Rna Virus

RNA VIRUSES OF MEDICAL IMPORTANCE

Nucleic Acid

Symmetry

Presence/Absence Enveloped

Physical State of Nucleic Acid

S Icosahedral

Naked S

R

Enveloped

S

S

N

Helical

Enveloped

S

A

S S

Complex

Complex Coat

Family

Specific Pathogenic Virus

Poliovirus S Non-segmentedPicornaviridae Coxsackie A and B virus Hepatitis A virus S Non-segmented Caliciviridae Norwalk virus Hepatitis E virus D S Segmented REOviridae Rotavirus Yellow Fever virus Dengue virus S Non-segmented Flaviviridae St. Louis Encephalitis vi Japanese Encephalitis v Hepatitis C virus S Non-segmentedCoronaviridae Respiratory Syncitial virus California Encephalitis v S S Segmented Bunyaviridae Rift Valley Fever virus Sandfly Fever virus Orthomyxoviridae Influenza virus Parainfluenza virus S Non-segmented Paramyxoviridae Respiratory Syncitial virus Mumps virus Measles virus S Non-segmentedRhabdoviridae Rabies virus Marburg virus S Non-Segmented Filoviridae (Acute Hemorrhagic Fever) Ebola virus (Acute Hemorrhagic Fever) Lymphatic Choriomengitis S S Segmented Arenaviridae Lymphocytic meningitis Lassa virus Human Immunodeficiency S S Diploid Retroviridae virus (HIV) type 1 & 11 (HTLV) type 1 & 11

Family Picornaviridae Picornavirus (small-rna virus)

= small-rna virus with single-stranded-rna genome, non-segmented = cubic/icosahedral nucleocapsid = not provided with envelope (naked) = 20-30nm diameter = acid stable = resistant to lipid solvent (ether, ethanol, detergents = inactivated by UV light, formalin, chlorine, sodium hypochlorite = can remain viable for hours moist surfaces = can survive GIT

2 Genera: 1. Genus Rhinovirus = replicate at 330C, inactivated at pH3 = over 100 serotypes affecting human = acid labile (destroyed by gastric acid) = do not replicate in the GIT Rhinovirus/Common cold virus (nose virus) = worldwide distribution = commonly isolated from nose, throat and conjunctiva = primary cause of common cold which occurs throughout the year with its peak during summer = human only natural host

Disease: Common Cold = an upper respiratory tract infection charac. by running nose, sneezing, sore throat, mild cough & headache = fever may be present (low grade) or absent = MOT- 1. Aerosol/Inhalation 2. Hand to nose contact (contaminated nasal) discharge = incubation period 2-4 days = more common in children than adult = illness may last for weeks = reputed to be one of the most common human infection

Laboratory Diagnosis : 1. Isolation virus (nose, throat washing, conjunctival) discharge Tissue Culture 1. Primary human embryonic cell 2. Hela cell + CPE = Serological test not useful Treatment: Symptomatic and Supportive = no specific antiviral drug available Prevention: = no vaccine available due to many serotypes

2. Genus Enterovirus = replicate 370C, acid stable at pH3-5 = inactivated when heated at 55OC for 30minutes = not affected by ether = infect primarily in the GIT Polio virus Coxsackie virus A and B ECHO virus Hepatitis A virus Poliovirus = 3 serologic types: Type 1 Brumhilde - most paralytogenic Type 2 Lansing Type 3 Leon - least paralytogenic = protection from polio virus infection requires antibodies to all 3 serotypes

Disease: Poliomyelitis/Infantile Paralysis/Hein–Medlin Dse. = acute infectious disease that in serious form affect CNS = found worldwide = epidemic occur year round = spread rapidly among densely populated area with poor sanitary hygiene = children (5 years & above) more susceptible than adults = human-only known reservoir of infection = MOT-fecal-oral route

Clinical Manifestation: = majority of infection (90-95%) are inapparent or asymptomatic especially among infants and children 1-3 year old = older children 5-10 years have higher rates to manifest sign and symptoms of disease with paralysis = can be found GIT of asymptomatic carrier

Pathogenesis: Mouth (portal entry) (ingestion of contaminated food H2O) ↓ ↓ Oropharyngeal mucosa (tonsil) Intestinal mucosa (payers patches of small intestine) ↓ ↓ Cervical LN Mesenteric LN (1o multiplication takes place) Systemic circulation (spread throughout the body) ↓ ↓ CNS Extranural tissues ↓ (fibers motor neuron of ant. horn of spinal cord) → destroy nerve cell → flaccid paralysis

4 Clinical types of infection 1. Inapparent/Asymptomatic/Abortive poliomyelitis = characterized by mild influenza-like manifestation such as fever, headache, malaise, sore throat and vomiting = appears few days after exposure = no CNS involvement = recovery spontaneous = most common form 2. Non-paralytic poliomyelitis = appears as Aseptic meningitis with fever, headache, vomiting, stiff neck & convulsion = usually last 2-10 days

