The world is facing an epidemic of multidrug-resistant typhoid fever. That’s the conclusion of the largest study to date of genomes of the bacterium that causes the diseases, Salmonella enterica Typhi. According to the researchers, a clone of the bacterium that’s frequently multidrug-resistant, called H58, is rolling across Asia and Africa. Its spread is likely to increase the cost of treatments and lead to more complications, they warn.
“There is a sense of urgency now,” says Gordon Dougan, a geneticist at the Wellcome Trust Sanger Institute in Hinxton, U.K., and an author of the paper.
Typhoid spreads through contaminated water or food, causing fever, headache, and other symptoms. If not treated, the disease can lead to complications like gastrointestinal perforation and kill up to 20% of patients. Estimates range from 10 million to 30 million cases a year. About 200,000 people die. S. enterica Typhi that are resistant to multiple antibiotics first appeared in the 1970s. But H58 has been particularly worrying to scientists, because it is cropping up in more and more countries.
To get an overview of its spread, scientists analyzed the genomes of 1832 samples from 21 countries in Asia, Africa, and Oceania. The clone likely emerged in South Asia around 1985 and then picked up resistance genes in the following years, before spreading to Southeast Asia and Africa, Dougan says.
In Africa, the clone was probably introduced several times to Kenya and has been spreading from there to the south, the authors report online today in Nature Genetics. In a paper last month in PLOS Neglected Tropical Diseases, Dougan and other scientists tracked the emergence of H58 in one hospital in Malawi. From 1998 to 2010, there were, on average, 14 diagnoses of typhoid fever a year at the hospital. About 7% of the isolates were resistant to multiple drugs. In 2014 there were 782 diagnoses, 97% with multidrug resistance. “As soon as this arrives in your country, you have to turn to more expensive antimicrobials,” Dougan says.
It is not clear why H58 is so successful. One possible explanation: The clone may have mutated to better survive in the tissue of carriers that spread the disease without getting sick themselves. There are some genetic changes in H58 that may point to that, Dougan says. “But that’s speculation,” he cautions. Why certain bacterial clones become dominant is still a mystery, says Mark Achtman, a microbiologist at the University of Warwick in the United Kingdom. “It’s a phenomenon we see again and again in different bacteria and it has never been understood.”
The paper is one of the largest bacterial genome samples that anybody has published, Achtman says. Much was already known about H58 spreading, he says. “But this is the first time that we’ve had such an exhaustive overview of Salmonella typhi and the H58 group within typhi.” Dougan says he and his colleagues are sequencing many more typhoid isolates to pin down the origins of H58.