What ticks do to the human immune system
- Thread starter ackleyman
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Uncle_Steve
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Good read, I need to follow up on this with my Dr.
That is a good read, Keith, thanks for sharing.
Quote:Most tick species feed only once during each stage of their life cycle (larva, nymph, adult), so they have to get a “voluminous blood meal” out of each host, says Sarah Bonnet, who studies ticks at the French National Institute for Agricultural Research. A tick might even wait years between feedings. In the meantime, it must subsist entirely on its previous blood meal. Each meal counts for a lot.
That must only apply to French ticks! These d*** south Texas ticks sure don't ever miss a meal. Thank the Lord for permethrin.
Regards,
hm
Quote:Most tick species feed only once during each stage of their life cycle (larva, nymph, adult), so they have to get a “voluminous blood meal” out of each host, says Sarah Bonnet, who studies ticks at the French National Institute for Agricultural Research. A tick might even wait years between feedings. In the meantime, it must subsist entirely on its previous blood meal. Each meal counts for a lot.
That must only apply to French ticks! These d*** south Texas ticks sure don't ever miss a meal. Thank the Lord for permethrin.
Regards,
hm
The last paper I wrote to finish up my Nurse Practioner Degree was concerning the Lymes disease and it's effects on the central nervous system. This is a portion some may find interesting, I. Read it at your own risk if you fall asleep, sorry. Randy
Lyme Neuroborreliosis in the Adult Population
Definition of Lyme Neuroborreliosis
Lyme neuroborreliosis is a disorder of the nervous system, which occurs after being bitten by a tick infected with spirochete Borrelia burgdorferi and subsequent migration of the bacteria in the peripheral and central nervous systems (Dersch et al., 2015).
Introduction
In 1975, the first recognized outbreak of this Lyme disease (LD) occurred in Lyme, Old Lyme, and Haddam in the state of Connecticut (Wright, 2016). It initially was recognized clinically as “Lyme arthritis”. Lyme disease is spirochaetal infection precipitated by the three pathogenic species of the Borrelia bacteria, which is transmitted through the bite of an infected tick (National Institute of Allergy and Infectious Diseases [NIAHD], n. d.; Wright, 2016). Numerous species of mammals are used as vectors for the tick borne illness, with rodents and deer acting as the primary reservoirs. The ticks then transmit the bacteria to a human host through their infected saliva. The spread of the disease has accelerated and since the mid-1980s, and the disease is now reported in rural areas of Eurasia (Center for Disease Control and Prevention [CDC], n.d.). It is currently the most common tick-borne disease in the Northern Hemisphere.
Lyme borreliosis is a multi-system inflammatory disease where it affects several organ systems, including the skin, joints, and the nervous system. Lyme disease precipitates numerous signs and symptoms for those who are infected including fever, facial palsies, chills, headache, fatigue, muscle, and joint pain (Dersch, Toews, Sommer, Rauer, & Meerpohl, 2015). Erythema migrans (EM) is a rash often appearing at the site of the tick bite and gradually expands to a ring with a central clear zone, before spreading to other parts of the body. If left untreated, infection can spread to the peripheral nervous system (PNS) and the nervous system (CNS) (CDC, n.d.).
A patient develops Lyme neuroborreliosis (LNB) when the bacteria, B. burgdorferi, transitions through the blood-brain barrier (BBB) and damages the peripheral nervous system (PNS) and the central nervous system (CNS) (Rupprecht & Fingerle, 2011). Neuroborreliosis can evolve within one to four weeks after initial infection, and can lead to nervous system dysfunction if left untreated. The spirochetes infect the neuronal cells by damaging the myelin sheaths, thus diminishing the ability of the action potential of one neuron to another (Rupprecht & Fingerle, 2011). Neuroimaging has shown that Lyme neuroborreliosis is similar to many neurodegenerative diseases such as myelitis, meningitis, and encephalitis (Rupprecht & Fingerle, 2011). These diseases are detrimental because they can undermine the motor system and cognitive ability of patients.
There is much confusion and controversy surrounding nervous system Lyme disease known as Lyme neuroborreliosis (LNB). This is due to misunderstandings about what does, and does not constitute evidence of nervous system infection. It includes three other entities often under the same nomenclature. These disorders are actually neurobiological but not truly neurologic; they include Lyme encephalopathy, posttreatment Lyme disease syndrome (PTLDS), and chronic Lyme disease (CLD) (Halperin, 2015). These disorders have no correlation to active CNS infection and have many nonspecific symptoms, including headache, fatigue, cognitive slowing, and memory difficulty associated with Lyme disease infection. However, these symptoms are not indicative of nervous system contamination and are common in many other infectious and inflammatory states.
Lyme neuroborreliosis is similar to neurosyphilis, nervous system involvement starts during the early disseminated phase of Lyme’s disease, when the spread of spirochetes results in meningeal seeding, where it may subside or become chronic (Hildenbrand, Craven, Jones, & Nemeskal, 2009). Just as in syphilis, appropriate antimicrobial agents result in a microbiologic cure, representing a true spirochaetal invasion regardless of the duration of the infection (Hildenbrand et al., 2009). Lyme encephalopathy, PTLDS, and CLD do not demonstrate active infection and therefore, will not be discussed. The focus of this paper is to discuss Lyme neuroborreliosis (LNB), the acute invasion of the nervous system by spirochaetal bacteria associated with LD.
In the city of New York, a recent study was conducted, which compared numerous diseases and their relation to poverty. According to Greene, Levin-Rector, Hadler, and Fine (2015), diseases like hepatitis C, are most prevalent in areas with endemic property and domestic zoonotic or vector-borne diseases such as LD, were higher in neighborhoods with low poverty (p. 30). It must also be considered that many people who become infected with LD, often do so in the pursuit of hobbies and extracurricular activities, which take place in rural or heavily wooded areas, away from the inner-city.
