An Ancient Killer Is Fast Becoming Antibiotic Resistant, Scientists Warn

Salmonella Typhi. (Credits: Microbewriter/Wikimedia Commons/CC BY SA 4.0)

Translated by Julio Batista
Original de Carly Cassella para o ScienceAlert

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

According to new research, the bacteria that cause typhoid fever are developing extensive drug resistance and rapidly replacing strains that are not resistant.

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Currently, antibiotics are the only way to effectively treat typhoid fever, which is caused by the bacteria. Salmonella enterica sorovar Typhi (S Typhi). However, in the last three decades, bacterial resistance to oral antibiotics has been growing and spreading.

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 (XDR) Typhi.

XDR Typhi is not only resistant to front-line antibiotics such as ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole, but 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.

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

Most of the strains have been exported to Southeast Asia, as well as eastern 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 the most at-risk countries,” said the disease expert. infectious diseases Jason Andrews of Stanford University.

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

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

Historically, most strains of XDR typhoid fever were fought with third-generation antimicrobials such as quinolones, cephalosporins, and macrolides.

But in the early 2000s, mutations conferring 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 hold.

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

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

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

Future outbreaks can be avoided 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 prevention measures, including the use of typhoid conjugate vaccines in typhoid-endemic countries,” the authors wrote.

“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, it should not be restricted 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 variants of the disease in our modern, globalized world are easily spread.

To prevent that from happening, health experts argue that countries must 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 in this regard. It is the first nation in the world to offer routine immunization for typhoid fever. Last year, millions of children received the vaccine, and health experts argue that more nations need to follow suit.

Antibiotic resistance is one of the leading causes of death in the world, claiming the lives of more people than HIV/AIDS or malaria. When available, vaccines are some of the best tools we have to prevent future catastrophes.

We have no time to lose.

The study was published in The Lancet Microbe.