Paratyphoid fever (together with typhoid fever, collectively known as enteric fever) is caused by Salmonella enterica serovars Paratyphi (S. Paratyphi) A, B and C. S. Paratyphi A is the most common serovar while Paratyphi C is uncommon. S. Paratyphi A, like S. Typhi, has adapted to human hosts; it causes similar clinical syndromes to typhoid, including fevers, chills, abdominal pain, and can be a life-threatening illness in severe cases.  

The Global Burden of Disease (GBD) study 2019 estimated 3.8 million cases of paratyphoid fever (due predominantly to paratyphoid A) and 23,300 deaths globally, and an age-standardized incidence of 51.3/100,000. Incidence rates of paratyphoid fever vary widely according to geography; it is most prevalent in South and South-East Asia, but is not as common in Africa. Incidence is highest among children, peaking in the 5–9-year age group.  Age-specific incidence may vary by country, and children with paratyphoid are generally older than those with typhoid. 

Paratyphoid fever is estimated to be responsible for approximately one-fifth of all enteric fever cases, but its overall relative burden compared to typhoid fever is highly variable depending on the geographic context, and is reportedly increasing.  There are observations that the increase may be associated with vaccination against typhoid, thus it is important to monitor the burden of paratyphoid fever, especially with the implementation of typhoid conjugate vaccines.  

S. Paratyphi infection is primarily treated with fluoroquinolones, third-generation cephalosporins, and azithromycin. Antimicrobial resistance (AMR) remains a major threat, including the potential for extreme drug resistance and azithromycin resistance. Carbapenems are reserved for suspected infection with extensively drug-resistant strains.

There is currently no vaccine available to prevent paratyphoid fever.  Similarities between S. Paratyphi and S. Typhi, and the fact that there are licensed vaccines for S. Typhi, suggest that paratyphoid vaccines are highly feasible. However, standalone paratyphoid vaccines are unlikely to be used at a national level. Given the availability of licensed typhoid conjugate vaccines which received a WHO policy recommendation in 2017, bivalent vaccine candidates targeting both typhoid and paratyphoid fever are more attractive, and they can potentially address the burden of enteric fever in countries where both pathogens are endemic.  Both monovalent S. Paratyphi A and bivalent vaccine candidates are now in clinical development; candidates based on lipopolysaccharide O-antigen, (O:2) conjugated to a range of protein carriers, live attenuated strains (LAV), and other platforms, are in the pipeline.  

A Phase 1 trial of a live attenuated, oral vaccine candidate against S. Paratyphi A (CVD 1902) has found the vaccine to be safe and immunogenic, and the vaccine will be further evaluated in a Controlled Human Infection Model (CHIM) study.  The O:2-tetanus toxoid (O:2-TT) vaccine candidate that targets lipopolysaccharide O-antigen (O:2), the protective antigen of S. Paratyphi A, has been found to be safe and immunogenic, and is the most advanced along the clinical development pathway (In Phase 2) compared to other paratyphoid A vaccine candidates.

References: 

1) Institute for Health Metrics and Evaluation (IHME). GBD 2019 Cause and Risk Summary: Paratyphoid fever. Accessed 6th October 2021. Seattle, USA: IHME, University of Washington, 2020.

2) Gibani M.M., Britto C., Pollard A.J. Typhoid and paratyphoid fever: A call to action. Curr. Opin. Infect. Dis. 2018;31:440–448.

3) Viral Vector Vaccine - Salmonella Typhi and Paratyphi vaccine