Parvovirus The smallest of the DNA viruses (18-26 nm) Has nonenveloped icosahedral virion Of all DNA viruses,

most dependent on host cell or a helper virus to replicate B19 replicates only in actively growing cells, is the only human pathogen & causes erythema infectiosum (fifth disease) Target: erythroid cells (stem cells) Exanthems Measles Scarlet fever Rubella Dukes disease Erythema infectiosum Exanthema subitum (Human Herpesvirus 6) Parvovirus Virions not enveloped. Capsids isometric. Nucleocapsids 18-22 nm in diameter, or 20-26 nm in diameter. Symmetry icosahedral. Nucleocapsids appear to be round. 60 capsomers per nucleocapsid (each a quadrilateral 'kite-shaped' wedge). Surface projections of nucleocapsid small and distinct (surface appears rough); spikes. Virions only of one kind, or may occur together with a dependent virus. Parvovirus

Epidemiology * Viral factors: capsid is resistant to inactivation; contagious period precedes symptoms; virus crosses placenta to infect fetus * Transmission: respiratory droplets * At risk: young children (fifth disease), pregnant women (fetal infection); chronic anemic Laboratory diagnosis: immune Electron Microscopy, enzyme & radioimmunoassay, PCR. Papovavirus DNA viruses having a nonenveloped 45-55 nm icosahedral virion with 72 capsomeres. Genome: single circular double-stranded DNA Contain 5 to 7 structural proteins Resistant to ether, acids and heat Intranuclear replication and assembly Virions released by cell destruction Host range is narrow Transmission by contact, airborne particles and arthropod vectors. 2 subfamilies: Papilloma- & Polyomavirinae Erythema Infectiosum 5th Dse Etiology: Parvovirus

 Affects any age group, mostly children Incubation pd: 7 -28 days S/sx: Low grade fever, anorexia, vomiting, slapped cheek (intense redness over cheek) followed by erythematous maculopapular rash over the trunk, pruritic with central clearing, HA, pharytngitis, coryza, GI disturbance, Human Papilloma Virus HPV found in the genital area is the most common STD encountered today and is considered primarily to be sexually transmitted. Current incidence in the US is estimated to be 20 million with one million new cases identified each year. This number of reported cases is up approximately 500% in the past 15 years. HPV is highly prevalent, being detected in more than 1/3 of college students. Human Papilloma Virus Epidemiology: * relatively stable to inactivation (fomites & direct contact) * plantar, common & flat warts less common in adults due to acquired immunity * laryngeal papillomas (HPV 6 & 11) seen in young children & young adults * genital warts: in sexually active individuals (HPV 6 & 11); rarely progress to cancer * cervical dysplasia: koilocytes (HPV 16 & 18) Human Papilloma Virus Pathogenesis: infect & replicate in the squamous epithelium of skin & mucous membranes to induce epithelial proliferation Oncogenic potential: HPV 16 & 18cervical papillomas and dysplasia (E6binds to p53 & E7proteinsbinds toRB, are the oncogenes) Immune response: spontaneous resolution of warts Laboratory Diagnosis of HPV Cytology Koilocytic cell Electron Microscopy Virus In situ DNA probe Viral nucleic acid Immunofluorescense Structural antigens Immunoperoxidase Structural antigens Southern blot Viral nucleic acid Culture ----- not useful ---Polyomavirus Causes disease in immunocompromised BK virus: renal disease JC virus: Progressive Multifocal Leuko- encephalopathy SV-40: simian pathogen Diagnosis: in urine, cytology reveals enlarged cells with dense basophilic intranuclear inclusions (resembles CMV); histology: brain tissue shows demyelinization Adenoviruses

Epidemiology: spread exclusively by human-to-human through respiratory or fecal-oral contact; no animal reservoirs. Laboratory Diagnosis: 1) cell cultures from epithelial cells HEK, HeLa, or Hep-2; cause lytic infection with inclusion body formation, 2) immunoassays: fluorescent antibody, EIA, DNA probe, 3: serology: rarely used; only for serotyping Adenoviruses Common diseases: RTI, conjunctivitis, gastro- enteritis, hemorrhagic cystitis Genome: linear ds DNA Virions: isometric; not enveloped. Nucleocapsids appear to be angular; 70-90 nm in diameter. Symmetry icosahedral. Surface capsomere arrangement obvious. 252 capsomeres per nucleocapsid (8-9 nm in diameter). Virions may occur together with a dependent virus; may provide helper functions to dependent virus. Adenoviruses Capsid: has fibers containing viral attachment protein. Surface projections of nucleocapsid distinct; one or two filaments; restricted to (12 vertices of capsid, but often not detected in negative stains). Latency: in lymphoid tissue and can be reactivated by immunosuppression or infection with other agents Oncogenic property: not observed in humans

Human Herpesvirus

Subfamilies:

VZV * Gamma: EBV CMV, HHV6, HHV7 Unique features: * ds DNA genome in large enveloped capsid * encode proteins that regulate mRNA/DNA synthesis & shutoff host cell functions * encode enzymes for own DNA replication * DNA replication in nucleus, virus buds from nuclear membrane, released with lysis Herpesvirus solved by cryo-electron microscopy and image reconstruction Herpesvirus Two herpes virus particles under transmission electron microscopy using the negative stain technique. Herpes Simplex Virus First of human herpesvruses to be recognized Herpes from Greek word for creep Types: * HSV 1: encephalitis, keratoconjunctivitis, ginigivostomatitis, tonsillitis, labialis, pharyngitis, esophagitis, genital lesions, whitlow

* Alpha: HSV 1 & 2, & * Beta:

* HSV 2: meningitis, oral lesions, pharyngitis, genital lesions, perianal lesions, whitlow Herpes Simplex Virus Epidemiology: * viral factors: causes recurrent & lifelong infection * transmission: in saliva, vaginal secretions & contact with lesional fluid; HSV 1 orally, HSV 2 sexually * at risk: children, sexually active individuals, health workers (whitlow); immunocompromised & neonates (disseminated disease) Whitlow : herpes infxn of finger. Herpes Simplex Virus Laboratory Diagnosis: * Cytology or histology: Tzanck test cells scraped from the base of lesions, stained with Wright/Giemsa, show syncytia, ballooning, & Cowdrys type A intranuclear inclusion * Virus isolation: most definitive assay * Serology: used only for primary and not recurrent disease

Varicella-zoster virus (VZV) member of the Herpesviridae family. etiologic agent of: primary infection * herpes zoster (HZ), the reactivation.

