OBJECTIVES:

Respiratory infections (RIs) are an important cause of morbidity and excessive antibiotic prescriptions in children attending day care centers (DCCs). We aimed to assess the effectiveness of an educational and hand hygiene program in DCCs and homes in reducing RI incidence and antibiotic prescriptions in children.

METHODS:

A cluster, randomized, controlled, and open study of 911 children aged 0 to 3 years attending 24 DCCs in Almería (Spain) with an 8-month follow-up. Two intervention groups of DCC families performed educational and hand hygiene measures, 1 with soap and water (SWG; n = 274), another with hand sanitizer (HSG; n = 339), and the control group (CG; n = 298) followed usual hand-washing procedures. RI episode rates were compared through multilevel Poisson regression models. The percentage of days missed were compared with Poisson exact tests.

RESULTS:

There were 5211 RI episodes registered. Children in the HSG had less risk of RI episodes (incidence rate ratio [IRR]: 0.77; 95% confidence interval [CI]: 0.68–0.88) and antibiotic prescriptions (IRR: 0.69; 95% CI: 0.57–0.84) compared with the those in the CG. Children in the SWG had a higher risk of RI episodes (IRR: 1.21; 95% CI: 1.06–1.39) and antibiotic prescriptions (IRR: 1.31; 95% CI: 1.08–1.56) than those in the HSG. Pupils missed 5186 DCC days because of RIs, and the percentage of days absent was significantly lower in the HSG compared with the CG (P < .001) and the SWG (P < .001).

CONCLUSIONS:

Hand hygiene programs that include hand sanitizer and educational measures for DCC staff, children, and parents, reduce absent days, RIs, and antibiotic prescriptions for these infections in children at DCCs.

What’s Known on This Subject:

Children attending day care centers (DCCs) have an increased risk of respiratory infections, according to previous studies. However, it is not clear which factors influence these infections and which measures can be adopted in these centers to reduce their transmission.

What This Study Adds:

This randomized study revealed that a multifactorial hand hygiene program including hand sanitizer and educational measures for DCC staff, children, and parents reduced episodes due to respiratory infections and antibiotic prescriptions for these infections in children attending DCCs.

Respiratory infections (RIs) in children <5 years old are a major public health problem because of their morbidity1,2 and being the most frequent cause of excessive antibiotic prescriptions in the pediatric population, especially from ambulatory care visits.3,4 In addition, attending day care centers (DCCs) increases the risk of these infections1,5,9 and antibiotic prescriptions.9,11 Children attending DCCs have between 6.5 and 10.4 RIs annually.5 A recent study12 revealed great variability in antimicrobial medication use across countries. Spain has 1 of the highest rates in Europe; among children aged 0 to 2 years, the rate of antimicrobial consumption per child-year was 1.55.

Hand-washing is the most important and effective measure to prevent infection transmission.13,14 The bactericide and virucide properties of hydroalcoholic gels or sanitizers against gastrointestinal and respiratory pathogens have been demonstrated.15,18 There are studies in which researchers assess the impact of hand hygiene programs on infectious disease transmission reduction in schools19,24 and households.25,26 However, there are few recent studies that reveal their effectiveness in DCCs,27,31 specifically, those in which researchers examine hand hygiene health education importance for day care staff and parents to reduce infection transmission in DCCs.26,32,33 

Few randomized studies revealing the effectiveness of hand hygiene programs (hand sanitizers versus hand-washing versus a control) linked to a decrease in RIs in DCCs in developed countries have been published. Our aims in this study were to assess the effectiveness of an educational and hand hygiene program in DCCs and homes in reducing the incidence of RIs and antibiotic prescriptions in children at the individual level.

A cluster randomized, controlled, and open study of 3 cohorts of families with children aged 0 to 3 years attending 25 state DCCs in the Almeria metropolitan area (Spain) was designed. The study duration was 8 months (November 2013–June 2014). The Delegation of Education provided the information for 52 state DCCs. These were randomized after the administration of each agreed to participate; 25 DCCs were randomly selected, and after DCCs were assigned to either an intervention group (IG) or the control group (CG) by means of computer randomization with a 1:1:1 ratio, we used statistical software for the selections. Twenty-five randomly assigned DCC administrations informed parents by mail with the following documents: a study information sheet, an authorization form, and a questionnaire about risk factors for RIs (Table 1). Before starting the study, parents authorized their children’s participation and knew which group their children belonged to.

TABLE 1

Risk Factors for RIs Included in the Multilevel Model

Factors
Child  
 Age at the beginning of the study 
 Age at the start of DCC attendance 
 Hours per wk in DCC 
 Sex (female or male) 
 Country of origin 
 Recurrent wheezing 
 Duration of breastfeeding, mo 
 13-valent pneumococcal conjugate vaccine 
 Sleeping arrangements (private or shared bedroom) 
 Siblings at home (0, 1–2, or ≥3) 
Home 
 Family size (≤3, 4–5, or ≥6 people) 
 Mother’s age 
 Father’s age 
 Mother’s professiona (I, II, III, IV, V, VI, VII, VIII, IX, or X) 
 Father’s professiona (I, II, III, IV, V, VI, VII, VIII, IX, or X) 
 Mother’s educational level (low, middle, or high) 
 Father’s educational level (low, middle, or high) 
 Housing (flat, house, semidetached house, or other) 
 Home smoking habits 
Season 
 Month of infection 
DCC  
 Hygiene IG at the DCC (none, soap, or hand sanitizer) 
 Average No. classrooms per DCC 
 Average space per child in classroom (children per square meter) 
 No. children per staff 
Factors
Child  
 Age at the beginning of the study 
 Age at the start of DCC attendance 
 Hours per wk in DCC 
 Sex (female or male) 
 Country of origin 
 Recurrent wheezing 
 Duration of breastfeeding, mo 
 13-valent pneumococcal conjugate vaccine 
 Sleeping arrangements (private or shared bedroom) 
 Siblings at home (0, 1–2, or ≥3) 
Home 
 Family size (≤3, 4–5, or ≥6 people) 
 Mother’s age 
 Father’s age 
 Mother’s professiona (I, II, III, IV, V, VI, VII, VIII, IX, or X) 
 Father’s professiona (I, II, III, IV, V, VI, VII, VIII, IX, or X) 
 Mother’s educational level (low, middle, or high) 
 Father’s educational level (low, middle, or high) 
 Housing (flat, house, semidetached house, or other) 
 Home smoking habits 
Season 
 Month of infection 
DCC  
 Hygiene IG at the DCC (none, soap, or hand sanitizer) 
 Average No. classrooms per DCC 
 Average space per child in classroom (children per square meter) 
 No. children per staff 
a

Professions are according to the European Socioeconomic Classification: I, managers and professionals of a high level; II, managers and professionals of a low level; III, white-collar employees of a high level; IV, small employers and self-employed nonagricultural workers; V, self-employed agricultural workers; VI, supervisors and technicians of a lower rank; VII, workers of services and commerce of a lower rank; VIII, skilled manual workers; IX, unskilled workers; and X, excluded labor market and long-term unemployed.34 

Children between 0 and 3 years old enrolled at the aforementioned DCCs and attending for at least 15 hours per week whose parents and/or guardians had signed an informed consent document were included.

