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Can a handwashing intervention make a difference? Results from a randomized controlled trial in Jerusalem preschools
Preventive Medicine 42 (2006) 27 – 32 www.elsevier.com/locate/ypmed
Can a handwashing intervention make a difference? Results from a randomized controlled trial in Jerusalem preschools Laura Rosen a,*, Orly Manor a, Dan Engelhard b, David Brody c, Bruce Rosen d, Hannah Peleg e, Marina Meir f, David Zucker g a
Hebrew University School of Public Health, P.O.B. 12272, Jerusalem 91120, Israel b Hadassah Hebrew University Hospital, Israel c Efrata Teacher’s College, Israel d JDC – Brookdale Institute, Israel e Israel Ministry of Health, Israel f Department of Public Health, Municipality of Jerusalem, Israel g Hebrew University, Department of Statistics, Israel Available online 21 November 2005
Abstract Background. Preschools are often focal points for the spread of illness among young children. The objective of this preschool intervention trial was to determine whether a hygiene program can promote handwashing and thereby reduce illness absenteeism. Methods. This cluster randomized trial included 40 Jerusalem preschools with 1029 children for 6 baseline days and 66 study days, yielding 73,779 child days. The main outcomes were rates of handwashing and illness absenteeism. The intervention included an educational program and environmental changes. A simultaneous subtrial was run to test a home component. Results. This multi-site intervention program produced sustained behavioral and environmental changes over a 6-month period. An approximately threefold increase in handwashing with soap was observed among preschool children exposed to the intervention. Neither the preschool nor the home intervention program reduced illness absenteeism or overall absenteeism. Conclusions. This trial illuminates the potential of the preschool as a promising venue for health promotion activities leading to sustained behavioral change, yet suggests the need for enhanced approaches for reducing illness absenteeism. D 2005 Elsevier Inc. All rights reserved. Keywords: Handwashing; Randomized controlled trial; Health promotion; Health education; Community intervention trial; Communicable disease prevention; Pediatric communicable disease; Preschool illness absenteeism
Introduction Communicable diseases, particularly lower respiratory infections and diarrhea, remain a major burden [1,2]. Schools and day care centers have repeatedly been implicated in the spread of communicable disease, both among the children themselves and among their families and communities [3,4]. Much attention has been given to handwashing as a means to prevent infection, particularly in hospitals [5]. A metaanalysis [1] found a 47% reduction in diarrhea in communitybased handwashing trials. In the past two decades, nine
controlled trials in schools or daycare centers [6 –14] have examined the effects of hand hygiene programs on illness absenteeism. While many of the trials exhibited significant decreases in illness absenteeism [7,8,10 – 13], most have serious methodological flaws. Of the trials just cited, only one [9] was a properly randomized trial whose analysis followed the intent-to-treat principle and accounted for the clustered nature of the data. The aim of our trial was to test a handwashing program for preschool children in a rigorous way, avoiding the deficiencies of other trials. Methods
* Corresponding author. Fax: +972 2 675 8803. E-mail address: [email protected] (L. Rosen). 0091-7435/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2005.09.012
The primary objective of this trial was to evaluate the effects of a comprehensive hygiene program on handwashing and illness absenteeism in
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L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
public preschools. A cluster randomization design was employed, with randomization at the level of the preschool, stratified by sector (secular and religious). All preschool teachers of 3- and 4-year-old children in the state-run public system of the Jerusalem region were potentially eligible for inclusion. Preschool teachers likely to comply with the trial protocol were recommended by Ministry of Education officials and were invited to join the project. Recommended teachers included 60% of eligible teachers, and this could have been increased if resources had permitted. Nearly 90% of invited teachers agreed to join. Teachers from the 40 admitted preschools were then randomized within each sector to preschool intervention and control groups on the basis of computer-generated random numbers. Twenty preschools were randomized to the intervention group and twenty to the control group. A total of 1029 children from 40 preschools were entered. The trial included 6 baseline days and 66 study days, yielding 73,779 child days. Afterward, the program was run in the control preschools, which made the trial more ethically acceptable and attractive to participants. A concurrent subtrial was run to test a home intervention on overall and illness absenteeism. This subtrial included 469 families. Randomization for this subtrial was performed by using computer-generated random numbers and was done at the family level within each intervention group preschool (a few families had two children in the same preschool). Only parents who agreed to participate were contacted. Institutional Review Board approval was obtained from the Hadassah Ethics Committee.
Intervention program The goal of the intervention was to improve hygiene: the main emphasis was on handwashing with soap before eating and after bathroom use, and the secondary emphasis was on eliminating shared cups and towels. The program development was overseen by an early childhood education expert. The program is fully described elsewhere [15]. Education professionals were hired and trained to coordinate the intervention. Children were encouraged to wash hands for at least 10 s, which they timed by singing the project’s special handwashing song. The program aimed to influence individual and group behavior and improve prevailing social norms. Frontal lectures by medical, epidemiological, and educational experts were delivered to the preschool educators, along with printed materials and experiential learning. The techniques used with the children included puppet theatre, a self-reward system, games, posters, puzzles, a video, and presentations by school nurses. Environmental changes included installing liquid soap dispensers, paper towel dispensers, and cup racks, providing individual cups, and supplying liquid soap and paper towels. An identical set of supplies was provided to each classroom. The bulk of program implementation in the intervention group (the first seminar for the educators, the puppet show, and the initiation of the environmental changes) occurred after the baseline measurements on behavior and absenteeism but before the start of the main survey. The classroom educational materials were meant for use just after the puppet show, but their actual use was at the discretion of the educators. Control group participants did not receive any supplies, educational materials, or seminars until the close of the study period. The home component, which included a video, a card, and a magnet, was sent home with the children in individually labeled packages about a month after the preschool intervention was launched. The home intervention materials dealt with handwashing, while the home control materials dealt with toothbrushing. Timing of use of these materials was at the discretion of the families.