* varicella (chickenpox), the

Varicella-zoster virus (VZV) A double-stranded DNA virus with a diameter of 150-200 nm, a lipid envelope bearing the host cell membrane, and glycoprotein spikes Intranuclear host cell replication of VZV occurs and produces an intranuclear inclusion body. Varicella-zoster virus (VZV) After primary infection, VZV enters the dorsal root ganglia (trigeminal--HZO; geniculate-HZ oticus), where it remains with lifetime latency The dermatologic involvement in HZ is similar to the centripetal distribution of initial varicella lesions. Varicella-zoster virus (VZV) Possible ways of spread to ganglia: 1) Pattern suggests that latency arises from contiguous spread of virus from infected skin cells (varicella) to sensory nerve endings with ascent to ganglia. 2) Pattern suggests that ganglia are infected hematogenously during the viremic phase of varicella and the dermatome involvement in HZ reflects the ganglia most often exposed to reactivating stimuli. Varicella-zoster virus (VZV)

Complications may be associated with: 1) inflammatory changes: a) infiltrative, eg, keratitis; or b) vasculitic, eg, episcleritis/scleritis, iritis, ischemic papillitis, orbital vasculitis. 2) nerve damage: neurotrophic keratitis, ocular motor palsies, and neuralgia 3) tissue scarring: lid deformities, neuralgia, and lipid keratopathy.

palsy.

Varicella-zoster virus (VZV) Ramsay Hunt syndrome (facial and auditory nerves transitory ipsilateral facial paralysis with possible hearing disorders): usually more severe symptoms than Bell

Studies show only 10-22% of individuals with significant facial paralysis recover completely. Although 66% of patients with incomplete paralysis had complete recovery. Varicella-zoster virus (VZV) elderly individuals, in whom, VZV-specific, cell-mediated immunity, and cell-mediated immunity in general declines with age; in individuals with immunosuppression (eg, HIV, AIDS); in individuals with immunosuppressive therapy; and after primary infection in utero or in early infancy, where the normal immune response is decreased. Chicken Pox

Peak incidence: 5-9 years of age Manner of spread: direct contact or droplet aspiration Incubation pd: 11 21 days Prodromal pd:1-2 days Papulovesicular rashes appear on trunk spreading to face & extremities Macules-papules-vesicles w clear fluid-crusting & scar formation pruritus Epstein-Barr Virus Gamma herpesvirus Discovery of herpes virions by Electro Microscopy in African Burkitts lymphoma Accidental discovery of association with IM Causes heterophile antibody positive IM, African Burkitts lymphoma (endemic BL), and nasopharyngeal CA Also associated with B-cell lymphomas in patients with acquired or congenital immunodeficiencies (mitogen for B lymphocytes) Epstein-Barr Virus Structure: genome with 172,000 genome Has very limited host range due to limited cellular expression of receptor ( on B cells and epithelial cells of oropharynx and nasopharynx) Infection outcomes: replication in epithelial cells permissve for EBV replication; latent infection of B cells; or stimulation and immortalization of B cells

Epstein-Barr Virus

Epidemiology: * Viral factors: recurrent & lifelong infection * Transmission through saliva * At risk: children are asymptomatic or with mild disease (source); IM in adults; neoplasms in immunocompromised * Geography: IM worldwide; African Burkitts lymphoma in malaria belt of Africa; nasopharyngeal CA in China Cytomegalovirus Beta herpesvirus Common pathogen: 2.5% newborns, 50% adults Most common viral cause of congenital defects Largest genome in herpesviruses family Important pathogen in immunocompromised Replicates only in human cells Pathogenesis: cell-to-cell spread even with circulating antibody, latency in host, reactivation in immunosuppression (corticosteroids, HIV), transient immunosuppression Cytomegalovirus Congenital infections: 10% of newborns with CMV show microcephaly, intracebral calcification, hepatosplenomegaly, rash, hearing loss, mental retardation (primary infection in pregnant mother) Perinatal infection: reactivation of virus latent in cervix during pregnancy (50% of infants acquire infection during birth); virus in milk. Asymptomatic. Adult infection: prevalent in low socioeconomic level, 50% by age 35 (close or sexual contact) Cytomegalovirus Transfusion & transplantation transmission: * often results in asymptomatic infection * pneumonia & mild hepatitis * transplant recipients may reactivate virus during immunosuppression Immunocompromised Host: * Opportuistic infections: retinitis, interstitial pneumonia, colitis, esophagitis Cytomegalovirus Laboratory diagnosis: * Histology: owls eye inclusion * Cytology of exfoliated cells (urine) * Immune & DNA Probe * Culture: definitive method, especially in immunocompromised (high titers)-diploid fibroblast cell culture (4-6 weeks) * Serology: excellent results in primary disease; IgM may mean reactivation

Human Herpesvirus 6 & 7 Not serologically related to other herpesvirus causes exanthem subitum (roseola) Infection occurs early in life

Spread by close contact or respiratory route Target cell: T lymphocyte Virus establishes a latent infection Cells show large with occasional intranuclear Resting lymphocytes are resistant

and intracytoplasmic inclusion bodies

Herpesvirus Simiae B virus to Asian monkeys, but can cause a lethal CNS infection in humans Simian counterpart of HSV Diagnosis: virus isolation & serology Poxvirus

Largest and most complex viruses. Genome linear double-stranded DNA of 130-300 kilobase pair. The 200-400 nm virion is oval or brick-shaped that is visible by light microscopy. The extracellular virion possesses 2 envelopes, while the intracellular virus has only 1 envelope. Poxvirus

Virus replication is complex. Infection is initiated by attachment of the virus to one of several cellular receptors. Unlike other DNA viruses, poxviruses replicate in the cytoplasm. The virus contains all the elements for genomic replication, but cellular functions appear necessary for complete viral maturation. The smallpox rash is characterized by skin lesions that are in the same stage of evolution. Poxvirus (Smallpox) Smallpox virus particles are visible by LM By cryoelectron microscopy, virions appear as smooth, rounded rectangles and measure approximately 302 to 350 nm by 244 to 270 nm . The smallpox genome: single linear ds DNA with a hairpin loop at each end and186 kbp Virion replication is cytoplasmic and uses viral-associated DNA-dependent RNA polymerase. Viral envelopes of modified Golgi membranes containing viral-specific polypeptides. Infectious enveloped and nonenveloped virions. Poxvirus (Smallpox) Infection: inhalational exposure to nasal, oral, or pharyngeal droplets. Incubation period: 1014 days. The virus replicates locally and spreads to local lymph nodes. An asymptomatic viremia ensues on day 34, with spread to the bone marrow and spleen. 2o viremia begins on day 8 with generalized symptoms of fever and a toxic appearance.

