Spatial and Genomic Data to Characterize Endemic Typhoid Transmission

Abstract

Background Diverse environmental exposures and risk factors have been implicated in the transmission of Salmonella Typhi, however, the dominant transmission pathways through the environment to susceptible humans remain unknown. Here, we utilize spatial, bacterial genomic, and hydrological data to refine our view of Typhoid transmission in an endemic setting. Methods 546 patients presenting to Queen Elizabeth Central Hospital in Blantyre, Malawi with blood culture-confirmed typhoid fever between April 2015 and January 2017 were recruited to a cohort study. The households of a subset of these patients were geolocated, and 256 S. Typhi isolates were whole genome sequenced. Pairwise single nucleotide variant (SNV) distances were incorporated into a geostatistical modeling framework using multidimensional scaling. Results Typhoid fever was not evenly distributed across Blantyre, with estimated minimum incidence ranging across the city from less than 15 to over 100 cases/100,000/year. Pairwise SNV distance and physical household distances were significantly correlated (p=0.001). We evaluated the ability of river catchment to explain the spatial patterns of genomics observed, finding that it significantly improved the fit of the model (p=0.003). We also found spatial correlation at a smaller spatial scale, of households living <192 meters apart. Conclusions These findings reinforce the emerging view that hydrological systems play a key role in the transmission of typhoid fever. By combining genomic and spatial data, we show how multi-faceted data can be used to identify high incidence areas, understand the connections between them, and inform targeted environmental surveillance, all of which will be critical to shape local and regional typhoid control strategies.

Genomic epidemiology and antimicrobial resistance transmission ofSalmonellaTyphi and Paratyphi A at three urban sites in Africa and Asia

“…Use of the same passive surveillance protocols across all sites, in defined study catchments and including all ages, allows the results to be compared between sites. The genotype prevalences we estimated are in line with other studies of enteric fever pathogens reported from the same cities 2, 3, 7–10, 21, 25, 26 , but we also specifically addressed pathogen diversity across age groups. We show that although the disease burden is highest in children 20 , the same pathogen variants (serovars, genotypes, and AMR) circulate across age groups (pre-school, school-age, and adult), with near-identical sequences (0-SNV clusters) identified across age groups ( Figs.…”

“…The Blantyre study area has a complex river system, comprising 10 river catchments in close proximity, and recent spatial modelling of S . Typhi sequences in this setting showed that dividing space into river catchments explained the spatio-genetic patterns much better than simple grid coordinates 26 . Detailed spatial modelling is beyond the scope of this study but is planned for all STRATAA sites.…”

The rpoS gene confers resistance to low osmolarity conditions in Salmonella enterica serovar Typhi

“…Our results indicate that rpoS is likely to play an important role in surviving this transition. In addition, since S. Typhi does not productively infect animals other than humans, it may have to exist for extended periods in wells, ponds, rivers and other freshwater collections that represent sources of infection in parts of the world where typhoid is endemic [20][21][22][23]. Thus, S. Typhi may be particularly dependent on rpoS for survival in such environments, raising the possibility that targeting this gene or its downstream functions could represent a strategy for interfering with transmission of the pathogen.…”

“…This requirement may be particularly relevant to S. Typhi, which does not have a non-human animal host that can act as an intermediary in transmitting infection. Although direct fecal-oral transmission of S. Typhi between humans may occur, indirect transmission via consumption of untreated water from wells, ponds and rivers probably plays an even more important role [20][21][22][23]. Thus, the pathogen must have the ability to adjust to and tolerate the low osmolarity of such freshwater sources.…”

Understanding the Mechanism of Antimicrobial Resistance and Pathogenesis of Salmonella enterica Serovar Typhi

“…The transmission of S. Typhi is classified into two patterns. Short-cycle transmission refers to the contamination of food and water sources by shedding of the bacterium through feces in the immediate environment or close proximity, which facilitates transmission through poor hygiene and sanitation practices, and is generally linked to food handlers [ 7 ]. Long-cycle transmission occurs when the broader environment (such as untreated water or sewage) is polluted with human feces or when it is used as a raw fertilizer for crops [ 8 ].…”