Epidemiology
Tick-borne diseases, such as Lyme disease, are rapidly evolving in the United States, due in part to climate change (Hildenbrand, Craven, Jones, & Nemeskal, 2009). Lyme disease is the most documented vector borne illness and the seventh most common reportable infectious disease, with cases increasing roughly 200% in the last 20 years (Adrion, Aucott, Lemke, & Wiener, 2015). In the U.S., there are between 240,000 to 440,000 of reported cases of Lyme disease (LD), resulting in a national incidence of 9.7 cases per 100,000 population (Hildenbrand, Craven, Jones, & Nemeskal, 2009). In 2013, state health departments reported 27,203 confirmed cases and 9,104 probable cases of Lyme disease (National Institute of Allergy and Infectious Diseases [NIAHD], n.d.). In Europe, cases are increasing as well, and in the United Kingdom (UK), the incidence is increasing with as many as 1,000 laboratory cases confirmed per annum (Pearson, 2015).
In the US, reported cases of LD are most common among boys between the ages of five and nine years old (CDC, n.d.). Lyme disease is more prevalent in males up to the age of 65, and more common in females between 70 to 90 years of age (CDC, n.d.). The majority of individuals infected with LD are most likely to have the onset of illness in the months of June, July, or August and less likely to have the illness onset from the months of December through March (CDC, n.d.). Clinical manifestations often include EM, but infections without EM are more often seen than in earlier years. The lack of extracutaneous symptoms eventually leads to cases, which are under diagnosed and therefore, under treated causing an increase incidence of LNB (Wormser et al., 2006).
Etiology
In America, the most commonly seen bacterium is Borrelia burgdorferi sensu stricto, although a second genospecies, B. mayonii was recently found to cause illness in the upper Midwestern United States (Mead, n.d.). In Eurasia, there are three bacteria that are known to cause illness; they include B. burgdorferi, B. garinii, and B. afzelii (Hildenbrand, Craven, Jones, & Nemeskal, 2009).
Lyme disease is transmitted by a number of Ixodes ticks, which vary by geography. The tick responsible in the northeastern and upper Midwestern states is the Ixodes scapularis and along the Pacific coast of the United States, particularly northern California, the culprit is often I. pacificus (CDC, 2015).
Over that span of two years, the Ixodes ticks go through three living stages, which include the six-legged larva, the-eight legged-nymph, and the dimorphic eight -legged it adult tick (CDC, n.d.). The larvae, the nymphs, and mature females require a blood meal from a vertebrate; it is this feeding that is the mechanism through which the bacteria are transferred. The adult male ticks are not known to transmit Lyme’s disease (CDC, n.d.).
The larvae hatch in the forest floor in early summer and searching for a blood meal which is small mammals, such as rodents. The larvae are not infected upon hatching, but acquire the bacteria during its first blood meal from the rodents, which often remains healthy despite being infected (CDC, n.d.). Once fed, the tick drops off the infected host; it molts and reemerges the next spring as an infected nymph.
It is during the nymph stage that the second blood meal transmits the bacteria to a new rodent, allowing the organism to spread to future generations, and complete the horizontal cycle of transmission (Wormser et al., 2006). This is the stage when LD is commonly transferred to humans. After the tick is fully engorged, the tick again drops from the host and in the fall molts to become an adult (CDC, n.d.)
When the adult emerges, it once again seeks a blood meal from their preferred host the white-tailed deer, but may also attach to coyotes, fox, raccoons, or even humans (CDC, n.d.). In the fall and early winter, after feeding, the female tick plunges upon the floor but does not lay eggs until the next spring, finishing the two-year life cycle.
B. burgdorferi is transferred through the saliva of infected ticks, and requires at least 24 to be 48-hour tick engorgement (CDC, 2015). The primary vector for the transmission to humans is the nymphal stage of the Ixodes tick. The nymphal stage is more effective at transmitting B. burgdorferi, in part due to their small size, which is often less than two millimeters and allows them to feed from their host undetected (Wormser et al., 2006). When compared to the nymphal tick the adult female is much larger and is sometimes removed before transmission can occur (Wormser et al., 2006).
Pathophysiology
The infection begins in the skin at the site of the bite, where after three to 32 days, the organisms migrate locally in the skin around the bite. The bacteria have an axial filament composed of flagella which run lengthways between its cell wall and outer membrane which allows the spirochete to move through tissue using corkscrew movement (Rupprecht & Fingerle, 2011). The spirochetes spread via the lymphatic system to cause regional adenopathy or disseminate in blood to numerous body systems, including the nervous system (Rupprecht & Fingerle, 2011).
The bacteria are adept at evading the host immune system and are able to up- and down-regulate their own antigens making it difficult for the immune system to detect (Wormser et al., 2006). The process that uses to accomplish this is to alter its own genome. The spirochetes are then able to alter the antigens on its own exterior shell so the host immune system can no longer recognize them as foreign allowing them to escape antibody mediated killing (Rupprecht & Fingerle, 2011). B. burgdorferi does not release endotoxins. The damage is caused when the spirochetes release the modified antigen which in turn causes an autoimmune reaction. It is this response by the body which causes damage to the surrounding tissue resulting in the symptoms associated with Lyme’s disease (Wormser et al., 2006).
It has also been suggested that there may be regional differences in the Borrelia species. In North America, the spirochete have been found to disseminate predominantly via the blood, while in Europe, they appear to prefer a migration along the other structures such as peripheral nerves directly to the nerve roots (Rupprecht & Fingerle, 2011). It has been suggested that this different mode of invasion may be responsible for the different clinical picture of LNB in North America when compared to Europe (Rupprecht & Fingerle, 2011). The presentation in Europe predominates with meningopolyradiculitis or Bannwarth syndrome, with the majority of pain close to this site of the tick bite (Rupprecht & Fingerle, 2011). This is in stark contrast to the presentation of LNB in North America, which is often more diffused with mostly meningitis or encephalopathy (Rupprecht & Fingerle, 2011).
Inflammatory reaction of the nervous system.
Once inside the nervous system the spirochetes induce an inflammatory reaction, presenting as Lymphocytic pleocytosis (Rupprecht & Fingerle, 2011). This is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF), which is considered to be an immuno privilege site, because there are only a few of immune cells to be found (Rupprecht & Fingerle, 2011). While a CSF does have a low population of dendritic and monocytic cells, which are responsible for immune surveillance, their numbers are very low when compared with those in systemic circulation (Rupprecht & Fingerle, 2011). Regrettably, neutrophils and components of the complement system are only rarely found, so the bacteria have crossed the blood-brain-barrier (BBB), the nervous system is virtually defenseless (Rupprecht & Fingerle, 2011).
