Lyme disease

from Wikipedia, the free encyclopedia
Classification according to ICD-10
A69.2 Lyme disease
Erythema chronicum migrans due to Borrelia burgdorferi
ICD-10 online (WHO version 2019)

The Lymeborreliose or Lyme disease is an infectious disease caused by the bacterium Borrelia burgdorferi related or Borrelia from the group of spirochetes is triggered. The disease, which runs in three stages, can affect different organs in different stages and characteristics, especially the skin, the nervous system and the joints . The third stage of the disease could be an autoimmune disease . Infection with Borrelia burgdorferi occurs in humans , various mammals and birds and usually occurs via a tick bite . The path of infection runs from a reservoir host via ticks such as the common wood tick (Ixodes ricinus) as a vector ( vector ), very rarely also through flying insects (horseflies, mosquitoes).

Discovery, naming and origin

The term Lyme disease consists of the name of the American town Lyme , where the disease was described in 1975 by increased incidence of joint inflammation associated with tick bites for the first time, and that after the French bacteriologist from the name of the exciting family Amédée Borrel named . The American bacteriologist Willy Burgdorfer succeeded in proving the newly discovered Borrelia species from ticks for the first time in 1981 and growing it in 1982. In his honor, this species was named Borrelia burgdorferi .

Pathogen

Borrelia

Borrelia are gram-negative spiral-shaped bacteria and belong to the spirochete family . They are anaerobes . The causative agents of Lyme borreliosis are the species Borrelia burgdorferi sensu stricto , B. garinii , B. afzelii and B. spielmanii .

In the USA Borrelia burgdorferi sensu stricto is common as a human pathogenic species; in Germany and other European countries the other types are more common, which is discussed as the cause of different manifestations in Europe and America. The term Borrelia burgdorferi sensu lato is used as a generic term for the pathogens that cause Lyme borreliosis . There are also other Borrelia species, such as B. recurrentis and B. hermsii , the causative agents of relapsing fever .

Biofilm

With the atomic force microscope , Eva Sapi was able to observe how the Borrelia form symmetrical structures within a few days and form a biofilm that consists of extracellular polymeric substances . It represents a considerable obstacle for the body's immune system and antibiotics. Among the pathogens there is a chemical communication called quorum sensing , which significantly contributes to the formation of biofilms.

Morphological changes

In vitro studies indicate that Borrelia are able to transform their original elongated shape into a spherical shape under stress . In addition, corresponding studies show that Borrelia can also occur in other form variants, which are summarized under the generic terms L-forms or spheroplasts . Sphaeroplasts have a deficient cell wall or are even without a cell wall (cystic). There are also indications that these forms can occur both intracellularly and extracellularly and are able to divide and develop back into complete forms despite their cell wallless form.

Generation time

The in vitro generation time of Borrelia is around half a day, more than ten times longer than that of most common bacteria. Their in vivo generation time is probably even longer.

Growth and metabolism

Their metabolism is microaerophilic , so they prefer to grow at an oxygen concentration that is significantly lower than that of normal air. Another peculiarity of this genus is that it works completely without iron and instead uses manganese as a cofactor for important enzymes .

statistics

distribution

Countries with reported cases

Lyme disease is the most common tick-borne disease in the northern hemisphere . In Germany there is a south-north divide when it comes to the contamination of the wooden ram. According to the Robert Koch Institute , around 6–35% of ticks in Germany are infected with Borrelia. After a tick bite, an infection occurs in 1.5–6% of cases. Disease occurs in 0.3–1.4% of cases.

There is a lack of comprehensive epidemiological studies and data on the spread and risk of infection as well as on the distribution of the respective genospecies. There are also still gaps in knowledge about the pathomechanisms and the long-term course of the disease. In contrast to the related syphilis , Borrelia recurrentis transmitted by lice and TBE , which is also transmitted by ticks, Lyme disease was not included in the Infection Protection Act. There is, however, a reporting requirement for Rhineland-Palatinate and Saarland, Bavaria as well as Berlin and the new federal states, which is regulated under state law . The case definitions of the Robert Koch Institute are used here as a basis, which requires a report of the early manifestations, i.e. H. of erythema chronicum migrans , early neuroborreliosis and Lyme arthritis. However, erythema migrans, a characteristic symptom of the first stage of the disease, only occurs in around 50% of new cases.

During the DNA sequencing of the 5300 year old glacier mummy Ötzi , traces of Borrelia burgdorferi were found. This is the oldest documented case of Lyme disease in human history and the first evidence ever in a no longer living individual. However, only a 60% match of the genetic material was found. There is also no information about which Borrelia species it is.

Infection risk and contamination rates

A Borrelia infection by ticks is - in contrast to the TBE caused by viruses  - possible throughout Germany and even in cities. As a study by the Robert Koch Institute in collaboration with the National Reference Center for Borrelia at the Max von Pettenkofer Institute for Hygiene and Microbiology in Munich showed, "direct contact with bushes in gardens, especially near the forest, represents a previously underestimated risk, to contract Lyme borreliosis through tick bites ”. Nevertheless, not every tick bite results in a Borrelia infection or even a disease of Borreliosis. In Germany, according to previous knowledge, a manifest disease is to be expected in 0.3–1.4% after a tick bite.

Lyme disease is the most common tick-borne disease in Europe. About 5-35% of the ticks are infected with Borrelia, with adult ticks being infected with an average of 20%, nymphs 10% and larvae only about 1%. Researchers go to high risk areas such as B. in parts of southern Germany , from 30 to 50% borrelia-infected ticks. In the Konstanz region on Lake Constance, the mean infection rate of ticks with Borrelia ( B. burgdorferi species) was 35%. In the English Garden and the Isar- Auen in Munich , around 30% of the ticks found were infected with Borrelia.

