Empirical estimation of the incubation period for hand-foot-and-mouth disease from school outbreaks

Abstract

Purpose: Outbreaks of hand-foot-and-mouth disease (HFMD) occurred frequently in Asia and occasionally in Europe and the US. The incubation period, defined as the time elapsed from infection to symptom onset, is important to guide disease control and prevention. The incubation period of HFMD is commonly described as 3–7 days but was supported by limited quantitative evidence. In this study we estimated the incubation period of HFMD from school outbreaks in Hong Kong. Methods & Materials: In 2015-2016, we recruited 24 kindergartens, 3 primary and 8 secondary schools which reported to have HFMD cases. We collected information on the dates of symptom onset and absence for the diagnosed HFMD cases, and potential epidemiological link to other HFMD cases in household. We extracted classes with ≥2 HFMD cases for the analysis. The distribution of incubation period was estimated allowing for interval censoring. We assumed the HFMD cases were infectious after symptom onset. For each HFMD case, the possible exposure period for other students in the same class was defined from the day of symptom onset to the school day before taking sick leave. The time differences between the exposure period to all potential infectors and the symptom onset day of the subsequent HFMD cases were used to estimate the incubation period. We fitted log-normal, gamma and Weibull distributions by maximum likelihood method and selected the best-fitted distribution by Akaike information criterion. We estimated the median, 5% and 95% percentiles and computed the relevant 95% confidence interval by bootstrap method. Results: Among the 35 schools, 105 cases from 29 classes in 19 schools were included for analysis. Weibull distribution was the best-fitted model with an estimated median incubation period of 4.5 (95% CI: 4.1-5.1) days. The estimated 5% and 95% percentiles were 0.6 and 14.3 days respectively. Conclusion: The median incubation period of HFMD is consistent to the range of 3–7 days commonly cited by different health agencies. However, the incubation period can be more variable and not uncommon to be longer than a week. The finding may have implications on the recommendation of disease control in a school setting.