When David Snydman returned from vacation in October 1975, he found two phone messages waiting on his desk. Both were from Connecticut mothers who were concerned about their children’s illness. Doctors had been annoyed by the women’s persistence, but Snydman was intrigued.1
Snydman, an Epidemic Intelligence Service (EIS) officer, was “on loan” to the Connecticut Department of Public Health, where he was acting director of preventable diseases. The EIS program at the Centers for Disease Control and Prevention (CDC) trained physicians in epidemiology, and they investigated outbreaks of new diseases, such as Legionnaire’s disease, toxic shock syndrome, and AIDS.1,2
Snydman called both women.
Polly Murray
Polly and Gil Murray lived with their four children in Lyme, Connecticut, on the east side of the Connecticut River. In March 1967, Polly, an artist with a gentle manner, began experiencing odd rashes, unexplained neurological symptoms, and painful, swollen joints. The symptoms got progressively worse in the late 1960s and early 1970s.1,3 At times, the arthritis was so bad she couldn’t paint, and she was repeatedly hospitalized.1
The 30-plus physicians Polly consulted were baffled by her strange array of symptoms, which seemed to come and go at will. The doctors were dismissive, even rude, and suspected her of hypochondria.1 But she persisted.
The 30-plus physicians Polly consulted were baffled by her strange array of symptoms, which seemed to come and go at will. The doctors were dismissive, even rude, and suspected her of hypochondria. But she persisted.
In November 1974, Polly’s oldest son, Sandy, developed a rash and painful joints. In January 1975, Gil Murray developed pain in his left knee, and in the early summer, their youngest son, Todd, had an expanding red rash behind his knee. Todd developed flu-like symptoms, and then multiple ringlike rashes appeared all over his body. Later that summer, both boys were on crutches from their severely swollen knees.1,2
Polly learned that other people in the neighborhood had similar symptoms. For lack of any other explanation, the affected children were being diagnosed with juvenile rheumatoid arthritis.1,2 One supportive rheumatologist referred Polly to the CDC (and Dr. Snydman’s office) on October 16, 1975. Another local doctor helped her arrange an appointment at Yale’s rheumatology clinic. That appointment was set for November 20, 1975.1
Judith Mensch
Judith and Arthur Mensch lived in Old Lyme, Connecticut, also on the eastern bank of the Connecticut River. In October 1975, their fourth-grade daughter, Anne, came home from school complaining that her knee hurt. The pain grew worse, and after excluding several other explanations, doctors concluded that Anne had juvenile rheumatoid arthritis. The pain became so intense that Anne was confined to a wheelchair and taking 10 adult aspirin tablets per day.1
Judith learned that other children in the community had also been diagnosed with juvenile rheumatoid arthritis.1 But no one was tracking the cases, because at that time, medical records were not computerized.
Like Polly, Judith was dissatisfied with the diagnosis and grew frustrated. So, she called the state health department in Hartford and then the CDC in Atlanta. After multiple phone transfers, she eventually reached David Snydman’s office.1
“A Lot of Arthritis”
Snydman was intrigued by the curious symptoms that the women described and wanted to know more. Polly and Judith gave him the phone numbers of the people in their communities who were experiencing the same mysterious illness. Snydman phoned those people, too, and soon realized, “There’s a heck of a lot of arthritis around here.”1
Snydman plotted the cases on a map, color coded by year of illness onset.1 He also drove to each patient’s home and gathered details of their symptoms. Patterns began to emerge.
On December 1, 1975, Snydman briefed his CDC supervisor. Most of the people affected were children, and most of them fell ill during the warmer months. Although the cluster of 10–15 cases was attributed to “juvenile rheumatoid arthritis,” Snydman ruled out rheumatic fever.1
Coincidentally, Snydman knew Allen Steere, a rheumatology fellow at Yale. After Steere completed his internship and residency in internal medicine, he had spent two years working as an EIS officer in Atlanta, where he met Snydman.1,2 Steere moved to New Haven in July 1975 to begin his rheumatology fellowship.