In Germany, most of the Borrelia treatment cases billed by statutory health insurance physicians occurred in Brandenburg, Saxony and Bavaria along the border with Poland and the Czech Republic, with Franconia and parts of the Palatinate being another focus. According to the bulletin of the Robert Koch Institute dated April 10, 2012, the data on the prevalence of Lyme borreliosis in the population is limited in many European countries because there are no national monitoring systems in place. This is partly due to the uncertain diagnosis of this disease and the associated misclassifications. In addition, monitoring data in this area is difficult to compare due to the different monitoring systems (voluntary and mandatory reporting, reporting of different manifestations of illness). In the East German federal states (Berlin, Brandenburg, Mecklenburg-Western Pomerania, Saxony, Saxony-Anhalt, Thuringia), erythema migrans, early neuroborreliosis and acute Lyme arthritis are notifiable manifestations as Lyme borreliosis. In 2009 the annual incidence in these federal states was 34.7 reported cases per 100,000 inhabitants. Results from two population-based prospective cohort studies in southern Germany showed annual incidences between 111 and 260 diseases per 100,000 inhabitants.

For Austria, incidences between 135 and 300 per 100,000 inhabitants are given. In Switzerland, depending on the region, 5 to 50% of ticks are infected with Borrelia, around 10,000 people develop Lyme disease every year.

The risk of infection after a tick bite was determined in a study at Heidelberg University : According to this, an average of 3.3% of all people bitten by ticks became infected. However, if you only consider the ticks infected with Borrelia burgdorferi , the risk of becoming infected is 25.6%. The infection rate of the ticks was 11%. With a higher infection rate, a higher risk of infection after a tick bite can be assumed.

According to the Robert Koch Institute, the following information can be found on the likelihood of illness after a tick bite (information for the whole of Germany, regardless of whether the ticks were infected or not):

  • According to previous knowledge, 1.5–6% of those affected by a tick bite can expect an infection (including clinically inapparent cases) in Germany.
  • a manifest disease, however, only in 0.3–1.4%.

Long-term clinical observations by Hassler show different results. He observed those patients who had a confirmed Borrelia infection and who became seropositive but were symptom-free (type “healthy forest worker”) the first occurrence of Borrelia-associated symptoms up to 8 years after their Borrelia infection.

There are no reliable figures on this. Based on the RKI figures, it can be assumed that 25 to 50% of people infected with Borrelia will also develop Lyme disease in the further course.

Unlike with the TBE virus  , a certain amount of time must pass before a tick bite can transmit Borrelia . The information about it varies between 6 and 48 hours. One thing is certain, however: the longer a tick infected with Borrelia has sucked, the higher the risk of transmission. However, some of the infections also result from improper removal of the tick when it is squeezed. Ticks should therefore be removed as quickly as possible using appropriate tools (see also in detail under tick bites ).

transmission

Ixodes ricinus - one of the main vectors of Borrelia

Carriers of the bacteria are usually ticks that the pathogen at the suction and tick bite after a few hours (usually within a time window of eight to twelve hours after the injection) to the people transferred. In Germany, the pathogens of the Borrelia-burgdorferi-sensu-lato complex are primarily transmitted by the tick Ixodes ricinus , also known as the common wood tick .

Mosquitoes are also discussed by scientists as a further carrier of Lyme disease , although previous studies have only found a very low level of mosquito contamination. In a study of more than 3,600 mosquitoes at 42 locations in Germany, pathogens were found in 0.13 to 8.33 percent of the mosquitoes examined. The tests were carried out for Borrelia afzelii, Borrelia bavariensis and Borrelia garinii.

Individual cases of transmission through braking have been documented, although broader studies have not yet confirmed whether these insects are actually a possible vector.

The tick larvae, known as nymphs , are barely visible to the naked eye. Since the nymphs fall off the skin after their mostly unnoticed meal of blood, in this case the stabbed does not know anything about a possible Lyme disease infection and only becomes aware when the symptoms appear.

There is a very small risk of the pathogen being transmitted from mother to child via the placenta during pregnancy . There is no reliable evidence of a disease in the uterus.

A person with Lyme disease is generally not contagious to other people.

diagnosis

The diagnosis of Lyme disease is based on two pillars. On the one hand, there is a characteristic clinical picture and a typical course. On the other hand, it is helpful to confirm the diagnosis through appropriate laboratory tests.

To date, there is no general medical-technical examination that can reliably prove or disprove an active disease. Therefore, the clinical picture and the course of the disease must always be examined and other causes must be excluded by differential diagnosis.

Among the clinical symptoms are considered krankheitsbeweisend only the eye rash and III. Stage the chronic skin inflammation akrodermatitis chronica atrophicans (ACA) . The number of unreported cases is high, however, and there is no reliable information about it, as wandering redness (erythema migrans) may not appear or it may have atypical manifestations ( neuroborreliosis ) . In a study at the Freiburg University Medical Center from 1990 to 2000, which included 86 cases of acute neuroborreliosis, only 23% of the patients reported wandering reddening. Erythema migrans either cannot occur or can be overlooked in areas of the body that are difficult to access.

In Borrelia serology, antibody tests are used in routine diagnostics. These are usually the ELISA and the Western Blot , also called immunoblot. Some laboratories also do an immunofluorescence test (IFT). Such tests can only measure the antibodies ; H. determine whether or not there has been an excitation contact. However, these procedures do not make it possible to determine whether the infection is acute or healed. It is therefore not possible, based on the serological results after treatment with antibiotics, to determine whether this was effective and whether the Lyme disease has now been cured. In addition, the individual test procedures are not standardized and have different specificities and sensitivities . With very sensitive tests there is often the problem of so - called cross - reactions . This means that the test shows a positive Borrelia result, but the person concerned does not have Lyme borreliosis ( positive predictive value , false positive ). False positive results can be caused, for example, by Borrelia species that are not pathogenic to humans and other spirochetes such as Treponema pallidum or Treponema denticola , Leptospira , but also by the Epstein-Barr virus or the cytomegalovirus . If very specific but not sufficiently sensitive tests are used, false negative results are possible ( negative predictive value , false negative ). In the early phase, as with other infectious diseases, there is also a diagnostic gap, as it takes some time for antibodies to form. The sensitivity is around 50% in the first few weeks. Newer tests should meanwhile show a somewhat higher reliability, which is indicated with a sensitivity of approx. 70 to 80%.

As a rule, a so-called two-stage test is carried out. First an ELISA test is used, which is considered to be more sensitive than a blot, but which can lead to cross-reactions or polyclonal antibody stimulation by other pathogens and can therefore be false-positive. A positive or borderline result is verified and confirmed by a more specific immuno or western blot.

