Ancient killer is rapidly becoming resistant to antibiotics, scientists warn

Typhoid fever may be rare in developed countries, but this ancient menace, thought to exist for millennia, is still a danger in our modern world.

According to new research, the bacterium responsible for typhoid fever is developing widespread drug resistance and rapidly replacing strains that are not resistant.

Currently, antibiotics are the only way to effectively treat typhoid, which is caused by the bacteria Salmonella enterica serotype Typhi (S Typhi). Yet over the past three decades, bacterial resistance to oral antibiotics has developed and spread.

By sequencing the genomes of 3,489 strains of S Typhi contracted from 2014 to 2019 in Nepal, Bangladesh, Pakistan and India, the researchers discovered a recent increase in extremely drug-resistant (XDR) Typhi.

XDR Typhi is not only insensitive to first-line antibiotics, such as ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole, but it is also becoming increasingly resistant to newer antibiotics, such as fluoroquinolones and third-generation cephalosporins.

Worse still, these strains are spreading globally at a rapid rate.

While most cases of XDR Typhi originate from South Asia, researchers have identified nearly 200 cases of international spread since 1990.

Most strains have been exported to Southeast Asia, as well as East and Southern Africa, but typhoid superbugs have also been found in the UK, USA and Canada.

“The rate at which highly resistant strains of S. Typhi have emerged and spread in recent years is a real cause for concern and underscores the need to urgently expand prevention measures, particularly in the least developed countries. more at risk,” says Jason, an infectious disease specialist. Andrews from Stanford University.

Scientists have been warning about drug-resistant typhoid for years, but the new research is the largest genome analysis of the bacteria to date.

In 2016, the first XDR typhoid strain was identified in Pakistan. By 2019, it had become the dominant genotype in the country.

Historically, most XDR typhoid strains have been combated with third-generation antimicrobials, such as quinolones, cephalosporins, and macrolides.

But in the early 2000s, mutations that confer resistance to quinolones accounted for more than 85% of all cases in Bangladesh, India, Pakistan, Nepal and Singapore. At the same time, resistance to cephalosporins was also gaining the upper hand.

Today, there is only one oral antibiotic left: the macrolide, azithromycin. And this drug might not work any longer.

The new study found that mutations that confer resistance to azithromycin are now also spreading, “threatening the efficacy of all oral antimicrobials for the treatment of typhoid.” Although these mutations have not yet been adopted by XDR S Typhi, if they are, we are in serious trouble.

If left untreated, up to 20% of typhoid cases can be fatal, and today there are 11 million cases of typhoid a year.

Future epidemics can be prevented to some extent with typhoid conjugate vaccines, but if access to these vaccines is not expanded globally, the world could soon face another health crisis.

“The recent emergence of azithromycin-resistant XDR and S Typhi creates greater urgency for the rapid expansion of preventive measures, including the use of typhoid conjugate vaccines in typhoid-endemic countries” , write the authors.

“Such measures are needed in countries where the prevalence of antimicrobial resistance among S Typhi isolates is currently high, but given the propensity for international spread, they should not be limited to these settings.”

South Asia may be the main hub for typhoid fever, accounting for 70% of all cases, but if COVID-19 has taught us anything it’s that disease variants in our modern, globalized world spread easily.

To prevent this from happening, health experts say countries need to expand access to typhoid vaccines and invest in new antibiotic research. A recent study in India, for example, estimates that if children are vaccinated against typhoid in urban areas, it could prevent up to 36% of typhoid cases and deaths.

Pakistan is currently leading the way on this front. It is the first nation in the world to offer routine typhoid vaccination. Last year, millions of children received the vaccine and health experts say more countries need to follow suit.

Antibiotic resistance is one of the leading causes of death worldwide, claiming more lives than HIV/AIDS or malaria. When available, vaccines are among the best tools we have to prevent future disaster.

We do not have time to lose.

The study was published in The lancet microbe.

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