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Influenza Respiratory virus a. RSV b. parinfluenza RSV and PIV c. human metapneumovirus Other Respiratory virus d. adenovirus e. coronavirus f. Picornovirus G. Reovirade Family: orthomyxociruses Particle: segmented – sense rna Surface proteins: neuraminidase (release of virus) & hemagglutin (attachment), M2 uncoats (only in type A) Incubation: 1-4 days, viral shedding 1-5 post inf. Spread: aerosol droplets, A- shift and drift, B- drift only Diagnosis: culture, serology, rapid viral diagnostic test: IF, EIA, PCR Prevention and treatment: 1. Immunization 2. Drugs Vaccine priority: elderly, nursing homes, young kids, pregnant women, travelers Type A: treat w. amantadine/rimatadine (block M2) Type A & B: oseltamivir (oral, kids)/ zanamivir (inhaled) both are neuramidase inhibitor (no resistance yet) 3 conditions for pandemic: no immunity, jump b/w species, human to human transmission (bird flu h5:N1 has all but last) Family: paramyxovirus Particle: enveloped, non-segmented, negative sense rna Diseases: measles, mumps, rsv, parainfluenza, metapneumovirus Surface protein: g glycoprotein (attachment to resp. cells) & F glycoprotein (facilitate fusion) Time: late fall/ early spring Spread: droplets, direct contact Incubation: 2-8 days, shedding: 1-2 wks Symptoms: cold-like, otitis media Infects: kids, older adults w/ chronic diseases Diagnosis: viral isolation, viral ag test, id vRNA, serology Prevent: close contact necessary so avoid it, no vaccine Treatment: supportive care, ribavirin - 2nd most common of lower respiratory tract inf. In kids -PIV1 most common cause of croop -serotypes: PIV1 most common Reinfections common, but milder, chronic, old 5-10% hosp, 7% mortality -similar to RSV - sever illness if co-infected w. rsV - severe disease in lung and hematopoietic cell transplants spread: close contacts Note: have different family than above Particle: naked, icosahedral, ds DNA Surface: fiber protein (attachment and internalization) Spread: droplet, fecal oral route Symptoms: ½ are asymptomatic, inf epithelial cells undergo necrosis & slough off; intense inflammation, latent inf may be present for yrs Diagnosis: culture/biopsy of lower respiratory tract, direct ag assay, pcr, serology Prevent and treatment: vaccine w/ an oral, live attenuated Drugs: cidofovir and intravenous immunoglobulin Particle: ss RNA, enveloped Surface: spike protein mediates receptor binding and fusion Symptoms: common cold Time: fall/winter Diagnosis: PCR, indirect IF, diagnosis clinically Treatment: no therapy, wash hands, cover mouth Diseases: ex. SARS SARS Incubation 2-7 days Symptoms: fever, muscle ache, lower respiratory symptoms, resp failure, mortality 10-20% Therapy: supportive Family: rhinovirus (common cold) Particle: small, naked ss RNA , + sense Spread: secretions and aerosols Time: spring/summer Replicates: 33 degrees C, same temp as Nose, and URT Diagnosis: clinical Prevention & treatment: wash hands, symptomic relief Particle: naked, segmented, double stranded RNA Symptoms: mild URI Diseases: reovirus (respiratory), rotavirus (GI), Colorado tick fever agent Incidence, epidemiology, treatment- unknown Dna virus and some important members Poxviridie: small pox Rna viruses and some important members Paramyxoviridae- measles Herpesviridae- herpes simplex types 1 and 2 .Adenoviridae- adenovirus Polyoma viridae- jc virus Papilloma viridae- papilloma virus Parvoviridae- parvovirus B19 Orthomyxoviridae- influenza virus types a, b, c Co ronaviridae- coronavirus, sars Arenaviridae- lass fever virus Rhabdoviridae- rabies virus Filoviridae- ebola virus Noroviridae- Norwalk virus Bunyaviridae- California encephalitis virus, hemorrhagic fever virus Retroviridae- human immunodeficiency virus Reovirida- rotavirus Picornaviridae- rhinoviruses, poliovirus Togaviridae- rubella virus Flaviviridae- yellow fever virus Enteric virus Transmitted fecal oral All acid resistant a. Rotavirus Particle segmented double stranded rna, non enveloped Surface protein: induce neutralizing ab, multiple serotypes Incubation: 1-3 days Symptoms: most common cause of diarrhea in kids Treatment: supportive, treat symptoms Immunity: most sever in kids less than age 2, b/c by age 3 have anti-rotavirus ab, breast feeding protects, previous infection- gives partial protection Vaccine: bovine reasssortment (2,4,& 6 months), and virus like particles (just protein coat) Particle: ds DNA, no envelope Incubation: 7-10 days Symptoms: similar to rota, worse diarrhea less vomiting Particle: ss RNA, positive sense, no envelop Family: calciviridae