Take on Typhoid April Newsletter

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In this issue:

Congratulations to Dr. Kathleen Neuzil, newly named director of Fogarty International Center and associate director of National Institutes of Health

Dr. Kathleen Neuzil, who has led the TyVAC project since it began in 2017, has been selected as the director of the Fogarty International Center (FIC) and National Institutes of Health associate director for international research. Although Dr. Neuzil will transition from her leadership position at the University of Maryland School of Medicine Center for Vaccine Development and Global Health, she will continue to champion typhoid vaccines. In her new role, Dr. Neuzil will lead FIC to support and facilitate global health research conducted by US-based and international investigators, build partnerships between health research institutions across the globe, and train the next generation of scientists to address global health needs. Congratulations on this next step in your incredible career, Dr. Neuzil! Welcome and congratulations to Dr. Matthew Laurens, Professor of Pediatrics, Medicine, and Pathology, who will be the new TyVAC director. Dr. Laurens has been part of the project since its inception and will take on the new role in early May.

Typhoid intestinal perforation in Francophone Africa

Typhoid intestinal perforation (TIP) is a severe and dreaded complication of typhoid. TIP is often diagnosed by surgeons in the operating room, based on its distinctive anatomical features.

Despite the high burden of typhoid in Francophone Africa, these countries are underrepresented in previous systematic reviews. To address this knowledge gap, a new scoping review in PLOS Global Public Healthand blog in French and English—sheds light on the incidence and high morbidity of TIP in Francophone Africa, exacerbated by limited access to appropriate and timely healthcare. These data—representing 12 countries—are critical for policymakers prioritizing new vaccine introductions. A coordinated approach—including typhoid conjugate vaccines (TCVs) and improvements in water, sanitation, and hygiene (WASH)—is key to taking on typhoid!

Expanding TCV options with a third WHO-prequalified product

In early March 2024, a new TCV received prequalification (PQ) from the World Health Organization (WHO). The prequalification process ensures that vaccines meet global standards of quality, safety, and efficacy. SKYTyphoid™, developed by SK bioscience and the International Vaccine Institute, is the third TCV to achieve PQ and is now eligible for introduction in countries utilizing Gavi, the Vaccine Alliance support. Diversifying the market and increasing vaccine supply is a great stride in efforts to take on typhoid. Dr. Emmanuel Mugisha, director of PATH’s work on the TyVAC project, explains the significance of this achievement and expressed that the time is now to prioritize TCVs in a recent blog.

Immune response to TCV in Nepal

TCVs administered as a single dose are highly effective in preventing typhoid. Researchers conducted a study in Nepal, where one hundred children who received TCV at either 9 or 12 months of age were given a second dose at 15 months of age. The study showed a single dose of TCV is immunogenic in both the 9- and 12-month age groups. The children vaccinated at 9 and 15 months exhibited a stronger immune response after the second dose compared to the group vaccinated at 12 and 15 months however, the magnitude of the rise in both the groups was modest compared with the increases after the primary dose.

This study provides additional evidence supporting the immunogenicity of a single dose. The benefits of a second dose may be more pronounced with much longer intervals – and studies are underway to investigate the need and response to additional doses. WHO recommends a single dose of TCV—in typhoid-endemic areas—for children 9 months of age, or in the second year of life—followed by introduction into routine immunization at 9- or 15-months.

Tuvalu introduces TCV

Tuvalu, a small island nation on the frontlines of climate change, launched a TCV campaign earlier this year in schools and local communities. The Tuvalu Ministry of Health strategically decided to introduce TCV. The campaign focused first in Funafuti, the capital, and subsequent phases will extend to the outer islands to ensure everyone between 9 months and 65 years is vaccinated.

As a low-lying nation, Tuvalu is exceptionally vulnerable to the impact of extreme weather events like floods and cyclones induced by climate change. Health officials in Tuvalu are optimistic about eliminating typhoid from their country through improved WASH interventions, as well as the introduction of TCV.

