Adenoviridae PDF

Adenoviridae Danielle Marie A. Allarey-Susa, RMT Introduction Naked icosahedral capsid, linear double stranded DNA ~70-90nm First isolated from cultures of human adenoids and tonsils in the 1950 Stable and viable for about a week at 37°C but inactivated at 50°C. Resistant to ether and bil...

Adenoviridae Danielle Marie A. Allarey-Susa, RMT Introduction Naked icosahedral capsid, linear double stranded DNA ~70-90nm First isolated from cultures of human adenoids and tonsils in the 1950 Stable and viable for about a week at 37°C but inactivated at 50°C. Resistant to ether and bile salts Tropism: nucleus of epithelial cells Genus: Mastadenovirus-causes human infection Aviadenovirus-infects birds  Introduction 85 serotypes of human adenovirus divided into seven species (A through G) Commonly causes respiratory and gastrointestinal disease but is also associated with conjunctivitis, keratitis and disseminated multi-organ disease for immunocompromised patients MOT: respiratory droplets, fecal-oral route, fomites Incubation period: 2-14 days (Respiratory infection), 3-10 days (gastroenteritis) Pathogenesis  pharyngitis-neolneatpical aute present respiratory · disaeelite Respiratory Diseases me for t 1. Pharyngitis: the major cause of nonbacterial pharyngitis and tonsillitis, presenting as febrile common cold. Types 1–7 are commonly responsible. 2. Pneumonia: Adenovirus types 3 and 7 are associated with pneumonia in adults resembling primary atypical pneumonia particularly types 3, 7, and 21 are thought to be responsible for about 10–20% of pneumonias in childhood. In infants and young children type 7 may lead to more serious and even fatal pneumonia. 3. Acute respiratory diseases: the cause of an acute respiratory disease (ARD) syndrome among military recruits. Serotypes 4, 7 and 21 are the agents commonly isolated  swimming, Po but 19637 usually 8 less patial unctivitis - 31 H- dira , Eye infections ,4, i pollina- conjunctivitis & admoviral s chlamydial conjunctivius is similar 1. Pharyngoconjunctival fever: tends to occur in outbreaks, such as at children’s summer camps (swimming pool conjunctivitis), and is associated with serotypes 3, 7 and 14. 2. Epidemic keratoconjunctivitis (EKC): a serious condition which may appear as an epidemics, usually caused by type 8 and less often by types 19 and 37. Occurs mainly in adults and is highly contagious. 3. Acute follicular conjunctivitis: Types 3, 4 and 11 are commonly responsible. Adenoviral and chlamydial conjunctivitis are clinically similar. Gastrointestinal Disease Diarrhea: Some fastidious adenoviruses can cause diarrheal disease in children (serotypes 40 and 41). Systemic Infection Meningitis (serotype 3 and 7) Adenovirus infection in immunocompromised patients  SCID-pneumonia and hepatitis  AIDS-latent kidney infections (urine), subgenus D seen in stool  Bone marrow transplant recipients Enzyme Immunoassay Treatment and Prevention No specific antiviral chemotherapy (supportive care only) For swimming poo-associated conjunctivitis-adequate levels of chlorine in water Vaccine: Non-attenuated live Adenovirus types 4, 7, and 21 packaged in enteric capsules (military only) AAVs (Adenovirus Associated Viruses) Members of Parvoviridae Dependent with Adenoviruses or Herpes Simplex Virus to provide missing functions Key Points Adenoviruses are ~70-90nm, first isolated in the adenoids Can cause various infections but commonly associated with respiratory and gastrointestinal infections Diarrhea and vomiting is caused by adenovirus serotypes 40 and 41 No treatment, supportive care only Vaccine available for military use only (Adenovirus 4, 7, 21)  PAPOVAVIRIDAE Danielle Marie A. Allarey-Susa, RMT Introduction Pa-Papilloma Po-Polyoma Va-Vacuolating Naked icosahedral capsid containing circular double stranded DNA 2 subfamilies:  Papillomaviridae-Warts, condylomas, papillomas, cervical cancer  Polyomaviridae-BK Virus, JC virus, Merkel Cell Polyomavirus, Trichodysplasia spinulosa Polyomavirus Papillomavirus Papillomaviruses ~55nm Can cause infections in humans, dogs, cattle, monkeys and many other species HPVs-causes warts Viral tropism-cutaneous/mucosal tissue Divided into more than 200 serotypes  Papillomaviruses Envelope proteins E6 and E7 are transforming proteins associated with initiating cancer HPV high risk genotypes cause cervical, vulvar, vaginal, squamous cell oropharynx, anal and penile cancer. 