B. burgdorferi inside the CSF are encountered by microglial cells, perivascular cells, and dendritic cells with toll like receptors (TLRs) which play an important role in the recognition of the invading bacteria (Rupprecht & Fingerle, 2011). The activation of the TLRs have an essential role in the control of B. burgdorferi. The TLR engagement results from nuclear translocation which in turn, induces the production bacteriocidal nitric oxide and superoxide, as well as the production and release of cytokines and chemokines (Rupprecht & Fingerle, 2011). Immune cells including B cells, from the systemic circulation are then attracted by the chemokines. The B cells mature into plasma cells, which in turn produce B. burgdorferi antibodies that can eventually destroy the invading spirochetes (Rupprecht & Fingerle, 2011). It is this response by the immune system which leads to the CSF pleocytosis.
The pathogenesis of Lyme neuroborreliosis is still a mystery. There are four mechanisms, which may be responsible for neuronal dysfunction produced by B. burgdorferi. They include the direct cytotoxic effect of the bacteria; secretion and release of cytotoxic mediators; host inflammatory reaction; and autoimmunity through molecular mimicry (Rupprecht & Fingerle, 2011). These mechanisms have been observed in animal studies but as of yet have not been confirmed in human subjects.
Review of Literature
The search engines utilized for this research paper included PubMed, CINAHL, Science Direct, Medline, EBSCO, and Cochrane library. The websites that were used in this study included the Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases (NIAID), European Centre for Disease Prevention and Control (ECDC), and the Infectious Disease Society of America (IDSA). Key terms used included “Lyme disease”, “neuroborreliosis “Lyme neuroborreliosis”, “Psycho-neurogenic effects of Lyme disease”, “Neuroborreliosis management”, and “treatment guidelines for neuroborreliosis”. The articles reviewed included topics, but not limited, on etiology, epidemiology, pathophysiology, social determinants, and treatment guidelines of Lyme disease and neuroborreliosis. The articles included in the review were peer reviewed and evidence based.
Stages of Lyme Disease
Clinical manifestations of Lyme disease vary greatly depending on the stage of disease and which body system is being effected. The most common clinical manifestation of Lyme disease is the erythema migrans (EM) rash, which accounts for up to 71% of confirmed cases (CDC, n.d.). The second most common manifestation of LD is myalgia and arthralgia manifestations accounting for 30% of reported symptoms (CDC, n.d.). The cardiac system symptoms of heart block and pericarditis are the least reported manifestations, accounting for only 1% of cases (CDC, n.d.). The remaining 15% of manifestations affect the central nervous system (CNS), which is the most frequent destination of dissemination, resulting Lyme neuroborreliosis (Rupprecht & Fingerle, 2011).
Early localized disease.
Early localized disease occurs within a few days to one month after the tick bite, with EM being the most prevalent sign. Associated signs and symptoms at this stage may include fatigue, malaise, lethargy, mild headache, mild neck stiffness, myalgias, arthralgias, and regional lymphedema neuropathy (CDC, 2015).
Disseminated disease.
Early disseminated disease occurs weeks to months after the tick bite and may elicit multi-system manifestations. Patients may present with cardiac manifestations such as AV normal block, mild cardiomyopathy, or mild pericarditis (CDC, 2015). Individuals may complain of musculoskeletal symptoms such as migratory arthralgias and myalgias (CDC, 2015). The bacteria can invade the liver causing inflammation and liver function test abnormalities as well as the kidneys with associated micro hematuria and a symptomatic proteinuria (CDC, 2015). The eyes may also become involved with associated conjunctivitis, iritis, choroiditis, vitritis, and retinitis (CDC, 2015). The patient may present with multiple EM lesions as well as regional or generalized lymphadenopathy (CDC, 2015). By definition, nervous system involvement only occurs in disseminated LD and it is during this stage is when neurologic manifestations occur.
Late or chronic disease.
Late or chronic disease often occurs months to years after the tick bite. Approximately 60% of untreated patients developed intermittent arthritis that may involve single or multiple joints, but usually involves the knees (CDC, 2015). Cutaneous involvement may also persist at this stage with acrodermatitis chronica atrophicans, and localized scleroderma like lesions (CDC, 2015).
Nervous system manifestation
Nervous system manifestations include cranial neuropathy which is most often facial and can be bilateral, peripheral neuropathy, lymphocytic meningitis, and rarely myelitis or encephalitis (CDC, 2015). Cranial neuropathy and radiculoneuritis are part of the classic triad of Bannwarth’s syndrome which includes cranial neuropathy, radiculoneuritis, and meningitis (Hildenbrand et al., 2009).
Cranial neuropathies associated with LD tend to occur early in infection and are usually have an abrupt onset. Virtually any cranial nerve can be involved, but the seventh cranial nerve, the facial nerve, is by far the most common (Hildenbrand et al., 2009). Occasionally the cranial neuropathy occurs before the patient has become seropositive, and in such patients a follow-up titer in several weeks is typically diagnostic. During spring and into fall, in areas known to have high levels of LD, adults who present with bilateral facial nerve palsies should be considered candidates for Lyme disease testing.
Another common manifestation of Lyme disease in the peripheral nervous system is radiculoneuritis. This disorder can mirror a mechanical radiculopathy with pain in one or several dermatomes accompanied by corresponding sensory, motor, and reflex changes (Hildenbrand et al., 2009). This dysfunction should be considered in patients with severe limb or truncal pain without an associated mechanical component (Hildenbrand et al., 2009).
Central nervous system involvement in Lyme disease can take several forms with meningitis, Lyme encephalomyelitis, and encephalopathy being the most common. Lymphocytic meningitis is the most common form of CNS involvement and often times presents either alone or in conjunction with cranial nerve or spinal nerve root involvement (Halperin, 2015). Patients presenting with lymphocytic meningitis of Lyme disease may complain of headache, fever, photosensitivity, as well as neck stiffness (Halperin, 2015). This disorder can be differentiated from viral meningitis by its slower onset, the presence of cranial neuropathy, and the presence of mononuclear cells in the CSF (Halperin, 2015).