The virus in WBC localize in dermal blood vessels with development of rash .

Poxvirus (Smallpox) Maculopapular lesions appear on the buccal and pharyngeal mucosa and on the face and extremities and move to the trunk. Over several days, these lesions first form firm vesicles imbedded in the epidermis. Pustules then form. Approximately 8 days after onset, the pustules umbilicate then form scabs. Mucosal lesions ulcerate, with the release of infectious virus into secretions. Poxvirus Molluscum contagiosum also is a poxvirus unique to humans. This virus is spread by close contact, often through sexual contact. Other human pox infections are the result of either zoonotic exposure to animal poxviruses or planned or accidental vaccinia administration.

Hepatitis B Virus A hepadnavirus; enveloped DNA virus; has limited tissue tropism and host range Virion is called Dane particle, which is unusually stable for an enveloped virus: resists treat- ment with ether, low pH, freezing, and moderate heat Virion has (1) a polymerase with reverse transcriptase activity, (2) a protein kinase around a core antigen, (3) an envelope with a glycoprotein surface antigen, (4) e antigen expresses different antigenic determinants Hepatitis B Virus Replication is unique: * virion has strict tropism for the liver * infected cells release large amounts of HBsAg without DNA * genome can integrate into the host chromosome * virus replicates through a circular RNA intermediate Hepatitis B Virus Viral factors: * labile to drying * virus shedding even when asymptomatic Transmission: in blood, semen, vaginal secretions, saliva & mothers milk Risk of superinfection or coinfection with HDV Sequelae: chronic hepatitis, cirrhosis and hepatoma Hepatitis C and E have similar epidemiology.

Hepatitis Viridae Viral Hepatitis Infection of the liver hepatocytes by viruses. 5 RNA Viruses Hepatitis A ( HAV) Hepatitis C (HCV) Hepatitis D (HDV) Hepatitis E (HEV) Hepatitis G virus

1 DNA virus Hepatitis B (HBV)

Hepatitis A & E transmitted via the fecal-oral route the rest are transmitted via blood-toblood (Parenteral) A= anal, E=enteric, BCD=Blood Hepatitis A 15 to 40 days incubation period before the patient develops acute hepatitis Serology Active infection Anti HAV IgM Old infection, no active disease Anti-HAV IgG Hepatitis B

Human body fluids Saliva, urine, semen, blood, breast milk,

Serology Hepatitis B surface antigen ( HBsAg) Means live virus & infection, either acute, chronic or carrier, when anti- HBsAg develop & HBsAg disappears patient is protected & immune

HBsAg : Disease ( Chronic or Acute) Anti-HBsAg : Immune, cure no active disease. Hepatitis B core antigen ( HBcAg) Not protective IgM anti HBcAg : new infection IgG anti HBcAg : old infection Hepatitis B envelop antigen (HBeAg) Connotes a high infectivity & active disease. Presence of anti-HBeAg suggest lower infectivity HBeAg: high infectivity Anti-HBeAg : low infectivity Treatment

Active immunization Recombinant vaccine Gene coding for HBsAg is cloned in yeast & used to produce mass quantities of HBsAg No risk of developing disease from vaccine because it contains only the surface envelope & proteins Anti viral agents For treatment of chronic active or persistent HBV infection Anti HIV drug lamivudine suppresses HBV DNA to undetectable levels, but most have relapses when disconinued Interferon alpha suppressed HBV DNA & HBeAg in 50% of treated patients Hepatitis D Can only replicate with the help of HBV IV drug use, blood transfusion, sexual contact No treatment, control of HBV is the only way to protect against HDV.

Hepatitis C Associated with hepatocellular carcinoma Parenteral transmission Anti HCV antibodies develop months after exposure Hepatitis E Fecal oral transmission ( Enteric) Frequently with consumption of fecally contaminated water Hepatitis G

Flavivirus family Transmissible by transfusion & parenteral route RNA viruses Picornaviridae Caliciviridae Reoviridae Togaviridae Flaviridae Arenaviridae Retroviridae Bunyaviridae Coronoviridae Orthomyxoviridae Paramyxoviridae Rhabdoviridae Filoviridae Nomenclature Pico: from It. piccolo small Calici: from L. calicis cup Reo: from respiratory enteric orphan Toga: from L. toga coat Flavi: from L. flavus yellow (fever) Arena: from L. arenaceous sandy or gritty (EM) Retro: for L. retro backward Bunya: from Bunyamwera, Uganda, where first Corona: from L. corona crown Nomenclature

isolated

Ortho: from Gr. orthos straight Para: from Gr. para to resemble or apart from Myxo: from Gr. myxa mucus (membrane) where the virus replicates Rhabdo: from Gr. rhabdos rod or bullet-shaped Filo: from L. filum thread Picornaviridae Small (pico) 25-30 nm RNA viruses with naked icosahedral capsid Genome is mRNA Virus replicaes in cytoplasm Virus is translated into a polyprotein which is cleaved into enzymatic & structural proteins