Incubation- 1-2 days Symptoms: vomiting at first, diarrhea for 5 days, most common cause of non-bacterial gastroenteritis in adults Spread facilitated by: low infectious dose, prolonged shedding, stable in environment, great strain diversity, no induction of lasting/protective immunity, asymptomatic infection Family: astrovirade Particle: ss RNA, + sense, no envelope Transmission: contaminated food Incubation: 1-2 days - common in young children Family: picornavirade Particle: ss RNA, + sense, no envelope Disease ez. Polio, coxsackie virus a & b, echovirus - very common infectious agent symptoms: infectious, frequently asymptomatic Incubation: 2-10 days infection result in serotype specific immunity Clinical outcomes: asymptomatic (90-95%), minor illness (uri, gi upset flu)- 4-8%, 1-2% nonparalytic poliomyelitis, 1-2 paralytic mylelitis Types of Paralytic poliomyelitis: a. spinal form (asymmetric legs), b. bulbar form (cranial nerves) c. bulbospinal (combination Post polio syndrome: not infectious process, detoriate of functional abilities Vaccine: 1. inactivated poliovirus vaccine (salk: IPV)- no paralysis 2. Live, attenuated, oral poliovirus (sabin:OPV)- better mucosa Immune Response IN USA we use IPV Elimination: humans is the only natural reservoirs Non specific febrile illness, meningitis, hand foot, and moth disease, acute myocarditis, and pericaraditis, disseminated infection in the neonate (acquired perinatally form mother)- may be fatal b. Enteric adenovirus c. Norwalk like and sappor like d. astroviurs e. Enterviorus also include members of picornavirade 1. Polio virus Other Syndromes due to enterovirus infections Example of viral attachment proteins Virus family Virus Adenoviridae Adenovirus Herpesviridae Herpes simplex virus Retroviridae Murine leukemia virus Viral attachment protein Fiber protein gD and gB Gp70 Example of virus receptors Virus Epstein barr virus Human immunodeficiency virus Herpes simplex virus Target cell B lympocyte Helper t cells Epithelial cells receptor C3 complement receptor (cr2) Cd4 molecule Heparin sulfate Herpes Viruses HSV 1 and HSV 2 Varicella-zoster virus (HHV3) CMV (hhv5) HHV6 HHV7 EPSTEIN BARR VIRUS (HHV4) HHV* (Kaposi sarcoma) HSV-1- oral, involves trigeminal ganglion (most fatalities b/c encephalitis, etc HSV-2- genital, sacral ganglions, newborns get type II in birth canal- can be fatal Pathogenesis: enter via lesionlymph nodecell enlarge, develop intranuclear inclusion w/ margination of chromatin vesiculate and fluid ulcer close to mucosa cutaneous junction, get vesicles at high viral load, crusting when viral load decreases ID: 1. Restriction endonucleases and then dna fingerprint 2. Neutralizing ab (tzank test) 3. Exam proteins: elisa assay Latency: herpes is forever, reactivation causes (fever, sun, stress, menestration), a recurrent lesion may be reminiscent of the primary lesion but more restricted in size severity and duration of outbreak Varicella- ubiquitous in childhood (2nd attacks uncommon) zoster: represent reactivation of VZV latent in dorsal root ganglia (freq. immunocompromised_ Transmission—probably respiratory droplets early in varicella; slight risk for vertical transmission (especially in 1 st trimester) Pathology—latency w/in sensory dorsal root ganglia; often reactivated after 50yo or immunocompromised to cause zoster Infection of conjunctivae or URI replication in lymph nodes primary viremia (by 4-6d) replication in liver & spleen secondary viremia infection of skin (vesicular rash, by 14d) Presentation—fever & pruritic rash (maculopapules vesicles pustules scabs in varying stages, localized to head & trunk, self-limiting) Complications—bacterial superinfection (group A strep); pneumonia; encephalitis or meningitis; Reye syndrome (aspirin in children) Congenital varicella—vertical transmission thru maternal viremia causing scarring, eye abnormalities & abnormal limbs Zoster—unilateral rash; complications of post-herpetic neuralgia (elderly), eye damage from CNV infection; encephalitis Ramsay-Hunt syndrome—reactivation of zoster in geniculate ganglion of ear canal resulting in facial palsy, loss of taste Diagnosis—characteristic rash; immunofluorescent staining of Ag; culture; known exposure; serology; PCR to detect viral DNA Treatment— Varicella: symptomatic therapy (Tylenol not aspirin), adults (acyclovir and foscarnet) Zoster: elderly- acyclovir, valacyclovir, sorivudine, immunocompromised (iv acyclovir) Prevention: vaccine- effective against varicells, effective against zoster and PHN (given to pts 60+ old, reduce incidence and severity of zoster