Occasionally, patients with Lyme encephalomyelitis (LE) will complain of radicular symptoms and will have segmental spinal cord involvement at the same level as the effective nerve root (Halperin, 2015). This disorder represents a true infection of the neuraxis. Patients may present with inflammatory appearing parenchymal abnormalities on the brain or spinal cord which superficially resemble multiple sclerosis (MS). Although LE is highly responsive to appropriate antibiotics there may be neurologic impairment caused by injury that occurred prior to treatment (Halperin, 2015).
Encephalopathy is a term that is often used to indicate alterations in brain function due to non-neurologic causes. Some patients with Lyme disease described fatigue, cognitive slowing, and memory difficulty although these symptoms are not specific of Lyme’s disease and are often associated with many inflammatory disorders (Halperin, 2015). These symptoms are not considered evidence of CNS infection with B. burgdorferi which must be confirmed through cerebral spinal fluid abnormalities and MRI findings (Halperin, 2015).
Psychosocial Impacts of Lyme Neuroborreliosis
Lyme neuroborreliosis can have dramatic psychological and social implications for those who are infected. Social isolation may be a byproduct of LNB due to inability to ambulate or perform activities of daily living (ADLs) (Watson, 2015). In such instances, individuals may lose their independence and must rely on others to meet their most basic needs until their symptoms improve. In some individuals LNB, they may become despondent and frustrated with prolonged and lingering symptoms, which may lead to loss of employment, financial difficulties, and a decline in their lifestyles (Garakani & Mitton, 2015).
In a study conducted by Ali, Vitulano, Lee, Weiss, and Colson (2014), they found participants had perceived negative experiences within the healthcare system, with reports of dismissive, patronizing, and condescending attitudes of providers (Ali et al., 2014). The study showed many of the participants sought out alternative medicine (CAM) practitioners in order to find and empathetic clinician. This highlights the fact those afflicted with LNB are not just dealing with a physical condition but also must endure the psychological and social impacts as well.
Management
Pharmacological
Prophylaxis treatment of Lyme disease is not recommended except under extenuating circumstances. The strongest indication of prophylactic antibiotic use is when an I. scapularis tick from a highly endemic area is partially engorged or attached for longer than 36 hours or when the duration of tick attachment or degree of engorgement is uncertain (Journal of the American Medical Association [JAMA], 2016). In the situation a single dose of 200 mg of doxycycline by mouth coupled with observation for signs and symptoms of LD (JAMA, 2016).
In patients with early Lyme disease who present with EM treatment with oral doxycycline 100 mg by mouth for 10 days shortens the duration of skin lesions and generally prevents development of late sequelae (JAMA, 2016). Doxycycline should not be used in children less than eight years of age or for pregnant or lactating women amoxicillin 500 mg by mouth twice a day for 14 days, cefuroxime axetil 500 mg by mouth twice a day for 14 days, or azithromycin 500 mg by mouth once a day for 7 to 10 days (JAMA, 2016).
For patients presenting with facial nerve palsy oral doxycycline has been shown to be effective with the course of 100 mg by mouth twice a day for 14 days (JAMA, 2016). Individuals presenting with another neurologic involvement, such as meningitis, other cranial nerve palsy’s, radiculopathy, or cognitive deficits should be prescribed 2 g of IV ceftriaxone every 24 hours for 14 days (JAMA, 2016).
For individuals with other systemic manifestations of LD such as cardiac disease or arthritis for antibiotics have shown efficacy they include doxycycline, amoxicillin, cefuroxime axetil (JAMA, 2016). These antibiotic should be prescribed as follows Doxycycline 100 mg by mouth twice a day for 14 days, amoxicillin or cefuroxime axetil 500 mg by mouth three times a day for 14 to 21 days, or IV ceftriaxone 2 g every 24 hours for 14 days (JAMA, 2016). Intravenous ceftriaxone is often used for manifestations that are more serious, persistent, or recurrent (JAMA, 2016).
Non-pharmacological
Nonpharmacologic management of patients with Lyme disease revolves around treatment and observation. Patients on ceftriaxone or cefotaxime should be monitored with weekly CBCs to monitor for leukopenia which can be seen with these antibiotics (JAMA, 2016). Use of ceftriaxone may lead to biliary sludging, which can be monitored with weekly hepatic panels to look for elevated hyperbilirubinemia in which case the patient should be switched to cefotaxime (Rupprecht & Fingerle, 2011). Doxycycline may cause photosensitivity while amoxicillin and cefuroxime are known to cause drug rashes (Rupprecht & Fingerle, 2011).
Follow-up and Referral
Individuals infected with Lyme disease may require weekly appointments before and after a diagnosis is made. For LNB patients like Greg, they may have to spend much of their time treating this disease. They may receive IV antibiotics, give blood for various lab studies, and be examined for lingering symptoms. Some patients infected with Lyme disease may experience manifestations that persist despite primary care management, and may require a referral to infectious disease specialists (Rupprecht & Fingerle, 2011).
Education
The current method that is most effective at averting Lyme disease is prevention through education. Individuals like Greg, who like to spend much of their time outdoors, should be taught prevention techniques. The use of protective clothing when they are outside especially in wooded areas is one such commonsense technique. One should wear a Long-sleeved shirt which should then be tucked into pants. The long pants are then tucked into socks effectively creating a barrier which interferes with tick attachment by increasing the time required for ticks to find exposed skin. Clothes should be light-colored, which provides a background which will contrast the tick, facilitating removal.
Tick and insect repellents containing diethyltoluamide (DEET) applied to the skin or clothing provide additional protection but may require reapplication for increased effectiveness (Wormser et al., 2006). Ticks detect DEET through olfactory sensing and are thus repelled. The repellents should not be applied to the face or head or skin that is irritated or braided. After returning indoors the skin should be washed with soap and water to remove the repellents.
Frequent visual inspection is another method, which may help identify text prior to attachment and in turn allowing removal before infection can be transmitted. The proper removal of ticks should be done preferably with the aid of tweezers or fine forceps. The attached tick should be removed promptly and if a portion of the mouth of the tick remains embedded in the skin only topical disinfection of the site is suggested.
