Lyme disease

Lyme disease can produce a broad range of symptoms. The incubation period is usually one to two weeks, but can be much shorter (days) or much longer (months to years). The rash is usually circular or oval, red or bluish, and may have an elevated or darker center. This can make obtaining a diagnosis particularly challenging, especially with the rise of co-infection. Asymptomatic infection exists, but some studies suggest that this occurs in less than 7% of infected individuals in the United States as opposed to about 50–70% of cases in Europe. Lymphocytic meningitis causes characteristic changes in the cerebrospinal fluid (CSF) and may be accompanied for several weeks by variable headache and, less commonly, usually mild meningitis signs such as inability to flex the neck fully and intolerance to bright lights but typically no or only very low fever. After several months neuroborreliosis can also present otolaryngological symptoms. Up to 76.5% of them present as tinnitus, the most common symptom. Vertigo and dizziness (53.7%) and hearing loss (16.7%) were the next most common symptoms. In children, partial loss of vision may also occur. Mononeuritis multiplex is an inflammation causing similar symptoms in one or more unrelated peripheral nerves. In European adults, the most common presentation is a combination of lymphocytic meningitis and radiculopathy known as Bannwarth syndrome, accompanied in 36-89% of cases by facial palsy. Symptoms may include heart palpitations (in 69% of people), dizziness, fainting, shortness of breath, and chest pain. Lyme arthritis occurs in up to 60% of untreated people, typically starting about six months after infection. A neurologic syndrome called Lyme encephalopathy is associated with subtle memory and cognitive difficulties, insomnia, a general sense of feeling unwell, and changes in personality. Lyme encephalopathy is controversial in the US and has not been reported in Europe. Problems such as depression and fibromyalgia are as common in people with Lyme disease as in the general population. There is no compelling evidence that Lyme disease causes psychiatric disorders, or neurodevelopmental disorders (e.g. ADHD or autism). Acrodermatitis chronica atrophicans is a chronic skin disorder observed primarily in Europe among the elderly. It begins as a reddish-blue patch of discolored skin, often on the backs of the hands or feet. The lesion slowly atrophies over several weeks or months, with the skin becoming first thin and wrinkled and then, if untreated, completely dry and hairless. ==Cause==

'' bacteria, the causative agents of Lyme disease, magnified Lyme disease is caused by spirochetes, gram-negative bacteria from the genus Borrelia. Spirochetes are surrounded by peptidoglycan and flagella. The Lyme-related Borrelia species are collectively known as Borrelia burgdorferi sensu lato, and show a great deal of genetic diversity. B. burgdorferi sensu lato is a species complex made up of 20 accepted and three proposed genospecies. Eight species are known to cause Lyme disease: B. mayonii (found in North America), B. burgdorferi sensu stricto (found in North America and Europe), B. afzelii, B. garinii, B. spielmanii, and B. lusitaniae (all found in Eurasia). Some studies have also proposed that B. valaisiana may sometimes infect humans. This species does not appear to be an important cause of disease. Tick appearance changes when feeding Both nymph and female ticks increase in size (engorge) when feeding. Types of ticks, and hosts Lyme disease is transmitted to humans by the bites of infected ticks of the genus Ixodes. In the United States, Ixodes scapularis is the primary vector. In Europe, Ixodes ricinus ticks may spread the bacteria more quickly. In North America, the bacterial species Borrelia burgdorferi and B. mayonii cause Lyme disease. In Europe and Asia, Borrelia afzelii, Borrelia garinii, B. spielmanii and four other species also cause the disease. While B. burgdorferi is most associated with ticks hosted by white-tailed deer and white-footed mice, Borrelia afzelii is most frequently detected in rodent-feeding vector ticks, and Borrelia garinii and Borrelia valaisiana appear to be associated with birds. Both rodents and birds are competent reservoir hosts for B. burgdorferi sensu stricto. The resistance of a genospecies of Lyme disease spirochetes to the bacteriolytic activities of the alternative complement pathway of various host species may determine its reservoir host association. Or, the nymphal ticks can be darker. The younger larval ticks are very rarely infected. Areas where Lyme is common are expanding. Prevalence Tick bites often go unnoticed because of the small size of the tick in its nymphal stage, as well as tick secretions that prevent the host from feeling any itch or pain from the bite. However, transmission is quite rare, with only about 1.2 to 1.4 percent of recognized tick bites resulting in Lyme disease. In pregnancy Lyme disease spreading from mother to fetus is possible but extremely rare, and with antibiotic treatment, there is no increased risk of adverse birth outcomes. NICE guidance is that antibiotics appropriate for pregnancy be used. There are no studies on developmental outcomes of children whose mothers had Lyme. Ticks in certain regions also transmit viruses that cause tick-borne encephalitis and Powassan virus disease. Co-infections of Lyme disease may not require additional treatment, since they may resolve on their own or—as in the case of HGA—can be treated with the doxycycline prescribed for Lyme. Persistent fever or compatible anomalous laboratory findings may be indicative of a co-infection. ==Pathophysiology==

