Spirochetal Flashcards
Lyme Disease
Multisystem illness caused by spirocheteBorrelia burgdorferi
Vector-borne disease transmitted to humans by infected ticks of the Ixodes genus
Lyme disease - most common vector-borne illness in the US, accounting for 29,959 reported cases in 2009
Emergence of Lyme disease is probably due to the explosion of deer and tick populations with the reforestation of the northeastern United States; subsequent contact between ticks and humans as people move into deer habitats
Also endemic in the rest of North America, Europe, and Asia
Stage 1 of Lyme Disease
Stage 1 is also known as primary or early localized infection; occurs within 30 days of the tick bite
Most patients present with a characteristic expanding rash (erythema migrans) at the site of the tick bite 7-14 days after the tick is removed
Other nonspecific symptoms include fatigue, myalgias, arthralgias, headache, fever, chills, and neck stiffness
Stage 2 or early disseminated disease of Lyme Disease
occurring generally weeks to months after the bite
Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac and dermatologic
Stage 3 or chronic Lyme disease
happens months to years after infection, which sometimes involves a period of latency
Musculoskeletal (mainly joints) and neurologic systems are most commonly affected
Systemic Manifestations of Lyme Disease
Fever is generally low grade
Fatigue is common
Myalgias and arthralgias occur early
Frank arthritis (i.e. joint swelling, redness, pain) usually is a later manifestation but can occur in the early disseminated phase
Flulike illness (undifferentiated febrile illness) may occur
Lyme disease with typical flulike symptoms of fevers, chills, myalgias, arthralgias, and malaise (without rash)
Season of onset, epidemiologic likelihood of a tick bite, paucity of respiratory and GI symptoms, and prompt response to antiborrelial therapy are diagnostic clues
Cutaneous symptoms of Lyme Disease
Classic rash, erythema migrans (EM), is present in about 75% of patients.
Neither pruritic nor painful (although it can be either), some patients may have the rash but not notice it
EM can occur in the same patient more than once
20% of patients withLyme diseasehave multiple lesions (from hematogenous dissemination)
Borrelial lymphocytoma, a nodule usually found on the ear lobe or areola of the nipple, develops in some patients early in the course of disease (more common in Europe)
Neurologic symptoms of Lyme Disease
Headache of Lyme disease typically is described as waxing and waning, and the severity varies from mild to severe, even in patients with frank meningitis
Facial weakness, which is similar to a typical Bell palsy and which can be the presenting symptom of Lyme disease; 25% of patients with borrelial facial palsy have bilateral involvement, which may be sequential and is a point of differential diagnostic significance (Lyme responsible for 34% of facial palsy)
Radicular pain can occur and present as acute disk disease
Late Lyme disease can cause paresthesias or pain due to peripheral neuropathy and personality, cognitive, and sleep disturbances from chronic encephalopathy
Neurologic syndromes caused by Lyme disease involve nearly every part of the CNS and peripheral nervous system
Cardiovascular involvement of Lyme Disease
< 10% of patients with untreated Lyme disease; more common in males
Palpitations, lightheadedness, and syncope may be a manifestation of varying degrees of heart block, including complete heart block, which occurs in 50% of patients with cardiac involvement
Lyme disease is an important reversible cause of heart block
Chest pain and dyspnea can occur in the setting of Lyme pericarditis, myocarditis, and myopericarditis
Joint Involvement of Lyme Disease
Migratory pain may occur from myositis, tendonitis, and bursitis, classically wax and wane over hours or days
Later, arthritis occurs generally with swelling, redness, and pain in one or a few large joints, typically the knees
Synovitis occasionally occurs in early-disseminated phase
Ocular Involvement of Lyme Disease
Red, itchy eyes are the most commonocular symptom; blurred vision and eye pain can occur from keratitis and iritis
Lyme Disease Workup
Solitary, typical EM requires no laboratory testing whatsoever
Positive culture forB burgdorferi, or
Two-tier testing interpreted using established criteria, where positive immunoglobulin M (IgM) is sufficient only when 30 days or less from symptom onset or positive immunoglobulin G (IgG) is sufficient at any point during illness
