Sunday, May 22, 2022

Lyme Disease Chain Of Infection

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Abundance And Spread Of I Ricinus

Chain of Infection Overview PowerPoint

Understanding which factors drive population densities of disease vectors is an important step in assessing disease risk and formulating possible intervention strategies. Ixodes ricinus has a four stage life-cycle, i.e. egg, larva, nymph and adult, requiring only one blood meal during every active stage. The time for I. ricinus to complete its life-cycle varies between three and six years, mostly depending on climate and host availability. Ixodes ricinus employs an ambush strategy for host finding , which implies climbing the vegetation, clinging to the tips of stems, and waiting for a vertebrate host. Questing ticks cling to a host animal as the animal passes through vegetation. After feeding for a few days, ticks detach from the host and fall in the litter layer. It takes several months to molt into their next developmental stage, or, in the case of adult females, to lay several thousand eggs and subsequently die. Only a small fraction of the ticks complete the life-cycle: about 10% of the questing larvae will develop into a questing nymph, and then again between only 1 and 10% of the nymphs manage to develop into a questing adult.

Ruling Out Other Diseases

Many other infections and medical conditions can produce fever, headache, muscle aches, and fatigue, including a very wide variety of common, generally benign viral illnesses. They can also produce some of the neurologic or cardiac features characteristic of early Lyme disease. The same tick that causes Lyme disease can also transmit other infections.

Co-Infections Transmitted by the Ixodes Tick

Babesiosis, Rocky Mountain Spotted Fever , and human granulocytic anaplasmosis are transmitted by the same tick that carries Lyme disease. People may be co-infected with one or more of these infections, all of which can cause flu-like symptoms. If these symptoms persist and there is no rash, it is less likely that Lyme disease is present.

Other Tick-Borne Infections

A number of other tick-borne diseases may resemble Lyme disease. The most important of these is southern tick-associated rash illness , which is caused by the bite of the Lone star tick, usually in southern and Southeastern parts of the United States. It causes a rash very similar to Lyme disease. The bacterium responsible for STARI remains unknown, but may be B. lonestari.

Allergic Reactions and Insect Bites

Other Diseases

What Is The Chain Of Infection For Lyme Disease

Lyme disease or Lyme borreliosis is a bacterial infection causedby several species of bacteria belonging to the genus Borrelia.These bacteria are maintained in nature in the bodies of wildanimals and transmitted from one animal to another by tick bites.Humans and pets are incidental hosts to ticks. The early phase ofthe disease begins at the site of the tick bite with an expandingring of redness which often resembles a bull’s-eye, with a red ringsurrounding a clear area and a red center. Later it can affect theskin, joints, heart, and the nervous system. The body does notmaintain a natural immunity to the disease. Thus, a person can bere-infected with the disease on subsequent tick bites.

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Treating Late Stage Lyme Disease

Most cases of Lyme disease involve a rash and flu-like symptoms that resolve within 1 month of antibiotic treatment. However, some people go on to develop late-stage Lyme disease, which includes Lyme arthritis and neurologic Lyme disease.

Untreated, slightly more than half of people infected with B. burgdorferi will develop Lyme arthritis. About 10% to 20 % of people develop neurologic Lyme disease. A very small percentage may develop acrodermatitis chronica atrophicans, a serious type of skin inflammation occurring more frequently in Europe. These conditions are treated for up to 28 days with antibiotic therapy.

If arthritis symptoms persist for several months, a second 2 to 4 week course of antibiotics may be recommended. Oral antibiotics are used for Lyme arthritis and acrodermatitis chronica atrophicans.

In rare cases, people with arthritis may need intravenous antibiotics. A 2 to 4 week course of intravenous ceftriaxone is used for treating severe cases of neurological Lyme disease. For milder cases, 2 to 4 weeks of oral doxycycline is an effective option.

How Do These Pathogens Cause Lyme Disease

The Chain of Infection

B. burgdorferi cycles two types of hosts between it ticks and mammals. It cannot live freely in the environment. It does not produce large numbers of proteins, and has a relatively small genome. It does produce a large number of lipoproteins that may help it evade the mammalian immune system.

The ways in which B. burgdorferi cause disease and evade the immune system are complex and not yet fully understood.

A protein called outer surface protein A assists in binding the bacterium to the tick midgut. When the tick bites a mammalian host, ospA is down-regulated and outer surface protein C is up-regulated, which assists with tissue invasion. B. burgdorferi that do not express OspC cannot effectively infect mammals.