B. burgdorferi can spread throughout the body during the course of the disease, and has been found in the skin, heart, joints, peripheral nervous system, and central nervous system. Therefore, many of the signs and symptoms of Lyme disease are a consequence of the immune response to the spirochete in those tissues. Tick saliva, which accompanies the spirochete into the skin during the feeding process, contains substances that disrupt the immune response at the site of the bite. This provides a protective environment where the spirochete can establish infection. The spirochetes multiply and migrate outward within the dermis. The host inflammatory response to the bacteria in the skin causes the characteristic circular EM lesion. Neutrophils, however, which are necessary to eliminate the spirochetes from the skin, fail to appear in necessary numbers in the developing EM lesion because tick saliva inhibits neutrophil function. This allows the bacteria to survive and eventually spread throughout the body. Days to weeks following the tick bite, the spirochetes spread via the bloodstream to joints, heart, nervous system, and distant skin sites, where their presence gives rise to the variety of symptoms of the disseminated disease. The spread of B. burgdorferi is aided by the attachment of the host protease plasmin to the surface of the spirochete. If untreated, the bacteria may persist in the body for months or even years, despite the production of B. burgdorferi antibodies by the immune system. The spirochetes may avoid the immune response by decreasing expression of surface proteins that are targeted by antibodies, antigenic variation of the VlsE surface protein, inactivating key immune components such as complement, and hiding in the extracellular matrix, which may interfere with the function of immune factors. Immunological studies Exposure to the Borrelia bacterium during Lyme disease possibly causes a long-lived and damaging inflammatory response, a form of pathogen-induced autoimmune disease. The production of this reaction might be due to a form of molecular mimicry, where Borrelia avoids being killed by the immune system by resembling normal parts of the body's tissues. Chronic symptoms from an autoimmune reaction could explain why certain symptoms persist even after the spirochetes have been eliminated from the body. This hypothesis may explain why chronic arthritis persists after antibiotic therapy, similar to rheumatic fever, but its wider application is controversial. ==Diagnosis==

