Spirochetes Notes

NOTES NOTES SPIROCHETES MICROBE OVERVIEW Morphology ▪ Thin-walled, Gram-negative flexible spiral rods ▪ Length: 5–250μm; diameter: 0.1–0.6μm ▪ Unique double membrane separated by periplasmic space ▪ Corkscrew-like motility via axial filament situated lengthwise between inner and outer membranes (endoflagella) Replication ▪ Reproduction: sexual transverse binary fission BORRELIA BURGDORFERI (LYME DISEASE) osms.it/lyme-disease PATHOLOGY & CAUSES ▪ An obligate parasite that causes Lyme disease, a systemic inflammatory disease ▪ Non-spore forming ▪ Life cycle includes mammals, birds, and ticks (genus Ixodes), principally in North America ▪ Killed when exposed to hypotonic or hypertonic environments, drying, disinfectants (e.g. bleach), or temperatures > 50°C/122°F ▪ Transmission ▫ Via tick bite → enters blood → spreads to tissues and organs; especially joints, heart, nervous system ▪ Infection progresses through three stages 1. Localized disease (occurs 3–30 days after exposure) 2. Disseminated disease (days to months after exposure; multisystem involvement) 3. Late/chronic disease (months to years after exposure) 540 OSMOSIS.ORG RISK FACTORS ▪ Exposure to ticks in endemic areas ▫ Living in areas bordering forests ▫ Outdoor employment, recreation ▪ Most cases occur in late spring to summer COMPLICATIONS ▪ Meningitis, cranial neuropathy ▪ Lyme carditis ▫ AV block, myopericarditis ▪ Chronic joint inflammation ▪ Post–Lyme disease syndrome SIGNS & SYMPTOMS Early signs/symptoms of localized disease ▪ Erythema migrans (EM) rash ▫ Non-painful, gradually expanding “bull’s-eye” rash appearing at the site of tick bite; feels warm to palpation; may itch

Chapter 97 Spirochetes ▪ Constitutional ▫ Low grade fever, chills, headache, fatigue, myalgia, arthralgia, lymphadenopathy Disseminated signs/symptoms ▪ Severe headaches and neck stiffness ▪ Formation of additional EM ▪ Joint pain and swelling; especially knees, other large joints ▪ Facial palsy ▪ Palpitations (Lyme carditis) ▪ Episodic dizziness, dyspnea ▪ Pain ▫ Shooting pains, numbness, or tingling in the hands or feet ▪ Short-term memory loss Late/chronic disease ▪ Presence of nonspecific symptoms (e.g. headache, fatigue, joint pain) that persists after treatment for Lyme disease DIAGNOSIS LAB RESULTS CDC testing criteria ▪ Two tiered testing for lyme disease ▫ First test: enzyme immunoassay (EIA) or immunofluorescence assay (IFA) ▫ Second test (as needed): IgM and/or IgG western blot Other laboratory findings ▪ Blood chemistry ▫ ↑ ESR, serum creatine phosphokinase, aspartate aminotransferase (AST) and/ or alanine aminotransferase (ALT) ▪ Blood studies ▫ Anemia, leukocytosis, thrombocytopenia OTHER DIAGNOSTICS ▪ History of exposure to ticks in an endemic area and characteristic clinical presentation TREATMENT MEDICATIONS ▪ Antibiotics ▫ Doxycycline, amoxicillin, or cefuroxime axetil Figure 97.1 A bulls-eye-shaped rash, known as erythema migrans, at the site of infection with Borellia burgdorferi, the causative agent of Lyme disease. OSMOSIS.ORG 541

BORRELIA SPECIES (RELAPSING FEVER) osms.it/borrelia-species PATHOLOGY & CAUSES ▪ Relapsing fever: bacterial infection caused by Borrelia spirochetes Tick-borne relapsing fever (TBRF) ▪ Endemic ▪ Found in endemic areas ▫ Mountainous areas of North America, plateau regions of Mexico, Central and South America, Mediterranean, central Asia, Africa ▪ Caused primarily by Borrelia hermsii, Borrelia turicatae, Borrelia parkeri in North America ▪ Spread by soft tick species Ornithodoros parkeri and Ornithodoros turicata ▪ Risk factors ▫ Occupying rodent-infested cabins, caves, or other dwellings ▫ Camping near rodent nests ▪ Tick attaches to human host (usually at night during sleep) → bites and feeds on blood → saliva and spirochete enter host’s circulation Louse-borne relapsing fever (LBRF) ▪ Epidemic ▪ Caused by Borrelia recurrentis ▪ Spread person-to-person via body louse ▪ Risk factors ▫ Primarily seen in low resource countries ▫ Famines, wars; causes epidemics among refugees, migrant populations ▫ Homelessness (exposure to lice) ▫ Poor hygiene ▪ B. recurrentis grows in the body cavity Pediculus humanus corporis → human host crushes louse/louse feces with fingers → spirochete enters either through bite site, through breaks in the skin caused by scratching, or through conjunctiva when 542 OSMOSIS.ORG fingers touch eyes After entry into human host ▪ Spirochete divides every 6–12 hours (can number up to 106–108 per mL) → leaves blood and enters tissues: brain, eye, inner ear, liver, heart, testes, and other organs Pattern of intermittent illness ▪ Relapsing fever caused by spirochetemia ▪ Characterized by recurrent episodes of fever and constitutional symptoms with intermittent periods of general well-being ▫ Interval range between fevers is 4–14 days ▫ Pattern of intermittent illness caused by outer membrane lipoproteins called variable major proteins (VMPs) ▫ Employed as multiphasic antigens to evade host adaptive immunity ▫ TBRF: multiple febrile periods last 1–3 days each ▫ LBRF: first episode lasts 3–6 days, followed by a single milder episode Complications ▪ Neurological ▫ Meningitis, subarachnoid hemorrhage, cranial nerve neuritis, Bell’s palsy, hearing loss ▪ Ocular ▫ Iridocyclitis, panophthalmitis, vision loss ▪ Cardiac ▫ Myocarditis, cardiac failure ▪ Respiratory ▫ Bronchopneumonia, acute respiratory distress syndrome ▪ Hematologic ▫ Thrombocytopenia ▪ Other ▫ Hepatitis, splenic rupture ▪ During pregnancy

