Scientists Sound the Alarm on Emerging Tick-Borne Disease Babesiosis

Tick Crawling on Skin

Researchers at the University of California, Riverside, and Yale University have sequenced and assembled the first high-quality nuclear genome of Babesia duncani, a pathogen responsible for a malaria-like disease called babesiosis. Published in Nature Microbiology, the study reveals that the parasite has evolved new classes of multigene families, allowing it to evade host immune responses. The research team identified potential inhibitors of the parasite’s development, such as pyrimethamine, which could lead to more effective therapies for treating and managing human babesiosis. The tick that spreads babesiosis is mainly found in wooded or grassy areas and is the same tick that transmits Lyme disease, with around 20% of babesiosis patients co-infected with Lyme disease.

UC Riverside and Yale University team sequences and mines genome of the pathogen Babesia duncani.

Scientists have sequenced the genome of Babesia duncani, a pathogen causing the malaria-like disease babesiosis, and identified potential inhibitors for more effective treatments.

‘Tis the season for hiking now that spring has arrived and temperatures are on the upswing. But with hikes come insect bites and on the increase in North America is babesiosis, a malaria-like disease spread especially between May and October by a tick.

Indeed, recent research suggests an increase in the incidence of diseases transmitted by ticks around the world, not just the United States and Canada, due likely to climate change and other environmental factors. Among the tick-borne pathogens, Babesia parasites, which infect and destroy red blood cells, are considered a serious threat to humans and animals. All cases of human babesiosis reported in the United States have been linked to either Babesia microti, B. duncani, or a B. divergens-like species.

Now a research team led by scientists at the University of California, Riverside, and Yale University reports the first high-quality nuclear genome sequence and assembly of the pathogen B. duncani. The team also determined the 3D genome structure of this pathogen that resembles Plasmodium falciparum, the malaria-causing parasite.

“Our data analysis revealed that the parasite has evolved new classes of multigene families, allowing the parasite to avoid the host immune response,” said Karine Le Roch, a professor of molecular, cell and systems biology at UC Riverside, who co-led the study with Choukri Ben Mamoun, a professor of medicine at Yale University.

B. duncani 3D Genome Structure

The figure illustrates the 3D genome structure of B. duncani. Yellow, green, light blue, purple, and pink are the five chromosomes of B. duncani. Dark blue shows the centromeres of the chromosomes. Red are the telomeres of the chromosomes. Observe that telomeres and centromeres are in close proximity. Credit: Todd Lenz/Le Roch lab, UC Riverside

According to Le Roch, who directs the UCR Center for Infectious Disease Vector Research, the study, published today (April 13) in the journal Nature Microbiology, not only identifies the molecular mechanism most likely leading to the parasite’s pathogenicity and virulence, but also provides leads for the development of more effective therapies.

“By mining the genome and developing in vitro drug efficacy studies, we identified excellent inhibitors of the development of this parasite — a pipeline of small molecules, such as pyrimethamine, that could be developed as effective therapies for treating and better managing human babesiosis,” Le Roch said. “Far more scientific and medical attention has been paid to B. microti. The genome structure of B. duncani, a neglected species until now, will provide scientists with important insights into the biology, evolution, and drug susceptibility of the pathogen.”

Human babesiosis caused by Babesia duncani is an emerging infectious disease in the U.S. and is often undetected because healthy individuals do not usually show symptoms. It has, however, been associated with high parasite burden, severe pathology, and death in multiple cases. Despite the highly virulent properties of B. duncani, little was known about its biology, evolution, and mechanism of virulence, and recommended treatments for human babesiosis against B. duncani are largely ineffective.

Researchers Warn of Tick-Borne Disease Babesiosis

Coauthors (from left to right) of the research paper include Loic Ciampossin, Karine Le Roch, Stefano Lonardi, and Sakshar Chakravarty. Ciampossin is a graduate student working with Le Roch. Chakravarty is a graduate student working with Lonardi. Credit: I. Pittalwala, UC Riverside

A strong immune system is required to fight the pathogen. A compromised immune system could lead to flu-like illness. The tick that spreads babesiosis is mostly found in wooded or grassy areas and is the same tick that transmits bacteria responsible for Lyme disease. As a result, around 20% of patients with babesiosis are co-infected with Lyme disease.