Since no measurable antibody levels against Borrelia antigens are formed in the first few weeks after infection ( diagnostic gap ), if erythema migrans occurs, the result of a blood test - which is not very informative - should be started immediately, instead antibiotic therapy should be started immediately. In addition, inflammatory parameters such as BKS , CRP and other acute phase proteins can remain inconspicuous even in the case of florid Lyme disease that requires treatment .

In later stages, the sensitivity of the serological test methods (ELISA and immunoblot) is usually higher in immunosound people. In the second stage it should be around 70 to 90%. If there is a suspicion of a neuroborreliosis that is sometimes clinically unspecific, a CSF examination is usually indicated. This can be confirmed by detecting inflammatory CSF changes and by detecting a Borrelia-specific intrathecal antibody synthesis. However, this can lead to false negative results in about 30%. In the early stages of neuroborreliosis there is often no evidence of an infection with Borrelia. Even if only peripheral nerves are involved, the CSF diagnostics can be negative. The reliability of CSF diagnostics also depends on the experience of the laboratory, the criteria used for the evaluation, the reliability of the preparation and the diagnostic methods used. In Germany there are numerous Borrelia serologies with different antigen compositions on the market, which have a wide range in terms of sensitivity and specificity. It is therefore possible that negative results are obtained with one test and positive results with another. Borrelia serology is not required to be approved, nor is participation in round robin tests mandatory. Corresponding round robin tests are carried out by INSTAND .

The PCR -Proof is another method of diagnosis, disease Lyme can be established with the active. Here, DNA is processed from the test material and a Borrelia-specific fragment is copied ( amplified ) using the PCR reaction . This test has a different specificity depending on the body materials examined. Blood and urine are not suitable, as contamination can lead to false positive results. The sensitivity also depends on the body materials (liquor in neuroborreliosis around 20 to 30%, synovial fluid in Lyme arthritis and skin in dermatoborreliosis around 70%). If contamination and dead pathogens could be excluded here, a positive result from these materials is an indication of active borreliosis. A negative result does not rule out active Lyme disease. There are different PCR methods on the market that are of different quality.

The direct detection of Borrelia DNA from ticks using PCR is offered by various companies. The costs for the service not borne by the health insurance companies are between 10 and 100 euros, depending on the provider. Positive evidence in the tick does not mean that an infection has also taken place in humans. This test is not recommended by any specialist society as the sole proof of a Borrelia infection. Therapies that rely solely on this finding without symptoms and without positive serology are not indicated.

Differential diagnosis

Depending on the stage of the disease, the differential diagnosis is wide-ranging. It is advisable to rule out other tick-borne diseases ( TBE , anaplasmosis , rickettsioses) and other infections such as syphilis and leptospirosis .

Lyme borreliosis can, like syphilis , “imitate” a variety of diseases. In the case of neurological involvement, other causes should be considered, in particular an infection with neurotropic viruses and bacteria (which act on the nerves). Reliable differentiation from multiple sclerosis is important for neurological complaints , as treatment with immunosuppressive drugs is contraindicated in bacterial infections. In the case of joint inflammation, activated osteoarthritis , rheumatoid arthritis and other joint inflammations come into question for differential diagnosis. The occurrence of Lyme encephalopathy has so far been reported mainly from North America, but is considered a questionable manifestation of Lyme borreliosis in Europe. A differential diagnostic differentiation from chronic fatigue syndrome is difficult, since the symptoms listed in the catalog of criteria from 2011 also occur in Lyme disease. However, Lyme disease differs through recurrent or persistent muscle and joint pain, whereby the knee joint is noticeably often affected.

Other important differential diagnoses - especially in the case of unsuccessful therapy - are tumors and other systemic diseases.

Negative laboratory tests (ELISA, immunoblot) by no means rule out Lyme borreliosis, as they have a high error rate. A CSF examination is usually not very meaningful because the CSF is only inflamed in acute neuroborreliosis or even then it can be falsely normal.

If the condition and course of the disease are typical of Borreliosis, the suspected diagnosis of Lyme borreliosis should be considered when excluding other diseases, even if corresponding tests are negative. This is why the diagnosis of Lyme borreliosis is also considered a "diagnosis of exclusion" by some doctors.

Course of disease

Erythema migrans as a result of a tick bite with borreliosis infection on the lower leg of an adult male. The typical target-shaped pattern is easy to see.

After infection, antibodies against Borrelia burgdorferi can develop without symptoms of the disease at the same time. The immunoglobulins , both IgM and IgG, can be positive for years after Lyme disease has healed. A reliable diagnosis can often be made on the basis of the symptoms of the disease, the course of the disease, the medical history and the serological findings as well as careful collection of anamnestic data and the current psycho-social situation. If there is sufficient suspicion but the findings are unclear, antibiotic treatment is sometimes carried out on a trial basis. However, a response to antibiotics does not mean that Lyme disease is active, and conversely, a failure to respond does not mean that the disease is cured. In particular, the optimal late-stage antibiotic treatment is unclear and therefore controversial.

Typically, Lyme disease manifests itself as severe symptoms that get worse over the years. However, symptom-free latency times are possible. A disappearance of the symptoms does not therefore mean that the pathogens have been eliminated. In the early phase, the symptoms of Lyme disease are similar to a flu-like infection (without a cough or runny nose). Myalgia (muscle pain) and arthralgia (joint pain), which can be confused with fibromyalgia (chronic pain disorder), are common at this stage . Similar symptoms are sometimes described after antibiotic treatment. The most common misdiagnoses of Lyme disease are multiple sclerosis, fibromyalgia, and chronic fatigue syndrome . A careful differential diagnosis can usually avoid such misdiagnoses. The cause is often also seen in depression , psychosomatic illnesses or even hypochondria . It must be noted here that mental illnesses can only be diagnosed after all physical causes have been excluded.

After suffering from Lyme disease, there is no immunity .

Stages

Lyme disease has three stages. There are a number of symptoms that are typical of each stage. This can be accompanied by a variety of symptoms such as tiredness, headache, fever, stiff neck, visual problems, dizziness, nausea and vomiting.

1st stage (early stage): local infection

Erythema migrans can occur in atypical forms.

