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Arboviruses Epi & Basic Characteristics Symptoms/Dx. Treatment/Prevention Remember that Rubella is a Togavirus also. Headache, Fever, Nuchal Rigidity, Altered mental status=viral meningitis All the above + focal neurological signs, seizures, altered consciousness, behavioral/speech problems=viral encephalitis Supportive for all, if bacterial meningitis is suspectedAbx Think of Paul Bunyon wearing a toga, bitten by a mosquito b/c of good flavor. Alphaviruses (Togaviridae) Specific viruses are listed below the underlined genus Category B (think alpha males wear togas) Dx. Of arboviruses CSF/CT then LP WBC of CSF 50->1000 x 109/L, normal glucose, slightly elevated protein Bioterrorism Eastern Equine Encephalitis (EEE) Eastern and Gulf Coast Caribbean and south America Western Equine Encephalitis (WEE) Venezuelan Equine Encephalitis (VEE) Western USA Flavivirus (Latin Flavus = Yellow, Found world wide Mosquito and Tick Transmission Yellow Virus)—Correlate this with Yellow Fever (also HCV is in this category— yellow bc of jaundice) SW USA South& Central Americas Worst prognosis of the alphaviruses (fulminant ds. w/ high mortality) High incidence of neurological problems Dx. IgM Ab Capture ELISA Lower incidence of neurological problems Dx. IgM Ab Capture ELISA Mild disease, rare neurological problems Dx. IgM Ab Capture ELISA Supportive for all, if bacterial meningitis is suspectedAbx Africa, Middle East, Russia, India. Outbreak in NYC in ’99. Culex, Anopheles, Aedes mosquito vectors. Severe muscle weakness Erythematous maculopapular rash (neck, trunk, arms legs) St. Louis Encephalitis August-October outbreaks Dx. IgM Ab Capture ELISA Dengue Virus Most important arbovirus in humans West Nile Virus WHO: 4 Criteria for Dx. Fever, Hemorrhage, Circulatory failure, Hepatomegaly Yellow Fever JBEV Encephalitis Bunyviruses (negative sense RNA) LaCrosse Encephalitis Hantavirus Rabies (Rhabdoviridae) (negative sense RNA) Mosquito Borne . Formerly in Memphis. Endemic in Africa and South America. Sylvatic (mosquitoanimalhuman) and urban (mosquitohuman) transmission cycles. Most common flavivirus. Found in Asia and south pacific Monitor birds and mosquitos Dx. IgM Ab Capture ELISA Dengue Fever, after fever breaks can get Dengue hemorrhagic fever (can have neurologic sequelae; prior infection of one serotype of dengue virus increases risk of DHF) or Dengue shock syndrome, strange metallic taste Dengue fever has centrifugal maculopapular rash and “Break bone disease” (extremely painful diffuse body pain) Fever, Hemorrhage, Circulatory failure, Hepatomegaly Dx. Serologic, Virus isolation (CPE), or RT-PCR genome detection Hemorrhage, hepatic failure, proteinuria, renal failure, death Lumbosacral myalgia Black Vomit (from hemorrhage of stomach lining) Vaccine Available Dx. Serologic, Virus isolation (CPE), or RT-PCR genome detection Vaccine available Supportive for all, if bacterial meningitis is suspectedAbx Most common Seizures and focal neurological signs Rodent borne infection (aerosolized excreta). Four corners area of USA (Sin Nombre Hantavirus is predominant form in US) Carnivorous animals and bats. Virus pathway: Bitemusclesensory nervesSpinal ganglialimbic system in brain Hantavirus pulmonary syndrome (HPS) Abdominal discomfort, myalgia involving large muscles of thigh and lower back Tetrad: thrombocytopenia, leukocytosis, elevated Hct, immunoblasts in peripheral blood smear Dx. RT-PCR, IgM and IgG titers via ELISA Uniformly fatal if not treated (respiratory arrest) Prodrome (malaise, chills, aches, headache, itching around bite)neurologic phase (acute) has paralysis w/hydrophobia, autonomic instability, hyperactivity “furious rabies” or paralysis “dumb rabies” coma (eventual respiratory arrest) Dx. Based on history, serology is not useful Negri bodies (eosinophilic inclusion bodies in cytoplasm of neurons). No treatment, only supportive. Avoid rodent contact Post exposure: HRIG Post infection vaccination (three possible inactivated vaccines: HDCV,RVA,PCEC) Wound cleansing. Must treat before acute phase Bacteria Epi & Basic Characteristics Symptoms/Dx. Treatment/Prevention Obligate intracellular (utilizes hosts ATP) Tick (dog ticks) defecates and fecal material is scratched into a woundBlood vesselsmultiplies in endothelial cells and smooth muscle layer of small blood vessels Microthrombosis, perivascular hemorrhage,edema RMSF (A