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Adenoviruses Poxviruses Parapoxvirus Features dsDNA, nonenveloped Large, DSDNA, enveloped, complex morphology, Infect...

Adenoviruses Poxviruses Parapoxvirus Features dsDNA, nonenveloped Large, DSDNA, enveloped, complex morphology, Infect ungulates and cause Hexons, Pentons, Fibers replicates in cytoplasm, potential biowarfare agent human occupational/work Over 50 serotypes, Most prevalent serotypes 1-7 Viriola: 1 serotype, eradicated vaccination with diseases of orf(sheep) and Subgroup A-F vaccinia viruses milkers( cow) nodes Most infections are asymptomatic Vaccinia (vaccine strain): hybrid of 1.Primarily infect children and less common adults cowpox+variola 2.Reactivated virus occurs in immunocompromised children + Molluscum contagiosum adults Orf Monkeypox Reservoir Humans and Animals Variola/smallpox: humans Cowpox: rodents reservoir infect cows + cats Monkeypox: monkeys + wild squirrels Molluscum contagiosum: humans Transmission Human – human: Respiratory, fecal oral, direct contact Variola: respiratory route Contact with infected sheep, Cowpox: milking cows cow Monkeypox: human to human unvaccinated community Molluscum: direct contact (sexual) + fomites Pathogenesis Penton + fibers : hemagglutinin (attachment) 1. Variola:enters upper respiratory tract by Penton: toxic to cells inhalation, spreads by lymphatics, *Lytic: mucoepethelia (permissive cells-virus is produced) viremai , infectsvall dermal tissues and *Latent: lymphoid+adenoid (nonpermissive- virus transformed) internal organs , POCKS *Transforming: hamster 2. Molluscum: replication in dermis Disease Acute respiratory disease+ Pneumonia : 1.Variola : Orf lesions: *serotype 4-7 * 5-17 day incubation Contagious pustular *spring + winter peak * flu like illness 2-4 days, followed by rash begins in dermatitis *children, young military, college student mouth spreads to face, arms, legs, hands, and Large and granulomatous *cough, conjunctivitis, fever, pharyngitis, hoarseness, cervical cover entire body inn24 hours Erythema multiform( skin adenitis(lymph node in neck) *all vesicles in same stage of development – rxn) *coldlike symptoms, laryngitis, bronchiolitis, pertussis- like synchronous rash Milkers nodes lesion: Pharyngoconjunctivitis: 2. Cowpox: Vascular, hemispherical *swimming pool conjunctivitis, pink eye, fever, sore throat, Ulcerative lesions/ milkers nodules on hands papules and nodules coryza(runny nose), nonpurulent/ no pus 3. Vaccinia: Pharyngitis: Localized skin infection Both are *in young children less than 3 Immunocompromised- spreads and cause severe 1. Self limiting *like streptococcal infection, mild flu like, nasal congestion, disease 2. Most common in cough, malaise, fever, headache, myalgia(muscle pain) 4.Molluscum: hand Acute hemorrhagic cystitis: Wart like tumors, molluscum bodies in central 3. Occupational *boys age 5-15 ,dysuria(painful urination) hematuria (blood in caseous material( eosinophilic cytoplasmic diseases seen in urine) inclusion bodies) farmers, Gastroenteritis : shepherds, *daycare( rotavirus more common) slaughterhouse *serotypes 40-41 worker, bucher *major cause of acute viral gastroenteritis -15% of cases in hospitalized patients Myocarditis Transplant patients Diagnosis Serology, ELISA, 1.clinical, Guarnieri bodies found in infected cells cell culture(epithelial cell- HeLa): 2-20 days virus causes lytic (intracytoplasmic) infection with characteristic inclusion bodies which are 2.molluscum: clinical, eosinophilic cytoplasmic distinguished from those produced by cytomegaloviruses inclusion bodies Treatment Supportive care – healthy patients 1.Supportive care Cidofovir + alpha globulin – immunocompromised or severely 2. Molluscum: self limiting in healthy diseased Rionavir, cidofovir for immunocopromised Prevention Live, nonattenuated vaccine 1.Live attenuated vaccine Alphaherpesvirus Herpes Simplex Viruses -1 HSV-2 Varicella- zoster virus Features of Large, Enveloped icosadeltahedral capsids, dsDNA , Found everywhere Herpesviruses Encode many proteins that control host cell + immune response Encode enzymes – DNA polymerase( DNA replication) good target for antiviral drugs DNA replication + capsid assembly in nucleus Released by exocytosis, cell lysis, cell-cell bridges Can cause: lytic, persistent, latent infections. Epstein-Barr virus immortalizing infection (cancer) Cell mediated immunity needed for control Benign diseases in children Morbidity + Mortality in immunocompromised Herpes simplex Initiated by direct contact, cause cytopathological effects virus mechanisms Avoids ab by cell to cell spread (syncytia) Primary target mucoepithelial Latency in neurons Reactivated by stress or immune suppression Reservoir human mucosa+ ganglia(latent) human mucosa+ ganglia(latent) human mucosa+ ganglia(latent) Transmission close personal contact- kissing, sexual Close contact (sexual transmitted) Respiratory droplets and close contact contact Pathogenesis Infects mucoepithelial cells and forms vesicles, then travels to ganglia cause life long latent Enters respiratory tract, replicate in local infection, stress reactivated virus in nerve and recurrence of vesicles lymph node, cause viremia, spread to spleen+ liver, skin rash Latent infections dorsal root ganglia Reactivation of virus cause vesicular lesions and severe nerve pain Disease Infects above the waist Infection below the waist 1.Chickenpox: 1.Gingivostomatitis( mouth and gum 1.Genital infection: painful genital vesicles, -fever, pharyngitis, malaise, rhinitis(runny inflammation)+ cold sores(tiny painful fever, malaise, myalgia(muscle pain), latency in nose) asynchronous rash (red dots, 1st chest, blisters): lesions on oral mucosa, latent sacral nerve ganglia face, back) infections trigeminal ganglion 2.Neonatal