Old tools, new applications: use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact

Abstract

ABSTRACTTyphoid-conjugate vaccines (TCVs) provide an opportunity to reduce the burden of typhoid fever, caused bySalmonellaTyphi, in endemic areas. As policymakers design vaccination strategies, accurate and high-resolution data on disease burden is crucial. However, traditional blood culture-based surveillance is resource-extensive, prohibiting its large-scale and sustainable implementation.SalmonellaTyphi is a water-borne pathogen, and here, we tested the potential of Typhi-specific bacteriophage surveillance in surface water bodies as a low-cost tool to identify whereSalmonellaTyphi circulates in the environment. In 2021, water samples were collected and tested for the presence ofSalmonellaTyphi bacteriophages at two sites in Bangladesh: urban capital city, Dhaka, and a rural district, Mirzapur.SalmonellaTyphi-specific bacteriophages were detected in 66 of 211 (31%) environmental samples in Dhaka, in comparison to 3 of 92 (3%) environmental samples from Mirzapur. In the same year, 4,620 blood cultures at the two largest pediatric hospitals of Dhaka yielded 215 (5%) culture-confirmed typhoid cases, and 3,788 blood cultures in the largest hospital of Mirzapur yielded 2 (0.05%) cases. 75% (52/69) of positive phage samples were collected from sewage. All isolated phages were tested against a panel of isolates from differentSalmonellaTyphi genotypes circulating in Bangladesh and were found to exhibit a diverse killing spectrum, indicating diverse bacteriophages were isolated. These results suggest an association between the presence of Typhi-specific phages in the environment and the burden of typhoid fever, and the potential of utilizing environmental phage surveillance as a low-cost tool to assist policy decisions on typhoid control.Highlights-Typhi-specific bacteriophages can be isolated from surface waters in endemic countries using low-cost methods-More Typhi-specific bacteriophages are obtained in areas with higher typhoid cases-Typhi-specific bacteriophages exhibit diverse activity spectrum against a panel ofSalmonellaTyphi isolates circulating in Bangladesh-Environmental surveillance can be used as a tool to predict typhoid burdenGraphical abstract