Sample size calculations Sample size was calculated to detect a 25% drop in illness absenteeism with power of 80% and a two-sided alpha level of 0.05, given a control group illness absenteeism rate of 6% per child day. A 60-day study period was decided upon based on logistic considerations (during the trial, this was extended to 66 days). Sample size was calculated using a modified version of Zucker’s [16] Eq. (8), involving the intraclass correlation coefficient (estimated at 0.0274) and the between day correlation coefficient (estimated at 0.0548). The calculated sample size was 36 preschools. This was rounded up to 40 preschools. Sample size for the home intervention was calculated to detect an illness absenteeism
reduction from 4.5% to 3.0%, with power of 80% and a two-sided alpha level of 0.05. Since the home intervention began some time after the preschool program, the study period was 35 days. The required sample size was 204 families per arm. The number of available families whose children were exposed to the preschool intervention was 469, yielding a power of 85% to detect a 33% change in event rate, and a power of 59% to detect a 25% change in event rate. The various parameters entering into the sample size calculations were estimated from previous studies [6 – 8]. See [15] for details.
Main outcome measures Overall absenteeism included absences from preschool for any reason. Illness absenteeism included absences that were determined to be illness related, based on combined information from parents and educators [15]. The main behavioral outcomes were percent of children in each preschool washing hands with soap before eating lunch and percent of children washing hands with soap after bathroom use.
Data collection methods Project staff visited the preschools to obtain information on the handwashing behavior of the children and existing hygienic conditions. Observer visits took place before and after program implementation in all preschools. Each visit lasted for several hours, during which time the project staff observed and recorded the children’s handwashing behavior and the availability of supplies (soap, towels, cups, and dispensers). The planned schedule included one baseline and 3 post-intervention visits in the preschool intervention group, and 2 baseline visits and one post-intervention visit in the preschool control group (which received the intervention after the trial period). There were 140 planned visits. Of these, 137 (97.9%) took place, and 3 were omitted due to logistical reasons. Study personnel collected daily absenteeism data by telephone from the educators using a structured questionnaire. Each absence was classified as due to illness, for unknown reason, or for reason unrelated to illness. If a child was absent due to illness or for an unknown reason, an attempt was made to contact the parents in the evening to clarify the reason for the absence, including the specific illness if the absence was illness related. Participating parents also underwent a one-time phone interview for socioeconomic and demographic information, as well as information on the health of the child in the study. In an attempt to avoid bias, the educators, parents, and field research staff were ‘‘blinded’’ to the study design in the sense that they were not told that the study included ‘‘intervention’’ and ‘‘control’’ groups that were being compared with respect to handwashing behavior and absenteeism. They were told simply that the children were being included in a health study and would receive a special program that would be delivered to different preschools at different times. In addition, the field research staff were blinded to the allocation status of the preschools, although they sometimes became aware that the program was being run in a certain preschool.
Statistical analysis Baseline handwashing rates, environmental conditions, sociodemographic characteristics, and absenteeism rates were compared between the study groups using analysis of variance, the mixed linear model [17], Fisher’s Exact Test, or generalized estimating equations analysis [17] (see Table 1). The preschool intervention effect on handwashing was analyzed using analysis of covariance, adjusting for religious sector and baseline handwashing levels. The mediumterm effect of the program was assessed by comparing Visit 3 in the Intervention Group (about 3 months after program launch) with Visit 2 in the Control Group (just before the end of the main study period). The longer term effect of the program was assessed by comparing Visit 4 in the Intervention Group (about 6 months after program launch) with Visit 2 in the Control Group. The preschool intervention effect on overall and illness absenteeism was analyzed in terms of the percentage of days the child was absent, or absent due to illness, during the study period. The analysis was performed on an intent-totreat basis. The mixed linear model was used, with study group and sector as fixed effects and preschool as a random effect. The model also included (as
L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
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Table 1 Jerusalem Handwashing Trial 2000 – 2001: comparisons of selected key variables at baseline Level Preschool
Family
Child
a b c d
Variable a
Average percent of children per preschool using soap before lunch Average percent of children per preschool using soap after bathrooma Average percent absenteeism (per child day)b Average percent illness absenteeism (per child day)b Percent of preschools with soap availablec Percent of preschools with cloth towelsc Percent of preschools with shared cupsc Crowding (number persons per room)b Years of maternal educationb Years of paternal educationb Percent of children in single parent householdd Percent of children with employed mothersd Percent of children with ‘‘very good’’ general health statusd Percent of children with no chronic health conditionsd Percent of children attending afternoon programd
Intervention group
Control group
N
P value
25 12 6.1 3.0 90 80 77 1.4 14 14 10 71 69 92 35
11 12 6.4 3.8 79 47 75 1.3 14 14 11 77 70 91 43
39 preschools 39 preschools 1029 children for 6 days 1029 children for 6 days 39 preschools 39 preschools 35 preschools 891 children 886 children 856 children 895 children 877 children 903 children 894 children 902 children
0.09 0.97 0.87 0.49 0.38 0.05 0.56 0.08 0.69 0.49 0.61 0.04 0.80 0.89 0.10
Analysis of covariance. Mixed linear model. Fisher’s Exact Test. Generalized estimating equations.
fixed effects) the relevant baseline absenteeism rate and various child-level, family-level, and preschool-level background factors (see [15]). The effect of the home intervention on overall and illness absenteeism was analyzed using analysis of covariance, with home intervention status, preschool, the relevant baseline absenteeism rate, various child-level, family-level, and preschool-level background factors (see [15]).