Lyme Neuroborreliosis in the Adult Population
Definition of Lyme Neuroborreliosis
Lyme neuroborreliosis is a disorder of the nervous system, which occurs after being bitten by a tick infected with spirochete Borrelia burgdorferi and subsequent migration of the bacteria in the peripheral and central nervous systems (Dersch et al., 2015).
Introduction
In 1975, the first recognized outbreak of this Lyme disease (LD) occurred in Lyme, Old Lyme, and Haddam in the state of Connecticut (Wright, 2016). It initially was recognized clinically as “Lyme arthritis”. Lyme disease is spirochaetal infection precipitated by the three pathogenic species of the Borrelia bacteria, which is transmitted through the bite of an infected tick (National Institute of Allergy and Infectious Diseases [NIAHD], n. d.; Wright, 2016). Numerous species of mammals are used as vectors for the tick borne illness, with rodents and deer acting as the primary reservoirs. The ticks then transmit the bacteria to a human host through their infected saliva. The spread of the disease has accelerated and since the mid-1980s, and the disease is now reported in rural areas of Eurasia (Center for Disease Control and Prevention [CDC], n.d.). It is currently the most common tick-borne disease in the Northern Hemisphere.
Lyme borreliosis is a multi-system inflammatory disease where it affects several organ systems, including the skin, joints, and the nervous system. Lyme disease precipitates numerous signs and symptoms for those who are infected including fever, facial palsies, chills, headache, fatigue, muscle, and joint pain (Dersch, Toews, Sommer, Rauer, & Meerpohl, 2015). Erythema migrans (EM) is a rash often appearing at the site of the tick bite and gradually expands to a ring with a central clear zone, before spreading to other parts of the body. If left untreated, infection can spread to the peripheral nervous system (PNS) and the nervous system (CNS) (CDC, n.d.).
A patient develops Lyme neuroborreliosis (LNB) when the bacteria, B. burgdorferi, transitions through the blood-brain barrier (BBB) and damages the peripheral nervous system (PNS) and the central nervous system (CNS) (Rupprecht & Fingerle, 2011). Neuroborreliosis can evolve within one to four weeks after initial infection, and can lead to nervous system dysfunction if left untreated. The spirochetes infect the neuronal cells by damaging the myelin sheaths, thus diminishing the ability of the action potential of one neuron to another (Rupprecht & Fingerle, 2011). Neuroimaging has shown that Lyme neuroborreliosis is similar to many neurodegenerative diseases such as myelitis, meningitis, and encephalitis (Rupprecht & Fingerle, 2011). These diseases are detrimental because they can undermine the motor system and cognitive ability of patients.
There is much confusion and controversy surrounding nervous system Lyme disease known as Lyme neuroborreliosis (LNB). This is due to misunderstandings about what does, and does not constitute evidence of nervous system infection. It includes three other entities often under the same nomenclature. These disorders are actually neurobiological but not truly neurologic; they include Lyme encephalopathy, posttreatment Lyme disease syndrome (PTLDS), and chronic Lyme disease (CLD) (Halperin, 2015). These disorders have no correlation to active CNS infection and have many nonspecific symptoms, including headache, fatigue, cognitive slowing, and memory difficulty associated with Lyme disease infection. However, these symptoms are not indicative of nervous system contamination and are common in many other infectious and inflammatory states.
Lyme neuroborreliosis is similar to neurosyphilis, nervous system involvement starts during the early disseminated phase of Lyme’s disease, when the spread of spirochetes results in meningeal seeding, where it may subside or become chronic (Hildenbrand, Craven, Jones, & Nemeskal, 2009). Just as in syphilis, appropriate antimicrobial agents result in a microbiologic cure, representing a true spirochaetal invasion regardless of the duration of the infection (Hildenbrand et al., 2009). Lyme encephalopathy, PTLDS, and CLD do not demonstrate active infection and therefore, will not be discussed. The focus of this paper is to discuss Lyme neuroborreliosis (LNB), the acute invasion of the nervous system by spirochaetal bacteria associated with LD.
In the city of New York, a recent study was conducted, which compared numerous diseases and their relation to poverty. According to Greene, Levin-Rector, Hadler, and Fine (2015), diseases like hepatitis C, are most prevalent in areas with endemic property and domestic zoonotic or vector-borne diseases such as LD, were higher in neighborhoods with low poverty (p. 30). It must also be considered that many people who become infected with LD, often do so in the pursuit of hobbies and extracurricular activities, which take place in rural or heavily wooded areas, away from the inner-city.
Epidemiology
Tick-borne diseases, such as Lyme disease, are rapidly evolving in the United States, due in part to climate change (Hildenbrand, Craven, Jones, & Nemeskal, 2009). Lyme disease is the most documented vector borne illness and the seventh most common reportable infectious disease, with cases increasing roughly 200% in the last 20 years (Adrion, Aucott, Lemke, & Wiener, 2015). In the U.S., there are between 240,000 to 440,000 of reported cases of Lyme disease (LD), resulting in a national incidence of 9.7 cases per 100,000 population (Hildenbrand, Craven, Jones, & Nemeskal, 2009). In 2013, state health departments reported 27,203 confirmed cases and 9,104 probable cases of Lyme disease (National Institute of Allergy and Infectious Diseases [NIAHD], n.d.). In Europe, cases are increasing as well, and in the United Kingdom (UK), the incidence is increasing with as many as 1,000 laboratory cases confirmed per annum (Pearson, 2015).
In the US, reported cases of LD are most common among boys between the ages of five and nine years old (CDC, n.d.). Lyme disease is more prevalent in males up to the age of 65, and more common in females between 70 to 90 years of age (CDC, n.d.). The majority of individuals infected with LD are most likely to have the onset of illness in the months of June, July, or August and less likely to have the illness onset from the months of December through March (CDC, n.d.). Clinical manifestations often include EM, but infections without EM are more often seen than in earlier years. The lack of extracutaneous symptoms eventually leads to cases, which are under diagnosed and therefore, under treated causing an increase incidence of LNB (Wormser et al., 2006).
Etiology
In America, the most commonly seen bacterium is Borrelia burgdorferi sensu stricto, although a second genospecies, B. mayonii was recently found to cause illness in the upper Midwestern United States (Mead, n.d.). In Eurasia, there are three bacteria that are known to cause illness; they include B. burgdorferi, B. garinii, and B. afzelii (Hildenbrand, Craven, Jones, & Nemeskal, 2009).