Snydman told Steere about his discussions with Polly, Judith, and the other people in the Lyme area. He wanted to know what was causing their symptoms, and he invited Steere to join his investigation.1
On Snydman’s recommendation, Steere spoke to Judith by phone in late October 1975. She was very articulate, giving him a clear description of her daughter’s symptoms and arthritis diagnosis.1
Then, on November 20, 1975, Polly drove to New Haven for her appointment. For three hours, Steere listened attentively, while she described her family’s unusual symptoms. She also gave him a copy of her voluminous medical history and a list on which she had cataloged the case histories, consultations, and lab tests of her friends and neighbors.1
Joining Force
Steere (still a first-year rheumatology fellow) received the backing of his Division Chief, Stephen Malawista, to join Snydman’s investigation. After a little homework, Malawista learned that clusters of juvenile rheumatoid arthritis had never been reported, and in fact, arthritis in children is relatively rare. In the combined populations of Lyme, Old Lyme, and East Haddam (12,000), he would have expected only one case of juvenile rheumatoid arthritis—not a dozen.1,3
“There’s a heck of a lot of arthritis around here.”
– David Snydman
Snydman’s survey of children and physicians in the Lyme area added more dots to his map. From Steere’s preliminary exams of the Murray family and descriptions of other afflicted Connecticut residents, this seemed to be a phenomenon never before described.1 And that heightened their interest.
Under Malawista’s supervision, Snydman and Steere wrote a protocol for systematically surveying this outbreak of arthritis: Protocol 1125. From December 1975 to May 1976, they gathered data from local doctors, school nurses, and health officials. They also reviewed discharge diagnosis lists from local hospitals, looking for juvenile rheumatoid arthritis and other diagnoses of arthritis in children.3
Steere collected detailed medical histories and conducted physical exams on all of the identified patients.1,3,4 In patients with swollen joints, he drew synovial fluid and took biopsies. He also submitted blood samples to test for numerous known pathogens.
Initial Results
Study 1125 identified 51 residents (39 children and 12 adults) of Lyme, Old Lyme, and East Haddam who developed an illness characterized by recurring attacks of joint swelling and pain, especially in the knee. The arthritis symptoms were usually short (about 1 week) but sometimes lasted longer. Recurrences were also usually short and separated by much longer periods of complete remission.3
Several of the adult patients, like Polly, reported episodic symptoms not usually associated with arthritis, such as severe headache, periorbital edema, photosensitive rash, or swelling of hands or feet. Many of the adults noted profound fatigue that sometimes persisted for months after the arthritis symptoms disappeared.3
Interestingly, one-fourth of the patients exhibited a red, circular rash on their legs or arms, and it spread to as large as 8–20 inches in diameter.3 In some cases, the rash was ring-shaped—like a bull’s eye.1 The rash appeared four weeks or more before the arthritic symptoms.3 Along with the rash, some patients had fever or neck stiffness. One patient experienced paralysis of half of the face (Bell’s palsy).
One-fourth of the patients exhibited a red, circular rash on their legs or arms, and it spread to as large as 8–20 inches in diameter. In some cases, the rash was ring-shaped—like a bull’s eye.
Many of the patients and their physicians thought the rash was the result of an insect bite, but only one patient remembered seeing the pest.3 And it was a tick.
The epidemiology data from Study 1125 confirmed Snydman’s earlier survey. All of the patients lived in heavily wooded areas, not in the town centers of Old Lyme, Lyme, and East Haddam.1,4 Even within these small towns, geographical clustering was readily apparent. But when neighbors or members of the same family fell ill, it was often in different years.3
Also, the symptoms clustered seasonally. The red skin rash appeared in patients from June through September. Patients developed arthritis in the late summer and early fall.1
This pattern of symptoms did not fit juvenile rheumatoid arthritis. The episodes of pain and swelling in juvenile rheumatoid arthritis were much longer and had never been known to cluster in time, space, or in families.1 Snydman and Steere were quite certain this was a new and as yet unrecognized type of arthritis. Because of that, they named it “Lyme arthritis,” after the community where it was first reported.3
The patterns of geographical and seasonal clustering strongly suggested that they were dealing with a vector-borne disease, most likely an infectious organism transmitted by an insect. They considered a number of known bacteria and viruses, but all their tests were negative. Bacteria would have been visible under the microscope, so they concluded it must be a new, previously unknown virus.3 Treatment would be challenging, because antibiotics are ineffective against viruses.