95% of all cervical cancers are HPV. 70% of which is caused by HPV 16 and 18 Papillomaviruses Epidemiology MOT: Sexual, Vertical, Direct contact with infected material Incubation period: genital warts- 3 months after exposure, cancer- several years from the acquisition of infection Papillomaviruses Clinical Manifestations Skin 1. Common Warts (Verruca vulgaris)-HPV 1, 2, 4 2. Flat Warts (Verrucae plana) HPV 3 3. Epidermodysplasia verruciformis Mucus Membrane 1. Genital Warts-HPV 6, 11 2. Laryngeal Warts-HPV 6, 11 Carcinoma 1. Cervical cancer-HPV 16, 18, 31, 33, 35 2. Other cancers-squamous cell carcinoma (penis, vulva, vagina, laryngeal carcinoma Verruca Vulgaris Verruca Plana Epidermodysplasia verruciformis → Papillomaviruses Diagnosis: Histopathologic or cytologic examination of cutaneous biopsy or cells, DNA probe assays, NAAT Treatment/Prevention: Self-limiting and normally recede in 6-12 months Ablative treatments with podophyllin or liquid nitrogen Vaccines: Cervarix, Gardasil (HPV 6 and 11), and Gardasil-9 (HPV 31, 33, 45, 52, 58) Early detection: pap smear Polyomavirus Polyomavirus ~40-45nm icosahedral, naked, circular double-stranded DNA John Cunningham (JC), BK Virus, Merkel Cell Polyomavirus, Trichodysplasia spinulosa polyomavirus Believed to be transmitted through respiratory or oral secretions Infections of these viruses usually occur during childhood and appears to have little clinical significance. Latency in kidney and B lymphocytes can result in symptomatic reactivation MOT: Respiratory droplets Polyomavirus BK Virus Common infection of childhood Had been isolated in urine from children with cystitis and evidence of infection has been demonstrated in children with acute respiratory illness Reactivation in renal transplant patients-urethral strictures, bone marrow transplant patients-hemorrhagic cystitis Treatment: Cidofovir Diagnosis: PCR (blood and urine), Electron Microscopy of urinary sediments Polyomavirus JC Virus Clinical importance is in patients who are immunosuppressed due to T-cell dysfunction in whom the virus reactivates to cause progressive multifocal leukoencephalopathy (PML) Diagnosis: PCR (Brain biopsy or CSF), Serological Assays, Histological examinations Polyomavirus Merkel Cell Polyomavirus MCPv integrates its DNA into the genome of Merkel Cells Diagnosis: Tumor biopsy, PCR | Treatment: Surgery, Immunotherapy Trichodysplasia Spinulosa Polyomavirus Growth of abnormal hair-like structures in the skin Clinical presentation: red scaly patches on skin, itching or discomfort, hair like growths Diagnosis: Skin biopsy | Treatment: Cidofovir cream, Corticosteriods, Laser therapy Key Points Papovaviruses are double-stranded DNA viruses and has two genera, Papillomavirus and Polyomavirus Papillomaviruses are species-specific DNA viruses that infect the squamous epithelia and mucous membranes of vertebrates, including man Over seventy types of human papillomaviruses (HPVs) are now recognized Papillomaviruses cause several different kinds of warts in humans, including cutaneous warts, genital warts, respiratory papillomatosis, oral papillomas and cancer Key Points Polyomaviruses: John Cunningham (JC), BK Virus, Merkel Cell Polyomavirus, Trichodysplasia spinulosa polyomavirus MOT-respiratory secretions JC virus is associated with progressive multifocal leucoencephalopathy (PML) BK virus has been associated with ureteric stenosis in renal transplant recipients and acute