Neglected Diseases
Salmonella infections are a group of diseases caused by the Salmonella enterica bacteria, and transmitted through contaminated food or drink. These include: typhoid (caused by Salmonella Typhi); paratyphoid fever (caused by Salmonella Paratyphi A, B or C) – collectively referred to as enteric fever; and thousands of non-typhoidal serotypes, referred to as non-typhoidal Salmonella (NTS). Enteric fevers affect only humans, while NTS affects both humans and animals.
Salmonella infections are more common where there is dirty water and poor sanitation or hygiene. Symptoms can include fever, malaise, headache, constipation or diarrhoea, and an enlarged spleen and liver. Occasionally rose-coloured spots appear on the chest. In the case of typhoid fever, a small proportion of people can recover but still carry and spread the bacteria for as long as a year after infection. Diagnosis of Salmonella infections may require a blood, stool or bone marrow sample.
Typhoid can be successfully treated with available antibiotics. However, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of S. typhi, the causative agent of typhoid, have emerged and are spreading rapidly. The emergence of the XDR strain is especially alarming as it is resistant to almost all the available therapeutic options. There is an urgent need for a next generation of antibiotics that are effective against resistant strains. Current pipeline candidates include several broad-spectrum antibiotics with the potential to be effective against drug-resistant strains of S. typhi, but most are in the pre-clinical stage of development. The WHO recommends typhoid conjugate vaccines (TCVs) as the preferred vaccine for use in Salmonella prophylaxis in endemic regions. Two such TCVs – Typbar TCV and TYPHIBEV are currently pre-qualified by the WHO.
The Salmonella infections pipeline predominantly targets typhoid & paratyphoid fever – accounting for 12 (out of 17) vaccines and all nine diagnostics in development, including all Phase III candidates, all but one Phase II candidate and two candidates in Phase I. Although NTS accounts for a smaller portion of the pipeline, all currently active vaccine clinical trials target NTS, including the bivalent vaccine iNTS GMMA, and trivalent vaccines iNTS-TCV and Trivalent Salmonella Conjugate Vaccine (TSCV). The latter entered Phase II trials in early 2023. iNTS GMMA and iNTS-TCV are the first NTS vaccines tested in humans; and are currently undergoing a joint Phase I/IIa trial. These vaccines will be evaluated in two stages: initially among European adults in stage 1, followed by African adults in stage 2. Prokarium has submitted results to the National Library of Medicine for their Phase I trial investigating a bivalent oral vaccine targeting both typhoid and paratyphoid fevers.