Lyme disease is diagnosed based on symptoms, objective physical findings (such as erythema migrans (EM) rash, facial palsy, or arthritis), history of possible exposure to infected ticks, and possibly laboratory tests. Several bordering areas of Canada also have high Lyme risk. In the absence of an EM rash or history of tick exposure, Lyme diagnosis depends on laboratory confirmation. The bacteria that cause Lyme disease are difficult to observe directly in body tissues and also difficult and too time-consuming to grow in the laboratory. Laboratory testing Tests for antibodies in the blood by ELISA and Western blot are the most widely used methods for Lyme diagnosis. A two-tiered protocol is recommended by the Centers for Disease Control and Prevention (CDC): the sensitive ELISA test is performed first, and if it is positive or equivocal, then the more specific Western blot is run. When an EM rash first appears, detectable antibodies may not be present. Therefore, it is recommended that testing not be performed and diagnosis be based on the presence of the EM rash. The number of IgM antibodies usually collapses 4–6 months after infection, while IgG antibodies can remain detectable for years. The use of nanotrap particles for their detection is being examined. The OspA protein has been linked to active symptoms of Lyme. High titers of either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies to Borrelia antigens indicate disease, but lower titers can be misleading, because the IgM antibodies may remain after the initial infection, and IgG antibodies may remain for years. Differential diagnosis Community clinics have been reported to misdiagnose 23–28% of erythema migrans (EM) rashes and 83% of other objective manifestations of early Lyme disease. Facial palsy caused by Lyme disease (LDFP) is often misdiagnosed as Bell's palsy. Although most cases of radiculopathy are compressive and resolve with conservative treatment (e.g., rest) within 4–6 weeks, guidelines for managing radiculopathy recommend first evaluating risks of other possible causes that, although less frequent, require immediate diagnosis and treatment, including infections such as Lyme and shingles. A history of outdoor activities in likely tick habitats in the last 3 months possibly followed by a rash or viral-like symptoms, and current headache, other symptoms of lymphocytic meningitis, or facial palsy would lead to suspicion of Lyme disease and recommendation of serological and lumbar puncture tests for confirmation. ==Treatment==

Antibiotics are the primary treatment. IgM and IgG antibody levels may be elevated for years even after successful treatment with antibiotics. In those with facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping. About a third of people with Lyme carditis need a temporary pacemaker until their heart conduction abnormality resolves, and 21% need to be hospitalized. Post-antibiotic Lyme arthritis may be symptomatically treated with NSAIDs, disease-modifying antirheumatic drugs (DMARDs), arthroscopic synovectomy, or physical therapy. People receiving treatment should be advised that reinfection is possible and how to prevent it. ==Prognosis==

Lyme disease's typical first sign, the erythema migrans (EM) rash, resolves within several weeks even without treatment. Treatment failure, i.e. persistence of original or appearance of new signs of the disease, occurs only in a few people. People treated only after nervous system manifestations of the disease may end up with objective neurological deficits, in addition to subjective symptoms. In another European study, 5 years after treatment for neuroborreliosis lingering symptoms were less common among children (15%) than adults (30%), and in the latter were less common among those treated within 30 days of the first symptom (16%) than among those treated later (39%); among those with lingering symptoms, 54% had daily activities restricted and 19% were on sick leave or incapacitated. Some data suggest that about 90% of Lyme facial palsies treated with antibiotics recover fully a median of 24 days after appearing and most of the rest recover with only mild abnormality. However, in Europe 41% of people treated for facial palsy had other lingering symptoms at followup up to 6 months later, including 28% with numbness or altered sensation and 14% with fatigue or concentration problems. Other research shows that synkinesis (involuntary movement of a facial muscle when another one is voluntarily moved) can become evident only 6–12 months after facial palsy appears to be resolved, as damaged nerves regrow and sometimes connect to incorrect muscles. Synkinesis is associated with corticosteroid use. Post-treatment Lyme disease syndrome Symptoms and prevalence Chronic symptoms like pain, fatigue, or cognitive impairment are experienced by 5–20% of people who contract Lyme disease, even after completing treatment. This is called Post-treatment Lyme disease syndrome, or PTLDS. Causes The cause is unknown. Hypotheses include; • that a persistent, difficult-to-detect infection remains. However, human and animal trials have not provided compelling evidence to support this hypothesis. • that the infection triggered autoimmunity. Autoimmune responses are known to occur following other infections, including Campylobacter (Guillain–Barré syndrome), Chlamydia (reactive arthritis), and strep throat (rheumatic heart disease). • that debris from a previous infection could remain. In studies of people who presented to clinics with concerns about Lyme disease, 47 to 80% had no evidence of Lyme infection while 15 to 55% (median 34%) were able to obtain other diagnoses. Prognosis Patients typically improve over time without additional antibiotics, but this may take several months. There is a lack of long-term data, with few studies of symptoms more than 12 months from initial infection. ==Epidemiology and prevalence==

