Typhoid fever, caused by the bacteria Salmonella Typhi, remains a major public health challenge in many developing countries. While widespread vaccination programs have helped control the disease in some parts of the world, typhoid still infects over 21 million people every year globally, killing over 200,000. An effective and low-cost vaccine is crucial to prevent further loss of lives from this preventable disease. In recent years, a new oral typhoid vaccine has shown promising results and could be a game changer in the fight against typhoid.

Development of the Oral Vaccine
Traditionally, typhoid vaccines were administered via injection. However, needle-based vaccines often require trained healthcare workers for administration and proper storage facilities for transportation which pose logistical challenges especially in remote areas. To address these issues, scientists at the University of Maryland School of Medicine developed an oral typhoid vaccine using a live, attenuated strain of S. Typhi. In laboratory studies starting in the 1980s, this vaccine strain was found to be safe and highly immunogenic in animal models. The first efficacy trials in humans were conducted in Chile in the 1990s which demonstrated the vaccine's protection against typhoid fever. This provided the proof-of-concept needed for further development of the vaccine.

Clinical Trials and WHO Prequalification
Large Phase 3 efficacy trials involving thousands of participants were subsequently conducted among children and adults in Vietnam and India between 2008-2014. These studies confirmed the oral vaccine's safety, immunogenicity and protection against typhoid infections ranging from 56-87% after 3-5 years of follow up. No serious adverse effects were reported.

Introduction and Roll-out in Countries
Following the WHO endorsement, the oral typhoid vaccine was introduced in vaccination programs in several countries. In 2014, Nepal became the first country to introduce the vaccine for children between 9 months to 15 years of age. Pilot programs were conducted in selected districts demonstrating the vaccine's feasibility of use in field settings. In 2019, the vaccine was introduced nationwide across Nepal. Pakistan also introduced the vaccine in Sindh province in late 2019 for all children between 9 months to 15 years of age.

Challenges and Opportunities
While the introduction of oral typhoid vaccine is gaining momentum, there are some challenges that need to be addressed. Ensuring adequate and sustained vaccine supplies remains the key hurdle as large-scale manufacturing is still scaled up. Affordability also needs to be optimized through resource mobilization and establishment of advance purchase agreements. Logistical requirements of administering the oral vaccine also present complexity as compared to injectable shots especially in remote communities with limited healthcare infrastructure.

Conclusion
The successful development of an effective oral typhoid vaccine after decades of research offers renewed hope in the fight against the deadly yet preventable disease. Initial widespread introduction programs in Nepal, Pakistan and other countries have delivered promising results. While challenges remain, concerted efforts to enhance supply stability, drive down costs and optimize delivery approaches can help revolutionize typhoid control globally.