Most are cytolytic Picornavirus Enteroviruses * usually asymptomatic * can cause mild coldlike disease to paralysis (polio) * enter via RT or intestinal mucosa * tropism determines disease * secretory antibody response * serum AB prevents viremia & symptoms * shed in feces for long

periods Picornavirus

Clinical Syndromes: * Polio: 90% asymptomatic * Coxsackievirus & Echovirus: herpangina, pleurodynia (devils grip), aseptic meningitis, fever & rash, handfoot-mouth disease (vesicular C A16), myocardial & pericardial infections; acute hemorrhagic conjunctivitis Laboratory diagnosis: CSF examination in polio / meningitis; culture (pharynx feces or CSF); suckling mice (Coxsackie A) ; serology (IgM) Poliomyelitis Abortive type: symptomal (fever, uneasiness, sore throat, HA, nausea, vomiting, abd pain) Non-paralytic: same + stiffness of the neck, back, legs, paresthesia Paralytic type: occurs after the body temp has dec. initial phase similar to abortive followed by normal state for 1-7days. Recurrence is severe w/ cns invasion Paralysis emerge in 1-2 days preceded by neck & back stiffness, inability to kiss the knee (+) kernigs & brudzinski Assymetrical with legs more vulnerable than arms Picornavirus

Rhinovirus * most important cause of common cold * 100 serotypes identified * ICAM-1 receptor in epithelial, fibroblast, & B-lymphoblastoid cell * unlike o enterovirus, cannot replicate in GI (labile to acid pH), prefer 33 C * enters through respiratory tract * immune protection is transient (IgA, IgG) * interferon limits progression Picornavirus-Hepatitis A Infectious hepatitis; spread by fecal-oral route; a picorna virus--Enterovirus 72 with 27 nm naked icosahedral capsid surround-ing a positive SS RNA genome; very stable Contagious period extends to before and after symptoms May cause asymptomatic shedding Hepatitis E has similar epidemiology as Hep A. Picorna-like virus-Hepatitis D The Delta agent Cause of 40% of fulminant hepatitis Can replicate only in HBV-infected cells RNA genome is very small (1700 nucleotides), single stranded and circular Virion consists of the genome and a delta antigen (surrounded by HBsAg envelope)

Delta agent is cytotoxic

Hepatitis D The hepatitis D virus is replication defective and therefore cannot propagate in the absence of another virus. In humans, hepatitis D virus infection only occurs in the presence of hepatitis B infection. A patient can acquire hepatitis D virus infection at the same time as he/she is infected with the hepatitis B virus. This is called co-infection. A patient with hepatitis B can be infected with hepatitis D virus at any time after acute hepatitis B virus infection. This is called super-infection. Hepatitis D HDV super-infection should be suspected in a patient with chronic hepatitis B whose condition suddenly worsens. There is usually an obvious history of continued exposure to blood or blood products (active IV drug user). A particularly aggressive acute HBV infection should suggest HDV co-infection. Coinfection or super-infection with HDV in a patient with hepatitis B is diagnosed by the presence of antibodies against the hepatitis D virus. IgM antibodies indicate acute infection. HBV, HCV and HDV Hepatitis C virus exhibits stronger inhibitory action in the reciprocal inhibition seen in coinfection with HBV and HCV. However, hepatitis delta virus HDV is the dominant virus in HBV/ HDV co-infection and in triple co-infection. It also has a greater unfavourable influence on HCV than on HBV replication. Levels of HBV-DNA and HCV-RNA were lower in co-infections than in single infections. Caliciviridae These viruses are very widely distributed worldwide & infection is very common, especially in children between 6 and 24 months of age and account for about 3 percent of hospital admissions for diarrhea. By 6 years of age, more than 90 percent of all children have developed immunity to the illness. Most adults appear to have been infected & may or may not be immune to reinfection. Calicivirus Calicivirus infection is associated with diarrhoea or vomiting lasting 1-4 days (incubation period 1-2 days). The most frequent source of infection appears to be contaminated food/beverages - may cause up to 90% of food-related gastroenteritis outbreaks. Treatment: supportive only (rehydration). Calicivirus Calicivirus infections cannot be diagnosed on clinical grounds. These viruses cannot be cultured in vitro & there are no animal models available other than experimental transmission to human volunteers. Human caliciviruses (HCV) are commonly identified by electron microscopy in faecal specimens from patients with diarrhoea. Serological assays are available.

Reoviridae The reovirus family is divided into nine genera with four known to infect humans: * Orthoreovirus * Rotavirusnamed for the wheel-like appearance (L. rota wheel) * Coltivirus * Orbivirusnamed for the ring-shaped capsomers comprising the inner capsid (L. orbi ring) Reoviridae Genome: double-stranded RNA genome, which makes it unlike any other RNA virus. This genome is linear and segmented. Replication: in the cytoplasm like other RNA viruses, but replication occurs within a mostly intact virion particle. In most other viral families, the virion disassembles and uncoats completely before replicating.

Reoviridae Virion: The reoviral capsid is unique among the human viral families as it has three layers: two concentric icosahedral capsids at the center of which is an icosahedral inner core. The capsid shape is icosahedral. The virion particle is naked (non-enveloped), and spherical in appearance. The rotaviruses are approximately 70 nm in diameter. Reoviridae -Rotavirus Type A: infantile gastroenteritis Type B: severe gastroentieritis in all ages Viral factors: * Capsid: resistant to environmental & GI conditions * Large amounts of virus in feces * Virus released even in asymptomatic * Transmission: oral-fecal; respiratory (?) * Control: experimental live vaccine with bovine or monkey rotavirus Reoviridae -Rotavirus Pathogenesis: * can survive in acidic environment of stomach after meal * adsorption on columnar epithelial cells * viral replication follows * causes permeability changes & cell lysis Immunity: IgA in gut lumen; actively or passively acquired AB lessens severity Laboratory diagnosis: serology for specific antibody; EM of viral particles; cell culture Togaviridae/Flaviviridae Togavirus * Alphavirus Arboviruses * Rubivirus Rubella virus * Pestivirus -nonpathogenic-

* Arterivirus -nonpathogenic Flavivirus Arboviruses Togavirus/Flavivirus All are cytolytic, except for rubella All establish systemic infections & viremia All induce interferon (flu-like symptoms) All are arboviruses, except rubella & hep C Flaviviruses infect monocytes-macrophages Non-neutralizing Abs can enhance flavivirus infection via Fc receptors on macrophage Togavirus/Flavivirus Viral factors: * enveloped virus inactivated by drying, soap, & detergents * rubella can be asymptomatic Transmission: rubellarespiratory route; othersspecific arthropods for each virus Endemicity depends on habitat of vector * Aedes: dengue, yellow fever (urban pools of water) * Culex: SL encephalitis (forest, urban) Dengue Fever Acute toxic illness w/ thrombocytopenia Fever, hemorrhage, thrombocytopenia, hemoconcentration Clinical spectrum Assymptomatic Symptomatic DFS : myalgia, flu-like symp. Minimal bleeding DHF DSS