Children with chronic illnesses or medication that could affect their likelihood of contracting an infection were excluded.

A cluster sampling design35 was used with proportional allocation to the size of the cluster. The clusters were the DCCs in Almeria.

There were 52 DCCs, each with an average of 50 children. As in other studies,29 we assume an 11% reduction in the RI incidence rate in the experimental groups with respect to the CG during the study period. Minimum selections of 6 DCCs per group were needed for a statistical power of 80% and a 5% significance level. Note that a 5% variation coefficient was considered, and the average sample size was 30 children per cluster to take into account those families that may not want to participate in the study. Furthermore, an increase of 2 DCCs per group were randomly selected for the CG and the soap-and-water group (SWG) and 3 DCCs for the hand sanitizer group (HSG), with at least 240 children per group for possible losses during the follow-up period. The expected loss to follow-up was higher in HSG because of a possible refusal of parents to apply hand sanitizer on the hands of their children.

One month before beginning the study (October 1–3, 2013), parents and DCC staff assigned to IGs (HSG and SWG) and the CG attended 1-hour hand hygiene workshops, which were designed and taught by researchers. The content included education about hand-washing practices and hand sanitizer use and possible side effects and precautionary measures (only for the HSG).

Children, parents, and DCC staff in the IGs were instructed by the researchers to maintain their usual hand-washing procedures after using the toilet and when their hands were visibly dirty. Both IGs had to follow protocol in the following circumstances: after coming into the classroom; before and after lunch; after playing outside; when they went home; after coughing, sneezing, or blowing their noses; and after diapering. In the HSG and SWG classrooms, hand sanitizer and liquid soap dispensers were installed, respectively, and an informational brochure about when and how to perform hand hygiene was made available, which was also provided to the participating families of both groups. The HSG also received a supply of hand sanitizer, and the SWG received liquid soap, to use at home during the study period. The HSG children were supervised by DCC staff and parents when using the hand sanitizer, and in the case of young children, it was administered by DCC staff and parents. The CG followed usual hand-washing procedures. The research assistant was responsible for providing hand hygiene materials to the DCCs, and they were responsible for giving these to the parents in the IGs. Characteristics of the hand sanitizer included 70% ethyl alcohol (pH = 7.0 to 7.5). The liquid soaps used for hand-washing in the SWG did not contain specific antibacterial components (pH = 5.5).

During the follow-up, 3 identical training sessions per DCC were given 1 month apart, the first 3 on RIs and their treatments and the second 3 on fever. These were organized by researchers for the parents and/or DCC staff of the IGs. Those who were unable to attend training in their own DCC were invited to attend sessions at other centers. The content of the workshops was sent by e-mail to the IGs.

Every 2 weeks, the research assistant and the DCC staff performed the same activities, including stories, songs, and posters in the classrooms and DCCs regarding hand hygiene and infection transmission.

During October 2013, the parents completed the baseline questionnaire and gave it to the DCC staff. Information about DCCs was provided by the staff (Table 1). Beginning on November 1, 2013, the parents of children who suffered RI episodes (with or without DCC absenteeism) reported RI symptoms, antibiotic treatment, contact with medical services, and complementary analyses and gave the completed form to the DCC staff weekly. The research assistant collected the episode sheets from the participating classes weekly and telephoned the parents of absent children to inquire about the cause of their absence. The DCC staff and/or parents in the IGs were asked if the hand sanitizer or soap caused any side effects in the children.

Respiratory illness was defined as the presence of 2 of the following symptoms during 1 day or the presence of 1 of these symptoms for 2 consecutive days25,26: (1) runny nose, (2) stuffy or blocked nose or noisy breathing, (3) cough, (4) feeling hot or feverish or having chills, (5) sore throat, or (6) sneezing.

During follow-up, the research pediatricians extracted RI episode medical data from the Department of Health’s electronic records. The following Anatomic Therapeutic Chemical Classification System (code J01)36 and International Classification of Diseases, Ninth Revision, Clinical Modification37 diagnosis codes were used: nonspecific upper respiratory tract infection (465.9), otitis media (382.9), pharyngotonsillitis (463), lower respiratory tract infections (485 and 486), acute bronchitis (490), and bronchiolitis (466.19). We combined the bronchopneumonia code (485) and pneumonia code (486) under the label “lower respiratory tract infections.” If >1 antibiotic was prescribed during an episode, we used the first prescription for analysis. The final diagnosis was done by the medical researchers on the basis of the symptoms described above and a review of the medical history of children with RIs.

In this study, a DCC absenteeism episode was defined as when a child fails to attend a DCC because of an RI. We also record RI episodes without absenteeism at DCCs. A new RI episode was considered to be the occurrence of an RI after a period of 3 symptom-free days, as in other studies.26,29 The duration of absenteeism was defined as the number of DCC days missed due to an RI, excluding weekends and holidays.

The primary outcome was the RI incidence rate, which was calculated by the number of RI episodes divided by the number of children during the study period. The incidence rate ratio (IRR) is defined as the ratio of RIs between 2 groups.

The secondary outcomes measured were as follows: (1) the presence or absence of at least 1 antibiotic prescription for each new RI episode during the study period (topical antibiotics were excluded), and (2) the percentage of RI absenteeism days in the 3 groups calculated as the ratio of RI absenteeism days to all possible days of attendance. Rates were calculated for the study period. The total possible days of attendance was calculated as the total number of children multiplied by the possible days of attendance.

Children’s sociodemographic and DCC characteristics in the 3 study groups were compared by using χ2 tests, Fisher-Snedecor distribution from analysis of variance, and Welch t and Brown-Forsythe tests with 95% confidence intervals (CIs).