3. Paralytic Poliomyelitis (Spinal poliomyelitis) = most severe form = charac. by asymmetric flaccid paralysis of limbs with no sensory deficits, resulting from lower motor neuron damage = recovery w/in 6 months with residual paralysis lasting much longer or permanent deformity

4. Bulbar poliomyelitis = form of paralytic poliomyelitis which results from involvement of the brain stem and

Lab. Diagnosis: 1. Virological = isolation of virus (stool, throat, CSF) cell culture- Monkey Kidney cell (CPE)

Indication of presence + Cytophatic effect 1. rounding of cell 2. formation of pyknotic nucleus

2. CSF studies →1. increase leucocyte count 2. protein content elevated 3. Serological: CF, NT (demonst. rise AB titer) = serum pat. taken during acute/convalescent stage

Treatment: Symptomatic & Supportive = no antiviral drug available 1) reduction of pain and muscle spasm 2) maintenance of respiration &hydration 3) physiotherapy affected muscle Prevention: Active immunization using killed or attenuated polio virus 1. Salk vaccine = inactivated/killed polio virus contains all 3 serotypes = parenterally given = induce IgG in the blood = does not induce secretory IgA = refrigeration not needed

2. Sabin vaccine (Trivalent oral polio vaccine - TOPV) = live attenuated polio virus contains all 3 erotypes = given orally = induce IgG and secretory IGA = prepared vaccine and routinely administered o children U.S. = widely used and 100% protection = must be kept refrigerated

Immunity: = lifetime immunity = passive immunity transferred from mother→ eonate = maternal antibodies disappear during 6 months of life

Coxsackie virus 2 types based on pathogenicity (lesion induced in suckling mice) Coxsackie A = 23 serotypes = site of predilection: skin and mucous membrane = causes widespread inflammatory reaction and necrosis of skeletal muscle (myositis) leading to flaccid paralysis and death MOT – 1) fecal-oral route 2) respiratory droplets = virus replicate oropharynx and intestinal tract →

Disease produced: 1. Aseptic meningitis = may be caused by either Coxsackie A & B = usually mild & may last 5-14 days 2. Herpangina = mild self-limiting disease charac. fever & sore throat with vesicular nodule in soft palate 3. Hands – Foot and Mouth disease = vesicular rashes in the hands and feet with ulceration in the mouth = common in children

Coxsackie B = 6 serotypes = site of predilection: heart and liver = leading cause of viral myocarditis and pericarditis Disease produced: 1) Pleurodynia (Bornholm Dse./Epidemic Myalgia/Devils Grip) = charac. by fever with severe pleuritic pain especially during inspiration 2) Aseptic meningitis 3) Primary pericarditis/Myocarditis = infection and inflammation of the heart muscle and pericardial membrane = charac. by fever, chest pain, sign of congestive heart failure

Laboratory Diagnosis: 1. Isolation virus - Intracerebral inoculation→suckling mice Cell culture – MKC/Hela cell + CPE 2. Serological – Neutralization test = significant rise AB titer during convalescent phase (diagnostic) Treatment - No specific antiviral drug - No vaccine available

ECHOvirus (Enteric Cytophatogenic Human Orphan Virus) = worldwide in distribution = 30 serotypes (not all can cause human disease) = called “orphan virus” not associated with any disease = diff. from Coxsackie by their failure to produce pathological changes in newborn mice (not pathogenic to mice) = one of the leading cause of aseptic meningitis = acquired by fecal oral route

Disease produced: 1. Aseptic Meningitis 2. Infantile Diarrhea 3. Febrile illness w/ or w/o rash (Boston Exanthem Dse.) 4. Common Cold 5. Acute Hemorrhagic Conjunctivitis Laboratory Diag.: Isolation of virus – (throat/rectal swab) Cell culture- MKC/Hela cell/Human/Ammion cell Treatment: Symptomatic Prevention: - No vaccine available = avoid contact with the virus

Hepatitis A virus (Enterovirus 72) = only 1 serotype Disease: Acute Hepatitis = occurs after short incb. 14-40 days (ave. 4 weeks) MOT- fecal-oral-route Pathogenesis: = virus replicate gastrointestinal mucosa → shed up to 2 week before sign and symptoms appear = spread → liver → via the bloodstream = charac. by fever, loss appetite, nausea, vomiting, and jaundice = mild undiagnosed cases common = younger patients fewer symptoms

Lab. Diagnosis : = detect IgM antibodies to HAV (most useful test) = isolation of virus from clinical specimen not done Treatment: Symptomatic Prevention: = Pooled-immunoglobulin (given to person expose to virus or during incubation period of the disease) = vaccine available given to people traveling to endemic areas (3 doses)