Lyme disease is transmitted by a number of Ixodes ticks, which vary by geography. The tick responsible in the northeastern and upper Midwestern states is the Ixodes scapularis and along the Pacific coast of the United States, particularly northern California, the culprit is often I. pacificus (CDC, 2015).
Over that span of two years, the Ixodes ticks go through three living stages, which include the six-legged larva, the-eight legged-nymph, and the dimorphic eight -legged it adult tick (CDC, n.d.). The larvae, the nymphs, and mature females require a blood meal from a vertebrate; it is this feeding that is the mechanism through which the bacteria are transferred. The adult male ticks are not known to transmit Lyme’s disease (CDC, n.d.).
The larvae hatch in the forest floor in early summer and searching for a blood meal which is small mammals, such as rodents. The larvae are not infected upon hatching, but acquire the bacteria during its first blood meal from the rodents, which often remains healthy despite being infected (CDC, n.d.). Once fed, the tick drops off the infected host; it molts and reemerges the next spring as an infected nymph.
It is during the nymph stage that the second blood meal transmits the bacteria to a new rodent, allowing the organism to spread to future generations, and complete the horizontal cycle of transmission (Wormser et al., 2006). This is the stage when LD is commonly transferred to humans. After the tick is fully engorged, the tick again drops from the host and in the fall molts to become an adult (CDC, n.d.)
When the adult emerges, it once again seeks a blood meal from their preferred host the white-tailed deer, but may also attach to coyotes, fox, raccoons, or even humans (CDC, n.d.). In the fall and early winter, after feeding, the female tick plunges upon the floor but does not lay eggs until the next spring, finishing the two-year life cycle.
B. burgdorferi is transferred through the saliva of infected ticks, and requires at least 24 to be 48-hour tick engorgement (CDC, 2015). The primary vector for the transmission to humans is the nymphal stage of the Ixodes tick. The nymphal stage is more effective at transmitting B. burgdorferi, in part due to their small size, which is often less than two millimeters and allows them to feed from their host undetected (Wormser et al., 2006). When compared to the nymphal tick the adult female is much larger and is sometimes removed before transmission can occur (Wormser et al., 2006).
Pathophysiology
The infection begins in the skin at the site of the bite, where after three to 32 days, the organisms migrate locally in the skin around the bite. The bacteria have an axial filament composed of flagella which run lengthways between its cell wall and outer membrane which allows the spirochete to move through tissue using corkscrew movement (Rupprecht & Fingerle, 2011). The spirochetes spread via the lymphatic system to cause regional adenopathy or disseminate in blood to numerous body systems, including the nervous system (Rupprecht & Fingerle, 2011).
The bacteria are adept at evading the host immune system and are able to up- and down-regulate their own antigens making it difficult for the immune system to detect (Wormser et al., 2006). The process that uses to accomplish this is to alter its own genome. The spirochetes are then able to alter the antigens on its own exterior shell so the host immune system can no longer recognize them as foreign allowing them to escape antibody mediated killing (Rupprecht & Fingerle, 2011). B. burgdorferi does not release endotoxins. The damage is caused when the spirochetes release the modified antigen which in turn causes an autoimmune reaction. It is this response by the body which causes damage to the surrounding tissue resulting in the symptoms associated with Lyme’s disease (Wormser et al., 2006).
It has also been suggested that there may be regional differences in the Borrelia species. In North America, the spirochete have been found to disseminate predominantly via the blood, while in Europe, they appear to prefer a migration along the other structures such as peripheral nerves directly to the nerve roots (Rupprecht & Fingerle, 2011). It has been suggested that this different mode of invasion may be responsible for the different clinical picture of LNB in North America when compared to Europe (Rupprecht & Fingerle, 2011). The presentation in Europe predominates with meningopolyradiculitis or Bannwarth syndrome, with the majority of pain close to this site of the tick bite (Rupprecht & Fingerle, 2011). This is in stark contrast to the presentation of LNB in North America, which is often more diffused with mostly meningitis or encephalopathy (Rupprecht & Fingerle, 2011).
Inflammatory reaction of the nervous system.
Once inside the nervous system the spirochetes induce an inflammatory reaction, presenting as Lymphocytic pleocytosis (Rupprecht & Fingerle, 2011). This is an abnormal increase in the amount of lymphocytes in the cerebrospinal fluid (CSF), which is considered to be an immuno privilege site, because there are only a few of immune cells to be found (Rupprecht & Fingerle, 2011). While a CSF does have a low population of dendritic and monocytic cells, which are responsible for immune surveillance, their numbers are very low when compared with those in systemic circulation (Rupprecht & Fingerle, 2011). Regrettably, neutrophils and components of the complement system are only rarely found, so the bacteria have crossed the blood-brain-barrier (BBB), the nervous system is virtually defenseless (Rupprecht & Fingerle, 2011).
B. burgdorferi inside the CSF are encountered by microglial cells, perivascular cells, and dendritic cells with toll like receptors (TLRs) which play an important role in the recognition of the invading bacteria (Rupprecht & Fingerle, 2011). The activation of the TLRs have an essential role in the control of B. burgdorferi. The TLR engagement results from nuclear translocation which in turn, induces the production bacteriocidal nitric oxide and superoxide, as well as the production and release of cytokines and chemokines (Rupprecht & Fingerle, 2011). Immune cells including B cells, from the systemic circulation are then attracted by the chemokines. The B cells mature into plasma cells, which in turn produce B. burgdorferi antibodies that can eventually destroy the invading spirochetes (Rupprecht & Fingerle, 2011). It is this response by the immune system which leads to the CSF pleocytosis.
The pathogenesis of Lyme neuroborreliosis is still a mystery. There are four mechanisms, which may be responsible for neuronal dysfunction produced by B. burgdorferi. They include the direct cytotoxic effect of the bacteria; secretion and release of cytotoxic mediators; host inflammatory reaction; and autoimmunity through molecular mimicry (Rupprecht & Fingerle, 2011). These mechanisms have been observed in animal studies but as of yet have not been confirmed in human subjects.