The patterns of geographical and seasonal clustering strongly suggested that they were dealing with a vector-borne disease, most likely an infectious organism transmitted by an insect.
Media Interest
By the summer of 1976, Lyme arthritis had gained notoriety and was attracting a great deal of media attention. Articles appeared in national news magazines and the tabloids, as well as the local press.1,5 People were panicking.
On August 3, 1976, Douglas Lloyd, Commissioner of the Connecticut Department of Health, sent a letter to all of the state’s health directors.6 Referring to Snydman and Steere’s findings, Lloyd told them to focus on detecting new cases and isolating the infectious agent.
He launched studies and surveys in collaboration with the state Agricultural Experimental Station, the University of Connecticut, Yale, local health departments, and CDC.5 “Any other action taken now to prevent contact with an unknown virus carried by an unknown insect would disrupt the community.”6
Shifting Focus
While their manuscript was in press, Steere saw 38 new patients and was able to follow the course of their symptoms. This confirmed that the red skin rash appeared before the onset of arthritis. And both symptoms seemed to be features of the same illness.3
In their paper, which was published in 1977, they cited reports in the European literature, as well as recent clinical cases in Groton, Connecticut, that described a red rash called “erythema migrans.”3
Since at least the 1920s, European clinicians had reported cases of erythema migrans.1 The expanding skin rash was accompanied by nerve pain, paralysis, or meningitis, but the Europeans never saw arthritis.1,4
In 1950, Sven Hellerstrom, a Swedish dermatologist, published his conclusions, based on twenty years’ experience. He maintained, based solely on clinical observations, that the red rash, which was fairly common in Stockholm, was caused by a spirochete, a type of bacteria.1 He was also convinced that this spirochete was transmitted by a tick, probably the sheep tick (Ixodes ricinus).
In 1955, a German physician, Erich Binder, and two colleagues took tissue samples from the outer ring of a patient’s erythema migrans and transplanted it into themselves. A few weeks later, all three men developed the same characteristic expanding red rash. They took penicillin and the skin rash disappeared.1
A Naval Perspective
In the summer of 1974 in Groton, Connecticut, twenty miles east of Old Lyme, a 73-year-old man went to the Navy Submarine Medical Center complaining of an odd rash.1 A couple of weeks earlier, he had noticed a small red itchy patch on his left thigh, and he thought it was due to an insect bite. The rash continued to grow in a ringlike pattern that eventually got so big he decided to seek medical advice.1
Lt. Cmdr. William Mast, an internist at the Medical Center, had never seen such a large skin rash, which had spread from the man’s thigh to his torso. Mast consulted Cmdr. William Burrows, a dermatologist at the Center, who was intrigued. The size, location, duration, and minor amount of pain did not fit any known pattern of skin rash. Burrows prescribed a course of antibiotic (erythromycin). Within a few days, the rash disappeared and did not return.1
Within a month, Burrows and Mast saw three additional patients with the same unusual skin rash: large, red, and inflamed.1,7 Some of these patients had fevers, muscle pain, chills, malaise, and rarely, meningitis. Each patient promptly improved after antibiotic treatment, and the clinicians concluded that the rash was likely due to a bacterium.1,7
Burrows regularly attended the Yale dermatology grand rounds in New Haven, and at one meeting, he presented his cases of this odd rash. One of the Yale dermatologists said that Burrows’s observations sounded very much like the European erythema migrans cases.1
In August 1976, Mast and Burrows published their four cases in JAMA, saying, “To the best of our knowledge, this is the first appearance of a cluster of cases of ECM [erythema migrans] in the United States.”1
The multiple cases within one month and within a limited geographic area led them to suspect that the rash resulted from an insect-borne bacterium. Because of that, they said, “it is possible that further incidence of this previously rare disease will ensue with the following summer season.”1 And, indeed, that’s what happened in Lyme.
