Background The effect of urbanization on the morbidity of hepatitis A remains unclear. We aimed to estimate the association between various urbanization-related indices and hepatitis A morbidity in China. Methods Data on the annual morbidity of hepatitis A, urbanization-related measures (i.e., gross domestic product per capita, the number of hospitalization beds per 1000 persons, illiteracy rate, tap water coverage, motor vehicles per 100 persons, population density, and the proportion of arable land), and meteorological factors in 31 provincial-level administrative divisions of Chinese mainland during 2005–2018 were collected from the National Population and Health Science Data Sharing Platform, China Statistical Yearbooks, and the China Meteorological Data Sharing Service System, respectively. Generalized linear mixed models were applied to quantify the impacts of different urbanization-related indices on the morbidity of hepatitis A in China after adjusting for covariates. Results A total of 537,466 hepatitis A cases were reported in China during 2005–2018. The annual morbidity had a decline of 79.4% from 5.64 cases to 1.16 cases per 100,000 people. There were obvious spatial variations with higher morbidity in western China. Nationally, gross domestic product per capita and the number of hospitalization beds per 1000 persons increased from 14,040 to 64,644 CNY and from 2.45 to 6.03 during 2005–2018, respectively. The illiteracy rate decreased from 11.0 to 4.9%. Gross domestic product per capita [relative risk (RR) = 0.96, 95% confidence interval (CI): 0.92–0.99], and the number of hospitalization beds per 1000 persons (RR = 0.79, 95% CI: 0.75–0.83) were associated with the declined morbidity of hepatitis A. By contrast, the increased morbidity of hepatitis A was linked to the illiteracy rate (RR = 1.04, 95% CI: 1.02–1.06). Similar influential factors were detected for children and adults, with greater effects witnessed for children. Conclusions People in the western region suffered the heaviest burden of hepatitis A in Chinese mainland. Nationally, there was a sharp decline in the morbidity of hepatitis A. The urbanization process was associated with the reduction of hepatitis A morbidity in China during 2005–2018. Graphical Abstract

Background Accurate estimation of the influenza death burden is of great significance for influenza prevention and control. However, few studies have considered the short-term harvesting effects of influenza on mortality when estimating influenza-associated excess deaths by cause of death, age, sex, and subtype/lineage. Objective This study aimed to estimate the cause-, age-, and sex-specific excess mortality associated with influenza and its subtypes and lineages in Guangzhou from 2015 to 2018. Methods Distributed-lag nonlinear models were fitted to estimate the excess mortality related to influenza subtypes or lineages for different causes of death, age groups, and sex based on daily time-series data for mortality, influenza, and meteorological factors. Results A total of 199,777 death certificates were included in the study. The average annual influenza-associated excess mortality rate (EMR) was 25.06 (95% empirical CI [eCI] 19.85-30.16) per 100,000 persons; 7142 of 8791 (81.2%) deaths were due to respiratory or cardiovascular mortality (EMR 20.36, 95% eCI 16.75-23.74). Excess respiratory and cardiovascular deaths in people aged 60 to 79 years and those aged ≥80 years accounted for 32.9% (2346/7142) and 63.7% (4549/7142) of deaths, respectively. The male to female ratio (MFR) of excess death from respiratory diseases was 1.34 (95% CI 1.17-1.54), while the MFR for excess death from cardiovascular disease was 0.72 (95% CI 0.63-0.82). The average annual excess respiratory and cardiovascular mortality rates attributed to influenza A (H3N2), B/Yamagata, B/Victoria, and A (H1N1) were 8.47 (95% eCI 6.60-10.30), 5.81 (95% eCI 3.35-8.25), 3.68 (95% eCI 0.81-6.49), and 2.83 (95% eCI –1.26 to 6.71), respectively. Among these influenza subtypes/lineages, A (H3N2) had the highest excess respiratory and cardiovascular mortality rates for people aged 60 to 79 years (20.22, 95% eCI 14.56-25.63) and ≥80 years (180.15, 95% eCI 130.75-227.38), while younger people were more affected by A (H1N1), with an EMR of 1.29 (95% eCI 0.07-2.32). The mortality displacement of influenza A (H1N1), A (H3N2), and B/Yamagata was 2 to 5 days, but 5 to 13 days for B/Victoria. Conclusions Influenza was associated with substantial mortality in Guangzhou, occurring predominantly in the elderly, even after considering mortality displacement. The mortality burden of influenza B, particularly B/Yamagata, cannot be ignored. Contrasting sex differences were found in influenza-associated excess mortality from respiratory diseases and from cardiovascular diseases; the underlying mechanisms need to be investigated in future studies. Our findings can help us better understand the magnitude and time-course of the effect of influenza on mortality and inform targeted interventions for mitigating the influenza mortality burden, such as immunizations with quadrivalent vaccines (especially for older people), behavioral campaigns, and treatment strategies.

BACKGROUND Accurate estimation of influenza death burden is of great significance for influenza prevention and control. However, few studies have considered the short-term harvesting effects of influenza on mortality when estimating influenza-associated excess deaths by cause of death, age, sex, subtype/lineage. OBJECTIVE This study aimed to estimate cause-, age- and sex-specific excess mortality associated with influenza and its subtypes/lineages in Guangzhou from 2015 to 2018. METHODS Distributed lag non-linear models were fitted to estimate the excess mortality related to influenza subtypes/lineages for different causes of death, age groups, and sex based on the daily time-series data on mortality, influenza, and meteorological factors. RESULTS A total of 199.8 thousand death certificates were included in the study. The average annual influenza-associated excess mortality rate (EMR) was 25.06 (95% empirical confidence interval [eCI], 19.85–30.16) per 100,000 persons, among which 81.2% were due to respiratory and cardiovascular (R&C) mortality (EMR: 20.36 [95% eCI:16.75–23.74]). Excess R&C deaths in people aged 60–79 years and those aged ≥80 accounted for 32.9% and 63.7%, respectively. The average annual excess R&C mortality rates attributed to influenza A(H3N2), B/Yamagata, B/Victoria, and A(H1N1) were 8.47 (95% eCI:6.60–10.30), 5.81 (95% eCI:3.35–8.25), 6.21 (95% eCI:2.31–9.97), and 0.07 (95% eCI:-5.57–5.70), respectfully. The male-to-female ratio of excess death from respiratory diseases was 1.34 (95% CI:1.17–1.54), while the ratio for cardiovascular diseases was 0.72 (95% CI:0.63–0.82). The mortality displacement of influenza A(H1N1), A(H3N2), and B/Yamagata was 2–5 days, but 5–13 days for B/Victoria. CONCLUSIONS This study suggests that the mortality burden of influenza B cannot be ignored. Including influenza A subtypes and B lineages in active surveillance and vaccination with quadrivalent vaccines would help to curb the mortality burden of influenza. The mechanisms of sex differences in influenza-associated mortality warrant further investigation. Our findings will help to better understand the magnitude and time-course of the effects of influenza on mortality.