THE PRIMER

Alleluia! Spring! It means the promise of more time in the fresh air – gardening, camping, or just enjoying the sunshine. Unfortunately, time outdoors increases the risk of contracting Lyme disease. As you may know, this illness comes courtesy of our favorite blood-sucking arthropods: ticks. Not just any tick, however. Only the diminutive deer tick (Ixodes scapularis) transmits this nasty disease. Lyme has been reported in every US state but most commonly occurs in the Northeast and the Upper Midwest. The disease gets its name from the tiny Connecticut town of Lyme, where doctors identified a cluster of cases in the 1970s. This article looks at the cause, treatment, and possible complications of this potentially debilitating disease. We’ll also preview a new Lyme vaccine that the FDA has awarded fast-track status.

The microbiological culprit behind Lyme is the bacterium Borrelia burgdorferi. These microorganisms inhabit deer, of course, but smaller animals, such as mice and birds. A hungry deer tick chomps on, say, an infected white-footed mouse. When the tiny black-legged parasite eventually feeds again, it passes on the gift of Lyme to its next victim, whether a gardener or groundhog.

In a human host, proteins on the surface of B. burgdorferi wreak havoc within and outside our cells. The bacterium disrupts the function of infected tissues at the cellular level. Combined with the body’s inflammatory response, the symptoms of Lyme disease ensue.

The most notorious sign of Lyme disease is the red bullseye rash that often develops near the bite. According to the Centers for Disease Control, other symptoms that may occur within the first 30 days of infection include fever, muscle, joint aches, and swollen lymph nodes. Unfortunately, not everyone develops the bulls-eye, and it’s easy to confuse Lyme disease with other illnesses. Failing prompt diagnosis and antibiotic treatment, a plethora of more severe symptoms can develop days or even months after exposure. These can include heart palpitations, severe joint pain, facial palsy, and short-term memory issues.

Healthcare providers primarily diagnose Lyme disease based on symptoms, known or potential exposure to deer ticks and an FDA-approved blood test for anti- B. burgdorferi antibodies. None of these approaches is ideal. Lyme disease’s rash fails to appear in about a quarter of infected people. Unfortunately, it usually takes a month or longer after infection for people to produce enough B. burgdorferi antibodies to show up in a blood test. This lag can delay treatment and create a window of severe outcomes such as nerve damage and heart problems. Thus, epidemiologists and other scientists are in hot pursuit of tests capable of detecting the bacterium earlier.

One innovative approach comes from Ceres Nanoscience (Manassas, VA) and their “nanotrap” technology. Rather than trying to detect a patient’s response to infection, the Ceres Nanotrap Lyme Antigen Test detects the presence of B. burgdorferi itself. It identifies the bacterial protein OspA in the urine of infected patients. Other researchers have tried this method but found themselves stymied due to the low concentration of the protein in the samples. Enter nanotrap technology. These nanoparticles (10-9 meter diameter) comprise an outer shell surrounding a “bait” molecule. The shell filters out proteins larger than the target. Meanwhile, the molecular bait inside captures only OspA. The nanotraps are then processed to remove any captured proteins and identify them.

The new Ceres test is available as a CLIA (Clinical Laboratory Improvements Amendment) test. This means that the test itself cannot be sold to a physician’s office or pharmacy but must be performed at a laboratory facility approved by the Centers for Medicare and Medicaid Services (Baltimore, MD). In suspected Lyme disease cases, a urine sample is sent to the Ceres lab, analyzed using the Nanotrap test, and the results sent back to the physician’s office.

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Another strategy for diagnosing infectious diseases sooner rather than later is PCR-based testing — detecting and amplifying specific pathogen-associated gene sequences. This approach works well with many viruses, including HIV and influenza. However, identifying a bacterial infection such as Lyme disease this way is more challenging. Why? During an active viral infection, viruses reach high concentrations within the bloodstream. This makes it relatively easy to find them in a simple blood draw.

In contrast, the Lyme bacterium tends to “hide out” in tissues, making obtaining gene sequences from a blood sample more challenging. Nonetheless, a DNA-based test for the disease is developed by DNA Connexions (Colorado Springs, CO). Like the nanotrap test, it’s available as a CLIA lab test.

People diagnosed with Lyme disease early are most likely to respond to the standard antibiotic treatment. Otherwise, debilitating symptoms are more likely to develop and linger. In a small percentage of patients, symptoms such as fatigue and pain linger for months or even years. This phenomenon is known as post-treatment Lyme disease syndrome.

For now, the best way to avoid contracting Lyme disease is to protect yourself by wearing long sleeves, pants, and a hat or scarf in areas where deer ticks are common. In addition, it’s important to check yourself or your loved ones for ticks after you’ve spent time outdoors.

Fortunately, a French company, Valneva, is giving lovers of the great outdoors something more than a bottle of DEET to ward off Lyme disease. The Lyon, France-based biotech company is developing a Lyme vaccine. Known as VLA15-101, it consists of the B. burgdorferi surface protein OspA. Researchers hope to train our bodies via needles to recognize the bacterium as a threat and rev up our immune response in case of actual infection. The vaccine includes all six types of OspA proteins. The FDA granted VLA15-101 fast-track status in 2017, and is currently in Phase III clinical studies.

Ticks have a few tricks up their teeny-tiny segmented sleeve when it comes to obtaining their blood banquet. People don’t always notice a bite because the sneaky little arachnids inject a neurotoxin (a local anesthetic) when they latch on. By the time the host finds the freeloader, the little parasite can be tough to remove. That’s because the tick secretes another secret weapon – a sticky substance called “cementum” near the bite, allowing it to hang on tight for chow time.