In the United States and Europe, Lyme disease is the most prevalent vector-borne infection, primarily due to the bacteria Borrelia burgdorferi. The Ixodes scapularis deer tick in the United States primarily transmits this bacteria. It can cause a variety of symptoms, ranging from the well-known bulls-eye rash to more serious neurological and cardiac issues. But these same ticks can also transmit and carry a variety of other illnesses, which can result in coinfections. The clinical appearance, diagnosis, and course of therapy of Lyme disease can be complicated by coinfections with diseases such as anaplasmosis, babesiosis, ehrlichiosis, and others. Since the symptoms of various diseases often overlap and worsen the sickness, understanding these coinfections is essential for an accurate diagnosis and successful treatment. 

Overview

Lyme disease is a common tick-borne transmission disease that is found not only in the United States but worldwide.¹ While it is usually not a fatal condition, it can negatively impact the quality of life of those infected. If the condition is chronic, it could cause fibromyalgia or chronic fatigue syndrome.² The progression of the disease can be divided into 3 stages – early stage, disseminated stage, and late stage. The Borrelia burgdorferi bacterial spirochete causes Lyme disease through the host – Ixodes scapularis, a deer tick species. Ticks are a host to many different symbiotic bacteria and pathogens not limited to the Borrelia burgdorferi. This means a tick bite could potentially result in not only Lyme disease but also a coinfection of a multitude of other diseases. Some other common tick-borne diseases include anaplasmosis, babesiosis, ehrlichiosis, and many more mentioned in this article.³ These bacteria are normally localised in the salivary glands, midguts, ovary, and or malpighian tubules (ammonia excretion pathway). In each of these areas, there are various different pathogens and microbiota.⁴ See this link for further information on symbiotic bacteria with ticks. 

Lyme disease

The Borrelia burgdorferi bacterium alters the surface proteins of cells to prevent detection of itself as a foreign pathogen, causing it to be able to evade detection and attack from the immune system. This function allows the bacteria to stay in the host’s body for a long period of time, hence chronic infection. This also means the body will be in a chronic inflammatory state as it tries to get rid of this foreign pathogen, causing arthritis or neurological conditions.⁵ 

• During the early stage after tick bite (about 1-28 days), the erythema migrans rash first presents. It is a telltale sign of Lyme disease. Its manifestation presents as a “bulls-eye rash” with a concentric ring. Alongside the rash, a low-grade fever is common and flu-like symptoms include myalgia (muscle pain), neck stiffness, and headache.¹
• Then 3-12 weeks after the initial infection is the disseminated stage. At this point in time, the patient would have generalised musculoskeletal aches and or neurological and cardiac symptoms. Lyme disease causes inflammation in the endocardium, epicardium and perivascular tissue. Heart conduction disturbances could also occur due to the direct invasion of cardiac tissues by the spirochetes.^6,7 It is possible that a temporary transvenous pacemaker for heartbeat regulation is required if the patient’s condition is unstable.⁸
• The late stage of Lyme disease could extend beyond a month depending on the disease’s manifestation. The common feature and chronic symptom of Lyme disease is arthritis, typically localised in the knee area. Arthritis is caused by inflammation in the synovial joints which causes it to swell and erode the bone.⁹ Without treatment, the condition of patients with Lyme disease could resolve over time. However, antibiotics are often prescribed to ensure an efficient and full recovery. Another manifestation in the late stage is Acrodermatitis chronica atrophicans, which impacts the skin, specifically presenting with sclerotic atrophic skin lesions.⁸ 

Chronic Lyme disease is difficult to diagnose because its symptoms often overlap with other diseases. Its most distinct characteristic is the erythema migrans rash that usually presents in the early stage.¹⁰ To screen for Lyme disease, a sensitive enzyme immunoassay (EIA) screening test will be conducted. The EIA screens for the presence of Borrelia burgdorferi by using enzyme-labelled antibodies which then bind to antigens of the bacteria, allowing its visualisation and quantification. A western blot test is also used often as a confirmatory test following the immunoassay. It screens two types of antibodies: IgM which indicates a more recent infection, and IgG which indicates a past or ongoing infection.¹ A serologic diagnosis is sensitive and effective for patients with neurologic and cardiac symptoms.¹ Treatment for Lyme disease relies on antibiotics and its dosage depends on the age and severity of each case. Usually, the doxycycline antibiotic is prescribed for individuals aged 8 or older, while children under 8 years old are prescribed amoxicillin and cefuroxime. Another antibiotic that is also commonly prescribed is ceftriaxone, which helps prevent and mitigate neurological and cardiac conditions associated with Lyme disease.¹¹ For more information on diagnostic tests on Lyme disease, see this link. 