Results Participation and compliance Educator recruitment rates and parental participation rates of the survey were very high (at least 88% of educators and 95% of parents). Dropout and loss to follow-up were minimal: no dropout of preschools occurred, dropout of children was 0.9%, and loss to follow-up of children was 0.7%. During the study, two intervention group preschools were unexpectedly exposed to raw sewage due to faulty plumbing. A sensitivity analysis excluding those preschools was conducted, and results were unchanged. Assessing the effects of behavioral interventions is often difficult due to poor compliance in the treatment group [18] and contamination in the control group, particularly in community trials [19]. In this study, compliance with the program in the intervention group was good but imperfect, and
contamination of the control group was minimal, as seem by comparing the control group handwashing rates at the beginning and the end of the main study period (before the program was run in the control group; generalized estimating equations, P = 0.3916, handwashing before lunch, and, P = 0.3981, handwashing after bathroom) [15]. Monitoring procedures for absenteeism were identical in the two groups, and no between-group differences were found in the validity of the reported information [15]. Baseline comparability Table 1 presents baseline comparisons of handwashing rates, absenteeism, illness absenteeism, and selected key background variables. There were few notable baseline differences between the groups. Comparisons on 17 additional background variables were conducted [15], none of which reached the P = 0.05 level of significance. Effect of the preschool intervention Table 2 presents data on behavioral changes by intervention group and educational sector over time. The baseline rates of
Table 2 Jerusalem Handwashing Trial 2000 – 2001: average percent of children handwashing in each preschool, by educational sector and intervention group Educational sector
Soap before lunch Soap after bathroom
Intervention group
Religious Secular Combined Religious Secular Combined
Control group
Preintervention visit Nov00 – Dec00
Post-intervention visit 1 Jan01 – Feb01
Post-intervention visit 2 Mar 01 – Apr 01
Post-intervention visit 3 May01 – Jun0
Preintervention visit 1 Nov00 – Dec00
Preintervention visit 2 Apr 01 – May01
Post-intervention visit Jun01
11 36 25 12 12 12
60 72 67 44 44 44
48 71 60 46 41 43
43 76 61 48 46 47
00 23 11 10 14 12
04 31 18 12 16 14
60 79 70 52 31 41
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L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
Table 3 Jerusalem Handwashing Trial 2000 – 2001: average per-day percentage of overall and illness absenteeism by preschool intervention group Type of absenteeism
Educational sector
Intervention group
Control group
All
Overall
Religious Secular Combined Religious Secular Combined
4.83 7.62 6.32 2.83 3.91 3.40
4.06 7.64 5.83 2.05 4.20 3.11
4.41 7.63 6.06 2.40 4.06 3.25
Illness
(N (N (N (N (N (N
= = = = = =
229) 260) 489) 229) 260) 489)
(N (N (N (N (N (N
= = = = = =
273) 267) 540) 273) 267) 540)
(N (N (N (N (N (N
= = = = = =
502) 527) 1029) 502) 527) 1029)
Intraclass correlation coefficient: overall absenteeism: 0.0634, illness absenteeism: 0.0747. Between day correlation: overall absenteeism: 0.0713, illness absenteeism: 0.0417.
handwashing with soap were low. In the religious sector, this was partly due to the practice of ritual handwashing before meals with water alone. The intervention had a significant effect on both the medium and longer term behavior. For handwashing after lunch, the medium-term adjusted relative risk (adjusted RR) was 2.77 (CI:[1.70,7.46], P < 0.01), while the long-term adjusted RR was 2.93 (CI:[1.86,6.97], P < 0.01). For handwashing after bathroom use, the medium-term adjusted RR was 2.90 (CI:[1.69,10.06], P < 0.01), while the long-term adjusted RR was 3.30 (CI:[1.83,16.67] P < 0.01). Table 3 presents average daily percentages of overall and illness absenteeism. There was no evidence of an intervention effect on absenteeism (adjusted RR = 1.00, CI: [0.90,1.14], P = 0.97) or illness absenteeism (adjusted RR = 1.00, CI: [0.81,1.32], P = 0.97). Effect of the home intervention Because handwashing data were available only at the level of the preschool and not at the level of the individual child, it was not possible to analyze the effect of the home intervention on handwashing. Table 4 presents the absenteeism and illness absenteeism data. The home component did not affect overall absenteeism (adjusted RR = 0.93, CI: [0.82,1.07], P = 0.28) or illness absenteeism (adjusted RR = 0.94, CI: [0.76,1.23], P = 0.57). Discussion This was the largest and most comprehensive randomized field trial of a hand hygiene intervention ever reported among toilet-trained preschool children. The design overcame methodological problems commonly seen in hand hygiene and community health trials, through cluster randomization and appropriate statistical analyses. For the first time in a school/
daycare-based trial, a home component was introduced and tested in an embedded individually randomized subtrial, which proved an efficient way to test a home component. The excellent medium-term and longer term behavioral results showed that health behavior change is achievable in a large and heterogeneous population in disparate locations. These results, along with the enthusiasm of the educators, illuminate the potential of the preschool as a promising venue for health promotion activities. The combination of cluster randomization with delayed delivery in the control group, which has previously been reported [9,20] but is not in widespread use, was an extremely useful design. Recruitment was very successful, with over 95% of the parents agreeing to cooperate and nearly 90% of invited educators joining the program, even with the demands of the research. None of the preschools dropped out of the trial, and only 0.9% of parents dropped out of the survey. The program was received enthusiastically by upper-echelon administrators, educators, children, and parents. Subsequent demand for the program has been high. The study’s internal validity can be regarded as high, in view of the trial’s cluster randomization design, baseline between-group balance on the response variable and potential confounding variables, identical monitoring procedures, similar reporting rates in the two groups, reasonable levels of behavioral compliance, low contamination rates, and blinding of observers to study design and treatment allocation. External validity was also high. Inclusion criteria for the preschools were broad, so that most Jerusalem preschools serving the relevant age groups and educational streams in the state-run school system were eligible. Most of the educators who were contacted agreed to participate. As indicated above, the program enjoyed a high level of program acceptability to the target population. Thus, the study results are generalizable
Table 4 Jerusalem Handwashing Trial 2000 – 2001: average per-day percentage of overall and illness absenteeism by home intervention group Type of absenteeism
Educational sector
Overall
Religious Secular Combined Religious Secular Combined
Illness related
Home component intervention group
Home component control group
All
Mean
Mean
Mean
4.07 6.72 5.47 2.22 3.54 2.92
(N (N (N (N (N (N
= = = = = =
112) 125) 237) 112) 125) 237)
4.19 7.54 5.99 2.31 3.67 3.04
(N (N (N (N (N (N
= = = = = =
107) 125) 232) 107) 125) 232)
4.13 7.13 5.73 2.26 3.61 2.98
(N (N (N (N (N (N
= = = = = =
219) 250) 469) 219) 250) 469)