After the pathogen has been transmitted , a local infection of the skin can occur after an incubation period of mostly 5–29 days , which is accompanied by a characteristic rash , the erythema (chronicum) migrans (wandering reddening). A spot, a bright red ring or double ring, typically paler in the center than on the edge, spreads outwards from the tick's puncture site (hence the name). Wandering redness can itch or burn, but it can also occur without any discomfort. Predilection sites in adults are the armpit, groin and hollow of the knees, in children it is the head and neck. Furthermore, there may be a cutaneous lymphoid hyperplasia come.

In addition, general symptoms such as fever, headache and a general feeling of illness with aching limbs and fatigue can occur. The erythema migrans is a clear sign of an immune system response to Borrelia, but not one eye rash occurs in all cases of Lyme disease infections - from the absence of a tick bite, so it can not be concluded that no Lyme disease infection has occurred. The erythema sometimes disappears without therapy, but it can persist for months. A decrease in erythema migrans is no evidence of a cure, as the pathogen may have spread.

In the first stage, borreliosis can still be treated with antibiotics ( doxycycline or amoxicillin ). However, a sufficiently long and high enough dose of therapy is necessary.

2nd stage: Dissemination of the pathogen

After about 4 to 16 weeks, according to other sources after 20 to 59 days, the pathogens spread throughout the body. The incubation and latency period can also be longer. The patient then has flu-like symptoms such as fever and headache, which make it difficult to identify the disease. Strong sweats are characteristic. The spread in the body can affect the organs, joints and muscles as well as the central and peripheral nervous system. The main symptoms at this stage are often the Bannwarth syndrome with severe radiculitic pain and facial paralysis , which manifests itself in a paralysis of the facial muscles, usually the face looks "crooked" on one side. In addition, reactive benign hyperplasias of lymphoid cells appear, which are visible in the form of swellings, especially in the area of ​​the ear lobes and are referred to as lymphadenosis cutis benigna. Arthritis and myalgia jumping from joint to joint are also typical . Furthermore, it can lead to disturbances of the sense of touch , to visual disturbances and to heart problems such as sinus tachycardia and carditis , which is sometimes noticeable by palpitations and high blood pressure as well as increased pulse rate. At this stage, the immune system is often no longer able to cope with the infection. It is believed that Borrelia stay briefly in the bloodstream, but can also migrate into the connective tissue .

A problematic special case is the so-called neuroborreliosis , which can lead to a variety of diseases of the peripheral nerves and, in around 10% of diseases, also of the central nervous system . As a rule, it occurs in the early phase of the disease (up to about 10 weeks) when no antibodies have yet been formed. Therefore, sufficient antibiotics must be given at this stage. Diagnosis is made more difficult by the fact that often no intrathecally formed antibodies are found. Instead, an increased albumin and protein level in the CSF can be assumed. The choice of antibiotic depends on the infestation and the form of the disease. If Lyme borreliosis is not treated with enough antibiotics in time, the disease can progress and lead to permanent organ damage.

3rd stage: late stage (late manifestation) / post-treatment Lyme disease syndrome (PTLDS)

After several months, infected people who have not received or received insufficient treatment can develop severe and chronic symptoms. Latency periods that are symptom-free for months, but also for years, followed by a flare-up of the disease are possible. So that occurs acrodermatitis chronica atrophicans (ACA) to often take years. Chronic recurrent Lyme arthritis with a wide variety of clinical pictures can also occur, or the central and peripheral nervous system ( neuroborreliosis ) with polyneuropathy , Borrelia meningitis , Lyme encephalomyelitis or encephalitis . Chronic diseases of the sensory organs and the joints and muscles are also possible. The chronic diseases of the joints are called Lyme arthritis . But it can also lead to inflammatory bursitis . The different pathogens seem to trigger different clinical pictures: While in some patients almost only the joints are affected, others mainly have neurological disorders. Diseases of the sensory organs and the heart usually do not occur in isolation, but rather in connection with neuroborreliosis or Lyme arthritis. Mixed forms are possible.

Late-stage Lyme borreliosis, also known as chronic borreliosis, is defined as a disease and is precisely represented in the literature. Even if pathogens were found in the blood and serum after a four-week antibiotic treatment in animal experiments , their presence does not prove any persistent infection. The presence of the bacteria in the late stage, as in individual cases in those affected e.g. B. detectable by the PCR method, does not prove that these are also the cause of the late manifestation. It remains unclear whether the symptoms in stage 3 can be traced back to the pathogen, or whether permanent organ damage or an autoimmune process triggered by the infection (post- infectious autoimmune disease) are responsible.

therapy

Due to the possibility of multiple organ involvement, the treatment of Lyme borreliosis requires interdisciplinary cooperation between various specialist disciplines. The prognosis after early antibiotic treatment in the first stage is good. The 95% “inconsequential” healing of neuroborreliosis cited in some sources only relates to the proportion of patients with acute neuroborreliosis who were symptom-free after one year. In contrast, the proportion of chronic neuroborreliosis was only 66%.

Early stage

Since no reliable evidence of disease is possible in the early stages apart from the red wandering disease, if flu-like symptoms or joint pain occur shortly after a tick bite, the question of weighing up the risks and side effects of a suspected, possibly superfluous antibiotic therapy on the one hand and on the other hand - if it is not carried out , but also a conceivable failure of such a measure - the possible health, social and financial consequences of years or decades of chronic illness, which can lead to disability.

In the early stages of infection (localized infection, erythema migrans, regional lymphadenopathy), tetracyclines such as doxycycline are the drug of choice because of their ability to penetrate cells and their effectiveness against other pathogens also transmitted by tick bites . Also Amoxicillin can be used during the first stage. A corresponding therapy usually takes place over three to four weeks. Alternative antibiotics for those with relevant allergies are cefuroxime , clarithromycin and azithromycin .

It should also be taken into account that a Herxheimer reaction can occur during treatment with antibiotics. Corresponding studies show that this reaction occurs primarily during treatment with cephalosporins and penicillins, which belong to the beta-lactam antibiotics. So far, they are not seen very often in Lyme disease. It is important to make a differential diagnostic distinction between side effects of the respective antibiotic, e.g. B. a superinfection or allergy to penicillins and penicillin derivatives.

