DOUBLE STRANDED, NAKED, ICOSAHEDRAL LINEAR RNA VIRUS PHYSIOLOGY AND PATHOGENESIS STRUCURE REOVIRIDAE - with 10-11 segments - infects the cells near the tips Rotavirus - MOST COMMON CAUSE of the SI villi ! impaired OF CHILDHOOD hydrolysis of CHO and excess DIARRHEA fluid loss ! malabsorption - Viral Gastroenteritis - increased motility and diarrhea
EPIDEMIOLOGY
CLINICAL MANIFESTATION
LAB DIAGNOSIS
TREATMENT
- race and gender not a factor - asymptomatic in adults
Signs and symptoms - anorexia - low grade fever - vomiting - watery, bloodless diarrhea - abdominal cramps
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- Supportive treatment - Rotateq (6-32wks) - Rotatrix (6-24wks)
enzyme immunoassay latex agglutination E microscopy Culture Electrolyte levels
PE findings - UO is most important sign ! dehydration - Hyperactive bowel sound - Dry mucosa and skin - Tachycardia - Depressed sensorium - Weight loss SINGLE STRANDED, (+) SENSE, ENVELOPED, ICOSAHEDRAL RNA VIRUSES • •
FLAVIVIRIDAE
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An ARBOVIRUS (arthropod borne) Life cycle involves between vertebrates and moquitos as vectors Vectors have lifelong infection without disease Transmitted during viremic stage Common in tropical region, urban and semi urban
PHYSIOLOGY AND STRUCURE
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Hepatitis C
6 genotypes MAJOR CAUSE OF POST TRASFUSION HEPATITIS
PATHOGENESIS
EPIDEMIOLOGY
CLINICAL MANIFESTATION
LAB DIAGNOSIS
TREATMENT
HCV binds to CD81 tetraspanin or scavenger receptor B1 in hepatocytes and B lymphocytes ! coat itself with LDL and VLDL and use lipoprotein receptor for hepatocyte uptake ! resemble and buds in ER ! bind to TNF recpetor and protein kinase R ! inhibition of apoptosis and interferon
- Chronic hepa C !
Hepa C virus Acute Infection can lead to: 1. recovery 2. rapid onset cirrhosis 3. Persistent infection a. Asymptomatic a. Asymptomatic b. chronic hepatitis ! liver failure / cirrhosis / hepatocellular Ca
1. HCV Ab – diagnosis - 4 wks before it appears so cannot be used in acute phase
1. Interferon – chronic active Hepa 2. Ribavirin 3. Screening of blood, organ and tissue donors 4. Blood and bodyfluid precaution 5. Limit alcohol drinking
Cirrhosis ! Hepa Ca - IV abusers, tattoo recipients, transfusion and organ recipients, hemophiliac and HIV pxs - Affects only humans and chimpanzees Immunity is not lifelong and protective
viremia: acute infection – 4-6 mos persistent infection - >10yrs
2. HCV RNA – diagnosis in acute phase – main use is for monitoring antiviral therapy
Predominant symptom: chronic fatigue
3. HCV Antigen - using EIA
Dengue
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4 serotypes: DENV 1-4 3 structural proteins - capsid, prM, envelope 7 other proteins found in infected cell - NS1, NS2a. NS2b, NS3, NS4a, NS4b, NS5
Life cycle: Attach! fusion and diasassembly ! translation ! rna replication ! assembly in ER ! maturation DHF and DSS ! 3rd to 7th day During defervescence: - rapid plasma leakage - altered homeostasis - live damage Initial viremia: Chills, headaches, backaches, flulike symptoms 3-7 days of infexn ! L and B interferon response to viremia
infection with one serotype provides lifelong immunity but only temporary and partial protection against other serotype " transmission between Aedes aegypti or Aedes albopictus that bread in water •
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dengue fever - high fever - nausea and vomiting - breakbone fever - rash – 24 hrs after fever
Initial infection – NS! With CBC Acute phase – NS1 and IgM Secondary infection – NSI and IgG