L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
to preschools in the Israeli state-run secular and religious streams. The study was limited in that it did not directly assess intervention effects on illness. Overall and illness absenteeism were not affected by either the preschool intervention or the home intervention. Of the nine controlled trials [6 –14] that examined the effects of hand hygiene on illness absenteeism in educational settings, six [7,8,10 –13] found a reduction in illness absenteeism, and one [14] found a reduction among younger children only. Both of the studies that found no reduction [6,9] were randomized. Of the six studies with positive results, only one of them was randomized [11]. Moreover, the analysis in this trial was not an intent-to-treat analysis but instead included only the 44% of classrooms with high compliance, and so the findings are prone to bias. Noncompliant schools were also excluded from analysis in [12]. Several additional factors further compromise some of the published evidence. In only three of the trials [9,12,14] did the analysis account for the clustered nature of the data. Thus, of the nine controlled trials, only one [9] was a properly randomized study whose analysis followed the intent-to-treat principle and accounted for cluster effects; in that study, no effect of the intervention on illness absenteeism was found. Thus, as regards the hypothesis that a hand hygiene program can reduce illness absenteeism in an educational setting, the published evidence is weak. The disparities between our results and most published results may be an illustration of the ‘‘stainless steel rule of evaluation’’ [21], which states that the better the evaluation, the less likely it is to find a positive result. Other factors may also have been at play. Different hand hygiene regimes or increased demand for hand hygiene may have affected results of other trials. The type of communicable disease present in the community at the time of the trial may have played a role, as the reduction in diarrhea due to handwashing has been estimated at 47% [1], while the reduction in upper respiratory infections due to handwashing has been estimated at 20% [22]. In the our trial, the rate of absenteeism due to gastrointestinal illnesses was 17%, as opposed to the 39% rate in [10] and the 29% rate in [11]. During our study period, diarrhea rates in Jerusalem were very low [23]. A higher base rate of gastrointestinal disease may have led to a stronger program effect on illness absenteeism. The reason for the lack of change in illness absenteeism rates in our trial, despite substantial behavioral improvement, is unclear. Given the strength of the existing evidence regarding the relationship between handwashing and illness [see [24] for a recent example], one likely explanation is that illness rates changed but not illness absenteeism rates; this may have occurred if many of the illnesses were mild enough so that the affected children did not stay home from preschool. Indeed, in the Roberts trial [9], a handwashing program was found to affect illness rates but not illness absenteeism rates. Conclusions This is the first report showing that a hygiene program can produce a sustained increase in handwashing rates among
31
toilet-trained preschool children at a large number of geographically disparate locations. The program did not reduce overall or illness absenteeism. The findings illuminate the potential of the preschool as a promising venue for health promotion activities leading to sustained behavioral change, while suggesting the need for enhanced and/or alternative approaches to illness absenteeism reduction. Acknowledgments The authors gratefully acknowledge grants received from The Chief Scientist’s Office of the Ministry of Health; Associate Director General’s Unit for Health Promotion of the Ministry of Health; and the National Institute for Health Services Research. We are also indebted to the Preschool and Public Health Departments of the Municipality of Jerusalem for logistical assistance. References [1] Curtis V, Cairncross S. Effect of washing hands with soap on diarrhoea risk in the community: a systematic review. Lancet, Infect Dis 2003;3: 275 – 81. [2] Murray JL, Lopez AD. Summary: the global burden of disease. WHO; 1996. [3] Fox JP, Hall CE. Viruses in families: surveillance of families as a key to epidemiology of virus infections. MA’ PSG Publishing Company; 1980. [4] Jordan W, Badger G, Curtiss C, Dingle J, Ginsberg S, Gold E. A study of illness in a group of Cleveland families X. Am J Hyg 1956;64:336 – 48. [5] Larson E. A causal link between handwashing and risk of infection? Examination of the evidence. Infect Control Hosp Epidemiol 1988;9:28 – 36. [6] Courtney K. The effect of a handwashing education program on illnessrelated absenteeism and attitudes toward handwashing [dissertation]. UMI Dissertation Information Service, 1995. [7] Kimel LS. Handwashing education can decrease illness absenteeism. J Sch Nurs 1996;12:14 – 6. [8] Master D, Longe SH, Dickson H. Scheduled handwashing in an elementary school population. Fam Med 1997;29:336 – 9. [9] Roberts L, Smith W, Jorm L, Patel M, Douglas R, McGilchrist C. Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized controlled trial. Pediatrics 2000;105:738 – 42. [10] Dyer D, Shinder D, Shinder F. Alcohol-free instant hand sanitizer reduces elementary school illness absenteeism. Fam Med 2000;32:633 – 8. [11] White C, Shinder F, Shinder A, Dyer D. Reduction of illness absenteeism in elementary schools using an alcohol-free instant hand sanitizer. J Sch Nurs 2001;17:258 – 65. [12] Hammond B, Ali Y, Fendler E, Dolan M, Donovan S. Effect of hand sanitizer use on elementary school absenteeism. AJIC 2000;28:340 – 6. [13] Guinan M, McGuckin M, Ali Y. The effect of a comprehensive handwashing program on absenteeism in elementary schools. AJIC 2002;30:217 – 20. [14] Ponka 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;32:2 – 7. [15] Rosen L. A controlled trial to assess the effect of a health promotion intervention on hygiene behavior and absenteeism in Jerusalem preschools. [Dissertation: Hebrew University, 2004]. [16] Zucker DM. Cluster randomization. In: Geller N, editor. Contemporary biostatistical methods in clinical trials. New York’ Marcel Dekker; 2000. [17] Murray D. Design and analysis of group randomized trials. Oxford Univ. Press; 1998. [18] Friedman L, Furberg C, DeMets D. Fundamentals of clinical trials. 3rd ed. New York’ Springer; 1998. [19] Donner A, Klar N. Design and analysis of cluster randomization trials in health research. USA’ Oxford Univ. Press; 2000.
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[20] Gortmaker SL, Peterson K, Wiecha J, Sobol A, Dixit S, Fox M, et al. Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health. Arch Pediatr Adolec Med 1999;153:409 – 18. [21] Petticrew M. Why certain systematic reviews reach uncertain conclusions. BMJ 2003;326:756 – 8. [22] Carabin H, Gyorkos T, Soto J, Joseph L, Payment P, Collet JP. Effectiveness of a training program in reducing infections in toddlers attending day care centers. Epidemiology 1999;10:219 – 27.
[23] Cohen D, Basal R, Vilenski L, et al. The cyclical nature of shigellosis outbreaks in Israel. Presented at the Annual Conference of the Israel Center for Disease Control, November 2004, Tel Aviv. [24] Luby S, Agboatwalla M, Painter J, Altaf A, Billhimer W, Hoekstra R. Effect of intensive handwashing promotion on childhood diarrhea in highrisk communities in Pakistan: a randomized controlled trial. JAMA 2004;291:2547 – 54.
