 Introduction Presently diagnostic tests for typhoid fever include serology and culture which both have relatively low sensitivity and specificity. Polymerase chain reaction (PCR) has exhibited mixed performance for blood specimens in the detection of Salmonella. This study compared the performance of serology test, stool culture and nested PCR and their feasibility in the Buea Health district in Southwest Cameroon.  Methods Three hundred and sixty (360) patients suspected of typhoid fever and sixty one (61) apparently healthy controls were selected for the study. Blood specimens were analyzed using Widal serology test. Stool was cultured and grown cells further analyzed using biochemical tests and nested PCR targeting the flagellin gene of Salmonella species. Performances of tests were determined using standard formulas.  Results Fifty (50) test group participants (13.9%), were stool culture positive for Salmonella following identification with API 20-E test kit. Nested PCR had the highest sensitivity of 91.9%, P = 0.000, while Widal slide and tube tests had the overall lowest performance. When nested PCR was considered as gold standard, stool culture had the highest specificity of 94.6%, P = 0.000. Based on cost, turnaround time and performance, stool culture and PCR appeared as suitable methods for reliable diagnosis of typhoid fever.  Conclusion Stool culture could be used as gold standard in conjunction with serology to improve diagnosis of typhoid fever in the study area. Additionally an algorithm should be explored using PCR for suspected or severe cases negative for both serology and stool culture.

Keywords : Typhoid fever, Salmonella, diagnosis, stool culture, nested polymerase chain reaction.