Introduction to Typhoid

Typhoid fever, also known simply as typhoid, is a bacterial infection caused by Salmonella Typhi. Those infected experience a sustained fever as high as 103-104°F, weakness, stomach pains, headache, and loss of appetite. Left untreated, it can serious complications and prove fatal in upto 20% of cases. It is estimated that over 11 million cases of typhoid occur globally each year resulting in over 128,000 deaths.

History of the Disease and Vaccine Development

Oral Typhoid has long plagued human populations throughout history. The earliest known accounts of an illness resembling typhoid date back to ancient Greece in the 4th century BC. It was a significant cause of morbidity and mortality in Europe during the 19th century, before the development of sanitation infrastructure. The first effective vaccine against typhoid was developed in 1914 by Turkish scientist Dr. Selman Waksman. However, this early vaccine required injection and multiple doses to induce protection, limiting its uptake and public health impact.

The Oral Typhoid Vaccine Option

In the late 1980s, scientists worked to develop an enteric fever vaccine that could offer broader protection with greater ease of administration compared to injectable versions. In 1995, the first live attenuated enteric fever vaccine (Ty21a) was licensed and has since been prequalified by the World Health Organization. This landmark oral vaccine is given in a very small enteric-coated capsule which protects the live but weakened bacteria as they pass through the stomach. Upon reaching the intestines, the bacteria are able to colonize and induce immune responses without causing disease. Several doses are required for full protection but the non-invasive nature of oral administration has had major public health benefits.

Efficacy and Implementation Studies

Following its initial licenses in the 1990s, numerous clinical efficacy studies were conducted with Ty21a in various typhoid endemic regions. A major trial in Vietnam involving over 40,000 children found 72% protective efficacy after 3 doses over 6 months. Programmatic effectiveness studies conducted as part of routine vaccination programs in Kolkata, India and Islamabad, Pakistan demonstrated real-world protection rates of over 60%. A recent long-term follow up study in Kolkata found persistent protective antibody levels over a decade later. Several countries in Asia and Latin America have now incorporated enteric fever vaccination into their routine immunization schedules targeting at-risk groups.

Potential for Expanded Global Use

Despite the demonstrated public health impact of enteric fever vaccination, global coverage remains low even in places with the highest burden such as South Asia and sub-Saharan Africa. Barriers to broader implementation include the multi-dose schedule, cold-chain requirements, programmatic complexity and relatively high vaccine costs. There is an urgent need for new and improved enteric fever vaccines to overcome these challenges. Developers are currently evaluating novel single-dose live attenuated strains as well as recombinant protein subunit vaccine options that could offer the advantages of oral administration with a simplified schedule. If successful, these next-generation vaccines may allow for mass vaccination campaigns and inclusion in routine childhood immunization programs. With expanded use, enteric fever vaccination has the potential to significantly reduce the global disease burden and achieve control or possible elimination in certain settings.

Conclusion

In conclusion, oral typhoid vaccination represents a major breakthrough for the prevention of this serious enteric fever. Since the licensure of the pioneering Ty21a vaccine over 25 years ago, clinical trials and public health studies have clearly shown significant protection provided through the non-invasive oral route of administration. However, global coverage of oral typhoid vaccines remains inadequate in relation to disease burden. New developments towards single-dose vaccines and alternate platforms hold promise to further revolutionize control efforts. With continued innovation and prioritization of implementation, oral typhoid vaccination stands to make major gains against this enduring global health threat.