Enterovirus 70 (Acute Hemorrhagic Conjunctivitis) = charac. by pain and swelling of the eyelids = very contagious disease = also seen with coxsackie A and B infection Enterovirus 71 (Hand – Foot and Mouth Disease) = charac. by the presence of herpetiform lesions in the hands, foot and mouth

Family REOviridae REOviruses (Respiratory-Enteric-Orphan virus) 2 Genera: 1. Genus Reovirus 2. Genus Rotavirus Properties: = segmented double-stranded rna genome = doubled layered icosahedral nucleocapsid which looks like a “rim of wheel” = no envelope (naked) = 60-80 NM = stable to heat = resistant to ether = inactivated by 70% ethanol = can agglutinate human and bovine rbc

Reovirus (Orthoreovirus) = 3 serotypes = widely distributed in nature = commonly infect human but asymptomatic hence they are called orphan virus = isolated from feces and respiratory secretion of apparently healthy human and among patient with minor URT and GIT infection = MOT- 1) fecal-oral-route 2) aerosol Disease produced: 1) Infantile diarrhea 2) Common cold Treatment: Symptomatic Lab. Diagnosis: 1. Virological-specimen from throat washing and feces

Rotavirus = 4 serotypes = responsible for almost 50% of infantile diarrheal cases that requires hospitalization = do not grow on tissue culture = found worldwide = peak of infection during winter and summer = resistant to stomach acid hence can reach GIT = primary cause of gastroenteritis (acute diarrhea) in infants and children 6 to 2 years and below = disease can be very severe with a high

Disease: Viral Infantile Gastroenteritis = major cause of death in underdeveloped countries = most common cause of death in infant less than 3 year of age = MOT- fecal-oral-route (contaminated food/water) = incubation period from 2-5 days = charac. by nausea, vomiting, explosive watery non-bloody diarrhea and fever = dehydration common in infant = virus infect. cells of villi of small intestine = no viremia

Lab. Diagnosis: 1. Direct demonst. virus particles from stool specimen during acute stage infection Electron Microscopy 2. Serological - demonst. rise AB titer during convalescent phase (diagnostic) Elisa, RIA, HI, CF, PCR Treatment: = Supportive and Symptomatic = No specific antiviral drug = IV fluid replacement and oral rehydration therapy very important Prevention: = no human measure of controlling rotavirus = Vaccine: live attenuated rotavirus

THE ARBOVIRUSES Family Togaviridae Togaviruses (cloak/mantle) = transmitted by bloodsucking arthropods (mosquito, tick, flies) = virus multiply both in bloodsucking arthropods & human host = man (incidental host)

Properties: = ss rna genome (infectious) = icosahedral nucleocapsid = non-segmented = enveloped with spikes containing neuraminidase and hemagglutinin enzymes = 60-70nm (medium size) = sensitive to ether = replicate in the cytoplasm = vector - mosquito 2 Genera of medical importance: 1. Genus Alphavirus 2. Genus Rubivirus

Genus Alphavirus A) Agents causing encephalitis and skin rashes Eastern Equine Encephalitis virus (EEE) = the deadliest and rarest of the encephalitis virus = fatality rate 30-50% Western Equine Encephalitis virus (WEE) = second deadliest transmitted by horses → mosquito, man (dead-end host) = fatality rate 3 – 5% Venezuelan Equine Encephalitis virus (VEE) Russian Summer Spring Encephalitis virus

= all arboviruses transmitted by insect-vector mosquitoes (except RSSE - tick) = neurotropic = most infection often inapparent and self limiting = when apparent-condition very serious & mortality rate high = charac. fever, myalgia, severe headache, nausea, vomiting = presence of maculo-popular skin rash = assoc. with changes in the mental status of patient like: confusion, stupor, signs of meningeal irritation

(rigidity of neck, convulsion, coma and paralysis)

Lab. Diagnosis: 1) Isolation of virus – CSF Intracerebral inoculation → suckling mice 2) Serological - demonstration of the rising AB titer NT, HI Treatment: Symptomatic Prevention: 1. No vaccine available for human 2. Mosquito eradication program

Genus Rubivirus Rubella virus (German Measles virus/3 Day Fever Virus) Properties: = envelope (contain hemaglutinin spike) = only 1 serotype = only genus not arthropod-borne = replicate in the cytoplasm = Man (natural host infection)

Disease: Rubella (German measles) = acute febrile illness charac. fever, skin rash & enlargement of post-auricular and suboccipital lymph node = acquired by: 1. aerosol/droplet inhalation 2. transplacental = worldwide distribution = infection occur throughout the year = peak incidence during spring = affect children and young adults = very communicable = most teratogenic of the virus disease 2 Clinical form: 1. Postnatal Rubella = acquired after birth = mild childhood disease (but can be seen in all ages)