Single-tier IgG immunoblot seropositivity using established criteria
CSF antibody positive forB burgdorferiby enzyme immunoassay (EIA) or immunofluorescence assay (IFA), when the titer is higher than it was in serum
Rocky Mountain spotted fever
Rocky Mountain spotted fever (RMSF) is a tick-borne disease caused by the organismRickettsia rickettsii
RMSF can be lethal, it is curable
RMSF is the most common rickettsial infection
Organism is endemic in parts of North, Central, and South America, especially in the southeastern and south-central United States
2 principaltick vectorsof RMSF in North America areDermacentor variabilis(dog tick), in the eastern United States, andD andersoni, in the Rocky Mountain region and Canada
RMSF - Etiology and Pathophysiology
Ticks become infected by feeding on the blood of infected animals, through fertilization, or by transovarial passage
Rickettsiae are transmitted from tick to human during feeding; needs to be attached to a host for 6-10 hours for rickettsiae to be released from the salivary glands, although transmission may not occur for 24 hours
Infection possible for people who remove ticks from other people or animals via contact with tick tissues and fluids
Notable characteristics ofR rickettsiiinclude its marked tropism for endothelial cells that line blood vessels and its enhanced ability to invade throughout the body compared with other rickettsiae; model examples of vasculitis with localization in endothelial cells
Pathophysiologic effect of endothelial cell injury is increased vascular permeability, which results in edema, hypovolemia, hypotension, and hypoalbuminemia
RMSF suspicion
Hallmark of RMSF is a petechial rash beginning on the palms of the hands and soles of the feet
High index of suspicion for RMSF in patients with the following:
Febrile illness
History of potential tick exposure
Travel to endemic area
Presentation in the spring or fall
RMSF should be considered in patients with unexplained febrile illness even if they have no history of a tick bite or travel to an endemic area (history of a tick bite is reported by only 70% of patients)
RMSF - Presentation
Fever greater than 102°F - 94%
Fever within 3 days after tick bite - 66%
Headache, frequently severe - 86%
Myalgias - 85%
CNS symptoms - 25% of patients develop signs of encephalitis (ie, confusion, lethargy); may progress to stupor, delirium, seizures, or coma
Cardiovascular (myocarditis; relative bradycardia; arrhythmias - 7-16% of patients; hypotension - 7-17% of patients)
GI symptoms - anorexia, nausea, vomiting, diarrhea, and abdominal pain
Also may have insomnia and photophobia
Some Lab Findings for RMSF
White blood cell (WBC) count - Leukopenia is present initially, then mild leukocytosis; patients usually have a normal WBC count
Platelets - Thrombocytopenia (< 150,000 cells/µL) occurs in 32-52% of patients; abnormalities indicative of DIC are present in severely ill patients
Hemoglobin and hematocrit - Anemia is present in 5-24% of patients
Aminotransferase levels - Mildly elevated in 36-62% of patients
Hyponatremia - Present in 19-56% of cases
Bilirubin levels – Increased in 8-9% of patients.
Mild cerebrospinal fluid pleocytosis with monocyte predominance
Azotemia - Develops in 12-14% of cases
Prothrombin time and activated partial thromboplastin time - May be elevated
Anemia, an increased blood urea nitrogen (BUN) level, or abnormal liver function test results are found in 30% of patients. Late findings associated with advanced disease include signs of multiorgan failure, such as elevated BUN, creatinine, and creatinine kinase levels.
Serology workup of RMSF
Diagnosis is confirmed based on indirect immunofluorescent antibody (IFA) test results, latex agglutination, or enzyme immunoassay. Serology specific forR rickettsiiinfection develops within 6-8 weeks. Serologic test results are negative prior to convalescence.
Blood and Lumbar puncture workup of RMSF
Blood Culture
Isolation ofR rickettsiifrom the blood is possible, but few laboratories perform this isolation
Lumbar puncture
Lumbar puncture usually is performed as part of the workup for suspected meningitis. Pleocytosis is found in 34-38% of cases. Usually 10-100 cells/µL with either lymphocytic or polymorphonuclear cell predominance are found. Increased protein is found in 30-35% of cases; the glucose level usually is normal.
