Introduction

Enteric  fever (typhoid and paratyphoid fever) is a systemic infection caused by the gram-negative bacteria Salmonella enterica serovar Typhi (S. Typhi) and Paratyphi  A, B &C (S. Paratyphi) which are highly contagious and rapidly spread through ingestion of contaminated water and food in poor sanitary conditions. The disease causes approximately 17.8 million cases and 75,000–208,000 deaths worldwide each year \cite{Antillón2017}, predominantly in those under five years of age  \cite{Arora2019} and mostly concentrated in South and South-East Asia and sub-Saharan Africa \cite{who2019}.  S. Typhi is the most prevalent infection with 10.9 million cases worldwide compared to 3.3 million cases of S. Paratyphi \cite{ghdx}. However, most paratyphoid infections are diagnosed in Asia and a estimated 97·4% of cases in Central Sub-Saharan Africa are S. Typhi \cite{Stanaway_2019}.
Enteric fever caused by either pathogen is treatable with antibiotics but its clinical management faces two challenges:
  1. the clinical signs and symptoms of typhoid fever are non-specific. They overlap with malaria and other febrile illness which makes the prognosis presumptive.
  2. the diagnostic tests report take up to seven days and hence has  led to the over use of antibiotics leading to antimicrobial resistance (AMR) and multidrug resistance (MDR) in Africa and elsewhere \cite{Park2018}.
There is therefore a need for rapid and accurate diagnosis of typhoid fever and our research is focused on addressing these diagnostic needs in low and middle income countries, using Cameroon as an in-depth case study while recognising that needs will differ across different contexts.
This review identifies the key design goals for a molecular diagnostic approach to typhoid diagnosis in low and middle income countries using best practice principles for point of care test development \cite{Land_2018}, the most recent target product profile (TPP) \cite{Mather2019} and preliminary data from stakeholder engagement performed in Cameroon. 
We then undertake a literature review of typhoid NAT development from 1996 to 2022 and  investigate the extent to which the field is progressing towards meeting these identified needs. We conclude with recommendations for future research as well as reporting practices that could further the development of typhoid NATs that are fit for purpose in low and middle income country contexts.

Enteric fever burden and the role of diagnostics