Quantifying the temperature-related fraction of hand, foot, and mouth disease using distributed lag non-linear models: lessons from the COVID-19 pandemic period.

Background: Hand, foot and mouth disease (HFMD) is a sudden infectious illness commonly seen in children under 5 years old. It has been reported that meteorological factors, particularly the temperature, influence the transmission of HFMD. However, the connection between the temperature effect and social contact patterns has not been clearly established yet. The occurrence of COVID-19 provided an accidental opportunity to investigate this problem. Methods: We studied 36,648 hand, foot and mouth disease (HFMD) cases in Liangjiang New Area, Chongqing, China from January 1, 2020 to December 31, 2024, combined with daily meteorological information (temperature, atmospheric pressure, wind speed and diurnal temperature range). A distributed lag non-linear model (DLNM) with a quasi-Poisson link was applied to investigate the relationship between temperature and HFMD. The population attributable fractions (PAF) were calculated using a lag-0 method. Stratified analyses were carried out according to different periods: the period of lockdown (2020), the period with partial controls (2021-2022) and the post-control period (2023-2024). Four sets of sensitivity analyses were conducted to examine the model's stability. Results: The full model (including the four meteorological factors) has the minimum QAIC value. There is a J-shaped correlation between the temperature and the risk of HFMD, with the minimum incidence temperature at -10.2 °C and slight rising effects. The total attributable fraction caused by the temperature is 4.99% (including 1,828 cases). The attributable fractions vary with different years: 0.48% in 2020 when the lockdown was enforced, 4.53-4.52% during partial controls and 6.57-5.87% after the lockdown (the average fraction from 2023 to 2024 is 6.33%). The attributable fractions of wind speed (PAF 1.67%) and atmospheric pressure (PAF 1.10%) are relatively small. Sensitivity analyses show that the results are similar to those under different time trends, lag periods, seasonal subsets and covariate settings. Conclusion: The temperature accounts for about one twentieth of the HFMD cases under usual social interactions, however, this influence is almost disappeared during the COVID-19 lockdown when children are separated. The results indicate that the temperature mainly serves as a permissive behavioral factor promoting child-to-child contacts - rather than acting directly on the viral kinetics. For the control of HFMD, the efforts should focus on improving the hygiene of kindergartens, isolating the cases and vaccinating, instead of monitoring the temperature, although temperature-related preparation according to the seasons is still significant.