Ancient killer rapidly becoming antibiotic resistant, scientists warn

(ORDO NEWS) — In developed countries, typhoid fever is rare, but this ancient threat, believed to have existed for millennia, is still a great danger in our modern world.

The bacterium that causes typhoid fever develops drug resistance and quickly outcompetes non-resistant strains, according to new research.

Currently, antibiotics are the only effective treatment for typhoid fever, which is caused by the bacterium Salmonella enterica serovar Typhi (S Typhi). However, over the past three decades, bacterial resistance to oral antibiotics has grown and spread.

By sequencing the genomes of 3,489 S Typhi strains infected between 2014 and 2019 in Nepal, Bangladesh, Pakistan and India, the researchers found that the number of extensively drug-resistant (XDR) strains has recently been on the rise.

Typhi XDRs are not only resistant to first-line antibiotics such as ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole, but are becoming increasingly resistant to newer antibiotics such as fluoroquinolones and third-generation cephalosporins.

Even worse, these strains are rapidly spreading around the world.

Although the majority of XDR Typhi cases originate in South Asia, researchers have identified about 200 cases of international spread since 1990.

Most strains have been exported to Southeast Asia and East and South Africa, but typhoid superbugs have also been found in the UK, US and Canada.

“The rate of emergence and spread of highly resistant strains of S. Typhi in recent years is a real concern and highlights the urgent need to scale up prevention efforts, especially in countries most at risk,” says infectious disease specialist Jason Andrews of Stanford University.

Scientists have been warning about drug-resistant typhoid fever for years, but the new study is the largest analysis of the bacterium’s genome to date.

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

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

But by 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, cephalosporin resistance was also on the rise.

Today, there is only one oral antibiotic left – the macrolide azithromycin. And this medicine may not last long.

A new study has found that the mutations that confer resistance to azithromycin are now also proliferating, “threatening the effectiveness of all oral antimicrobials for the treatment of typhoid fever.” Although these mutations have not yet been accepted by XDR S Typhi, if they are accepted we will be in serious trouble.

If left untreated, up to 20 percent of typhoid cases can be fatal, and today there are 11 million cases of typhoid fever per year worldwide.

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

“The recent emergence of XDR and azithromycin-resistant S Typhi creates great urgency to rapidly scale up prevention efforts, including the use of typhoid conjugate vaccines in typhoid-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 distribution, should not be limited to such conditions.”

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

To prevent this from happening, health experts say countries should expand access to typhoid vaccines and invest in research into new antibiotics. One recent study in India, for example, found that vaccinating children against typhoid in urban areas could prevent up to 36 percent of typhoid cases and deaths.

Currently, Pakistan is a leader in this direction. It is the first country in the world to provide routine immunization against typhoid fever. Millions of children received the vaccine last year, and health experts say other countries should follow suit.

Antibiotic resistance is one of the world’s leading causes of death, killing more people than HIV/AIDS or malaria. Vaccines, if available, are among the best tools to prevent future disasters.


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