After the Navy doctors’ JAMA paper was published, Steere called Burrows, and they compared data.1 The Navy doctors also referred some of their patients to Steere’s study. Some of those patients, who had been treated with antibiotics, later developed arthritis. So, Steere and Malawista were still convinced that the infectious organism was a virus.1
But the Navy doctors, who by the summer of 1975 had treated ten patients, felt more strongly than ever that antibiotics clearly helped. Mast and Burrows followed these ten patients, and only one developed arthritis.1 That was a 90% cure rate.
Yale Prospective Study
After the Study 1125 survey, Steere and Malawista followed up by studying Lyme arthritis prospectively, starting in the summer of 1976.1,4 The team, consisting of Yale scientists in epidemiology and public health, contacted 33 physicians and four visiting nurse organizations in the area and also asked dermatologists and rheumatologists to refer patients with the skin rash or Lyme arthritis to Yale.1
Steere was still a junior fellow at Yale, but he took the lead and personally evaluated all of the referred patients. He also analyzed their blood, synovial fluid, and skin biopsies for hundreds of microorganisms.1
They asked the patients and their families to save insects that bit them. Most patients did not recall seeing an insect, but several submitted the offending ticks.1
One of them was Joe Dowhan, a biologist in Connecticut’s Department of Environmental Protection.1 He was sampling specimens in Bluff Point, east of Lyme. A little tick bit him and he saved it, along with his other specimens. Yale’s epidemiology department identified it as a black-legged tick (Ixodes scapularis), also known as a deer tick. It was a relative of the European sheep tick, which had been implicated as the vector for the erythema migrans skin rash in Europe.1
Yale’s 1976 study was the first concentrated, extensive, prospective epidemiological study of this new disease.1 More than half of the patients with skin rashes developed arthritis. Some of them also developed meningitis or Bell’s palsy, which they did not expect. And some developed cardiac abnormalities, which they also didn’t expect.1
These observations strengthened the connection between the initial skin rash and the later development of arthritis. But the newly identified symptoms (e.g., Bell’s palsy, fever, and cardiac arrhythmias) made the “Lyme arthritis” description too restrictive. So, the term “Lyme disease” was born.1
The newly identified symptoms made the “Lyme arthritis” description too restrictive. So, the term “Lyme disease” was born.
The Vector
In the summer and fall of 1977, the Yale team identified 43 patients from 12 communities along the Connecticut River. Lyme disease was 30 times more common on the east bank than on the west bank of the river. Nine of the 43 patients remembered being bitten by a tick, usually a week or two before the rash appeared.1
The research team also trapped small mammals in the area and examined them for ticks. They found that the black-legged tick nymphs were 13 times more abundant on white-footed mice on the river’s east bank.1 The nymphs are about the size of a poppy seed.4
In the fall, the nymphs molt into adult ticks, which feed on large animals, deer in particular.4 They found that the adult black-legged tick was 16-times more common on the east bank.
These observations pointed to the black-legged (deer) tick as the vector for Lyme disease, but it was still unclear whether the infectious organism was a virus, bacteria, or something else.1
These observations pointed to the black-legged (deer) tick as the vector for Lyme disease, but it was still unclear whether the infectious organism was a virus, bacteria, or something else.
