In 2005, over 600 clinically diagnosed typhoid fever cases occurred in South Africa, where an outbreak had been previously described in 1993. Case-control and molecular investigations, including Salmonella enterica serovar Typhi (S. Typhi) isolates from that area from 1993, 2005 and later, were undertaken. Controls were significantly older than cases (P=0.003), possibly due to immunity from previous infection, and a significantly larger proportion had attended a gathering (P=0.035). Exposure to commercial food outlets and person-to-person transmission
was not significant. Pulsed-field gel electrophoresis and multi-locus tandem repeat analysis revealed common clusters of S. Typhi strains identified in 1993 and 2005 as well as in 2007 and 2009. This outbreak probably occurred in a non-immune population due to faecally
contaminated water. S. Typhi strains appeared to be related to strains from 1993; failure to address unsafe water may lead to further outbreaks in the area if the current population immunity wanes or is lost.