Fig. 4.

Schematic model for the influence of phage on cholera seasonality and serogroup emergence. Seasonal cholera epidemics (increased cases over time) occur in waves, with different serogroups (e.g., O1 or O139) dominating. Corresponding conditions that exist in the aquatic environment are diagramed in the circles shown. The absence of yellow phage specific for yellow oval cells provides an opportunity for that serogroup to begin the seasonal epidemic and transmit efficiently. However, yellow phages eventually amplify in the environment and attack this serogroup, ending that epidemic. A different serogroup (red oval cells) is resistant to the yellow phage. In the case shown, red cells actually carry a prophage (yellow intracellular circle) and thus shed yellow phage. A second epidemic wave due to the red serogroup follows and runs its course until red phages bloom and prevent environmental transmission of this serogroup. The interepidemic period is dominated by sporadic disease due to other serogroups (blue cells) resistant to both phages. These strains usually lack typical virulence factors but are more environmentally adapted than virulent strains. However, blue cells may harbor prophages that kill virulent serogroups and may acquire virulence determinants by horizontal gene transfer. Thus, blue cells may eventually emerge to become a new epidemic serogroup.