herpes: during passage through -one of the 5 childhood exanthems, less 2.Keratoconjunctivitis: swollen eyelid infected birth canal, sever, spread with liver common due to vaccination and vesicles, dendritic ulcers, if involvement, high mortality, encephalitis, skin, - sever in adults-interstitial pneumonia untreated blindness occurs eyes, mouth -Severe in neonates + immunocompromised 3.Encephalitis: fever, headache, **Herpetic Whitlow: Doctors, dentist risk of 2.Shingles: confusion, focal temporal lesion, infection of fingers by HSV-1,2 -zoster, pain and vesicles restricted to one perivascular cuffing( inflammation around dermatome blood vessels), if untreated 70% mortality -50-70 years old **Herpetic Whitlow: Doctors, dentist - reactivation of latent infection risk of infection of fingers by HSV-1,2 Diagnosis Oral lesions : clinical Genital infection :Tzank smear to show Tzanck smear-cowdry type A, intranuclear Encephalitis : PCR on CSF, large numbers formation of multinucleated gaint cells + inclusions of RBCs in CSF Cowdry type A intranuclear inclusions can Antigen detection by PCR distinguish HSV-1 from HSV-2 Treatment Acyclovir: a nucleotide analog that is only activated in infected cells Oral acyclovir-healthy adults with shingles Famciclovir, valacyclovir, penciclovir: Acyclovir resistant IV acyclovir-immunocompromised Aspirin- Reye syndrome ( swollen brain, Prevention Live, attenuated vaccine, booster for 60 year olds to prevent shingles VZIG for postexposure prophylaxis of immunocompromised  Epstein-Barr Virus = EBV Kaposi sarcoma-associated Cytomegalovirus= CMV HHV-7 + herpesvirus= KSHV HHV-6: herpes lymphotropic virus Large, Enveloped icosadeltahedral capsids, dsDNA , Found everywhere Encode enzymes – DNA polymerase( DNA replication) good target for antiviral drugs DNA replication + capsid assembly in nucleus , Released by exocytosis, cell lysis, cell-cell bridges Can cause: lytic, persistent, latent infections. Epstein-Barr virus immortalizing infection (cancer) Cell mediated immunity needed for control Benign diseases in children, Morbidity + Mortality in immunocompromised Features Gammaherpesvirus, HHV-4 Gammaherpesvirus , HHV-8 Betaherpesvirus, HHV-5 Betaherpesvirus, Target cells: B cells +epithelial Target: lymphocyte + other Target: monocyte, lymphocyte, Target: t cells Latency: B cell cells epithelial Latent: t cell Latent : B cell Latent: monocyte, lymphocyte Reservoir Human Humans Human Human Transmission Saliva (kissing disease) Sexual contact, saliva, vertical Saliva, sexual, parenteral, Respiratory droplets 90% of adult population is seropositive transplantation transplacental Pathogenesis Infects nasopharyngeal epithelial cell, salivary Gene turns on vascular Infects salivary gland epithelial cells Replicate in peripheral blood and lymphoid tissue, endothelial growth factor (VEGF- and causes a persistent infection in mononuclear cells Latent infection in B cells( binds to CD21, proliferation of vessels, fibroblasts, epithelial, macrophages induces mitosis producing Heterophile ab) angiogenisis), causes results in production of atypical reactive T cells( development of Kaposi sarcoma Downey cells) constitute up to 70% WBC count Disease Heterophile- positive mononucleosis= Kaposi sarcoma Cytomegalic inclusion disease: Roseola/ exanthem kissing disease: Primary effusion lymphoma: Most common in utero infection, subitum Fatigue, fever, sore throat, B-cell lymphoma jaundice, hepatosplenomegaly *fever 3-5 days followed lymphadenopathy(swollen lymph+ spleen), Multicentric Castlemans ( swollen spleen+ liver) by Lacy body rash splenomegaly, disease thrombocytic purpura( blueberry Lymphoproliferative disease: muffin baby), pneumonitis, CNS Immunocompromised, T cell cannot damage to death control B cell growth Hairy oral leumoplakia: Heterophile- negative AIDs patient, hyperproliferation of lingual/ Mononucleosis tongue epithelial cells *children + adults Cancer: *no pus pharyngitis 1. Burkitt lymphoma: Africa cancer of maxilla, mandible, abdomen Immunocompromised: Malaria cofactor, AIDS 1.pneumonia + pneumonitis 2. Nasopharyngeal carcinoma: 2.retinitis(10-15% AIDS patient) Asia(S.china) 3. Interstitial pneumonia + 3. Hodgkin + non Hodgkin encephalitis lymphoma 4.colitis, esophagitis(10% of AIDS patient) 5. Related with GVHR after bone marrow transplant Diagnosis Heterophile-ab positive: nonspecific, ebv ab Clinical Clinical binds Paul-Bunnell antigen on sheep, horse, Serology Owl-eye inclusion in biopsy and urine bovine rbc PCR Basophilic intranuclear inclusions Monotest, Elisa: specific ab Serology, DNA detection, culture VCA-IgM, an to early antigen: recent infection VCA-IgG, EBNA: previous infection Treatment Healthy : supportive Symptomatic Symptomatic, supportive: uncomplicated Immunocompromised: mononucleosis ganciclovir/foscranet with/out immunoglobulin UL97 Gene helps resistance to ganciclovir Prevention Safe sex, screening of blood, organ donor Herpes virus simiae (B virus) : Asian monkeys, bites, saliva, encephalopathy in humans, fatal  Human Papilloma Virus= HPV Human Polyomaviruses Features Circular dsDNA, icosahedral capsid, small genome 8kbp, Smaller genome 5kbp, dsDNA, icosahedral capsid Papilloms on Skin (warts), Mucosal+ Genital surface(chondylomas) with 72 pentameric capsomers Most common warts in older children and adults JCV-brain tissue with progressive multifocal High risk serotype 16.18.31.35: cause cervical dysplasia + carcinoma leukoencephalopathy-PML Low risk genital mucosal strains HPV-6,11,57: laryngeal, respiratory, nasal,oral cavity BKV- urine of renal transplant patient papillomas HPV16: oral cavity cancer, smoking + alcohol risk factor Pathogenesis Encodes capsid proteins : L1+L2 Primary site of replication in oropharynx, then Encodes non structural proteins: E genes(DNA replication) cause