Late stage

Microbiological examinations indicate various difficulties in the antibiotic treatment of Lyme borreliosis in the late stage : the formation of cystic forms, the formation of a so-called biofilm, a colony of pathogens that is surrounded by extracellular polymeric substances that prevent antibiotics from penetrating, as well as the intracellular stay and the fact that a considerable proportion of the pathogens reside in the CNS . In this respect, it is questionable whether antibiotics can still achieve pathogen elimination in the late stage.

The form of administration and length of antibiotic therapy depends on the stage of the disease , but especially on the manifestation of the disease. Individual risk factors of the patient (such as an antibiotic allergy or renal insufficiency ) must be taken into account. The longer a Borrelia infection lasts, the more difficult it is to achieve a complete elimination of the pathogen. A distinction is made between extracellular (outside the body cells) and intracellular forms (in cells of the connective tissue, cartilage, adipose tissue and skin) of the pathogen. Laboratory tests have shown that the pathogen can switch between the two forms within hours. However, it has not yet been clarified whether these are reversible forms of the pathogen. There are basically various antibiotics available for therapy.

An extracellular antibiotic is ceftriaxone , which is given intravenously over 14 to 21 days at a dose of 2 g per day. In a meta-analysis of eight European studies with a total of 300 patients with definitive neuroborreliosis, there was no statistically significant difference in the success of treatment between oral doxycycline therapy compared to intravenous therapy with penicillin G or ceftriaxone. Therapy failures have been identified with all antibiotics and treatment regimens based on them. Antibiotic treatment according to the standard (IDSA, other guidelines of the AWMF) in the late stage has a failure rate of 50%. There is so far only little study material on antibiotic treatment of more than 14 to 30 days in patients with Lyme borreliosis; accordingly, longer antibiotic use in Lyme borreliosis has not been adequately researched in scientific studies. Long-term antibiosis can cause serious side effects. What all antibiotics have in common is that long-term use damages the microbiome irreversibly. Taking antibiotics for months or years can lead to severe intestinal infections, which can be life-threatening. Infection with the bacterium Clostridioides difficile is particularly feared . It occurs when competing species of the normal intestinal flora are suppressed by antibiotics, C. difficile can multiply unhindered and produce poisons (toxins). Due to the risk of side effects and the lack of scientific evidence for long-term antibiotic use, this form of treatment is advised against by the majority of medical professionals.

A placebo-controlled study from 2008 showed only a temporary improvement in Lyme encephalopathy after ten weeks of ceftriaxone treatment. It remained open, however, whether these improvements were due to a direct effect or to "positive side effects" of the antibiotic.

As stated in the recommendations of the German Society for Neurology on Neuroborreliosis, the optimal duration of treatment, especially with the intravenous antibiotics ceftriaxone and cefotaxime, is unclear. However, according to the company, a treatment duration of more than three weeks does not produce any additional effect. In the meantime, antibiotics other than cephalosporins are also used in advanced stages , including doxycycline ( tetracycline ), since the β-lactam antibiotics (such as ceftriaxone , cefotaxime ) are suspected of causing so-called cystic or cell-wall- less forms and in the case of intracellular persistence they are not effective . Doxycycline, however, also favored the biofilm formation of the pathogen in more recent in vitro studies. Some forms of treatment consist of a combination of intravenous and oral antibiotics. There is also the possibility of a combination therapy of two or more antibiotics.

It is questionable to what extent Lyme borreliosis is still curable in the late stage. At this stage, chronic neuroborreliosis (according to the guidelines) is treated with cephalosporin or doxycycline, Lyme arthritis and chronic acrodermatitis with doxycycline, amoxicillin or cefuroxime axetil. There is no scientific rationale for treating Lyme borreliosis with cholestyramine , nor are there any arguments from controlled studies. Such treatment is not recommended.

Guidelines

Medical guidelines exist as practical guidelines for doctors for the treatment of Lyme borreliosis . The guidelines of the "Infectious Diseases Society of America" ​​(IDSA guidelines) published in 2006 were drawn up in consensus with other major American specialist societies and, taking into account the current, so far still sparse study situation, provide recommendations for the diagnosis and treatment of this disease in the USA. The recommendations are largely based on expert opinion; There are no large-scale randomized studies on this topic with sufficient evidence. There is also another guideline of the International Lyme and Associated Diseases Society (ILADS guidelines), which has been listed in the American National Guideline Clearinghouse website since 2015 and is used in practice. In Germany, a number of large medical specialist societies have been working on the creation of a joint S3 guideline for some time. Completion is planned for the end of 2015. The S2k guidelines of the German Dermatological Society and the S3 guidelines of the German Society for Neurology for the treatment of neuroborreliosis are already available. Furthermore, the German Borreliose Society has created its own recommendation for all manifestations of Lyme disease. This was not developed within the framework of the AWMF . The recommendations for diagnostics and antibiotic treatment differ considerably from those of the AWMF specialist societies.

Criticism of the guidelines

The S3 level of the guideline of the German Society for Neurology has been criticized because there is insufficient evidence-based scientific literature on this topic.

The guideline coordinator of the German Society for Neurology Rauer is accused of having potential conflicts of interest.

controversy

In the late stage, symptoms can occur in addition to the main symptoms that do not regress even after antibiotic therapy ( post-treatment Lyme disease syndrome, PTLDS ). The symptoms consist of tiredness, exhaustion and muscle and joint pain. The cause has not yet been clarified. The fact that Borrelia is the cause of the symptoms in the late stage is controversial and is considered an unusual thesis, especially in conventional medicine. In particular, the high failure rate for antibiotic therapy in the late stage speaks against this thesis that there is an infectious event.

Post-infectious processes and organ damage due to a long-standing infection process are discussed as the cause of a non-effective antibiotic. Chronic complaints after a proven Lyme borreliosis are called chronic borreliosis or borreliosis in the late stage. The term “post-Lyme syndrome” is also common, which means that the symptoms of the disease are not causally triggered by Borrelia. It is discussed whether the late onset of Lyme borreliosis is an autoimmune disease that was originally triggered by an infectious event. The bacteria cause inflammations in the early stages, which become independent or become chronic through autoreactive processes and lead to more and more extensive complaints and damage.

