Lyme disease is the most common vector-borne disease in the US. It is also one of the most controversial diseases. While in many people it can be treated successfully with antibiotics, there is a number of those who continue to experience symptoms for months and years after treatment. Read on to learn more about Borrelia, the bacterium that causes Lyme disease. We will review what’s known about Lyme so far, and complementary strategies that can help you combat Lyme disease.
What is Lyme Disease?
Borrelia the Bacteria
Borrelia is a group of bacteria, best known for causing Lyme disease [1].
There are over 50 species of Borrelia. These bacteria cause diseases that are transmitted by ticks or lice, including:
- Lyme disease
- Relapsing fever
- Borrelia miyamotoi disease
Around a dozen of the Borrelia species are known to cause Lyme disease (also called borreliosis). All are transmitted by ticks. Four species, B. burgdorferi, B. afzelii, B. garinii, and B. bavariensis cause the majority of human disease in Europe, whereas two species, B. burgdorferi and B. mayonii, cause Lyme disease in the United States [2].
People get the bacteria when they are bitten by infected ticks (deer ticks) [3]. Borrelia enters the skin at the site of the tick bite. From there, it can disperse and cause inflammation in the heart, joints, or the brain [4].
Small mammals (like mice) and birds are reservoirs/carriers of Lyme disease. Humans are accidental hosts [5].
How Prevalent is Lyme Disease?
Lyme disease is the most common vector-borne disease in the US, Europe and Northern Asia [6].
20,000 – 30,000 cases are reported to CDC each year [7].
However, CDC estimates that the annual incidence of Lyme disease in the US exceeds 300,000 cases – that is 10 times higher than the number of reported cases [3, 2].
There are about 85,000 cases reported each year in Europe. However, this number may also be largely underestimated, as many infections go undiagnosed [2].
Who’s at Risk?
Those with High Exposure
The risk of Lyme disease is related to tick abundance and exposure. Therefore you are more likely to get infected if you [8]:
- live in rural areas
- work as forestry or farm workers
- do hunting, mushroom gathering or berry picking
Most infections occur in the spring, summer, and early autumn, when the ticks are in the immature (nymph) stage and people are more likely to be active [8].
Those Living in Endemic Areas
In the US, 93% of the reported cases were identified in 10 states: Connecticut, Delaware, Massachusetts, Maryland, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, and Wisconsin [8].
Lyme disease also occurs, although much less frequently, on the Pacific Coast, primarily in Northern California and Oregon [9].
In highly endemic areas of the United States, such as Connecticut and Southern New York, there is about 1 case per 2,000 persons a year. The incidence is highest in children aged 5 to 10 years [9].
In Europe, most cases occur in Scandinavia and the southern part of central Europe (Germany, Austria, north-east Italy, and Slovenia). The reported incidence is more than 3 cases per 1,000 people [8].
Those of Certain Age
Children are at the highest risk of Lyme disease [8].
The peak incidence is found in children aged 5–9 years [8].
Adults aged 45–59 years are also frequently infected [8].
Ways to Prevent Lyme Disease
Reduce the Risk of Tick Bites
Reducing the risk of tick bites is the best strategy to prevent Lyme disease.
Infection can be prevented by avoiding tick-infested environments. When in such environments, one should cover as much bare skin as possible and use tick repellents on skin or clothing [8].
In endemic areas, clearing brush and trees, removing leaf litter and woodpiles, and keeping grass mowed may reduce exposure to ticks. The application of pesticides to residential properties is effective but may be harmful to other wildlife and people [9].
Tick and insect repellents that contain DEET applied to the skin provide additional protection but require frequent reapplication [9].
Caution: serious neurological complications in children from the frequent or excessive application of DEET-containing repellents have been reported, but these are rare and the risk is low when these products are used according to instructions on the labels [9].
Check for Ticks Regularly
Shower and checks for ticks daily when living in or visiting Lyme-endemic sites [10].
The risk of Lyme disease is higher from bites that are unrecognized because the tick can feed to repletion and is more likely to transmit the infection [9].
A good strategy is to inspect oneself and children’s bodies and clothing daily after possible exposure to ticks [9].
Remove Ticks Promptly
It is important to know that not all ticks are infected. Even when they are infected, transmission doesn’t necessarily occur [8].