A multilevel Poisson regression model was applied to fit the number of RI events. Two levels were considered: children grouped into classrooms by age (0–1, 1–2, and 2–3 years) and DCC random effect level. In addition, infant random effect was included to take into account overdispersion in the Poisson mode.38,40 We used observation-level random effects to model overdispersion in counting data for ecology and evolution. First, an unadjusted covariate model was applied to check the IRR of RI for each covariate of the study applied. Thus, adjustment for infant group, sex, and age when starting at a DCC was calculated. Finally, a full multivariate model with all variables under study was applied, and model reduction was conducted by using a backward procedure. Covariates were removed if no significant association with the parameter was detected, if no interaction effect with a group was found, and when no change in the rest of the parameters was observed after removal (considering a 30% change as a possible confounder).41,42 Goodness of fit of the model in each step was performed by checking residuals and the Bayesian information criteria. The adjusted IRR from the multivariate model is provided along with its 95% CI. The number of times antibiotics were prescribed was analyzed by using a predicted Poisson regression mixed model with subject random variation to account for overdispersion and DCC as well as classrooms random effects. The percentage of days absent from a DCC was compared with Poisson exact test results.

The statistical tests were performed at a 5% significance level by using SPSS version 19.0 (SPSS, Inc, Chicago, IL) and R version 3.1.3 (R Foundation, Vienna, Austria).

This study was reviewed and approved by the ethical review board for clinical trials at Hospital Torrecardenas (Almeria, Spain), and permission to review medical records was also granted.

Fifty-two DCCs were initially contacted, of which 25 were randomized with 1176 children and 960 (81.63%) had parental participation authorization. Approximately 95% of the children’s parents returned the completed questionnaire and data collection notebook on RIs; the final simple size was 911 children. Approximately 5% of the children did not complete the study; this did not affect the results as confirmed by using nonreported analyses. One child in the HSG showed a worsening of localized atopic dermatitis due to hand sanitizer gel use and was excluded during the follow-up (Fig 1).

FIGURE 1

Participant flow diagram.

FIGURE 1

Participant flow diagram.

Close modal

Table 2 includes the 3 groups’ sociodemographic and DCCs characteristics. Although significant differences between groups were found, among others, the SWG families have a higher proportion with immigrant status, and the parents had lower social class and educational levels. All DCCs met the requirements regarding facilities, material conditions, square meter per child, number of courses per DCC, and number of children per staff member stipulated by the government.43 The potential biases were controlled by including these variables in the multilevel analysis, adjusting the incidence rates of RIs and antibiotic prescriptions by them (Table 1).

TABLE 2

Sociodemographic and DCC Characteristics in Experimental Groups and CGs

CG (N = 298)SWG (N = 274)HSG (N = 339)P
Age at the beginning of the study, mean (SD) 20.67 (7.94) 21.10 (7.73) 21.59 (8.21) .13a 
Age at the start of DCC attendance (SD) 11.32 (5.56) 11.91 (5.79) 12.63 (6.31) .02b 
Hours per wk in a DCC, mean (SD) 27.6 (7) 29.6 (7.7) 28.2 (7.1) .05b 
Duration of breastfeeding in mo, mean (SD) 5.85 (6.45) 6.38 (6.14) 5.83 (6.28) .81a 
Female sex, n (%) 126 (42.28) 146 (53.28) 149 (43.95) .018c 
Immigrant status, n (%) 20 (6.71) 43 (15.69) 20 (5.90) .001c 
Recurrent wheezing, n (%) 47 (15.77) 58 (21.17) 50 (14.75) .086c 
13-valent pneumococcal conjugate vaccine, n (%) 263 (88.26) 191 (69.71) 294 (86.73) <.001c 
Family size, people, n (%)    .050c 
 ≤3 124 (41.61) 108 (39.42) 123 (36.28)  
 >3–≤5 161 (54.03) 137 (50) 187 (55.16)  
 >5 13 (4.36) 29 (10.58) 29 (8.55)  
Siblings at home, n (%)    .017c 
 0 135 (45.30) 117 (42.70) 128 (37.76)  
 1–2 158 (53.02) 139 (50.73) 191 (56.34)  
 ≥3 5 (1.68) 18 (6.57) 20 (5.90)  
Father’s age, mean (SD) 35.4 (6.6) 34.3 (6.7) 35.5 (5.7) .06a 
Mother’s age, mean (SD) 33.1 (5.7) 31.2 (5.7) 33.3 (5.2) .21a 
Father’s educational level, n (%)    <.001c 
 Low 91 (30.06) 108 (40.00) 91 (27.16)  
 Middle 162 (52.29) 114 (42.22) 151 (45.07)  
 High 40 (13.65) 48 (17.78) 93 (27.76)  
Mother’s educational level, n (%)    .002c 
 Low 69 (23.15) 87 (31.75) 78 (23.01)  
 Middle 146 (48.99) 117 (42.70) 134 (39.53)  
 High 83 (27.85) 70 (25.55) 127 (37.46)  
Father’s profession,dn (%)    .002c 
 I–III or VI 74 (25.26) 59 (21.85) 107 (31.94)  
 IV–V 53 (18.09) 43 (15.93) 71 (21.19)  
 VII or X 95 (32.42) 76 (28.15) 74 (22.09)  
 VIII or IX 71 (24.23) 92 (34.07) 83 (24.78)  
Mother’s profession,dn (%)    .001c 
 I–III or VI 93 (31.21) 72 (26.28) 136 (40.12)  
 IV–V 47 (15.77) 34 (12.41) 40 (11.80)  
 VII or X 43 (14.43) 29 (10.58) 44 (12.98)  
 VIII or IX 115 (38.59) 139 (50.73) 119 (35.10)  
Type of dwelling, n (%)    <.001c 
 Flat 226 (75.84) 161 (58.76) 204 (60.18)  
 House 33 (11.07) 68 (24.82) 59 (17.40)  
 Semidetached house 35 (11.74) 44 (16.06) 69 (20.35)  
 Other 4 (1.34) 1 (0.36) 7 (2.06)  
Shared bedroom, n (%) 206 (69.13) 190 (69.34) 214 (63.13) .166c 
Smoking at home, n (%) 63 (21.14) 63 (22.99) 53 (15.63) .054c 
DCC characteristics N = 7 N = 8 N = 9  
 No. classrooms per DCC, mean (SD) 4.9 (3.2) 3.6 (1.9) 3.6 (1.4) .035b 
 Children per square meter of space in classroom, mean (SD) 3.7 (1.7) 3.1 (1.1) 2.8 (1.4) .452a 
 No. children per staff, mean (SD) 6.6 (1.8) 7.2 (2.1) 7.7 (3.1) .029a 
CG (N = 298)SWG (N = 274)HSG (N = 339)P
Age at the beginning of the study, mean (SD) 20.67 (7.94) 21.10 (7.73) 21.59 (8.21) .13a 
Age at the start of DCC attendance (SD) 11.32 (5.56) 11.91 (5.79) 12.63 (6.31) .02b 
Hours per wk in a DCC, mean (SD) 27.6 (7) 29.6 (7.7) 28.2 (7.1) .05b 
Duration of breastfeeding in mo, mean (SD) 5.85 (6.45) 6.38 (6.14) 5.83 (6.28) .81a 
Female sex, n (%) 126 (42.28) 146 (53.28) 149 (43.95) .018c 
Immigrant status, n (%) 20 (6.71) 43 (15.69) 20 (5.90) .001c 
Recurrent wheezing, n (%) 47 (15.77) 58 (21.17) 50 (14.75) .086c 
13-valent pneumococcal conjugate vaccine, n (%) 263 (88.26) 191 (69.71) 294 (86.73) <.001c 
Family size, people, n (%)    .050c 
 ≤3 124 (41.61) 108 (39.42) 123 (36.28)  
 >3–≤5 161 (54.03) 137 (50) 187 (55.16)  
 >5 13 (4.36) 29 (10.58) 29 (8.55)  
Siblings at home, n (%)    .017c 
 0 135 (45.30) 117 (42.70) 128 (37.76)  
 1–2 158 (53.02) 139 (50.73) 191 (56.34)  
 ≥3 5 (1.68) 18 (6.57) 20 (5.90)  
Father’s age, mean (SD) 35.4 (6.6) 34.3 (6.7) 35.5 (5.7) .06a 
Mother’s age, mean (SD) 33.1 (5.7) 31.2 (5.7) 33.3 (5.2) .21a 
Father’s educational level, n (%)    <.001c 
 Low 91 (30.06) 108 (40.00) 91 (27.16)  
 Middle 162 (52.29) 114 (42.22) 151 (45.07)  
 High 40 (13.65) 48 (17.78) 93 (27.76)  
Mother’s educational level, n (%)    .002c 
 Low 69 (23.15) 87 (31.75) 78 (23.01)  
 Middle 146 (48.99) 117 (42.70) 134 (39.53)  
 High 83 (27.85) 70 (25.55) 127 (37.46)  
Father’s profession,dn (%)    .002c 
 I–III or VI 74 (25.26) 59 (21.85) 107 (31.94)  
 IV–V 53 (18.09) 43 (15.93) 71 (21.19)  
 VII or X 95 (32.42) 76 (28.15) 74 (22.09)  
 VIII or IX 71 (24.23) 92 (34.07) 83 (24.78)  
Mother’s profession,dn (%)    .001c 
 I–III or VI 93 (31.21) 72 (26.28) 136 (40.12)  
 IV–V 47 (15.77) 34 (12.41) 40 (11.80)  
 VII or X 43 (14.43) 29 (10.58) 44 (12.98)  
 VIII or IX 115 (38.59) 139 (50.73) 119 (35.10)  
Type of dwelling, n (%)    <.001c 
 Flat 226 (75.84) 161 (58.76) 204 (60.18)  
 House 33 (11.07) 68 (24.82) 59 (17.40)  
 Semidetached house 35 (11.74) 44 (16.06) 69 (20.35)  
 Other 4 (1.34) 1 (0.36) 7 (2.06)  
Shared bedroom, n (%) 206 (69.13) 190 (69.34) 214 (63.13) .166c 
Smoking at home, n (%) 63 (21.14) 63 (22.99) 53 (15.63) .054c 
DCC characteristics N = 7 N = 8 N = 9  
 No. classrooms per DCC, mean (SD) 4.9 (3.2) 3.6 (1.9) 3.6 (1.4) .035b 
 Children per square meter of space in classroom, mean (SD) 3.7 (1.7) 3.1 (1.1) 2.8 (1.4) .452a 
 No. children per staff, mean (SD) 6.6 (1.8) 7.2 (2.1) 7.7 (3.1) .029a 
a

