Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis shows.
Resistant strains of Salmonella enterica serovar Typhi (s Typhi) — almost all of them native to South Asia — have spread across borders nearly 200 times since 1990.
So far, the analysis has been limited to small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan and India.
The findings of the study, led by Kesia Esther da Silva, PhD, of the Department of Infectious Diseases and Geographical Medicine at Stanford University in California, were published online June 21 in The Lancet microbe.
Worldwide deaths: 100,000 annually
Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid is also significantly present in sub-Saharan Africa, Southeast Asia and Oceania.
The findings are further evidence of the need for a global response, the authors write.
Jason Andrews, MD, co-author and associate professor in the Department of Infectious Diseases and Geographical Medicine at Stanford University, told Medscape Medical News that the research helps identify where the greatest burden is and where there is the greatest need for the two highly effective typhoid vaccines.
“We’re seeing higher levels of resistance than we’ve ever seen to our latest and greatest antibiotics,” he said.
He said that until now, typhoid control strategies have led to country-level decisions and local funding, and that should be shifted to a global priority. “Given today’s travel migration patterns, we see that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”
Andrews says the US sees about 300 to 500 cases of typhoid per year. “About 80% of those cases involve people traveling from South Asia,” he said.
Infections also come from people from the US who visit heavily taxed countries, especially to see family. Often they don’t see the risk and skip the vaccination, he said. US clinicians can help educate patients traveling to typhoid-endemic regions about pre-travel vaccination, he added.
Physician awareness is also important when patients have recently returned from such regions. Data from this study show that it is necessary to carefully consider which antibiotics are effective in the event of increasing resistance.
Only one oral option left in Pakistan
“We’re running out of treatment options for typhoid,” Andrews said. For example, the resistance pattern in Pakistan has left only one oral option, azithromycin, and resistance is growing towards that.
Without that option, “we will have to hospitalize patients and give intravenous antibiotics,” he said. “That’s worrying.”
In addition, some resistant strains from Pakistan are popping up in the US.
“There are even cases that have not been tracked at all for travelers going to Pakistan that are thought to come from local transmission in the United States,” he said.
Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai in New York City, told Medscape Medical News that in addition to vaccinating travelers before going to typhoid-endemic areas, doctors should educate patients about avoiding fecal typhoid transmission by vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.
Bajrovic, who leads antimicrobial stewardship efforts at Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, as well as the United States.
“Restricting antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions should be part of a global effort.
Strains in the study were classified as multidrug resistant (MDR) if they contain genes resistant to ampicillin, chloramphenicol and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.
Initially, fluoroquinolones were effective against MDR s Typhi and in the 1990s became the primary therapy. By the 2010s, the majority of the s Typhi in South Asia contained mutations in the quinolone resistance defining regions.
The authors write: “We found evidence of frequent international (n=138) and intercontinental transfers (n=59) of antimicrobial resistant s typhi.”
According to the analysis, MDR . since 2000 s Typhi has steadily declined in Bangladesh and India, remaining on less than 5% of typhoid strains in Nepal, although it has increased slightly in Pakistan.
However, these are being replaced “by strains containing ceftriaxone resistance (extremely drug resistant), high fluoroquinolone resistance, or azithromycin resistance, which reverse the decrease in the effective population size of s Typhi,” the authors write.
The analysis supports the urgency of prevention measures, including the use of conjugated typhoid vaccines in typhoid-endemic countries, the authors say.
But given the proliferation of increasingly resistant strains internationally, they say preventive measures should not be limited to those countries.
The research was funded by the Bill & Melinda Gates Foundation. Da Silva, Andrews and Bajrovic have not disclosed any relevant financial relationships.
lancet microbe† Published June 21, 2022. Full text
Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and Nurse.com, and was an editor for the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter on @mfrellick†
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