Expires: August 2024
Tick-borne disease testing algorithm
Bobbi Britt, M.D., is the Director of the Clinical Parasitology Laboratory and Vice Chair of Education of the Department of Laboratory Medicine and Pathology at Mayo Clinic in Rochester, Minnesota. She holds the academic rank of Professor of Laboratory Medicine and Pathology.
Contact us: MMLHotTopics@mayo.edu.
Hi, I’m Ross Reichard, Vice Chair of Quality, for the Department of Laboratory Medicine and Pathology at Mayo Clinic. Did you know that ticks are not insects? They are arachnids— just like spiders, having eight legs as adults. Although this is an interesting tidbit, a more important fact is that ticks can transmit multiple disease-causing bacteria, viruses, and parasites through their bite, and they are now out in force looking for their next meal. In this month’s “Hot Topic,” my colleague, Dr. Bobbi Pritt, will talk about the different ticks that commonly bite humans, where they can be found, and how to avoid them. I hope you enjoy this month’s Hot Topic, and I want to personally thank you for allowing Mayo Clinic the opportunity to be a partner in your patients’ health care.
Thank you for that introduction, Dr. Reichard. It’s summertime, and the ticks are definitely out. Therefore, it’s a great time to talk about ticks—what types there are, where they are found, the diseases they transmit, and how you can protect yourself against them. We are also going to talk briefly about the laboratory methods used for detecting tick-borne diseases and follow up with more information on specific diseases in the other Hot Topic presentations in this series.
Now, before we begin, I’d like to say that I have no disclosures to make.
I’d also like to share some utilization messages that apply to all of the tests that we offer for tick-borne diseases. As you view this presentation and others in this series, consider the following important points regarding testing:
So, with this introduction, I’d like to set the stage—or I should say “forest” for our discussion.
We’ll start with some tick basics. Many people don’t know that ticks are arachnids, along with mites and spiders. They are not insects. Like other arachnids, they have eight legs as adults. They can be further divided into hard and soft ticks. Laboratory testing is primarily focused on diseases transmitted by hard ticks, since these comprise the bulk of tick-borne diseases. Ticks have a complicated life cycle, undergoing four life-cycle stages: egg, larva, nymph, and adult. Importantly, they require a blood meal in order to molt into the next stage. The blood meal could be from a number of animals, including bird, rodents, and humans.
Here is the general life cycle for a hard-bodied tick provided by the Centers for Disease Control and Prevention (or CDC). It is specifically the life cycle for Ixodes scapularis, commonly known as the “black-legged tick” or “deer tick,” but the general concepts apply to all hard-bodied ticks.
Let’s start in the spring when eggs are laid by adult ticks that have survived the winter by staying under thick layers of leaves and snow. The eggs hatch to release larvae, some of which are actually born infected, having acquired the infection from their mom. The larvae need a blood meal in order to molt into the nymphal form, and they usually seek out small rodents and birds for this purpose. But I should mention the bacterium that causes Lyme disease, Borrelia burgdorferi, is not transmitted from the female tick, and therefore, the larvae have to acquire it when they take their first blood meal from an infected host. You can see from the life cycle how the larvae hatch after winter, feed, and then emerge as nymphs in the spring. Many of these nymphs are infected with various pathogens, having acquired them from their first blood meal the summer beforehand. In general, nymphs pose the greatest risk to humans since they are very small—as small as a poppy seed—and therefore, they are harder to identify on your body. They can easily be overlooked. After the nymphs take their second blood meal, they molt into adults. Adults are usually active in the fall, where they seek out meals from larger hosts such as deer and humans, and they may also be infected with multiple pathogens and transmit those pathogens through their bite. For some ticks, like the black-legged tick, it is only the female who takes a blood meal. However, males of some species, like the “lone star tick,” will also take a blood meal and transmit pathogens during feeding. The female tick then “overwinters” and lays eggs in the spring, starting the whole cycle over again. So, you may be asking yourself, “How do ticks find all of these hosts?”
Well, they don’t have wings, and therefore, they can’t fly, but they can pursue their hosts by crawling toward them or by using a behavior called questing.
When questing, ticks climb to a nearby high surface and extend their front legs (like we can see here) hoping to grab onto a host that is passing by. That is why we can avoid ticks by staying away from tall grasses, particularly at the edges of fields and forests.
As I alluded to earlier, ticks vary in size by their life cycle stages. They can also vary based on the type of ticks that they are. This image from the CDC nicely shows that black-legged ticks are smaller than the lone star and dog ticks at each of the life cycle stages. Of course, when ticks are partially or fully engorged with blood, size is not a reliable method for telling the ticks apart, and therefore, it should not be used in general as a key differentiating feature.
As I mentioned before, the nymphal stage of the black-legged tick can be as small as a poppy seed. Can you find all five ticks in this somewhat disturbing photo from the CDC?