vasculitis w/ inflammation, microthrombi, edema responsible for rash and headache) Hallmark Features: Severe headache, high fever, maculopapular rash (starts on ankles/wrist and spreads as petechial rash to palms/soles and trunk so is centripetal/inward spreading), history of tick bite Must treat immediately if you suspect RMSF Tickborne Bacterial Zoonosis All are intracellular parasites Rickettsia rickettsii Treat adults and children with doxycycline Highest from NC to OK including TN (not much in Rocky Mountain area). Also in Wyoming. Don’t memorize this picture. Differential for rash on palms/soles of feet: Coxsackie A (hand,foot,mouth disease), RMSF, or Syphilis. Drive CARS with palms/soles Ehrlichia & Ananplasma HME (human monocytic ehrlichiosis): E. chaffeensis HGA (human granulocytic anaplasmosis): Anaplasma Can’t culture Most common form of death in tickborne infections Obligate intracellular (infect WBC’s) Human Monocytic Ehrlichia (HME) Human granulocytic anaplasmosis (HGA) Tick transmission (different tick than RMSF ticks so different geographic area) Flu like symptoms early, followed by rash (3-5days after symptoms), as rash spread the symptoms become systemic and can involve CNS (meningitis) Can effect heart: Myocarditis, or lung (pneumonitis) Dx. Low platelets (thrombocytopenia), low RBC count, renal failure, blood and protein in urine, hyponatremia Dx.Cross reacts with various proteus strains (OX Strains) and get agglutination which is the basis for the Weil-Felix test/reaction that is non-specific but still used. Confirm Weil-Felix with a specific serological rickettsial test (only positive until several weeks after a tick bite) Symptoms overlap with RMSF (close relative), can’t distinguish w/o RMSF rash Milder than RMSF typically and rash is less common (rash very rare with HGA) No Weil Felix rxn!!! HME: Has intracellular inclusions called morulae in monocytes. HGA: has morulae in granulocytes. Can’t culture Collectively referred to as Ehrlichia Coxiella burnetii Not on test Category B Bioterrorism Bartonella (Think of Bart Simpson singing Cat Scratch Fever) Can’t culture. Obligate intracellular parasite. Related to Legionella. Cow, Sheep, Goat reservoir. Transmitted by aerosol, handling viscera. (aminotic fluid, raw milk, sometimes ticks). Spore form permits distribution by wind (Cat. B Bioterrorism). Pediatric patients HME Flu like illness (Q Fever) Atypical pneumo. Maculopapular rash, chronic infections can lead to endocarditis Dx. Serological HGA Cat Scratch Disease Swollen lymph glands near site of scratch or bite (no symptoms in cats and dogs though) Flu like symptoms in adults Can cause disseminated disease in immunocompromised Dx. Clinical mainly (history of cat bite/scratch), not routinely cultured Treat with Doxycycline Borrelia burgdorferi Spirochete, transmited from Ixodes Tick BAKE a key lyme pie: Bell’s palsy, arthritis, cardiac problems, erythema chronicum migrans Think: New England (named after Lyme, CT) Seen by direct light microscopy. Surface proteins undergo Ag variationrelapsing fever, humoral and CMI response get rid of bug, untreated pt. can develop chronic Lyme Disease (see below). Hosts cellular immune response controls infection but is responsible for pathology. LD has a tropism for: skin, CNS, heart, joints, and eyes “Bull’s eye rash” (Erythema Chronica Migrans): Outer red border with inner clearing, rash expands over time and can have additional new ones show up. Life cycle involves mice and white tailed deer Early: Doxycycline or amoxicillin in children Chronic: Prolonged IV cephalosporins (inneffective rx. With HLA-D4 pt.) Prevention: Pull off tick within 24h and can entirely avoid disease NO Vaccine in USA (pulled off market) Occurs when ticks are active (May through October) Most common tick-borne disease in US Initial symptoms: Nonspecific Flu Like Symptoms (Fever, headache, lethargy, muscle pain, stiff neck, joint inflammation, lymphadenopathy) Late manifestions: Nervous System: Facial nerve (Bell’s) Palsy (CN VII) Heart: Arrythmia, myocarditis, Pericarditis, AV block Joints: Erosive, painful arthritis of large joints (immune complexes, migratory arthritis), think of Osteoarthritis of the Knee Dx. ELISA/indirect IFA , then must confirm with western blot (serodiagnosis produces lots of FN— since most of these pt. are seen by Rheumatologists) Relapsing Fever (comes and goes)—ag variation Dx. Is serological. Also large spirochete