verimea and seeding in kidney where Integration of HPV genome into host chromosome, disruption of e2, clinical late infection is established upregulate e6 (targets p53 cell cycle checkpoint protein, inhibits proteosome) + e7( degrades Rb) Upregulated DNA replication, inhibit apoptosis Transmission Direct contact with lesions of infected individual contact with surface that Inhalation, close contact has the virus BKV- contaminated food, water, respiratory spread Replication 1.Virus enters through breaks in skin, mucous membrane BKV + JCV share 75% of nucleotide sequence 2.Gene expression e1,e2,e5,e6,e7( hyper proliferation + dysplasia) + DNA replication, homology, 70% with SV40 basal cell division with extra-chromosomal episome. Genome is divided into Early and Late 3.Cell moves upwards to epithelium and differentiate, late Gene expression e4,l1,l2 Early: LT, MT, sT antigens expressed from + vegetative viral DNA replication begin different spliced mRNA Incubation 2-6months Late: VP1,VP2,VP3 expressed from different spliced mRNA Disease Cutaneous Warts: palms, fingers, soles, neck, face. Spontaneously resolves PML : 1-5y *Decreased myelin production, de-myelination, Condylomas on mucosal epithelium, larynx, oral cavity, genitalia, anus likely to infection of oligodendrocytes (Anogenital warts- homosexual, increased incidence of cervical cancer 10-30 years in *muscle weakness, abnormal walking, speech future ) defect, visual blind spot Caused by: Parakeratosis( nucleus stays in skin cells) BK neuropathy: Hyperkeratosis( hypertrophy of skin) *temains latent in lymphocyte, uregintal tract, Epidermodysplasia verruciformis: autosomal recessive disease flat, crusty wart, on face, trunk, hand, undergo malignant transformation into cancer brain, reactivate when host is on Sun exposed areas. Usually young adults 0-10 years immunocompromised *associated with disease in renalntransplant Recurrent respiratory papillomatosis: most common laryngeal neoplasm in patients, graft failure children (2-4 years) at birth. Papillomas occur at vocal cords, larynx cause *treatment to decrease immunosuppresion hoarseness, airway/laryngeal obstruction *cidofovir reduce BKV Diagnosis Paper smear: cervical dysplasia DNA + capsid antigen detected in mononuclear cells of PCR: specific strains, high risk HPV types on cervix patient with PML, AIDS Visual inspection: genital warts CT, MRI Lumbar puncture for JCV PCR Treatment Surgery, cryotherapy removal of warts AIDS: highly active antiretroviral therapy -HAART Prevention Limit sexual partner, virus like particle vaccin Gardasil: induce immune response to L1 proteins of HPV6,11,16,18 Cervarix: targets HPV16, 18  Hepatitis B Virus=HBV Hepatitis D/Delta Virus Parvovirus B19 Features Enveloped, partial dsDNA, circular DNA, has ss RNA, small, amorphous, Smallest virus known to infect and cause human disease reverse transcriptase, Encodes 1 protien: delta ssDNA, icosahedral capsid, no envelope Strict tropism to liver antigen, Replication by RNA intermediate Delta antigen required for Viral DNA can integrate into host Replication which is chromosome catalyzed by host RNA Carriers are 200x more likely to develop polymerase 2, primary hepatocellular carcinoma Co-infection with HBV 40-90% maternal -neonatal infection result in chronic infection Reservoir Wide distribution among warm blooded animals B19: only human parvovirus Replicate in erythroid progenitor cells 1. Adult: bone marrow 2. Fetal: liver Transmission Sexual, parenteral, perinatal Transmission by close contact, airborne droplets, household, students HBV is high in blood, serum, wound exudates. Moderate in semen, vaginal fluid, saliva Pathogenesis HBV enters hepatocyte by blood, immune response causes clinical syndrome. Release large amounts of HBsAg lacking DNA Disease Incubation : 60-90 day Fifth disease: Erythema infectiosum Acute disease symptoms : *rash on child’s body Fever, rash, arthritis, jaundice, dark urine, * incubation 7-10 days, lasts 5-7 days malaise, anoroxea, nausea, right upper *First phase- peak level of virus and RBC destruction: fever, malaise, chills, bright quarter liver pain, itching red, slap cheek rash *Second phase-rash + arthritis (joint pain) :virus disappeared, not infectious, Chronic HBV infection: parvovirus IgM appears, *95% infant acquired infection erythematous maculopapular rash on arms, trunk caused by immune complex, *3-5% adult acquired infection lacy rash on extremities Cause chronic hepatitis, cirrhosis, liver *Third phase- clearing, recurrence for weeks due to stimuli: exercise, irritation, failure, hepatocellular carcinoma, death bathing, sunlight Aplastic Crisis: no new RBC 1.Anemic Patients: pallor, fatigue, drop in hemoglobin, destroys infected RBC, No reticulocytes to replace, this normally happens in disease but is symptomatic in anemic patient 2.Thrombocytopenic Patient: bruising Hydrops Fetalis: * pregnant woman infected need have IgM+IgG serology, development of IgM indicates acutely infection *can be fat to fetus Diagnosis Lab studying Not done because it resolves in 5-7 days Serology of Igm+IgG: ELISA, radioimmunoassay, immunofluorescence, Polymerase chain rxx(PCR): clinical diagnosis, detects viral DNA in serum Can NOT be cultured in cells Treatment Supportive care Fever: acetaminophen, ibuprofen Itching: typical anesthetic, antihistamine Chronic parvovirus:intravenous immunoglobulin -IVIG Aplastic crisis: RBC transfusion Vaccine in trails Prevention Prevent perinatal HBV transmission: HBsAg screening of pregnant woman Vaccine of infants: Mother HBsAg -= birth, 1-2m, 6-18m Mother HbsAg+= vaccine+ HepB immune globulin within 12 hours of birth, 1-2m, generalized infection RSV + Parainfluenza produce only respiratory infection Penetrate the cell by fusion with plasma membrane, Replicates in