B. duncani mostly infects deer, which serve as the reservoir host during the pathogen’s asexual development. The parasite’s sexual cycle occurs in the tick after the tick bites the infected deer. When this tick bites humans, infection begins. The full life cycle of Babesia parasites has not yet been determined. The tick that spreads babesiosis, called Dermacentor albipictus, lives longer than mosquitoes and could facilitate a long life cycle for B. duncani.

Even though scientists are discovering more Babesia species, diagnostics are mostly developed for B. microti. Le Roch is already working with Stefano Lonardi, a professor of computer science and engineering at UCR and co-first author of the study, on new Babesia strains that have evolved.

“The Babesia genomes are not very long,” said Lonardi, who assembled the B. duncani strain. “But they are challenging to assemble due to their highly repetitive content and can require years of research. Once the genome is assembled and annotated, it can provide valuable information, such as how the genes are organized, which genes are transcribed during infection, and how the pathogen avoids the host’s immune system.”

In older and immunocompromised people, if B. duncani is left unattended, babesiosis could worsen and lead to death. Once the pathogen enters the body and red blood cells start to get destroyed, fever, headache, and nausea can follow. People who get bitten by the ticks often don’t feel the bite, which complicates diagnosis. Skin manifestations of babesiosis are rare, Lonardi said, and difficult to separate from Lyme disease.

Le Roch and Lonardi urge people to be mindful of ticks when they go hiking.

“Check yourself for tick bites,” Le Roch said. “When you see your physician don’t forget to let them know you go hiking. Most physicians are aware of Lyme disease but not of babesiosis.”

Next the team plans to study how B. duncani survives in the tick and find novel vector control strategies to kill the parasite in the tick.

Le Roch, Mamoun, and Lonardi were joined in the study by colleagues at UCR, Yale School of Medicine, Université de Montpellier (France), Instituto de Salud Carlos III (Spain), Universidad Nacional Autónoma de México, and University of Pennsylvania. Pallavi Singh at Yale and Lonardi contributed equally to the study. The B. duncani genome, epigenome, and transcriptome were sequenced at UCR and Yale.

The study was supported by grants from the National Institutes of Health, Steven and Alexandra Cohen Foundation, Global Lyme Alliance, National Science Foundation, UCR, and Health Institute Carlos III.

The research paper is titled “Babesia duncani multi-omics identifies virulence factors and drug targets.”

Reference: “Babesia duncani multi-omics identifies virulence factors and drug targets” by Pallavi Singh, Stefano Lonardi, Qihua Liang, Pratap Vydyam, Eleonora Khabirova, Tiffany Fang, Shalev Gihaz, Jose Thekkiniath, Muhammad Munshi, Steven Abel, Loic Ciampossin, Gayani Batugedara, Mohit Gupta, Xueqing Maggie Lu, Todd Lenz, Sakshar Chakravarty, Emmanuel Cornillot, Yangyang Hu, Wenxiu Ma, Luis Miguel Gonzalez, Sergio Sánchez, Karel Estrada, Alejandro Sánchez-Flores, Estrella Montero, Omar S. Harb, Karine G. Le Roch and Choukri Ben Mamoun, 13 April 2023, Nature Microbiology.
DOI: 10.1038/s41564-023-01360-8

Funding: NIH/National Institutes of Health, Steven and Alexandra Cohen Foundation, National Science Foundation, NIH/National Institute of Allergy and Infectious Diseases, University of California, Riverside, Health Institute Carlos III

2 Comments on "Scientists Sound the Alarm on Emerging Tick-Borne Disease Babesiosis"

  1. I have babesiosis. I use atovaquone & azithro to treat it – but it keeps coming back. It took a long time to get a correct diagnosis. I hope your work will help fix those problems. I was bit by a tick in the Spring of 2001. I never had flu like sx. Shortly after I was bit I had fatigue, anorexia, felt like my toes were broken & attacks of fear followed by sweating and shaking. Over many years, the acute fear diluted to a constant low grade feeling of fear – not to mention the profound sweating. I lost life as I knew it.

  2. My 33 yo daughter has had Lyme & Babesia Duncani for a long time. (diagnosed 2014) She has been taking clindamycin + quinine for the last 7 years. The Babesia got so bad she was having regular blood transfusions. (Over 230 units in 3 years.) She finally had a total body blood exchange, replacing 80% of her red blood cells. Since then she has been able to maintain her Hgb. After the exchange she tested negative for B.Duncani from Igenx so she cut drugs in half to see what would happen. But recently she has again tested positive and now it is hard to get clindamycin. We keep waiting for new drugs.

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