Spirochetes: Spirochetes Borrelia spp Leptospira spp Treponema spp


Borrelia sp.: Borrelia sp. Microaerophilic-to-anaerobic Loose, irregular coils many not cultivated in vitro Visualization silver staining darkfield microscopy Highly-adapted to arthropod transmission


Slide5: Acute infection with febrile episodes septicemia, with fever, headache, muscle pain immune response: lysis of bugs, shock due to endotoxin release patient returns to normal, usually 5-14 days between relapses Sporadic in US, distributed worldwide Antigenic variation single strain of B. hermsii progeny may represent more than 25 serotypes occurs without selective pressure of host immune response Relapsing Fever


Slide6: Transmitted animal-to-animal, animal-to-human by ticks, human-to-human by lice Speciation louseborne disease: B. recurrentis tickborne disease: named after transmitting tick Relapsing Fever


Relapsing Fever: Relapsing Fever Tickborne disease transmitted by soft ticks (genus Ornithodoros) O. turicatae, O. parkeri, O. hermsi in US, 15 others worldwide US: AZ, OK, CA, NM, CO, WA, TX, KS Louseborne disease: body/headpubic lice (Pediculus humanus corporis/capitis/pubis) also bedbugs


Lyme Borreliosis: Lyme Borreliosis Late 1970s, Old Lyme, CT Higher-than-expected incidence of childhood arthritis Pestered health officials, led to description of Lyme disease Caused by Borrelia burgdorferi Found in museum voucher specimens (mice, ticks) from early 20th century Most prevalent human tick-borne disease in the US, Europe, parts of Asia


Lyme Borreliosis: Incubation period: 7 - 14 days (range 3 - 30 days) may be subclinical, manifest only nonspecific symptoms: fever, headache, myalgia. First sign: erythema migrans spirochetes multiply in skin, quickly enter circulation rash appears days-to-weeks after tick bite surround site of inoculation, expand in concentric rings disappear spontaneously after several weeks Second stage: musculoskeletal signs (migratory joint, muscle pains), rare CNS signs, cardiac damage Lyme Borreliosis


Lyme Borreliosis: Delayed humoral response circulating organisms killed by phagocytes, complement complement-independent antibody effects lack of LPS limits MAC formation without antibodies Some spirochetes not cleared from circulation localize inside host cells cross endothelium by disruption of tight junctions, transcytosis cell invasion key factor cardiac muscle, CNS damage Human transplacental transmission reported Lyme Borreliosis


Lyme Borreliosis: Lyme Borreliosis Inflammation: likely root cause of symptoms synovial cell colonization activates IL-8 production potently chemotactic for PMN fibrin deposition, fluid accumulation Cellular response shifts to lymphocytes, plasma cells Chronic disease may be autoimmune-mediated anti-flagellar antibodies bind to cardiac, CNS antigens


Canine Lyme BorreliosisMost common domestic animal host: any breed, age, sex: Canine Lyme Borreliosis Most common domestic animal host: any breed, age, sex Sudden onset lethargy, inappetence, fever, swollen LN acute arthritis, increased synovial fluid Inflammation in joint space high synovial fluid cell counts (90% PMN), fibrin Swollen, edematous LN Also CNS infection cervical pain, depression, anorexia, seizures Fatal renal disease: Lyme-specific immune complexes, complement deposition in glomeruli


Epidemiology: Epidemiology Human encroachment into habitat of white-tailed deer Spread from deer, mice to humans by the bite of soft ticks adults, nymphs genus Ixodes, primarily I. scapularis (dammini) 2 year life cycle adult females produce ~ 2000 eggs in spring hatch as uninfected larvae feeding on initial, infected hosts (mouse, lizards) emerge from dormancy following spring as infected nymphs


Slide14: quest for new hosts, mate after attaching to deer/other mammals female feeds to repletion, drops off, remains on ground until spring, cycle complete. Infection rate in nymphs 10 - 25%, adult ticks ≤ 60% Important factor: spirochete migration in tick during feeding migrates (24 - 48 h) from midgut to salivary glands short-term tick exposure ==> no infection Intrauterine transmission in dogs Transplacental infections: only direct human-to-human transmission Dogs not reservoirs for human infection


Prevention, Control, and Therapy: Prevention, Control, and Therapy Antimicrobial therapy successful for primary disease secondary or tertiary disease Rx often unsuccessful doxycycline, amoxicillin duration usually 4 weeks (slow multiplication, in vivo persistence) Dogs recover clinically in 24 - 48 h


Prevention, Control, and Therapy: Prevention, Control, and Therapy Immune response primary target : outer surface proteins (Osps) humoral response develops slowly bactericidal antibodies peak after 3 - 5 weeks Serum antibody levels decline with Rx often rise over subsequent months suggest persistent infection Tick control important for prevention use of acaricides, repellents, daily grooming little positive from genocidal approach to deer populations


Leptospira interrogans: Leptospira interrogans 13 serogroups, >200 serovars Disease in humans, domestic animals Zoonosis: rodents, domestic animals Emerging infectious disease of humans? Most widespread zoonosis?