Review of Literature
The search engines utilized for this research paper included PubMed, CINAHL, Science Direct, Medline, EBSCO, and Cochrane library. The websites that were used in this study included the Centers for Disease Control and Prevention, National Institute of Allergy and Infectious Diseases (NIAID), European Centre for Disease Prevention and Control (ECDC), and the Infectious Disease Society of America (IDSA). Key terms used included “Lyme disease”, “neuroborreliosis “Lyme neuroborreliosis”, “Psycho-neurogenic effects of Lyme disease”, “Neuroborreliosis management”, and “treatment guidelines for neuroborreliosis”. The articles reviewed included topics, but not limited, on etiology, epidemiology, pathophysiology, social determinants, and treatment guidelines of Lyme disease and neuroborreliosis. The articles included in the review were peer reviewed and evidence based.
Stages of Lyme Disease
Clinical manifestations of Lyme disease vary greatly depending on the stage of disease and which body system is being effected. The most common clinical manifestation of Lyme disease is the erythema migrans (EM) rash, which accounts for up to 71% of confirmed cases (CDC, n.d.). The second most common manifestation of LD is myalgia and arthralgia manifestations accounting for 30% of reported symptoms (CDC, n.d.). The cardiac system symptoms of heart block and pericarditis are the least reported manifestations, accounting for only 1% of cases (CDC, n.d.). The remaining 15% of manifestations affect the central nervous system (CNS), which is the most frequent destination of dissemination, resulting Lyme neuroborreliosis (Rupprecht & Fingerle, 2011).
Early localized disease.
Early localized disease occurs within a few days to one month after the tick bite, with EM being the most prevalent sign. Associated signs and symptoms at this stage may include fatigue, malaise, lethargy, mild headache, mild neck stiffness, myalgias, arthralgias, and regional lymphedema neuropathy (CDC, 2015).
Disseminated disease.
Early disseminated disease occurs weeks to months after the tick bite and may elicit multi-system manifestations. Patients may present with cardiac manifestations such as AV normal block, mild cardiomyopathy, or mild pericarditis (CDC, 2015). Individuals may complain of musculoskeletal symptoms such as migratory arthralgias and myalgias (CDC, 2015). The bacteria can invade the liver causing inflammation and liver function test abnormalities as well as the kidneys with associated micro hematuria and a symptomatic proteinuria (CDC, 2015). The eyes may also become involved with associated conjunctivitis, iritis, choroiditis, vitritis, and retinitis (CDC, 2015). The patient may present with multiple EM lesions as well as regional or generalized lymphadenopathy (CDC, 2015). By definition, nervous system involvement only occurs in disseminated LD and it is during this stage is when neurologic manifestations occur.
Late or chronic disease.
Late or chronic disease often occurs months to years after the tick bite. Approximately 60% of untreated patients developed intermittent arthritis that may involve single or multiple joints, but usually involves the knees (CDC, 2015). Cutaneous involvement may also persist at this stage with acrodermatitis chronica atrophicans, and localized scleroderma like lesions (CDC, 2015).
Nervous system manifestation
Nervous system manifestations include cranial neuropathy which is most often facial and can be bilateral, peripheral neuropathy, lymphocytic meningitis, and rarely myelitis or encephalitis (CDC, 2015). Cranial neuropathy and radiculoneuritis are part of the classic triad of Bannwarth’s syndrome which includes cranial neuropathy, radiculoneuritis, and meningitis (Hildenbrand et al., 2009).
Cranial neuropathies associated with LD tend to occur early in infection and are usually have an abrupt onset. Virtually any cranial nerve can be involved, but the seventh cranial nerve, the facial nerve, is by far the most common (Hildenbrand et al., 2009). Occasionally the cranial neuropathy occurs before the patient has become seropositive, and in such patients a follow-up titer in several weeks is typically diagnostic. During spring and into fall, in areas known to have high levels of LD, adults who present with bilateral facial nerve palsies should be considered candidates for Lyme disease testing.
Another common manifestation of Lyme disease in the peripheral nervous system is radiculoneuritis. This disorder can mirror a mechanical radiculopathy with pain in one or several dermatomes accompanied by corresponding sensory, motor, and reflex changes (Hildenbrand et al., 2009). This dysfunction should be considered in patients with severe limb or truncal pain without an associated mechanical component (Hildenbrand et al., 2009).
Central nervous system involvement in Lyme disease can take several forms with meningitis, Lyme encephalomyelitis, and encephalopathy being the most common. Lymphocytic meningitis is the most common form of CNS involvement and often times presents either alone or in conjunction with cranial nerve or spinal nerve root involvement (Halperin, 2015). Patients presenting with lymphocytic meningitis of Lyme disease may complain of headache, fever, photosensitivity, as well as neck stiffness (Halperin, 2015). This disorder can be differentiated from viral meningitis by its slower onset, the presence of cranial neuropathy, and the presence of mononuclear cells in the CSF (Halperin, 2015).
Occasionally, patients with Lyme encephalomyelitis (LE) will complain of radicular symptoms and will have segmental spinal cord involvement at the same level as the effective nerve root (Halperin, 2015). This disorder represents a true infection of the neuraxis. Patients may present with inflammatory appearing parenchymal abnormalities on the brain or spinal cord which superficially resemble multiple sclerosis (MS). Although LE is highly responsive to appropriate antibiotics there may be neurologic impairment caused by injury that occurred prior to treatment (Halperin, 2015).
Encephalopathy is a term that is often used to indicate alterations in brain function due to non-neurologic causes. Some patients with Lyme disease described fatigue, cognitive slowing, and memory difficulty although these symptoms are not specific of Lyme’s disease and are often associated with many inflammatory disorders (Halperin, 2015). These symptoms are not considered evidence of CNS infection with B. burgdorferi which must be confirmed through cerebral spinal fluid abnormalities and MRI findings (Halperin, 2015).
Psychosocial Impacts of Lyme Neuroborreliosis
Lyme neuroborreliosis can have dramatic psychological and social implications for those who are infected. Social isolation may be a byproduct of LNB due to inability to ambulate or perform activities of daily living (ADLs) (Watson, 2015). In such instances, individuals may lose their independence and must rely on others to meet their most basic needs until their symptoms improve. In some individuals LNB, they may become despondent and frustrated with prolonged and lingering symptoms, which may lead to loss of employment, financial difficulties, and a decline in their lifestyles (Garakani & Mitton, 2015).
