Lyme Disease—Don’t Let the Bugs Bite You

A Growing Silent Pandemic

It’s a serious disease shrouded in controversy that captivates our attention. A disease transmitted by a blood-feeding bug that already bit an animal, such as a mouse or other mammal, infected with the spirochaete bacteria Borrelia burgdorferi. It is this pathogen, which has profound effects throughout the body, which is the cause of Lyme disease. Ticks may sound more like an annoyance than anything else, but if you research ticks and the infections they transmit, you may very well end up having nightmares.

Ticks are a highly specialized group of bloodsucking parasitic arachnids that feed on mammals, birds, and reptiles.[1] Their distribution is widening, and bites occur most frequently in woodland areas, in temperate climates, and in late spring or summer.[2]

Their bite makes a lot of us sick every year. The numbers are surprising; according to the Center for Disease Control, approximately 476,000 Americans are treated for Lyme disease yearly.[3] In Canada, the number of Lyme disease cases increased from 144 in 2009 to 992 in 2016. This is likely a significant underestimation, and research suggests that the real range could be from 8,432 to 56,147 cases per year.[4] In 2016, 88% of the cases reported were from Ontario, Québec, or Nova Scotia.[5] Infections are concentrated on the east coast of North America, but surveillance data shows that Lyme disease is emerging in Canada as the range of the tick that causes Lyme disease expands.[6] However, the big difference between the USA and Canada is likely due to the difficulties in laboratory testing, emerging science, and biased lab results in the USA, as described below. Environmental factors such as increased distribution of ticks, encroachment on habitat favourable to ticks, climate change, and increased outdoor activity have contributed to an increasing number of cases of Lyme disease.[7] The number of cases has been increasing ever since the infection was discovered.

Pathogenesis and Clinical Diagnosis

The diagnosis is centered on clinical symptoms supported by blood tests.[8] In 60–80% of patients, a rash known as erythema migrans develops several days to weeks after the tick bite.[9] This rash expands by 2–3 cm per day over several days, reaching an average diameter of 16 cm, with some parts clearing to result in a bullseye image.[10] Context is extremely important for accurately identifying Lyme—the risk of a tick bite is highest in individuals who spend time outdoors, in an endemic area, and at certain times of the year. The early summer months are when the nymphal ticks are seeking blood. In the United States, July is the most common month for illness onset.[11] Patient travel history is therefore important.[12]

Once a bite occurs, the bacteria spreads throughout the body in approximately 50% of untreated patients.[13] Infection can be divided into three stages: early (1 to 4 weeks following tick bite), early disseminated (1 to 4 months following tick bite), and late disseminated.[14] In the early stages of the infection, symptoms may include an expanding circular red rash (as described above, and the most important target or bullseye rash) and flu-like symptoms which include a lack of energy, headaches, fever, muscle and joint pain, as well as swollen lymph nodes. Early dissemination can involve the skin, muscles, joints, or the nervous system. Symptoms may include pain and weakness in the arms or legs, paralysis of facial muscles, headaches and repeated fainting episodes, brief episodes of pain, swelling and redness in one or more large joints, palpitations, and pink eye.[15]

In the later stages of the disease, damage to the nervous system (and neurological), joints, and heart can become permanent. Symptoms may include arthritis that most commonly affects the knees, lasting up to 6 months at a time; numbness in hands, feet, or back; extreme fatigue; memory problems; problems affecting speech; and heart problems including inflammation of the tissues surrounding the heart. Arthritis is the most common late-stage symptom in the US.[16]

Testing for Lyme Disease

Probably the most controversial aspect of Lyme disease is the diagnosis through blood tests. Most Lyme disease tests are designed to detect antibodies made by the body in response to infection. Antibodies can take up to several weeks to be detected in the blood, so patients may test negative if infected and tested within 1–3 weeks. Antibody testing should be performed in patients presenting with clinical signs suggestive of current infection of 2–3-week duration or a past untreated infection.[17] If a clinical diagnosis was made based on symptoms and antibiotics were given in a timely manner, laboratory testing is up to the doctor and patient. If, however, a previous exposure is suspected but no treatment was given, then testing becomes more important to provide public health with real cases and diagnosis, and to understand the cause of symptoms or a collection of symptoms.

Antibody testing for Lyme disease should use a two-step approach. This is not uncommon; confirmatory tests are often used in the diagnosis of infections. As an example, the diagnosis for strep throat often relies on an initial rapid strep-throat test followed by a more specific throat-culture test. In the case of Lyme disease, an initial enzyme immunoassay (EIA) screening test is performed to detect antibodies to B. burgdorferi.[18] This test has low specificity but high sensitivity. This means that negative results do not need further testing. Alternatively, positive results need to be confirmed. EIA tests may cross-react with antibodies to other infectious agents and certain autoimmune diseases. Therefore, following a positive EIA, a confirmatory immunoblot (IB) test is needed—this test is more specific than the EIA, because it detects antibodies to several proteins of B. burgdorferi.

Most laboratories now perform both IgG and IgM immunoblots.[19] IgM is associated with a more recent infection, with titers peaking at 6–8 weeks and disappearing after 6 months, while IgG antibodies are slower to develop, beginning to show 6–8 weeks after exposure, and remain elevated. For patients with signs of illness lasting over a month, only IgG testing should be performed. Following an infection, IgG can persist in the blood for many years. These tests cannot be used to know if a patient is cured, however, and only detects exposure, and not severity of symptoms.

