Emerging Trends in Tick-borne Diseases in the United States

In a webinar presented on June 9 by The Department of Health and Human Services (HHS) Working Group on Lyme and Other Tick-borne Diseases, a panel of speakers discussed trends in tick-borne diseases (TBDs) in the United States.

Ben Beard, PhD, Chief of the Bacterial Diseases Branch, US Center for Disease Control and Prevention (CDC), Fort Collins, Colorado, introduced and moderated the webinar, highlighting the large number of TBDs that comprise a significant public health problem in the United States. Dr. Beard noted the increased incidence of TBDs in recent decades and added that, although Lyme disease remains the most common of these diseases in this country, novel TBDs also continue to emerge.

Lyme Disease

Rebecca Eisen, PhD, and Kiersten Kugeler, PhD, MPH, both also from the CDC, Fort Collins, Colorado, discussed the geographic expansion of Lyme disease and its vectors.

According to Dr. Eisen, Lyme disease is a systemic disease, caused by the spirochete Borrelia burgdorferi, which is spread to humans by the bite of two types of infected ticks—the blacklegged tick (Ixodes scapularis) and the western blacklegged tick (Ixodes pacificus). The infected nymphal tick is responsible for most cases of Lyme disease in humans because this tick stage is very small and often goes unnoticed after it attaches to a person’s skin.

Dr. Eisen emphasized the changing landscape of risk for transmission of Lyme disease to humans. Although about 95% of Lyme disease cases occur in the northeastern and northcentral states, she discussed how its range is now expanding geographically in all directions from these foci, adding that oceans provide natural landscape barriers to expansion. Indeed, research has identified the two tick vectors in 49% of continental US counties, Dr Eisen said. This represents a 45% increase in the number of US counties that have reported the presence of these ticks since 1998.

In conjunction with this shifting distribution of tick vectors, Dr. Kugeler discussed how the distribution of Lyme disease in humans has also changed over time. She shared data from a study conducted to define counties in which residents have a high risk of acquiring Lyme disease. In particular, in high-risk areas in the United States, the results quantified a substantial increase over time in the number of counties identified as having high incidence of Lyme disease. In the northeastern states, the incidence of Lyme disease increased by greater than 320% over a 20-year period, rising from 43 cases between 1993 and 1997, to 182 between 2008 and 2012; similarly, in the northcentral states, its incidence increased by about 250%, rising from 22 cases to 78 cases over the same time period.

Nevertheless, it is important to remember that human Lyme disease risk is influenced not only by the presence of tick vectors, but by numerous other factors, Dr. Eisen concluded. These factors include awareness and use of tick precautions.

Borrelia mayonii—a New Cause of Lyme Disease

Borrelia burgdorferi was originally believed to be the only borrelial species to cause Lyme disease in North America. However, Elitza Theel, PhD, from Mayo Clinic, Rochester, Minnesota, discussed the recent identification of Borrelia mayonii, a novel cause of Lyme disease in humans.

This discovery unfolded when scientists at Mayo Clinic tested diagnostic specimens from 6 patients with suspected Lyme disease. They obtained atypical polymerase chain reaction (PCR) results in the specimens, indicating that the causative bacterium in these cases was genetically distinct from B. burgdorferi. The greatest genetic similarity occurred in one specimen that showed 95% sequence homology to B. burgdorferi, said Dr. Theel. As a consequence, because at least 98.3% nucleotide sequence similarity between 2 organisms is required to identify them as the same species, Dr Theel added that the causative agent in these 6 cases was designated as a new species and the name B. mayonii was proposed for it.

According to Dr. Theel, the 6 patients involved were residents of Minnesota, North Dakota, and Wisconsin. They ranged from ten to 65 years old, and four of them were male. Clinical features in these cases included fever, headache, rash, and arthralgia—symptoms similar to those of Lyme disease caused by B. burgdorferi. However, cases of Lyme disease caused by B. mayonii involved more severe disease that required hospitalization, with nausea, vomiting, and diffuse rash. In contrast to Lyme disease cases due to B. burgdorferi, these cases due to B. mayonii were also associated with a much higher spirochetemia, and the causative organism was also found in whole blood specimens. Five of these patients recovered completely with antibiotic therapy. Dr. Theel also noted that B. mayonii DNA was detected in 19 of 658 ticks collected from one patient exposure site in Wisconsin. Ixodes scapularis ticks are therefore believed to be the likely vector for B. mayonii, she concluded.

Update on Borrelia miyamotoi

Alan Barbour, MD, a professor at the School of Medicine, University of California, Irvine, discussed Borrelia miyamotoi, another Borrelia group spirochete that is transmitted by ixodid tick species and may be the cause of another emerging TBD in this country.

According to Dr Barbour, in the United States, B. miyamotoi disease (BMD) was first reported in 2013 in the Northeast, but is becoming increasingly common and should be considered in all areas where infections transmitted by deer ticks are endemic. B.miyamotoi is distributed across a similar geographic range as B. burgdorferi in North America, Dr. Barbour said. However, although B. burgdorferi prevalence is about ten times that of B. miyamotoi in most areas, he noted that the prevalence of B. miyamotoi is similar to that of B. burgdorferi—and often higher—in some areas of of California. Another important feature, Dr. Barbour noted, is that most cases of BMD have occurred in July and August, suggesting disease transmission by larval ticks.

