Typhoid conjugate vaccine shows 81% protection in phase 3 trial

Typhoid is a major cause of fever in children in low- and middle-income countries and is responsible for nearly 11 million cases and more than 116,000 deaths a year worldwide. It is caused by the bacterium Salmonella Typhi.

World Health Organization (WHO) has been recommending the use of vaccines against typhoid fever since 2008, to date no vaccines have been deemed suitable for widespread use in children in endemic areas. Although typhoid conjugate vaccine (TCV) has been shown to protect against the disease in studies involving healthy volunteers in the UK, no efficacy studies in endemic populations had been completed.

The researchers from the University of Oxford, the University of Maryland School of Medicine, and PATH have found that a single dose of a typhoid conjugate vaccine (TCV) was found to be immunogenic and effective in reducing typhoid fever in Nepalese children, according to interim results of a phase 3 trial.

The results of the interim analysis of a large field study in Nepal has been published in the New England Journal of Medicine.

The study involved 20,000 children aged 9 months to <16 years of age, who were randomly given one of two vaccines; half received TCV and half received the Group A meningococcal (MenA) vaccine - the latter acted as the control group.

Blood tests showed that typhoid occurred in 7 participants who received TCV and 38 receiving Men A vaccine. The researchers noted that these were preliminary results and that the study will continue to follow-up the participants for two years.

Andrew Pollard, Professor of Paediatric Infection and Immunity at Oxford University's Department of Paediatrics, said: "This is the first study to show that a single dose of TCV is safe, immunogenic, and effective, which provides clear evidence that vaccination will help efforts to control this serious disease and is a strong endorsement of the WHO policy for vaccine implementation."

"The efficacy of these results in an endemic population adds to a growing body of evidence supporting the use of TCV to reduce disease and save lives in populations that lack clean water and improved sanitation," said Dr. Kathleen Neuzil, MD, MPH Director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine and director of TyVAC.

These results show the vaccine has the potential to significantly reduce the burden of typhoid in high-risk populations. This is especially timely with the recent spread of extensively drug-resistant typhoid, which threatens child health in affected regions.

Pakistan's current typhoid outbreak is the first-ever reported outbreak of ceftriaxone-resistant typhoid and represents an alarming trend in the spread of drug-resistant typhoid. Not only is the strain resistant to ceftriaxone, the standard treatment in many parts of the world, but it is also resistant to the majority of antibiotics commonly used for typhoid, making it increasingly challenging and costly to treat.

TCVs have the potential to overcome many of the challenges that impeded the uptake of earlier vaccines, including longer-lasting protection, fewer doses, and suitability for children under two years of age, allowing for inclusion in routine childhood immunization programs.

The study, "Phase 3 Efficacy Analysis of a Typhoid Conjugate Vaccine Trial in Nepal," is published in the New England Journal of Medicine.

DOI: 10.1056/NEJMoa1905047