Several issues have been reported with private laboratories not using standardized testing methods, leading to high rates of false positives and discordant results. An independent evaluation reported alarming false-positive rates for samples from healthy controls submitted to an alternative testing centre that used invalidated criteria to interpret IgM and IgG immunoblots.[20] For example, a recognized leader in the research and development of tests to detect Lyme disease and other tick-borne diseases clearly states on its website that “based on internal validation studies, […] it was established the following criteria for its IgG Immunoblot: Positive: If two or more of the following bands are present: 23, 31, 34, 39, 41 and 93 kDa,” whereas the CDC considers a test positive if 5 of the following 10 bands are present: 18, 23, 28, 30, 39, and 41, 45, 58, 66 and 93 kDa.[21] The company also used a different set of protein sequences when it came to the interpretation of its IgM immunoblot. This change in interpretation leads to a high rate of discordance in results when results are compared to those obtained with the CDC criteria. Independent testing shows that using this criteria, 23 out of 40 healthy controls were diagnosed with potential Lyme disease on IgG or IgM immunoblot—at 58%, this is an unacceptably high rate of false positives.[22] Lyme specialty laboratories often rely on their own in-house laboratory criteria for the diagnosis of Lyme disease, leading to questionable results.[23] In 2014, it was estimated that in the United States, less than 12% of Lyme-disease tests were for true infections.[24] As of May 2015, there were 42 tests for Lyme disease approved by the FDA for use in the United States, and 22 approved by Health Canada Medical Devices Branch for use in Canada. Unfortunately, most of these tests have not been evaluated in the primary literature.[25]

Current evidence suggests that none of the available blood tests can determine if a patient has ongoing infection. The presence of antibodies in patients who have been treated for Lyme is normal and not indicative of ongoing infection.[26] However, when performed and interpreted properly and according to the CDC criteria, two-tiered blood analysis using a combination of the EIA and IB has a high sensitivity and specificity for disseminated Lyme disease.[27] The latest meta-analysis shows that CDC-recommended western blot algorithm has equivalent or superior specificity over other proposed test algorithms.[28]

Treatment

Health Canada recommends antibiotic treatment with three different antibiotics for 2–3 weeks if patients meet treatment guidelines (which consist of history, clinical symptoms, and laboratory testing). Conditions are required for a tick to transmit the pathogen to a human. If a tick has been attached to the skin for over 36 hours, and if there is evidence of B. burgdorferi in over 20% of ticks in the area that the person visited, treatment is given. Guidelines from Germany stress the importance of identifying the Ixodes species of tick before treatment begins.[29] The blacklegged (deer) tick, as opposed to the American dog tick, is responsible for transmitting Lyme. Identifying the type of tick is not always possible if the tick has been removed by the patient; taking a picture of the tick helps for identification.

Currently, there is a lack of evidence to support the use of antibiotics for more than 4 weeks. Also, controversy continues around whether infection persists and causes chronic symptoms, despite antimicrobial treatment. Clinical manifestations could be a result of active infection or postinfectious autoimmunity.[30]

After treatment has been administered, it becomes challenging to determine whether patients still exhibiting symptoms are affected by untreated late-stage infection, posttreatment Lyme-disease syndrome, or chronic Lyme disease.[31] Symptoms could be related to the presence of other untreated infections, tissue damage from the infection, conditions triggered by the initial infection and persisting despite bacterial eradication, immune dysfunction, and/or persistent infection.[32] The evidence overwhelmingly shows elimination of the spirochaetes in patients treated with antibiotics.[33] This means that patients suffering from persisting symptoms are likely suffering from consequences of the infection and not from a continuing chronic infection.

Lyme disease needs to be treated with antibiotics. In terms of natural treatments, there is a paucity of information available. Like many other infections, natural treatments may help to improve outcomes and promote recovery. For chronic manifestations of Lyme disease, they focus on lifestyle, as well as proper sleep and nutrition. Also, any nutritional deficiency should be corrected at once. In mice, vitamin A deficiency worsens Lyme arthritis.[34] In forestry workers, it has been suggested that low serum concentration of vitamins A and E may have influence on B. burgdorferi infection development, with studies showing significantly lower vitamins A and E levels in workers having antibodies against Borrelia.[35] Test-tube studies in human immune cells have demonstrated that infection with B. burgdorferi leads to a ten-fold increase in intracellular glutathione levels.[36]

Given that immune cells produce more glutathione when infected with B. burgdorferi, supplementing in glutathione is key for prevention and treatment.[37] Other dietary supplements often recommended including antioxidants such as N‑acetylcysteine and alpha‑lipoic acid, respectively precursor and cofactor of recycling for glutathione. Moreover, because infections lead to inflammatory reactions, natural anti-inflammatory supplements are also often used—like turmeric, resveratrol, and fish oils—although no studies are available for their use in Lyme disease. There are other potential botanical candidates; however, this is beyond the scope for this short introduction on Lyme disease. Most natural treatments are considered for people living with chronic manifestations or difficult-to-treat Lyme disease.

Lifestyle Precautions

During the spring, summer, and fall, many individuals and families head outdoors, especially during the pandemic, and while it is very advisable to enjoy the outdoors, important safety considerations when going hiking are:

• sticking to trails (and not bushwhacking through wooded areas); and
• wearing long sleeves and pants, light-coloured clothing (easier to see possible ticks, and mosquitoes are less attracted), a hat, and closed shoes to minimize uncovered skin areas.

Doing a thorough check after going out into the woods is also a good idea, and better if you have someone to help you for the areas you cannot see, since removal of a tick under 36 hours is less likely to transmit Lyme. There are also some important tick-repelling sprays that are more natural, including oil of lemon eucalyptus or its synthetic version, PMD.[38]