Supportive treatment IV and oral rehydration Blood transfusion Vector control No dark colored foods to check bleeding in feces
Presence of antirubella IgM
Live attenuated vaccine for prophylaxis - Not for pregnant and IC pxs
Dengue Hemorrhagic Fever – high fever with hepatomegaly Dengue shock syndrome
Dengue Classification: Grade 1- bruising and (+) tourniquet with fever Grade2 – spontaneous bleeding Grade 3 – clinical shock Grade 4- severe shock, bp and pulse not detected
Second viremia: Virus-Ab complex ! higher no of mononuclear cells ! release of cytokine, procoagulants ! DIC in DHF or spread in other organs
Yellow Fever
Severe systemic disease with liver, kidney and heart degeneration . Massive Gi hemorrhage and jaundice
TOGAVIRIDAE
Rubella
- German measles or 3 day measles
Transmission: - Respiratory droplets - Transplacental
Incubation 14-21 days ! 3 day maculopapular rash ! posterior LAD
Humans are the only host
Immune complex polyarthritis in adults
RT-PCR of viral RNA
Infection promotes lifelong immunity CONGENITAL RUBELLA SYNDROME - During 1st trimester - Abnormalities: PDA Congenital cataracts – bilateral leukocoria, loss of ROR Sensoneural deafness Mental retardation Bulag, bingi, bobo, butas ang
puso, blueberry baby
RETROVIRIDAE
Human Immunodeficiency Virus
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Presence of reverse transcriptase: ssRNA ! dsDNA Hepa B also contain reverse transcriptase LAMIVUDINE for treatment of hepa and HIV
- Diploid - Many serotypes Structural genes: 1. GAG gene
- Kills helper CD4 T cells
Transmission:
- Main immune response: cytotoxic CD8 T cells
Original source – chimpanzees, diet Transfer of semen, transplacental and perinatal Needlestick – more of HEPA B Most common means - Sex
Stages of Infection: P24- nucleocapsid - Found in core - Important serologic marker of infexn P7 – nucleocapsid P17 – matrix 2. POL gene Reverse transcriptase – transcribe RNA to DNA Protease – cleaves precursor polypeptide Integrase – integrates viral DNA to host cell 3. ENV gene Gp120 – attachment to CD4 - Mutates rapidly ! antigenic variation Gp 41 - Fusion with host cell Regulatory gene: tat – activation of transcription rev – transport of mRNA to cyto nef – dec CD4 and MHC1 vif – hypermutation vpr – transport in nondividing cell vpu – virion release
Phase 0 INFECTION - HIV acquired Phase 1 WINDOW PERIOD - Viral replication with (-) HIV test Phase 2 SEROCONVERSION - Peak of viral load, (+) HIV test, flu like illness 1-2wks Phase 3 LATENT PERIOD - Asymptomatic for 1-15yrs - Low CD4 Phase 4 EARLY SYMPTOMATIC - CD4 500-200 - last 5 yrs, mucocutaneous, derma and hema illness Phase 5 AIDS - CD4<200 last 2 years, AIDS defining illnesses present
Clinical Syndromes: TB – no.1 killer C. neoformans – meningoencephali tis presented as chronic headache CMV – blindness Candida – esophagitis Toxoplasma – ring in CT AIDS defining illnesses 1. P. carinii pneumoni 2. Esophageal candidiasis 3. Wasting – Inc IL-12, TNF 4. Kaposi sarcoma – HHV8 5. Diss Mac
Presumptive Dx – Ab detection by ELISA Definitive DX - Western blot analysis - using gel electrophoresis Gold Standard – PCR - Detect HIV DNA in cells and plasma viral RNA - For prognostication
1. HAART 2 nucleoside inhibitors - zidovudine and lamivudine - lactic acidosis protease inhibitor - indinavir - Fat redistribution syndrome Immune reconstitution syndrome - HBV, HCV, MAC/MAI 2. General prevention – responsible sex 3. Perinatal prevention - perinatal prophylaxis -Abs CI to breastfeeding is galactosemia, HIV is only relative CI 4. Post exposure therapy - AZT
HTLV-1
- ADULT T-CELL LYMPHOCYTIC LEUKEMIA (ATLL)
Spread in cells after BT, sex of breast feeding.