Varicella-zoster immunoglobulin (VZIG)- passive immunization, most eff. before lesion occur, immunocompromised, pregnant women, infants up to 2wks 1. ubiquitous virus that can cause dz in individuals with immature or malfunctioning immune systems epidemiology: 70% of adults are seropositive, site of latency may be peripheral blood mononuclear cells, monocytes clinical manifestations: asymptomatic most common, mononucleosis, congenital (most common in us)- .5-1%, Congenital symptomatic at birth—ONLY 1% of fetal infections; 20% die during infancy or suffer brain damage, 80% hearing, vision loss or mental Congenital asymptomatic at birth—may develop hearing defects or impaired intelligence Immunocompromised:Transplant recipients (leukopenia & hepatitis); BM recipients (pneumonitis); AIDS (25% developed CMV infection before HAART) Diagnosis: pcr, ag detection, serology Transmission—shed in saliva, semen, vaginal secretions & breast milk w/o clinical symptoms; blood transfusion (1-5%) & transplantation (60-80%), vertical transmission or horizontally Prevention—blood & transplant screening; prophylactic therapy for bone marrow & solid organ transplant patients Treatment—NONE in normal persons; antivirals drug therapy in immunocompromised, iv ganciclovir in neonates Is the causative agent of roseola infantum Two variants a (lymphoproliferative disease or aids & b (roseola infantum Epidemiology: up to 70% of people acquire hhv-6 during 1st yr of life Manifestations: roseola infantum (benign dz of children, fever which subsides w/ rash (no-puiritic, slightly elevated, blanches) liver dsy, febrile seizures, mono in adults, can be isolated from cd4 cells, transplant pts- present in 50%, febrile syndrome, bone marrow suppression Diagnosis; easily detected in peripheral blood during febrile phase of disease: (culture virus), IFA, western blot, elisa, and pcr (x-reactive w HH& Treatment: ganciclovir and foscarnet Acquired during 3rd year of life Disease: roseola infantum?, can be isolated from saliva, may have two variant Diagnosis: pcr on pbmc and throat swabs or culture virus, IFA, western blot, Elisa Treatment: ganciclovir and foscarnet Two strains: ebv-1, ebv-2,, highly conserved, diff in genes to maintain latency (ebna’s), 90:10 ratio in usa, 50:50 in Africa Epidemiology: widely disseminated, spread by intimate contact, primary inf are subclinical and inapparant, 90-95% worldwide Spread: infection probably begins in epithelial cells of the oropharynx and spreads to b-cells in adjacent lymph tissues, early stages (10% of b cells affect) Clinical manifestation: infectious mono (self limiting, atypical lympocytes (nk and t cells), heterophile ab, (rash if treated w. ampicilin Primary infection in infants and children is frequently asymptomatic Malignancies: burkitts lymphoma (in jaw), post transplant lymphproliferate disorder (b-cells), HIV associated (non-Hodgkin’s, and oral hairy leukoplakia), Hodgkin’s disease, nasopharyngeal carcinoma, t cell lymphoma Diagnosis: presence of atypical lymphocytes, ant-ebv ab, heterophile ab Transmission: primary through saliva (low titer virus is detectable for life in saliva, sporadic replication of virus in epithelial cells of oropharynx Treatment: supportive care (non steroidal anti-inflammatory), oral leukoplakia responds to acyclovir associated w/ KS b/c vDBA found in ks epidemiology: seroprevalence is 10-20, endemic places 32-100% Clinical manifestation: KS- tumor(multiple cells or pluripotent precursor), proliferation of spindle shaped cells,& irregular slit-like vascular channels, inflamm infiltrate of lymphocytes and macrophages, tumor appear fist on skin Non-Aids KS: classic (elderly), immunosuppresion (may appear upon withdrawal of IS therapy, poss graft rej, lesions may recur, endemic (common Africa Aids KS: spread from skin to viscera, male homosexual & bisexual aids (20x more likely), viremia associate w/ ks Associated primary effusion lymphoma (PEL)- aka non-Hodgkin’s- no solid tumor mass, primary in visceral body cavities Multicentric castleman’s disease(MCD)- atypical lymphoproliferative disorder, generalized lymphoid hyperplasia Diagnosis: detection of viral DNA (PCR or southern blot), elisa or IFA serum Transmission: sex, needle sharing, in endemic areas(nonsexual, horizontal spread), organ transplant (3-8% of all post transplant tumors Treatment: KS- radiation & chemo, excision, IFN, lowering or removal of immunosuppressive therapy – sirolimus (rapamycin), may have antiviral action HAART lowers incidence of KS and may cause remission of KS Ganciclovir for mcd, foscarnet and cidfovir