The symptoms of BMD are nonspecific and include fever, headache, chills, myalgia, and arthralgia. BMD can also be severe and include meningoencephalitis. Symptoms can persist for weeks to months, and relapse of fever can also occur in some cases. Some patients with BMD may also be coinfected with B. burgdorferi. Compared with patients with Lyme disease, those with BMD tend to have a higher fever and are more likely to require hospitalization, in particular because of meningoencephalitis; they also have a low platelet count and abnormal liver enzyme levels. The public health significance of BMD therefore relates to its similar presentation to human granulocytic anaplasmosis (HGA), Dr. Barbour said.

Detection of B. miyamotoi in diagnostic specimens by using phase contrast or dark field microscopy can be difficult, and Dr. Barbour recommended examination of a thick blood smear and immunofluorescence staining to identify spirochetes. PCR is also available to detect the organism, as is a serological assay to detect antibodies to the glycerophosphodiester phosphodiesterase (GlpQ) of B. miyamotoi.

Doxycycline is the preferred initial treatment choice for patients with BMD, Dr. Barbour said, in particular because it is also effective against Lyme disease and HGA. Treatment with a beta lactam antibiotic may also be necessary for patients with central nervous system disease, he said.

Emerging Tickborne Viral Diseases

According to Nicholas Komar, PhD, from CDC, Fort Collins, Colorado, although tick-borne viruses known to cause disease in the United States are rare, their incidence may be changing. He discussed four such viruses—none of which causes more than a mean of 10 cases annually in the United States.

Colorado tick fever virus (CTFV) causes the greatest number of human cases of tick-borne viral diseases in this country, he said. CTFV is transmitted to humans by the bite of an infected Rocky Mountain wood tick (Dermacentor andersoni). The disease is typically mild and manifests as fever, chills, headache, body aches, and fatigue. In most cases, these symptoms resolve without treatment. Some patients have developed symptoms such as skin rash and abdominal pain. And, in rare cases, encephalitis, hemorrhage, and death have been reported.

Powassan virus, a flavivirus, causes the second highest number of human cases of tick-borne viral diseases in the United States, and is transmitted by the bite of an infected tick, including Ixodes ticks as well as tick species that feed on small mammals. Although typical disease manifestations of Powassan virus illness include fever, vomiting, headache, speech difficulties, and seizures, more severe disease—including encephalitis—can also occur. No specific treatments exist for Powassan virus illness, but with good supportive care, 90% of patients with severe disease will survive. However, persistent neurological sequlae are common.

Heartland virus (HRTV), a phlebovirus, was first isolated in 2009 from a patient at Heartland Regional Medical Center in Missouri. The virus is transmitted by the bite of an infected lone star tick (Ambylomma americanum), and so far, less than 20 cases have been reported to the CDC, all occurring in Missouri, Oklahoma, and Tennessee, where the tick vector is in prevalent. These cases have all involved men, although it is unknown whether this reflects a biological risk factor, or merely a behavioral risk factor because all affected men were active outdoors in heavily-infested habitats.

Symptoms in these patients included fever, fatigue, headache, nausea, and diarrhea. The patients also had low white blood cell counts and most required hospitalization because of their symptoms. Because these features are similar to those in cases of ehrlichiosis, the patients with HRTV disease were treated with antibiotics, but did not respond to therapy. Although no specific treatments exist for HRTV disease, supportive therapies can help improve symptoms. The case fatality rate is approximately 10%.

Bourbon virus, a thogotovirus, was first isolated in June 2014 from a man in Bourbon County, Kansas, who died after a period of illness following a tick bite. The patient’s symptoms were similar to those of HRTV disease and included fever, weakness, headache, nausea, diarrhea, anorexia, myalgia, and arthralgia. He also had a low white blood cell count. However, overall, this virus still remains poorly understood, Dr. Komar said.

Tick-Induced Meat Allergy

Scott Commins, MD, PhD, from the University of North Carolina, discussed the emergence of a tick-related meat allergy triggered by sensitization to lone star tick bites.

According to Dr. Commins, people who have been bitten by Ambylomma americanum ticks may occasionally develop an allergic reaction to galactose-alpha-1,3-galactose—a carbohydrate also known as alpha-gal—after eating red meat. Scientists currently believe the ticks acquire alpha-gal after biting a deer, he said. When the tick bites a person, it injects alpha-gal into the person in its saliva. In some people, it is thought that alpha-gal then triggers the immune system to produce antibodies directed against this carbohydrate.

Because alpha gal is found in all red meats, including beef, pork, and lamb, the next time the person eats red meat, the alpha-gal activates these antibodies and results in an allergic reaction that, in many cases, has occurred during the night. The reaction typically manifests as delayed urticaria (hives) or delayed anaphylaxis (involving a host of symptoms, including swollen lips, eyes, tongue and throat; respiratory issues; and increased heart rate and low blood pressure). However, some people may experience gastrointestinal symptoms, such as vomiting or diarrhea, without cutaneous features. The key feature of this condition that differentiates it from typical food allergies is the delay of four to six hours, or longer, from consumption of the meat to onset of symptoms, Dr. Commins said.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.