It’s Bacteria
Steere maintained that it was a virus, but after talking to Mast and Burrows, he decided to test the antibiotic hypothesis. In the summer of 1977, he gave penicillin to all of the patients who exhibited symptoms of Lyme disease. Then, he monitored the course of their symptoms, measuring how fast the rash improved and how many patients went on to develop secondary symptoms, such as joint, nerve, and heart problems.1
The next summer (1978), Steere withheld antibiotics. Comparing the two groups, the results indicated that antibiotics helped. So, in the summer of 1979, he began routinely prescribing antibiotics. When the Yale team analyzed the data from all four summers (1976–1979), they clearly established that antibiotics reduced both the duration of the skin rash and the likelihood of subsequent symptoms, including arthritis.1
By this time, at least five groups, including the Yale team, were trying to identify the responsible bacterium.1 Steere and Dick Root, the head of Yale’s infectious diseases division, consulted Bergey’s Manual of Systematic Bacteriology. They first considered staphylococci, because it came first in the book. Then, streptococci. Later, they came to the spirochetes.1
Spirochetes are Gram-negative bacteria characterized by a wavelike body and flagella.4 The Borrelia genus in the book’s spirochete section seemed to fit their clinical and lab observations better than anything else, and Steere asked about culturing Borrelia. Root replied, “It’s a real bitch.”1
For decades, culturing Borrelia had been unsuccessful. The best that researchers could do was to keep Borrelia spirochetes alive by passing them into rodents and then harvesting the bacterium from the rodents’ brains when they died.1
Then in 1971, Richard Kelly, a pathologist in Tennessee, added the amino sugar, N-acetylglucosamine, to his culture medium. Borrelia spend much of their life cycle inside ticks, and a polymer of this sugar forms chitin, a major component of the tick exoskeleton and gut lining.1 Kelly reasoned that Borrelia bacteria might favor it, too, and he was right.
Later, researchers at Rocky Mountain Laboratories improved Kelly’s media recipe by adding a few more ingredients, and the Borrelia cultures thrived.1
New York Ticks
In 1975, in parallel with Steere’s studies, Edgar Grunwaldt observed his first case of babesiosis.8 Grunwaldt had just established a family medical practice on Shelter Island, at the eastern end of Long Island, New York.
Babesiosis is a malaria-like disease that causes fever and hemolytic anemia. It is caused by a parasitic single-celled protozoan that is transmitted by ticks.1,8 Cases of babesiosis on Shelter Island rapidly accumulated over the next summer.8
New York health officials were seeing a sharp increase in tick populations across eastern Long Island. Along with the growing tick population and babesiosis cases, there was also an increase in cases of Rocky Mountain spotted fever.8 Rocky Mountain spotted fever is a serious tick-borne infection that causes severe headaches, high fever, and rash, and it can be fatal.
Jorge Benach, a pathologist in the New York Health Department, investigated the spotted fever outbreak. He was transferred from Albany to the Department of Pathology in the School of Medicine at SUNY Stony Brook and charged with determining how to control the ticks.8
Benach also teamed with Grunwaldt to investigate babesiosis, which had been exceedingly rare in humans until Grunwaldt’s sudden surge of cases. In 1978, Benach and the CDC conducted a survey of the prevalence and incidence of babesiosis on Shelter Island.8
Benach analyzed serum samples from both asymptomatic and confirmed babesiosis patients and banked the samples. Some of the individuals with babesiosis also reported a history of the Lyme skin rash. Later, Grunwaldt identified scores of patients who had Lyme disease, as well as babesiosis.8
Willy Burgdorfer
Because Benach lacked expertise with Rocky Mountain spotted fever, he contacted Willy Burgdorfer at the Rocky Mountain Laboratories in Hamilton, Montana.8 In 1909, Howard Ricketts had isolated the bacterium responsible for spotted fever (later named Rickettsia rickettsii in his honor) and showed that the disease was transmitted by the Rocky Mountain wood tick.