can be seen in Wright-Giemsa-stained blood smear Borrelia hermsii (tick) Borrelia recurrentis (louse) Not on Test Leptospira interrogans Not on Test Spirochete, thin with hooks (question mark shaped, hence name) Seen by direct light microscopy, but usually DF microscopy is used Doxycycline or Penicillin Swineherd’s ds, swamp or mud fever, flu like illness, can progress to hepatitis if not treated Prevention: Vaccination of domestic livestock and pet’s Symptoms: flu-like symptoms to jaundice, nephritis, meningitis Water contaminated w/animal urine (Jet skiier’s, Hawaii has the highest incidence, triathlon contestants, etc.) R. prowazekii Not on Test Category B Bioterrorism Not transmitted by an arthropod! Human-human spread by lice, associated with close quarters (military) Typhus, symptoms similar to RMSF (fever, headache, rash) but rash moves from trunk to periphery. Think RMSF starts near wrists while Typhus starts near trunk. Category B Bioterrorism Agent Murine Typhus (R. Typhi): Mild version of typhus on texas gulf coast Bacteria (Bioterrorism) Epi & Basic Characteristics Symptoms/Dx. Treatment/Prevention Bacillus anthracis (Anthrax) Domesticated farm animals are reservoir Potential Bioweapon Dx. Cluster of flu like illnesses (mail handlers), papular to pustular skin lesion that develops into an eschar (cutaneous form), dry non productive cough, Widened mediastinum (inhalation anthrax) on XR Use ciprofloxacin IV or Doxy IV and at least one other Abx (to cross BBB) Category “A” Agent G+ Aerobic spore former (spore must be finely milled for bioterrorism to be infectious) Large Boxcar G+ chains Post –exposure prevention: 40 days of ciprofloxacin prophylaxis since there is a long incubation period of the spores Phases of inhalation anthrax: Flu like symptoms followed by severe fever, shortness of breath, and chest pain (infection of lymph nodes rather than a pneumonia) (more N/V less rhinorrhea to diff. from influenza. Key symptoms of inhalational anthrax: infection of hilar/mediastinal lymph nodes (not a true pneumonia) and mediastinal widening on xray Vaccine exists for military Virulence factor: Antiphagocytic non-antigenic capsule containing p-glutamic acid, AB toxin that contributes to symptoms AB Toxin: B=Binding component and is the protective antigen (PA) allows binding to host receptor and facilitates endocytosis and entry of A A= Active subunit, two A subunits: Edema Factor (EF) is a calmodulin-activated adenylate cyclase (responsible for mediastinal edema), Lethal Factor (LF) is a metalloprotease that cleaves MAP kinases and disrupts immune response Spore is infectious form, spores germinate and become encapsulated forming vegetative cells that release toxin (swelling, sepsis, necrosis) Yersinia pestis (Plague) Transmission via flea from ground rodents Dx. Rapid flu test to rule out flu, culture of blood and CSF, Gram stain , IF Ab stain of CSF and blood to see G+ boxcars Cause of Bubonic Plague, Secondary and primary plague pneumonia (primary is expected in bioterrorism attack) Category “A” Agent New Mexico and adjoining states Bubonic: Infection from flea bite, swollen lymph node (Buboes), w/ fever, chills, headache, etc. Gentamicin Use Streptomycin if available No response to B-lactams nor macrolides Chubby gram negative rods with bipolar inclusion bodies (“safety pins”) (same as Tularemia) West of Mississippi river Septicemic: w/ and w/o buboes, rapid progression and general organ failure w/vomiting diarrhea (petechiae to extreme DIC) Pneumonic: Secondary pneumonic plague (disseminates from primary infection), very contagious and requires isolation of pt. and prophylaxis for all exposed individuals sputum is more bloody and watery than purulent (productive cough). Primary pneuomic plague (due to direct inhalation) respiratory symptoms are same but precede septicemia. Would be seen in terrorist attack. Keys to Dx. are history, large swollen nodes Dx. By serology to Abs to F1 surface Ag (confirmatory), gram stains of buboes may reveal safety pin rods, culture, IF, and RADT can be used Francisella tularensis Category “A” Agent High incidence in Arkansas Direct contact with infected animals (tick and deer fly) Most common reservoir is rabbit Small g- coccus hard to see in gram stain No human human transmission Tularemia: “Rabbit Fever” Very infectious with only 10-100 organisms required (only specialized labs culture due to danger!) Keys to