RMSF - Treatment
In adults with Rocky Mountain spotted fever (RMSF), the drug of choice is doxycycline
Chloramphenicol is an alternative, although doxycycline is preferable because tetracyclines have been shown to be associated with a higher survival rate than chloramphenicol
In vitro and in ovoR rickettsiiare also susceptible to rifampin
Doxycycline therapy also treats Lyme disease, ehrlichiosis, and relapsing fever—entities often clinically confused with RMSF
1997, AAP revised treatment options for children with RMSF: doxycycline became the preferred drug choice for treating children of any age because of the potential for severe or fatal cases.
Short courses of doxycycline to treat RMSF do not cause significant dental staining
Corticosteroids suppress active disease, which is assumed to be due to inflammatory mechanisms
RSMF - Prognosis
Mortality rates in RMSF vary according to the following criteria:
Delay in diagnosis
Delay in effective antibiotic treatment - In a 1995 study, antirickettsial therapy within the first 5 days of illness reduced the risk of mortality 5-fold compared with treatment initiation after the 5-day mark[9]
Age
Race
Gender - Mortality risk is higher in males
Severity of the disease
Presence of chronic alcohol abuse
Presence of glucose-6-phosphate-dehydrogenase deficiency
The mortality rate in untreated cases of RMSF is 20-25%; rates can be as low as 5% with proper antibiotic therapy and as high as 70% in untreated elderly individuals
RMSF - Prevention
Protective measures against tick bites include the following:
Avoid dogs with ticks and tick-infected areas
Use protective, light-colored clothing that covers arms and legs; tuck pants in socks to protect legs
Apply tick-repellent chemicals, such as diethyltoluamide (DEET, Autan) or permethrin, to pants and sleeves
Search the entire body every 3-4 hours when in an infested area; common areas of attachment are in scalp, pubic, or axillary hair
Syphilis
Syphilis is an infectious venereal disease caused by the spirocheteTreponema pallidum
Syphilis is transmissible by sexual contact with infectious lesions, from mother to fetus in utero, via blood product transfusion, and occasionally through breaks in the skin that come into contact with infectious lesions
Syphilis has a myriad of presentations and can mimic many other infections and immune-mediated processes in advanced stages
Hence, it has earned the nickname “the great impostor” - its complex and variable manifestations of the disease prompted Sir William Osler to remark, “The physician who knows syphilis knows medicine”
Three genera of spirochetes cause human infection:
Treponema,which causes syphilis,yaws, andpinta (syphilis is T pallidum)
Borrelia,which causesLyme diseaseandrelapsing fever
Leptospira,which causesleptospirosis
Acquired Syphilis
In acquired syphilis,T pallidumrapidly penetrates intact mucous membranes or microscopic dermal abrasions and, within a few hours, enters the lymphatics and blood to produce systemic infection
Incubation time from exposure to development of primary lesions, which occur at the primary site of inoculation, averages 3 weeks but can range from 10-90 days
(CNS) is invaded early in the infection; during the secondary stage, examinations demonstrate that more than 30% of patients have abnormal findings in the cerebrospinal fluid (CSF)
During the first 5-10 years after the onset of untreated primary infection, the disease principally involves the meninges and blood vessels, resulting in meningovascular neurosyphilis
Later, the parenchyma of the brain and spinal cord are damaged, resulting in parenchymatous neurosyphilis
Syphilis - Pathophysiology
Regardless of the stage of disease and location of lesions, histopathologic hallmarks of syphilis include endarteritis (which in some instances may be obliterative in nature) and a plasma cell–rich infiltrate
Endarteritis is caused by the binding of spirochetes to endothelial cells (mediated by host fibronectin molecules bound to the surface of the spirochetes)
Resultant endarteritis can heal with scarring
Syphilitic infiltrate reflects a delayed-type hypersensitivity response toT pallidum; in certain individuals with tertiary syphilis, this response by sensitized T lymphocytes and macrophages results in gummatous ulcerations and necrosis
Antigens ofT palliduminduce host production of treponemal antibodies and nonspecific reagin antibodies
Immunity to syphilis is incomplete