Can a handwashing intervention make a difference? Results from a randomized controlled trial in Jerusalem preschools Laura Rosen a,*, Orly Manor a, Dan Engelhard b, David Brody c, Bruce Rosen d, Hannah Peleg e, Marina Meir f, David Zucker g a
Hebrew University School of Public Health, P.O.B. 12272, Jerusalem 91120, Israel b Hadassah Hebrew University Hospital, Israel c Efrata Teacher’s College, Israel d JDC – Brookdale Institute, Israel e Israel Ministry of Health, Israel f Department of Public Health, Municipality of Jerusalem, Israel g Hebrew University, Department of Statistics, Israel Available online 21 November 2005
Abstract Background. Preschools are often focal points for the spread of illness among young children. The objective of this preschool intervention trial was to determine whether a hygiene program can promote handwashing and thereby reduce illness absenteeism. Methods. This cluster randomized trial included 40 Jerusalem preschools with 1029 children for 6 baseline days and 66 study days, yielding 73,779 child days. The main outcomes were rates of handwashing and illness absenteeism. The intervention included an educational program and environmental changes. A simultaneous subtrial was run to test a home component. Results. This multi-site intervention program produced sustained behavioral and environmental changes over a 6-month period. An approximately threefold increase in handwashing with soap was observed among preschool children exposed to the intervention. Neither the preschool nor the home intervention program reduced illness absenteeism or overall absenteeism. Conclusions. This trial illuminates the potential of the preschool as a promising venue for health promotion activities leading to sustained behavioral change, yet suggests the need for enhanced approaches for reducing illness absenteeism. D 2005 Elsevier Inc. All rights reserved. Keywords: Handwashing; Randomized controlled trial; Health promotion; Health education; Community intervention trial; Communicable disease prevention; Pediatric communicable disease; Preschool illness absenteeism
Introduction Communicable diseases, particularly lower respiratory infections and diarrhea, remain a major burden [1,2]. Schools and day care centers have repeatedly been implicated in the spread of communicable disease, both among the children themselves and among their families and communities [3,4]. Much attention has been given to handwashing as a means to prevent infection, particularly in hospitals [5]. A metaanalysis [1] found a 47% reduction in diarrhea in communitybased handwashing trials. In the past two decades, nine
controlled trials in schools or daycare centers [6 –14] have examined the effects of hand hygiene programs on illness absenteeism. While many of the trials exhibited significant decreases in illness absenteeism [7,8,10 – 13], most have serious methodological flaws. Of the trials just cited, only one [9] was a properly randomized trial whose analysis followed the intent-to-treat principle and accounted for the clustered nature of the data. The aim of our trial was to test a handwashing program for preschool children in a rigorous way, avoiding the deficiencies of other trials. Methods
* Corresponding author. Fax: +972 2 675 8803. E-mail address: [email protected] (L. Rosen). 0091-7435/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ypmed.2005.09.012
The primary objective of this trial was to evaluate the effects of a comprehensive hygiene program on handwashing and illness absenteeism in
28
L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
public preschools. A cluster randomization design was employed, with randomization at the level of the preschool, stratified by sector (secular and religious). All preschool teachers of 3- and 4-year-old children in the state-run public system of the Jerusalem region were potentially eligible for inclusion. Preschool teachers likely to comply with the trial protocol were recommended by Ministry of Education officials and were invited to join the project. Recommended teachers included 60% of eligible teachers, and this could have been increased if resources had permitted. Nearly 90% of invited teachers agreed to join. Teachers from the 40 admitted preschools were then randomized within each sector to preschool intervention and control groups on the basis of computer-generated random numbers. Twenty preschools were randomized to the intervention group and twenty to the control group. A total of 1029 children from 40 preschools were entered. The trial included 6 baseline days and 66 study days, yielding 73,779 child days. Afterward, the program was run in the control preschools, which made the trial more ethically acceptable and attractive to participants. A concurrent subtrial was run to test a home intervention on overall and illness absenteeism. This subtrial included 469 families. Randomization for this subtrial was performed by using computer-generated random numbers and was done at the family level within each intervention group preschool (a few families had two children in the same preschool). Only parents who agreed to participate were contacted. Institutional Review Board approval was obtained from the Hadassah Ethics Committee.
Intervention program The goal of the intervention was to improve hygiene: the main emphasis was on handwashing with soap before eating and after bathroom use, and the secondary emphasis was on eliminating shared cups and towels. The program development was overseen by an early childhood education expert. The program is fully described elsewhere [15]. Education professionals were hired and trained to coordinate the intervention. Children were encouraged to wash hands for at least 10 s, which they timed by singing the project’s special handwashing song. The program aimed to influence individual and group behavior and improve prevailing social norms. Frontal lectures by medical, epidemiological, and educational experts were delivered to the preschool educators, along with printed materials and experiential learning. The techniques used with the children included puppet theatre, a self-reward system, games, posters, puzzles, a video, and presentations by school nurses. Environmental changes included installing liquid soap dispensers, paper towel dispensers, and cup racks, providing individual cups, and supplying liquid soap and paper towels. An identical set of supplies was provided to each classroom. The bulk of program implementation in the intervention group (the first seminar for the educators, the puppet show, and the initiation of the environmental changes) occurred after the baseline measurements on behavior and absenteeism but before the start of the main survey. The classroom educational materials were meant for use just after the puppet show, but their actual use was at the discretion of the educators. Control group participants did not receive any supplies, educational materials, or seminars until the close of the study period. The home component, which included a video, a card, and a magnet, was sent home with the children in individually labeled packages about a month after the preschool intervention was launched. The home intervention materials dealt with handwashing, while the home control materials dealt with toothbrushing. Timing of use of these materials was at the discretion of the families.
Sample size calculations Sample size was calculated to detect a 25% drop in illness absenteeism with power of 80% and a two-sided alpha level of 0.05, given a control group illness absenteeism rate of 6% per child day. A 60-day study period was decided upon based on logistic considerations (during the trial, this was extended to 66 days). Sample size was calculated using a modified version of Zucker’s [16] Eq. (8), involving the intraclass correlation coefficient (estimated at 0.0274) and the between day correlation coefficient (estimated at 0.0548). The calculated sample size was 36 preschools. This was rounded up to 40 preschools. Sample size for the home intervention was calculated to detect an illness absenteeism
reduction from 4.5% to 3.0%, with power of 80% and a two-sided alpha level of 0.05. Since the home intervention began some time after the preschool program, the study period was 35 days. The required sample size was 204 families per arm. The number of available families whose children were exposed to the preschool intervention was 469, yielding a power of 85% to detect a 33% change in event rate, and a power of 59% to detect a 25% change in event rate. The various parameters entering into the sample size calculations were estimated from previous studies [6 – 8]. See [15] for details.