Overview Lyme disease occurs regularly in Northern Hemisphere temperate regions. Over 200,000 people a year are diagnosed and treated in Europe. Climate change Climate change is seen as potentially supportive for ticks. There is a suggestion that tick populations and Lyme disease occurrence are increasing and spreading into new areas, owing in part to the warming temperatures of climate change. However, tick-borne disease systems are complex, and determining whether changes are due to climate change or other drivers can be difficult. North America Many studies in North America have examined ecological and environmental correlates of the number of people affected by Lyme disease. A 2005 study using climate suitability modelling of I. scapularis projected that climate change would cause an overall 213% increase in suitable vector habitat by 2080, with northward expansions in Canada, increased suitability in the central U.S., and decreased suitable habitat and vector retraction in the southern U.S. A 2008 review of published studies concluded that the presence of forests or forested areas was the only variable that consistently elevated the risk of Lyme disease whereas other environmental variables showed little or no concordance between studies. The authors argued that the factors influencing tick density and human risk between sites are still poorly understood, and that future studies should be conducted over longer periods, become more standardized across regions, and incorporate existing knowledge of regional Lyme disease ecology. The 2022 surveillance case definition classifies cases as confirmed, probable, and suspect. The number of reported cases of the disease has been increasing, as are endemic regions in North America. The CDC emphasizes that, while surveillance data have limitations, they are useful due to "uniformity, simplicity, and timeliness." While cases are under-reported in high-incidence areas, over-reporting is likely in low-incidence areas. Additionally, surveillance cases are reported by the county of residence and not where an infection was necessarily contracted. In recent years, five to ten cases a year of a disease similar to Lyme have been occurring in Montana. It occurs primarily in pockets along the Yellowstone River in central Montana. Symptons have bee a red bull's-eye rash around a tick bite, followed by weeks of fatigue and a fever. Lyme disease is rare in Iceland. On average, around 6 to 7 cases are diagnosed every year, primarily localised infections presenting as erythema migrans. None of the cases had a definitive Icelandic origin and the yearly number of cases has not been increasing. United Kingdom In the United Kingdom, Lyme disease is the primary human tick-borne disease of concern, with a 1-year Lyme disease incidence of 12/100,000 reported in 2019. The number of laboratory-confirmed cases of Lyme disease has been rising steadily since voluntary reporting was introduced in 1986 Africa In northern Africa, B. burgdorferi sensu lato has been identified in Morocco, Algeria, Egypt and Tunisia. Asia B. burgdorferi sensu lato-infested ticks are being found more frequently in Japan, as well as in northwest China, Nepal, Thailand and far eastern Russia. While there have been reports of people acquiring Lyme disease in Australia, and even evidence of closely related Borrelia species in ticks, the evidence linking these cases to local transmission is limited. Ongoing research on resolving potential Borrelia species to Debilitating Symptom Complexes Attributed to Ticks (DSCATT) in Australia is ongoing. ==Prevention==