Fisher-Snedecor.

b

Welch t test.

c

χ2 test.

d

Professions are according to the European Socioeconomic Classification: I, managers and professionals of a high level; II, managers and professionals of a low level; III, white-collar employees of a high level; IV, small employers and self-employed nonagricultural workers; V, self-employed agricultural workers; VI, supervisors and technicians of a lower rank; VII, workers of services and commerce of a lower rank; VIII, skilled manual workers; IX, unskilled workers; and X, excluded labor market and long-term unemployed.

During the study period, 5211 RI episodes occurred (1907 CG, 1633 SWG, and 1671 HSG); diagnoses were confirmed by a doctor in 87% of episodes. Antibiotics were prescribed in 39.4% of RIs, 28.20% of nonspecific upper respiratory tract infections, 83.20% of otitis media cases, 87.20% of pharyngotonsillitis cases, 87.50% of lower respiratory tract infections, 16.6% of acute bronchitis cases, and 25% of bronchiolitis cases.

Figure 2 includes the mean RI episodes and antibiotic prescriptions per child and per month. The significant differences between the HSG versus the SWG and CG were found when children had more RI episodes, in winter and late spring.

FIGURE 2

RI episodes and antibiotic prescriptions due to RI means in the CG, SWG, and HSG per child per month at DCCs in Almeria (Spain), November 2013 to June 2014. A, Mean RI episodes per child per month. * P < .05 for the HSG versus CG; P < .05 for the HSG versus SWG. B, Mean antibiotic prescriptions due to RIs per child per month. * P < .05 for the HSG versus CG. ** P < .05 for the HSG versus CG.

FIGURE 2

RI episodes and antibiotic prescriptions due to RI means in the CG, SWG, and HSG per child per month at DCCs in Almeria (Spain), November 2013 to June 2014. A, Mean RI episodes per child per month. * P < .05 for the HSG versus CG; P < .05 for the HSG versus SWG. B, Mean antibiotic prescriptions due to RIs per child per month. * P < .05 for the HSG versus CG. ** P < .05 for the HSG versus CG.

Close modal

Pupils missed 5186 DCC days because of RIs (1891 days for the CG versus 1627 for the SWG versus 1668 for the HSG). The total possible days of attendance were 44 998 (CG), 41 374 (SWG), and 51 189 (HSG). The percentage of RI absenteeism days were significantly lower in the HSG (3.25%; 95% CI: 3.1%–3.4%) compared with the SWG (3.9%; 95% CI: 3.71%–4.09%; P < .001) and CG (4.2%; 95% CI: 4.01%–4.39%; P < .001) and in the SWG versus CG (P = .026).

The adjusted final multivariate model (Table 3) reveals that the adjusted RI episodes rate was significantly lower in the HSG (IRR: 0.77; 95% CI: 0.68–0.88) than the CG; for the SWG, the IRR was ∼21% higher than for the HSG. The adjusted final multivariate model (Table 4) revealed that the IRR for antibiotic prescriptions was significantly lower in the HSG (IRR: 0.69; 95% CI: 0.57–0.84) than the CG; for the SWG, the IRR was ∼30% higher than for the HSG.