Etiology Dengue virus type 1,2,3,4 Type 3 most virulent assocted w/ encephalitis Vector: aedes aegypti (daytime) Incubation: 3-10days (mean 4-6d)

Spectrum of DHF based on severity DHF G1: no mortality - fever, non specific symp DHF G2: - G1+ spontaneous bleeding, rashes pathognomonic DHF G3 - G2 + circulatory failure, rapid weal pulse, hypotension, cold clammy skin, restlessness

DHF G4 -shock

Diagnosis: Tornique test Get bp by covering 2/3 arm with cuff Get the mean blood pressure Mean bp= (systole+diastole)/2 Maintain for 10min at mean bp Check petechia using 1x1 inch opening on a cardboard Positive result Atleast 20 petechia/ square inch CBC APC ( serial) NS1 Ag : day 1 fever. Togavirus/Flavivirus-Arbovirus

Alphaviruses: * Equine encephalitis, Chikungunya Flaviviruses: * Dengue, yellow fever, encephalitis Usually spread by arthropod vectors Have broad host range Flavivirus-Hepatitis C Virus A flavivirus with a SS (+) RNA genome Approximately 170,000,000 people worldwide and 4,000,000 in the United States are infected with HCV. Major cause of post-transfusion hepatitis (5% to 10% of transfusions); chronic hepatitis in 50-85% of cases Viremia 1 to 3 weeks after transfusion, and lasts for 4 to 6 months Antibody to HCV is not protective Who May Have HCV Infection Persons who ever injected illegal drugs Persons who were treated for clotting problems with a blood product made before 1987 when more advanced methods for manufacturing the products were developed Persons who were notified that they received blood from a donor who later tested positive for hepatitis C Who May Have HCV Infection

Persons who received a blood transfusion or solid organ transplant before July 1992 when better testing of blood donors became available Long-term hemodialysis patients Persons who have signs or symptoms of liver disease (e.g., abnormal liver enzyme tests) Healthcare workers after exposures (e.g., needle sticks or splashes to the eye ) to HCVpositive blood on the job Children born to HCV-positive women Togavirus/Flavivirus-Rubella Rubella (Latin word for little red) German measles A mild exanthematous childhood disease Serious disease in neonate after maternal infection: congenital defects Virus first infects cells of URT, goes to lymph nodes, viremia ensues (rash) Lifelong immunity follows natural infection Disease is not cytolytic & usually benign Laboratory diagnosis: specific IgM, 4x IgG German measles (Rubella) 3day measles Manner of spread: oral droplet/transplacental Incubation pd: 14-21 days S/Sx Fever, rashes appear all over the body w/in 24 hrs disappear 2-3 days w/o desquamation, Anorexia, lymphadenophathy, malaise, conjunctivitis, coryza

Treatment supportive Prevention Vaccine @ 15 months of age Congenital rubella 1st 4wks: 50% Next 4wks: 25% Last 4wks: 8%

Arenavirus Electronmicrographs of the virus that show they have a granular or sandy surface. The granular appearance may be due to the presence of ribosomes in the virus. They contain single-stranded segmented RNA. Their complex morphology is hidden with an envelope. These viruses commonly produce chronic carrier states in their host.

Arenavirus The members of this family causing human disease are: 1) Lymphocytic choriomeningitis virus - agent of lymphocytic choriomeningitis 2) Junin virus - agent of Argentinean hemorrhagic fever 3) Bolivian hemorrhagic fever virus - agent of Bolivian hemorrhagic fever 4) Lassa fever virus - agent of Lassa hemorrhagic fever Retroviruses Enveloped spherical virion 80-120nm, around a capsid containing 2 copies of +strand RNA genome RNA-dependent DNA polymerase (reverse transcriptase) and integrase enzymes Tropism due to cell-specific virus receptor Replication through DNA intermediate (provirus) Virus assembles/buds from plasma membrane Retroviridae-HIV Viral factors: * enveloped virus easily inactivated and must be transmitted in body fluids * disease has long prodrome * virus shedding before symptoms appear Transmission * in blood, semen, and vaginal secretions At risk: IV drug abusers, multipartner, Comercial Sex Worker, newborns of HIV + mothers

Retroviridae-HIV

Disease Mechanisms: * HIV infects CD4+ T cells, macrophages and microglial cells * Causes initially lytic then latent infection of CD4+ T cells with persistent low-level virus production in macrophages * Syncytia are formed with subsequent lysis * Alters T cell and macrophage functions Retroviruses-HIV Immune Suppression: * HIV cytocidal effect on CD4 cells * Syncytia formation * Functional defects in infected CD4 cells * Impaired antigen presentation * Impaired monokine production * Generation of suppressor T cells/factors * Induction of autoimmune phenomenon * Cytotoxic cell activity against virus * Decreased humoral immune response Pneumocystis Carinii Pneumonia Most children infected with Pneumocystis carinii dont get pneumonia because their immune systems are normal. Children whose immune systems are badly damaged by HIV can get PCP. PCP: most common serious infection among children with AIDS in the United States.

Retroviruses-HIV

Laboratory Diagnosis: * Serology: screening by agglutination or EIA, Western blot, immunofluorescent assay * Reverse Transctase & Antigen Assays: p24 during initial acute phase, lost during latency period * Culture: can detect latent virus * Immunologic Studies: T lymphocyte subsets (CD4/CD8 ratio) Bunyaviridae The family Bunyaviridae is the largest virus family with more than 350 registered viruses, and comprises enveloped RNA viruses with helical nucleocapsids. Many bunyaviruses are found in tropical regions where they may cause severe human disease, but a few occur also in the Nordic countries. Bunyaviridae Most bunyaviruses are arthropod (arbo)- or rodent-borne, i.e. transmitted via arthropods or from infected rodents. Bunyaviruses are usually highly specific for a certain arthropod species, and the vectors therefore constitute a large number of different species of ticks, mosquitoes and sandflies.

viruses.

