Uncovering a Hidden Epidemic

An antibiotic-resistant strain of typhoid has swept across Asia and Africa over the last three decades.
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Salmonella typhi. (Photo: Sanofi Pasteur/Flickr)

Salmonella typhi. (Photo: Sanofi Pasteur/Flickr)

Salmonella is perhaps most well-known for its ability to cause food poisoning. It can be more deadly though: One variation of the bacteria—Salmonella typhi—is the cause of typhoid fever. Dozens of researchers from the world’s leading typhoid laboratories have teamed up to study the bacteria’s genome, and find that a single, multi-drug resistant lineage, known as H58, has spread across Asia and Africa in just the last 30 years.

“The study shows the H58 clade of Typhi is displacing other typhoid fever strains that have been established over decades and centuries throughout the typhoid endemic world,” says Vanessa Wong, an infectious disease specialist at the United Kingdom’s Wellcome Trust Sanger Institute and lead author of the study, published yesterday in Nature Genetics.

Salmonella typhi is a strictly human pathogen. It spreads between people via feces-tainted food. Consider, for example, the most infamous of typhoid spreaders: Mary Mallon (a.k.a. Typhoid Mary), the New York City cook that infected at least 50 people with the disease at the turn of the 20th century. As many as 30 percent of those infected—Typhoid Mary included—have no symptoms at all, but the strain can cause a range of problems for humans, from stomach pain to death. While there are still tens of millions of cases of typhoid fever worldwide (mostly in developing nations), deaths have seen a steady decline, thanks in large part to antibiotics. But the emergence of antibiotic-resistant strains of bacteria is changing the delicate balance between man and microbe.

"In H58 the genes that result in antimicrobial resistance have become a stable part of the genome, which means antibiotic-resistant typhoid is here to stay."

Wong and her colleagues sequenced the genomes of 1,832 samples of Salmonella typhi, collected from 63 countries spanning six continents between 1905 and 2013. The large distribution across time and geographic space allowed the researchers to make fairly accurate calculations about the patterns of the disease over the last century.

Nearly half of the samples—47 percent—were found to be the H58 strain, which first appeared in samples from 1992. Comparing the genomes of the H58 samples revealed that South Asia was a hub for the drug-resistant variant 25 to 30 years ago, and from there, the strain likely radiated out to Southeast and Western Asia, Africa, and Fiji. Isolated reports of typhoid have been increasing across Africa, but this study allowed the authors to identify the scale of this previously unreported wave of H58 expansion across the continent—evidence of an ongoing epidemic in Eastern and South Africa, according to Wong.

The drug-resistant characteristics of H58 no doubt give the strain an advantage that contributed in part to its rapid spread. “In H58 the genes that result in antimicrobial resistance have become a stable part of the genome,” Wong says, “which means antibiotic-resistant typhoid is here to stay.”

The study provides a framework for monitoring this drug-resistant pathogen and others in the future, Wong says. “It allows us to better understand how antimicrobial resistance emerges and spreads globally and thus will enable us to develop effective strategies to control typhoid.”

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