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Better Prevention and Treatment of Tick-borne Diseases Needed

Diana Phillips
August 06, 2018

The incidence of tick-borne disease in the United States is increasing at an alarming rate, officials from the National Institute of Allergy and Infectious Diseases say. They call on public health and biomedical researchers to double down on efforts to better understand the pathogenesis of tick-borne illnesses and to develop improved strategies for prevention and management.

Citing a report released earlier this year from the Centers for Disease Control and Prevention (CDC) indicating that the number of tick-borne diseases reported in the United States has more than doubled in the last 13 years, Catharine I. Paules, MD, from the Office of the Director, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, and colleagues suggest this is a conservative estimate.

"The public health burden of tickborne pathogens is considerably underestimated," the authors write in a perspective article published online July 25 in the New England Journal of Medicine. "For example, the CDC reports approximately 30,000 cases of Lyme disease per year but estimates that the true incidence is 10 times that number." The authors attribute this discrepancy to limitations in surveillance and reporting systems, as well as constraints imposed by diagnostics that rely heavily on serologic assays.

Lyme disease, which accounts for 82% of reported tick-borne illnesses nationally, is commonly caused by the Borrelia burgdorferi bacterium in the United States. The surge in reported cases is at least partially a result of the increased density and range of tick vectors, the authors explain. For example, the black-legged deer tick Ixodes scapularis, the primary source of Lyme disease in the northeastern United States, was detected in nearly 50% more US counties in 2015 than in 1996, they write.

The clinical manifestations of Lyme disease are generally classified as localized, disseminated, or persistent. They span a broad spectrum and vary in severity, as a result of differences in the infecting species and treatment timing. Although most individuals with Lyme disease respond well to antibiotic therapy, up to 20% continue to have symptoms after treatment, Paules and colleagues explain. "Despite more than four decades of research, gaps remain in our understanding of Lyme disease pathogenesis, particularly its role in these less well-defined, post-treatment symptoms."

In addition to Lyme disease, the CDC in its report identified other tick-borne diseases that have also seen rises in incidence during the same period. These include spotted fever rickettsioses, babesiosis, and anaplasmosis/ehrlichiosis.

Further, potentially dangerous tick-borne viral infections such as Powassan virus (POWV) infection are increasing. For example, only 20 US cases of POWV infection, which causes fever followed by progressive neurologic manifestations and death in 10% to 15% of individuals, and long-term complications in 50% to 70%, were reported before 2006, whereas 99 cases were reported between 2006 and 2016.

"The increase in POWV cases coupled with the apparent expansion of the I. scapularis range highlight the need for increased attention to this emerging virus," the authors stress.

The current state of the science for identifying and understanding the pathogenesis of tick-borne infections is insufficient, according to the commentary's authors. "Diagnostic utility is affected by variability among laboratories, timing of specimen collection, suboptimal sensitivity during early infection, imperfect use of diagnostics (particularly in persons with low probability of disease), inability of a single test to identify coinfections in patients with acute infection, and the cumbersome nature of some assays," they write. "Current diagnostics also have difficulty distinguishing acute from past infection — a serious challenge in diseases characterized by nonspecific clinical findings."

In the case of less common infections, such as POWV, "serologic testing can be performed only in specialized laboratories, and currently available tests fail to identify novel tick-borne organisms," Paules and colleagues write.

Promising new technologies, such as a multiplex serologic platform that can detect antibodies to more than 170,000 distinct epitopes, may improve diagnostic capabilities, as well as the identification of emerging pathogens, the authors write. "In addition, sensitive, specific and, where possible, point-of-care assays will facilitate appropriate clinical care for infected persons, guide long-term preventive efforts, and aid in testing of new therapeutics and vaccines."