A minority of doctors are in favor of therapy methods that also include long-term antibiotic therapy for months or years, but which, in the opinion of those in favor of the medical guidelines, have no evidence. In the United States, physicians and patients who agree and who advocate antibiotic therapy for periods longer than 14 days to four weeks have initiated legal proceedings against the authors of the IDSA's official Lyme disease guidelines. On May 1, 2008, Connecticut Attorney General Richard Blumenthal reviewed these IDSA guidelines. Conflicts of interest kept secret and violations of antitrust law were suspected. In order to counter the allegations, the IDSA ordered a re-examination of the guidelines by an independent medical panel. After a renewed examination of the current study and data situation, the validity of the IDSA guidelines 2010 was confirmed. In the USA, the International Lyme And Associated Diseases Society (ILADS) and in Germany the German Borreliose Society are proponents of long-term antibiotic treatment. Some medical professionals also carry out parenteral antibiotic treatments over many months or years.

In particular, warnings are given against serious side effects in long-term antibiotic therapies. Long-term antibiosis deaths are known in the United States.

Particularly controversial was the new S3 guideline of the German Society for Neurology (DGN), which was stopped at the beginning of 2018 by the participating German Borreliose Society (DGB) and patient organization Borreliose und FSME Bund Deutschland (BFBD) through an injunction. The DGN only wanted to include his dissent notices in the attached guideline report, while the two associations demanded that it be included in the guideline text. After the decision of the court, the injunction was lifted in March 2018 and the guideline was put into effect in its original form.

immunization

Active and passive immunizations are still not available for Europe, despite intensive research since the 1980s. In 1998 an effective recombinant vaccine based on OspA (outer membrane protein from Bbsl) was approved in the USA. The manufacturer GlaxoSmithKline took it off the market in 2002. For one thing, only around 10,000 people a year - and not 100,000 as hoped - were vaccinated. On the other hand, 170 cases of joint inflammation were reported that could have been triggered by the vaccine in people with a certain genetic predisposition. There were lawsuits against the manufacturer.

Because of the heterogeneity of the strains (at least 7 OspA serotypes), the development of an effective vaccine for Europe is difficult, according to the Robert Koch Institute in 2007. In veterinary medicine , however, a vaccination can also be carried out in Germany to protect dogs against Lyme borreliosis become. Since the antibody levels drop quickly again, an annual booster vaccination is necessary in order to achieve adequate protection against the borrelia strains it contains. A cross-immunity against other Borrelia species is not expected. However, the pathogenicity of most Borrelia species in dogs has not yet been fully clarified and vaccination is controversial due to possible serious side effects.

A vaccine approved for horses has been on the market since 2015.

Clinical studies on a human Lyme disease vaccine are currently (2014) being carried out.

literature

Monographs

  • Petra Hopf-Seidel: Sick after a tick bite. Recognize Lyme disease and treat it effectively. Knaur, Munich 2008. ISBN 978-3-426-87392-2 .
  • Hans Horst: Lyme disease tick borreliosis in humans and animals. Thieme, Stuttgart 2003, ISBN 3-934211-49-6 . 3-934211-49-6
  • H. Krauss, A. Weber, M. Appel, B. Enders, A. v. Graevenitz, HD Isenberg, HG Schiefer, W. Slenczka, H. Zahner: Zoonoses. Infectious diseases that can be transmitted from animal to human. 3. Edition. Deutscher Ärzte-Verlag, Cologne 2004, ISBN 3-7691-0406-4 .
  • Wolfgang Kristoferitsch: Neuropathies in Lyme borreliosis . Springer, Vienna 1989, ISBN 3-211-82108-2 .
  • Patrick Oschmann, Peter Kraiczy: Lyme borreliosis and early summer meningoencephalitis. Uni-med, Bremen 1998, ISBN 3-89599-408-1 .
  • Norbert Satz: Clinic of Lyme Borreliosis . Huber, Bern 2002, ISBN 3-456-83430-6 , new edition 2010, ISBN 978-3-456-84763-4 .

Essays

  • Brian Fallon: The Neuropsychiatric Manifestations of Lyme Disease . (PDF) Translation of the English version 1992
  • Hans-Peter Wirtz: Ticks as a disease carrier: what to do if you get a bite? In: Biology in Our Time. 2001, Vol. 31, No. 4, pp. 229-238.
  • Helge Kampen: vector-borne infectious diseases on the rise? How environmental changes pave the way for disease carriers and pathogens. In: Naturwissenschaftliche Rundschau. Year 2005, Vol. 58, No. 4, pp. 181-189.
  • H. Krauss et al. a .: Borrelioses ( Memento from December 27, 2013 in the Internet Archive ) (PDF; 6 pages) In: Zoonoses. Infectious diseases that can be transmitted from animal to human. 3. Edition. Deutscher Ärzteverlag, 2004.
  • Dieter Hassler: Phased therapy of Lyme borreliosis . ( Memento of September 28, 2007 in the Internet Archive ) (PDF; 6 pages) In: Chemother. J. Jg. 2006, Vol. 15, pp. 106-111.
  • R. Nau et al. a .: Lyme borreliosis - current state of knowledge . In: Dtsch Arztebl Int . No. 106 (5) , 2009, pp. 72–81 ( article , PDF ).
  • Marianne Abele-Horn: Antimicrobial Therapy. Decision support for the treatment and prophylaxis of infectious diseases. With the collaboration of Werner Heinz, Hartwig Klinker, Johann Schurz and August Stich, 2nd, revised and expanded edition. Peter Wiehl, Marburg 2009, ISBN 978-3-927219-14-4 , pp. 211-213 ( Lymne-Borreliose ).