cytoplasm, Exit by budding. HN(paramyxovirus), H(morbilivirus),G(pneumovirus),F glycoprotien spikes Features 4types and 2 Acute viral illness Rubeola virus Winter months Affects all Emerging Emerging subtypes(4a+4b) Contagious viral Between family, birds, zoonosis zoonosis Common infect infants, infection of hospital contagious, Severe, fatal Severe young children throat, airways, Strain A more harmful to in horses and disease in lungs, skin common than B poultry humans animal and Inoculate: eyes, NOT humans nose harmful to eat them Reservoir Human host Fruit bats, pigs Transmission Droplets, direct contact Coughing, sneezing, Contact with Close contact Human – fomites droplets from respiratory human 3d before to 4d nose, mouth, droplets, nasal transmissi after onset throat. secretion, on Sneeze, cough fomities Eating date contaminate air palm sap Pathogenesis Spreads locally in ciliated Enters the body, Destruct epithelial epithelial cells of goes to back of cells cause other respiratory mucosal throat, nose, lymph bacteria to infect gland where it Incubation 3-5d replicates Symptoms occur Viremia 12-25d within days- hours after exposure, of exposure Incubation- 2-7d infects tissue Disease Mild to sever upper + lower Early onset: sore Measle: Most sever in People Asymptomati Mild influenza Asymptom respiratory tract infection throat(cant 8-12d after children under 2y exposed to c, mild like like to fatal atic, acute particularly in children swallow), fever, exposure Symptoms in infected cold respiratory or respiratory HPIV1+2: croup- barking tired, muscle + body Red eyes, cough, children, adults birds : Young neurological disease, cough, swollen, narrow pain, loss of fever, light are mild: headache, children, old, disease fatal voice box, breathing tube, appetite, chills sensitivity, muscle Stuffy nose, low flu-like, immunocomp encephaliti causing it hard for children pain, Kopliks fever, wheezing, conjunctivi romised may s to breath Mumps: spots(white spots rapid breath, ear tis for 1-2d have: HPIV3: bronchitis, Incubation: 14-18d in mouth), rash( infection wheezing, Cause bronchiolitis, pneumonia Muscle pain(myalgia end of infection hard disease in HPIV4:mild to sever ,headache, low ,1st forehead), Bronchiolitis breathing, pigs, respiratory tract infection fever, parotitis runny nose, sore Asthma pneumonia, domestic Reinfection: serious lower (neck lymph throat, Pneumonia asthma, poor animals respiratory tract infection : inflammation) Complications: COPD feeding pneumonia, bronchitis in Complication- CNS, pneumonia, Death- old and orchitis, encephalitis, immunocomprom immunocompromise pancreatitis, bronchitis, otitis ised child) Children above 5y have ab deafness media Diagnosis IL-18 Treatment Warm, steamy atmosphere Dexametyasone- help airway function Prevention Health care providers MMR Vaccine, live MMR should wear gloves… virus  Arboviruses Togaviruses Flavivirus Bunyavirus (Alpha Virus) (Hanataviruses) Features 3 major families Spherical, enveloped, ssRNA Spherical, ssRNA Bunyavirus features : 1.Togaviridea Arthropod-borne 2.Flaviviridea 1. Alpha virus Rodent-borne 3.Bunyaviridea 2.Rubivirus(NOT Arbovirus) Spherical, enveloped RNA virus 4 minor families 1.Reoviridea 2.Rhabdoviridea 3.Arenaviridea 4.Nodaviridea Reservoir Human, arthropod, animal: birds, pigs, monkey, rodents Transmission Vector: mosquito Urban cycle: human-mosquito-human Dengue: 4 serotypes Hanatvirus: Ticks Enzootic cycle: animal-mosquito-human/animal *se Asia, Africa, Caribbean, S America *transmission: No arthropod vector Sandflies Rural epizotic cycle: horse-mosquito-human *transmission: urban cycle -mosquito *enveloped ssRNA Man- arthropod-man which reside in water-filled containers *genome consists of 3 RNA segment: Animal-vector-man * classical symptoms: high fever, L, M, S lymphadenopathy, myalgia(muscle pain) *square grid like structure Pathogenesis Arthropod bite, through Eastern Equine Encephalitis -EEE: , bone+joint pain, headache, Multisystem pathology of HVD: reticuloendothelial Sleeping Sickness maculopapular rash damage capillaries and small vessel system causing viremia *reservoir- birds, small mammals * sever case: hemorrhagic fever + shock walls, cause vasodilation, congestion that effects CNS, *transmission-mosquito, ticks, lice, mites syndrome, mortality 5-10 %, appear in with hemorrhages capillary endotgelium, *infect: mammals, birds, reptile, amphibian patients preveiosly infected by different 5 phases live *high mortality serotype of dengue 1. Febrile phase Disease Fever +Rash *encephalitis, sore neck, headache, vision *diagnosis: serology 2. Hypotension phase Encephalitis problems, seizures, coma, neurological problems 3. Oliguric phase Haemorrhagic fever in survivors Yellow Fever: 4. Diuretic phase *diagnosis: clinical symptoms, serology, PCR, * West Africa, S America 5. Convalescent phase isolation * 2 forms of transmission: Urban + Jungle Treatment: supportive care 1. Jungle yellow fever: Hantavirus pulmonary Syndrome- Prevention: vaccine to horses, mosquito control ~cycle involving primates/monkeys and HPS forest mosquito, Human incident infected *fibrile phase Western Equine Encephalitis- WEE 2. Urban yellow fever *damage predominantly capillaries *infect: human, horses, bird, small mammals ~transmitted between humans by aedes of lungs not kidney *sever in infants and children mosquito *shock, cardiac complications cause *mortality rate is low 3-4% *symptoms: chills, Fever, headache, death *reservoir: birds myalgia(muscle pain) , GI complain *caused by Sin Numbre Virus *vector: mosquito After 3-4d bradycardia(Fagets sign), *CNS diseases in horse+human, headache, stiff jaundice, haemorrhage, oliguria( less Diagnosi: neck, stumbling walking, coma urine) , hypotension serology- IF, HAI, ELISA *prevention: vaccine direct detection