hemorrhagic cystitis following bone marrow transplantation. Diagnosis: PCR of diagnostic specimen, serological assays, tissue biopsy Parvoviridae Danielle Marie A. Allarey-Susa, RMT Introduction Smallest of the DNA viruses (~22nm) Small, non-enveloped icosahedral capsid Linear single stranded DNA genome 2 subfamilies Densovirinae—infects invertebrates (insects and crustaceans) Parvovirinae—infects vertebrates 3 important genus affecting humans (Dependoparvovirus, Erythroparvovirus, Bocaparvovirus) Faudovirus (Canine Parvovirus), Protoparvovirus (Feline Parvovirus), Tetraparvovirus (Porcine parvovirus) Dependoparvovirus Characterized by their dependance on helper viruses such as adenoviruses or herpesviruses for replication Adeno-associated viruses (AAV) Can cause mild respiratory illness Can be used in gene-replacement therapy because of its low immunogenicity and wide tissue tropism Bocaparvovirus Human Bocavirus (HBoV) Associated with a variety of respiratory infections including bronchiolitis, pneumonia, and upper respiratory tract infections which may become severe in young children MOT: respiratory droplets Diagnosis: PCR, Antigen detection, Immunofluorescence, Electron microscopy detection Antigen PCR Immopha a Erythroparvovirus Parvovirus B19 Cell receptor: P antigen found in the surface of red blood cells, erythroid progenitors, vascular endothelium and fetal myocytes Infections causes no symptom or mild illness such as flu symptoms, rashes and joint pains. slapped cheek” rash in children, and joint pains in adults Individual with weakened immune system it can cause low blood count Infection during pregnancy can lead to miscarriage Parvovirus B19 Epidemiology Virus spreads by respiratory and oral secretions Worldwide prevalence typically in children Incubation period: 12-18 days At risk groups: Pregnant women, immunocompromised patients and those with hemolytic anemia Parvovirus B19 Clinical Diseases 1. Mild respiratory tract illness 2. Polyarthropathy Syndrome—swelling of joints. Usually lasts 1-3 weeks but can last for months. Goes away without any long-term problems 3. Aplastic crisis due to infection of red blood cell pre-cursors and immune-mediated destruction 4. Erythema infectiosum (fifth disease)-”slapped-cheek disease” Common in children aged 4-11 years May be associated with lymphadenopathy and joint symptoms 5. Hydrops Fetalis—excessive fluid build up in the fetus Parvovirus B19 MOT: Respiratory droplets Diagnosis: Antibody Testing (Parvovirus IgM)- acute infection PCR-acute infection in immunocompromised and patients with aplastic crisis PCR and Antibody testing using cord blood-diagnosis of fetal infection Treatment: supportive care Summary Parvovirus smallest DNA virus ~22nm Naked icosahedral DNA 2 subfamilies: Parvovirinae and Densovirinae Densovirinae-insects Parvovirinae-vertebrates Dependoparvovirus-Adeno-associated virus Bocaparvovirus-Human Bocavirus Erythrovirus-Parvovirus B19 P Antigen Erythema Infectiosum-5th disease HERPESVIRIDAE Danielle Marie A. Allarey-Susa, RMT Introduction Enveloped icosahedral capsid, linear double stranded DNA ~120-300nm herpes=to creep Virion consists of 4 components: nucleic acid core, capsid, tegument and envelope 3 known subfamilies:  Alphaherpesvirinae-HSV type 1 and 2, VZV  Betaherpesvirinae-CMV, HHV-6, HHV-7  Gammaherpesvirinae-EBV, HHV-8 Introduction Hallmark characteristic: latency Reactivation can be caused by various stimuli Fever, stress, UV exposure, axonal injury, immunosuppression Form Cowdry Type A intranuclear inclusion bodies Herpes Simplex Virus (HSV) was the first human herpesvirus to be recognized HUMAN HERPESVIRUS 1. Herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) 2. Varicella-zoster virus (VZV) 3. Epstein-barr virus (EBV) 4. Cytomegalovirus (CMV) 5. Human herpesviruses 6 and 7 (HHV-6 and HHV-7 6. HHV-8, (associated with Kaposi sarcoma) Herpes Simplex Virus-1 & 2 Herpes Simplex Virus Infection