This 4-year surveillance study showed that enteropathogen infections remain the major cause of diarrhea in Shanghainese children and could be responsible for 58.4% of outpatient visits due to diarrhea episodes. The overall detection rate of enteropathogens in Shanghai was higher than the national average level (44.6%) based on the pooled data from 92 surveillance network laboratories (9), which is possibly correlated with the variation of detection capacity by laboratories. However, the prevalence of enteropathogens was lower than that in Vietnam, where 75.2% of diarrheal episodes in outpatient children were potentially attributable to infectious diarrhea and rotavirus and norovirus were more frequently detected than in Shanghai (10). Although the overall detection rate of enteropathogens was similar to that in Salt Lake City of the United Sates (52%), we also noticed the difference in the etiological spectrum, for example, lower prevalence of rotavirus and NTS and higher prevalence of Clostridium difficile were observed, which was not included into our target pathogen tested (11). Our finding showed that rotavirus, norovirus and NTS were the major etiological agents responsible for diarrhea annually in Shanghainese children, which should be the priority targets for intervention.
WHO recommended rotavirus vaccine as the priority vaccine included the national immunization program in 2008 based on the global disease burden of rotavirus diarrhea (12). With the widely introduction of rotavirus vaccination at the global level, the disease burden incurred by of rotavirus-associated diarrhea has reduced remarkably in countries with rotavirus vaccination including national immunization program (13). Although monovalent lamb-derived G10P[15] rotavirus vaccine has been used in China since 2001, the coverage of vaccination is quite low, rotavirus remains the leading cause of diarrhea in Chinese children (14). Pentavalent rotavirus vaccine was introduced in China in 2018. It is worthy of attention to monitor the changing trend of rotavirus diarrhea with the increased demand and uptake of new rotavirus vaccine among infants in China.
The prevalence of norovirus was almost similar to the prevalence of rotavirus in this study and the high activities of sporadic norovirus diarrhea usually occurred earlier than that of rotavirus diarrhea in Shanghai. Norovirus has replaced rotavirus as the leading cause of pediatric gastroenteritis requiring medical attention in countries with a successful implementation of rotavirus vaccination, such as in the US and Nicaragua (15–17). Considering the public health effect of norovirus gastroenteritis in the community and outbreak settings, candidate norovirus vaccines are under development (18). Thus, monitoring the changing trend of norovirus activity is important to predict the potential emerging new GII.4 variants and recombinants, which could result in epidemics and sometimes global pandemics of acute gastroenteritis (21). In addition, adenovirus, sapovirus and astrovirus accounted for 12.9% of diarrhea in outpatient children. These viruses are sometimes associated with outbreaks in semi-closed communities in all age groups, thus, dynamic surveillance of activities of these three viruses is also clinically important (19, 20).We also noticed the detection rates of adenovirus and astrovirus increased in 2017–2018 compared to 2015–2016. It is worthy of attention to whether the shift of prevalent serotypes was associated with increased activities of adenovirus and astrovirus (21–24).
In this study, NTS was the third common pathogen causing 10.3% of diarrhea and was the leading bacterial pathogen in outpatient children with diarrhea. Globally, NTS is an important pathogen of sporadic and outbreak foodborne gastroenteritis and children < 5 years are most susceptible, especially in developed countries (25, 26). The annual prevalence of NTS during 2015–2018 was stable with S. typhimurium and S. enteritidis serovars remaining predominant. Our latest study suggested the transmission sources of S. typhimurium and S. enteritidis in Shanghainese children were diverse, which imposes difficulty to control and prevent NTS infections in Shanghai (27). Currently, the priority strategy of controlling NTS diarrhea is strengthening food safety, which has reduced the incidence of NTS foodborne diseases in the US and in some European countries (28, 29). Campylobacter infection is gradually increasing in recent years in both developing and developed countries (30). C. jejuni is responsible for about 13% of diarrhea in children under five years old in Poland and Campylobacter infection was the most common foodborne pathogen in 2017 in the US (31). However, the prevalence of Campylobacter infection was much lower than the prevalence of NTS infection in Shanghainese children with diarrhea. Campylobacter infection is usually linked with exposure to chicken and its products (32). Since 2013 China government started strengthening the management of live chicken to prevent the transmission of avian influenza, which indirectly reduced the transmission sauce of Campylobacter infection. Urbanization and improvement of water supplies, sanitation, and hygiene have resulted in a remarkable decrease in shigellosis in China since the late 1990s (33). The prevalence of shigella is very low in Shanghai.
DEC was detected in 12.7% of children with acute diarrhea in the study and most DEC isolates were EAEC and EPEC, which is consistent with studies conducted in Israel (34). However, our previous case-control study conducted in 2014 didn’t demonstrate the pathogenic significance of EAEC and EPEC (8). Therefore, we are uncertain the role of EAEC and EPEC as an etiological agent of infectious diarrhea in Shanghainese children. Despite ETEC is a common pathogen causing adult diarrhea in shanghai (35), ETEC was not a common pathogen in children with diarrhea. EHEC was also a rare pathogen.
In conclusion, infectious diarrhea remains a major cause of diarrheal illnesses in Shanghainese children. The disease burden of diarrheal illnesses will be promisingly reduced with increased coverage of rotavirus vaccines in susceptible infants and strengthened intervention of foodborne illnesses in Shanghai and China. The findings of this study are useful for public health policy-makers to formulate the effective strategy of controlling and preventing childhood diarrhea in China.