Extensive exposure to multidrug-resistant superbugs among visitors to the tropics
Escherichia coli: Scanning electron micrograph of Escherichia coli (E. coli) , grown in culture and adhered to a cover slip. Credit: Public Domain - Rocky Mountain Laboratories, NIAID, NIH.
Before the corona pandemic, tens of millions of international travelers annually headed to the tropics, getting exposed to local intestinal bacteria. A total of 20-70% of those returning from the tropics carry extended-spectrum β-lactamase-producing (ESBL) Gram-negative bacteria resistant to multiple antibiotics. The likelihood of acquiring such superbugs depends on destination and health behavior abroad. The risk is greatest in South and Southeast Asia, and a substantial increase is associated with contracting travelers’ diarrhea and taking antibiotics while abroad.
An investigation led by professor of Infectious diseases Anu Kantele at Helsinki University together with MD Esther Kuenzli from Swiss Tropical and Public Health Institute involved real-time scrutiny of superbug acquisition among a group of 20 Europeans over a three-week visit to Laos. The participants’ daily stool samples were initially screened on-site in Vientiane, Laos, and later, in Europe, the superbug strains isolated were analyzed in detail by whole-genome sequencing.
The study was recently published in the Lancet Microbe. It belongs to a series of Kantele’s studies exploring the spread of antimicrobial resistance by international travel.
“Our study revealed that travelers to the tropics are much more predisposed to acquiring superbugs than previously thought. In conventional studies, stool samples are only collected before and after travel, not while abroad as we did now. Travelers to the tropics are known to be exposed to superbugs, but the extent of the risk revealed by our real-time sampling was unexpected,” Kantele says.
Travelers contracted superbugs within the first week abroad
In Laos, daily stool samples from the participants were analyzed locally in the Lao-Oxford-Mahosot Hospital-Wellcome Trust -Research laboratory. Had samples only been collected before and after travel, the proportion of superbug carriers had been approximately 70%. Daily real-time scrutiny already while abroad revealed, however, that all travelers had contracted a superbug within a week after arrival.
The findings varied day by day. While some participants carried superbugs for several days, others had a couple of days’ breaks after which superbugs were found again. Part of the travelers acquired several strains.
“It became evident that acquisition of superbugs is a dynamic process: bacteria come and go, some strains persisting for a lengthy period of time,” Kantele says.
Whole-genome sequencing revealed the great variety among superbug strains
After returning home, to explore the isolated superbug strains in more detail, the researchers established a collaboration with Jukka Corander, professor of Statistics at the Universities of Helsinki and Oslo, and Alan McNally, professor of Microbial genetics at the University of Birmingham, England. Whole-genome sequencing and analyses proved colonization to be a dynamic process involving constant switches between the various strains. Indeed, all the travelers had been exposed to a much wider range of superbugs than generally thought. Applying the traditional approach, about 20 new strains would have been detected after travel, but daily sampling abroad and whole-genome sequencing enabled the researchers to unravel that the participants acquired 83 different strains altogether.
Only in four cases did two travelers share the same strains, indicating that the bacteria were not in general transmitted from one to another.
None of the participants developed a clinical infection caused by the superbugs. Had they not been delivered their screening results on a daily basis, the study participants would have remained totally unaware of them carrying superbugs.
“It was wonderful to see how our intestinal bacteria stand up to the incomers: the great majority of all alien strains disappeared already before the end of the journey,” Kantele rejoices.
Professor Jukka Corander points out that the study provides a completely new perspective to the bacterial colonization diversity in geographic regions where superbugs are endemic.
“We have earlier obtained robust modeling results concerning the stability of E. coli colonization in populations with low levels of antibiotic resistance, however, the new study conducted in Laos implies that we need to start building the model anew, so that we gain a thorough understanding about the role of superbugs also in those circumstances where they colonize the majority of the people,” Corander says.
Antibiotic resistance increases at an alarming rate in the tropics
The worldwide growth of antibiotic resistance is particularly alarming in tropical regions with inadequate hygiene and uncontrolled use of antibiotics. Multidrug-resistant bacteria are carried both by animals and local inhabitants. Returning from such environments, many visitors carry superbugs to their home countries.
Increasing resistance is also being witnessed by research: the proportion of travelers carrying these bacteria is growing. Usually, acquisition of ESBL or other superbugs does not cause any symptoms. After travelers return home, the strains usually disappear over time. Carriers can, however, pass these bacteria on to others. Among a small proportion, the superbugs cause symptomatic infections, most typically a urinary tract infection. Treatment of infections caused by superbugs is more challenging than of those caused by sensitive bacteria. In some cases, the infection may even turn out life-threatening.
Antibiotic use during travel further adds to the risk of carriage: favoring the resistant bacteria, antibiotic treatment makes space for newcomers.
Kantele stresses the grave threat increasing resistance poses to healthcare worldwide.
“Antibiotics are not only needed to treat infections, but they also enable high-risk operations such as major surgery and organ transplants, where they are given to prevent infections,” she says.
Materials provided by the University of Helsinki. Content may be edited for clarity, style, and length.