Typhoid have plagued humans for millennia and many believe that in developed countries it is no longer considered a threat. However, this ‘ancient killer’ is still dangerous and a Lancet study published in 2022, titled: The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study, noted that typhoid fever is evolving extensive drug resistance, and is rapidly replacing strains that are not resistant.
As of now, antibiotics are the only effective treatment for typhoid, caused by the bacterium Salmonella enterica serovar Typhi (S. Typhi). However, in the past three decades, the bacteria’s resistance to oral antibiotics have been growing.
What Did The Study Find?
In this large-scale investigation, researchers from several countries analyzed the genetic sequences of 3,489 Salmonella Typhi (S. Typhi) samples collected between 2014 and 2019 from Nepal, Bangladesh, Pakistan, and India. Their findings revealed a concerning increase in extensively drug-resistant (XDR) Typhi strains across the region.
XDR Typhi is resistant not only to commonly used first-line antibiotics such as ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but is also increasingly showing resistance to more advanced treatments, including fluoroquinolones and third-generation cephalosporins.
More alarmingly, these highly resistant strains are spreading quickly beyond national borders.
Although the majority of XDR Typhi cases originate in South Asia, researchers have documented close to 200 cases of international transmission since 1990. Many of these strains have spread to Southeast Asia and parts of East and Southern Africa. Additionally, cases of these drug-resistant typhoid strains have been detected in countries such as the United Kingdom, the United States, and Canada.
“The speed at which highly resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern, and highlights the need to urgently expand prevention measures, particularly in countries at greatest risk,” said Stanford University infectious disease researcher Jason Andrews when the results were published.
Drug-resistant Typhoid And Warnings
Scientists have warned about the drug-resistant typhoid for years now. In 2016, the first XDR typhoid strain was identified in Pakistan.
By 2019, this had become a dominant genotype in the nation. However, by the early 2000s, mutations that confer resistance to quinolones accounted for more than 85 per cent of all cases in Bangladesh, India, Pakistan, Nepal and Singapore. At the same time, cephalosporin resistance was also taking over.
Today, only one oral antibiotics is left: the macrolide, azithromycin. However, scientists believe that this medicine may also not work for much longer.
The 2022 Lancet study reported that mutations responsible for resistance to azithromycin are increasingly emerging and spreading, raising fresh concerns among scientists. Researchers warned that this development “threatens the efficacy of all oral antimicrobials for typhoid treatment,” significantly narrowing the pool of effective medicines. Although these particular mutations have not yet been observed in extensively drug-resistant (XDR) S. Typhi strains, experts caution that if XDR variants acquire azithromycin resistance as well, treatment options would become extremely limited, creating a potentially dire public health scenario.
Typhoid fever remains a serious and potentially life-threatening illness. If left untreated, as many as 20 percent of cases can result in death. In 2024 alone, more than 13 million typhoid cases were reported worldwide, underscoring the scale of the burden.
While typhoid conjugate vaccines offer a promising tool to help prevent future outbreaks and reduce transmission, their impact depends heavily on widespread and equitable access. Without significant global expansion of vaccination coverage, health experts warn that the world could face another major public health crisis driven by increasingly drug-resistant typhoid strains.
“The recent emergence of XDR and azithromycin-resistant S. Typhi creates greater urgency for rapidly expanding prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries,” the authors write.
What Could Be Done To Prevent This From Happening?
Experts say that nations must now expand their access to typhoid vaccines and invest in new antibiotic research.
A 2021 study in India published in journal Vaccine estimated that if children are vaccinated against typhoid in urban areas, it could prevent up to 36 per cent of typhoid cases and death. Pakistan is also leading the front as it was the first nation in the world to offer routine immunization for typhoid. A small number of countries have followed the suit or are “planning or considering introduction”.
The World Health Organization (WHO) too have prequalified four typhoid vaccines as of April 2025.