of either the skin or genitalia HSV type 1 (Human herpes virus type 1 or HHV type 1) is usually isolated from lesions in and around the mouth and is transmitted by direct contact or droplet spread from cases or carriers. Infections above the waist HSV type 2 (HHV type 2) is transmitted sexually or from a maternal genital infection to a new born. Infection below the waist Herpes Simplex Virus PATHOGENESIS Initially infect and replicate in mucoepithelial cells and then establish latent infection of the innervating neurons. Skin and mucous membranes are the portals of entry in which the virus also multiplies, causing lysis of cells and formation of vesicles. After replication is under way in the skin or a mucous membrane, virions travel to the root ganglia via the sensory nerves supplying the area. Herpes Simplex Virus Clinical features 1. Cutaneous Infections a. Most common site is the face—on the cheeks, chin, around the mouth or on the forehead; b. Napkin rash; c. ‘fever blister’ or herpes febrilis Some sensitive persons, very minor stimuli, like common cold, exposure to sun or even mental strain or menses may bring on such reactivation; d. Herpetic whitlow- an infection of the finger; e. Herpes gladiatorum an infection of the body; f. Eczema herpeticum. Herpes Simplex Virus Clinical features 2. Oral infection: Acute gingivostomatitis, herpetic stomatitis, pharyngitis, tonsillitis and localized lymphadenopathy may occur. 3. Ophthalmic: Severe keratoconjunctivitis, follicular conjunctivitis with vesicle formation on the lids, dendritic keratitis or corneal ulcers or as vesicles on the eyelids, corneal scarring and impairment of vision. Herpes Simplex Virus Clinical features 4. Nervous system: HSV encephalitis; Sporadic encephalitis; HSV meningitis; Sacral autonomic dysfunction; Rarely transverse myelitis or the Guillain–Barre syndrome and Bell’s palsy. 5. Visceral: HSV esophagitis; Tracheobronchitis and pneumonitis; Hepatitis; Erythema multiforme; Disseminated HSV infection. Herpes Simplex Virus Clinical features 6. Genital infections: Genital disease is usually caused by HSV-2. Genital herpetic ulcers are known to increase the risk of transmission of infection with human immunodeficiency virus (HIV). In male patients: The lesions typically develop on the glans or shaft of the penis and occasionally in the urethra; In female patients: The lesions may be seen on the vulva, vagina, cervix, perianal area, or inner thigh Inguinal lymphadenopathy: In patients of both sexes; Herpetic proctitis: in homosexuals; Herpes Simplex Virus Clinical features 7. Neonatal Herpes: Transplacental infection with HSV1 or 2 can lead to congenital malformations 8. Infections in immunocompromised hosts Herpes Simplex Virus LABORATORY DIAGNOSIS Direct Detection Electron microscopy of vesicle fluid - rapid result but cannot distinguish between HSV and VZV Immunofluorescence of skin scrapings - can distinguish between HSV and VZV PCR - now used routinely for the diagnosis of herpes simplex encephalitis and other herpes simplex infections. Virus Isolation HSV-1 and HSV-2 are among the easiest viruses to cultivate. It usually takes only 1 - 5 days for a result to be available. Serology Not that useful in the acute phase because it takes 1-2 weeks for before antibodies appear after infection. Used to document to recent infection. Herpes Simplex Virus TREATMENT 1. Acyclovir – this the drug of choice for most situations at present. It is available in a number of formulations:- I.V. (HSV infection in normal and immunocompromised patients) Oral (treatment and long term suppression of mucocutaneous herpes and prophylaxis of HSV in immunocompromised patients) Cream (HSV infection of the skin and mucous membranes) Ophthalmic ointment 2. Famciclovir and valacyclovir – oral only, more expensive than acyclovir. 