For the transmission to happen, the tick needs to be allowed to feed for an extended duration of time. Borrelia lives in the gut of the tick, which needs to become engorged with blood before it can migrate to the salivary glands and saliva, through which the bacteria are injected into humans [9].
Based on animal studies, to transmit the disease, an infected immature tick must feed for at least 36 to 48 hours and an infected adult tick must feed for at least 72 hours [9].
Case in point: in an area with a high incidence of Lyme disease, only 75/397 ticks were carriers of the disease, and only 1/64 subjects bitten by infected ticks developed symptoms of Lyme disease in the following 3 months [8].
A study shows that in humans, the risk of transmission from ticks was 25% for immature ticks that had fed for at least 72 hours and 0% for those that had fed for less than 72 hours [9].
Because most people who recognize that they were bitten by a tick remove the tick within 48 hours, the risk of Lyme disease from recognized tick bites is low, approximately 1 – 3% in areas with a high incidence of Lyme disease [9].
An attached tick should be grasped with tweezers as close to the skin as possible and removed by gently pulling the tick straight out [9].
If parts remain embedded in the skin, they should be left alone. They are thrust out eventually. Attempts to remove them can result in unnecessary damage to tissue and may increase the risk of local bacterial infection [9].
If not certain how to proceed, consult a medical professional.
Antibiotic Prophylaxis
Taking antibiotics as preventive agents can further reduce the risk of developing Lyme disease after tick removal [8].
A single dose of doxycycline was 87% effective in preventing Lyme disease in a study with 482 subjects [9].
However, this requires recognizing the tick bite and identifying the type of tick. People often mistake the more common and larger wood or dog ticks for the small deer tick [11].
Work with your doctor to weigh the risk of developing Lyme disease against the cost and risks from potentially unnecessary antibiotic administration [11].
Some scientists are against the routine use of antibiotics to prevent Lyme disease. This is because even in highly endemic areas, the overall risk of Lyme disease is low (1 – 3%), and if Lyme disease develops, treatment is effective [9].
Don’t Let Your Guard Down
Previous infection (whether with or without symptoms) does not make you immune to Lyme disease. You remain vulnerable to reinfection [2].
Symptoms and Diagnosis
Symptoms of Lyme disease can be classified into 3 stages: early stage, dissemination stage, and late disease [9].
People infected may experience some of the symptoms described below, or none at all.
In the US, the frequency of infections without symptoms is between 0% and 50% [2].
Early recognition is important because proper antibiotic treatment decreases acute and long-term symptoms [8].
Early Stage
In early Lyme disease, the infection is localized to the skin. A rash will usually develop within 3 to 30 days of a bite (typically 7 to 14 days) [9, 8].
The rash occurs in 70 up to 90% of reported Lyme disease cases in the US [3, 12, 8, 9].
Most often the rash is solid and oval. It can contain a central red spot. Less commonly it may appear as a bulls-eye lesion [9, 3].
The rash expands and fades over several weeks [3].
It can persist without other symptoms. It may also be itchy or painful. Or it can be accompanied by flu–like symptoms such as fever, malaise, headache, fatigue, neck stiffness, muscle or joint pain [9, 13].
In the absence of the rash, Lyme disease can be difficult to diagnose due to these nonspecific flu-like symptoms [13].
All the signs and symptoms of the disease, including the skin lesions, usually disappear spontaneously after about a month [8].
Although it will resolve without treatment, antibiotics hasten the resolution of rash and flu-like symptoms [3].
Dissemination Stage
Days to weeks after the infection, the disease progresses to a dissemination stage. This is when the bacteria travel away from the site of the tick bite through the bloodstream to invade and colonize various tissues, such as the heart, joints, and the brain [13].
People can develop a secondary rash away from the original site of the bite/infection [13].
A solitary bluish-red swelling (borrelial lymphocytoma) can sometimes be found on the earlobe in children, or in the breast region in adults. It resolves spontaneously [8].
Symptoms, such as fever, muscle and joint pain, headache, or fatigue, are common in this stage of Lyme disease [9].
During and after this period, muscle pain, as well as brain- and heart-related complications can ensue [14, 9].
Late Stage
Late infection, the third stage of the disease, develops months to years after exposure [13].
If left untreated, the infection can lead to complications such as [6]:
- Arthritis
- Neurological symptoms
- Carditis (Inflammation of the heart)
- Skin disorders
From 2001 to 2010, the CDC reports that 31% of confirmed Lyme disease cases presented with Lyme arthritis, 14% with neurologic symptoms, and 1% with heart involvement [5].