However, OspC is a potent target for IgM antibiodies, and is soon down-regulated after initial infection. The organisms utilize host proteins to move through tissue . Other virulence factors include P66 which binds integrin receptors on platelets and can facilitate bacteremia and complement regulator acquiring surface proteins that bind complement Factor H, which blocks the complement from killing the organism.

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Roles Of Bacterial And Host Proteinases In Dissemination And Inflammation

In addition to binding to extracellular matrix proteins, B.burgdorferi needs a mechanism for breaking down the molecules in theextracellular matrix that impede its movement and that promote the inflammatoryresponse that might clear the infection. B. burgdorferi appears tohave adopted several strategies for accomplishing this, as reviewed in .

B. burgdorferi encodes a homolog of the high temperaturerequirement A family of proteins. HtrA in B. burgdorferi, anortholog of DegP, a periplasmic chaperone and quality control protein, is bound toouter membranes and released into the milieu . Ithas been shown to play a role in degradation of B. burgdorferiproteins such as the basic membrane protein, BmpD, the chemotaxis phosphatase CheX,and outer membrane porin, P66, the monomeric but not polymerized form of flagellin,and the cellular fission protein BB0323 . In vitro, HtrA also has aggrecanase activity and isable to degrade the extracellular matrix components fibronectin and aggrecan . An HtrA mutant isnon-infectious in mice, but also exhibits significant growth defects invitro , hasdecreased motility, and produces less pyruvate . It is unclear whether the activity of HtrA onB. burgdorferi proteins and/or degradation of extracellularmatrix proteins are important to the loss of infectivity of the HtrA mutant .

Protecting Property From Tick Infestation

To decrease the tick population around your yard:

  • Clear the yard regularly by raking leaves, trimming bushes, pruning low-lying branches, mowing lawn.
  • Create a 3-foot wide barrier around the perimeter of your lawn with wood chips, gravel, or mulch.
  • Place cardboard tubes stuffed with permethrin-treated cotton in places where mice can find them. These tubes are available in hardware stores. Mice collect the cotton for lining their nests the pesticide on the cotton kills any immature ticks that feed on the mice. For best results, do several tube applications from early to late summer.
  • Erect fences or use repellants or deer-resistant plants to keep deer away.
  • Consider spraying once a year a small amount of tick-killing insecticide such as permethrin or bifenthrin around the perimeter of your yard. To avoid health and environmental risks, consult a licensed professional experienced with tick control.

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Chemically Targeting Reservoirs With Insecticides

Another approach is to reduce tick populations by passive application of chemicals to deer and mice, although there is little evidence for the effectiveness of this approach. At present, these approaches are only experimental. For example, a 4-poster bait station can be used to passively apply insecticide to the neck and head of the deer in order to decrease the number of ticks attached to the deer as shown in the photograph below.

While this may be a very effective method, the display can be expensive and a licensed insecticide applicator needs to replenish the display frequently, making it a less popular option. For more information about four posters, follow this link: American Lyme Disease Foundation.htm.

Another method is to use “tick tubes,” shown below, which contain cotton treated with Permethrin, which kills ticks. Mice will enter the tube to retrieve cotton for their nests, and the Permethrin will adhere to the mice. For more information see the Damminix Tick Tube Fact Sheet.

Dissemination And Tissue Colonization: A Plethora Of Adhesins

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Adhesins that bind to extracellular matrix components

Laminins constitute a family of widely distributed heterotrimericextracellular matrix glycoproteins that serve a variety of functions manybacteria produce laminin-binding adhesins. B. burgdorferiencodes at least three laminin-binding adhesins: ErpX, BmpA and BB0406. ErpXwas shown to bind laminin produced by a murine sarcoma cell line , but no assessments of apotential in vivo role have been reported.

Similar in vitro approaches were used to identifythe Bmp proteins as candidate laminin-binding adhesins, although only BmpAwas investigated in depth . In vivo, there is evidence that BmpA andB contribute to joint colonization and arthritis development , and BmpD wasselected in vivo for vascular adhesion . More recent structurebased predictions suggest a role for Bmp proteins in nutrient uptake , although this activity hasnot been experimentally verified. Furthermore, BmpB, C, and D all areassociated with the cytoplasmic membrane, i.e. notavailable to serve as adhesins . Therefore, potential roles of Bmp proteins asadhesins are in serious doubt, as independent lines of evidence suggest that they are not located on the B.burgdorferi surface.

Integrin binding proteins

Borrelia burgdorferi-host interactions that contribute toinfection.

