Current approaches to typhoid diagnosis
Blood culture is considered the reference standard for typhoid diagnosis but requires sophisticated equipment, a large blood sample of 2 - 10 ml due to the low bacterial load in peripheral blood. It has very high specificity but and have poor sensitivity estimated at only 61% in a recent systematic reviewIn low-resource settings, serological tests are most commonly used. Infections can be detected in blood or stool samples but blood is preferred for differential diagnosis of active infections because there can be asymptomatic faecal shedding following the infection which may coincide with a different symptomatic illness, giving an incorrect diagnosis \cite{standards2018}. The Widal test is the oldest and most popular method that tests antibodies against the O and H antigen of S. Typhi by agglutination in the serum of an infected individual. However, it lacks specificity due to cross-reactivity with many other infections and has to be interpreted carefully in populations where the infection is endemic or actively vaccinated to account for pre-existing antibodies that do not indicate a current or recent infection \cite{Olopoenia2000}. The current commercially available rapid enteric fever diagnostics used globally detect immunoglobulin antibodies IgG or IgM e.g. Typhidot (Malaysian Biodiagnostic Research Sdn Bhdd, KL, Malaysia) detects the antibody against the S. Typhi outer-membrane protein \cite{Choo1999}, Tubex TF (IDL Biotech, Sollentuna, Sweden) detects antibody against LPS antigen \cite{Lim1998,Tam_2003}.