Pathogenesis: Inhalation ↓ URT (nasopharynx and cervical LN) initial site of infection ↓ multiply ↓ bloodstream (viremia) ↓ general circulation (throughout body→ can pass placenta) ↓ Skin

Clinical Findings: = low grade fever, body malaise, maculopapular “rubelliform” skin rashes that forms small discrete blotch that do not coalase which starts from forehead → face → trunk → extremities and last for 3-5 days = enlargement of the postauricular & suboccipital lymphnodes (characteristic of the disease) = no conjunctivitis, no catarrhal manifestation = arthritis → frequent complication = after infection → permanent immunity

2. Congenital Rubella Syndrome = transplacental transmission of rubella virus acquired by neonate during intrauterine life = result from maternal infection of the virus which also involve infection of the placenta and fetus producing congenital abnormalities = mother can transmit the virus even if she is asymptomatic = congenital defect greatest if acquired during first trimester of pregnancy or even worst during the first month = abnormalities to the fetus is the results of:

= Clinical findings of newborn w/ congenital rubella syndrome: 1. Brain Microcephaly, Mental retardation, Cerebral palsy 2. Heart and Great vessel Patent ductus arteriosus, Stenosis pulmonary artery, Atrial/Ventricular septal defect 3. Eyes Total or partial blindness, Cataract, Glaucoma and Chorioretinitis 4. Deafness = infants may also display transient symptoms of: growth retardation, failure to thrive, hepato-

Lab. Diagnosis: 1. Virological = isolation of virus from clinical materials (maternal/cord blood) Tissue culture - Monkey kidney cell Viral Interference 2. Serological = demonstrate rising rubella AB titer CF, NT, HI (most commonly used) ELISA = demonstrate anti-rubella IgM in fatal cord blood Congenital Rubella Syndrome = demonstrate rubella AB of the IgM class in infant serum = indicate recent infection = diagnostic of CRS = if found in pregnant women should undergo amniocentesis to check for the presence of

Treatment: = Symptomatic and Supportive = No specific antiviral drug Prevention: 1.) Avoid contact of patient with rubella infection 2.) Exposed pregnant woman - Immune gammaglobulin

3.) Active immunization–Rubella vaccine = contains live attenuated rubella virus = routinely administered subcutaneously to infan in conjunction with mumps and measles (MMR) = effective and long lasting

Family Caliciviridae (Calicivirus) Species: 1. Norwalk virus 2. Hepatitis E virus = all ill-defined group of enteric viruses that causes diarrhea Norwalk virus = ss rna genome, non-segmented, naked (nonenveloped) = cup-shape depression on capsid = major cause of gastroenteritis = 35 - 39nm = 5 antigenic types = almost all children have antibodies to the virus by the age of 5 years

= transmitted fecal-oral (contaminated H2O & shellfish) = incubation period 1 - 2 days = charac. by fever, nausea, severe vomiting, abdominal pain and diarrhea = symptoms resolve within 4-5 days = recovery rapid and complete = infant death may be due loss of fluid and electrolytes (dehydration) = infection can occur at only time of the year and in people of all ages Lab. Diagnosis: Virological = Electron microscopy - detect virus in the stool = ELISA

Hepatitis E virus

= major cause of GIT transmitted hepatitis = most common cause of water-borne hepatitis in Asia, Africa, India and Mexico but uncommon in U.S. = acquired by fecal-oral route = disease resembles hepatitis A = high fatality rate among perinatal & pregnant women

Family Flaviviridae

= arthropod-borne viruses causing fever, arthralgia & jaundice 1.) Dengue fever virus 2.) Yellow fever virus 3.) Japanese B encephalitis virus 4.) St. Louis encephalitis virus 5.) Hepatitis C virus Properties: = ss RNA genome, non-segmented, icosahedral ucleocapsid = enveloped with E & M protein spikes = antibodies against protein E are protective = 40-55nm = replicate in the cytoplasm = vector: Aedes mosquito (Yellow fever & Dengue ever virus)

Dengue Fever Virus = found worldwide including Philippines = mosquito-borne Species: 1.) Aedes aegypti = domestic mosquito found inside houses & buildings (urban areas) 2.) Aedes albopectus = found outside houses and buildings, forested areas, bush,

le = commonly breeds in standing water

ed outdoors = more efficient vector of dengue virus

n A. aegypti = female mosquito transmit virus

= 4 Serotypes 1- Hawaii 2- New Guinea 3 Philippines 4 = all serotypes shows cross-reactivity = Serotype 2 most commonly assoc. with hemorrhage = endemic in Southeast Asia and India = affect all ages, but more common in children = first reported case of Dengue hemorrhagic fever Phil. 1950