Main outcome measures Overall absenteeism included absences from preschool for any reason. Illness absenteeism included absences that were determined to be illness related, based on combined information from parents and educators [15]. The main behavioral outcomes were percent of children in each preschool washing hands with soap before eating lunch and percent of children washing hands with soap after bathroom use.
Data collection methods Project staff visited the preschools to obtain information on the handwashing behavior of the children and existing hygienic conditions. Observer visits took place before and after program implementation in all preschools. Each visit lasted for several hours, during which time the project staff observed and recorded the children’s handwashing behavior and the availability of supplies (soap, towels, cups, and dispensers). The planned schedule included one baseline and 3 post-intervention visits in the preschool intervention group, and 2 baseline visits and one post-intervention visit in the preschool control group (which received the intervention after the trial period). There were 140 planned visits. Of these, 137 (97.9%) took place, and 3 were omitted due to logistical reasons. Study personnel collected daily absenteeism data by telephone from the educators using a structured questionnaire. Each absence was classified as due to illness, for unknown reason, or for reason unrelated to illness. If a child was absent due to illness or for an unknown reason, an attempt was made to contact the parents in the evening to clarify the reason for the absence, including the specific illness if the absence was illness related. Participating parents also underwent a one-time phone interview for socioeconomic and demographic information, as well as information on the health of the child in the study. In an attempt to avoid bias, the educators, parents, and field research staff were ‘‘blinded’’ to the study design in the sense that they were not told that the study included ‘‘intervention’’ and ‘‘control’’ groups that were being compared with respect to handwashing behavior and absenteeism. They were told simply that the children were being included in a health study and would receive a special program that would be delivered to different preschools at different times. In addition, the field research staff were blinded to the allocation status of the preschools, although they sometimes became aware that the program was being run in a certain preschool.
Statistical analysis Baseline handwashing rates, environmental conditions, sociodemographic characteristics, and absenteeism rates were compared between the study groups using analysis of variance, the mixed linear model [17], Fisher’s Exact Test, or generalized estimating equations analysis [17] (see Table 1). The preschool intervention effect on handwashing was analyzed using analysis of covariance, adjusting for religious sector and baseline handwashing levels. The mediumterm effect of the program was assessed by comparing Visit 3 in the Intervention Group (about 3 months after program launch) with Visit 2 in the Control Group (just before the end of the main study period). The longer term effect of the program was assessed by comparing Visit 4 in the Intervention Group (about 6 months after program launch) with Visit 2 in the Control Group. The preschool intervention effect on overall and illness absenteeism was analyzed in terms of the percentage of days the child was absent, or absent due to illness, during the study period. The analysis was performed on an intent-totreat basis. The mixed linear model was used, with study group and sector as fixed effects and preschool as a random effect. The model also included (as
L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
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Table 1 Jerusalem Handwashing Trial 2000 – 2001: comparisons of selected key variables at baseline Level Preschool
Family
Child
a b c d
Variable a
Average percent of children per preschool using soap before lunch Average percent of children per preschool using soap after bathrooma Average percent absenteeism (per child day)b Average percent illness absenteeism (per child day)b Percent of preschools with soap availablec Percent of preschools with cloth towelsc Percent of preschools with shared cupsc Crowding (number persons per room)b Years of maternal educationb Years of paternal educationb Percent of children in single parent householdd Percent of children with employed mothersd Percent of children with ‘‘very good’’ general health statusd Percent of children with no chronic health conditionsd Percent of children attending afternoon programd
Intervention group
Control group
N
P value
25 12 6.1 3.0 90 80 77 1.4 14 14 10 71 69 92 35
11 12 6.4 3.8 79 47 75 1.3 14 14 11 77 70 91 43
39 preschools 39 preschools 1029 children for 6 days 1029 children for 6 days 39 preschools 39 preschools 35 preschools 891 children 886 children 856 children 895 children 877 children 903 children 894 children 902 children
0.09 0.97 0.87 0.49 0.38 0.05 0.56 0.08 0.69 0.49 0.61 0.04 0.80 0.89 0.10
Analysis of covariance. Mixed linear model. Fisher’s Exact Test. Generalized estimating equations.
fixed effects) the relevant baseline absenteeism rate and various child-level, family-level, and preschool-level background factors (see [15]). The effect of the home intervention on overall and illness absenteeism was analyzed using analysis of covariance, with home intervention status, preschool, the relevant baseline absenteeism rate, various child-level, family-level, and preschool-level background factors (see [15]).