ELISA RT-PCR
AZT and interferon alpha
- HTLV-ASSOCIATED MYELOPATHY (tropical spastic paraparesia) SINGLE STRANDED, (+) SENSE, ENVELOPED, HELICAL RNA VIRUSES PHYSIOLOGY AND PATHOGENESIS STRUCURE CORONAVIRIDAE - 2 serotypes - infection in URT Coronavirus - 2nd MOST COMMON - optimum viral growth temp of CAUSE OF COMMON 33C to 35C COLDS - longer incubation of 3 days than rhino - virus binds to ACE 2 receptors ! kills alveolar epithelium
EPIDEMIOLOGY
CLINICAL MANIFESTATION
LAB DIAGNOSIS
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Incubation: 2-10 days
Chest Xray: non cavitary ground glass infiltrates
reservoir: horseshoe bat intermediate host: civet cat respeoratory droplet CIVET CAT ! SARS
TREATMENT
SARS ! ARDS Viral RNA in respiratory and stool by RT-PCR
SINGLE STRANDED, (+) SENSE, NAKED, ICOSAHEDRAL RNA VIRUSES •
CALICIVIRIDAE
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VP1 protein with S domain (structure) and P domain (cuplike) 5 genera: norovirus, sapovirus, vesivirus, lagovirus, nebovirus norovirus and sapovirus ! human caliciviruses
PHYSIOLOGY AND STRUCURE
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Norovirus •
main cause of gastroenteritis outbreak with contaminated water and food ! SHELLFISH MOST COMMON CAUSE OF NONBACTERIAL DIARRHEA IN ADULT
PATHOGENESIS
EPIDEMIOLOGY
CLINICAL MANIFESTATION
LAB DIAGNOSIS
TREATMENT
HBGA on enterocyte act as host receptor ! dec sucrose, trehalase and ALP act in intestinal brush border ! villous atrophy, epithelia disarrangement, crypt hyperplasia, cyto vacuolization ! malabsorption and delayed gastric emptying ! vomiting and diarrhea
BREASTMILK -inhibit transmission by inhibition of binding of norovirus
Incubation: 12-60 hours, persist for at least 7 days – 2mos.
RT-PCR
Bismuth subsalicylate Handling food carefully
Self limited nonbloody diarrhea, nausea and vomiting nd low fever 1-2 days in outbreak and 5-6 days in endemic cases <1 yr old ! vomiting infant and adult ! diarrhea
Genotyping based on region D for strain differentiation EIA for stool antigen detection
Hepatits E
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Resembles HAV
Do not progress to chronic infection
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Chronic Hepa E ! impaired HEV specific T cell response in transplant patient
PICORNAVIRIDAE
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FECAL-ORAL ROUTE Teens and young adults are most commonly affected
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Initial ! flu, arthralgia and weakness Jaundice, uncolored stool and inc liver enzymes
Anti HEV IgM ! acute Anti HEV IgG ! recent
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Clears sponatenously Interferon alpha and ribavirin
Rhinovirus Enteroviruses: poliovorus, echovirus, cosxackie virus A and B, Hepa A Acid stable and survive GI CYTOPLASMIC REPLICATION When cell if infected, the ER will not fuse to the CIS side of golgi Replication in mucosa, lymphoid tissue pf pharynx and tonsils ! GI ! target tissue viremia FECAL ORAL ROUTE
LAB Dx: IgM ! acute IgG ! chronic RT-PCR of CSF(headache and stiffneck) , blood (rash, fever, vomiting) and stool (diarrhea, fever, abdominal pain)
Poliovirus
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3 serologic types COWDRY TYPE B INTRANUCLEAR INCLUSION
- Bind to anterior horn cell of SC and muscle cells
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FECAL ORAL ROUTE
Poliomyelitis ! poliovirus + coxsackie virus A
SALK vaccine – killed IPV
1. Asymptomatic Infection - Infexn limited to oropharynx and gut 2. Abortive poliomyelitis -mild illness, fever, headache 3. Non paralytic poliomyelitis (aseptic meningitis) -fever, headache, stiffneck and pleocytosis in CSF 4. Paralytic poliomyelitis (major illness) - Flaccid paralysis from LMN lesion - Spinal paralysis ! one or more limbs - Bulbar paralysis ! CN and medullary respi center
SABIN VACCINE – live OPV - Prevent dse and inc IG