TABLE 3

Factors Associated With Episodes Due to RI in Children at DCCs: Multivariate Final Adjustment

VariablesIRR95% CI
Groups   
 SWG versus CG 0.94 0.82–1.08 
 HSG versus CG 0.77* 0.68–0.88 
 SWG versus HSG 1.21* 1.06–1.39 
Age at the start of DCC attendance 1.01 1.01–1.02 
Duration of breastfeeding, mo 0.99** 0.99–1.00 
Mother’s age 0.99* 0.98–0.99 
Female sex 0.98 0.91–1.05 
Recurrent wheezing 1.37* 1.25–1.50 
No 13-valent pneumococcal conjugate vaccine 0.90** 0.81–1.00 
No smoking at home 0.88* 0.80–0.96 
Siblings at home (reference category = 0)   
 1–2 0.94 0.87–1.01 
 3–4 0.81* 0.66–0.98 
VariablesIRR95% CI
Groups   
 SWG versus CG 0.94 0.82–1.08 
 HSG versus CG 0.77* 0.68–0.88 
 SWG versus HSG 1.21* 1.06–1.39 
Age at the start of DCC attendance 1.01 1.01–1.02 
Duration of breastfeeding, mo 0.99** 0.99–1.00 
Mother’s age 0.99* 0.98–0.99 
Female sex 0.98 0.91–1.05 
Recurrent wheezing 1.37* 1.25–1.50 
No 13-valent pneumococcal conjugate vaccine 0.90** 0.81–1.00 
No smoking at home 0.88* 0.80–0.96 
Siblings at home (reference category = 0)   
 1–2 0.94 0.87–1.01 
 3–4 0.81* 0.66–0.98 

The final multilevel analysis was adjusted for age at the start of DCC attendance, sex (female versus male), siblings at home (0 vs 1–2 and ≥3), mother’s age, home smoking habits (no versus yes), children’s recurrent wheezing (yes versus no), history of breastfeeding (mo), and 13-valent pneumococcal conjugate vaccine (no versus yes). The DCC characteristics considered were hygiene IGs at the DCCs (none, soap, or hand sanitizer).

*

P < .05

**

P < .1

TABLE 4

Factors Associated With Antibiotic Prescriptions Due to RIs in Children at DCCs: Multivariate Final Adjustment

VariablesIRR95% CI
Groups   
 SWG versus CG 0.91 0.75–1.10 
 HSG versus CG 0.69* 0.57–0.84 
 SWG versus HSG 1.31* 1.08–1.59 
Age at the start of DCC attendance 1.01* 1.00–1.02 
Duration of breastfeeding 0.99* 0.98–0.99 
Female sex 0.88* 0.79–0.99 
Recurrent wheezing 1.17* 1.02–1.35 
Shared bedroom 1.14* 1.02–1.29 
VariablesIRR95% CI
Groups   
 SWG versus CG 0.91 0.75–1.10 
 HSG versus CG 0.69* 0.57–0.84 
 SWG versus HSG 1.31* 1.08–1.59 
Age at the start of DCC attendance 1.01* 1.00–1.02 
Duration of breastfeeding 0.99* 0.98–0.99 
Female sex 0.88* 0.79–0.99 
Recurrent wheezing 1.17* 1.02–1.35 
Shared bedroom 1.14* 1.02–1.29 

The final multilevel analysis was adjusted for age at the start of DCC attendance, sex (female versus male), recurrent wheezing (yes versus no), history of breastfeeding (mo), and sleeping arrangements (shared bedroom or private). The DCC characteristics considered were hygiene IGs at the DCCs (none, soap, or hand sanitizer).

*

P < .05

With this trial, we support the importance of hand hygiene programs for DCCs and families to reduce RIs and antibiotic prescriptions in children attending DCCs, with relevant repercussions seen in public health and the prevention of bacterial resistance, as other authors state.44,47 

To our knowledge, this study is the first in which researchers measure the individual impacts of hand-washing with soap and hand sanitizer use as well as compare with a CG in DCCs. We found a 21% and 31% higher risk of RI episodes and antibiotic prescriptions, respectively, when belonging to the SWG instead of the HSG. Lennell et al31 separately measure both interventions and found a 12% reduction of absenteeism due to infections in the HSG compared with using soap, probably because of the virucidal effect and greater adherence to the hand hygiene program with hand sanitizer than to the soap-and-water program because educational measures were the same in both groups in our study.

The 23% reduction in RI episodes in the HSG compared with the CG coincides with estimates from previous randomized studies,27,29,48 meta-analyses, and systematic reviews49,50 in diverse populations, revealing that hand hygiene programs decrease RIs between 9% and 21%, especially in the youngest children.51 Researchers of intervention cohorts and other randomized studies52,53 didn’t observe a significant reduction in RI episodes in children attending DCCs related to hand hygiene interventions. Our results may have differed for several reasons. We also collected data on RI episodes with and without DCC absenteeism; 87% had medical diagnoses. Pupils washed their hands more frequently than in previous studies.29,31,52 Families and/or DCC staff used 1660 L of hand sanitizer during the study period; with an expected use of 1 to 2 mL of hand sanitizer per disinfection, we estimated that each child used hand sanitizer between 6 and 8 times per day, a point that is supported by Pandejpong et al.54 To our knowledge, this is the first multicomponent intervention in which researchers provide educational measures and hand hygiene products to DCC staff, children, and parents. Previous studies reveal that the individual measures used in our study are effective. Zomer et al55 showed that DCC staff intervention increased caregiver compliance to a hand hygiene program. Moreover, the use of a hand sanitizer at home can greatly reduce the exposure of family members to viruses in the household.18 The children whose parents attended a health education session about RIs had fewer RIs in comparison with the CG.48 Researchers in a systematic review56 concluded that the effectiveness of hand hygiene interventions varies depending on the setting, the context, and compliance. Interventions to improve hand hygiene in educational settings may reduce RI incidence among younger children.51,57 

Approximately 40% of those with RIs were prescribed antibiotics. The 30% reduction of antibiotic prescriptions for RIs in the HSG compared with the CG in our study correspond with previous reports27,48 of 18% to 24%. Previous researchers44,58,59 found that interventions directed toward parents and/or clinicians can reduce rates of antibiotic prescriptions for RIs in children.

The pupils in the HSG had fewer DCC absence days due to RIs than those in the CG. These results coincide with those from previous studies31,48; this can reduce the use of medical resources and parent work absenteeism.