3. Other older agents – e.g. idoxuridine, trifluorothymidine, Vidarabine (ara-A). These agents are highly toxic and is suitable for topical use for ophthalmic infection only Varicella-Zoster Virus Varicella-Zoster Virus Varicella—causing Chicken Pox (Bulutong)-1° infection Zoster—Shingles-2° infection Classic disease of childhood with the highest prevalence occurring in the 4-10 years old age group Highly communicable-attack rate of 90% in close contacts MOT: Respiratory droplet, Direct contact with lesion. Gain entry via the respiratory tract and spreads to the lymphoid system Incubation period: 14 days Following the primary infection, the virus remains latent in the sensory ganglia Varicella-Zoster Virus VARICELLA Primary infection Incubation period: 14-21 days Presents fever, lymphadenopathy. a widespread vesicular rash. The features are so characteristic that a diagnosis can usually be made on clinical grounds alone. Complications are rare but occurs more frequently and with greater severity in adults and immunocompromised patients. Most common complication is secondary bacterial infection of the vesicles. Severe complications which may be life threatening include viral pneumonia, encephalitis, and hemorrhagic chickenpox. Varicella-Zoster Virus HERPES ZOSTER (Shingles) Herpes Zoster mainly affect a single area of the skin. It may occur at any age but the vast majority of patients are more than 50 years of age. The latent virus reactivates in a sensory ganglion and tracks down the sensory nerve to the appropriate segment. eruption of vesicles in the skin often accompanied by intensive pain which may last for months (postherpetic neuralgia) Complications include: Ophthalmic zoster Generalized zoster Ramsay Hunt Syndrome Clinical Indication Specimens Test Interpretation of a Positive Result Chickenpox Vesicle fluid Electron Indicates a herpes virus infection (all herpes microscopy viruses look alike in the EM, so cannot distinguish between VZV and HSV) Vesicle fluid swab of the base of the PCR Indicates VZV infection lesion in virus transport medium Vesicle fluid swab of the base of the Virus culture Indicates VZV infection (takes 10-14 days to lesion in virus transport medium grow) Clotted blood taken at least 7 days after VZV IgM Indicates recent VZV infection onset Shingles Vesicle fluid Electron Indicates a herpes virus infection (VZV or microscopy HSV) Vesicle fluid in virus transport medium PCR Indicates VZV infection Vesicle fluid in virus transport medium Virus culture Indicates VZV infection Clotted blood VZV IgM Indicates recent VZV infection (but may be negative in cases of shingles) Paired clotted blood samples (first taken VZV IgG A significant rise in VZV IgG titer indicates in first 5 days of illness) recent shingles Encephalitis/meningit CSF PCR Indicates VZV CNS infection is (if the patient has had VZV infection Clotted blood VZV IgG Indicates previous VZV infection before) Varicella-Zoster Virus TREATMENT Self-limiting Acyclovir For Herpes zoster: Famciclovir and Valacyclovir PREVENTION Chicken pox: Live attenuated vaccine (2 doses)-Varivax®, ProQuad® Zoster: Zostavax, Shingrix (for adults > 50 y.o) Prophylaxis: Passive immunization of Varicella-zoster immunoglobulin (VZIg) Epstein-Barr Virus Epstein-Barr Virus (EBV) Human herpesvirus 4 MOT: saliva and sexual contact, hence the name “kissing disease” Common in younger children and sexually active adolescents Site of latency: memory B-cells EBV infected B-cells are transformed so that they become capable of continuous growth in vitro Associated with various infections Epstein-Barr Virus CLINICAL MANIFESTATIONS 1. Infectious Mononucleosis 2. Burkitt's lymphoma 3. Nasopharyngeal carcinoma 4. Lymphoproliferative disease and lymphoma in the immunosuppressed. 