Typhoid Fever: Rising Drug Resistance Threatens Global Health
Typhoid fever, a disease with ancient roots, is experiencing a resurgence due to the alarming rise of antibiotic-resistant strains. While often considered a threat of the past in developed nations, this bacterial infection remains a significant public health challenge worldwide, particularly in areas with limited access to safe water, sanitation, and hygiene.
The Growing Threat of Drug Resistance
Salmonella enterica serovar Typhi (S. Typhi), the bacterium responsible for typhoid fever, is evolving extensive drug resistance, rapidly replacing strains that are not resistant. For decades, antibiotics have been the primary treatment for typhoid fever. Yet, over the past three decades, the bacterium’s resistance to oral antibiotics has been steadily increasing and spreading [1].
A 2022 study analyzing the genomes of 3,489 S. Typhi strains contracted between 2014 and 2019 in Nepal, Bangladesh, Pakistan, and India revealed a significant increase in extensively drug-resistant (XDR) Typhi. This strain is not only impervious to common antibiotics like ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, but is also developing resistance to newer drugs, including fluoroquinolones and third-generation cephalosporins [1].
Global Spread of XDR Typhi
While most XDR Typhi cases originate in South Asia, the bacterium is spreading globally. Since 1990, researchers have identified nearly 200 instances of international spread, with strains exported to Southeast Asia, East and Southern Africa, as well as detected in the UK, the US, and Canada [1].
Scientists have warned about drug-resistant typhoid for years. The first XDR typhoid strain was identified in Pakistan in 2016, and by 2019, it had become the dominant genotype in the nation [1].
Limited Treatment Options
Historically, XDR typhoid strains were treated with third-generation antimicrobials, such as quinolones, cephalosporins, and macrolides. However, resistance to quinolones became widespread in Bangladesh, India, Pakistan, Nepal, and Singapore by the early 2000s, accounting for over 85% of cases. Cephalosporin resistance also increased during this period. Currently, azithromycin is the only remaining effective oral antibiotic. However, mutations conferring resistance to azithromycin are now emerging, potentially jeopardizing the efficacy of all oral antimicrobial treatments [1].
Impact and Prevention
Typhoid fever can be fatal in up to 20% of untreated cases, with over 13 million cases reported in 2024. Prevention strategies are crucial, and typhoid conjugate vaccines offer a promising solution. However, expanding access to these vaccines globally is essential to prevent future health crises [1].
The World Health Organization has prequalified four typhoid conjugate vaccines for leverage in childhood immunization programs in typhoid-endemic countries [2].
Who is at Risk?
Typhoid and paratyphoid fever are caused by Salmonella enterica serotypes Typhi, Paratyphi A, Paratyphi B (tartrate negative), and Paratyphi C [2]. The risk of infection is highest in low- and middle-income countries with endemic disease, poor access to safe food and water, and inadequate sanitation [2]. Travelers to these regions, particularly those visiting friends and relatives or attending mass gatherings, are also at increased risk [2].
The Need for Urgent Action
“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 [1].
Expanding access to typhoid vaccines and investing in research for new antibiotics are critical steps to combat this growing threat. A study in India estimated that vaccinating children against typhoid in urban areas could prevent up to 36% of cases and deaths [1]. Pakistan has taken a leading role by becoming the first nation to offer routine immunization for typhoid.
Antibiotic resistance is a leading cause of death globally, surpassing HIV/AIDS and malaria. Vaccines remain one of the most effective tools for preventing future catastrophes, and swift action is imperative.