Families from different socioeconomic levels and countries of origin as well as children who used public and private health services took part in our study, so our findings can be representative of the RI episodes in children at DCCs in our area. These could be generalized in similar DCCs in Spain because most of the RI episodes were diagnosed by a doctor. As other authors indicate,60,61 the risk and protective factors of infections in children at DCCs are difficult to identify, and their importance may vary between societies and countries. Therefore, these results may not be generalizable to DCCs where sociodemographic factors or infrastructure are substantially different.

Future studies are needed to assess which factors of multicomponent interventions may be most effective in reducing infections in children attending DCCs.

Although 87% of those with RI episodes had medical diagnoses, microbiological confirmation wasn’t conducted. Approximately 90% of children <3 years old in Almeria attend state and state-subsidized, privately run DCCs, but we did not have access to exclusively private centers. The number of parents who did not authorize the study was greater in the CG; however, this does not affect the sample size. The absence of masking both participants and researchers was not feasible given the characteristics of this study, so the statistical analyses were masked until completion. We did not monitor compliance to the programs through continuous observation of hand hygiene behaviors in the IGs as is done in most DCC intervention studies30,31,52; however, previous researchers55,62,63 found that individuals might change their behavior when they know they are being observed. Nevertheless, we monitored hand hygiene material consumption in the IGs. Only the IGs received educational intervention, making the relative contributions of education versus hand hygiene in the reduction of RI episodes unattainable in this study.

Hand hygiene programs that include hand sanitizer and educational measures for DCC staff, children, and parents reduce absent days, RIs, and antibiotic prescriptions for these infections in children at DCCs.

     
  • CG

    control group

  •  
  • CI

    confidence interval

  •  
  • DCC

    day care center

  •  
  • HSG

    hand sanitizer group

  •  
  • IG

    intervention group

  •  
  • IRR

    incidence rate ratio

  •  
  • RI

    respiratory infection

  •  
  • SWG

    soap-and-water group

Dr Azor-Martinez conceptualized and designed the study, drafted the initial and final manuscript as submitted, supervised data collection, conducted the statistical analyses, and reviewed and revised the manuscript; Dr Yui-Hifume and Mr Torres-Alegre acquired data, supervised data collection, interpreted the data, and revised the manuscript; Dr Muñoz-Vico participated in the conception and design of the study, interpreted the data, and revised the manuscript; Dr Jimenez-Noguera and Ms Martinez-Martinez acquired and interpreted the data and revised the manuscript; Dr Strizzi conducted the initial analyses, interpreted data, and drafted and critically reviewed the manuscript; Dr Garcia-Fernandez conducted the statistical analyses, interpreted the data, and reviewed and revised the design of the study and the manuscript; Drs Seijas-Vazquez and Fernandez-Campos participated in the conception and design of the study and drafted the manuscript; Dr Gimenez-Sanchez participated in the conception and design of the study, critically reviewed the manuscript, and provided expertise on infectious diseases; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

This trial has been registered at www.clinicaltrials.gov (identifier NCT03294772).

FUNDING: Supported by a grant (PI-0782/2012) from the Andalusia Department of Health.

This work was supported by a grant from the Andalusia Department of Health. We thank the managers of and caregivers at the DCCs, parents at all participating child care centers, and collaborators from the Department of Health and Education of Almeria.