Tick-Induced Anaphylaxis After Red Meat Consumption Also Rising

Another emergent tick-borne illness not addressed in the commentary is anaphylaxis resulting from immunoglobulin E antibodies to galactose-alpha-1,3-galactose (α-gal) caused by bites of larval or adult lone star ticks, which are found in eastern and southeastern states. In a recent study published online July 30 in the Annals of Allergy, Asthma and Immunology, Debendra Pattanaik, MD, associate professor of medicine at the University of Tennessee Health Science Center in Memphis, and colleagues report that bites from the lone star tick are implicated in approximately one third of all potentially life-threatening allergic reactions in the Tennessee region.

Pattanaik and colleagues reviewed 218 anaphylaxis cases treated between 2006 and 2016 at the University of Tennessee Health Science Center. Of 85 cases classified as having a definitive cause on the basis of history and testing, 33% were caused by an allergic sensitivity to α-gal that develops after the consumption of red meat. The lone star tick is the likely cause, the authors report.

Unlike other food allergies that prompt near-immediate anaphylactic reactions, the allergic reaction resulting from a lone star tick bite is usually delayed, the authors write. Symptoms can occur 2 to 6 hours after eating red meat, which makes the source of the reaction more difficult to pinpoint.

Although most lone star tick bites will not lead to this allergic reaction, in regions where the tick is endemic and becoming more prevalent, "it is reasonable to test for this allergic antibody. It's typically done with a blood test and can be ordered by any allergist," Pattanaik told Medscape Medical News.

Whereas the link between lone star tick bites and a-gal allergy is now clear, the biology of the connection is still uncertain, Pattanaik said, noting that at this time, "avoidance is the only option to prevent allergic response."

Prevention and Improved Treatment Urgently Needed

To date, strategies for the prevention and management of tick-borne diseases in the United States have included efforts to reduce tick exposure and treat infections, although no treatment exists for tick-borne viruses. The "biggest gap" on the prevention and management front is the lack of vaccines targeting US tick-borne pathogens, Paules and colleagues write, noting that concerns about adverse effects, potential liability, and poor sales led to the withdrawal of a previously marketed Lyme vaccine.

Given the likelihood that similar concerns could continue to stymie human vaccine development, the commentary authors suggest a more viable option might be an agent that targets the vector, rather than specific pathogens. "This approach could reduce transmission of multiple pathogens simultaneously by exploiting a common variable, such as vector salivary components," they write. "Phase 1 clinical trials are under way to evaluate mosquito salivary-protein–based vaccines in healthy volunteers living in areas where most mosquito-borne diseases are not endemic. Since tick saliva also contains proteins conserved among various tick species, this approach is being explored for multiple tickborne diseases."

In the absence of improved diagnostics, more comprehensive treatment options, and effective vaccines, the burden of tick-borne diseases will continue to grow. "If public health and biomedical research professionals accelerate their efforts to address this threat, we may be able to fill these gaps," the authors conclude. "Meanwhile, clinicians should advise patients to use insect repellent and wear long pants when walking in the woods or tending their gardens — and check themselves for ticks when they are done."

According to Lyle R. Petersen, MD, MPH, director of the Division of Vector-Borne Diseases, CDC, ticks are thriving in regions of the country that were previously too cold for them. "This, together with suburban reforestation, increasing deer populations, and the absence of effective vaccines, means that more people are exposed and vulnerable to tickborne infection," he told Medscape Medical News.

At this time, Peterson said, "the most pressing need is research on how to best prevent ticks from spreading disease." In the absence of an effective vaccine, "the best 'prevention' approach is educating at-risk populations to recognize the ticks if they see them on themselves or their children and remove them immediately, which will largely reduce the risk for transmission if caught early (within a day after the tick has attached)," he explained.

The authors of the Paules commentary and Peterson have disclosed no relevant financial relationships. One coauthor of the Pattanaik study reported relationships with Genentech, Novartis, Bayer, Kaleo, Serono, Boehringer Ingelheim, and Shire. Another coauthor of the Pattanaik study is an associate editor of the Annals of Allergy, Asthma and Immunology and serves on the advisory board of Aimmune Therapeutics.

Reviewed on 8/6/2018

SOURCE: Medscape, August 06, 2018. N Engl J Med. Published online July 25, 2018. Ann Allergy Asthma Immunol. Published online July 30, 2018.

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