 years may acquire some immunity to ILI.

ACKNOWLEDGMENTS

The authors are grateful to Mr. Rody Zuidema for help in data collection.

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Keywords:

risk factors; burden; preschool children; influenza-like illness; family study

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