BackgroundThis study aimed to investigate epidemiologic characteristics of major human infection with avian influenza and explore the factors underlying the spatial distributions, particularly H5N6 and H9N2, as H9N2 could directly infect mankind and contribute partial or even whole internal genes to generate novel human-lethal reassortants such as H5N6. They pose potential threats to public health and agriculture.MethodsThis study collected cases of H5N1, H5N6, H9N2, and H7N9 in China, along with data on ecoclimatic, environmental, social and demographic factors at the provincial level. Boosted regression tree (BRT) models, a popular approach to ecological studies, has been commonly used for risk mapping of infectious diseases, therefore, it was used to investigate the association between these variables and the occurrence of human cases for each subtype, as well as to map the probabilities of human infections.ResultsA total of 1,123 H5N1, H5N6, H9N2, and H7N9 human cases have been collected in China from 2011 to 2024. Factors including density of pig and density of human population emerged as common significant predictors for H5N1 (relative contributions: 5.3, 5.8%), H5N6 (10.8, 6.4%), H9N2 (11.2, 7.3%), and H7N9 (9.4, 8.0%) infection. Overall, each virus has its own ecological and social drivers. The predicted distribution probabilities for H5N1, H5N6, H9N2, and H7N9 presence are highest in Guangxi, Sichuan, Guangdong, and Jiangsu, respectively, with values of 0.86, 0.96, 0.93 and 0.99.ConclusionThis study highlighted the important role of social and demographic factors in the infection of different avian influenza, and suggested that monitoring and control of predicted high-risk areas should be prioritized.