In a study conducted by Ali, Vitulano, Lee, Weiss, and Colson (2014), they found participants had perceived negative experiences within the healthcare system, with reports of dismissive, patronizing, and condescending attitudes of providers (Ali et al., 2014). The study showed many of the participants sought out alternative medicine (CAM) practitioners in order to find and empathetic clinician. This highlights the fact those afflicted with LNB are not just dealing with a physical condition but also must endure the psychological and social impacts as well.
Management
Pharmacological
Prophylaxis treatment of Lyme disease is not recommended except under extenuating circumstances. The strongest indication of prophylactic antibiotic use is when an I. scapularis tick from a highly endemic area is partially engorged or attached for longer than 36 hours or when the duration of tick attachment or degree of engorgement is uncertain (Journal of the American Medical Association [JAMA], 2016). In the situation a single dose of 200 mg of doxycycline by mouth coupled with observation for signs and symptoms of LD (JAMA, 2016).
In patients with early Lyme disease who present with EM treatment with oral doxycycline 100 mg by mouth for 10 days shortens the duration of skin lesions and generally prevents development of late sequelae (JAMA, 2016). Doxycycline should not be used in children less than eight years of age or for pregnant or lactating women amoxicillin 500 mg by mouth twice a day for 14 days, cefuroxime axetil 500 mg by mouth twice a day for 14 days, or azithromycin 500 mg by mouth once a day for 7 to 10 days (JAMA, 2016).
For patients presenting with facial nerve palsy oral doxycycline has been shown to be effective with the course of 100 mg by mouth twice a day for 14 days (JAMA, 2016). Individuals presenting with another neurologic involvement, such as meningitis, other cranial nerve palsy’s, radiculopathy, or cognitive deficits should be prescribed 2 g of IV ceftriaxone every 24 hours for 14 days (JAMA, 2016).
For individuals with other systemic manifestations of LD such as cardiac disease or arthritis for antibiotics have shown efficacy they include doxycycline, amoxicillin, cefuroxime axetil (JAMA, 2016). These antibiotic should be prescribed as follows Doxycycline 100 mg by mouth twice a day for 14 days, amoxicillin or cefuroxime axetil 500 mg by mouth three times a day for 14 to 21 days, or IV ceftriaxone 2 g every 24 hours for 14 days (JAMA, 2016). Intravenous ceftriaxone is often used for manifestations that are more serious, persistent, or recurrent (JAMA, 2016).
Non-pharmacological
Nonpharmacologic management of patients with Lyme disease revolves around treatment and observation. Patients on ceftriaxone or cefotaxime should be monitored with weekly CBCs to monitor for leukopenia which can be seen with these antibiotics (JAMA, 2016). Use of ceftriaxone may lead to biliary sludging, which can be monitored with weekly hepatic panels to look for elevated hyperbilirubinemia in which case the patient should be switched to cefotaxime (Rupprecht & Fingerle, 2011). Doxycycline may cause photosensitivity while amoxicillin and cefuroxime are known to cause drug rashes (Rupprecht & Fingerle, 2011).
Follow-up and Referral
Individuals infected with Lyme disease may require weekly appointments before and after a diagnosis is made. For LNB patients like Greg, they may have to spend much of their time treating this disease. They may receive IV antibiotics, give blood for various lab studies, and be examined for lingering symptoms. Some patients infected with Lyme disease may experience manifestations that persist despite primary care management, and may require a referral to infectious disease specialists (Rupprecht & Fingerle, 2011).
Education
The current method that is most effective at averting Lyme disease is prevention through education. Individuals like Greg, who like to spend much of their time outdoors, should be taught prevention techniques. The use of protective clothing when they are outside especially in wooded areas is one such commonsense technique. One should wear a Long-sleeved shirt which should then be tucked into pants. The long pants are then tucked into socks effectively creating a barrier which interferes with tick attachment by increasing the time required for ticks to find exposed skin. Clothes should be light-colored, which provides a background which will contrast the tick, facilitating removal.
Tick and insect repellents containing diethyltoluamide (DEET) applied to the skin or clothing provide additional protection but may require reapplication for increased effectiveness (Wormser et al., 2006). Ticks detect DEET through olfactory sensing and are thus repelled. The repellents should not be applied to the face or head or skin that is irritated or braided. After returning indoors the skin should be washed with soap and water to remove the repellents.
Frequent visual inspection is another method, which may help identify text prior to attachment and in turn allowing removal before infection can be transmitted. The proper removal of ticks should be done preferably with the aid of tweezers or fine forceps. The attached tick should be removed promptly and if a portion of the mouth of the tick remains embedded in the skin only topical disinfection of the site is suggested.
Bob_Atl
Well-known member
Well done Randy (Doc), A++++ in my book !!
Got curious about EM, here's a www site with pics on LD-EM info ,
As outdoors people, I think we should know what that looks like..imho..
Got curious about EM, here's a www site with pics on LD-EM info ,
As outdoors people, I think we should know what that looks like..imho..
crapshoot
Well-known member
You should see the damage this Tick can do.
http://www.tick4nevada.com/
http://www.tick4nevada.com/
Originally Posted By: crapshootYou should see the damage this Tick can do.
http://www.tick4nevada.com/
Absolutely, the two legged sub-species is the most destructive of all ticks!
Regards,
hm
http://www.tick4nevada.com/
Absolutely, the two legged sub-species is the most destructive of all ticks!
Regards,
hm
spotstalkshoot
Well-known member
Nothing about diagnostic tests for Lymes. Has blood test accuracy improved in the last decade?
capitol
Active member
Originally Posted By: hm1996Originally Posted By: crapshootYou should see the damage this Tick can do.
http://www.tick4nevada.com/
Absolutely, the two legged sub-species is the most destructive of all ticks!
Regards,
hm
This is pretty funny. Thanks for the laugh.
http://www.tick4nevada.com/
Absolutely, the two legged sub-species is the most destructive of all ticks!
Regards,
hm
This is pretty funny. Thanks for the laugh.
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