Results Participation and compliance Educator recruitment rates and parental participation rates of the survey were very high (at least 88% of educators and 95% of parents). Dropout and loss to follow-up were minimal: no dropout of preschools occurred, dropout of children was 0.9%, and loss to follow-up of children was 0.7%. During the study, two intervention group preschools were unexpectedly exposed to raw sewage due to faulty plumbing. A sensitivity analysis excluding those preschools was conducted, and results were unchanged. Assessing the effects of behavioral interventions is often difficult due to poor compliance in the treatment group [18] and contamination in the control group, particularly in community trials [19]. In this study, compliance with the program in the intervention group was good but imperfect, and
contamination of the control group was minimal, as seem by comparing the control group handwashing rates at the beginning and the end of the main study period (before the program was run in the control group; generalized estimating equations, P = 0.3916, handwashing before lunch, and, P = 0.3981, handwashing after bathroom) [15]. Monitoring procedures for absenteeism were identical in the two groups, and no between-group differences were found in the validity of the reported information [15]. Baseline comparability Table 1 presents baseline comparisons of handwashing rates, absenteeism, illness absenteeism, and selected key background variables. There were few notable baseline differences between the groups. Comparisons on 17 additional background variables were conducted [15], none of which reached the P = 0.05 level of significance. Effect of the preschool intervention Table 2 presents data on behavioral changes by intervention group and educational sector over time. The baseline rates of
Table 2 Jerusalem Handwashing Trial 2000 – 2001: average percent of children handwashing in each preschool, by educational sector and intervention group Educational sector
Soap before lunch Soap after bathroom
Intervention group
Religious Secular Combined Religious Secular Combined
Control group
Preintervention visit Nov00 – Dec00
Post-intervention visit 1 Jan01 – Feb01
Post-intervention visit 2 Mar 01 – Apr 01
Post-intervention visit 3 May01 – Jun0
Preintervention visit 1 Nov00 – Dec00
Preintervention visit 2 Apr 01 – May01
Post-intervention visit Jun01
11 36 25 12 12 12
60 72 67 44 44 44
48 71 60 46 41 43
43 76 61 48 46 47
00 23 11 10 14 12
04 31 18 12 16 14
60 79 70 52 31 41
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L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
Table 3 Jerusalem Handwashing Trial 2000 – 2001: average per-day percentage of overall and illness absenteeism by preschool intervention group Type of absenteeism
Educational sector
Intervention group
Control group
All
Overall
Religious Secular Combined Religious Secular Combined
4.83 7.62 6.32 2.83 3.91 3.40
4.06 7.64 5.83 2.05 4.20 3.11
4.41 7.63 6.06 2.40 4.06 3.25
Illness
(N (N (N (N (N (N
= = = = = =
229) 260) 489) 229) 260) 489)
(N (N (N (N (N (N
= = = = = =
273) 267) 540) 273) 267) 540)
(N (N (N (N (N (N
= = = = = =
502) 527) 1029) 502) 527) 1029)
Intraclass correlation coefficient: overall absenteeism: 0.0634, illness absenteeism: 0.0747. Between day correlation: overall absenteeism: 0.0713, illness absenteeism: 0.0417.
handwashing with soap were low. In the religious sector, this was partly due to the practice of ritual handwashing before meals with water alone. The intervention had a significant effect on both the medium and longer term behavior. For handwashing after lunch, the medium-term adjusted relative risk (adjusted RR) was 2.77 (CI:[1.70,7.46], P < 0.01), while the long-term adjusted RR was 2.93 (CI:[1.86,6.97], P < 0.01). For handwashing after bathroom use, the medium-term adjusted RR was 2.90 (CI:[1.69,10.06], P < 0.01), while the long-term adjusted RR was 3.30 (CI:[1.83,16.67] P < 0.01). Table 3 presents average daily percentages of overall and illness absenteeism. There was no evidence of an intervention effect on absenteeism (adjusted RR = 1.00, CI: [0.90,1.14], P = 0.97) or illness absenteeism (adjusted RR = 1.00, CI: [0.81,1.32], P = 0.97). Effect of the home intervention Because handwashing data were available only at the level of the preschool and not at the level of the individual child, it was not possible to analyze the effect of the home intervention on handwashing. Table 4 presents the absenteeism and illness absenteeism data. The home component did not affect overall absenteeism (adjusted RR = 0.93, CI: [0.82,1.07], P = 0.28) or illness absenteeism (adjusted RR = 0.94, CI: [0.76,1.23], P = 0.57). Discussion This was the largest and most comprehensive randomized field trial of a hand hygiene intervention ever reported among toilet-trained preschool children. The design overcame methodological problems commonly seen in hand hygiene and community health trials, through cluster randomization and appropriate statistical analyses. For the first time in a school/
daycare-based trial, a home component was introduced and tested in an embedded individually randomized subtrial, which proved an efficient way to test a home component. The excellent medium-term and longer term behavioral results showed that health behavior change is achievable in a large and heterogeneous population in disparate locations. These results, along with the enthusiasm of the educators, illuminate the potential of the preschool as a promising venue for health promotion activities. The combination of cluster randomization with delayed delivery in the control group, which has previously been reported [9,20] but is not in widespread use, was an extremely useful design. Recruitment was very successful, with over 95% of the parents agreeing to cooperate and nearly 90% of invited educators joining the program, even with the demands of the research. None of the preschools dropped out of the trial, and only 0.9% of parents dropped out of the survey. The program was received enthusiastically by upper-echelon administrators, educators, children, and parents. Subsequent demand for the program has been high. The study’s internal validity can be regarded as high, in view of the trial’s cluster randomization design, baseline between-group balance on the response variable and potential confounding variables, identical monitoring procedures, similar reporting rates in the two groups, reasonable levels of behavioral compliance, low contamination rates, and blinding of observers to study design and treatment allocation. External validity was also high. Inclusion criteria for the preschools were broad, so that most Jerusalem preschools serving the relevant age groups and educational streams in the state-run school system were eligible. Most of the educators who were contacted agreed to participate. As indicated above, the program enjoyed a high level of program acceptability to the target population. Thus, the study results are generalizable
Table 4 Jerusalem Handwashing Trial 2000 – 2001: average per-day percentage of overall and illness absenteeism by home intervention group Type of absenteeism
Educational sector
Overall
Religious Secular Combined Religious Secular Combined
Illness related
Home component intervention group
Home component control group
All
Mean
Mean
Mean
4.07 6.72 5.47 2.22 3.54 2.92
(N (N (N (N (N (N
= = = = = =
112) 125) 237) 112) 125) 237)
4.19 7.54 5.99 2.31 3.67 3.04
(N (N (N (N (N (N
= = = = = =
107) 125) 232) 107) 125) 232)
4.13 7.13 5.73 2.26 3.61 2.98
(N (N (N (N (N (N
= = = = = =
219) 250) 469) 219) 250) 469)
L. Rosen et al. / Preventive Medicine 42 (2006) 27 – 32
