The Typhoid fever Surveillance in Africa Program (TSAP), funded by the Bill & Melinda Gates Foundation, was conducted from 2011 to 2013 at thirteen different healthcare facilities within ten countries in Sub-Saharan Africa.  My PhD program was embedded within this multi-center multi-country study. The findings from these studies suggest that the true burden of S. Typhi might be underestimated by blood culture alone. PCR based diagnosis can also be used for better diagnosis of suspected typhoid fever cases in hospitals and surveillance programs in sub-Saharan Africa. Majority of S. Typhi and NTS isolates from that region are resistant to ampicillin, chloramphenicol, cotrimoxazole and ciprofloxacin, which might threaten the effective patient management in the near future. For example, in some areas in Kenya, the physicians had to be aware that empirical antibiotic therapy with ampicillin, chloramphenicol, Trimethoprim/sulfamethoxazole and ciprofloxacin for S. Typhi infections might not be effective. In Burkina Faso, Tanzania, Madagascar, Senegal and Guinea-Bissau continuous antibiotic susceptibility surveillance is required to detect the emergence of ciprofloxacin resistant isolates in order to adjust treatment protocols in a timely manner.