Now that we’ve discussed some general tick features, let’s review the types of hard-bodied ticks found in the United States and the primary pathogens that they carry.
This first image shows the distribution in orange of Rhipicephalus sanguineus, the brown dog tick. Discouragingly, you can see that the brown dog tick is found in all 48 contiguous states.
It can transmit Rickettsia rickettsiae, the cause of Rocky Mountain spotted fever, predominantly in the southwestern United States and bordering regions of Mexico.
Then, there is Dermacentor variabilis, the American dog tick, found east of the Rocky Mountains and limited areas of the Pacific Coast. This tick can also transmit the agent that causes Rocky Mountain spotted fever, as well as Francisella tularensis, which causes tularemia.
The western Rocky Mountain states and parts of southwestern Canada harbor a related tick, Dermacentor andersoni, also known as the Rocky Mountain wood tick. This tick can transmit the agents responsible for tularemia, Colorado tick fever, and Rocky Mountain spotted fever.
Then, there is Amblyomma americanum, the lone star tick, which is widespread throughout the southeastern and eastern United States. It transmits the causative agents of tularemia, ehrlichiosis, and an enigmatic condition called the southern tick-associated rash illness (or STARI). It also most likely transmits heartland virus and possibly bourbon virus. And importantly, bites with this tick are also associated with a meat allergy. Patients who develop a meat allergy after a lone star tick bite are unable to eat the meat from most mammals, including beef, pork, venison, and mutton, without risking a potentially life-threatening allergic reaction.
For completeness sake, I’ve also include the distribution of Amblyomma maculatum, the Gulf Coast tick, in this talk. This tick transmits a bacterium called Rickettsia parkerii, which causes a similar but milder illness to Rocky Mountain spotted fever.
Now, last—but certainly not least—are the black-legged ticks. Ixodes scapularis has a very broad distribution throughout the eastern and upper midwestern United States and transmits all of the pathogens shown on this slide, including two bacteria that cause Lyme disease. You can watch our two related Hot Topics on Lyme disease to learn more about these organisms. Under certain circumstances, all of the disease listed on this slide can be fatal. As with all ticks, more than one pathogen can be transmitted at one time when it bites a human. Therefore, we may be at risk for multiple diseases with serious pathogens from a single tick bite.
The Western black-legged tick is associated with a similar spectrum of tick-borne illnesses and is found along the Pacific Coast of the United States.
Another important point I’d like to mention is that as the tick distributions change over time, ticks can expand into new territories.
We are seeing this with a number of ticks, including the black-legged ticks that transmit Lyme disease. The existing ranges are expanding laterally, as well as up into Canada. Therefore, it is important to keep up to date on which ticks are in your area and how to avoid them.
The laboratory detection of tick-borne diseases uses both direct and indirect methods. Direct methods are those that detect the organism, its antigens, or its DNA/RNA. Direct methods commonly employ real-time PCR, but also morphologic methods, such as blood smears. These are commonly used for detection of the Babesia species and morulae of the Anaplasma and Ehrlichia species.
In contrast, indirect methods detect the host’s immune response to the organism, specifically, the presence of pathogen-specific IgM and IgG-class antibodies. The preferred test is dependent on the time of infection, and therefore, it is important to know the stage of the illness when selecting a test.
Serology-based tests take a while to become positive because they are dependent on the host’s ability to produce detectable levels of IgM and IgG. If we consider “day 1” to be the point of infection, then we can expect to see IgM antibodies rising within the first week of infection, followed later by IgG antibodies. IgM antibodies will eventually decline to undetectable levels, but they can remain detectable for many months, whereas in contrast, IgG can remain detectable for years or even the life of the patient.
In contrast to serologic detection, direct methods such as those that detect DNA or RNA tend to be positive earlier in the disease, and then they disappear much earlier than antibodies. Now, the red line shown here is just a general pattern; it may vary by organism. Often, but not always, the periods of positivity for direct methods overlap with the time that the patient is symptomatic. There are some important exceptions, which is why my colleague, Dr. Elitza Theel, and I made an algorithm outlining the types of preferred testing for each pathogen, broken down by the time point in each patient’s illness.
This algorithm is shown here, and it is freely available on our Mayo Medical Laboratories website. We will reference this algorithm in greater detail in the other presentations in this series on tick-borne diseases.
You can watch our two prior Hot Topic presentations on Lyme disease and also look for our Hot Topics coming soon on non-Lyme tick-borne diseases and neuroinvasive Lyme disease.
For now, I will refer you to our educational offering called the “ABCs of Ticks” as shown on this slide, which provides the essentials of ticks and tick-borne diseases, including many helpful hints for avoiding ticks. You can find this information at the URL listed at the end of this presentation: https://news.mayocliniclabs.com/ticks/.
With that, I would like to thank you for joining me today for this session on tick essentials.