Nepal’s success in typhoid vaccine trial

Just as Nepal was recovering from the Covid pandemic in 2022, the government with GAVI, the Vaccine Alliance, inoculated almost 8 million school-children against typhoid. 

What was even more remarkable was that this vaccine was earlier trialled among 20,000 people in Lalitpur, showing a significant reduction in typhoid incidence with efficacy rate of an impressive 80%, and was the subject of a research paper in the New England Journal of Medicine in 2019. 

This kind of Typhoid Conjugate Vaccine (TCV) has also been used in Malawi and Pakistan where there has been a drop in typhoid cases.

The trial was undertaken by the Oxford University Clinical Research Unit (OUCRU) Nepal which was set up in Lalitpur in 2003 to control endemic typhoid fever in Nepal and the region.

Besides vaccines, OUCRU-Nepal has also carried out ground breaking randomised controlled trials in the treatment of typhoid fever. Its seminal paper in the journal Lancet Infectious Disease in 2016 influenced WHO to suggest that the fluoroquinolone drugs which was chosen at the time for typhoid fever should not be used in the empirical treatment of typhoid fever in South Asia.

Nepal’s successes both in the prevention and treatment of typhoid fever will be showcased at the 17th Asian Conference on Diarrhoeal Diseases and Nutrition (ASCODD) in Kathmandu 8-11 December titled Emerging Enteric Infections and Impact of Climate Change.

Over 300 experts will attend the conference, including Andrew Pollard who helped develop the Oxford AstraZeneca Covid vaccine and Edward Thomas Ryan, immunologist at Harvard University and Massachusetts General Hospital, among others. Buddha Basnyat and Andrew Pollard were the two principal investigators for the typhoid conjugate vaccine trial in Lalitpur.

“The conference is a one of a kind platform bringing together researchers, policymakers, and public health professionals from across Asia and beyond to address critical challenges in diarrhoeal diseases, nutrition, and public health,” says Abhilasha Karkey, medical microbiologist and director of OUCRU Nepal.

Typhoid fever is prevalent in countries with poor hygiene and is transmitted through the faecal-oral route. If untreated, it can cause complications leading to death. Treatment is straightforward, but antibiotic resistance is a growing problem.

“Typhoid, much like tuberculosis, is a biblical disease,” explains Buddha Basnyat, chair at the OUCRU Nepal. “It is hardly heard of in developed countries, except in travelers from our part of the world.”

Indeed, South Asia including Nepal has an incidence of about 500 cases per 100,000 population. Anything over 100 per 100,000 is regarded as ‘alarming’. Hotspots include cities like Kathmandu, Karachi, New Delhi, Dhaka and Kolkata.

It goes without saying that the best antidote to diseases like typhoid fever and cholera is safe drinking water and better hygiene, which can only be guaranteed with political accountability and education.

“Careful study of typhoid burden, and performance of typhoid vaccines in children, led by OUCRU-Nepal based at the time in Patan Hospital in Nepal in collaboration with the Oxford Vaccine Group, has been central to the development of policy by the World Health Organisation,” Andrew Pollard told Nepali Times.

He added: “As a result of the contribution of the Nepali investigators, more than 60 million children have been protected against typhoid around the world in the past two years and many tens of millions more will be protected in the decade ahead.”

Typhoid fever is also often misdiagnosed. Nine years ago in the aftermath of the Nepal earthquake, there were several deaths across the country as they were wrongly diagnosed because of the widespread use of the Widal test that is consistently known to give false results.

In reality, these patients had typhus fever which is spread to humans by fleas, lice, and chiggers, and required a different antibiotic, not ceftriaxone, a potent antibiotic for typhoid fever.  

ASCODD 2024

The ASCODD 2024 is a platform for Nepal to present its public health research, including in the prevention and treatment of enteric illnesses like typhoid. The conference theme is Emerging Enteric Infections and Impact of Climate Change.

Another key highlight is the launch and discussion of Nepal’s National Cholera Control Plan which reflects the country’s commitment to eliminating the disease. The last big cholera outbreak was in Jajarkot in 2009 that killed 111 people, mainly children, and in 2016 in Kathmandu with 169 cases.

“At the conference, we will explore the latest scientific advancement in diagnostics, treatment, vaccines while emphasising equitable access to these tools in resource-limited settings and in climate vulnerable countries like Nepal,” says Abhilasha Karkey, director of OUCRU Nepal.

Keynote speaker is the former director general of the International Vaccine Institute (IVI) John Clemens and other sessions will look at the latest trends in antimicrobial resistance, the impact of the climate crisis on enteric diseases and community-based interventions.

What is the difference between typhoid fever and typhus fever?

Typhoid fever is often confused with other illnesses not just because they sound the same, but have common symptoms.

Typhoid fever is caused by the bacteria Salmonella typhi or Salmonella paratyphi via water or food contaminated with fecal matter. It leads to high fever, rashes, headache, general weakness, diarrhoea. Typically, these last for a week but are clearly preventable with better hygiene and vaccines. Treatment is a course of antibiotics. There is an alarming increase in antibiotic resistance.

Typhus fever is a rickettsial disease mainly transmitted through vectors such as mites, fleas, lice and ticks, and have non-specific symptoms similar to a bad cold, including fever, chills, headache, muscle pains and rash. A common antibiotic called Doxycycline is used in the treatment of the disease, but misdiagnosis has led to deaths in Nepal.