Lyme disease ‘keeps moving and carries on’
Lyme disease, the leading vector-borne infection in the United States, affects thousands of Americans every year, especially those in the Northeast and upper Midwest.
This disease was first recognized in Lyme, Connecticut, in the 1970s, when a high incidence of juvenile arthritis was observed. In 2013, the Centers for Disease Control and Prevention (CDC) estimated approximately 300,000 new cases in the United States. Deer ticks spread the infection-causing pathogen, Borrelia burgdorferi, between humans and small rodents, like mice, and birds, both of which can serve as a reservoir. In other words, the disease naturally occurs in the environment in these smaller animals, but cannot survive in soil or water. Deer ticks, also known as Ixodes scapularis, are much smaller than other commonly observed ticks, thus making it difficult to see when they are biting.
Borrelia burgdorferi is a unique type of bacteria called a spirochete. “They’re stealth pathogens and able to avoid the immune system,” said Jenny Hyde, PhD, assistant professor in the Department of Microbial Pathogenesis and Immunology at the Texas A&M College of Medicine, whose research focus is Lyme disease. “Borrelia burgdorferi causes a multi-stage disease beginning at the initial site of the tick bite developing a localized infection before traveling to other tissues in the body to develop an inflammatory disease.”
The initial symptoms of Lyme disease are similar to the flu, with people experiencing fever, chills, fatigue, headache and general aches. Approximately 70 to 80 percent of cases develop a painless bullseye rash, which is called an erythema migrans, at the location of the tick bite and represents a distinctive feature of early Borrelia burgdorferi infection. Because the symptoms are so general, infected individuals may not seek medical care immediately. Lyme disease is readily treatable with antibiotics if they are administered shortly after initial infection. If left untreated, about half of infected individuals will go on to develop a disseminated infection—the second stage of disease—weeks or months later.
After the initial stage, it can be days or months later that the bacteria travel to other parts of the body—especially the heart, joints and central nervous system—and the secondary infection occurs. Lyme arthritis, especially in one knee, is the characteristic symptom of disseminated infection in North American cases. “We’re not sure all the ways it causes inflammation in patients,” Hyde said. “We know some of the mechanisms, but clearly our knowledge is incomplete.” Inflammation is a major contributor to the symptoms experienced by Lyme disease patients. Sometimes the second-stage infection also presents with secondary bullseye rashes that tend to be smaller than the primary and occurring on the skin and at locations not associated with the tick bite.
Hyde said the current diagnostics are unable to detect early Lyme infection and therefore can indicate a false negative. Diagnostics are also unable to determine if an active infection is occurring because they detect an immune response to the bacteria that can persist for years.
“Diagnostic tests to detect Lyme infections are suboptimal, because there can be false positives and false negatives, and that’s one of the things the field is working on,” Hyde said. There is a good deal of heterogeneity, or differences, between Borrelia burgdorferi strains that cause human infection, and sometimes people don’t have a strong immune response to the pathogen—and that response by the immune system is what the test detects. Also, the bacteria tend not to remain in the blood but to congregate in heart, joint and brain tissue—which are, of course, much more difficult to sample from patients. Even if a test shows that some Borrelia burgdorferi were present, it doesn’t always indicate whether they were viable and able to cause an active infection.
“It’s difficult for the bacteria to have to go between these two worlds, the body of a tick and that of a mammal,” Hyde said. The pathogen has to travel through the entire body of the tick and undergo certain genetic adaptations before it can efficiently colonize a mammal. Although this process is still poorly understood, some of these steps may possibly be why it takes more than 24 hours after being bitten by the tick before transmission to humans occurs.
There is also a seasonality to when infections are likely to happen, with most people acquiring the infection in late summer or early fall. This is because the larval ticks do not hatch infected, but become infected when they feed on an infected animal. When larvae—the first stage of the lifecycle of this type of tick—become infected, they molt into nymphs and then adults as the lifecycle progresses. At each stage they feed, and if infected with Borrelia burgdorferi, they transmit the bacteria to a small rodent, dog or human. Therefore, a tick has to be a nymph or an adult in order to infect a human.
The ticks that transmit Lyme disease are so small that they can be difficult to see, even as adults. Also, the bite doesn’t cause itching or pain because the ticks have immune-suppressing proteins in their saliva. That’s why it is so important to check yourself after you’ve been outside in tick-prone areas, Hyde said. “As soon as you see a deer tick, remove it, and make sure you remove it at the head,” she added. “It’s very important to talk to your health care provider if you think you may have been infected with Lyme disease or another tick-borne illness.”
Ticks that carry the disease have been found in Texas, but infection rates in the state are very low (only 18 confirmed cases in 2015) compared with the Northeastern and Midwestern United States, where there are thousands of cases. Those 18 cases may not have necessarily even been acquired in Texas, because the Centers for Disease Control and Prevention tracks incidence by county of residence, not where the person was exposed.
Hyde’s laboratory is working to characterize the mechanisms utilized by Borrelia burgdorferi to disseminate and maintain infection in distinct tissues. Her group is also interested in the immune response elicited in response to Borrelia burgdorferi infection and how the pathogen is able to avoid clearance. Various molecular techniques, along with imaging to detect Borrelia burgdorferi that Hyde engineers to produce light (termed in vivo bioluminescence), are employed to augment experimentation within her research team.