Post polio syndrome – 30-40 yrs later, deterioration of muscle ASEPTIC MENINGITIS WITH RASH – CoxA + Echovirus
Cosxackie A Virus
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FECAL ORAL ROUTE AEROSOL
Herpangina - Fever, sorethroat and vesicles in oropharynx, pain in swallowing - Self limited Hand, Foot and Mouth Dse - Vesicular lesion with mild fever - CoxA 16 - Lesion in hand, foot, mouth and tongue Acute hemorrhagic conjunctivitis - Enterovirus70 and Cox A24
Cosxackie B Virus
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Life threatening in infants Asymptomatic or mild in adults
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FECAL ORAL ROUTE AEROSOL
Pleurodynia - Fever with severe pleuritic chest pain Epidemic pleurodynia - Bornholm disease / devils grip - Sharp paroxysmal chest pain with fever in adolescent and young adult Myocarditis and Pericarditis - Fever, chest pain and congestive failure
EchoVirus
Enteric Cytopathic Human Orphan
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FECAL ORAL ROUTE AEROSOL
Aseptic meningitis URTI Fever w or w/o rash Infantile diarrhea Hemorrhagic conjuctivitis
Rhinovirus
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Acid labile 100 serotypes MOST COMMON CAUSE OF COMMON COLDSAND URTI Same receptor with Coxsackievrouses (ICAM-1)
Replication in nasal mucosa and conjunctiva ! growth as 33C !inflammatory mediators such as bradykinin! runny nose, sinusitis, watery discharge
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Hepatitis A
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Enterovirus 72
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Aerosols Hand nose contact (hand as major vector) Person to person contact is predominant mode of spread Fomites Host limited to humans and chimpanzees IgA and interferon for response to infection Fecal oral route Common in STREETFOODS and SHELLFISH Self Limited
URTI ! rhinorrhea ! sorethroat ! malaise Infection ! 3-4 days Cough and nasal symptoms ! 7-10 days Asymptomatic Shedding
Symptoms occur 15-50 days after exposure (fever, nausea, loss apetite, abdominal pain) ! jaundice phase (no symptom) !recovery
Anti HAV IgM
CLINICAL MANIFESTATION
LAB DIAGNOSIS
SINGLE STRANDED, (-) SENSE, ENVELOPED, HELICAL RNA VIRUSES •
PARAMYXOVIRIDAE
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Unsegmented genome RNA dependent RNA polymerase Hemaglutinin – attachment Neuraminidase fusion proteins – fusion of cell to multinucleated giant cell for Ab protection
PHYSIOLOGY AND STRUCURE
Measles
RUBEOLA (+) hemaglutinnin and fusion protein
PATHOGENESIS
URTI ! retisculoendothelial cells ! depress cell mediated immunity transiently ! multinucleated GC (WARTHIN FINKELDEY BODIES) ! skin by hematogenous spread ! vasculitis ! Rash – CD8 attacking the measles infected vascular endothelium
EPIDEMIOLOGY
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Respiratory droplet transmission Lifelong immunity for px who had the dse
Incubation: 10-14 days Koplik spot in stensen duct of parotid gland ! maculopapular rash in face, trunk, ext, palms and soles Complications: 1. Post infectious Encephalitis - Px with inactivated vaccine and exposed to wilder strain 2. Pneumonia – worst
TREATMENT
VITAMIN A – reduced severity Live attenuated Vaccine for prevention
3. SSPE – virus persist in body acts as slow virus but cannot spread -DAMSON INCLUSION BODIES 3 Cs Cough, Coryza, Conjunctivitis, Koplik spot
Mumps
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(+) hemaglutinnin, neuraminidase and fusion protein
URT ! local replication -> viremia ! systemic infection 1. Parotid gland 2. Testes, ovaries, PNS and CNS, eyes and ears 3. Pancreas – juvenial diabetes
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Respiratory droplet transmission Lifelong immunity for px who had the dse
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Incubation: 18-21 days Bilateral swelling of parotids when drinking citrus juice Self limited within 1 week