Bunyaviridae Bunyaviruses are grouped into five genera, four of which include arbo- or rodent-borne

LaCrosse virus, which is a common cause of meningoencephalitis in the USA, is an important example within the California group viruses. Phleboviruses may be exemplified by viruses which cause sandfly-fever in the Mediterranean region. Bunyavirus Within the third group, Nairovirus, Crimean-Congo hemorrhagic fever virus (CCHFV) causes severe hemorrhagic fever occurring in Africa, south-east Europe and in the former Soviet Union. CCHFV is mainly spread via ticks but has also caused severe hospital outbreaks. Viruses within the genus Hantavirus cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Epidemiology Humans are usually dead-end hosts for all these viruses, except phleboviruses. There is a secondary nosocomial spread of Crimean-Congo hemorrhagic fever. Hantaan virus cycles among rodents, probably by aerosol or fomite transmission from infected rodent urine. Human infection is incidental.

Diagnosis Knowledge of the geographic site of exposure, season, and presence of arthropods leads to presumptive diagnosis in febrile cases. Diagnosis is confirmed by virus isolation, presence of specific IgM, an antibody titer rise in paired sera, or detection of RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Coronavirus Clinical Presentation: Coronaviruses cause acute, mild upper respiratory infection (common cold) and lately SARS. Structure: spherical or pleomorphic enveloped particles containing singlestranded (positive-sense) RNA associated with a nucleoprotein within a capsid comprised of matrix protein. The envelope bears club-shaped glycoprotein projections. Coronaviruses Classification: Coronaviruses (and toroviruses) are classified together on the basis of the crown or halo-like appearance of the envelope glycoproteins, and on characteristic features of chemistry and replication. Most human coronaviruses fall into one of two serotypes: OC43-like and 229E-like. Coronaviruses Multiplication: virus enters the host cell, and the uncoated genome is transcribed and translated. The mRNAs form a unique "nested set" sharing a common 3' end. New virions form by budding from host cell membranes. Coronaviruses Pathogenesis: transmission is usually via airborne droplets to the nasal mucosa. Virus replicates locally in cells of the ciliated epithelium, causing cell damage and inflammation. Coronavirus-SARS (CDC) Revised clinical criteria for SARS "to reflect the possible spectrum of respiratory illness : 1) Asymptomatic or mild respiratory illness. 2) Moderate respiratory illness: temp > 100.4 oF with one or more of: cough, shortness of breath, difficulty breathing or hypoxia. 3) Severe respiratory illness: above, plus x-ray evidence of pneumonia, or RDS, or autopsy findings consistent with pneumonia or RDS without an identifiable cause. Coronavirus-SARS (CDC) Under the new laboratory criteria, a SARS case is laboratory-confirmed if one of the following criteria is met: 1) Detection of antibody to SARS-CoV by indirect fluorescent antibody (IFA) or enzymelinked immunosorbent assay (ELISA). 2) Isolation of SARS-CoV in tissue culture.

3) Detection of SARS-CoV RNA by reverse transcriptase-polymerase chain reaction (RTPCR), which must be confirmed by a second PCR test. Coronavirus-SARS (CDC) A negative PCR, viral culture, or antibody test for SARS-Coronavirus obtained within 21 days of illness does not rule out coronavirus infection. "In these cases, an antibody test of a specimen obtained more than 21 days after illness begins is needed to determine infection" Orthomyxoviridae Members of this family are influenza viruses, which reproduce in the mucous membranes of the upper and lower respiratory tract. Contain a segmented ssRNA genome and exhibit helical symmetry. Possess a layer of surface projections (spikes) as part of outer wall, which are major antigenic determinants. The genome consists of eight pieces of RNA. Replicate in the nucleus unlike other RNA viruses Influenza Virus

Influenza serotypes A, B, & C Enveloped & 8 different segmented negative-sense RNA genome (genetic diversity) Virions are pleomorphic, spherical or tubular Two envelope glycoproteins: hemagglutinin and neuraminidase Transcribes & replicates in nucleus but buds from cytoplasm Antiviral amantadine inhibits coating step Influenza Virus Classified according to surface antigens: hemaglutinin and neuraminidase H1N1, H1N2 and H3N2 (human subtypes) Serotype A undergoes antigenic shifts and drifts to cause major pandemics. Serotype B cause localized epidemics. Serotype C is antigenically stable and causes sporadic disease Paramyxoviridae Members of this family are morphologically similar to the Orthomyxoviridae but are larger; exhibit helical symmetry, have an envelope, segmented single-stranded RNA and 15-25 genes. Paramyxoviridae Belongs to family Paramyxoviridae (as with morbillivirus & pneumovirus) Morbillivirus: measles Paramyxovirus: parainfluenza, mumps Pneumovirus: respiratory syncytial virus Paramyxoviridae

Members of causing human disease are: 1) Parainfluenza virus - causes parainfluenza 2) Mumps virus - causes parotitis 3) Measles virus (rubeola virus): cause measles and Subacute Sclerosing Panencephalitis 4) Respiratory syncytial virus - causes respiratory syncytial disease, croup

Paramyxoviridae-Measles Measles virus: * virus can pass directly from cell to cell and escape antibody control * cytoplasmic inclusions consist of incomplete viral particles * infection leads to cell lysis; persistent infection in brain cells * highly contagious by droplet * local replication in respiratory cells leads to lymphatic spread & viremia

Paramyxoviridae-Measles

Viral factors: * large, relatively unstable enveloped virion, easily inactivated * contagion period precedes symptoms * disease only in humans * only one serotype (vaccine) * immunity is lifelong At risk: unvaccinated Control: live attenuated vaccine (Schwartz or Moraten variants of Edmonston B strain; post-exposure imune serum globulin Paramyxoviridae-Measles Complications * Encephalitis * Pneumonia (giant cell pneumonia) * Atypical measles: exposure to wild form after vaccination with older form * Subacute sclerosing panencephalitis: acts as a slow virus Laboratory diagnosis: rarely indicated. * Immunofluorescence * Histopathology: giant cells * Serology Measles ( Rubeola) Manner of spread: droplet aspiration Incubation pd: 8-12 days Stages Prodromal 3-4 days (infective) Fever, slight conjunctivitis, photophobia, runny nose, cough, kopliks spot: appear 12-48 hrs prior to eruptive phase appearing as grayish white dots w/ slight reddish areolae, hemorrhagic opposite the 2nd molar and may spread to labial mucosa lasting 12-18hrs.