1
Chen
Y
,
Williams
E
,
Kirk
M
.
Risk factors for acute respiratory infection in the Australian community.
PLoS One
.
2014
;
9
(
7
):
e101440
[PubMed]
2
Chonmaitree
T
,
Alvarez-Fernandez
P
,
Jennings
K
, et al
.
Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development.
Clin Infect Dis
.
2015
;
60
(
1
):
1
9
[PubMed]
3
Hersh
AL
,
Shapiro
DJ
,
Pavia
AT
,
Shah
SS
.
Antibiotic prescribing in ambulatory pediatrics in the United States.
Pediatrics
.
2011
;
128
(
6
):
1053
1061
[PubMed]
4
Fleming-Dutra
KE
,
Hersh
AL
,
Shapiro
DJ
, et al
.
Prevalence of inappropriate antibiotic prescriptions among US ambulatory care visits, 2010-2011.
JAMA
.
2016
;
315
(
17
):
1864
1873
[PubMed]
5
Brady
MT
.
Infectious disease in pediatric out-of-home child care.
Am J Infect Control
.
2005
;
33
(
5
):
276
285
[PubMed]
6
Zutavern
A
,
Rzehak
P
,
Brockow
I
, et al;
LISA Study Group
.
Day care in relation to respiratory-tract and gastrointestinal infections in a German birth cohort study.
Acta Paediatr
.
2007
;
96
(
10
):
1494
1499
[PubMed]
7
Côté
SM
,
Petitclerc
A
,
Raynault
MF
, et al
.
Short- and long-term risk of infections as a function of group child care attendance: an 8-year population-based study.
Arch Pediatr Adolesc Med
.
2010
;
164
(
12
):
1132
1137
[PubMed]
8
de Hoog
ML
,
Venekamp
RP
,
van der Ent
CK
, et al
.
Impact of early daycare on healthcare resource use related to upper respiratory tract infections during childhood: prospective WHISTLER cohort study.
BMC Med
.
2014
;
12
:
107
9
Del Castillo-Aguas
G
,
Gallego-Iborra
A
,
Gutiérrez-Olid
M
,
Pérez-González
O
,
Moreno-Muñoz
G
,
Ledesma-Albarrán
JM
.
Infectious morbidity and resource use in children under 2 years old at childcare centres.
J Paediatr Child Health
.
2017
;
53
(
2
):
116
122
[PubMed]
10
Thrane
N
,
Olesen
C
,
Md
JT
,
Søndergaard
C
,
Schønheyder
HC
,
Sørensen
HT
.
Influence of day care attendance on the use of systemic antibiotics in 0- to 2-year-old children.
Pediatrics
.
2001
;
107
(
5
). Available at: www.pediatrics.org/cgi/content/full/107/5/e76
[PubMed]
11
Hedin
K
,
Andre
M
,
Håkansson
A
,
Mölstad
S
,
Rodhe
N
,
Petersson
C
.
Physician consultation and antibiotic prescription in Swedish infants: population-based comparison of group daycare and home care.
Acta Paediatr
.
2007
;
96
(
7
):
1059
1063
[PubMed]
12
Youngster
I
,
Avorn
J
,
Belleudi
V
, et al
.
Antibiotic use in children - a cross-national analysis of 6 countries.
J Pediatr
.
2017
;
182
:
239
244.e1
[PubMed]
13
Boyce
JM
,
Pittet
D
;
Healthcare Infection Control Practices Advisory Committee
;
HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force
.
Guideline for hand hygiene in health-care settings. Recommendations of the Healthcare Infection Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. Society for Healthcare Epidemiology of America/Association for Professionals in Infection Control/Infectious Diseases Society of America.
MMWR Recomm Rep
.
2002
;
51
(
RR–16
):
1
45, quiz CE1–CE4
[PubMed]
14
World Health Organization
. WHO guidelines on hand hygiene in health care. 2009. Available at: http://apps.who.int/iris/bitstream/handle/10665/44102/9789241597906_eng.pdf;jsessionid=7B49BB6C8F91C1E194FA2A843F05871F?sequence=1. Accessed November 14, 2013
15
Fendler
EJ
,
Ali
Y
,
Hammond
BS
,
Lyons
MK
,
Kelley
MB
,
Vowell
NA
.
The impact of alcohol hand sanitizer use on infection rates in an extended care facility.
Am J Infect Control
.
2002
;
30
(
4
):
226
233
[PubMed]
16
Sattar
SA
,
Abebe
M
,
Bueti
AJ
,
Jampani
H
,
Newman
J
,
Hua
S
.
Activity of an alcohol-based hand gel against human adeno-, rhino-, and rotaviruses using the fingerpad method.
Infect Control Hosp Epidemiol
.
2000
;
21
(
8
):
516
519
[PubMed]
17
Kampf
G
,
Kramer
A
.
Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs.
Clin Microbiol Rev
.
2004
;
17
(
4
):
863
893
[PubMed]
18
Tamimi
AH
,
Carlino
S
,
Edmonds
S
,
Gerba
CP
.
Impact of an alcohol-based hand sanitizer intervention on the spread of viruses in homes.
Food Environ Virol
.
2014
;
6
(
2
):
140
144
[PubMed]
19
White
CG
,
Shinder
FS
,
Shinder
AL
,
Dyer
DL
.
Reduction of illness absenteeism in elementary schools using an alcohol-free instant hand sanitizer.
J Sch Nurs
.
2001
;
17
(
5
):
258
265
[PubMed]
20
Bowen
A
,
Ma
H
,
Ou
J
, et al
.
A cluster-randomized controlled trial evaluating the effect of a handwashing-promotion program in Chinese primary schools.
Am J Trop Med Hyg
.
2007
;
76
(
6
):
1166
1173
[PubMed]
21
Sandora
TJ
,
Shih
MC
,
Goldmann
DA
.
Reducing absenteeism from gastrointestinal and respiratory illness in elementary school students: a randomized, controlled trial of an infection-control intervention.
Pediatrics
.
2008
;
121
(
6
). Available at: www.pediatrics.org/cgi/content/full/121/6/e1555
[PubMed]
22
Agolory
SG
,
Barbot
O
,
Averhoff
F
, et al
.
Implementation of non-pharmaceutical interventions by New York City public schools to prevent 2009 influenza A.
PLoS One
.
2013
;
8
(
1
):
e50916
[PubMed]
23
Azor-Martínez
E
,
Gonzalez-Jimenez
Y
,
Seijas-Vazquez
ML
, et al
.
The impact of common infections on school absenteeism during an academic year.
Am J Infect Control
.
2014
;
42
(
6
):
632
637
[PubMed]
24
Azor-Martinez
E
,
Cobos-Carrascosa
E
,
Seijas-Vazquez
ML
, et al
.
Hand hygiene program decreases school absenteeism due to upper respiratory infections.
J Sch Health
.
2016
;
86
(
12
):
873
881
[PubMed]
25
Lee
GM
,
Salomon
JA
,
Friedman
JF
, et al
.
Illness transmission in the home: a possible role for alcohol-based hand gels.
Pediatrics
.
2005
;
115
(
4
):
852
860
[PubMed]
26
Sandora
TJ
,
Taveras
EM
,
Shih
MC
, et al
.
A randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home.
Pediatrics
.
2005
;
116
(
3
):
587
594
[PubMed]
27
Uhari
M
,
Möttönen
M
.
An open randomized controlled trial of infection prevention in child day-care centers.
Pediatr Infect Dis J
.
1999
;
18
(
8
):
672
677
[PubMed]
28
Carabin
H
,
Gyorkos
TW
,
Soto
JC
,
Joseph
L
,
Payment
P
,
Collet
JP
.
Effectiveness of a training program in reducing infections in toddlers attending day care centers.
Epidemiology
.
1999
;
10
(
3
):
219
227
[PubMed]
29
Roberts
L
,
Smith
W
,
Jorm
L
,
Patel
M
,
Douglas
RM
,
McGilchrist
C
.
Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized, controlled trial.
Pediatrics
.
2000
;
105
(
4, pt 1
):
738
742
[PubMed]
30
Pönkä
A
,
Poussa
T
,
Laosmaa
M
.
The effect of enhanced hygiene practices on absences due to infectious diseases among children in day care centers in Helsinki.
Infection
.
2004
;
32
(
1
):
2
7
[PubMed]
31
Lennell
A
,
Kühlmann-Berenzon
S
,
Geli
P
, et al;
Study Group
.
