Urban rats spread a deadly bacteria as they migrate within cities that can be the source of a potentially life-threatening disease in humans, according to a six-year study by Tufts University researchers and their collaborators that also discovered a novel technique for testing rat kidneys.
Leptospirosis is a disease caused by a type of bacteria often found in rats. It's spread through their urine into soil, water, or elsewhere in the environment, where it becomes a source of infection and contamination for humans, dogs, and other species. While it's prevalent worldwide, it's more common in tropical regions, though a changing climate means it could become more common in colder regions as they warm.
In Boston, leptospirosis persists in local rat populations, and different strains of the bacteria move around the city as groups of rats migrate, according to a new study by Marieke Rosenbaum , M.P.H., D.V.M., assistant professor in the Department of Infectious Disease and Global Health at Cummings School of Veterinary Medicine at Tufts University, along with co-authors at Northern Arizona University (NAU), the United States Department of Agriculture (USDA), and the Centers for Disease Control and Prevention (CDC). In addition, their genetic analysis of a 2018 human leptospirosis case in Boston strongly suggests a link to rats as the source.
The paper, published recently in the journal PLOS Neglected Tropical Diseases , is the latest work conducted by Rosenbaum and collaborators as part of the Boston Urban Rat Study, a research group investigating whether rats in Boston carry pathogens that pose a risk to public health. For this study, she joined forces with the City of Boston's Inspectional Services Department and other groups throughout the city to track rats from 2016 to 2022 and test rats for leptospirosis. She and researchers then employed advanced molecular techniques to figure out exactly what type of leptospirosis was present. The researchers analyzed DNA from 328 rat kidney samples collected from 17 sites in Boston, and 59 rats representing 12 of 17 sites were positive for Leptospira bacteria.
"The primary way to get a full genomic sequence of a virus or bacteria is to culture it, which was a challenge in this case because Leptospira is considered a fastidious organism," says Rosenbaum. "It has specific requirements for temperature, pH, and nutrients. But our USDA collaborators cultured the bacteria from not only fresh but also frozen rodent kidneys, which has never been reported in the literature before, to get isolates."
From there, the Northern Arizona University collaborators at the Pathogen & Microbiome Institute (PMI) used targeted DNA capture and amplification to pick out and enhance leptospirosis DNA in the samples, which resulted in a lot of fine-scale genomic information about the isolates.
"The new genetic and tools that we developed and used in this study are real game changers for leptospirosis research, as we can now use the power of the whole genome to look for relatedness among samples, something that just wasn't possible before," said Dave Wagner, Ph.D., professor of biological sciences and executive director of the PMI at NAU.
"Because we were able to do the culturing and the sequencing, we were able to look more closely at how the different strains of leptospirosis are related, which helps us understand how the bacteria are getting transmitted between rats and rat populations in the city," Rosenbaum says.
The researchers hope their findings will help guide rat control and human leptospirosis mitigation efforts in urban settings.
On Human Cases
For this paper, Rosenbaum and the other authors examined one human case of leptospirosis in collaboration with the CDC, which had an isolate obtained from a patient in a Boston hospital that was reported to the federal level. Researchers at Northern Arizona University used molecular tools to get a genomic sequence, which they found to be nearly identical to a sequence obtained in three different rats spanning multiple years from the same location in Boston.
"It's very strong evidence that the source of that human case was a rat," says Rosenbaum.
Rats are the most well-established source of leptospirosis infection in humans. But not all cases get diagnosed or reported. Some people may get infected, not develop any symptoms, and never know they were infected. Others might develop a mild fever or other nonspecific symptoms before their immune system clears the infection. However, a small percentage of people will go on to develop a more serious case of the disease, which can affect different organs and, ultimately, cause multi-organ failure and death.
"Human exposure to rats is not very common. But certain populations might be at higher risk, like unhoused people or people who engage in outdoor injection drug use, which are situations that lead to more direct contact with rats," says Rosenbaum.
There are challenges to collecting data on leptospirosis cases, as well. Few clinicians would think to test a patient for leptospirosis without some knowledge that the person may have been exposed to it. And even if they do test for it, sometimes positive results are not reported to state or national systems that compile such data. In addition, leptospirosis is responsive to antibiotics, so if a physician prescribes antibiotics for a patient to treat a suspected infection, then the bacteria may not get picked up by a test anyway, Rosenbaum explains.
On Rat Migration
"Rats have a high degree of genetic structure, which means there are distinct rat populations throughout the city that are highly related to each other," says Rosenbaum. "It doesn't look like they're intermingling with other populations a lot, and that's contributing to a stable population over time, but when they do disperse, they can take leptospirosis with them. The actual genetic sequence of leptospirosis is also stable within a population of rats over time. Rats in Boston Common have a strain of leptospirosis that they maintain over years in that location, and it's different from the strain we saw in another area that also was persisting over time."
They found that a rat in Boston would have to travel over 600 meters, or just over a 1/3 of a mile, to encounter another genetic population of rats. They also found evidence that large, multi-lane roads disrupted all connectivity between populations of rats on either side of the road, and that rats used greenways and biological corridors for travel and intermingling. Construction is another well-known disruptor of rat burrows that forces rats to look for other places to persist, which can increase the spread of the bacteria.
When it comes to pest control, Rosenbaum says an important next step is to better understand how pest management interventions impact rat migrations and their population structure, as well as how they impact humans and the environment.
"Extermination is not realistic," she says, "but I think better understanding of how the different pest control interventions are impacting rat migrations and transmission of pathogens amongst the rat population would be really helpful."
This project was supported by the National Institutes of Health under award numbers R01AI172924 and K-24 AI 106822 (Institute of Allergy and Infectious Diseases); K08ES035460 (Institute of Environmental Health Sciences); and KL2TR002545 (National Center for Advancing Translational Sciences). This research was supported in part by an appointment to the Animal and Plant Health Inspection Service (APHIS) Research Participation Program administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664. Complete information on authors, methodology, funders, and conflicts of interest is available in the published paper.
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