The Laboratories were established in 1928 to research and find a vaccine for Rocky Mountain spotted fever, which had plagued settlers in Montana’s Bitterroot Valley for decades. In 1937, Rocky Mountain Laboratories became part of the National Institutes of Health (NIH). That heritage established the Laboratories’ preeminence within NIH for research on tick-borne diseases.8
For his thesis project at the Swiss Tropical Institute in Basel, Willy Burgdorfer studied the tick-borne spirochete that caused relapsing fever in the Belgian Congo. Ticks have hemolymph, which functions similar to blood. As part of his research, Burgdorfer developed the hemolymph test, an innovative way to determine whether a tick was infected with the spirochete.1
After completing his PhD in 1951, Burgdorfer received a Swiss research grant and a U.S. Public Health Service fellowship to continue his studies at the Rocky Mountain Laboratories in Montana.8,9 Over the next 30 years, he spent much of his time studying Rocky Mountain spotted fever, relapsing fever, Colorado tick fever, and other diseases that are spread by blood-feeding insects and ticks.9,10
By 1953, interest in and research support for tick-borne spirochetes had completely vanished, because they no longer presented a public health problem. Officially, Burgdorfer moved on to higher priority diseases, but he also continued his work on tick-borne spirochetes as “a moonlighting job.”1,8
A self-described “tick surgeon,” Burgdorfer dissected tens of thousands of them during his career.9 He was one of the few scientists in the country, if not the world, who had extensive knowledge and the expertise to evaluate ticks and their associated pathogens.1
Burgdorfer made friends easily and had a reputation as a caring and generous mentor.8 One colleague said, “He was one of the last real gentlemen scientists. He shared his wealth of knowledge with anyone.”9
As part of Yale’s efforts to identify the organism responsible for Lyme disease, Steere had called Burgdorfer in 1977 to ask his advice.1 Steere sent several patient serum samples to Montana, and Burgdorfer tested them. But he found no antibodies to Rickettsia species.8
In 1974–1975, Burgdorfer trained Benach on his hemolymph test, as well as the biology of ticks and Rickettsia. Benach then returned to his lab and documented about 150 cases of Rocky Mountain spotted fever, including several deaths, on Long Island.8
Benach also sent ticks to Burgdorfer, who analyzed them, attempting to determine the reason for the surge of spotted fever cases. When he found no Rickettsia in the American dog tick (Rickettsia’s natural host), they decided to look at black-legged (deer) ticks as a possible vector.1
It’s a Spirochete
In October 1981, Benach sent Burgdorfer a batch of black-legged (deer) ticks that had been collected on Shelter Island.8 In the first 44 male and female ticks, Burgdorfer found no Rickettsiae using his hemolymph test.1 But two of the female ticks contained organisms that he had seen as a graduate student. He reasoned that if that organism was present in the hemolymph, it must also be in the tick’s mid-gut.1
He dissected the ticks, which were the size of a sesame seed, and stained cells extracted from the mid-gut. Under the microscope, he saw long, slender, coiled bacteria—so familiar from his thesis project. “Once my eyes focused on these long snake-like organisms, I recognized what I had seen a million times before: spirochetes.”9
Within hours, Burgdorfer dissected the remaining 124 ticks and examined their mid-gut tissues microscopically. The mid-gut of 75 ticks contained the spirochetes.1 He immediately notified Benach.
The next logical step was to culture the spirochetes. Burgdorfer contacted Alan Barbour, a physician and microbiologist at Rocky Mountain Laboratories. Barbour had learned how to culture the pesky Borrelia organisms using the improved Kelly culture media that had recently been developed at the Rocky Mountain Laboratories.1
“Once my eyes focused on these long snake-like organisms, I recognized what I had seen a million times before: spirochetes.” – Willy Burgdorfer
On November 13, 1981, Barbour began incubating the tick mid-gut specimens. On November 18, he told Burgdorfer that several of the culture tubes contained spirochetes, and after two more weeks of work, he successfully isolated the new spirochete from other contaminating organisms.8
Benach then sent to Montana serum samples that he had stored from Grunwaldt’s Shelter Island patients and from the 1978 babesiosis survey.8 Using an immunofluorescent assay, Burgdorfer found that the patients’ sera contained antibodies against this new spirochete organism. By contrast, the sera from control patients who never had Lyme disease were uniformly negative.4,8
Burgdorfer then allowed ticks from Shelter Island to feed on lab rabbits, and the rabbits developed a skin rash similar to that seen in patients with Lyme disease. The rabbits’ serum was also positive for spirochete antibodies in the immunofluorescent assay.1,8
Naming the Thing
They called this new strain of spirochete “B31.” It was the first spirochete isolated by the three Bs: Burgdorfer, Benach, and Barbour.8
In June 1982, Burgdorfer, Barbour, Benach, and Grunwaldt published their findings in Science.11 The Science article was entitled, “Lyme Disease—a Tick-Borne Spirochetosis?”