Dx. History, papules, regional lymphadenopathy, atypical pneumonia, failure to respond to beta lactams and macrolides Symptoms: Ulceroglandular: Most common form. Maculopapular, pustular, rash at site of entry, swollen painful lymph nodes, fever Systemic: Most lethal form. Toxicity (septicemia), swollen glands Pneumonic: non productive cough, patchy infiltrates on XR, hilar lymphadenopathy, atypical pneumonia, dyspnea, pleuritic chest pain, Gentamicin Use Streptomycin if available No response to B-lactams nor macrolides Dx. Culture of blood and sputum (specialized lab), serological, RADT Brucella abortus (cows) suis (pigs) melitensis (sheep and goats) Category “B” Agent G-aerobic coccobacillus Undulant Fever Facultative intracellular parasite of RES, Symptoms: slow moving chronic infection, relapsing fever w/ night sweats, weakness, back ache (can infect vertebrae), wt. loss, fatigue, typical biopsy of lesion shows a granuloma Animal reservoir is cow, sheep, pig, and wild animal reservoir Prolonged Abx Control of pasteurization, vaccine for cattle, destroy infected herds Differential: TB Transmission: Contact and consumption of raw milk or unpasteurized cheese. No human-human transmission Lab Dx. Serological, can be cultured on rich medium (may take a week) Seen in recent immigrants from Mediterranean area and Mexico Prions (Proteinaceous Infectious Particle) Disease Characteristics Transmissable Spongiform Encephalopathies (Human) -Spongiform changes Kuru -Ritual Cannabilism in Papa New Guinea -This is a pic of the cannibal tribe (fun fact only) Molecular Biology & Clinical Symptoms -Single exon on chromosome 20 encodes a protein highly expressed in neurons -209 Amino Acid Glycoprotein produced from this codon -Normal form is PrPc Disease form is PrPSc Resistant to proteases, nucleases, radiation, formalin,etc. -the normal protein is not crucial for survival, but is needed in order to have any of the pathology Improper folding causes aggregates (β pleated sheets) in neuronsapoptosis by unknown mechanism -Mechanism: PrPc is required, some mutation happens and PrPSc accumulatescauses binding to PrP* intermediate which leads to more and more PrPScchain reaction produces tons of PrPSc -Species barrier exists (probably due to varying homology of proteins between species) -Very rare to get the mutation (which is why it happens later in life) -Also explains why seeding of prions has a much quicker effect -Template prion and not amino acid sequence dictates final conformation -He will eat you and get Kuru Treatment Generally none, genetic counseling and prophylactically managing cattle/blood transfusions, etc. Creutzfeldt-Jakob Disease (don’t memorize this picture) Gerstmann-Straussler-Scheinker Disease (GSS) Fatal Familial Insomnia (FFI) Variant CJD (vCJD) Transmissable Spongiform Encephalopathies (Animal) Scrapie Bovine spongiform encephalopathy (BSE) -Most common TSE -Average age of onset is 60 years, accounts for 85% of CJD -Sporadic (Chance) and iatrogenic forms -Iatrogenic (dural grafts, corneal grafts, etc. present quicker due to location near CNS) -Familial form (AD pattern)—associated with specific mutations (age of onset is earlier, less rapid deterioration in familial) -Rapidly progressing Dementia/Myoclonus are main signs -Cerebellar ataxia, akinetic mutism also -Sporadic CJD has periodic complexes in an EEG, KNOW THIS -AD pattern of inheritance -Associated with a mutation at codon 102 of prion protein -Average age of onset is 48, 5 year mean time to death -numerous amyloid plaques in addition to spongiform changes -AD inheritance, mutation at codon 129 and 178 -Gait abnormalities and ataxia, dementia is less common but there is NO characteristic EEG -Same as Mad Cow Disease -Transmission is from contaminated beef but can also be from blood transfusions -Homozygous for codon 129 mutation (met), KNOW(He said in class this is the one we want to know) -Higher level of infection in periphery than in classical CJD -anxiety, depression, visual problems -Atypical EEG, prion positive tonsil biopsy -“Florid plaques and spongiform changes in basal ganglia” -Sleep disturbances and autonomic dysfunction -Ataxia of sheep and goats -Alimentary tract transmission -Found in lymphatic tissue at 1 yr -Mad Cow Disease Infected Cow Chronic Wasting disease -was not elaborated on -No treatment, dead within a year (2-4 in familial form) -None, average age of onset is 29 with a 14 month survival time