Infectious diseases of poverty · 2025
Co-infection and interaction of enteric pathogens in acute diarrhea among children under five years: a large-scale multicenter observational study from China.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Zhang Shun-Xian, Zuo Qin-Yan, Zheng Jin-Xin, Wang Ji-Chun, Chen Mu-Xin, Qin Yu, Yang Jian, Lv Shan, Duan Lei, Tian Li-Guang, Liu Qin, Lv Wen-Wen, Liu Rui-Tao, Chen Guang-Hua, Xu Wan-Fu, Zheng Can-Jun, Li Shi-Zhu, Wang Hong-Li
Аннотация
BACKGROUND: Diarrhea remains a major health concern in children under five years, with enteric pathogens being key contributors. However, the interactions among these pathogens and their combined effects on disease severity are not well understood. The study investigates the interactions among co-infecting enteric pathogens on diarrhea pathogenesis within an epidemiological framework.
METHODS: This large-scale, multicenter case-control study was conducted from January 1, 2024 to December 31, 2024, across four tertiary hospitals in Guangzhou, Guangdong Province, China. Stool samples were collected from children under five years with diarrhea (cases) and those without (non-diarrheal children). 21 enteric pathogens in each specimen were identified. Potential interactions between co-infecting pathogens were assessed using both additive and multiplicative models.
RESULTS: Enteric pathogens were more frequently detected in children with diarrhea than in non-diarrheal children (53.6% vs. 27.8%, P < 0.001), with significantly higher detection of both viral (23.3% vs. 13.3%) and bacterial pathogens (34.2% vs. 12.5%). Pathogens independently associated with diarrhea included diarrheagenic Escherichia coli (DEC), Vibrio parahaemolyticus, Clostridioides difficile (CD), group A rotavirus (RVA), and Norovirus GII (NoVs GII). The proportion of children with any form of co-infection was also significantly higher in the diarrhea group compared with non-diarrheal children (16.1% vs. 4.5%, χ2 = 32.594, P < 0.001). Several specific dual-pathogen combinations-namely RVA + DEC (χ2 = 4.956, P = 0.026), RVA + CD (χ2 = 10.313, P < 0.001), RVA + NoVs GII (χ2 = 15.503, P < 0.001), and DEC + Blastocystis hominis (Bh)-were significantly more common among diarrhea cases (χ2 = 4.207, P = 0.041). Multiplicative interaction analysis further identified significant synergistic effects for RVA + DEC [odds ratio (OR) = 2.304, 95% confidence interval (CI): 1.194-5.089], RVA + CD (OR = 6.199, 95% CI: 1.701-10.601), RVA + NoVs GII (OR = 6.296, 95% CI: 2.061-10.723), and DEC + Bh (OR = 4.602, 95% CI: 2.213-9.878).
CONCLUSION: This study demonstrates the frequent occurrence of co-infections in diarrheal children, and enteric pathogens may interact synergistically or antagonistically. It highlights the central role of RVA in exacerbating the severity of these co-infections. The findings emphasize the critical role of RVA vaccination in alleviating the burden and severity of diarrhea. Trial Registration The study was registered in the Chinese Clinical Trial Registry (ChiCTR-ROC-17013620).
METHODS: This large-scale, multicenter case-control study was conducted from January 1, 2024 to December 31, 2024, across four tertiary hospitals in Guangzhou, Guangdong Province, China. Stool samples were collected from children under five years with diarrhea (cases) and those without (non-diarrheal children). 21 enteric pathogens in each specimen were identified. Potential interactions between co-infecting pathogens were assessed using both additive and multiplicative models.
RESULTS: Enteric pathogens were more frequently detected in children with diarrhea than in non-diarrheal children (53.6% vs. 27.8%, P < 0.001), with significantly higher detection of both viral (23.3% vs. 13.3%) and bacterial pathogens (34.2% vs. 12.5%). Pathogens independently associated with diarrhea included diarrheagenic Escherichia coli (DEC), Vibrio parahaemolyticus, Clostridioides difficile (CD), group A rotavirus (RVA), and Norovirus GII (NoVs GII). The proportion of children with any form of co-infection was also significantly higher in the diarrhea group compared with non-diarrheal children (16.1% vs. 4.5%, χ2 = 32.594, P < 0.001). Several specific dual-pathogen combinations-namely RVA + DEC (χ2 = 4.956, P = 0.026), RVA + CD (χ2 = 10.313, P < 0.001), RVA + NoVs GII (χ2 = 15.503, P < 0.001), and DEC + Blastocystis hominis (Bh)-were significantly more common among diarrhea cases (χ2 = 4.207, P = 0.041). Multiplicative interaction analysis further identified significant synergistic effects for RVA + DEC [odds ratio (OR) = 2.304, 95% confidence interval (CI): 1.194-5.089], RVA + CD (OR = 6.199, 95% CI: 1.701-10.601), RVA + NoVs GII (OR = 6.296, 95% CI: 2.061-10.723), and DEC + Bh (OR = 4.602, 95% CI: 2.213-9.878).
CONCLUSION: This study demonstrates the frequent occurrence of co-infections in diarrheal children, and enteric pathogens may interact synergistically or antagonistically. It highlights the central role of RVA in exacerbating the severity of these co-infections. The findings emphasize the critical role of RVA vaccination in alleviating the burden and severity of diarrhea. Trial Registration The study was registered in the Chinese Clinical Trial Registry (ChiCTR-ROC-17013620).