Web links

Commons : Borreliosis  - collection of images, videos and audio files

Individual evidence

  1. ^ Guideline on neuroborreliosis of the German Society for Neurology . In: AWMF online (as of 2005)
  2. ↑ a b c Helmut Hahn: Medical microbiology and infectiology. Springer, Heidelberg 2009, ISBN 978-3-540-46359-7 , pp. 383-387.
  3. ↑ a b Thomas Meißner: Borreliosis: The underestimated syphilis from the forest. Doctors newspaper, accessed October 15, 2018 .
  4. ↑ VP Mursic u. a .: Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants. In: Infection. Volume 24, No. 3, 1996, pp. 218-226. PMID 8811359 .
  5. ↑ Joachim Gruber: Neuroborreliosis: Some Backgrounds for the Course of the Disease and Long Duration of Treatment. In: Lyme Disease Information . February 1, 2008, accessed July 29, 2014 .
  6. ↑ Preac Mursic V, Marget W, Busch U, Pleterski Rigler D, Hagl S: Kill kinetics of Borrelia burgdorferi and bacterial findings in relation to the treatment of Lyme borreliosis Infection 1996 Jan-Feb; 24 (1): 9-16
  7. ↑ Michael T. Madigan, John M. Martinko, Jack Parker: Brock Microbiology. German translation edited by Werner Goebel, 1st edition. Spektrum Akademischer Verlag GmbH, Heidelberg / Berlin 2000, ISBN 3-8274-0566-1 , pp. 349, 597-600, 971.
  8. ^ JE Posey, FC Gherardini: Lack of a role for iron in the Lyme disease pathogen . In: Science . Volume 288, No. 5471, June 2000, pp. 1651-1653. PMID 10834845 .
  9. ^ A b Heidrun Wothe: Lyme borreliosis can be acquired in gardens. Robert Koch Institute, press release from June 1, 2001 at the Informationsdienst Wissenschaft (idw-online.de), accessed on September 15, 2015.
  10. ^ Lyme borreliosis RKI guide for doctors
  11. ^ Infection Protection Act : Rhineland-Palatinate, Saarland
  12. ↑ Dr. Volker Fingerle Bavarian State Office for Health and Food Safety: Health: Lyme disease reporting obligation - Internet offer. Retrieved November 15, 2017 .
  13. ↑ Ötzi had Lyme disease and could not tolerate milk. In: oe24.at. Online edition February 28, 2012, accessed March 9, 2012.
  14. ↑ Hubert Filser: The risk patient from the ice. In: Süddeutsche Zeitung . online February 29, 2012, accessed March 9, 2012.
  15. ↑ a b c RKI guide for doctors on Lyme borreliosis
  16. ^ C. Rauter, R. Oehme, I. Diterich, M. Engele, T. Hartung: Distribution of Clinically Relevant Borrelia Genospecies in Ticks Assessed by a Novel, Single-Run, Real-Time PCR. In: J Clin Microbiol. 2002 January; 40 (1), pp. 36-43.
  17. ↑ a b c B. Wilske u. a .: Lyme borreliosis in southern Germany: Epidemiological data on the occurrence of cases of disease and the infection of ticks (Ixodes ricinus) with Borrelia burgdorferi.
  18. ↑ Thomas Kistemann: Regional distribution of Lyme borreliosis. (PDF; 350 kB) National Atlas of the Leibniz Institute for Regional Geography , April 20, 2012; accessed April 27, 2012; dynamic version (requires Adobe Flash ). The third accounting quarter (July to September) of the years 2007 to 2009 was considered.
  19. ↑ Epidemiological Bulletin , No. 14/2012. (PDF) RKI, April 10, 2012.
  20. ↑ R. Smith, J. Takkinen, Editorial team: borreliosis Lyme: Europe-wide coordinated surveillance and action needed? In: Eurosurveillance . 2006; 11 (25), p. 2977 (English); Retrieved April 27, 2012.
  21. ↑ E. Lindgren, T. Jaenson: Lyme borreliosis in Europe. (PDF; 1.1 MB) WHO Europe (English) accessed on April 27, 2012.
  22. ↑ Borreliosis / Lyme disease ( memento of the original from March 8, 2018 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , Information from the Federal Office of Public Health @1@ 2Template: Webachiv / IABot / www.bag.admin.ch
  23. ↑ a b O. March: Transmission risk of Borrelia burgdorferi after a tick bite: Follow-up study. (PDF)
  24. ↑ Dr. Petra Hopf-Seidel: The chronic-persistent borreliosis. (PDF) Retrieved October 15, 2018 .
  25. ↑ D. Kosik-Bogacka, K. Bukowska, W. Kužna-Grygiel: Detection of Borrelia burgdorferi sensu lato in mosquitoes (Culicidae) in recreational areas of the city of Szczecin . In: Ann Agric Environ Med . tape 9 , no. 1 , 2002, p. 55-57 , PMID 12088398 ( online [PDF]). Detection of Borrelia burgdorferi sensu lato in mosquitoes (Culicidae) in recreational areas of the city of Szczecin ( Memento of the original from June 8, 2007 in the Internet Archive ) Info: The archive link was automatically inserted and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice.  @1@ 2Template: Webachiv / IABot / www.aaem.pl
  26. ↑ DI Kosik-Bogacka, W. Kužna-Grygiel, K. Górnik: Borrelia burgdorferi sensu lato infection in mosquitoes from Szczecin area . In: Folia Biol. (Kraków) . tape 54 , no. 1-2 , 2006, pp. 55-59 , PMID 17044261 .
  27. ↑ Local mosquitoes could transmit Lyme disease. Der Spiegel Online, accessed on October 17, 2018 .
  28. ↑ SW Luger: Lyme disease transmitted by a biting fly . In: N. Engl. J. Med. Band 322 , no. June 24 , 1990, pp. 1752 , PMID 2342543 .
  29. ↑ a b R. Kaiser: Course of acute and chronic neuroborreliosis after treatment with ceftriaxone. In: Neurologist. 2004 Jun; 75 (6), pp. 553-557.
  30. ↑ Recommendations of the German Society for Neurology (DGN) for the diagnosis and treatment of neuroborreliosis (PDF; 180 kB).
  31. ↑ J. Evison et al .: Clarification and therapy of Lyme borreliosis in adults and children. (PDF) Recommendations of the Swiss Society for Infectious Diseases - Part 2: Clinic and Therapy. (No longer available online.) In: Schweizerische Ärztezeitung No. 42. 2005, pp. 2375–2384 , archived from the original on March 21, 2016 ; accessed on March 16, 2016 . Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.labor-spiez.ch