Epidemiology - Human Disease: Epidemiology - Human Disease Temperate climates few serovars infection via direct contact: infected farm animals (urine aerosols in milking parlors, milk of infected cows) Tropical climates: many serovars (humans, domestic animals) many reservoirs exposure via environmental contamination Urban environment rodent-borne leptospirosis frequently misdiagnosed


Epidemiology: Epidemiology Many serovars apparently host-adapted disease relatively mild, sporadic venereal transmission, lifelong colonization of genitourinary tract serovars hardjo (cattle), bratislava, tarassovi (swine) Others nonadapted catastrophic infections: abortion storms, death of adults carrier state brief serovars pomona (swine, cattle), canicola (dogs)


Pathogenesis: Pathogenesis Enter through cuts, abrasions; conjunctivae Evade local defenses, produce bacteremia: shorter (host-adapted strains) or longer (nonadapted strains) Proliferate in liver, kidneys, spleen, meninges Antibodies, complement eliminate leptospires from blood stream, tissues other than brain, eye, kidneys multiply in proximal convoluted tubules excreted in urine by asymptomatic reservoir hosts: few days to life


Pathogenesis: Human disease nearly-subclinical, flu-like illness fulminant, fatal: pulmonary hemorrhage; hepatic, renal failure fatal human congenital infection Domestic animals fetal death, abortion Pathogenesis


PathogenesisMechanisms: Motility, attachment (fibronectin binding) Exotoxins: sphingomyelinase Outer envelope antiphagocytic? Immune complexes associated with CNS inflammation Autoantibodies (anticardiolipin) in acute human illness Antileptospiral antibodies cross-react with equine ocular tissues involved in pathogenesis of recurrent uveitis retinal damage relates to presence of B lymphocytes in retina Pathogenesis Mechanisms


Disease in Domestic Animals: Disease in Domestic Animals Cattle: commonly serovars hardjo and pomona hardjo host-adapted sporadic abortions, infertility, mild clinical signs. female upper reproductive tract colonized, organism available for interaction with embryos localization in seminal vesicle: infections transmitted at breeding pomona non-adapted more dramatic signs fever, icterus, hemoglobinuria abortion storms


Disease in Domestic Animals: Disease in Domestic Animals Swine: serovars pomona and bratislava bratislava host-adapted clinical picture similar to hardjo in cattle subclinical disease, lifelong shedding pomona non-adapted infections similar to pomona in cattle abortion storms, fever, icterus, anemia, metritis, meningoencephalitis, death source may be wildlife (skunks, raccoons, opossums, deer) Horses bratislava adapted mild, sporadic infection of adults late-term abortions pomona, kennewicki nonadapted fever, icterus, abortion


Disease in Domestic Animals: Disease in Domestic Animals Dogs bratislava adapted: mild disease, infertility, weak pups canicola non-adapted high fever, myalgia, bloody vomit vascular damage: disseminated intravascular coagulation, melena, epistaxis, petechial hemorrhage renal localization, leptospiruria by 2 weeks PI acute nephritis progresses to chronic interstitial nephritis, renal failure


Treponema pallidumEndemic treponematoses affect > 2.5 million worldwide: Treponema pallidum Endemic treponematoses affect > 2.5 million worldwide T. pallidum ss carateum (pinta), ss pertenue (yaws) ss pallidum: 3stages of syphilis primary: chancre, disappears spontaneously secondary: penetrate mucus membranes, enter blood-stream, fever, rash tertiary: invade heart, musculoskeletal system, CNS, relatively noninfectious


Syphilis: Syphilis Transplacental transmission during latency congenital syphilis:1,000 US cases annually malformed teeth, long bones, cardiac lesions, CNS effects (learning disabilities, mental retardation)


Treponema pallidumVirulence Mechanisms: Treponema pallidum Virulence Mechanisms Knowledge limited lack of in vitro cultivation maintained by serial passage in rabbit testicles no suitable in vivo model Lack of outer membrane proteins Protection from immune response by cloaking with host proteins Fibronectin binding treponemal antigen-fibronectin complex may ==> antibodies vs fibronectin immune-mediated damage to cardiopulmonary, musculoskeletal, and central nervous systems in tertiary syphilis


Treponema brennaborensePapillomatous digital dermatitis (hairy foot warts): Treponema brennaborense Papillomatous digital dermatitis (hairy foot warts) 40% of US dairy herds Clinical signs episodic lameness, variable severity acute/chronic ulceration of skin on hoof cows walk on their toes Erosions of superficial epidermal layers, foul odor Lesions often surrounded by ridge of hyperkeratotic skin with hypertrophied hairs (“hairy”) Spirochetes deep in lesions