Thirty years of drug resistance

During the past three decades, there has been a rise in drug-resistant enteric fever in low-and middle-income countries. A new study by the Global Research on Antimicrobial Resistance Project, published in The Lancet Global Healthestimates drug-resistant Salmonella Typhi and Paratyphi A prevalence in 75 endemic countries, including 30 locations with limited data. Researchers developed a spatiotemporal model, including more than 600 data sources, to provide a 30-year snapshot of drug-resistant enteric fever. This study is the largest and most comprehensive synthesis of drug resistant data and trends in enteric fever. Knowing the magnitude of drug resistance could help pave the way for targeted public health interventions, including TCVs.

Understanding typhoid burden in Africa

recent surveillance study, conducted at 25 sites across 6 African countries—Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria—found typhoid is a major cause of illness in sub-Saharan Africa. These findings are complementary to other surveillance studies conducted in Africa. Across all study sites, the highest disease burden was in children younger than 15 years old. Other key results suggest typhoid burden is comparative—and sometimes higher—in rural areas than urban centers, which is a different pattern than what has been observed in parts of Asia. Additionally, the study found a high prevalence of drug-resistant typhoid infections, which are harder to treat, across the study sites.

As more countries consider TCV introduction, these data support evidence-based decisions about typhoid control. The study highlights the urgent need for TCV introduction into routine childhood immunization and the importance of reaching children, regardless of where they live. TCVs are also highly effective against drug-resistant typhoid strains and can decrease the risk of typhoid transmission, potentially delaying the emergence and spread of drug-resistant strains.

TCV introduction projected to be cost saving in Bangladesh

recent modeling study projects the cost-effectiveness and public health impact of TCV introduction in Bangladesh. Researchers used a mathematical model to compare no vaccination to eight different vaccine introduction strategies, including routine and one-time campaign strategies that differed by age group and geographic focus. The results project all TCV strategies examined would be cost saving compared to no vaccination. The preferred strategy from a cost-effectiveness perspective was a nationwide introduction of TCV at 9 to 12 months of age with a single catch-up campaign for children ages 1 to 15 years. Compared to no vaccination, this strategy is projected to avert nearly 4 million cases, more than 11,000 deaths, and save more than US$172 million in 10 years following implementation. The government of Bangladesh has made the decision to introduce TCV into the routine immunization program to protect children from typhoid throughout the country.

Outbreak Reports

Pakistan: An outbreak of typhoid has been identified in Rumbur Kalash Valley and the neighboring Attani village of Ayun in Lower Chitral district. Dr. Fayaz Rumi, the district health officer for Lower Chitral, said that blood and urine samples from suspected patients have tested positive for extensively drug-resistant typhoid. Samples from patients admitted to the District Headquarters Hospital have been sent to the National Institute of Health in Islamabad for further analysis.

Scientific publications

Incidence of typhoid fever in Burkina Faso, Democratic Republic of the Congo, Ethiopia, Ghana, Madagascar, and Nigeria (the Severe Typhoid in Africa programme): A population-based study

Efficacy of typhoid vaccines against culture-confirmed Salmonella Typhi in typhoid endemic countries: A systematic review and meta-analysis

Typhoid intestinal perforation in Francophone Africa, a scoping review

Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age

Old tools, new applications: Use of environmental bacteriophages for typhoid surveillance and evaluating vaccine impact

A phase II clinical trial of a Vi-DT typhoid conjugate vaccine in healthy Indonesian adolescents and adults: One-month evaluation of safety and immunogenicity

A description of a pre-emptive typhoid Vi capsular polysaccharide vaccination campaign after the 2015 earthquake in Nepal and vaccine effectiveness evaluation

Prevalence and antimicrobial resistance profile of Salmonella Typhi infection in Iraq, 2019-2021

Variations of blood viscosity in acute typhoid fever: A cross-sectional study

Visit our publications page for more recent research

Typhoid conjugate vaccine is an important preventative tool during times of water scarcity

Eliminating the risk of typhoid while confronting climate change

Typhoid intestinal perforations: valuable disease indicator in Francophone Africa

A ripple effect – navigating the waters of typhoid transmission

A third TCV receives WHO prequalification amidst rising rates of drug resistant typhoid

Understanding typhoid burden in Africa

The importance of inclusivity to take on typhoid

Immune response to TCV in Nepal

The opportunities and challenges that shaped Malawi’s integrated TCV campaign

Previous posts available on the blog