Cutaneous leishmaniasis is one of the “neglected tropical diseases,” a disparate group of conditions that affect some of the world’s poorest people and receive relatively little global attention. Caused by parasites spread by sand fly bites, the disease is not fatal, but skin lesions, the main symptom, can bring about all sorts of issues relating to depression and stigma. “You get facial scarring for life, which causes all sorts of issues relating to depression and stigma,” says parasitologist David Molyneux of the Liverpool School of Tropical Medicine in England.
The disease is endemic in the Middle East, Asia, Africa and Latin America. Until recently, it was not widely believed to be native to the U.S. Cases have long been seen in Texas, but most were presumed to have been contracted by travelers returning from Mexico. Over the past decade or so, reports started cropping up of cases in people with no history of travel outside the U.S., suggesting that they may have caught the illness locally.
A U.S. Centers for Disease Control and Prevention team has now found nontravelers who were infected with a form of the parasite that is genetically different from those sometimes brought back from overseas, suggesting that cutaneous leishmaniasis is endemic in the U.S. The researchers hope to improve detection of cases across the country by raising awareness that this is no longer a parasitic disease that is only picked up abroad.
During a presentation at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH) on October 19, the researchers described their analysis of 2,133 tissue samples sent to the CDC for testing between 2005 and 2019. In their study, which has not yet been published, they found that most of the positive samples came from people who had traveled to countries where cutaneous leishmaniasis was endemic, but 86 people who were infected had not traveled outside the U.S.
The researchers used genetic sequencing to reveal two distinct “strains” and found that one of these was present in an overwhelming majority of patients who had travelled abroad, while the other predominated in people who had not. “This species of parasite has a different genetic signature in travelers and non-travelers,” says Vitaliano Cama, a microbiologist with the CDC who worked on the study. “That’s a trend we hadn’t seen before.”
A hint of what was going on came from a 2018 study that showed an increase in cases of cutaneous leishmaniasis in the U.S. “That was the first thing that caught my attention,” says molecular biologist Marcos de Almeida, who led the new investigation that was reported at the conference. “Then we started looking at the data we had, and we found a lot of cases.” The genetic evidence suggests the disease is being spread by local sand fly populations. “This study confirms things we already suspected but gives us a more solid evidence base to show what’s going on,” says virologist Daniel Bausch, president of the ASTMH, who was not involved in the work. “The power of genomic sequencing is incredible for figuring things out we didn’t use to be able to.”
The team found this “American strain” in samples going back 18 years. “Throughout the analysis we conducted, both signatures appear every year,” Cama says. “It seems it’s been there for some time.” Most samples harboring the local strain were from Texas, but this could be partly because of heightened awareness of the disease there. A lack of awareness in other states makes it difficult to know if it is elsewhere. “From a public health perspective, we want to raise awareness among physicians that cases may occur without international travel,” Cama says, “at least in Texas and perhaps other states.”
Currently cutaneous leishmaniasis is reportable (meaning it is mandatory for health providers to notify public health officials of cases) in Texas but not federally, so assessing its prevalence in the rest of the U.S. would be guesswork right now. The researchers hope that raised awareness will increase detection of cases, which could in turn drive changes in where it is reportable. Having this “genetic fingerprint” should also make it easier for future studies to track where the disease is being transmitted. “We need better surveillance, and genomic surveillance is a powerful tool,” Bausch says.
Sand flies (known as “vectors” of the disease) pick the parasite up from feeding on infected animals. These animal “reservoirs” maintain the disease in specific geographical locations. The new study says nothing about possible reservoirs, but parasitologists have long known that leishmania parasites exist in Southern Plains wood rats, says Molyneux, who was not involved in the study. Investigating this could have practical benefits. “If you can identify reservoirs and be more specific about routes of transmission, that has potential for prevention efforts,” Bausch says. “You could theoretically say, ‘Here’s the way to avoid this.’”
Another important source of information will be more detailed human behavioral data. The samples sent to the CDC had limited data attached, but the team hopes its work will spur more research. “This is going to generate other kinds of studies, which can collect more information,” Cama says. “Because now we have a reason.”
One factor driving the disease’s northward creep may be climate change. “It’s increasing the likelihood sand flies can move further north,” Molyneux says. “They thrive in warm conditions.” Climate modeling suggests this trend will continue.
The CDC team next plans to explore more of the parasite’s genome. “Our data is a strong indication we have something happening exclusively in the southern border of the U.S.,” de Almeida says. “But to confirm this, we need to explore the whole genome and compare the Texas strain with the Central American strain to see how different they are.” Future research could then investigate possible clinical differences. “The next step will be how important this is for disease development, but this is a long-term process,” de Almeida says.
The news comes amid concern that a more severe form of the disease, called visceral leishmaniasis, could also gain a foothold in the U.S. This disease, which is caused by a related parasite, affects internal organs and kills between 20,000 and 30,000 people per year globally. The worry is that local sand flies could bite dogs that are imported from places where the parasite is common and then bite humans. “We don’t want to put this out as a panic thing; we have no evidence this circulates in the U.S.,” Bausch says. “But there’s evidence it could.” Another presentation at the conference described a risk assessment tool to promote better screening of dogs being imported to the U.S.
One thing that seems certain is cutaneous leishmaniasis is no longer solely a tropical disease. “The idea that there’s the tropical diseases and they’re not our problem is certainly not true,” Bausch says. “Whether we like it or not, we have to recognize we’re all in this together.”