An Ancient Killer Is Rapidly Becoming Resistant to Antibiotics

Although typhoid fever is considered to have existed for thousands of years, it is still a serious concern in the modern world even if it is uncommon in industrialized nations.

New research indicates that the bacteria that causes typhoid fever is quickly displacing non-resistant variants and acquiring widespread antibiotic resistance.

Typhoid, which is brought on by the bacteria Salmonella enterica serovar Typhi, can only now be adequately treated with drugs (S Typhi). The bacteria has become increasingly resistant to oral antibiotics during the past three decades, though.

Researchers discovered a recent increase in extensively drug-resistant (XDR) Typhi after sequencing the genomes of 3,489 S Typhi strains acquired from 2014 to 2019 in Nepal, Bangladesh, Pakistan, and India.

XDR Typhi is resistant to older antibiotics like fluoroquinolones and third-generation cephalosporins, as well as frontline medicines like ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole.

Even worse, these strains are rapidly dispersing over the globe.

Researchers have discovered approximately 200 instances of international dissemination of XDR Typhi since 1990, despite the fact that the majority of cases originate in south Asia.

Typhoid superbugs have also been discovered in the United Kingdom, the United States, and Canada. The majority of strains have been transferred to Southeast Asia as well as East and Southern Africa.

"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," according to infectious disease expert Jason Andrews from Stanford University.

Although drug-resistant typhoid has been a concern for researchers for some time, the latest study represents the broadest genomic analysis of the bacteria to date.

The first XDR typhoid strain was discovered in Pakistan in 2016. It had taken over as the country's prevalent genotype by 2019.

Third-generation antibiotics like quinolones, cephalosporins, and macrolides have traditionally been used to treat the majority of XDR typhoid strains.

In Bangladesh, India, Pakistan, Nepal, and Singapore, however, mutations that confer quinolone resistance accounted for more than 85% of all instances by the early 2000s. Cephalosporin resistance was also spreading at the same period.

The macrolide azithromycin is the only oral antibiotic still in use today. And the duration of this medication's efficacy is uncertain.

The effectiveness of all oral antimicrobials for the treatment of typhoid is threatened, according to the current study, which discovered mutations that confer azithromycin resistance are now also proliferating. Although XDR S Typhi has not yet adapted to these changes, if they do, we are in big danger.

There are about 11 million cases of typhoid each year, with up to 20% of untreated cases ending in death.

Typhoid conjugate vaccines can help to some extent avoid future outbreaks, but if availability to these injections is not increased internationally, the world may soon face another health emergency.

"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.

"Such measures are needed in countries where antimicrobial resistance prevalence among S Typhi isolates is currently high, but given the propensity for international spread, should not be restricted to such settings."

Typhoid fever may have its major epicenter in South Asia, where 70 percent of cases occur, but COVID-19 has shown us that disease variations are easily transmitted in today's worldwide society.

Health professionals contend that in order to stop it from happening, countries need to increase access to typhoid vaccinations and fund new antibiotic research. According to a recent study conducted in India, vaccination of children living in urban areas might avert up to 36% of typhoid infections and fatalities.

Right now, Pakistan is setting the bar high in this area. It is the first country in the world to provide typhoid vaccinations on a regular basis. Health experts suggest that additional countries should follow the example set by the millions of youngsters who received the vaccination last year.

More people die from antibiotic resistance than from malaria or HIV/AIDS combined, making it one of the world's major causes of mortality. Vaccines are among the finest weapons we have to avert disaster in the future when they are accessible.

We don't have time to waste.

The study was published in The Lancet Microbe.