Coinfections with lyme disease

Ticks not only carry Lyme disease but also other pathogens. This can result in coinfections, where a person is simultaneously infected with Lyme disease and one or more other tick-borne diseases. The overlapping symptoms and events can complicate the clinical presentation hence affecting the treatment effectiveness and outcomes. With multiple different diseases causing various and possible overlapping symptoms, it is essential to understand coinfection for accurate diagnoses and appropriate treatment. 

The following are the major coinfections that Lyme disease is commonly associated with: 

• Anaplasmosis: Caused by the Anaplasma phagocytophilum bacteria. Similarly, its symptoms include fever, headache, and muscle pain. Rashes are also fairly common but more so with coinfections. In more severe cases, manifestation of this bacteria on the peripheral nervous system could cause brachial plexopathy or nerve palsy in the cranial or facial region. This type of neurological function recovery could possibly take up to months.¹² Like Lyme disease, the first line treatment for anaplasmosis is the doxycycline antibiotic.
• Babesiosis: Caused by the Babesia microti pathogen. Its symptoms present with flu-like symptoms like fever and chills, and even hemolytic anaemia (hemo – meaning red blood cell, lytic – meaning lysis or splitting, and anaemia – lack of red blood cells). Depending on the immunocompetence of the host, the severity of the infection varies. An immunocompromised individual would have more adverse reactions to the infection compared to a healthy individual. Patients may also display hepatosplenomegaly (enlarged liver and spleen), jaundice and retinopathy during clinical examinations. For mild cases, atovaquone and azithromycin could be prescribed. For severe cases like those hospitalised, clindamycin and quinine could be administered.¹³
• Ehrlichiosis: Caused by the Ehrlichia family like Ehrlichia chaffeensis or ewingii. The symptoms of cough, fever, headache, and fatigue present usually 1-2 weeks after tick bite. The rash is common in children and typically presents 5 days into the infection as maculopapular rash or diffuse erythema. More severe infections involving the central nervous system can also cause meningitis and meningoencephalitis. Like Lyme disease and anaplasmosis, its treatment includes the doxycycline antibiotic for 5-7 days depending on the condition.¹⁴
• Bartonellosis: Caused by the Bartonella family including Bartonella henselar, quintana, and bacilliformis. Its symptoms include fever, skin lesions, and lymphadenopathy where lymph nodes near the area of infection are enlarged. The antimicrobial agents that are commonly used to alleviate the infection include azithromycin, rifampin, and ciprofloxacin.¹⁵
• Rocky Mountain Spotted Fever (RMSF): Caused by Rickettsia rickettsii pathogen. This bacteria causes the loss of barrier function in endothelial cells, altering the vascular permeability throughout the whole body. This leads to inflammation and symptoms of rashes, fever, cardiovascular instability, and central nervous system symptoms including severe headaches and even confusion. These symptoms usually present in 4-10 days post tick bite and overlap with Lyme disease and anaplasmosis. Its treatment includes doxycycline for 7-10 days. This disease can be perceived as higher risk and more severe compared to the other diseases with its mortality rate being as high as 20–30% without prompt antibiotic treatment.¹⁶

To diagnose these coinfections, PCR and serology tests are conducted. Serology is highly sensitive and specific which allows interpretation of an active infection and past contact with the disease. However, non-specific serological reactions can lead to false diagnoses of coinfections due to overlapping symptoms.¹⁷ Overlapping symptoms means that the pathogenicity of two or three microorganisms are often unable to be distinguished from one another.¹⁷  

Prevention of tick-borne diseases

It is important to prevent tick-borne diseases altogether rather than treating them. Some avoidance strategies include using protective garments like long sleeves and long pants, especially in the wilderness where ticks are most often present. Insect repellents could also provide protection from not only ticks but also mosquitos which are also hosts of diseases like malaria. Regularly check for ticks after going to places that are prone to tick infections and remove the insect safely when found. Environmental management like host reduction or biological control can also help reduce the presence of ticks altogether. This could include the use of chemical sprays and repellents. 

Summary

Understanding the association between Lyme disease and its coinfections is important as it allows effective and efficient treatment for these complex conditions. While diagnoses and treatment work well to mitigate the pain and discomfort of patients, it is best dealt with through direct prevention of the event.