  32. ↑ zecken.de
  33. ↑ Tick bite what now? bfbd.de
  34. ↑ Lyme-Borreliose, AKH-Consilium ( Memento of the original of July 12, 2010 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / lyme-borreliose.universimed.com
  35. ↑ Epidemiological Bulletin 38
  36. ↑ a b Study Shows Evidence of Severe and Lingering Symptoms in Some after Treatment for Lyme Disease , website of the Johns Hopkins University of February 1, 2018 (English).
  37. ↑ Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis 1999; 180 (2): 377-83.
  38. ↑ Brorson O, Brorson SH. An in vitro study of the susceptibility of mobile and cystic forms of Borrelia burgdorferi to hydroxychloroquine. Int Microbiol 2002; 5 (1): 25-31
  39. ↑ Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol 1994; 21 (3): 454-61
  40. ↑ Ziska MH, ST Donta, Demarest FC. Physician preferences in the diagnosis and treatment of Lyme disease in the United States. Infection 1996; 24 (2): 182-6
  41. ↑ Cameron DJ. Clinical trials validate the severity of persistent Lyme disease symptoms. Med Hypotheses 2009; 72 (2): 153-6
  42. ↑ Petra Hopf-Seidel: Sick after a tick bite. Recognize Lyme disease and treat it effectively. Knaur, Munich 2008, pp. 184-257.
  43. ↑ Marianne Abele-Horn (2009), p. 212.
  44. ^ O. Brorson, SH Brorson: A rapid method for generating cystic forms of Borrelia burgdorferi, and their reversal to mobile spirochetes. In: APMIS. 1998 Dec; 106 (12), pp. 1131-1141. PMID 10052721
  45. ↑ JJ Halperin, ED Shapiro, E. Logigian et al. a .: Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology . In: Neurology . tape 69 , no. 1 , July 2007, p. 91-102 , doi : 10.1212 / 01.wnl.0000265517.66976.28 , PMID 17522387 .
  46. ↑ Steere AC. Lyme disease. N Engl J Med 1989; 321 (9): 586-96.
  47. ↑ Steere AC, Dhar A, Hernandez J et al. Systemic symptoms without erythema migrans as the presenting picture of early Lyme disease. On J Med 2003; 114 (1): 58-62
  48. ↑ Preac-Mursic V, Weber K, Pfister HW et al. Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection 1989; 17 (6): 355-9
  49. ↑ Gasser R, Reisinger E, Eber B et al. Cases of Lyme borreliosis resistant to conventional treatment: improved symptoms with cephalosporin plus specific beta-lactamase inhibition. Microb Drug Resist 1995; 1 (4): 341-4
  50. ↑ BA Fallon, JG Keilp, KM Corbera u. a .: A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy . In: Neurology . tape 70 , no. 13 , March 2008, p. 992-1003 , doi : 10.1212 / 01.WNL.0000284604.61160.2d , PMID 17928580 .
  51. ↑ Sapi E, Kaur N, Anyanwu S, Luecke DF, Datar A, Patel S, Rossi M, Stricker RB. Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infection and Drug Resistance. 2011; 4: 97-113
  52. ↑ Datar A, Kaur N, Patel S, Luecke DF, Sapi E. In Vitro Effectiveness of Samento and Banderol Herbal Extracts on the Different Morphological Forms of Borrelia Burgdorferi. Townsend Letter, The Examiner of Alternative Medicine. 2010
  53. ↑ Marianne Abele-Horn (2009), p. 212 f.
  54. ↑ IDSA guidelines
  55. ^ Treatment Guidelines for Lyme Disease from ILADS. Retrieved May 4, 2017 (American English).
  56. ↑ ILADS Treatment Guidelines Are Now Summarized on the National Guideline Clearinghouse website . ( ilads.org [accessed May 4, 2017]).
  57. ↑ Guideline Lyme Borreliosis . AWMF
  58. ↑ internet agency bonn cologne sunzinet typo3 and reddot programming: AWMF: Detail. Retrieved May 4, 2017 .
  59. ↑ internet agency bonn cologne sunzinet typo3 and reddot programming: AWMF: Detail. Retrieved October 18, 2018 .
  60. ↑ AWMF guideline: Neuroborreliosis
  61. ↑ DBG guideline: Lyme borreliosis (PDF; 534 kB)
  62. ↑ Guidelines for Diagnostics and Therapy in Neurology, Edition 5, September 2012: Declarations on Conflicts of Interest: Tabular summary. Retrieved October 22, 2018 .
  63. ^ GP Wormser, I. Schwartz: Antibiotic Treatment of Animals Infected with Borrelia burgdorferi. In: Clinical Microbiology Reviews. 22, 2009, p. 387, doi: 10.1128 / CMR.00004-09 . PMC 2708393 (free full text).
  64. ↑ Christiane Hawranek , Bayerischer Rundfunk: Months of antibiotic treatment: Borreliosis: Doctors warn of controversial therapies | BR.de . October 8, 2017 ( br.de [accessed September 10, 2019]).
  65. ↑ Attorney General's Investigation Reveals Flawed Lyme Disease Guideline Process, IDSA Agrees To Reassess Guidelines, Install Independent Arbiter . ct.gov
  66. ↑ Stephen Singer: No changes to Lyme disease treatment . NBC News, April 22, 2010.
  67. ↑ Doctors newspaper: Landgericht Berlin: preliminary injunction stops new guideline. Retrieved October 18, 2018 .
  68. ↑ Doctors newspaper: DGN may publish: Applications against Lyme disease guidelines rejected. Retrieved October 18, 2018 .
  69. ↑ www.uni-heidelberg.de/uni/presse/RuCa3_97/kramer.htm: Vaccines against tick-bite borreliosis
  70. ↑ Lyme disease vaccine withdrawn from the US market. Die Welt , May 3, 2002, archived from the original on April 5, 2015 ; accessed on September 7, 2017 .
  71. ↑ Lyme disease in dogs
  72. ↑ Paul Ehrlich Institute Federal Institute for Vaccines and Biomedical Medicines - Announcement No. 407 on the approval of vaccines and biomedical medicinal products and other official acts of March 8th - Granting of approval in accordance with Section 23 of the TierImpfStV
  73. ^ Design and Development of a Novel Vaccine for Protection against Lyme Borreliosis . 19th November 2014.
  74. ↑ Table of Contents.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Toter Link / images.buch.de