Importance: Hemorrhagic fever with renal syndrome (HFRS), a neglected zoonotic disease, has received only short-term attention in postflood prevention and control initiatives, possibly because of a lack of evidence regarding the long-term association of flooding with HFRS.

Objectives: To quantify the association between severe floods and long-term incidence of HFRS in the Yangtze River basin and to examine the modifying role of geographical factors in this association.

Design, setting, and participants: This cross-sectional study collected data on HFRS cases between July 1, 2013, and June 30, 2019, from 58 cities in 4 provinces (Anhui, Hubei, Hunan, and Jiangxi) in the Yangtze River basin of China, with a breakpoint of flooding in July 2016, generating monthly data. The 3 years after July 2016 were defined as the postflood period, while the 3 years before the breakpoint were defined as the control period. Statistical analysis was performed from October to December 2023.

Exposures: City-level monthly flooding, elevation, ruggedness index, and closest distance from each city to the Yangtze River and its tributaries.

Main outcomes and measures: The primary outcomes were the number of city-level monthly HFRS cases and the number of type 1 (spring or summer) and type 2 (autumn or winter) HFRS cases.

Results: A total of 11 745 patients with HFRS were reported during the study period: 5216 patients (mean [SD] age, 47.1 [16.2] years; 3737 men [71.6%]) in the control period and 6529 patients (mean [SD] age, 49.8 [15.8] years; 4672 men [71.6%]) in the postflood period. The pooled effects of interrupted time series analysis indicated a long-term association between flooding and HFRS incidence (odds ratio, 1.38; 95% CI, 1.13-1.68), with type 1 cases being at highest risk (odds ratio, 1.71; 95% CI, 1.40-2.09). The metaregression results indicated that elevation and ruggedness index were negatively associated with the risk of HFRS, while the distance to rivers interacted with these associations.

Conclusions and relevance: This cross-sectional study of the long-term association between flooding and HFRS incidence, as well as the modification effects of geographical factors, suggests that severe floods were associated with an increased risk of HFRS within 3 years. This study provides evidence for the development of HFRS prevention and control strategies after floods.