Genetic analysis suggests that virulent strain of Salmonella typhi emerged in South Asia 25 to 30 years ago.
A newly identified strain of antibiotic-resistant typhoid bacteria has swept the world over the last 30 years — and it is now driving a quiet epidemic in Africa, researchers report on 11 May in Nature Genetics1.
Salmonella typhi remains a major health threat in developing countries, particularly in areas with poor sanitation. The World Health Organization estimates that there are between 20 and 30 million cases of typhoid per year worldwide.
The situation is particularly acute in Africa, where the number of infections is rising and resistance to older antibiotics, such as penicillin or sulfa-based drugs, is growing. One particularly striking example comes from Blantyre, Malawi, which saw 782 cases of typhoid last year, after averaging just 14 cases per year between 1998 and 2012. The percentage of antibiotic-resistant infections there jumped from 7% to 97% over the same period.
To trace the origin of the antibiotic-resistant typhoid bacteria, a team led by Vanessa Wong, an infectious disease clinician at the Wellcome Trust Sanger Institute in Hinxton, UK, sequenced the genomes of more than 1,800 S. typhi samples from 63 countries.
One strain known as H58 comprised 47% of those samples, the researchers found, and most of the H58 specimens were resistant to multiple antibiotics. The strain was not only the most widespread, but it appears over time to have been outcompeting other varieties of S. typhi that did not resist antibiotics to the same degree.
By comparing the genomes of the H58 samples, the researchers were able to trace the strain’s path around the world and estimate when it arrived in each region. Drug-resistant H58 seems to have originated in South Asia within the past 30 years before spreading to other nations in the Middle East and the Pacific Islands. The strain also jumped multiple times from Asia into East Africa, and then into southern Africa through trade routes. The drug-resistant strains of H58 were most common in areas where older antibiotics are common treatments for typhoid, suggesting that overuse of such drugs has helped to drive the epidemic in Africa.
Although health workers have known about the rising number of typhoid cases in Africa for some time, the extent of the antibiotic resistant epidemic was not clear until now. “People locally were noticing high typhoid rates, but they didn’t realize it was a problem in lots of other countries,” Wong says. “We were able to link all the dots together.”
Another reason why the epidemic has flown under the radar could be that clinicians have missed it, says Mark Achtman, a microbiologist at the University of Warwick in the UK. Typhoid is difficult to distinguish from other fever-causing diseases such as malaria. The only way to be certain is to culture the bacteria, which takes days and is not always feasible in developing countries.
Achtman points out that S. typhi strains that are resistant to old antibiotics have been seen for many decades. Today, these antibiotics are rarely used outside of Africa because more effective drugs are now available to countries that can afford them. But Wong says that researchers are already starting to see H58 cases that are resistant to more modern antibiotics, such as fluoroquinolone and ciprofloxican. Eventually, she says, clinicians will run out of options.
Wong says that her team now wants to find out why H58 is so successful at spreading and outcompeting other strains. It is unclear whether the strain is actually easier to spread or just got lucky. One theory, Wong says, is that while most drug resistant bacteria carry their genes for drug resistance on a plasmid – an extra piece of DNA that requires a great deal of energy from the cell– H58 has integrated these genes into its chromosome and may have more energy to expend. But she says that there is no evidence for that yet; for now, its success remains a mystery.
Until these questions are figured out, Achtman says, it may be difficult to know how to address the epidemic. There is a vaccine for typhoid, but it is only effective for a short time and is not widely administered. With the disease’s resurgence in Africa, he says, it might be a good idea to start testing its effectiveness in different populations.
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Reardon, S. African typhoid epidemic traced to newfound drug-resistant bacteria. Nature (2015). https://doi.org/10.1038/nature.2015.17514