Tick bites can be prevented by avoiding or reducing time in likely tick habitats and taking precautions while in and when getting out of one. Tick densities tend to be highest in woodlands, followed by unmaintained edges between woods and lawns (about half as high), ornamental plants and perennial groundcover (about a quarter), and lawns (about 30 times less). Ixodes larvae and nymphs tend to be abundant also where mice nest, such as stone walls and wood logs. In Northeastern United States, 69% of tick bites are estimated to happen in residences, 11% in schools or camps, 9% in parks or recreational areas, 4% at work, 3% while hunting, and 4% in other areas. Permethrin is odorless and safe for humans but highly toxic to ticks. Permethrin-treated closed-toed shoes and socks reduce by 74 times the number of bites from nymphs that make first contact with a shoe of a person also wearing treated shorts (because nymphs usually quest near the ground, this is a typical contact scenario). Better protection can be achieved by tucking permethrin-treated trousers (pants) into treated socks and a treated long-sleeve shirt into the trousers so as to minimize gaps through which a tick might reach the wearer's skin. Light-colored clothing may make it easier to see ticks and remove them before they bite. The EPA recommends several tick repellents for use on exposed skin, including DEET, picaridin, IR3535 (a derivative of amino acid beta-alanine), oil of lemon eucalyptus (OLE, a natural compound) and OLE's active ingredient para-menthane-diol (PMD). Unlike DEET, picaridin is odorless and is less likely to irritate the skin or harm fabric or plastics. The following areas should be checked especially carefully: armpits, between legs, back of knee, bellybutton, trunk, and in children ears, neck and hair. After tick removal, any tick parts remaining in the skin should be removed with a clean tweezer, if possible. Instead, a product should be sprayed on the tick to cause it to freeze and then drop off. Preventive antibiotics The risk of infectious transmission increases with the duration of tick attachment. These include keeping lawns mown, removing leaf litter and weeds and avoiding the use of ground cover. U.S. workers in the northeastern and north-central states are at highest risk of exposure to infected ticks. Ticks may also transmit other tick-borne diseases to workers in these and other regions of the country. Worksites with woods, bushes, high grass or leaf litter are likely to have more ticks. Outdoor workers should be most careful to protect themselves in the late spring and summer when young ticks are most active. Host animals Ticks can feed upon the blood of a wide array of possible host species, including lizards, birds, mice, cats, dogs, deer, cattle and humans. The extent to which a tick can feed, reproduce, and spread will depend on the type and availability of its hosts. Whether it will spread disease is also affected by its available hosts. Some species, such as lizards, are referred to as "dilution hosts" because they don't tend to support Lyme disease pathogens and decrease the likelihood that the disease will be passed on by ticks feeding on them. White-tailed deer are both a food source and a "reproductive host", where ticks tend to mate. The white-footed mouse is a reservoir host in which the pathogen for Lyme disease can survive. The availability of hosts can have significant impacts on the transmission of Lyme disease. A greater diversity of hosts, or of those that don't support the pathogen, tends to decrease the likelihood that the disease will be transmitted. In the United States, one approach to reducing the incidence of Lyme and other deer tick-borne diseases has been to greatly reduce the deer population on which the adult ticks depend for feeding and reproduction. Lyme disease cases fell following deer eradication on an island, Monhegan, Maine, Another study done in New Jersey removed deer and also did not see a reduction in the number of questing ticks and determined that deer culling is an unlikely way to control tick populations effectively. One study summarized the results of multiple studies all looking at deer reduction controlling tick populations and determined that deer control can't be used as a standalone reduction for Lyme disease. It also claims that most studies examining this are not representative of areas with high human Lyme disease risk. There is varying information on whether or not the removal of deer is actually a way to control the Lyme disease epidemic. Removal of smaller mammals that are fed on by juveniles who are more actively acquiring and spreading the pathogen would decrease Lyme disease risk the most. Others have noted that while deer are reproductive hosts, they are not Borrelia burgdorferi reservoirs. This is because it was found that white-tailed deer blood actually kills the Borrelia burgdorferi bacteria. Researchers have suggested that smaller, less obviously visible Lyme reservoirs, like white-footed mice and Eastern chipmunks, may more strongly impact Lyme disease occurrence. Ecosystem studies in New York state suggest that white-footed mice thrive when forests are broken into smaller, isolated chunks of woodland with fewer rodent predators. With more rodents harboring the disease, the odds increase that a tick will feed on a disease-harboring rodent and that someone will pick up a disease-carrying tick in their garden or while walking in the woods. Data indicates that the smaller the wooded area, the more ticks it will contain and the likely they are to carry Lyme disease, supporting the idea that deforestation and habitat fragmentation affect ticks, hosts and disease transmission. They also affect cats, dogs, and other pets. Routine veterinary control of ticks of domestic animals through the use of acaricides has been suggested as a way to reduce exposure of humans to ticks. However, chemical control with acaricides is now criticized on several grounds. Ticks appear to develop resistance to acaricides; acaricides are costly; and there are concerns over their toxicity and the potential for chemical residues to affect food and the environment. In Europe, known reservoirs of Borrelia burgdorferi were 9 small mammals, 7 medium-sized mammals and 16 species of birds (including passerines, sea-birds and pheasants). "The reservoir species that contain the most pathogens are the European roe deer Capreolus capreolus; (incompetent host for B. burgdorferi and TBE virus) but it is important for feeding the ticks, as red deer and wild boars (Sus scrofa), in which one Rickettsia and three Borrelia species were identified", Nevertheless, in the 2000s, in roe deer in Europe "two species of Rickettsia and two species of Borrelia were identified". ==Vaccination==