Chapter 97 Spirochetes ▫ Spontaneous abortion, prematurity, neonatal death ▪ Jarisch–Herxheimer reaction ▫ During treatment with antibiotics → release of proinflammatory cytokines triggered by products released from dead microbes SIGNS & SYMPTOMS ▪ Characteristics of febrile episodes ▫ Sudden onset of high fever → crisis phase: chills, ↑ ↑ temperature, ↑ HR, ↑ BP → diaphoresis, ↓ fever, ↓ BP ▫ ↑ mortality during crisis and immediate aftermath ▪ Constitutional ▫ Sudden onset of high fever and chills; followed by headache, myalgia, arthralgia, nausea ▪ Neurologic ▫ Dizziness, delirium, stupor, facial palsy ▪ Cardiac ▫ Prolonged QTc interval. ▪ Respiratory ▫ Nonproductive cough, signs of respiratory distress ▪ Hematologic ▫ Epistaxis, petechiae, ecchymoses, blood-tinged sputum ▪ Other ▫ Hepatomegaly, abdominal pain, photophobia, skin rash DIAGNOSIS LAB RESULTS Visualization of microbe ▪ Blood: thick or thin smears ▫ Giemsa, Wright, or acridine orange stain ▫ Direct or indirect immunofluorescence ▫ Phase contrast or dark field microscopy ▪ PCR, culture, serology ▪ Tissue specimen ▫ Silver stain (e.g. Warthin-Starry, modified Dieterle) ▫ Immunofluorescence TREATMENT MEDICATIONS ▪ Antibiotics ▫ Penicillin G, ceftriaxone, doxycycline OTHER INTERVENTIONS Prevention ▪ Avoidance and eradication of vector OSMOSIS.ORG 543

LEPTOSPIRA osms.it/leptospira PATHOLOGY & CAUSES ▪ A spirochete that causes the disease leptospirosis ▫ AKA Weil's disease, Weil–Vasiliev disease, swineherd's disease, rice-field fever, waterborne fever, nanukayami fever, cane-cutter fever, swamp fever, mud fever, Stuttgart disease, canicola fever ▪ Infected mammal excretes microbe in urine which remains viable in stagnant water and wet soil → environmental exposure by humans → microbe usually enters via non-intact skin, mucous membranes, or conjunctivae (rarely via contaminated food, water, or aerosols) ▪ Effects of microbe ▫ Damages blood vessel endothelium → organ damage ▫ Inhibits the Na+-K+-Cl- cotransporter activity in the thick ascending limb of Henle → hypokalemia, hyponatremia COMPLICATIONS Electrolyte imbalance, kidney failure Hepatitis, hepatic hemorrhage Aseptic meningitis Pulmonary hemorrhage, acute respiratory distress syndrome (ARDS) ▪ Uveitis, optic neuritis ▪ Myocarditis ▪ Rhabdomyolysis ▪ ▪ ▪ ▪ SIGNS & SYMPTOMS ▪ Variable clinical course ▫ Ranges from mild disease that resolves uneventfully to severe and potentially fatal ▪ Common symptoms ▫ Abrupt onset of fever, chills ▫ Headache 544 OSMOSIS.ORG ▫ Nonproductive cough ▫ Pharyngitis ▫ Myalgias, arthralgias ▫ Conjunctival suffusion (redness without exudate) ▫ Lymphadenopathy ▫ Jaundice ▫ Uremia, bacteremia, oliguria, hypokalemia DIAGNOSIS DIAGNOSTIC IMAGING Chest X-ray ▪ Nodular densities, consolidation; may have a ground-glass appearance LAB RESULTS ▪ Identification of microbe ▫ PCR, ELISA, microscopic agglutination ▪ Other laboratory studies ▫ Leukocytosis with left shift ▫ Hypokalemia, hyponatremia ▫ ↑ hepatic transaminases, ↑ direct bilirubin ▫ Urinalysis: proteinuria, pyuria, granular casts, hematuria, ↑ creatine kinase ▫ CSF: neutrophilic pleocytosis, ↑ protein OTHER DIAGNOSTICS ▪ History and physical examination

