Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by bacteria of the Borrelia type. The most common sign of infection is an expanding area of redness, known as erythema migrans, that begins at the site of a tick bite about a week after it has occurred. The rash is typically neither itchy nor painful. Approximately 25–50% of infected people do not develop a rash. Other early symptoms may include fever, headache and feeling tired. If untreated, symptoms may include loss of the ability to move one or both sides of the face, joint pains, severe headaches with neck stiffness, or heart palpitations, among others. Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, people develop shooting pains or tingling in their arms and legs. Despite appropriate treatment, about 10 to 20% of people develop joint pains, memory problems, and feel tired for at least six months. Lyme disease is transmitted to humans by the bite of infected ticks of the Ixodes genus. Usually, the tick must be attached for 36 to 48 hours before the bacteria can spread. In North America, Borrelia burgdorferi sensu stricto and Borrelia mayonii are the cause.In Europe and Asia, the bacteria Borrelia afzelii and Borrelia garinii are also causes of the disease. The disease does not appear to be transmissible between people, by other animals, or through food. Diagnosis is based upon a combination of symptoms, history of tick exposure, and possibly testing for specific antibodies in the blood. Blood tests are often negative in the early stages of the disease. Testing of individual ticks is not typically useful. Prevention includes efforts to prevent tick bites such as by wearing long pants and using DEET. Using pesticides to reduce tick numbers may also be effective. Ticks can be removed using tweezers. If the removed tick was full of blood, a single dose of doxycycline may be used to prevent development of infection, but is not generally recommended since development of infection is rare. If an infection develops, a number of antibiotics are effective, including doxycycline, amoxicillin, and cefuroxime. Treatment is usually for two or three weeks. Some people develop a fever and muscle and joint pains from treatment which may last for one or two days. In those who develop persistent symptoms, long-term antibiotic therapy has not been found to be useful. Lyme disease is the most common disease spread by ticks in the Northern Hemisphere. It is estimated to affect 300,000 people a year in the United States and 65,000 people a year in Europe. Infections are most common in the spring and early summer. Lyme disease was diagnosed as a separate condition for the first time in 1975 in Old Lyme, Connecticut. It was originally mistaken for juvenile rheumatoid arthritis. The bacterium involved was first described in 1981 by Willy Burgdorfer. Chronic symptoms are well described and are known as post-treatment Lyme disease syndrome, although it is often called chronic Lyme disease. Some healthcare providers claim that it is due to ongoing infection; however, this is not believed to be true. A previous vaccine is no longer available. Research is ongoing to develop new vaccines.

Signs and symptoms Lyme disease can affect multiple body systems and produce a broad range of symptoms. Not all patients with Lyme disease have all symptoms, and many of the symptoms are not specific to Lyme disease, but can occur with other diseases, as well. The incubation period from infection to the onset of symptoms is usually one to two weeks, but can be much shorter (days), or much longer (months to years). Symptoms most often occur from May to September, because the nymphal stage of the tick is responsible for most cases. Asymptomatic infection exists, but occurs in less than 7% of infected individuals in the United States. Asymptomatic infection may be much more common among those infected in Europe. Early localized infection Early localized infection can occur when the infection has not yet spread throughout the body. Only the site where the infection has first come into contact with the skin is affected. The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans (EM), which occurs at the site of the tick bite three to 32 days after the tick bite. The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated (is thicker and firmer), the outer edge remains red, and the portion in between clears, giving the appearance of a bull's eye. However, partial clearing is uncommon, and the bull's-eye pattern more often involves central redness. The EM rash associated with early infection is found in about 70-80% of people infected.It can have a range of appearances including the classic target bull's-eye lesion and nontarget appearing lesions. The 20-30% without the EM and the nontarget lesions can often cause misidentification of Lyme disease. Affected individuals can also experience flu-like symptoms, such as headache, muscle soreness, fever, and malaise. Lyme disease can progress to later stages even in people who do not develop a rash. Early disseminated infection Within days to weeks after the onset of local infection, the Borrelia bacteria may begin to spread through the bloodstream. EM may develop at sites across the body that bear no relation to the original tick bite.Another skin condition, apparently absent in North American patients, but found in Europe, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum.Various acute neurological problems, termed neuroborreliosis, appear in 10–15% of untreated patients. These include facial palsy, which is the loss of muscle tone on one or both sides of the face, as well as meningitis, which involves severe headaches, neck stiffness, and sensitivity to light. Inflammation of the spinal cord's nerve roots can cause shooting pains that may interfere with sleep, as well as abnormal skin sensations. Mild encephalitis may lead to memory loss, sleep disturbances, or mood changes. In addition, some case reports have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis. The disease may adversely impact the heart's electrical conduction system and can cause abnormal heart rhythms such as atrioventricular block. Late disseminated infection After several months, untreated or inadequately treated patients may go on to develop severe and chronic symptoms that affect many parts of the body, including the brain, nerves, eyes, joints, and heart. Many disabling symptoms can occur, including permanent impairment of motor or sensory function of the lower extremities in extreme cases. The associated nerve pain radiating out from the spine is termed Bannwarth syndrome, named after Alfred