3 Clinical types of infection 1.) Classic Dengue Fever (Breakbone fever) = most common & usually least serious arboviral infection = very hard to diagnose clinically = mild, self-limiting and rarely a fatal disease = charac. by: sudden onset high grade fever w/c may last for 2-7 days (saddle back/biphasic charac.) headache, malaise, weakness, severe muscle and joint pain (breakbone fever), lymphadenopathy, maculo-papular skin rashes (herman’s) appears

2.) Dengue Hemorrhagic Fever (DHF) = one of the leading cause of morbidity and mortality among Southeast Asian children = usually occurs among children with history of previous exposure to virus = more severe type, mortality rate 10% = due to production of large amount of cross – reacting antibody (virus – antibody complex) w/c are formed few days during the second dengue infection = WHO criteria of DHF: fever, hemorrhagic manifestation, thrombocytopenia, increase capillary permeability (hypoalbuminemia, hemoconcentration, pleural effusion) 3.) Dengue Shock Syndrome (DSS)

Pathogenesis: = patient w/ dengue caused by one of 4 serotypes–recover→ antibody against that serotypes produced = when that same patient is infected with another dengue virus serotypes ↓ anammestic reaction occur ↓ overproduction of cross-reacting AB ↓ immune complex formed bet. virus & AB ↓ activate the complement system ↓ damage blood vessel ↓ increase vascular permeability ↓ loss of platelet (thrombocytopenia)

Lab. Diagnosis: 1) Patient with clinical manifestation and history of going to endemic areas (Tourniquet test) 2) Platelet count – below 50,000 (indication of bleeding) 3) Virological = demonst. virus by inoculating blood: A.) Mosquito culture medium = commonly used = 2 weeks virus can be isolated B.) Mouse Inoculation (suckling mice) = Disadvantage: take 1 month before virus isolated 4) Serological 1.) NT - commonly used method AB detected within 7 days of

Treatment: = No specific Rx (No antiviral drug available) = Supportive and Symptomatic = Fluid and Electrolyte = Replace platelet with platelet concentrate Prevention Control: = General mosquito control measures 1.) Elimination of breeding places 2.) Insecticides 3.) Fogging = Vaccine (still under study) Sabin – Schlessinger Vaccine (attenuated dengue virus)

Yellow Fever Virus = endemic in Central and South America, Central Africa and Caribbean Island = mosquitoborne (A. aegypti) = 2 patterns of transmission in nature 1. Urban - transmitted from infected person to uninfected person by mosquito bite 2. Sylvan or jungle type - normally transferred from monkey to insect to monkey cycle = human as accidental host = produce severe form of life-threatening disease = charac. fever, chill, headache, myalgia, arthralgia,

Lab. Diagnosis: 1. Virological – isolation virus from clinical material (blood) ↓ intracerebral inoculation (suckling mice) 2. Punch Biopsy Liver (histopathologic exam) demonst. ↓ charac. inclusion body “councilman body” 3. Serological – CF, NT (detect rise in AB titer) Treatment: Symptomatic Prevention: 1. Eradication and control of mosquito breeding site 2. Vaccine – (live attenuated yellow fever virus

Japanese B Encephalitis Virus

= found throughout Asia = most prevalent in Southeast Asia (Phil.) = mosquitoborne→Culex species (endemic to asian cefield) = most common cause of Epidemic Encephalitis (Asia) = charac.: sudden onset of fever, severe headache

= = = =

nuchal rigidity, tremor, convulsion & altered state of consciousness majority of infection mild/inapparent mortality rate high especially in children neurologic sequelae severe if patient recover → permanent immunity

Lab. Diagnosis: 1. Virological – isolation of virus from brain tissue of infected person (at autopsy) Fluorescent- Antibody staining 2. Serological – detect rise antibody titer Treatment: Symptomatic Prevention: 1. Immunization–Vaccine (inactivated purified Japanese B) encephalitis virus given 3 subcutaneous doses = very effective = recommended esp. for person living or travelling endemic area 2. Mosquito – Eradication program

St Louis Encephalitis Virus (SLE) = widespread throughout the U.S. especially in Texas, Mississippi and Florida = most common arbovirus encephalitis in U.S. = has been the major cause of arboviral-born encephalitis over the last 3 decades = peak activity during summer and spring = the only arbovirus infection which occurs in urban areas = disease mild but outbreak carry a 10% mortality = mosquito (vector), wild birds (reservoir) = more common in adults (55 years and above) = no vaccine or treatment available = human are dead-end-host

Hepatitis C (Non A, Non B hepatitis virus) = enveloped virion containing a single-stranded RNA genome = 6 serotypes = most prevalent blood-borne virus Disease: Hepatitis C

MOT: Parenteral route (blood transfusion) = infect the body after parenteral entry causing hepatitis after 14-20 days incubation period = most often leads to chronic hepatitis therefore person infected are carrier of virus = most common cause of post-transfusion hepatitis Lab. Dx: Elisa (detect antibodies)