Eruptive phase Temperature reaches 40-45 deg C as maculopapular rash appears at the face on day 1 moving downward towards the feet at day 2-3. The rash is slightly hemorrhagic with slight pruritus.

As the rash disappears, there is desquamation & discoloration of the skin disappearing in 7-10 days

Complication Bronchopneumonia, otitis media, obstructive laryngitis, laryngotracheal bronchitis, encephalitis, mental retardation, convulsions, dawson subacute sclerosing panencephalitis (SSPE), appendicitis, reactivation of previous tb, exacerbation of malnutrition Paramyxoviridae-Parainfluenza A respiratory virus; mild coldlike disease 4 serologic tpes: types 1, 2, 3 are important causes of severe LRTI in infants and young children (laryngotracheobronchitis), second only to RSV; type is mild Only local disease; no viremia Cell-mediated immune response is reason for cell damage Short-term immunity induced by infection Vaccination is ineffective Paramyxoviridae-Mumps Causes acute benign viral parotitis Isolated in embryonated eggs (1945) and cell culture (1955) Though related to parainfluenza virus 2, there is no cross-immunity Only one serotype, which causes lytic infection Virus replicates in epithelial cells of RT and infects the parotid gland through the duct or following viremia Virus spreads to testes, ovary, pancreas, thyroid, and other organs Paramyxoviridae-Mumps

Viral factors * large relatively unstable enveloped capsid, easily inactivated * Contagion period precedes symptoms * May cause asymptomatic shedding * Host: only humans * Immunity is lifelong Transmission is by large droplet aerosol At risk: unvaccinated; immunocompromised Control: live attenuated vaccine (Jeryl Lynn) Laboratory: culture, serology (4x or IgM) Mumps

Incubation pd: 14-24 days Manner of spread: direct contact, droplet injxn fr saliva Pd. Of communicability: 6days b4 salivary gland involvement up to 9 days thereafter Most common site: parotid, submaxillary, submental Affect children 5-10years Complication

Epididymoorchitis, oophoritis, meningoencephalitis, pancreatitis, myocarditis, arthritis, hepatitis Paramyxoviridae-RSV First isolated from a chimpanzee (1956) Usually self-limited; common cold Most frequent cause of fatal acute RTI in infants & young children (laryngotracheobronchitis, pneumonia, and SIDS) No one is immune and repeated infections occur throughout life, but mild Only local disease; no viremia Pneumonia due to virus cytopathic effects Bronchiolitis is immune-mediated Breast-feeding: passive immunity for neonate Rhabdoviridae Members of family Rhabdoviridae: * Vesiculovirus: vesicular stomatitis * Lyssavirus: rabies & rabies-like virus * Plant rhabdovirus * Animal rhabdovirus Morphology: bullet-shaped enveloped virions; spikes of glycoprotein (G) cover surface (viral attachment protein; immunogenic); coiled helical nucleocapsid of ss RNA in envelope Rhabdovirus Members of this family causing human disease are: 1) Vesicular stomatitis virus - causes vesicular stomatitis, an infection of the oral mucosa 2) Rabies virus - causes rabies, an encephalitis rabies virus

Bullet-shaped, enveloped, single-stranded RNA virus that is 75 to 80 nm in diameter and belongs to the genus Lyssavirus within the rhabdovirus family. The viral glycoproteins bind to acetylcholine receptors, contribute to the neurovirulence of rabies virus, elicit neutralizing and hemagglutination-inhibiting antibodies, and stimulate cytotoxic T cell immunity. Pathogenesis Introduction of live virus through the epidermis or onto a mucous membrane. Initial viral replication appears to occur within striated muscle cells at the site of inoculation. The peripheral nervous system is exposed at the neuromuscular and spindles of unmyelinated sensory nerve cell endings. The virus then spreads centripetally up the nerve to the CNS, probably via peripheral nerve axoplasm, at a rate of ~3 mm/h. Once the virus reaches the CNS, it replicates almost exclusively within the gray matter and then passes centrifugally along autonomic nerves to other tissuesthe salivary glands, adrenal medulla, kidneys, lungs, liver, skeletal muscles, skin, and heart. Passage of the virus into the

salivary glands and viral replication in mucinogenic acinar cells facilitate further transmission via infected saliva. incubation period variable, ranging from 7 days to >1 year (mean, 1 to 2 months) depending on the amount of virus the amount of tissue involved host defense mechanisms the actual distance that the virus has to travel from the site of inoculation to the CNS. Rates of infection and mortality are highest from bites on the face, intermediate from bites on the hands and arms, and lowest from bites on the legs. Cases of human rabies with an extended incubation period (2 to 7 years) have been reported, but they are rare. The most characteristic pathologic finding of rabies in the CNS is the formation of cytoplasmic inclusions called Negri bodies which are distributed throughout the brain. clinical manifestations Divided into four stages: (1) a nonspecific prodrome, (2) an acute encephalitis similar to other viral encephalitides, (3) a profound dysfunction of brainstem centers that produces the classic features of rabies encephalitis, (4) death or, in rare cases, recovery. The prodromal period usually lasts 1 to 4 days and is marked by fever, headache, malaise, myalgias, increased fatigability, anorexia, nausea and vomiting, sore throat, and a nonproductive cough. The prodromal symptom suggestive of rabies is the complaint of paresthesia and/or fasciculations at or around the site of inoculation of virus. These sensations, which may be related to the multiplication of virus in the dorsal root ganglion of the sensory nerve supplying the area of the bite.

The encephalitic phase is usually ushered in by periods of excessive motor activity, excitation, and agitation. Confusion, hallucinations, combativeness, bizarre aberrations of thought, muscle spasms, opisthotonic posturing, seizures, and focal paralysis soon appear. Characteristically, the periods of mental aberration are interspersed with completely lucid periods, but as the disease progresses the lucid periods get shorter until the patient lapses into coma. Hyperesthesia, with excessive sensitivity to bright light, loud noise, touch, and even gentle breezes, is very common. On physical examination, the temperature may be found to be as high as 40.6C (105F). Abnormalities of the autonomic nervous system include dilated irregular pupils; increased lacrimation, salivation, and perspiration; and postural hypotension. Evidence of upper motor neuron paralysis, with weakness, increased deep tendon reflexes, and extensor plantar responses, is the rule. Paralysis of the vocal cords is common. Unfortunately, the presenting signs and symptoms of rabies are indistinguishable from those of other viral and neurologic diseases.