All of the other groups researching Lyme disease immediately shifted their work to this new B31 spirochete.1 And within a year, the question mark on the Science paper title was dropped. Several research groups, including collaborations between Burgdorfer, Steere, Benach, and Barbour, reported finding the B31 spirochete in the blood of patients with Lyme disease.8,12
Researchers had fulfilled Koch’s postulates: Lyme disease was caused by a spirochete (B31) that was transmitted by the black-legged (deer) tick.8 The natural mammalian hosts of this tick are primarily white-footed mice and white-tailed deer.1,13 Humans are “accidental” or “inadvertent” hosts, who wander into areas where the ticks breed.8,13,14
Researchers had fulfilled Koch’s postulates: Lyme disease was caused by a spirochete that was transmitted by the black-legged (deer) tick.
In November 1983, Steere, Malawista, and their Yale colleagues hosted the First International Symposium on Lyme Disease in New Haven, Connecticut. Researchers presented data showing that the B31 spirochete belonged to the Borrelia genus.8 But it was clearly a new species.
The attendees discussed various options. Some argued that the species should reflect its clinical features, such as rheumatica. Others thought the species should reflect the location of the initial outbreak, such as lymeii. Klaus Weber from Germany nominated “burgdorferi.” They took a vote, and B31 officially became Borrelia burgdorferi in honor of Willy Burgdorfer’s discovery.8
They took a vote, and B31 officially became Borrelia burgdorferi in honor of Willy Burgdorfer’s discovery.
Stages of Disease
Within a few years, medical textbooks began including Lyme disease and described three stages of symptoms. In about 80% of patients, Lyme disease begins as a red rash (erythema migrans), which appears a few weeks after the tick bite and slowly expands over days or weeks, often in characteristic bull’s eye rings.15,16
The rash may go unnoticed because it is often asymptomatic and resolves spontaneously within weeks. But some patients experience flu-like symptoms, including fever, headache, neck stiffness, malaise, and muscle and joint pain.15,16 Antibiotics usually treat the rash and minimize the risk of subsequent symptoms.
Untreated patients may exhibit multiple patches of rash. Within weeks to months, about 15% of untreated patients develop neurologic symptoms including brain fog, meningitis, Bell’s palsy, and spinal nerve inflammation. About 5% of untreated patients experience myocarditis or heart rhythm problems.15,16
About 60% of untreated patients develop arthritis, months to years after the initial infection. Joint swelling and pain, particularly in the knee, occur in brief but repeating episodes.15,16 About 10% of patients have persistent joint inflammation for months or even several years. A small percentage of patients have persistent subjective symptoms such as cognitive difficulties, altered mood, forgetfulness, and fatigue.15
For example, Joe Dowhan, the biologist who brought the first black-legged tick to Steere in 1976, was not treated at that time. He kept detailed notes of his symptoms and recovered. Then, in 1990, he developed neurologic symptoms: generalized malaise, headaches, neck stiffness, and debilitating fatigue. He went for a checkup and the doctor found neurological Lyme disease, 13 years after his initial infection.1
Some evidence suggests that B. burgdorferi may remain active and is responsible for these long-term symptoms. Alternatively, the persistent symptoms may be due to undefined neurological damage and immune system malfunctions secondary to the initial infection.2
By the 1990s, physicians suspected that many people complaining of late neurological symptoms did not, in fact, have Lyme disease.2 Except for patients who live in tick-endemic areas, these late/lagging symptoms are more likely due to fibromyalgia or chronic fatigue syndrome than an active Lyme disease infection.15,17
Diagnosis
A skin rash expanding to larger than five inches is sufficient to diagnosis Lyme disease in endemic areas.15,17 But the diagnosis can be challenging if the rash is not present or the patient does not notice it. In such cases, diagnostic tests may be ordered.4,15 The standard lab diagnostics are performed in two steps. The first is an ELISA assay.18,19 If that is positive, a confirmatory Western blot test is performed.19
