An ancient killer is fast becoming resistant to antibiotics, scientists warn

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

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

Currently, antibiotics are the only way to effectively treat typhus, which is caused by the bacterium Salmonella enterica serotype Typhi (S Typhi). Yet, over the past three decades, the bacterium’s resistance to oral antibiotics has grown and spread.

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

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

Even worse, these strains are spreading globally at a rapid pace.

Although the majority of XDR Typhi cases 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, US and Canada.

“The speed with 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,” says the specialist. in infectious diseases Jason Andrews of Stanford University.

Scientists have been warning of drug-resistant typhus for years, but the new research is the largest genome analysis on the bacterium to date.

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

Historically, most XDR typhus strains have been fought 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 taking over.

Today there is only one oral antibiotic left: the macrolide, azithromycin. And this medicine may not work for much longer.

The new study found that mutations conferring resistance to azithromycin are now also spreading, “threatening the efficacy of all oral antimicrobials for the treatment of typhus.” While 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 typhus cases can be fatal and today there are 11 million cases of typhus per year.

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

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

“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 such contexts.”

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 is that variants of the disease in our modern, globalized world spread easily.

To prevent this from happening, health experts say nations need to expand access to typhoid vaccines and invest in new research on antibiotics. A recent study in India, for example, estimates that if children were vaccinated against typhus in urban areas, up to 36% of typhus cases and deaths could be prevented.

Pakistan is currently at the forefront on this front. It is the first nation in the world to offer routine typhoid vaccinations. Last year, millions of children were given the vaccine and health experts say more nations need to follow suit.

Antibiotic resistance is a leading cause of death worldwide, claiming more victims than HIV / AIDS or malaria. Where available, vaccines are some of the best tools we have to prevent future disasters.

We have no time to waste.

The study was published in The Microbe Lancet.


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