Alcohol-based hand-disinfection reduced children’s absence from Swedish day care centers.
Acta Paediatr
.
2008
;
97
(
12
):
1672
1680
[PubMed]
32
Rosen
L
,
Manor
O
,
Engelhard
D
, et al
.
Can a handwashing intervention make a difference? Results from a randomized controlled trial in Jerusalem preschools.
Prev Med
.
2006
;
42
(
1
):
27
32
[PubMed]
33
Zomer
TP
,
Erasmus
V
,
van Empelen
P
, et al
.
Sociocognitive determinants of observed and self-reported compliance to hand hygiene guidelines in child day care centers.
Am J Infect Control
.
2013
;
41
(
10
):
862
867
[PubMed]
34
Segura del Pozo
J
. Social classes in 21st century Spain (I): The European Socioeconomic Classification (ESeC). Available at: www.madrimasd.org/blogs/salud_publica/2012/02/12/133091. Accessed November 14, 2013
35
Manatunga
AK
,
Hudgens
MG
,
Chen
S
.
Sample size estimation in cluster randomized studies with varying cluster size.
Biom J
.
2001
;
43
(
1
):
75
86
36
WHO Collaborating Centre for Drug Statistic Methodology
. ATC index with DDDs 2014. Available at: www.whocc.no/atc_ddd_index. Accessed December 5, 2014
37
Centers for Disease Control and Prevention
. International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]. Available at: https://www.cdc.gov/nchs/icd/icd9cm.htm. Accessed December 5, 2014
38
Gelman
A
,
Hill
J
.
Data analysis using regression and multilevel/hierarchical models.
JEM
.
2007
;
45
(
1
):
94
97
39
Gardiner
JC
,
Luo
Z
,
Roman
LA
.
Fixed effects, random effects and GEE: what are the differences?
Stat Med
.
2009
;
28
(
2
):
221
239
[PubMed]
40
Harrison
XA
.
Using observation-level random effects to model overdispersion in count data in ecology and evolution.
PeerJ
.
2014
;
2
:
e616
[PubMed]
41
Miettinen
OS
,
Cook
EF
.
Confounding: essence and detection.
Am J Epidemiol
.
1981
;
114
(
4
):
593
603
[PubMed]
42
Hak
E
,
Verheij
TJ
,
Grobbee
DE
,
Nichol
KL
,
Hoes
AW
.
Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications.
J Epidemiol Community Health
.
2002
;
56
(
12
):
951
955
[PubMed]
43
BOJA
. Decreto 149/2009 de 12 de mayo, por el que se regulan los centros que imparten el primer ciclo de educación infantil. Available at: www.juntadeandalucia.es/boja/2009/92/boletin.92.pdf. Accessed June 15, 2012
44
Francis
NA
,
Butler
CC
,
Hood
K
,
Simpson
SA
,
Wood
F
,
Nuttall
J
.
Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial.
BMJ
.
2009
;
339
(
7717
):
b2885
45
Costelloe
C
,
Metcalfe
C
,
Lovering
A
,
Mant
D
,
Hay
AD
.
Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis.
BMJ
.
2010
;
340
:
c2096
[PubMed]
46
Chavanet
P
,
Atale
A
,
Mahy
S
, et al
.
Nasopharyngeal carriage, antibiotic susceptibility and serotyping of Streptococcus pneumoniae and Haemophilus influenzae in children attending day care centers [in French].
Med Mal Infect
.
2011
;
41
(
6
):
307
317
[PubMed]
47
Bryce
A
,
Hay
AD
,
Lane
IF
,
Thornton
HV
,
Wootton
M
,
Costelloe
C
.
Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis.
BMJ
.
2016
;
352
:
i939
48
Alexandrino
AS
,
Santos
R
,
Melo
C
,
Bastos
JM
.
Impact of caregivers’ education regarding respiratory infections on the health status of day-care children: a randomized trial.
Fam Pract
.
2016
;
33
(
5
):
476
481
[PubMed]
49
Rabie
T
,
Curtis
V
.
Handwashing and risk of respiratory infections: a quantitative systematic review.
Trop Med Int Health
.
2006
;
11
(
3
):
258
267
[PubMed]
50
Aiello
AE
,
Coulborn
RM
,
Perez
V
,
Larson
EL
.
Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis.
Am J Public Health
.
2008
;
98
(
8
):
1372
1381
[PubMed]
51
Jefferson
T
,
Del Mar
CB
,
Dooley
L
, et al
.
Physical interventions to interrupt or reduce the spread of respiratory viruses.
Cochrane Database Syst Rev
.
2011
;(
7
):
CD006207
52
Gudnason
T
,
Hrafnkelsson
B
,
Laxdal
B
,
Kristinsson
KG
.
Does hygiene intervention at day care centres reduce infectious illnesses in children? An intervention cohort study.
Scand J Infect Dis
.
2013
;
45
(
5
):
397
403
[PubMed]
53
Zomer
TP
,
Erasmus
V
,
Looman
CW
, et al
.
A hand hygiene intervention to reduce infections in child daycare: a randomized controlled trial.
Epidemiol Infect
.
2015
;
143
(
12
):
2494
2502
[PubMed]
54
Pandejpong
D
,
Danchaivijitr
S
,
Vanprapa
N
,
Pandejpong
T
,
Cook
EF
.
Appropriate time-interval application of alcohol hand gel on reducing influenza-like illness among preschool children: a randomized, controlled trial.
Am J Infect Control
.
2012
;
40
(
6
):
507
511
[PubMed]
55
Zomer
TP
,
Erasmus
V
,
Looman
CW
, et al
.
Improving hand hygiene compliance in child daycare centres: a randomized controlled trial.
Epidemiol Infect
.
2016
;
144
(
12
):
2552
2560
[PubMed]
56
Warren-Gash
C
,
Fragaszy
E
,
Hayward
AC
.
Hand hygiene to reduce community transmission of influenza and acute respiratory tract infection: a systematic review.
Influenza Other Respir Viruses
.
2013
;
7
(
5
):
738
749
[PubMed]
57
Willmott
M
,
Nicholson
A
,
Busse
H
,
MacArthur
GJ
,
Brookes
S
,
Campbell
R
.
Effectiveness of hand hygiene interventions in reducing illness absence among children in educational settings: a systematic review and meta-analysis.
Arch Dis Child
.
2016
;
101
(
1
):
42
50
[PubMed]
58
Andrews
T
,
Thompson
M
,
Buckley
DI
, et al
.
Interventions to influence consulting and antibiotic use for acute respiratory tract infections in children: a systematic review and meta-analysis.
PLoS One
.
2012
;
7
(
1
):
e30334
[PubMed]
59
Vodicka
TA
,
Thompson
M
,
Lucas
P
, et al;
TARGET Programme Team
.
Reducing antibiotic prescribing for children with respiratory tract infections in primary care: a systematic review.
Br J Gen Pract
.
2013
;
63
(
612
):
e445
e454
[PubMed]
60
Hatakka
K
,
Piirainen
L
,
Pohjavuori
S
,
Poussa
T
,
Savilahti
E
,
Korpela
R
.
Factors associated with acute respiratory illness in day care children.
Scand J Infect Dis
.
2010
;
42
(
9
):
704
711
[PubMed]
61
Gudnason
T
,
Hrafnkelsson
B
,
Laxdal
B
,
Kristinsson
KG
.
Can risk factors for infectious illnesses in children at day care centres be identified?
Scand J Infect Dis
.
2012
;
44
(
2
):
149
156
[PubMed]
62
Sax
H
,
Allegranzi
B
,
Chraïti
MN
,
Boyce
J
,
Larson
E
,
Pittet
D
.
The World Health Organization hand hygiene observation method.
Am J Infect Control
.
2009
;
37
(
10
):
827
834
[PubMed]
63
van Beeck
AH
,
Zomer
TP
,
van Beeck
EF
,
Richardus
JH
,
Voeten
HA
,
Erasmus
V
.
Children’s hand hygiene behaviour and available facilities: an observational study in Dutch day care centres.
Eur J Public Health
.
2016
;
26
(
2
):
297
300
[PubMed]

Competing Interests

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

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