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Magnitude Of The Problem

In 2009 there were 29,959 confirmed and 8,509 probable cases of Lyme disease reported to CDC, for an incidence of 13.4 cases per 100,000 population. During the same year, Massachusetts had 4,019 confirmed and 1,237 probable cases, an incidence of 61.0 per 100,000 population. The annual number of confirmed cases has been rising steadily over the past 15 years.

Full Recommendations For The Prevention Diagnosis And Treatment Of Lyme Disease

I. Which measures should be used to prevent tick bites and tick-borne infections?

Personal Protective Measures
Recommendation
  • Individuals at risk of exposure should implement personal protective measures to reduce the risk of tick exposure and infection with tick-borne pathogens .
  • Summary of the Evidence
    Rationale for Recommendation

    Although there is little systematic evidence supporting some of these measures for the prevention of Lyme disease, they may offer potential benefits with little effort, risk, or cost.

    Knowledge Gaps

    Properly designed studies performed with human subjects under realistic conditions are required to test the efficacy of personal protection measures. Similarly, research is needed to inform how to motivate the adoption and continued use of best practice personal protection measures.

    Repellents to Prevent Tick Bites
    Recommendation
  • For the prevention of tick bites, we recommend N,N-Diethyl-meta-toluamide , picaridin, ethyl-3- aminopropionate , oil of lemon eucalyptus , p-methane-3,8-diol , 2-undecanone, or permethrin .
  • Summary of the Evidence

    In laboratory and field experiments involving human subjects, the use of DEET, picaridin, IR3535, oil of lemon eucalyptus , p-methane-3,8-diol , 2-undecanone, and permethrin reduced the number of ticks detected crawling on or attached to subjects compared with controls . Other commercially available products, including botanical agents and essential oils cannot be recommended due to insufficient evidence.

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    Health In All Policies

    Most, if not all, of the available environmentally-based preventive and control measures suffer from the fact that they are not highly effective on their own . Probably, long-term implementation of control strategies, i.e. the integrated use of two or more control measures, are necessary to effectively reduce disease risk. Only a few studies on the effectiveness of control strategies have been carried out in the USA, but not in Europe . The successful implementation of environmentally-based preventive and control measures requires involvement of stakeholders from both nature management and human health . Of key importance is that the environmental control options for TBDs are put into the context of other aims and ambitions, such as nature conservation, ecosystem services or heat mitigation in urban areas. Indeed, sectors involved in nature management and environmental planning are often more familiar with a so-called Health in All Policies approach. The Health in All Policies approach integrates and articulates many health considerations, far broader than infectious diseases alone, into policymaking across sectors. A future challenge is to integrate the risk of TBDs, but also of wildlife- and other vector-borne diseases, into the Health in All Policies in local nature organizations, such as Municipal Health Services and nature owners, but also governmental institutions and national organizations responsible for nature and health.

    Other Types Of Laboratory Testing

    Tick molecules involved in Borrelia transmission ...

    Some laboratories offer Lyme disease testing using assays whose accuracy and clinical usefulness have not been adequately established. Click here for more information. Patients should be encouraged to ask their physicians whether their testing for Lyme disease was performed using validated methods and whether results were interpreted using appropriate guidelines.

    In the early stages of infection Lyme disease is completely curable with antibiotics such as:

    • Doxycycline
    • Amoxicillin
    • Cephalexin

    The treatment during later stages of Lyme disease is more difficult, and some patients may still experience symptoms up to three months

    after treatment. An intravenous drug, such as Ceftriaxone , is recommended for the later stages. Pain killers, such as Ibuprofen, can also be prescribed along with antibiotics to relieve joint pain.

    Link to guidelines for treatment of Lyme disease

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    Diagnosis Of Lyme Disease

    to take a sample of the fluid that surrounds the brain and spinal cord . Fragments of the bacteriaâs genetic material may be present and detected using the polymerase chain reaction technique Polymerase chain reaction Genetic diagnostic technologies are scientific methods that are used to understand and evaluate an organism’s genes. Genes are segments of deoxyribonucleic… read more . This technique produces many copies of a gene and enables doctors to identify Borrelia burgdorferi bacteria rapidly.