Thus delays in diagnosis are frequent. The presence of hydrophobia or aerophobia (seen in about two-thirds of recent cases) increases the likelihood of antemortem diagnosis. The manifestations of brainstem dysfunction begin shortly after the onset of the encephalitic phase. Cranial nerve involvement causes diplopia, facial palsies, optic neuritis, and the characteristic difficulty with deglutition. The combination of excessive salivation and difficulty in swallowing produces the traditional picture of "foaming at the mouth." Hydrophobia, the painful, violent, involuntary contraction of the diaphragmatic, accessory respiratory, pharyngeal, and laryngeal muscles initiated by swallowing liquids, is seen in ~50% of cases. Involvement of the amygdaloid nucleus may result in priapism and spontaneous ejaculation. The patient lapses into coma, and involvement of the respiratory center produces an apneic death. The prominence of early brainstem dysfunction distinguishes rabies from other viral encephalitides and accounts for the rapid downhill course. The median period of survival after the onset of symptoms is 4 days, with a maximum of 20 days, unless artificial supportive measures are instituted.

If intensive respiratory support is used, a number of late complications may appear. These include inappropriate secretion of antidiuretic hormone, diabetes insipidus, cardiac arrhythmias, vascular instability, adult respiratory distress syndrome, gastrointestinal bleeding, thrombocytopenia, and paralytic ileus. Recovery is very rare and, when it occurs, gradual. Rabies may also present as an ascending paralysis resembling the Landry/Guillain-Barre syndrome (dumb rabies, rage tranquille).

Filovirus These are enveloped helical nucleocapsids that have a uniform diameter of 80 nm but a variable length up to 14,000 nm. They are pleomorphic with branched, circular and U-shaped forms common. They contain linear single-stranded RNA. These are the most lethal of the human viruses. The target tissue is vascular endothelium. Filovirus

Members of this family include: 1) Marburg virus 2) Ebola virus Both cause acute hemorrhagic fever. Marburg virus

Marburg virus Direct contact with their fluids or cell cultures of infected monkeys. Spread of the virus between humans after close contact, often in a hospital, by exposure to droplets of body fluids, or direct contact with persons, equipment, or other objects contaminated with infectious blood or tissues. Complications after recovery: orchititis, recurrent hepatitis, transverse myelitis or uvetis. Marburg virus Incubation period of 5-10 days followed by the onset of the disease is sudden and is marked by fever, chills, headache, and myalgia. Around the fifth day, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea then may appear. Symptoms become increasingly severe to include jaundice, pancreatitis, severe weight loss, delirium, shock, liver failure, and multi-organ dysfunction. Marburg virus

Ebola Virus Ebola hemorrhagic fever (Ebola HF) is a severe, often-fatal disease in humans and nonhuman primates (monkeys, gorillas, and chimpanzees) that has appeared sporadically since its initial recognition in 1976. Named after a river in the Democratic Republic of the Congo (formerly Zaire). The virus is zoonotic Ebola-Reston was isolated from infected cynomolgous monkeys that were imported to the United States and Italy from the Philippines. Ebola Virus People can be exposed to Ebola virus from direct contact with the blood and/or secretions of an infected person. Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM ELISA, polymerase chain reaction (PCR), and virus isolation can be used to diagnose a case of Ebola HF within a few days of the onset of symptoms. Persons tested later in the course of the disease or after recovery can be tested for IgM and IgG antibodies; Ebola Virus Special Viral Groups Functional or organizational groups: * arbo: from arthropod-borne * onco: from Gr. onkos tumor because of ability to induce tumor formation Arboviruses The name indicates that these are arthropod-borne viruses, i.e., they are transmitted by a member of the Arthropoda (insects, mites, ticks, lice).

The arboviruses include the Togaviridae (except for the rubella virus), the Bunyaviridae, some of the Rhabdoviridae, some of the Arenaviridae and some of the Reoviridae. Oncoviruses Viruses that are oncogenic or cancer- causing belong in this group. Oncoviruses are either RNA- or DNA- containing types. This group includes: 1) all of the Retroviridae 2) some of the Papovaviridae, Adenoviridae, Parvoviridae, and Herpesviridae. Unclassified viruses 1. Astrovirus - A naked five to six-pointed star-shaped virus with single-stranded RNA. It causes acute gastroenteritis. There are five serotypes. 2. Torovirus - The nucleocapsid has a tubular shape which may be bent into an open torus (a bulging projection) conferring a biconcave disk- or kidney-shaped morphology. It contains single-stranded RNA. It causes enteric infections.

Slow Virus Infections The term refers to the tempo of the disease, not to the growth rate of the virus. Such diseases have a prolonged incubation period, which can be months or years, and a protracted, progressive clinical course. May be caused by conventional viruses or by the unconventional viruses Conventional Viruses Progressive multifocal leukoencephalopathy (PML) Subacute sclerosing panencephalitis (SSPE) Progressive rubella panencephalitis (PRP): Other slow virus infections: - Human immunodeficiency virus and AIDS - Rabies

Unconventional Viruses--Prions Suspected to be viruses, but lack detectable nucleic acids and consist of aggregates of protease-resistant, hydrophobic glycoprotein Cause: spongiform encephalopathy and slow neurodegenerative disease Human diseases: * Kuru * Creutzfeldt-Jacob disease (CJD) * New variant CJD disease * Gerstmann-StrausslerScheinker syndrome * Fatal Familial Insomnia

Kuru Kuru- from a dialect in New Guinea, which means trembling Uniformly fatal, chronic progressive disease of CNS due to ingestion of brain of affected. Sx: truncal and limb ataxia, tremor, dysarthria. Brain shows spongiform changes: neuronal loss, astrogliosis, amyloid plaques. Human Form of BSE LONDON (AFP) - Fri May 21, 5:56 AM ET. Some 3,800 people in Britain could be harbouring the human form of mad cow disease without knowing it, government-funded research suggests. The scientists looked for accumulations of the abnormal prion protein molecules believed to trigger both BSE and vCJD.