Typhoid fever may be rare in developed countries, but this ancient threat, thought to have existed for millennia, remains a major danger in our modern world.
According to new research, the bacterium that causes typhoid fever is developing strong 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). However, over the past three decades, bacterial resistance to oral antibiotics has been growing and spreading.
By sequencing the genomes of 3,489 strains of S Typhi contracted between 2014 and 2019 in Nepal, Bangladesh, Pakistan, and India, the researchers found a recent increase in extremely drug-resistant (XDR) Typhi.
XDR Typhi is not only impermeable 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.
Worse yet, these strains are spreading globally at a rapid rate.
While the majority of XDR Typhi cases have come 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 United Kingdom, the United States, and Canada.
“The speed at 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 scale up prevention measures, especially in countries most at risk,” says Jason, an infectious disease specialist. Andrews of Stanford University.
Scientists have been warning about drug-resistant typhoid for years, but the new research is the largest genome analysis of the bacterium to date.
In 2016, the first strain of XDR typhoid fever was identified in Pakistan. By 2019, it had become the dominant genotype in the nation.
Historically, most XDR typhoid strains have been treated 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 hold.
Today there is only one oral antibiotic left: the macrolide, azithromycin. And this medicine might not work for much longer.
The new study found that mutations that confer resistance to azithromycin are also now 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, if they are, we are in deep trouble.
If left untreated, up to 20 percent of typhoid cases can be fatal, and there are currently 11 million cases of typhoid fever each year.
Future outbreaks can be prevented to some extent with typhoid conjugate vaccines, but if access to these shots is not expanded globally, the world could soon have another health crisis on its hands.
“The recent emergence of S. Typhi resistant to azithromycin and XDR creates further urgency to rapidly expand prevention measures, including the use of conjugate typhoid vaccines in typhoid-endemic countries,” the authors write.
“Such measures are necessary 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 center of 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 that from happening, health experts argue that nations 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, up to 36 percent of typhoid cases and deaths could be prevented.
Pakistan is currently leading the way on this front. 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 should do the same.
Antibiotic resistance is one of the leading causes of death in the world and kills more people than HIV/AIDS or malaria. Where available, vaccines are some of the best tools we have to prevent future catastrophes.
No time to lose.
The study was published in The lancet microbe.