Family Rhabdoviridae Rhabdovirus (Lyssavirus/Rabies virus) Characteristic: = rna virus with ss rna genome, non-segmented = bullet-shaped nucleocapsid = envelope with spikes containing 2 enzymes neuraminidase and hemagglutinin = size 180 nm = replicate in the cytoplasm = sensitive to chemical agents: (phenol, formaldehyde, ether and chloroform) = inactivated by physical agents: U-V radiation, heat 50°C for 1 hour = survive at temperature 4°C for weeks

= a zoonotic virus with wide host range (all warm-blooded animals are reservoir of virus like) dog, cat, skunk, raccoon and foxes = virus infect most mammals including human (accidental host) = not found human body = human to human transmission rare = normally present → vampire bat (only known carrier and reservoir of the virus and don’t) manifest disease = dog (animal reservoir), man (accidental host) = rabbit and rodents are the only mammals unable to transmit

Disease: Rabies/Hydrophobia = acute infection of the CNS charac. by: chill, fever, headache, sore throat, malaise, anorexia & nausea = tingling and burning sensation at site of bite followed by hyperactivity and agitation = confusion, seizure, lethargy, nervousness and apprehension, disorder of coordination = painful contraction of pharyngeal muscle when swallowing liquid → hydrophobia → foaming of the mouth = profuse sweating, lacrimation, dilatation of pupil, seizure,

= MOT: 1. bite of infected animals which introduced the virus through the skin and mucous embrane 2. licking of infected animals to damaged ucous membrane 3. aerosol transmission from an infected animal usually a bat (rare) = incubation period varies from 2 weeks to a year (depends on how large the infecting dose and ow fast) the virus travels to the CNS - human - 10 days to 1 year with most cases curring 20 - 90 days after exposure - bite occurring in the head, neck & upper xtremity

Pathogenesis: when human bitten → virus inoculated → grow & multiply → peripheral nerve at site bite locally at wound site for few days salivary ← peripheral nerve ← CNS gland ↓ death of neuron & demyelination = prognosis very poor = disease always fatal = death is due to respiratory center dysfunction

Lab. Diagnosis: Rapid diagnosis a.) Direct microscopic demonst. of virus antigen

by:

virus in

Direct immunoflourescence staining → detect

brain tissue and corneal scrapings (most rapid & accurate method to identify rabies virus) b.) Brain biopsy→ histologic staining of brain tissue (seller stain) ↓ demonst. intracytoplasmic eosinophilic inclusion body “negri body” = negri bodies and rabies antigen are

c.) Animal inoculation → mice (tissue or saliva inoculated intracerebrally into mice) = presence of rabies virus is indicated by 1. flaccid paralysis of leg 2. encephalitis 3. death d.) Serological = detect rabies antibodies by 1. Immunofluorescence test 2. Complement fixation test 3. Neutralization test = antibodies are developed during progression of the disease

Treatment: Supportive & Symptomatic Prevention: = Vaccination of domestic animal (dogs, cats) using attenuated virus vaccine grown in chick embryo LEP (low egg passive virus) - used for dogs HEP (high egg passive virus) - used for cattle = Effective urban control of dog population

Post exposure treatment: 1. If human is bitten by a suspected rabid dog: a. Clean the wound with soap and water b. Give passive and active immunization (necessary to eliminate risk of infection) Rabies Immune Globulin (RIG) Human Diploid Cell Vaccine (HDCV) Duck Embryo Vaccine (DEV) = administered at site of the bite and IM followed by 4 additional doses = the idea is to develop immunity while the virus is still in the prolonged incubation period (variable length) 2. Suspected animal should be captured and confined = observe animal for 10 days - if no symptoms develop → animal (-) for rabies virus

= Prophylactic vaccine against rabies (human) 1. Human Diploid Cell Vaccine (HDCV) = given to people at high risk of exposure = harvested & inactivated with beta– propiolactone = given for 4-6 dose (I. M) = very antigenic 2. Nerve tissue vaccine (Semple vaccine) = derived from brain of infected animals inactivated with formaldehyde (sheep, goat, mouse) = not commonly use because it causes sensitization of nerve tissue → post-vaccinial encephalitis

3. Duck Embryo vaccine (DEV) = prepared from developing chick embryo and inactivated by beta-propiolactone = given for 14 days (Subcutanous injection)

4. Herperimmune serum

Family Orthomyxoviridae Orthomyxovirus (Influenza viruses) = has special affinity for glycoprotein Characteristic: = segmented, single- stranded RNA virus = helical nucleocapsid = provided w/ envelope contg 2 glycoprotein spikes Hemagglutinin (H antigen) Neuraminidase (N antigen) = size 80–120 nm = genetic ressortment common = replicate in the host nucleus