of antigen- blood, Diagnosis Serology Venezuelan Equine Encephalitis- VEE urine Culture *transmission: aerosol, human-human Japanese Encephalitis: RT-PCR Direct detection test *vector: mosquito *includes= West Nile Virus Virus isolation- urine Reservoir: bats, bird, rodent, horses, small *transmission: culex mosquito, Immunochemistry tropical mammals transmission cycle stays in nature *diagnosis: symptoms, serology, PCR involving mosquito, birds, pigs Treatment: supportive care, rabavirin *treatment: supportive Treatment *1:300 human infection, life threatening (HVD) * mortality very low 1% in humans, high encephalitis mortality in horses Prevention *vaccine Chikungunya: West Nile Virus *vector: mosquito *reservoir: migratory birds(crow,black *symptoms: fever, joint pain, lymphadenopathy, birds) conjunctivitis, rash, hemorrhagic, reveal after1- *3-15 ld after being bitten become ill: 6d fever, headache, body pain, skin rash, swollen glands West Nile encephalitis- brain inflammation, high fever, stiff neck, unconscious, mental confusion, coma, shaking(tremor,convulsion), muscle weakness, paralysis  Togaviruses Hepatitis C Virus Hepatitis E Virus Hepatitis G Virus (Rubivirus) Features 3 day Measles, German Measles, Rubella Family: Flaviviridae Only acute infection New virus identified in +ssrna, enveloped, hemaggglitinin, multiply in cytoplasm + ssRNA, enveloped with glycoprotein Calicivirus-like viruse humans spikes, 6 genotypes Unenveloped, + strand RNA, Not grown in culture Non cytopathic virus Very labile and sensitive, lines Non A/B virus Rna is cloned Only infect humans Found in acute, chronic, Like HBV infection fulminant hepatitis (liver Not grown in culture begins to fail quickly), hemophilkacs, patients with multiple transfusion Resemble HCV Reservoir Post Natal Rubella: *reservoir- active human cases *transmission- airborne droplets from upper respiratory tract active human cases Virus also present- urine, feces, skin *incubation-2-3w Transmission * in neonates and childhood Percutaneous: IV drug, clotting factors Fecal oral transmission Adult infection- through mucosa of upper respiratory tract, before viral infection, transfusion, Fecal Contaminated drinking spread to transplant from infected donor, cervical lymph nodes therapeutic practice, * viremia after 7-9d, lasts for 13-15d, development of ab Permucosal, Perinatal, sexual cause the infrequent appearance of rash (immunological basis) Pathogenesis Malaise, law fever, morbilliform rash( starts on face, extremities), lasts for 5 days *Complications- arthritis(joint pain particularly in woman), thrombocytopenia, purpura, encephalitis Congenital Rubella Syndrome: *pregnant veremia with rubella infection cause infection of Disease placenta, fetus Incubation: 2-26wk Incubation: 15-60days Jaundice: 30-40% Fatality: Overall-1-3% Leading to reduced growth rate of fetal cells, less number of Chronic hepatitis : 70% Pregnant-15-25% cells after birth, causing deranged and hypoplastic/ underdeveloped organ development, result in structural Persistent infection: 85-100% Illness severity: increase with damage and abnormalities Immunity: no protective ab age  May lead fetal death and spontaneous abortion Chronic: NO  Development abnormalities appear during All manifestation of chronic HBV childhood and adolescents: catartact, cardiac infection may be seen but with lower abnormalities, deafness, microcephaly( small frequency head) , growth + mental retardation, rash, 1. Chronic persistent hepatitis hepatosplenomegaly, jaundice, 2. Chronic active hepatitis meningoencephalitis 3. Cirrhosis 4. Hepatocellular carcinoma  Arenavirus Filovirus Features SS +bi-segmented RNA, liped envelop + cloned shaped protein Ebola Virus ( EVD)  Infectious , Fatal disease ( fever, severe internal bleeding)  Transmission- contact with body fluids, blood, infected animals, sexual contact with infected person, contaminated objects, Reservoir Junin Virus: Argentine hemorrhagic fever bushmeat( bats, monkeys, deer, rats, snake) *corn harvesting period, male agriculture workers mostly infected  Incubation – 2-21 days *fatality 20%  Fatality – 50-90% *reservoir- small/ drylands vesper mouse Transmission  Primary target – hepatocytes, endothelial cells (produce most *inhalation of infected aerosols, rodents caught in mechanical furin) harvesters * tretment-  Stable at room temp., destroyed at 60c / gamma or UV radiation/ 1. immune plasma therapy, lipid solvents/ bleach 2. herbal, 3. Candid 1, live attenuated vaccine: increase neutralizing ab response, Marburg Pathogenesis  Incubation – 2-14 day develop virus specific ab-cellular cytotoxicity  Fatality – 23-25% Machupo Virus: Bolivian hemorrhagic fever  Stable at room temp., destroyed at 60c/ gamma or UV radiation/ *fatality 20% lipid solvents/ bleach * larger vesper mouse * treatment- Pathology : Disease 1. Immune plasma therapy from survivors 1. Early stage: 2. Ribavirin - Lesions in liver, spleen, kidney 3. Candid 1 - Necrosis in liver, lymph tissue, spleen - Little inflammatory response Symptoms- - Virus particles invade phagocytes *incubation 7-16 day 2. Late stage: *first symptoms : fever, malaise, headache, muscular pain, anorexia, - Enlarged Liver and spleen with excess blood nausea, vomiting - Hemorrhage in GIT, pleural, pericardial, peritoneal * between 3-5 day: dehydration, hypotension, infrequent urination, spaces and in renal tubular with fibrin deposition bradycardia - Leukopenia with bacteremia *hemorrhagic phase: Early symptoms : Begins with-petechial( blood spots) on upper trunk and oral mucosal  Prolonged fever not effected by antimalarial treatment or Hemorrhaging starts- nose, gums, stomach, intestines antibiotics Severe blood loss cause hypotensive shock and neurological crisis  Joint pain/ arthritis, body