Chapter 97 Spirochetes OTHER INTERVENTIONS TREATMENT MEDICATIONS ▪ Antibiotics ▫ Doxycycline (mild cases), penicillin (severe cases) ▪ Address complications ▪ Prevention ▫ Avoidance of potential infectious sources of infection, domestic animal vaccination TREPONEMA PALLIDUM (SYPHILIS) osms.it/syphilis PATHOLOGY & CAUSES ▪ The spirochete bacterium that causes syphilis, a localized and systemic disease ▪ Transmission ▫ Sexually: by direct contact with an infectious lesion (primarily) → enters via microscopic abrasions ▫ Perinatally: crosses placenta easily → congenital syphilis ▪ Progresses through stages ▫ Primary: localized sores (chancre) appear after about three weeks at site of infection ▫ Secondary: 2–8 weeks after chancre resolution, hematogenous bacterial dissemination causes systemic symptoms ▫ Latent: asymptomatic ▫ Tertiary (late): organ damage develops 10–30 years after initial infection ▪ Neurosyphilis and ocular syphilis can occur at any stage ▫ Neurosyphilis begins when the microbe invades the CSF RISK FACTORS Unprotected sex Multiple sexual partners Biologically male Biologically-male individuals engaging in same-sex sexual contact (MSM) ▪ IV drug use ▪ Existing sexually-transmitted disease, especially HIV ▪ ▪ ▪ ▪ COMPLICATIONS ▪ Cardiovascular: syphilitic aortic aneurysms, dilated aorta, aortic valve regurgitation; coronary artery narrowing ▪ Congenital syphilis: hemolytic anemia, deafness, keratitis, periostitis ▪ Neurosyphilis: dementia, meningitis, brain or spinal cord ischemia/infarction, seizures, ischemic stroke ▪ Ocular syphilis: uveitis, vitritis, retinitis, optic neuropathy, blindness ▪ Otosyphilis: hearing loss, tinnitus SIGNS & SYMPTOMS Stages ▪ Presentation will vary according to stage of disease ▪ Primary ▫ Chancre: painless ulcers at inoculation site (in contrast to painful lesions seen in genital herpes or chancroid) ▫ Single or multiple; usually firm, round, painless ▫ Heals with or without treatment; treatment prevents progression to secondary stage ▪ Secondary ▫ May be asymptomatic ▫ Rash: diffuse rough, reddish-brown maculopapular on extremities, palms of hands and/or soles of feet, back; raised, gray-whitish lesions on mucous membranes ▫ Condylomata lata OSMOSIS.ORG 545

▫ Myalgia ▫ Fatigue ▫ Lymphadenopathy ▫ Fever ▫ “Moth-eaten” alopecia ▫ Resolves without treatment; treatment prevents progression to latent and tertiary stages ▪ Latent ▫ Positive serology; asymptomatic ▪ Tertiary (late) ▫ Gummas: non-cancerous, granulomatous growths on internal organs, bones, skin; more common in HIV-infected individuals ▫ Evidence of organ involvement; charcot joints, aoritis (due to destruction of vasa vasorum) Complications ▪ Neurosyphilis ▫ Meningitis: headache, nausea and vomiting, stiff neck ▫ Tabes dorsalis: muscle weakness, locomotor ataxia, ↓ proprioception, incoordination ▫ General paresis (paralytic dementia) ▫ Facial and limb hypotonia, intention tremors ▫ Forgetfulness, personality changes ▪ Ocular syphilis ▫ ↓ visual acuity; loss of vision ▫ Argyll Robertson pupil: small pupils that constrict poorly in response to direct light ▪ Serum treponemal tests ▫ Fluorescent treponemal antibody absorption (FTA-ABS) ▫ Treponema pallidum particle agglutination assay (TPPA) ▫ Syphilis enzyme immunoassays (EIAs) ▪ If neurologic symptoms, lumbar puncture and CSF examination ▫ ↑ lymphocytes, ↑ protein ▫ CSF-VDRL reactivity OTHER DIAGNOSTICS ▪ History and physical examination Figure 97.2 A painless penile chancre, seen here, is the clinical manifestation of primary syphilis. Congenital syphilis ▪ Presents with vesicular/bullous rash, rhinitis, hepatosplenomegaly, jaundice, and pseudoparalysis DIAGNOSIS LAB RESULTS ▪ Identification of microbe ▪ Serum nontreponemal tests (may be nonreactive in late neurosyphilis) ▫ Venereal disease research laboratory (VDRL) ▫ Rapid plasma reagin (RPR) 546 OSMOSIS.ORG Figure 97.3 Condylomata lata, seen here, are the clinical manifestation of secondary syphilis.

Chapter 97 Spirochetes TREATMENT MEDICATIONS ▪ Parenteral (IM/IV) penicillin G ▫ Doxycycline or tetracycline (PO); ceftriaxone (IM, IV) if penicillin allergy OTHER INTERVENTIONS ▪ Treat partners ▪ Screening during first prenatal visit (VDRL or RPR) OSMOSIS.ORG 547