Neglected Diseases
Diarrhoeal diseases are a group of illnesses caused by viruses, bacteria and protozoan parasites that spread through contaminated food or water. Without treatment, diarrhoeal diseases can cause severe illness and death. Children under the age of five and immunocompromised individuals are most at risk.
Rotavirus is the leading cause of severe diarrhoeal disease in young children worldwide, causing fever, vomiting and watery diarrhoea. Other diarrhoeal diseases include enteroaggregative E. coli (EAEC) and enterotoxigenic E. coli (ETEC), both of which can also cause fever and watery diarrhoea. For some people, cholera (caused by Vibrio cholerae) is asymptomatic but for others, infection can lead to severe diarrhoea and vomiting, and even kill within hours if left untreated. Shigellosis, caused by the Shigella bacterium, is highly contagious. Giardiasis is caused by the Giardia protozoan parasite found in soil, food and water contaminated by faeces. Cryptosporidium is a protozoan parasite that can survive in soil, food and water, causing cryptosporidiosis primarily in people who work with animals or live in overcrowded settings.
Approved vaccines against diarrhoeal diseases are sometimes ineffective or unsuitable for infants. New multivalent vaccines suitable for infants and with longer-term protection in high-burden settings are urgently needed. Such next-generation candidates for rotavirus include non-replicating parenteral vaccines, the most advanced being PATH’s trivalent NRRV (P2-VP8) candidate, undergoing Phase III trials. Other potential candidates remain in preclinical development, except for Mitsubishi Tanabe’s VLP rotavirus vaccine, MT 5625, which has progressed to Phase I development. Oral rehydration therapy and zinc supplementation are the mainstay of management in LMICs but are insufficient in many cases. Safe, effective, and affordable pathogen-specific drugs are also needed. The therapeutic pipeline currently includes both small molecule drugs and biologics, with only a few candidates in early-stage clinical development. Likewise, rapid diagnostic tests capable of differentiating between different diarrhoeal diseases, as well as diagnosing multiple diseases, are required; however, only one candidate, RLDT, is in late-stage development.
Bharat Biotech International’s inactivated cholera vaccine, Hillchol entered a Phase III trial in February 2023. ETVAX, a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit, has shown promising results in Phase I and II studies, suggesting that a safe and effective ETEC vaccine will soon be available, with Zambian Phase III trials to begin in 2024. After generating positive human results with its monovalent Shigella vaccine, LimmaTech began developing a multivalent vaccine in 2018. Results of its Phase I and Phase II studies are expected in December 2023. A positive outcome for safety and immunogenicity will support the further development with pivotal efficacy trials in the target paediatric population.