An old killer is quickly becoming resistant to antibiotics, scientists warn

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

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

Currently, antibiotics are the only way to effectively treat typhoid fever, which is caused by the bacteria Salmonella enterica serovar Typhi (S Typhi). But over the past three decades, the bacteria’s resistance to oral antibiotics has increased and spread.

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

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

Worse, these species are spreading rapidly worldwide.

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

Most of the species have been exported to Southeast Asia, as well as East and South Africa, but typhoid superbugs have also been found in the United Kingdom, United States, and Canada.

“The rate at which highly resistant S. Typhi strains 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 the highest risk” , says infectious disease specialist Jason. Andrews from Stanford University.

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

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

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

But by the early 2000s, mutations conferring resistance to quinolones accounted for more than 85 percent of all cases in Bangladesh, India, Pakistan, Nepal and Singapore. At the same time, cephalosporin resistance also took over.

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

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 typhoid fever.” While these mutations have not yet been adopted by XDR S Typhi, we are in serious trouble if they are.

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

Future outbreaks may be prevented to some extent with conjugated typhoid vaccines, but if access to these injections is not expanded globally, the world could soon face another health crisis.

“The recent emergence of XDR and azithromycin-resistant S Typhi creates greater urgency for rapidly expanding prevention measures, 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 spread, they should not be limited to such settings.”

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 disease variants are easily spread in our modern, globalized world.

To avoid that, health experts argue that countries should expand access to typhoid vaccines and invest in new antibiotic research. For example, a recent study in India estimates that vaccinating children in urban areas against typhoid could prevent up to 36 percent of typhoid cases and deaths.

Pakistan is currently leading the way on this front. It is the first country in the world to offer routine immunization against typhoid fever. Last year, millions of children were given the vaccine, and health experts argue that more countries should 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. Where available, vaccines are some of the best tools we have for preventing future disasters.

We have no time to lose.

The study is published in The lancet microbe

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