Take on Typhoid Newsletter January 2021

Taking on Typhoid

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In this issue:

2021, the year of the vaccine

Kathleen Neuzil, TyVAC Director

As we leave a year marked by fear, loss, and hardship, promise abounds in 2021. COVID-19 has been a harsh reminder of the rampant devastation an infectious disease can cause. Many vaccine-preventable diseases—including typhoid—continue to take a tremendous toll on families in low- and middle-income countries.

2021 brings hope and a light at the end of a long tunnel.

Just as COVID-19 vaccines hold promise of a return to some normalcy, typhoid conjugate vaccines (TCVs) offer a lifesaving intervention to communities in typhoid-endemic countries.

In December 2017, the World Health Organization (WHO) prequalified the first TCV and in December 2020, WHO prequalified a second TCV. Both vaccines are safe and immunogenic and can be administered to children as young as 6 months of age. Multiple vaccines, manufacturers, and formulations help increase supply and lower cost as countries introduce TCV into their routine immunization programs.

Zimbabwe and Liberia are preparing for nationwide introduction of TCV in 2021. These efforts, which follow the first phase of introduction in Pakistan in 2019, are especially monumental because they will be the first countries to introduce TCV into routine immunization in sub-Saharan Africa. Pakistan is poised to continue with the next phase of introduction as well. The vaccination campaigns will reach millions of children and have a positive impact on families, healthcare systems, and economies. TCV introduction is part of an integrated typhoid prevention and control strategy that includes improved access to safe water, sanitation, and hygiene.

This year also brings additional data from the TyVAC studies in Bangladesh, Burkina Faso, Malawi, and Nepal. Be on the lookout for study results, including efficacy data as well as more data on co-administration, safety, and immunogenicity. Furthermore, our partners continue to make critical strides in epidemiology, cost-effectiveness, and drug-resistance research.

We look forward to taking on typhoid in 2021!

More typhoid conjugate vaccines, more impact

TCVs are a lifesaving innovation and WHO recommended for use in routine immunization in typhoid-endemic countries. Last month, WHO prequalified a second TCV, TYPHIBEV, manufactured by Biological E, India. WHO prequalification—the international approval for vaccine safety, efficacy, and quality—is a key step for global procurement and support from Gavi, the Vaccine Alliance. This newly prequalified TCV is a single-dose injectable vaccine that can be administered to children as young as 6 months of age. Clinical studies demonstrated that TYPHIBEV is safe and immunogenic.

Additionally, the International Vaccine Institute and SK bioscience recently announced that its Vi-DT TCV has met its primary endpoints in a Phase 3 study in Nepal, confirming the new candidate induces an immune response similar to Typbar TCV®, the first prequalified TCV. The WHO prequalification of TYPHIBEV and development of additional TCVs with different formulations will help improve supply, lower costs, and provide countries with more freedom to choose which vaccine works best for their population and specific context.

From Asia to Africa, new data illustrate why we need to take on typhoid

While typhoid is a centuries-old disease, we continue to learn more about it through the on-going collection and analyses of data. New findings not only help us to better understand the true burden of typhoid, but they also inform public health policies and intervention strategies, such as the introduction of TCV. In a new supplement sharing results from Phase 2 of the Surveillance for Enteric Fever in Asia Project, we learned that the cost of a single case of typhoid often surpasses the total health expenditure per capita in many endemic communities in South Asia. Additionally, high rates of hospitalization for typhoid cases frequently subverts care for those affected by other non-vaccine preventable diseases.

This high burden of typhoid is similarly felt in much of sub-Saharan Africa, where a new systematic review and meta-analysis on the complications and mortality of typhoid indicates that there is a higher case fatality ratio in sub-Saharan Africa compared to Asia, likely due to delays in care. This is further illustrated by the devastating impact of typhoid intestinal perforations in sub-Saharan Africa, in which regional studies indicate that 20 percent of patients with this complication die.

As these new data illustrate, the widespread introduction of TCV in endemic settings is likely to be cost-effective and reduce the burden on the overall healthcare system—important considerations for policy- and decision-makers considering TCV introduction.

Data on TCV efficacy, safety, delivery presented at ASTMH

Updates on typhoid surveillance, drug resistance, and TCV efficacy, safety, and delivery were provided across dozens of presentations and posters at the all-virtual 2020 conference of the American Society of Tropical Medicine and Hygiene (ASTMH). Of note, new findings from several studies confirm TCV has a strong safety and efficacy profile among children. In Nepal, high TCV efficacy was sustained after 2 years of follow-up. Publications from these studies are expected soon.

