Although typhoid fever has affected humans for thousands of years, it is no longer viewed as a major danger in developed nations. However, recent scientific findings show that this ancient disease remains a serious global threat, especially as the bacterium continues to evolve drug resistance.
Drug Resistance Is Rising at an Alarming Pace
A 2022 study revealed that Salmonella enterica serovar Typhi (S. Typhi)—the bacterium responsible for typhoid fever—is rapidly developing extensive drug resistance. Over the past three decades, its resistance to oral antibiotics has steadily increased and is now spreading across continents.
Currently, antibiotics are the only effective treatment for typhoid. Yet S. Typhi is becoming resistant not just to frontline medicines such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but also to newer antibiotics like fluoroquinolones and third-generation cephalosporins.
Genomic Data Reveals a Rapid Spread of XDR Typhi
Researchers from several countries analyzed the genomes of 3,489 S. Typhi strains collected between 2014 and 2019 from Nepal, Bangladesh, Pakistan, and India. They observed a significant rise in extensively drug-resistant (XDR) strains.
Even more concerning, XDR Typhi has spread internationally. Since 1990, nearly 200 cases have been exported from South Asia to Southeast Asia, Africa, the UK, the US, and Canada.
“The speed at which highly resistant strains of S. Typhi have emerged and spread is alarming,” said Jason Andrews, an infectious disease researcher at Stanford University. He emphasized the urgent need to expand prevention measures in high-risk regions.
Azithromycin: The Last Oral Antibiotic Under Threat
Until recently, most XDR typhoid cases were managed using third-generation antimicrobials—quinolones, cephalosporins, and macrolides. However, by the early 2000s, mutations conferring quinolone resistance dominated in South Asia and Singapore, while cephalosporin resistance continued to rise.
As reported by Science Alert, today, azithromycin is the only remaining oral treatment option. Yet the 2022 study found emerging mutations that reduce its effectiveness. Although these mutations have not yet combined with XDR Typhi strains, researchers warn that such a development would severely limit treatment options.
If typhoid remains untreated, mortality rates can reach 20 percent. In 2024 alone, more than 13 million cases were reported worldwide.
Vaccination Is Critical to Prevent Future Outbreaks
While typhoid conjugate vaccines can help prevent disease outbreaks, access to these vaccines remains limited globally. Public health experts stress that expanding vaccination programs is crucial, especially given how easily diseases spread in a globalized world.
A study from India in 2021 estimated that vaccinating children in urban areas could reduce typhoid cases and deaths by up to 36 percent. Pakistan has already taken the lead as the first country to introduce routine typhoid immunization, with several other nations now planning similar programs.
According to the CDC, the World Health Organization has prequalified four typhoid conjugate vaccines as of April 2025. These vaccines are being introduced into childhood immunization schedules in typhoid-endemic regions.
Global Action Needed to Fight Antibiotic Resistance
Antibiotic resistance remains one of the world’s leading causes of death, surpassing HIV/AIDS and malaria. Vaccines, where available, represent one of the most powerful tools for preventing future crises. Health experts argue that nations must urgently expand vaccine access and invest in new antibiotic development.
The warning is clear: the world cannot afford to delay action.