5. X-linked lymphoproliferative syndrome 6. Chronic infectious mononucleosis 7. Oral leukoplakia in AIDS patients 8. Chronic interstitial pneumonitis in AIDS patients. Epstein-Barr Virus CLINICAL MANIFESTATIONS 1. Infectious Mononucleosis “mono” 2. Burkitt's lymphoma Occurs in adolescents and 3. Nasopharyngeal carcinoma young adults Symptoms: Fatigue, fever, 4. Lymphoproliferative disease and sore throat, swollen lymph lymphoma in the immunosuppressed. nodes and splenomegaly 5. X-linked lymphoproliferative Treatment: Self-limiting, most syndrome cases resolve on their own 6. Chronic infectious mononucleosis 7. Oral leukoplakia in AIDS patients 8. Chronic interstitial pneumonitis in AIDS patients. Epstein-Barr Virus (EBV) LABORATORY DIAGNOSIS Hematologic approach Absolute lymphocytosis—30% Atypical lymphocytes/Downy Cells Immunologic approach Specific Antibody Test EBV Virus Capsid Antigen (VCA) Antibody (Current or past infection) EBV Nuclear Antigen (EBNA) Antibody (Past infection) EBV Early Antigen (EA) antibody (acute infection especially in immunosuppressed) Non-specific Antibody Test Heterophile Antibody Test/Monospot test (early diagnosis of IM)- positive only for 2-3 weeks after exposure EBV DNA molecular assays using whole blood Epstein-Barr Virus (EBV) TREATMENT AND PREVENTION No antiviral drug Self-limiting for 2-3 weeks No vaccine Avoid sharing personal items like utensils, drinking glasses etc. Cytomegalovirus Cytomegalovirus Has the largest genome of the human herpesvirus Replicates only in human cells Fibroblasts, epithelial cells, granulocytes, macrophages and others Establish latency in T-cells, macrophages Acquired from blood, tissue and body secretions MOT: depends on the time, development and population 1. Early Life During pregnancy (transplacental) During birth (passage to birth canal) After birth (breastfeeding) 2. Childhood Saliva (kissing) 3. Adult Sexual transmission Blood transfusion Organ transplantation Cytomegalovirus Incubation period: 3-6 weeks Causes lifelong infection May cause asymptomatic shedding Symptoms vary: A. Immunocompetent persons-mild or asymptomatic B. Immunocompromised patients HIV/AIDS: retinitis, colitis, and encephalitis Transplant recipient: severe/fatal disease C. Congenital and perinatal Cytomegalic inclusion disease, fetal death D. Neonates Microcephaly, seizure, deafness, mental retardation, jaundice, purpura, hepatitis, Cytomegalovirus Due to the severity of the infection to the unborn, it is included for pre-natal screening. TORCH test T: Toxoplasmosis O: Other infections (including syphilis and hepatitis B) R: Rubella C: Cytomegalovirus H: Herpes simplex virus Cytomegalovirus LABORATORY DIAGNOSIS NAAT (PCR, RT-PCR)-blood, urine, saliva, CSF Serological assays (CMV IgM, IgG, pp65 antigen) Viral culture Direct enzyme-linked fluorescent antibody (DEAFF) test Direct microscopic examination of lung, liver and kidney biopsy (Owl’s eye inclusion body) Cytomegalovirus TREATMENT AND PREVENTION Ganciclovir-retinitis and pneumonia Valganciclovir Foscarnet Cidofovir Prevention is indicated only in high risk cases. Screening of blood and organ donors and administration of CMV immunoglobulins have been employed in prevention. No vaccine is available. Human Herpesvirus 6, 7, 8 HHV-6 and 7 HHV-6 and HHV-7 are ubiquitous and are found worldwide. They are transmitted mainly through contact with saliva and through breast feeding. HHV-6 and HHV-7 infection are acquired rapidly after the age of 4 months when the effect of maternal antibody wears off. Like other herpesviruses, HHV-6 and HHV-7 remains latent in the body after primary infection and reactivates from time to time. HHV-6: Roseola Infantum-fever and rash in babies HHV-8 Originally isolated from cells of Kaposi’s sarcoma (KS) Now appears to be firmly associated with Kaposi’s sarcoma as well as some lesser known malignancies such as Castleman’s disease and primary effusion lymphomas HHV-8 DNA is found in almost 100% of cases of Kaposi’s sarcoma MOT: sharing utensils, kissing or close contact with infected individual, blood transfusion, organ transplantation, needle sharing, sexual transmission  Poxviridae Danielle Marie A. Allarey-Susa, RMT Introduction Largest and most complex of viruses that infect vertebrates, large enough to be seen under the light microscope. 