Additionally, a study in Burkina Faso found a strong immune response when TCV was co-administered with other routine vaccines at 15 months of age. This study provides the first published TCV immunogenicity data to guide introduction strategies in sub-Saharan Africa, where young children are frequently ill with typhoid. These results will aid policymakers in their decision-making and support applications to Gavi for vaccine introduction. Read more in English or French.

Other studies at ASTMH presented evidence from TCV campaigns and introductions. In Zimbabwe, a study found that vaccination with TCV may help reduce the prevalence of decreased ciprofloxacin susceptibility—a positive sign that TCVs can help stop drug-resistant typhoid. Analyses from Pakistan, which introduced TCV in 2019, and a regional introduction in Navi Mumbai, India, highlighted how widespread vaccination with TCV is possible.

New drug-resistant typhoid resources

Drug-resistant typhoid poses a serious risk to health. There is widespread prevalence of known multidrug-resistant typhoid and increasing identification of extensively drug-resistant typhoid strains that do not respond to multiple classes of antibiotics. Take on Typhoid continues to spotlight this issue by developing new resources to explain drug resistance and the increasing burden it places on typhoid-endemic communities. During the past few months, our blog has featured several stories from different regions highlighting new research that demonstrates the scope and prevalence of this issue. Topics include how DNA sequencing data help the Philippines tackle drug resistance, the use of genomic data to better understand the burden of drug-resistant typhoid globally, major increases in resistance to all antibiotics recommended for typhoid treatment during the past 30 years, and recent discoveries of azithromycin-resistant typhoid strains in Pakistan, Bangladesh, Nepal, and India. Together, these data demonstrate the urgency of prevention measures to take on typhoid.

Tackling drug-resistant typhoid will require effective prevention with TCVs alongside safe water and sanitation systems. We recently launched a new infographic depicting the evolution of drug-resistant typhoid and how TCV introduction at any point can slow its spread. By preventing infections and stopping transmission, TCVs are powerful tools to combat drug-resistant typhoid.

Outbreak reports

The COVID-19 pandemic dominated the global health landscape in 2020 and will continue to for the foreseeable future. While this presents one of the biggest challenges the global community has faced, low- and middle-income countries continue to face a myriad of endemic infectious diseases such as typhoid. From the water crisis in the suburbs of Harare in Zimbabwe to the rise of drug-resistant typhoid in multiple locations across South Asia and increasing adverse weather events, the potential for an outbreak is always looming. It is important to maintain surveillance, sustain the progress made through proven interventions including vaccines, and plan strategically as we look to the future.

Scientific publications


NOTE: New Global Burden of Disease 2019 estimates for all diseases, including typhoid, are now available online in the GBD Results tool

Associations among Water, Sanitation, and Hygiene, and Food Exposures and Typhoid Fever in Case–Control Studies: A Systematic Review and Meta-Analysis

Can Existing Improvements of Water, Sanitation, and Hygiene (WASH) in Urban Slums Reduce the Burden of Typhoid Fever in These Settings?

Complications and mortality of typhoid fever: A global systematic review and meta-analysis

A novel Vi-diphtheria toxoid typhoid conjugate vaccine is safe and can induce immunogenicity in healthy Indonesian children 2–11 years: a phase II preliminary report

Role of extreme weather events and El Niño Southern Oscillation on incidence of Enteric Fever in Ahmedabad and Surat, Gujarat, India

Safety and immunogenicity of co-administration of meningococcal type A and measles–rubella vaccines with typhoid conjugate vaccine in children aged 15–23 months in Burkina Faso

Strategies to Improve Coverage of Typhoid Conjugate Vaccine (TCV) Immunization Campaign in Karachi, Pakistan

Surveillance for Enteric Fever in Asia Project (SEAP) — Phase II

Visit our publications page for more recent research

More typhoid conjugate vaccines, more impact

Beyond Morbidity and Mortality, Understanding the Burden of Enteric Fever in South Asia: New Results from Phase II of the Surveillance for Enteric Fever in Asia Project (SEAP)

At ASTMH, more evidence that TCVs work – and just in time

The power of vaccines against drug-resistant typhoid

One step closer to untreatable typhoid

Complications and mortality of typhoid fever

A new study from Burkina Faso further confirms typhoid conjugate vaccines (TCV) are safe, immunogenic and can be co-administered

The link between cities and our health

COVID-19 as an awakening for hand hygiene access

Stories of Typhoid: Dr. James Meiring

Multidrug-resistant iNTS: A growing threat in Kenya

Tackling typhoid with environmental surveillance

All posts available on the blog