aches, headache, weakness, nausea, vomit, abdominal pain, diarrhea, fatigue, sore throat, rash, hiccups After 5-7 days: Diagnosis  Fever with spontaneous bleeding( gums, nose, eyes, ears)  Conjunctivitis (red eyes)  Analysis bleeding, bloody diarrhea, GIT bleeding  Genital swelling  Bleeding from skin, increase sense of pain  Blood does not clot  Difficult in swallowing, Dryness In throat  Depression, hypotensive shock  Liver damage Treatment: Isolation and quarantine Supportive thetapy- give fluids, electrolytes, maintain oxygen and blood pressure Mechanical ventation, renal dialysis, antizeizure therapy  Reoviruses- Rotaviruses Retroviruses Caliciviruses Astrovirus 4 genus of Reoviruses infect humans: 2 genus of human intrest: Calicivirus: 1. Noroviruses Astrovirus human 1. orthoreovirus, 1. Lentivirus- human immunodeficiency 2. Sapoviruses serotypes: HuAstV 1-8 2. orbivirus, virus(HIV 1/ 2) the cause of AIDs 3. coltivirus, 2. Human T-cell lymphotropic virus-bovine 4. rotavirus: A-G, group A are the major leukemia virus group (HTLV 1 -adult t-cell cause of acute gastroenteritis in leukemia/ 2- hairy cell leukemia) infants and young children Features Non enveloped, 11 segments of ds RNA 2 identical copies of + ss RNA( diploid), enveloped, Non enveloped, +ss rna, Non enveloped Resistant, for that it won’t die by hand washing icosahedral single capsid protein, Small ss rna and sanitation RNA is a template for DNA synthesis producing ds Resistant to environmental Round with an Found in mammals and birds cause diarrhea DNA called Provirus pressure: detergents, unbroken smooth 3 major Groups: Has Reverse Transcriptase Enzyme, Integrase, drying, acid surface A- Infections are most common Protease EM with 5/6 pointed B-ourbreaks in china star within smooth C-sparodic cases of diarrhea in infants edge Transmission More frequent in winter Transfusion: Fecal oral route In Person to person by Fecal oral route Contaminated needles: drug users contaminated water and Fecal oral route Fomites Sexual contact: HIV is present in semen and vaginal food Contamination of see Food, water borne spread secretion food or water Respiratory route Perinatal: transplacental, during birth/ breast milk Pathogenesis Only 10-100 viruses are needed to cause Virus enveolpe formed from the host cell membrane infection contains 72 spiked knobs that consist of: Produce NSP4- viral enterotoxin  Transmembrane protein TM : gp41 VP6- viral antigen (diagnosis)  Surface protein SU: gp120 – binds to cell receptors- CD4 on helper T-cells, monocytes, dendritic cells  Major capsid protein CA: p24  Outer matrix protein MA: p17 Disease 50-80% of viral gastroenteritis HIV Replication: Gastroenteritis resolves Gastroenteritis Most severe symptom in neonates and young 1. First phase: virus enters, reverse after 48 HR Affects infants and children, over 60 years transcriptase and integration into host children less than 7 Incubation: 24-48 HR less than 4 days DNA accomplished by viral protiens years, elderly and Followed by: 2. Second phase: synthesis and processing immunocompromised vomiting, of viral genome, mRNA, structural Incubation 1-4 days diarrhea- 3-9 days, usually watery, Hemorrhagic proteins, by using host machinery Nausea, vomit, gastroenteritis/ necrotizing enterocolitis seen in Acute phase viremia: 1/3-2/3 of individuals abdominal pain, neonates (enterotoxin) experience an acute disease syndrome similar to watery diarrhea, Low grade fever or high infectious mononucleosis. After 1-10 weeks of initial fever, malaise, 30% Fatality in malnourished children, infection circulating ab appears + (seroconversion) headache dehydration is the main contributor to mortality Latent period: months to years (10 years). By the age of 3- 80% of population have ab Continuous loss of CD4 cells but stays more than against rotavirus 200. The infection remains asymptomatic as long as the immune system is functional. Lymphandenopathy, diarrhea, chronic fever, night sweats, weight loss, opportunistic infection such as herpes zoster and candidiasis may occur repeatedly, Diagnosis Electron microscope Antigen /ab detection: Elisa-Detection of rotavirus antigen in feces 1. Elisa, serum 2. HIV -1/2 ab, HIV 1 CA(p24) antigen 3. Screening of blood donors 4. Western blotting Pcr: viral rna or DNA provirus, blood or tissue specimens, quantitative pcr Treatment Supportive: oral, IV rehydration Anti retroviral drug Live attenuated vaccine Nucleotide analog reverse transcriptase inhibitor Non nucleotide reverse transcriptase inhibitors Protease inhibitors Multidrug therapy Early therapy  Coronavirus Rhabdovirus Prion disease Features Human coronavirus: Ss rna Fatal neurodegenerative disorder 229E + OC43 : major cause of common Codes for 5 proteins cold Bullet shaped capsid HCoV NL-63 + HKU1: upper and lower Liped envelope respiratory tract infection Glycoprotein polymers: bind to certain SARS-cov: emerged from bats, receptors on host cell adapted in other small animals (civet cat) , acquired human transmission Enveloped, replicates in cytoplasm, ss rna Acquire genes by horizontal transfer and co-infection Reservoir Transmission Bite of infected animals Inculation or ingestion Eating infected meat Airborne transmission Corneal transplantation Pathogenesis Enters local tissue through bites travels PrPsc( scarpie) : through sensory nerves to CNS and Disease producing protein, infectious, Beta secondary structure, multiplies their causing hippocampus insoluble in solvents, resistant to digestion by proteases, and cerebellum viremia and infects other organs Creutzfeldt-jakob disease(CJD)- sporadic: Person to person transmission Disease Respiratory Infections, enteric, Fever, malaise, headache, sensory Dementia- vision abnormalities hepatic, neurological disturbance, respiratory muscle spasm, Ataxia-cerebellar dysfunction, muscle