Both of these tests rely on an antibody reaction. They are not useful for early diagnosis, because it takes several weeks for a person’s immune system to produce sufficient quantities of antibodies against B. burgdorferi. Also, the tests cannot differentiate between an active infection and a previous exposure, because B. burgdorferi antibodies remain long after the patient recovers from an initial infection.17,19,20
Treatment
It takes at least 36 hours for a tick to feed on blood and transmit B. burgdorferi, so quickly removing an attached tick with fine-tipped tweezers usually prevents infection.15,16 For those who live in a highly endemic area and the tick was identified as a black-legged tick that was attached for more than 36 hours, a single dose of doxycycline within three days of tick removal is recommended to prevent Lyme disease.16,18
Antibiotic treatment for 10–14 days is usually sufficient to treat Lyme disease symptoms, with the greatest efficacy seen in patients starting treatment soon after the appearance of the skin rash.15,18,19 Antibiotics shorten the duration of the skin rash and usually prevent development of further symptoms.15,16,19
About 10–20% of patients report lingering symptoms despite appropriate antibiotic treatment.15,20 These persistent subjective symptoms (e.g., fatigue, muscle pain, and brain fog) may last for years.15,16 Controlled studies have confirmed that retreating with additional antibiotics is of no benefit against these late-stage symptoms.17,21 In fact, high-dose, long-term antibiotic therapy in such patients may cause serious adverse drug reactions, including death.17
Lyme disease accounts for more than 80% of all tick-borne diseases in the U.S., but the black-legged tick is also a vector for babesiosis, relapsing fever, ehrlichiosis, Powassan virus, and other pathogens.15,19,20 Those pathogens produce symptoms similar to Lyme disease but are not effectively treated with antibiotics.19
Co-infection might account for the atypical symptoms seen in some cases of Lyme disease, and some data suggest that patients who are co-infected have more and worse symptoms. Also, co-infecting organisms may interfere with the diagnostic lab results for Lyme disease.1
Prevention
Several manufacturers have pursued developing a Lyme disease vaccine, but currently no such vaccine is on the market. Avoiding ticks is the best way to prevent infection in highly endemic areas: the Northeast, mid-Atlantic, and upper Midwest.16
Protective measures include wearing clothing that minimizes skin exposure and using a tick repellant containing DEET when walking in the woods or tending gardens.15,18,20 Placing clothes in a dryer for up to 1 hour effectively kills ticks. Also, daily body checks for ticks and bathing or showering within two hours of tick exposure helps prevent tick attachment.15,18
Climate Change
In 2023, CDC received reports of 89,000 Lyme disease cases but cautioned that many other cases were likely not reported.22 Surveillance efforts are difficult, many individuals are treated as outpatients, and diagnostic lab tests have limitations.5 CDC estimates that about 476,000 Americans may actually be diagnosed and treated for Lyme disease each year.22
When DNA sequencing became available, researchers examined tick and animal specimens from various museum collections, including the Smithsonian. B. burgdorferi was present in mice as far back as 1894.1 If the spirochete had been around for so long, why did it only surface as Lyme disease in the 1970s?
The answer was deer. Ticks not only obtain their blood meal from deer but also adult ticks mate there.4 In Connecticut, the deer herd steadily increased from 4000 in 1936 to about 30,000 in 1976.1 In parallel, suburban residential land use and outdoor recreation areas expanded, so that larger numbers of deer were living closer to humans.5 This led to a corresponding increase in the tick population and the dramatic increase in Lyme disease.1,4,5,15
Due to climate change, the tick season is lengthening and now lasts throughout most of the year.14 There is also evidence that Lyme disease is spreading geographically to areas beyond the original endemic areas.17 A word of caution as we enter summer.