Major antigenic types producing human infection Influenza Type A = undergo major and minor antigenic changes often exhibit antigenic shifting and drifting ↓ ↓ caused by reassortment due to mutation of the RNA genome in the genome = assoc. with epidemic outbreak of influenza = 13 serotypes (hemaglutinatin H1-13) (neuraminidase N1-N9) Influenza Type B = undergo only antigenic drifting, no antigenic shifting Influenza Type C

Disease: Influenza/Flu/La Grippe = self-limiting disease lasting for 3-7 days = charac. by URT manif.: cough, fever, sore throat, chill, myalgia, arthralgia = highly contagious and spread by person to person contact or by aerosol = incubation period 24 – 48 hours = site of predilection – ciliated respiratory epithelium of the respiratory tract Complication: Reye’s syndrome (Post influenza B encephalitis & fatty degeneration

Lab. Diagnosis: throat swab 1. Virological – specimen nasopharyngeal washing A. MKC – + hemadsorption B. Yolk Sac Chick Embryo +hemagglutinatin C. Madin Darby Canine Kidney (M D C K) + hemadsorption 2. Serological C F test (C F antibody first to be formed) HI

Treatment: Symptomatic/Supportive Amantadine – effective for type A infection (Symmetril) Prevention: Influenza vaccine (inactivated influenza virus) = given by I. M. = against influenza type A & B

Family Paramyxoviridae Paramyxoviruses = ss rna virus, non-segmented = helical nucleocapsid = enveloped with 1 glycoprotein spike containing neuraminidase and hemagglutinin = 150-300 NM = sensitive to ether = has special affinity for mucin = members of this family can cause wide spectrum of disease in human = replicate in the cytoplasm

3 Genera: 1. Genus Paramyxovirus = Parainfluenza virus = Mumps virus 2. Genus Morbillivirus = Rubeola/Measle virus 3. Genus Pneumovirus = Respiratory Syncitial Virus (RSV)

A. Genus Paramyxoviruses Parainfluenza virus Properties: = second leading cause of lower respiratory tract infection in young children = 4 serologic types affecting human a) Type 1 & 2 parainfluenza virus = assoc. with laryngotracheo-bronchitis (croup) infants and children (6 months –3yrs. old) = charac. stridor (high pitched noisy respiration signalling resp. obstruction) and barking

b) type 3 parainfluenza virus = assoc. with bronchiolitis and pneumonia = common in infants less than 1 year old c) type 4 parainfluenza virus = less common = occur- adult = assoc. with mild URT manif. (pharyngitis & common cold syndrome) Pathogenesis: = infection confined resp. epith. without systemic spread of virus = all 4 types of infection occurs year round = acquired by inhalation of infectious particles (resp. secretion)

Lab. Diagnosis. 1) Isolation of virus Cell culture- MKC-+ hemadsorption 2. Serological HI – demonst. four- fold rise AB titer bet. acute and convalescent sera. 3. Flourescence staining of exfoliated epithelial cell to demonstrate virus Treatment: Symptomatic & Supportive Prevention: - No Vaccine available = avoid contact with the virus

Differentiating Influenza points 1. Size dia. 2. Genome

Parainfluenza

80-120 NM. dia. Single stranded segmented

150 – 300 NM.

Single stranded non-

segmented 3. Spikes Hemagglutinin

Hemagglutinin and neuraminidase in

&

neuraminidase separate spikes 4. Fusion (F)

absent

in one spikes present

Mumps virus = enveloped containing 2 types of glycoprotein spikes< HN = 1 serotype = human (natural host) Disease: Mumps/Epidemic Parotitis = worldwide = prevalent -children 5-14 years old = MOT- respiratory droplet or inhalation/person to person contact = inc. pd. 18-21 days = initial site of infection → URT = mild self-limiting disease associated with: fever, malaise, anorexia, tenderness &

= disease benign and self-limiting = resolves 10-15 days = 30% children –asymptomatic Complications: 1. Orchitis - infection of testicles - postpubertal male - usually unilateral involvement 2. Sterility - rare complication 3. Aseptic meningitis - self limiting and has no sequelae Lab. Diagnosis: 1. Physical appearance of the patient 2. Virological - (saliva, blood, urine, CSF) MKC + hemadsorption Yolk sac developing chick embryo + hemagglutination

Treatment: = Symptomatic = No antiviral drug available Prevention: = vaccine contg.-live attenuated mump virus given in combination with measle and rubella (MMR) = hyperimmune - gamma globulin Immunity – recovery is associated with lifetime immunity

Genus Morbillivirus Rubeola/Measle virus = only 1 serotype = sensitive to ether Disease: Measle/Rubeola MOT- contact with respiratory droplet or secretion/inhalation = inc. pd. 7-14 days = initial site of infection mucosa URT ↓ multiply (disseminate) ↓ LN ↓ bloodstream (viremia) ↓