Saliva, urine and CSF IgM Ab
Live attenuated Vaccine for prevention
Wheezing in broncholitis
Ribavirin - Same with hepa E
Croup: Steeple sign in xray
Croup – racemic epi
Thumbprint sign - epiglotittis
Epiglottitis - ceftriaxone
Complications: orchitis and meningitis, parotitis, menningits, pancreatitis Pleomorphic adenoma – tumor in parotids MATERNAL Ab – passes in placenta and protection for first 6 months of life RSV
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(+) fusion protein ! multinucleated GC ! syncytia
Parainfluenza Virus
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(+) hemaglutinnin, neuraminidase and fusion protein
Plugs in small airways of neonates ! pneumonia and bronchiolitis (wheezing) ! localized infection in URT
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Local disease in upper and lower RT No viremic spread
Four types Ab to H or F protein ! less infectivity
Virus 1 and 2 – major cause of CROUP or laryngotracheobronchitis Inspiratory stridor, cough and hoarseness seal bark Steeple sign in xray Virus 3 -
Most common in children
Humans are natural hosts No systemic spread
Bronchiolitis and pneumonia ! fever, cough , dyspnea, cyanosis
Severe disease with IMMUNOLOGIC CROSS REACTION WITH MATERNAL AB
Febrile rhinitis and pharyngitis ! children
Humans and animals both affected but animal strains do not affect humans
CROUP - Inspiratory stridor, cough and hoarseness seal bark - Subglottic stenosis
Common cold ! adults
with LRTI Virus 4 – common codl, rare cause
ORTHOMYXOVIRIDAE
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Influenza Virus
8 segments interact with mucus
Majot antigens: 1. hemaglutinin – attachment - target of neutralizing Ab 2. Neuraminidase - release of virus by breaking sialic acid - degrade respi epithelium •
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INFLUENZA A Antigenic shift !sudden major change ! reassortment ! new strain ! pandemic
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INFLUENZA B Antigenic drift ! mutation ! epidemics
Influenza A – worldwide epidemic (pandemic) - Most common cause of RTI - 16 HA and 9 NA •
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Influenza B – major outbreak of influenza - No pandemic Influenza C – mild RTI - do not cuase outbreal
SINGLE STRANDED, (-) SENSE, ENVELOPED, BULLET RNA VIRUSES
Respiratory droplet transmission
Incubation: 24-48 hr
Human bites can transmit virus
Clinical presentation Myalgia Fever Headache pharyngitis cough
Influenza A – animal reservoir - Aquatic birds or waterfowl – common source - Pigs – mixing bowl - Waterfowl – H1 tp H16 and N1 to N9 - Humans – H1 to H3 and N1 to N2 Influenza B – human reservoir - Must be included in the new vaccine for influenza - No common antigen with inf A
Complication staph pneumonia reye syndrome
Oseltamivir or Zanamivir – drug of choice targeting neuroaminidase Amantidine or rimantidine – influenza A only - prevents uncoating of virus – less transmission Yearly vaccine to influenza B during rainy season
PHYSIOLOGY AND STRUCURE
PATHOGENESIS
EPIDEMIOLOGY
CLINICAL MANIFESTATION
- bullet shaped - assembly in cytoplasm - NEGRI BODY intracytoplasmic eosinophilic inclusion
Multiply locally at animal bite ! sensory neuron ! axonal transport to CNS
- Animal reservoir: dogs, cats, skunks, raccoons and bats - Transmission by animal bites - US ! skunk - Philippines ! dogs
Incubation: 2-16 weeks
LAB DIAGNOSIS
TREATMENT
RHABDOVIRIDAE Rabies virus
Incubation period 20-80 days ! prodromal period (pain and itch in bite) ! acute neurologic period (fasciculation, priapism and convulsion, furious rabies) ! coma due to respi depression Symptoms: - Confusion - Lethargy - Hypersalivation - laryngospasm, - hydrophobia (pain in attempt to swallow h20) - encephalitis - aerophobia
Pre-exposure: vaccine Post-exposure: vaccine and Ig Rabies vaccine: >4 sessions Do not bring rabid animal to ER
