Vaccine vs. Drug-Resistant Typhoid

Superbug Showdown: Can New Vaccines Stop Drug-Resistant Typhoid?

Elliot Brynn in Health & Wellness December 2025 • 4 min read.

"Extensively drug-resistant typhoid is spreading, but innovative vaccines offer a glimmer of hope. Will they arrive in time?"

Imagine a bacterial infection so resistant to antibiotics that common treatments become useless. That's the reality of extensively drug-resistant (XDR) typhoid, a dangerous strain of Salmonella Typhi now spreading rapidly, especially in densely populated areas of Asia. The emergence of this superbug poses a significant threat to global health.

In November 2016, an outbreak of XDR typhoid was identified in Hyderabad, Pakistan. This outbreak, resistant to multiple antibiotics, has since spread to Karachi, a city of over 14 million people. With confirmed cases exceeding 1,000 and likely many more due to empirical treatment practices, the situation is alarming.

But there's hope on the horizon. New conjugate vaccines offer a promising strategy to combat this growing threat. These innovative vaccines could potentially revolutionize typhoid control, especially in regions where drug resistance is rampant. Let's delve into the crisis and explore how these vaccines might offer a solution.

Why is Drug-Resistant Typhoid Such a Big Deal?

Before antibiotics, typhoid fever was a deadly disease, with case fatality rates exceeding 20%. The introduction of chloramphenicol in 1948 marked a turning point, but resistance soon emerged. Over the decades, typhoid has developed resistance to multiple drugs, including ampicillin, trimethoprim-sulfamethoxazole, and fluoroquinolones, making treatment increasingly difficult.

The current XDR strain, belonging to the H58 clade, is particularly concerning. It carries a chromosomally integrated antimicrobial-resistance cassette and an IncY plasmid, rendering it resistant to a wide range of antibiotics, including third-generation cephalosporins. With typhoid already causing 12 to 22 million infections annually, the emergence of this XDR variant threatens to overwhelm healthcare systems, particularly in resource-limited settings.

Resistance to multiple antibiotics limits treatment options.
High potential to overwhelm healthcare systems in endemic regions.
Increases the risk of complications and fatalities.
Economic burden on affected communities due to treatment costs and lost productivity.

The concerning aspect is that clinicians are now turning to carbapenems, which are both expensive and often inaccessible in resource-limited settings where typhoid is most common. Reduced susceptibility to azithromycin has also been reported, signaling a closing window for effective treatments. This situation underscores the urgent need for alternative prevention and treatment strategies.

Will Vaccines Turn the Tide Against Typhoid?

Traditional typhoid vaccines have limitations, including the need for frequent revaccination and ineligibility for children under two. However, a new tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine (Typbar TCV) offers a promising alternative. This vaccine, prequalified by the WHO in 2018, demonstrates high and sustained immunogenicity and is effective in children as young as 6 months.

The WHO now recommends the use of typhoid conjugate vaccines in endemic countries, prioritizing those with high typhoid burdens or antimicrobial resistance. Gavi, the Vaccine Alliance, has committed $85 million to support the rollout of these vaccines. While these vaccines won't protect against paratyphoid fever, they represent a crucial tool in the fight against typhoid.

The rise of XDR S. Typhi in densely populated areas underscores the urgent need for action. With improved sanitation and water infrastructure lagging behind rapid urbanization, vaccination offers a feasible control method. The availability of effective vaccines, coupled with WHO recommendations and Gavi funding, presents a unique opportunity to combat typhoid. The critical question is whether we will act decisively to deploy these vaccines and prevent further spread of this dangerous superbug.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1056/nejmp1803926, Alternate LINK

Title: Extensively Drug-Resistant Typhoid — Are Conjugate Vaccines Arriving Just In Time?

Subject: General Medicine

Journal: New England Journal of Medicine

Publisher: Massachusetts Medical Society

Authors: Jason R. Andrews, Farah N. Qamar, Richelle C. Charles, Edward T. Ryan

Published: 2018-10-18

Everything You Need To Know

What exactly makes extensively drug-resistant typhoid, or XDR typhoid, such a serious concern?

Extensively drug-resistant typhoid, or XDR typhoid, is a strain of Salmonella Typhi that is resistant to multiple antibiotics. This resistance makes common treatments ineffective, leading to increased complications, fatalities, and a higher burden on healthcare systems, especially in resource-limited settings. The H58 clade, a concerning XDR strain, carries resistance to a wide range of antibiotics, including third-generation cephalosporins, posing a significant threat to global health and requiring the use of expensive and less accessible carbapenems.

What are the major threats associated with the emergence and spread of extensively drug-resistant typhoid?

The emergence of extensively drug-resistant typhoid poses several major threats. Firstly, it severely limits treatment options, potentially leading to higher fatality rates. Secondly, it can overwhelm healthcare systems, particularly in regions where typhoid is already endemic. Thirdly, the increased treatment costs and lost productivity place a significant economic burden on affected communities. Finally, with reduced susceptibility to azithromycin being reported, the window for effective treatments is closing, necessitating alternative prevention and treatment strategies.

How do conjugate vaccines offer an improvement over traditional typhoid vaccines?

Conjugate vaccines, like the tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine (Typbar TCV), represent a significant advancement over traditional typhoid vaccines. Typbar TCV, prequalified by the WHO in 2018, can be administered to children as young as 6 months and demonstrates high and sustained immunogenicity. Unlike older vaccines that require frequent revaccination and are unsuitable for young children, Typbar TCV offers longer-lasting protection and broader applicability, making it a crucial tool in controlling typhoid, especially in areas with high drug resistance.

How does the tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine (Typbar TCV) actually work to protect against typhoid?

The tetanus-toxoid conjugated Vi polysaccharide typhoid vaccine (Typbar TCV) works by stimulating the immune system to produce antibodies against Salmonella Typhi, the bacteria that causes typhoid fever. The conjugation with tetanus toxoid enhances the immune response, particularly in young children, providing longer-lasting protection compared to older vaccines. This vaccine is especially valuable in regions where extensively drug-resistant typhoid is prevalent, offering a preventative measure against infection and reducing the reliance on antibiotics.

Beyond vaccines, what other strategies are needed to effectively combat extensively drug-resistant typhoid?

While conjugate vaccines like Typbar TCV offer hope, overcoming extensively drug-resistant typhoid requires a multifaceted approach. Improving sanitation and hygiene practices, ensuring access to clean water, and enhancing disease surveillance are crucial. Additionally, promoting responsible antibiotic use is essential to slow the development and spread of drug resistance. Investment in research for new antibiotics and therapies is also necessary to combat the evolving threat of typhoid and other superbugs. These measures, combined with widespread vaccination, can effectively reduce the burden of typhoid and mitigate the impact of drug resistance.