Humans have a troublesome relationship with ticks due to the latter being pesky disease-causing parasites. What many people don’t know however is that ticks themselves are not the culprit behind disease but rather the pawn of something barely visible under a microscope. In this article we will learn who exactly is the mastermind causing Lyme disease and how we can prevent and treat this infection.

What is Lyme disease?

Lyme disease is an infectious disease caused by bacteria from the Borrelia genus. B. burgdorferi is the leading cause of Lyme disease in humans in the US, followed by B. mayonii. On the other hand, B. afzelii and B. garinii cause Lyme disease predominantly in Europe and Asia.¹ For simplicity, we will refer to B. burgdorferi from here on. B. burgdorferi is a Gram-negative bacteria shaped like a corkscrew for which it is classified as a spirochete together with other similarly looking bacteria like Treponema pallidum - the causative agent of syphilis. B. burgdorferi uses ticks as a vector to infect humans and cause Lyme disease.

What are the Vectors for Lyme disease?

The primary vectors for B. burgdorferi are the so-called hard ticks from the Ixodes genus. I. ricinus is the predominant vector in Europe, I. persulcatus in Asia, I. scapularis Northeastern and Midwestern USA, and I. pacificus in Western USA.² Apart from B. burgdorferi, Ixodes ticks also serve as vectors for other pathogenic microorganisms such as Babesia species which cause babesiosis.³ Only Ixodes ticks can transmit Lyme disease due to the intimate co-evolution between the bacteria and their vector. Below we will discuss how B. burgdorferi has adapted to the biology of Ixodes ticks to use them as ‘perfect vessels’.

Ixodes ticks go through four life stages: egg, larva, nymph, and adult. In order to transition from one stage to the next, they need to have blood meals. Nymphs of Ixodes ticks usually spread Lyme disease more easily compared to adult ticks. That, and the fact that nymphs are much smaller and harder to notice, makes them very effective vectors.

Ticks get infected with B. burgdorferi usually at the larva or nymph stage whenever they have a blood meal from small infected animals, usually a wild rodent. By consuming blood they transition into adults and start hunting for larger animals and humans. Meanwhile, spirochetes enter the tick’s digestive system where they multiply and await their next victim.⁴

Interestingly, spirochetes are able to bypass the digestive properties of the tick’s gut and the innate immune system even in an unfed tick with no available nutrients, and persist for a significant time, surviving throughout multiple tick life stages. This is due to the specific protein composition of B. burgdorferi that adapts it to the internal environment of the tick’s gut.

When an infected tick is about to have its next blood meal from a non-infected animal, spirochetes traverse the gut epithelium and enter the hemolymph from where they reach the salivary glands of the tick and accumulate into saliva. When a tick’s mouthpart penetrates the victim’s skin and blood vessels, infected saliva is transferred into the new host’s blood.⁵ Ticks secrete proteins in saliva that act as anticoagulants and inhibitors of the host’s complement system, which helps the tick eat more but also facilitates infection with B. burgdorferi by blocking the host’s innate defense.⁶

The membrane of B. burgdorferi is coated with multiple outer surface proteins (Osp) that play the role as important virulence factors, i.e. they help the spirochetes infect their host and cause disease more effectively. The three primary surface proteins are OspA, OspB, and OspC and each one of them serves a different purpose. OspA is used by spirochetes as an adhesive by which they attach to proteins in the tick’s gut and colonize the vector.⁷ When a tick is having a blood meal, B. burgdorferi downregulate the expression of OspA proteins and switch their coat to OspB-predominant which presumably helps the invaders enter their target⁸ and subsequently to OspC that aids the infection process.⁹

Pathophysiology of Lyme disease

Usually, an infected tick has to stick to its host for at least 24 hours in order to transmit Lyme disease.¹⁰ When spirochetes enter the host, they first cause local inflammation of the skin at the site of entry. The bullseye rash (also known as erythema migrans) is a common characteristic of early Lyme disease. In the next few days spirochetes travel throughout the body and infect internal organs, causing inflammation of the heart, joints, and kidney.