Children experience shorter-lasting symptoms and have better outcomes [8].
Arthritis
Months after the infection, untreated patients can develop arthritis which can last for several years with marked joint swelling and pain, primarily in large joints, especially the knee [15].
In fact, arthritis is the most frequent late-stage symptom of Lyme disease in the US.
Approximately 30 – 60% of untreated infections in US patients result in Lyme arthritis [2, 16, 17].
On the other hand, in Europe, arthritis is less common, reported in only 3% – 15% of patients [17, 18].
Children are more likely to develop arthritis than adults and are also more likely to have arthritis as the sole presenting symptom of disease [8].
Neurological Disorders
Neurological symptoms are more often encountered in people infected with B. garinii, the Lyme disease-causing bacterium found in Europe [19].
The American B. burgdorferi can also cause neurological symptoms, however not at such a high rate [18].
Although it occurs in only a few cases, the invasion of a child’s nervous system by B. burgdorferi can cause facial palsy and meningitis, the most common clinical manifestations of pediatric Lyme disease [8].
Facial palsy occurs in about 5% of children with Lyme disease [8].
Lyme meningitis is diagnosed in about 2% of children with Lyme disease. About 13% of aseptic meningitis diagnosed in an endemic region during the peak period of Lyme disease are due to Lyme disease [8].
Similarly, studies carried out in Scandinavia and the USA have found that Lyme disease was the cause of 34-65% of facial palsy cases [8].
Rarely, people can also experience myoclonus (twitches, jerks, or seizures), ataxia (lack of muscle coordination), vertigo, brain inflammation (encephalitis), or nerve damage (polyneuropathy) [8, 9].
Heart Disorders
4 – 10% of adults and 1 – 16% of children with Lyme disease develop heart inflammation or carditis [8].
In a small percentage of cases, people can develop dangerous heart arrhythmias [14].
Skin disorders
Skin disorders are more often encountered in infections with B. afzelii, another European species [19].
Infected people can develop rash, benign bluish-red lumps on the skin (lymphocytoma), and acrodermatitis chronica atrophicans – a chronically progressive condition that leads to widespread atrophy of the skin [18].
Lyme Disease Tests
Testing for Lyme disease remains problematic [20].
Antibody Tests
CDC recommends a 2-tier procedure (ELISA followed by Western immunoblot). Both of these need to be positive to confirm infection [9, 20].
However, antibody test results are generally not useful for the diagnosis of Lyme disease for the following reasons:
- The rash usually develops before antibodies are detectable. IgM antibodies are undetectable until 2 – 3 weeks after the appearance of skin lesions, and IgG antibodies can only be detected after 4 weeks [8].
- The sensitivity of the two-tier approach in Lyme disease patients tested at least 4 to 6 weeks after infection is only 44% to 56%, which is inadequate for a clinical diagnostic test [20].
- The antibody test result is often negative in the acute phase even in those with multiple skin lesions [9].
- Although antibody levels wane over time, some people who have recovered fully will continue to have measurable antibody levels for years. Thus, a positive result does not necessarily mean there is an ongoing infection [3].
- Negative results are not indicative of cure. Many patients treated for Lyme disease do not develop a measurable IgG response following antibiotic therapy [3].
- Antibody tests for Lyme disease can be falsely positive. An erroneous diagnosis of Lyme disease is frequently made, and such patients often are treated with antimicrobials unnecessarily [9].
- Some degree of cross-reactivity occurs between Borrelia that causes Lyme disease, relapsing fever and B. miyamotoi disease [21].
The low specificity of these tests explains why most experts do not suggest immunological tests but believe it is enough to know that a person lives in an endemic area and has one or more of the characteristic skin lesions [8].
Molecular Tests
Molecular testing for B. burgdorferi has been unreliable and expensive [20].
Direct molecular tests in blood for early Lyme disease can be insensitive due to a low amount of circulating bacteria. Results of a DNA analysis showed detection of B. burgdorferi in 13 of 21 patients (62%) [7].
However, new methods are constantly being developed and improved. We hope for better tests in the near future [22].
Treatment
Antibiotics
Antibiotics are the only proven treatment for Lyme disease.
People with Lyme disease usually respond well to antibiotics, when they are administered early [6].