, no human vaccines for Lyme disease were available. The only human vaccine to advance to market was LYMErix, which was available from 1998, but discontinued in 2002. The vaccine candidate VLA15 was scheduled to start a phase 3 trial in the third quarter of 2022, with other research ongoing. Multiple vaccines are available for the prevention of Lyme disease in dogs. LYMErix The vaccine LYMErix was available from 1998 to 2002. The recombinant vaccine against Lyme disease, based on the outer surface protein A (OspA) of B. burgdorferi with aluminum hydroxide as adjuvant, was developed by SmithKline Beecham. In clinical trials involving more than 10,000 people, the vaccine was found to confer protective immunity to Lyme disease in 76% of adults after three doses with only mild or moderate and transient adverse effects. VLA15 The hexavalent (OspA) protein subunit-based vaccine candidate VLA15 was developed by Valneva. It was granted fast track designation by the U.S. Food and Drug Administration in July 2017. In April 2020 Pfizer paid $130 million for the rights to the vaccine, and the companies are developing it together, performing multiple phase 2 trials. A phase 3 trial of VLA15 was scheduled for late 2022, recruiting volunteers at test sites located across the northeastern United States and in Europe. Participants were scheduled to receive an initial three-dose series of vaccines over the course of five to nine months, followed by a booster dose after twelve months, with both the initial series and the booster dose scheduled to be complete before the year's peak Lyme disease season. The vaccine contains mRNAs for the body to build 19 proteins in tick saliva which, by enabling quick development of erythema (itchy redness) at the bite site, protects guinea pigs against Lyme disease. It also protects the test animals if the tick is not removed, if only one tick, but not three, remains attached. Sanofi, in cooperation with the Choumet Group and the Pardi lab, also developed and evaluated new mRNA vaccine candidates targeting the bacterium's outer surface protein A (OspA), delivered via lipid nanoparticles. In mouse models, the mRNA-OspA vaccine elicited robust immune responses and offered complete protection against infection—outperforming traditional protein-based vaccines. The findings suggest that mRNA-OspA vaccines hold promise for preventing Lyme disease in humans. Canine vaccines Canine vaccines have been formulated and approved for the prevention of Lyme disease in dogs. Currently, three Lyme disease vaccines are available. LymeVax, formulated by Fort Dodge Laboratories, contains intact dead spirochetes, which expose the host to the organism. Galaxy Lyme, Intervet-Schering-Plough's vaccine, targets proteins OspC and OspA. The OspC antibodies kill any of the bacteria that the OspA antibodies did not kill. Canine Recombinant Lyme, formulated by Merial, generates antibodies against the OspA protein, so a tick feeding on a vaccinated dog draws in blood full of anti-OspA antibodies, which kill the spirochetes in the tick's gut before they are transmitted to the dog. == Etymology ==

Lyme disease was diagnosed as a separate condition for the first time in 1975 in Lyme, Connecticut. ==History==