Systemic symptoms of Lyme disease include fever, fatigue, and joint swelling and pain. If left untreated, Lyme disease can lead to serious organ damage such as third-degree heart block and kidney failure which can be fatal.¹¹ 

About 25% of Lyme disease cases present with no rash at all¹² which could pose a challenge for clinicians trying to differentiate the disease from other conditions with similar symptoms (such as rheumatism), without the obvious bullseye rash, leading to delayed treatment and greater risk of disease-related complications.

Preventing Lyme disease

Avoiding ticks 

The best way to prevent contraction of Lyme disease is to avoid ticks. They are usually found in natural areas such as forests and usually attach to humans in outdoor activities such as picnics and hiking. Suburban green spaces like parks and gardens are other potential tick-infested areas.¹³ 

It is recommended for people in high-risk areas to protect themselves from tick bites by wearing closed shoes, trousers tucked into socks, and long-sleeved shirts. Clothes and shoes can be pretreated with permethrin to keep ticks at bay. Permethrin is an acaricide (a tick-killing substance) that acts on ion channels in tick neurons inhibiting depolarization and causing paralysis and death of treated pests.¹⁴ 

Repellents such as DEET and oil of lemon eucalyptus can be applied directly on the skin before entering tick-infested areas. Upon return from high-risk areas people should conduct a full body check, including in not-so-visible parts of the body such as the armpits, in the ears, inside the belly button, between toes, and the scalp. Pets that might have been exposed to ticks should also get checked.¹⁵

Removing ticks

Ticks should be removed as soon as possible as the risk of infection increases with prolonged exposure. It is important to follow a set of rules when removing ticks:¹⁶

• Ticks are removed carefully with blunt forceps by holding the tick as close to the skin as possible and slowly pulling the tick vertically upwards
• Don’t twist the forceps as this can tear the tick apart and leave its mouthpiece and infected salivary glands that continue to spread the infection
• Avoid using bare hands to remove ticks as bacteria can get into the body even through small skin cracks. Handling the tick with bare hands also has the risk of squishing the tick and releasing tick saliva and vomit into the host’s bloodstream, spreading infection even further
• Don’t lubricate the tick with oil or petroleum jelly as this can damage the tick and induce regurgitation of bacteria into the bite wound

After removing a tick it is best to send it in a secured container to a clinical laboratory where it gets tested for contagiosity with B. burgdorferi. Plasma levels of antibodies against Osp can be tested to evaluate whether infection with Lyme disease has occurred. Laboratory testing and monitoring of symptoms are important steps needed to make clinical decisions on the management of Lyme disease.

Antibiotic prophylaxis

Generally, it is not recommended to take antibiotics after a tick bite if no symptoms have occurred. In some occasions, such as tick bites in an area endemic for Lyme disease, a single dose of an antibiotic like doxycycline might be prescribed.¹⁷

Treatment of Lyme disease

If symptoms of Lyme disease develop, patients should be treated with antibiotics such as amoxicillin, doxycycline, and cefuroxime axetil all of which are taken orally.¹⁷

B. burgdorferi has a notable ability to shapeshift from corkscrew-shaped spirochetes to ball-shaped round bodies that are remarkably resistant to recommended antibiotics. Round bodies can further aggregate and secrete protective extracellular substances that glue them together into so called biofilms that serve as a shield from host immune responses and allow B. burgdorferi to build even stronger antibiotic resistance.¹⁸

Summary

Ticks are an important public health concern due to their ability to transmit Lyme disease as well as other infectious diseases. This brings up the importance of national strategies for preventing tick-borne infections. Further understanding of the biological connection between B. burgdorferi and the Ixodes ticks might lead to the development of novel methods for preventing Lyme disease, such as by interrupting the life cycle of the bacteria or their vector.