Chronic cases may require prolonged treatment, and the treatment is often less effective [23].
Antibiotics such as penicillin, amoxicillin, ceftriaxone, doxycycline, and erythromycin are the most commonly prescribed for the treatment of Lyme disease [23].
Nonspecific symptoms, such as fatigue, joint or muscle pain, may persist for several weeks, even in patients with early Lyme disease who are treated successfully. These nonspecific symptoms will usually resolve without additional antimicrobial therapy [9].
Most adult cases of Lyme arthritis resolve after 4 weeks of oral antibiotic treatment. 10% of people have persistent arthritis that requires a second course of antibiotics, and 1 – 3% of these develop refractory disease requiring treatment with steroids administered into the joints, synovectomy (a type of surgery), or immunomodulating agents [8].
Non Antibiotic Therapies
Additional treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) may help with inflammation [9].
IV immunoglobulin has been useful for cases of autoimmune polyneuropathy secondary to Lyme disease [3].
Neurontin (gabapentin) was effective in reducing Lyme-induced neuropathic pain [3].
Vaccines
Two vaccines for Lyme disease were developed in the 1990s and were shown to be safe and efficacious in placebo-controlled studies in the US [2].
They were also well-tolerated and efficient in a study of 4k children and adolescents [24].
However, an assumption that these might trigger arthritis in some recipients, contributed to the limited acceptance and subsequent discontinuation of the vaccine in 2002 [2].
The assumption was since then proven wrong. With over 1.4 million Lyme vaccines distributed in the US, there were 905 reports of mild self-limited reactions and 59 reports of arthritis. The arthritis incidence in the patients receiving Lyme vaccine occurred at the same rate as in unvaccinated individuals [2, 11].
Some studies, however, indicate that an OspA Lyme vaccine may result in autoimmunity in genetically predisposed individuals. Although causality is difficult to demonstrate, one study reported four male patients with the DR4+ genotype who developed autoimmune arthritis after receiving the vaccine [11].
Currently, Lyme vaccine is available for dogs but not for humans. However, new vaccines are being tested in Europe, and hopefully, they may soon be available again.
The protection the vaccine provides diminishes over time. So if you received a vaccine before 2002, it’s safe to assume you are no longer protected.
Other Borrelia Diseases
Relapsing fever
Relapsing fever is also caused by bacteria of the Borrelia group. It is transmitted by soft ticks or lice. However, in most respects, relapsing fever is a very severe, acute disease compared to Lyme disease [10].
It is endemic in the western United States, southern British Columbia, the plateau regions of Mexico, Central and South America, the Mediterranean, Central Asia, and throughout much of Africa [25].
In the United States, exposure sites typically are in limestone caves in central Texas and in forested areas at varying elevations in mountainous regions (Cascade, Rocky Mountain, San Bernardino, and Sierra Nevada ranges) [25].
The average incubation period is 7 days (range, 4 to more than 18 days) [25].
The fever can last from several hours to 4 days (up to 10 days), and is accompanied by chills, headache, nausea and vomiting, sweating, stomach pain, joint pain and cough. Diarrhea may occur in 25% of cases [25].
Persons with lice-transmitted relapsing fever are more likely to have jaundice, nervous disorders, red spots on the body, and cough blood [25].
The average time between the first episode and the first relapse is 7 to 9 days. People may have symptoms such as malaise between fevers or may feel well [25].
Complications can include the liver, spleen, lung, heart, gut, eyes, or the brain [25].
There are a bunch of fever-associated diseases relapsing fever can be confused with. A history of travel, place of residence, and animal exposures is useful [25].
Relapsing fever is successfully treated with antibiotics [25].
Prevention includes avoiding rodent and tick-infested dwellings and infested natural sites, such as animal burrows or caves, rodent-proofing of homes, and chemical treatment of rodent-infested areas [25].
Borrelia Miyamotoi Disease
B. miyamotoi is transmitted by the same hard-bodied tick species that transmit Lyme disease [26].
B. miyamotoi infection should be checked for in patients with acute fever who have been exposed to ticks in a region where Lyme disease occurs [26].
Virtually all infected present with fever. The next most common signs and symptoms are chills, nausea and muscle and joint pain (30–60% of the patients). Rashes were observed in fewer than 10% of the patients [10].
Symptoms of the infection generally resolve within a week of the start of antibiotic therapy [26].