Bannwarth. The late disseminated stage is where the infection has fully spread throughout the body. Chronic neurologic symptoms occur in up to 5% of untreated patients. A polyneuropathy that involves shooting pains, numbness, and tingling in the hands or feet may develop. A neurologic syndrome called Lyme encephalopathy is associated with subtle cognitive difficulties, insomnia, a general sense of feeling unwell, and changes in personality. Other problems, however, such as depression and fibromyalgia, are no more common in people with Lyme disease than in the general population. Chronic encephalomyelitis, which may be progressive, can involve cognitive impairment, brain fog, migraines, balance issues, weakness in the legs, awkward gait, facial palsy, bladder problems, vertigo, and back pain. In rare cases, untreated Lyme disease may cause frank psychosis, which has been misdiagnosed as schizophrenia or bipolar disorder. Panic attacks and anxiety can occur; also, delusional behavior may be seen, including somatoform delusions, sometimes accompanied by a depersonalization or derealization syndrome, where the patients begin to feel detached from themselves or from reality. Lyme arthritis usually affects the knees. In a minority of patients, arthritis can occur in other joints, including the ankles, elbows, wrists, hips, and shoulders. Pain is often mild or moderate, usually with swelling at the involved joint. Baker's cysts may form and rupture. In some cases, joint erosion occurs. Acrodermatitis chronica atrophicans (ACA) is a chronic skin disorder observed primarily in Europe among the elderly. ACA 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 Lyme disease is caused by spirochetal bacteria from the genus Borrelia. Spirochetes are surrounded by peptidoglycan and flagella, along with an outer membrane similar to other Gram-negative bacteria. Because of their double-membrane envelope, Borrelia bacteria are often mistakenly described as Gram negative despite the considerable differences in their envelope components from Gram-negative bacteria.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 made up of 21 closely related species, but only three clearly cause Lyme disease: B. burgdorferi sensu stricto (predominant in North America, but also present in Europe), B. afzelii, and B. garinii (both predominant in Eurasia). Some studies have also proposed B. bissettii and B. valaisiana may sometimes infect humans, but these species do not seem to be important causes of disease. Further information: Weather and climate effects on Lyme disease exposure Transmission Lyme disease is classified as a zoonosis, as it is transmitted to humans from a natural reservoir among small mammals and birds by ticks that feed on both sets of hosts. Hard-bodied ticks of the genus Ixodes are the main vectors of Lyme disease (also the vector for Babesia). Most infections are caused by ticks in the nymphal stage, because they are very small and thus may feed for long periods of time undetected. Larval ticks are very rarely infected. Although deer are the preferred hosts of the adult stage of deer ticks, and tick populations are much lower in the absence of deer, ticks generally do not acquire Lyme disease spirochetes from deer. Rather, deer ticks acquire Borrelia microbes from infected small mammals and occasionally birds, including the white-footed mouse, Peromyscus leucopus. Within the tick midgut, the Borrelia's outer surface protein A (OspA) binds to the tick receptor for OspA, known as TROSPA. When the tick feeds, the Borrelia downregulates OspA and upregulates OspC, another surface protein. After the bacteria migrate from the midgut to the salivary glands, OspC binds to Salp15, a tick salivary protein that appears to have immunosuppressive effects that enhance infection. Successful infection of the mammalian host depends on bacterial expression of OspC. 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% of recognized tick bites resulting in Lyme disease. In Europe, the vector is Ixodes ricinus, which is also called the sheep tick or castor bean tick.In China, Ixodes persulcatus (the taiga tick) is probably the most important vector.In North America, the black-legged tick or deer tick (Ixodes scapularis) is the main vector on the East Coast. The lone star tick (Amblyomma americanum), which is found throughout the Southeastern United States as far west as Texas, is unlikely to transmit the Lyme disease spirochetes, though it may be implicated in a related syndrome called southern tick-associated rash illness, which resembles a mild form of Lyme disease. On the West Coast of the United States, the main vector is the western black-legged tick (Ixodes pacificus). The tendency of this tick species to feed predominantly on host species such as lizards that are resistant to Borrelia infection appears to diminish transmission of Lyme disease in the West. Transmission across the placenta during pregnancy has not been demonstrated, and no consistent pattern of teratogenicity or specific congenital Lyme borreliosis has been identified. As with a number of other spirochetal diseases, adverse pregnancy outcomes are possible with untreated infection; prompt treatment with antibiotics reduces or eliminates this risk. While Lyme spirochetes have been found in insects, as well as ticks,reports of actual infectious transmission appear to be rare. Lyme spirochete DNA has been found in semen and breast milk, but transmission has not been known to take place through sexual contact. According to the CDC, live spirochetes have not been found in breast milk, urine, or semen. However, more recent studies published in 2014, suggest a link might exist. Tick-borne coinfections Ticks that transmit B. burgdorferi to humans can also carry and transmit several other parasites, such as Theileria microti and Anaplasma phagocytophilum, which cause the diseases babesiosis and human granulocytic anaplasmosis (HGA), respectively. Among early Lyme disease patients, depending on their location, 2–12% will also have HGA and 2–40% will have babesiosis. Ticks in certain regions, including the lands along the eastern Baltic Sea, also transmit tick-borne encephalitis. Coinfections complicate Lyme symptoms, especially diagnosis and treatment. It is possible for a tick to carry and transmit one of the coinfections and not Borrelia, making diagnosis difficult and often elusive. The Centers for Disease Control and Prevention studied 100 ticks in rural New Jersey, and found 55% of the ticks were infected with at least one of the pathogens.

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