Prevalence and Patterns of Enteric Co-Infections Among Individuals Presenting with Cholera-like Diarrheal Disease During Seasonal Cholera Outbreaks

Cholera remains a major public health challenge, and co-infections can complicate out-comes and case management. In a cross-sectional study, we investigated the prevalence and patterns of enteric co-infections during Zambia’s 2023–2024 cholera outbreak and evaluated their implications for disease severity. 240 suspected cholera patients were enrolled from five healthcare facilities in Lusaka. Stools were tested for 11 enteric pathogens using the Bosphore® Gastroenteritis Panel Kit v2 on the QuantStudio 5 qPCR, with Vibrio cholerae confirmed by real-time PCR (quantitative PCR). Co-infections were highly prevalent, affecting 79.2% of participants. Campylobacter was the most frequently detected pathogen (70.0%), followed by Norovirus GI/GII (20.0%), while EIEC/Shigella, Adenovirus, VTEC, Astrovirus, Clostridioides difficile, and Salmonella occurred in < 10% of cases. Persons living with HIV were significantly more likely to present with co-infections than their counterparts (adjusted PR 1.27, 95% CI: 1.07–1.51; P = 0.008). Participants with confirmed V. cholerae + coinfections (N=62) were less likely to developed moderate to severe disease compared to those with mono-infections (adjusted PR 0.59, 95% CI: 0.38–0.90; P = 0.014). These findings highlight the high prevalence and complexity of co-infections during cholera outbreaks, potentially contributing to antimicrobial re-sistance. They also highlight the need for targeted clinical management, particularly among persons living with HIV.