incoordination, gait, speech Initial symptoms : fever, headache, swallowing muscle spasm abnormalities body ache, malaise Abnormal reflex, spasm, tremors, rigidity Week later: dry cough, difficult Paralytic Rabies/ dump rabies Psychiatric manifestation : behavior changes, depression, breathing, severe diarrhea, Flaccid paralysis including respiratory confusion Recivery: 5-6 days after muscle, coma and death Myoclonus, death CJD-familial: Furious rabies: Autosmal dominant inheritance with family history Excitability – CNS disturbance Personality changes progression to dementia and parkinson ,recurrent spasm of muscle involved in Spongiform changes, neural loss, mild gliosis in frontal and swallowing, hydrophobia, chocking temporal lobe panic, delirium(mental confusion), convulsion(muscle contract and relax Gerstmann-str aussler-scheinker syndrom(GSS) repeatedly) Familial diesea with autosomal dominate inheritance Neurological sign and symptoms : cerebellar ataxia, gait abnormalities, dementia, dysarthria, lcular dysmetria, hyperflexia/ Diagnosis Early diagnosis: give antibiotics, areflexia in lower extremities antiviral, steroids used for atypical Mutations in codon 102 of prion protein gene pneumonia, quarantine patient Laboratory test: Fatal familial insomnia (FFI) RT-PCR- detect rna Familial disease with autosomal dominant inheritance EIA- detect serum ab to rna Severe Dementia and bilateral symmetrical degeneration of the Elisa- detect ab against the virus thalamus Treatment Wash bite Mutation in codon 178 of prion protein gene Rabies antiserum around bite Kuru : Vaccinate with HDCV Eating humans Tetanus antiserum and antibiotics Superficial Malassezia furfur Yeast skin infect Dermatophytes Sporothrix schenckii Fungi Fungal Features Eukaryotic, Complex carbohydrate cell wall- chitin, glucan, mannan Ergosterol- membrane sterol: imidazole( inhibit ergosterol synthesis ) polyene(bind tightly to ergosterol) Features Filamentous (monomorphic) Subcutaneous Infect the skin, hair, nails Dimorphic 3 genera: Environment: on plant 1. Trichophyton- skin, hair, nails material, hyphae with rosettes 2. Microsporum- hair, skin and sleeves of condia 3. Epidermophyton-nails, skin Tissue: cigar shaped yeast Transmission High inflammation – from animals Traumatic implantation: Little inflammation – from humans rose/plum tree throns, wire/sphagnum moss Reservoir Normal skin flora (lipophilic Opportunistic fungi yeast) Disease Pityriasis / Tinea versicolor: Cutaneous or Tineas / Ringworm: Sporotrichosis *superficial infection of mucocutaneous candidiasis *itching (rose Gardner disease): keratinized skin Disseminate in - tinea capitis: scalp, cause hair loss, very *subcutaneous, *moist, warm climates(bathing) compromised patients contagious lymphacutaneuos lesion *Blotchy suntan- -tinea barbae: bearded region *treatment : itraconazole hypopigmented spots on chest, - tinea corporis: skin or potassium iodide in milk back - tinea faciei: face Fungemia: premature infants -tinea cruris: butt Pulmonary sporotrichosis on intravenous lipid -tinea pedis : athletes foot (alcoholic rose garden sleeper supplement -tinea mannum : hand disease): -tinea unguium(onychomycosis) : nails *alcoholics, homeless Kerion: tinea capitis/ facieci/ corporis *treatment: itraconazole for with abscess bone/ joint infection. Amphotericin B for severe/systemic infection Diagnosis KOH mount of skin: spaghetti + Wood lamp: Microsporum( fluoresces meatball (yeast cluster and short bright yellow-green ) curved septate hyphae) KOH: mount of nail or skin (arthroconidia Wood lamp(uv): coppery- + hyphae) orange fluorescence Treatment Topical selenium sulfide, Topical imidazole or tolnaftate topical adolescents antifungal Systemic fungal Histoplasma capsulatum Coccidioides Immitis Blastomyces dermatitidis Paracoccidiodes brasiliensis infection Features Dimorphic Dimorphic Dimorphic Dimorphic Environmental: hyphae with Environment: hyphae breaking Environment : hyphae with Environment : septate hyphae microconidia and tuberculate up into arthroconidia nondescript conidia with intercalated ydoconidia macroconidia Tissue: spherules with endospores Tissue: broad-based budding Tissue: round yeast cells with Tissue: small intracellular yeast yeast and double refractile cell wall with narrow neck on bud double refractory walls and Facultative intracellular parasite multiple buds found in reticuloendothelial cells Transmission Cave exploring, cleaning chicken Inhalation of arthroconidia and coops, bulldozing becoming spherules inside cells forming endospores Reservoir soil (dust) enriched with bird Dessert sand Rotting wood – beaver dams Areas with high humidity, or bat feces moderate temp, heavy vegetation, acidic soil Disease Fungus flu (pneumonia) Valley fever: Blastomycosis: Acute(juvenile)form: * flu like, self resolving *asymptomatic to self resolving *acute/chronic pulmonary *flu like symptoms, * hepatospleenomegaly pneumonia disease lymphadenopathy, (enlarged spleen, liver) * dessert bumps/ erythema *less likely to self resolve hepatosplenomegaly( enlarged *common in summer in nodosum, arthritis(joint pain) *disseminated disease spleen and liver) children, newcomers *pulmonary lesion calcify as skin lesions *lesion calcify as the heal the heal * systemic infection in AIDs, Chronic(adult) form: Disseminated infection: immunocompromised: *primary pulmonary infection, mucocutaneous lesions , also meningitis, mucocutaneous pulmonary fibrosis, bullae/ common in AIDs lesion blister and emphysematous *disseminate in 3rd trimester changes, oral and cutaneous lesion Diagnosis Sputum cytology (calcofluor white helpful) Sputum culture on blood agar and special fungal media ( inhibitory mold agar, sabouraud) Peripheral blood culture is useful for histoplasma since it circulates in reticuloendothelial