Prodromal manif: = fever, rhinitis, conjunctivitis, photopobia and cough = maculo- papular skin rashes usually appears during fever face → neck → trunk → extremities = presence of koplik’s spots buccal mucosa (diagnostic) = period of communicability 4 days before and 4 days after the appearance of rashes Complications: 1. Bronchopneumonia 2. Encephalitis 3. Subacute sclerosing Panencephalitis (rare and late complication)

Lab. Diagnosis: 1. Virological- isolation virus clinical material (nasopharyngeal and conjunctival secretions) MKC/Human Embryonic Kidney + CPE – syncithium formation = presence of Warthin-Fenkeldy cell (diagnostic) 2. Serological- det. rise AB titer CF, HI, NT, Elisa Treatment: Supportive & Symptomatic = Immune serum globulin for immunocompromised patient Prevention: MMR vaccine = live attenuated measle virus vaccine = given IM = 100% protection

Genus Pneumovirus Respiratory Syncitial Virus (RSV) = enveloped and contain 1 type of fusion protein spikes which causes cell to fuse forming a multinucleated syncitial which gives rise to the name of virus (charac. of RSV only) = possess no hemagglutinin or neuraminidase activity = human only natural host RSV = 1 antigenic type

Diseases: Bronchiolitis, Pneumonia and Croup (infants) Upper Resp. tract infection (children & adult) = self-limiting disease of the URT charac. by profuse rhinorrhea, nasal congestion, pharyngitis, cough and fever accompanied with labored and rapid respiration with prolonged expiration = primarily a resp. tract pathogen involving both the upper and lower respiratory tract = acquired by respiratory droplets = inc. pd. 1-4 days

Lab. Diagnosis: 1. Isolation of virus from nasal & pharyngeal secretion → tissue culture + presence of multinucleated giant cells 2. Detection of RSviral antigen from exfoliated cells of resp. tract by immunofluorescence test 3. Serological - ELISA Treatment: Symptomatic & Supportive Aerosolized Ribavirine → infants Prevention: = No vaccine available = recovery from infection does not induce immunity

Family Filoviridae ↓ “filament” – describe the filamentous shape of the virus Filoviruses:

Marburg virus Ebola virus

Properties: = ss non-segmented rna viruses = helical nucleocapsid = envelope = size 80nm dia. X 800nm L = pleomorphic form (circular, branched or U-shaped) = endemic in African countries (Uganda, Kenya, Sudan &

Zaire)

= no known reservoir host = natural host are probably monkey (african green monkeys)

Disease: Acute Viral Hemorrhagic Fever = a disease affecting human which is thought to originate from monkeys = mechanism of transmission is via the skin and mucous membrane through: 1) direct contact of virus infected body fluids (blood, vomitus, feces, semen) 2) nosocomial infection from contaminated materials (medical/surgical instrument) 3) preparation of body for burial = not transmitted by aerosol = incubation period 1 – 2 weeks accompanied with S & Sx of: fever, headache, myalgia, weakness,

= mortality rate high (80 – 90%) = death is due to multiorgan failure = autopsy of the patient shows hemorrhagic diasthesis and necrosis of the liver Diagnosis: PCR, ELISA Treatment: Symptomatic and Supportive = no known effective antiviral drugs available Prevention: = avoid contact with bodyfluid coming from infected body fluids = proper disposal of corpses = any material used must be incinerated and

Family Retroviridae Retroviruses = = = =

diploid, single-stranded RNA genome icosahedral nucleocapsid spherical envelope virus presence of reverse transcriptase enzyme

which converts genome RNA to DNA and 2 copies of its genome so it is a diploid virus = can cause cancer or immune deficiency disease in human

1. Human T – cell leukemia virus (HTLV) = assoc. with T – cell malignancies (Leukemia & Lymphomas) = transmission similar to HIV Disease: T-cell Leukemia/Lymphoma 2. Human immunodeficiency virus (HIV-1, HIV-2) Disease: Acquired immunodeficiency syndrome (AIDS) = result from suppression of the immune system = charac. by opportunistic infection and unusual malignancies = most disease in human is cause in HIV -1 = infected cell include CD4 helper T-lymphocytes, monocytes and some cells of the CNS = MOT: 1. Sexual contact 2. Blood product exposure 3. Perinatal = site of latency: CD4 T-lymphocytes

Epidemiology: Those at risk of infection: 1. Homosexual and Bisexual male 2. Intravenous drug users 3. Sexual contact of HIV infected individual 4. Infant of infected mother Lab. Diagnosis: 1. Clinical sign and symptoms 2. Serologic assay: Elisa/Western Blot Treatment: AZT

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