A meta-analysis of infection rates of Schistosoma japonicum in sentinel mice associated with infectious waters in mainland China over last 40 years

Background: Schistosomiasis japonica is a zoonotic parasitic disease. After nearly 70 years of control efforts in China, Schistosomiasis transmission has been reduced to a much lower level. The absence or near absence of infections in humans or livestock, based on traditional fecal and serological tests, has made the targets and priorities of future control efforts difficult to determine. However, detection of schistosome cercariae in waters using sentinel mice could be an alternative way of identifying remaining foci of infection, or even serve as a tool for evaluation of control efficacy. This method has been employed in China over last forty years. We therefore performed a meta-analysis of the relevant research to investigate if infections in sentinel mice mirror the ongoing trend of schistosomiasis transmission in China. Methods: We conducted a meta-analysis of studies reporting infection rates of S. japonicum in sentinel mice in China before Sep 1, 2018 in accordance with the PRISMA guidelines. We retrieved all relative studies based on five databases (CNKI, WanFang, VIP, PubMed and Web of Science) and the reference lists of resulting articles. For each individual study, the infection rate in sentinel mice is presented together with its 95% confidence interval (CI). Point estimates of the overall infection rates and their 95% CIs were calculated. Subgroup analyses were performed according to study periods, seasons or regions. Results: We identified 90 articles, including 290 studies covering eight endemic provinces. The overall rate in sentinel mice was 12.31% (95% CI: 10.14–14.65%) from 1980 to 2018. The value of 3.66% (95% CI: 2.62–4.85%) estimated in 2004 to 2018 was significantly lower than in 1980 to 2003 (22.96%, 95% CI: 19.25–26.89%). The estimate was significantly higher in the middle and lower reaches than in the upper reaches of the Yangtze River. The highest estimates were obtained in Hunan (30.11%, 95% CI: 25.64–34.77%) followed by Anhui (26.34%, 95% CI: 12.88–42.44%) and then Jiangxi (13.73%, 95% CI: 6.71–22.56%). Unlike the other provinces in the middle and lower reaches, no significant reduction was seen in Hubei after 2003. Even in Hubei two studies carried out after 2014 reported infections in sentinel mice, although no infected snails were reported across the province. Infections were most found in April (17.40%, 95% CI: 1.13–45.49%), July (24.98%, 95% CI: 15.64–35.62%) and October (17.08%, 95% CI 5.94–32.05%). High degrees of heterogeneity were observed. Conclusion: This meta-analysis provides a comprehensive analysis of schistosome infection in sentinel mice across China. The estimates largely mirror the ongoing trends of transmission in terms of periods and regions. Infections were most likely to occur in April, July and October. In areas where no infected snails were reported infections in sentinel mice were still observed. Due to the presence of snails and infected wildlife, detection of schistosomes in waters using such a highly sensitive method as the deployment of sentinel mice, remains of importance in schistosomiasis monitoring. We would suggest the current criteria for transmission interruption or elimination of schistosomiasis in China be adjusted by integrating the results of sentinel mice based surveys. Author summary: With the continued activities of the prevention and control programme in China, the prevalence and intensity of Schistosoma japonicum infection have been reduced to low levels. This makes it impossible to detect any infections in humans or livestock using the traditional approach of fecal and serological testing, so as to evaluate properly the risk map of infection. However, detection of existence of schistosome cercariae in waters could be an alternative way of detecting a potential focus of transmission. We therefore performed a meta-analysis of studies performed over the last 40 years to estimate the overall infection rates of S. japonicum in sentinel mice. The estimate across China in 2004 to 2018 was 3.66%, significantly lower than in 1980 to 2003. The highest estimates were observed in Hunan, followed by Anhui and Jiangxi. Two studies conducted in Hubei in 2015 and 2016 respectively, reported infected sentinel mice where no infected snails had been reported across the province since 2014. Transmission was found be most likely in April, July and October. The estimates largely mirror the ongoing trends of S. japonicum infections in terms of periods and regions. Due to the presence of snails and other infected wildlife, detection of schistosome cercariae in waters with a highly sensitive tool remains of great importance in schistosomiasis monitoring and evaluation. To the authors’ knowledge, this is the first time that the potential threat of S. japonicum in nature, to humans and livestock has been assessed in this manner. We would suggest that the current criteria for transmission interruption or elimination of S. japonicum in China be adjusted by integrating the results of sentinel mice.