system cells Treatment Mild: Intraconazole Mild:Azole(intraconazole) Mild: Intraconazole Mild: Intraconazole Severe: amphotericin B Severe: amphotericin B Severe: amphotericin B Severe: amphotericin B Opportunisti Aspergillus fumigatus Candida albicans Cryptococcus neoformans Mucor, Rhizopus, Absidia Pneumocystis jirovecii c fungal Zygomycophyta P.carinii infection Features Monomorphic filamentous, Yeast endogenous Capsulated yeast, Nonseptate filamentous Obligate extracellular parasite dichotomously branching, Form germ tubes at 37c in monomorphic Silver stained cysts in tissue sepatate hyphae with 45 serum Ribotyping angles Form pseudohyphae and Recycler-compost pits, moldy true hyphae when it invades marijuana tissue Imp Candida auris : Resistant to drugs that treat candida: Multi drug resistant Hard to identify Caused outbreaks Reservoir Black mold on walls Mucous membrane normal Soil enriched with pigeon Soil, sparogiospores are Obligate extracellular parasite flora droppings inhaled Disease Predisposing conditions: *perleche- crevices of Predisposing conditions: Penetrates from sinuses to Interstitial pneumonia 1.Allergic bronchopulmonary mouth/ malnutrition Meningitis / Hodgkin in brain tissue *AIDs patients, malnourished aspergillosis/ asthma, *oral thrush-antibiotic use, AIDs, *rhinocerebral infection- babies, premature neonates, 2.cystic fibrosis immunocompromised, AIDs acute Pulmonary infection mucor immunocompromised adults *Fungus ball: free in lung *esophagitis- antibiotic use, *paranasal swelling, necrotic and kids cavity, surgical removal to immunocompromised, AIDs tissue, hemorrhagic exudates *fever, cough, shortness of reduce coughing, may cause *gastritis- antibiotic use, from nose and eyes, mental breath, sputum nonproductive pulmonary hemorrhage immunocompromised, AIDs lethargy except in smokers *invasive aspergillosis/ severe *septicemia, with Occurs In: ketoacidotic and * serum leaks into alveoli neutropenia, CGD, CF, burn endophthalmitis and leukemia patients causing exudate with foamy/ -invades tissue cause necrosis, macronodular skin lesion- honeycomb appearance on hemorrhages immunocompromised, H&E stain -pneumonia, meningitis cancer, intravenous patient * X-ray patchy infiltrate/ -cellulitis in burn patients *endocarditis-intravenous ground glass appearance drug abusers *cutaneous infection- obesity, infants, rubber gloves *yeast vaginitis-diabetic woman *chronic mucocutaneous candidas-endocrine defects Diagnosis KOH- pseudohyphae, true Meningitis by CSF: Koh: Broad ribbon like Silver stain cyst in bronchial hyphae, budding yeast *detect capsular antigen: nonseptate hyphae with 90 alveolar lavage fluid or biopsy latex particle agglutination angles on branches Culture formation of germ OR counter tubes: septicaemia immunoelectrophoresis *india ink mount: budding yeast with capsular halos *culture(urease positive) Treatment Invasive: Voriconazole Topical, oral imidazole, Amb+5fc(flucytosine) until Debridement of necrotic Mild: Trimethoprim/ Abpa: glucocorticoids, nystatin, amphotericin B, afebrile and – culture Then tissue and amphotericin B sulfamethoxazole intraconazole fluconazole fluconazooe Fatality is high due tonrapid Severe: dapsone growth and invasion Protozoa Plasmodium vivax Plasmodium ovale Plasmodium falciparum Plasmodium malaria Definitive Host Anopheles mosquito Intermediate Host Humans, primates-monkeys, Humans Humans Humans, primates chimpanzee Greatest killer of humans in the Transfusion malaria tropics Location in intermediate Liver and red blood cells host Transmission Injected during mosquito bite Pathogenesis Schizonts rupture liver cells and RBC Disease Benign tertian malaria: Mild tertian malaria: Malignant tertian malaria: Quartan malaria: *Least virulent * Invades young rbc *invades all RBC *invades old rbc *Invades young rbc *fever + chills every 48hr cycle creates knobs on RBC to embed it *fever+chills in 72hr *fever + chills every 48hr cycle * mainly in tropics, old and new on endothelium of blood vessels, *relapse after 53 years *relapse after 8 years world ->avoids spleen damage, *resistant to antibiotics ->creates cluster in blood vessels *most common in temperate *fever+chills every 48hr cycle regions *relapse after 1-3 years *65% of rbc infected at the same Only invade rbc if there is time specific receptor Complications: 1.Cerebral malaria *headache, psychotic symptoms, convulsion, coma, death 2.Pulmonary edema 3.Blackwater fever *massive lysis of RBC lead to hemoglobin in urine, black urine, renal failure, death, *autoimmune rxn or due to drugs to prevent /treat malaria Diagnosis Blood smear: RBC have scuffner Blood smear: RBC are larger Hard to diagnose in circulating Blood smear: Band troph dots and larger than normal than vivax with Shuffner dots blood in primary infection, since Differentiate from vivax by DNA infected rbc cluster up - skin biopsy: gametocytes -elisa -oblong gametes + multi ring Treatment Chloroquine- kills erythrocytes Chloroquine, primaquine Chloroquine Cloroquine stage Sulfadoxine + pyrimethamine used Primaquine-kills exoerythrocytic for chloroquine resistant + erythrocytic stage Melfoquine strains resistant to other drugs Artemisinin for melfoquine resistant Protozoa Toxoplasma gondii Cryptosporidium parvum Entamoeba histolytica Giardia lamblia G.intestinalis/duodenalis Definitive Host Cats, lions, tigers…. Human, most mammals Humans Humans Chicken, turkeys, Reservoir: dog, pigs, monkey Reservoir: beaver, cows, sheep, cats, dogs, mammals Intermediate Anything a cat would eat: Host -Domestic-sheep, cow -Wild animal Humans accidental host Location in Mostly: Intestines of cats Invades cells lining the small Cecum, intestines Small intestine- duodenum, jejunum, upper defenitive host May go to other organs intestine, particularly ileum