200-450nm, ovoid to brick shaped with a complex morphology. Virion particle must carry many enzymes- deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase - allow viral messenger RNA (mRNA) synthesis to occur in the cytoplasm. Inside is a core structure shaped like a dumb bell, and two accompanying lateral bodies, so named after their location in the virion Introduction Family poxviridae contains two subfamilies 1. Chordopoxvirinae - poxviruses of vertebrates, Orthopoxvirus-Variola, Cowpox, Vaccinia and Monkeypox Molluscipoxvirus-Molluscum Contagiosum Virus 2. Entomopoxvirinae - poxviruses of insects. Replication of poxviruses is unique among the DNA-containing viruses, in that the entire multiplication cycle takes place within the host cell cytoplasm Cytopathology: produce eosinophilic inclusion bodies called Guarnieri bodies and membrane hemagglutinins in infected cells. Variola Virus Variola Virus Causative agent of Smallpox 2 subtypes Variola Major-caused the most severe disease (case fatality rate of 30%), occurred mainly in Asia Variola Minor-less severe disease (case fatality rate of 0.1%-2%) Completely eradicated in 1980 All known stocks are held at two WHO laboratories CDC (Atlanta, Georgia) State Center of Virology and Biotechnology (Koltsovo, Russia) Variola Virus MOT: Respiratory droplets, direct skin-to- skin contact, fomites Incubation period: 7-14 days Clinical Manifestation: fever, malaise, rash starts from face then downward to trunk and extremities Recovery: 2-3 weeks Complications: pneumonia, encephalitis, death Variola Virus PREVENTION Vaccination-live attenuated virus vaccine made from Vaccinia Virus Monkeypox Virus Main reservoir: Rodents (Squirrels and rats) Clade I: Congo Basin-high mortality rate Clade II: West Africa Clade III: 2022 European/North American outbreak Related to Clade 2 Sequences similar to 2019-2019 outbreak in Nigeria More mutation than expected in DNA genome MOT: Close contact with infected animals/individuals, fomites, transplacental Monkeypox Virus Symptoms: skin rash or mucosal lesions which can lasts 2-4 weeks, fever, headache, body aches, fatigue, swollen lymph nodes Some people have one or few skin lesions and other have hundreds or more. Lesions may appear anywhere in the body Transmission of disease is still possible until all sores have healed and a new layer of skin is formed. Some people can be asymptomatic Monkeypox Virus LABORATORY DIAGNOSIS Clinical diagnosis can be difficult because other infections and conditions can look similar Diagnostic specimen: Skin, fluid, crusts, throat swab/anal swab if skin lesions are absent Detection of E9L gene and B5R gene through molecular techniques Cowpox Virus Zoonosis lesions are seen on the udder and teats of cows and may be transmitted to humans during milking. Lesions in humans usually appear on the hands or fingers. Natural reservoir of cowpox seems to be a rodent Edward Jenner used cowpox virus to develop the smallpox vaccine in 1796. Vaccinia Virus Agent used for smallpox vaccination Causes mild/asymptomatic disease but can cause severe disease in immunocompromised individuals Mild rash and fever Molluscum Contagiosum Virus Incubation period: 1 week to 6 months Lesions are small, pink, wart-like tumors on the face, arms, back, and buttocks are more frequent in children than in adults. MOT: direct contact with an infected person, sharing contaminated items spread to other parts of their body by touching or scratching a lesion and then touching their body somewhere else- called autoinoculation Molluscum Contagiosum Virus DIAGNOSIS Diagnosis can be done by clinical appearance of the lesions Electron microscopy to visualize virus particles in skin tissue samples PCR of genetic material Presence of Henderson-Petterson bodies on keratinocytes