to preschools in the Israeli state-run secular and religious streams. The study was limited in that it did not directly assess intervention effects on illness. Overall and illness absenteeism were not affected by either the preschool intervention or the home intervention. Of the nine controlled trials [6 –14] that examined the effects of hand hygiene on illness absenteeism in educational settings, six [7,8,10 –13] found a reduction in illness absenteeism, and one [14] found a reduction among younger children only. Both of the studies that found no reduction [6,9] were randomized. Of the six studies with positive results, only one of them was randomized [11]. Moreover, the analysis in this trial was not an intent-to-treat analysis but instead included only the 44% of classrooms with high compliance, and so the findings are prone to bias. Noncompliant schools were also excluded from analysis in [12]. Several additional factors further compromise some of the published evidence. In only three of the trials [9,12,14] did the analysis account for the clustered nature of the data. Thus, of the nine controlled trials, only one [9] was a properly randomized study whose analysis followed the intent-to-treat principle and accounted for cluster effects; in that study, no effect of the intervention on illness absenteeism was found. Thus, as regards the hypothesis that a hand hygiene program can reduce illness absenteeism in an educational setting, the published evidence is weak. The disparities between our results and most published results may be an illustration of the ‘‘stainless steel rule of evaluation’’ [21], which states that the better the evaluation, the less likely it is to find a positive result. Other factors may also have been at play. Different hand hygiene regimes or increased demand for hand hygiene may have affected results of other trials. The type of communicable disease present in the community at the time of the trial may have played a role, as the reduction in diarrhea due to handwashing has been estimated at 47% [1], while the reduction in upper respiratory infections due to handwashing has been estimated at 20% [22]. In the our trial, the rate of absenteeism due to gastrointestinal illnesses was 17%, as opposed to the 39% rate in [10] and the 29% rate in [11]. During our study period, diarrhea rates in Jerusalem were very low [23]. A higher base rate of gastrointestinal disease may have led to a stronger program effect on illness absenteeism. The reason for the lack of change in illness absenteeism rates in our trial, despite substantial behavioral improvement, is unclear. Given the strength of the existing evidence regarding the relationship between handwashing and illness [see [24] for a recent example], one likely explanation is that illness rates changed but not illness absenteeism rates; this may have occurred if many of the illnesses were mild enough so that the affected children did not stay home from preschool. Indeed, in the Roberts trial [9], a handwashing program was found to affect illness rates but not illness absenteeism rates. Conclusions This is the first report showing that a hygiene program can produce a sustained increase in handwashing rates among
31
toilet-trained preschool children at a large number of geographically disparate locations. The program did not reduce overall or illness absenteeism. The findings illuminate the potential of the preschool as a promising venue for health promotion activities leading to sustained behavioral change, while suggesting the need for enhanced and/or alternative approaches to illness absenteeism reduction. Acknowledgments The authors gratefully acknowledge grants received from The Chief Scientist’s Office of the Ministry of Health; Associate Director General’s Unit for Health Promotion of the Ministry of Health; and the National Institute for Health Services Research. We are also indebted to the Preschool and Public Health Departments of the Municipality of Jerusalem for logistical assistance. References [1] Curtis V, Cairncross S. Effect of washing hands with soap on diarrhoea risk in the community: a systematic review. Lancet, Infect Dis 2003;3: 275 – 81. [2] Murray JL, Lopez AD. Summary: the global burden of disease. WHO; 1996. [3] Fox JP, Hall CE. Viruses in families: surveillance of families as a key to epidemiology of virus infections. MA’ PSG Publishing Company; 1980. [4] Jordan W, Badger G, Curtiss C, Dingle J, Ginsberg S, Gold E. A study of illness in a group of Cleveland families X. Am J Hyg 1956;64:336 – 48. [5] Larson E. A causal link between handwashing and risk of infection? Examination of the evidence. Infect Control Hosp Epidemiol 1988;9:28 – 36. [6] Courtney K. The effect of a handwashing education program on illnessrelated absenteeism and attitudes toward handwashing [dissertation]. UMI Dissertation Information Service, 1995. [7] Kimel LS. Handwashing education can decrease illness absenteeism. J Sch Nurs 1996;12:14 – 6. [8] Master D, Longe SH, Dickson H. Scheduled handwashing in an elementary school population. Fam Med 1997;29:336 – 9. [9] Roberts L, Smith W, Jorm L, Patel M, Douglas R, McGilchrist C. Effect of infection control measures on the frequency of upper respiratory infection in child care: a randomized controlled trial. Pediatrics 2000;105:738 – 42. [10] Dyer D, Shinder D, Shinder F. Alcohol-free instant hand sanitizer reduces elementary school illness absenteeism. Fam Med 2000;32:633 – 8. [11] White C, Shinder F, Shinder A, Dyer D. Reduction of illness absenteeism in elementary schools using an alcohol-free instant hand sanitizer. J Sch Nurs 2001;17:258 – 65. [12] Hammond B, Ali Y, Fendler E, Dolan M, Donovan S. Effect of hand sanitizer use on elementary school absenteeism. AJIC 2000;28:340 – 6. [13] Guinan M, McGuckin M, Ali Y. The effect of a comprehensive handwashing program on absenteeism in elementary schools. AJIC 2002;30:217 – 20. [14] Ponka 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;32:2 – 7. [15] Rosen L. A controlled trial to assess the effect of a health promotion intervention on hygiene behavior and absenteeism in Jerusalem preschools. [Dissertation: Hebrew University, 2004]. [16] Zucker DM. Cluster randomization. In: Geller N, editor. Contemporary biostatistical methods in clinical trials. New York’ Marcel Dekker; 2000. [17] Murray D. Design and analysis of group randomized trials. Oxford Univ. Press; 1998. [18] Friedman L, Furberg C, DeMets D. Fundamentals of clinical trials. 3rd ed. New York’ Springer; 1998. [19] Donner A, Klar N. Design and analysis of cluster randomization trials in health research. USA’ Oxford Univ. Press; 2000.
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[20] Gortmaker SL, Peterson K, Wiecha J, Sobol A, Dixit S, Fox M, et al. Reducing obesity via a school-based interdisciplinary intervention among youth: Planet Health. Arch Pediatr Adolec Med 1999;153:409 – 18. [21] Petticrew M. Why certain systematic reviews reach uncertain conclusions. BMJ 2003;326:756 – 8. [22] Carabin H, Gyorkos T, Soto J, Joseph L, Payment P, Collet JP. Effectiveness of a training program in reducing infections in toddlers attending day care centers. Epidemiology 1999;10:219 – 27.
[23] Cohen D, Basal R, Vilenski L, et al. The cyclical nature of shigellosis outbreaks in Israel. Presented at the Annual Conference of the Israel Center for Disease Control, November 2004, Tel Aviv. [24] Luby S, Agboatwalla M, Painter J, Altaf A, Billhimer W, Hoekstra R. Effect of intensive handwashing promotion on childhood diarrhea in highrisk communities in Pakistan: a randomized controlled trial. JAMA 2004;291:2547 – 54.