Early evidence The earliest known evidence of Lyme disease was found in Oetzi, a 5300 year old mummy in the Eastern Alps near the Italian border. The evolutionary history of Borrelia burgdorferi genetics has been examined by scientists. One study has found that before the reforestation that accompanied post-colonial farm abandonment in New England and the wholesale migration into the Midwest that occurred during the early 19th century, Lyme disease had been present for thousands of years in America and had spread along with its tick hosts from the Northeast to the Midwest. The examination of preserved museum specimens has found Borrelia DNA in an infected Ixodes ricinus tick from Germany dating back to 1884, and an infected mouse from Cape Cod that died in 1894. The early European studies of what is now known as Lyme disease described its skin manifestations. The first study dates to 1883 in Breslau, Germany (now Wrocław, Poland), where physician Alfred Buchwald described a man who for 16 years had had a degenerative skin disorder now known as acrodermatitis chronica atrophicans. reported that "penicillin was found to be the most effective." In 1949, Nils Thyresson, who also worked at the Karolinska Institute, was the first to treat ACA with penicillin. The full syndrome now known as Lyme disease was not recognized until a cluster of cases originally thought to be juvenile rheumatoid arthritis was identified in three towns in southeastern Connecticut in 1975, including the towns Lyme and Old Lyme, which gave the disease its popular name. This was investigated by physicians David Snydman and Allen Steere of the Epidemic Intelligence Service, and by others from Yale University, including Stephen Malawista, who is credited as a co-discover of the disease. The recognition that the people in the United States had EM led to the recognition that "Lyme arthritis" was one manifestation of the same tick-borne condition known in Europe. In 1980, Steere, et al., began to test antibiotic regimens in adults with Lyme disease. After the identification of B. burgdorferi as the causative agent of Lyme disease, antibiotics were selected for testing, guided by in vitro antibiotic sensitivities, including tetracycline antibiotics, amoxicillin, cefuroxime axetil, intravenous and intramuscular penicillin and intravenous ceftriaxone. The mechanism of tick transmission was also the subject of much discussion. B. burgdorferi spirochetes were identified in tick saliva in 1987, confirming the hypothesis that transmission occurred via tick salivary glands. ==Society, culture, and controversy==

Landscape changes and urbanization Urbanization and other anthropogenic factors can be implicated in the spread of Lyme disease to humans. In many areas, the expansion of suburban neighborhoods has led to the gradual deforestation of surrounding wooded areas and increased border contact between humans and tick-dense areas. Human expansion has also resulted in a reduction of predators that hunt deer as well as mice, chipmunks and other small rodents—the primary reservoirs for Lyme disease. As a consequence of increased human contact with host and vector, the likelihood of transmission of the disease has greatly increased. Chronic Lyme disease The term "chronic Lyme disease" (CLD) is controversially applied to people suffering a range of signs and symptoms attributed to Lyme disease or its treatment. CLD is controversial and not recognized in the medical literature, Conspiracy theories about origins Prolific but unfounded conspiracy theories have alleged that Lyme disease was a biological weapon that originated in the Plum Island laboratory, which is near Old Lyme, Connecticut. A 2004 book entitled ''Lab 257: The Disturbing Story of the Government's Secret Plum Island Germ Laboratory'' fueled the conspiracy theories. Archived specimens show that Lyme disease was endemic well before the establishment of Plum Island laboratory. ==Other animals==

Dogs Prevention of Lyme disease is an important step in keeping dogs safe in endemic areas. Prevention education and a number of preventive measures are available. First, for dog owners who live near or visit tick-infested areas, routine vaccinations of their dogs are an important step. In two cases, the infected cats experienced cardiac irregularities similar to symptoms of Lyme in both dogs and humans. However, cats who are infected with Lyme disease are likely to be asymptomatic, and show no noticeable signs of the disease. Additional symptoms include muscle tenderness, swollen joints, arthritis, and neck stiffness. Chronic symptoms of the disease typically include neurological manifestations, such as meningitis, cranial neuritis, radiculoneuritis, and encephalitis. Furthermore, some horses do not slow clinical signs of Lyme disease. There are three main testing strategies used to diagnose horses with Lyme disease. They include clinical evaluation, serological testing, and polymerase chain reaction (PCR) testing. Typical treatment involves antibiotics such as oxytetracycline, doxycycline, ceftriaxone, or minocycline. Currently, there is no approved Lyme disease vaccine for horses. However, a study demonstrated that ponies could be protected using an aluminum adjuvanted recombinant outer-surface protein A (rOspA) vaccine. While horses have been administered a Lyme disease vaccine designed for dogs, it elicits only a short-lasting antibody response. == References ==