    Clinical Practice Guidelines By The Infectious Diseases Society Of America American Academy Of Neurology And American College Of Rheumatology : 2020 Guidelines For The Prevention Diagnosis And Treatment Of Lyme Disease

    Clinical Infectious Diseases, Volume 72, Issue 1, 1 January 2021, Pages e1-e48, 30 November 2020

    Paul M Lantos, Jeffrey Rumbaugh, Linda K Bockenstedt, Yngve T Falck-Ytter, Maria E Aguero-Rosenfeld, Paul G Auwaerter, Kelly Baldwin, Raveendhara R Bannuru, Kiran K Belani, William R Bowie, John A Branda, David B Clifford, Francis J DiMario, Jr, John J Halperin, Peter J Krause, Valery Lavergne, Matthew H Liang, H Cody Meissner, Lise E Nigrovic, James J Nocton, Mikala C Osani, Amy A Pruitt, Jane Rips, Lynda E Rosenfeld, Margot L Savoy, Sunil K Sood, Allen C Steere, Franc Strle, Robert Sundel, Jean Tsao, Elizaveta E Vaysbrot, Gary P Wormser, Lawrence S Zemel

    For the full document, including complete tables and references, please visit the Oxford University Press website.

    A summary guideline for clinicians may be found here.

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    Clinical Manifestations And Disease Pathogenesis

    To maintain its complex enzootic cycle, B. burgdorferi must adapt to markedly different environments, the tick and the mammalian or avian host. The spirochete survives in a dormant state in the nymphal tick midgut during the fall, winter, and early spring, where it expresses primarily OspA . When the tick feeds in the late spring or early summer, the expression of a number of spirochetal proteins is altered . For example, OspA is downregulated, and OspC is upregulated . OspC expression is required for infection of the mammalian host . In addition, the spirochete binds mammalian plasminogen and its activators, present in the blood meal, which facilitates spreading of the organism within the tick . Within the salivary gland, OspC expression predominates, but some organisms express only OspE and OspF OspA and OspB are absent .

    Racial Differences In Incidence

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    Lyme disease is reported primarily in whites, although it occurs in individuals of all races. No genetic explanation is known for this the disparity most likely stems from social or environmental factors and possibly to the fact that erythema migrans is more difficult to diagnose in dark-skinned individuals.

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    Emergence Of Human Lyme Borreliosis

    The earliest known American cases of Lyme disease occurred in Cape Cod in the 1960s . However, B. burgdorferi DNA has been identified by PCR in museum specimens of ticks and mice from Long Island dating from the late 19th and early 20th centuries , and the infection has probably been present in North America for millennia . During the European colonization of North America, woodland in New England was cleared for farming, and deer were hunted almost to extinction . However, during the 20th century, conditions improved in the northeastern US for the ecology of Lyme disease. As farmland reverted to woodland, deer proliferated, white-footed mice were plentiful, and the deer tick thrived. Soil moisture and land cover, as found near rivers and along the coast, were favorable for tick survival . Finally, these areas became heavily populated with both humans and deer, as more rural wooded areas became wooded suburbs in which deer were without predators and hunting was prohibited.

    As in America, the European agents of Lyme borreliosis have probably been present there for many thousands of years. They are now known to be widely established in Europes remaining forested areas . The highest reported frequencies of the disease are in middle Europe, particularly in Germany, Austria, Slovenia, and Sweden . In 1995, the yearly incidence of the disease in Slovenia and Austria was estimated to be 120130 cases per 100,000 residents , similar to the frequency in Connecticut.

    Adaptation To The Mammalian Host

    When an Ixodes vector tick begins feeding on amammalian host, there is a dramatic alteration in the tick midgut environment. Theblood meal and proximity to the mammal results in changes in temperature, pH,availability of nutrients, and exposure to antibodies, complement and other hostprotective factors. In response to changing environmental conditions, B.burgdorferi replicates rapidly in the midgut during and followingtick feeding, with the number of Borrelia increasing from< 500 prior to feeding to about 1.7 Ã 105 per tick after72 hours of feeding, a > 300-fold increase . Along with thispopulation expansion, B. burgdorferi undergoes dramatic changesin gene expression, primarily but not exclusively via theRrp2-RpoN-RpoS regulatory cascade .

    Some of these changes are reflected at the mRNA level invitro with changes in culture temperature and pH, as well asincubation in dialysis membrane chambers or in the presence of blood. Thesein vitro environmental changes have been used as models tostudy gene regulation during the tick to mammal transition, and in part reflectthe tick to mammal transition, with upregulation of mammalianinfection-associated surface proteins such as OspC, DbpA, DbpBvia the Rrp2-RpoN-RpoS sigma factor pathway. However,changes in the in vitro culture conditions do not affectexpression of other genes, including p66, or result indownregulation of tick-related gene products OspA and OspB.

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