The Widal test being the most popular method . Blood samples most popularly used for diagnosis and stool samples are recommended to be avoided due to asymptomatic faecal shedding following the infection.
While NAT tests have higher that are developed are mostly conventional PCR and LAMP have been demonstrated to have specificity of . the Merieux foundation is validated a NAT in Bangladesh and currently in progress in Democratic Republic of the Congo, Burkina Faso, Malawi and Ghana.
A recent stakeholders engagement summarized that the current challenges in diagnostics needs to improve the sensitivity of the tests to >90% and specificity >95% (Richard et al., 2019)
Add WHO guidelines
CRISPR Scissors for molecular detection
With the pressing need for a NAT for enteric fever, the gudiWHO the ASSURED (Affordable Specific Sensitive User-friendly Rapid Equipment-friendly Delivered) characteristic diagnostics for low-resource settings \citep{S2016} . CRISPR-Cas based molecular detection are gaining popularity due to some of their ASSURED attributes like high sensitivity and specificity. Additionally, these methods rely on iso-thermal amplification of the target which results in rapid results and with dependency on simple equipment that could be battery powered for field deployment. However, to employ these methods for diagnosis of enteric fever, the ? needs to be further optimized to achieve affordability.
PCR has been the 'gold standard' for diagnostics due to his high sensitivity and specificity. However, using PCR depends on thermocycler which could be expensive and also slow .The discovery of isothermal methods of amplifying the nucleic acid target in the last two decades has revolutionized the POC diagnostics by reducing the amplification time and bypassing the need for expensive thermocycler. Recombinase polymerase amplification (RPA) \cite{Piepenburg_2006} and loop mediated isothermal amplification (LAMP)\cite{Notomi2000} are the two most popular PCR alternatives that could be applied for low cost POC diagnostics in LMICs.
CRISPR-Cas based bacterial adaptive immunity depends on RNA to direct the Cas endonuclease to detect and destroy the foreign nucleic acid. Since the first demonstration of the ability of Cas13a to cleave non-targeted RNA after recognizing and cleaving the targeted RNA template \cite{East_Seletsky_2016}, CRISPR-Cas platform like Cas12-DETECTR \cite{Chen_2018}, Cas14-DETECTR \cite{Harrington_2018}, Cas13-SHERLOCK \cite{Gootenberg_2017} are finding wide application in molecular diagnosis. While Cas13a recognizes RNA as a template strand, Cas14 recognizes ssDNA and Cas12 recognizes ds/ss DNA. The choice of any these molecular scissors depends on the needs of the detection molecule and the end product. CRISPR-Cas technique has now widely been applied to detect human papillomavirus \cite{Chen_2018}, ZIKA virus \cite{Kellner_2019} and also the 2020 pandemic Sars-CoV-2 \cite{Broughton_2020,Ding_2020}.