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USMLE Step 1 Web Prep — Medically Important Viruses, Part 3 131580 >>> 0:00:00.2 SLIDE 1 of 53 Parvoviridae ssDNA (linear) Naked icosahedral B-19 Virus Fifth disease = erythema infectiosum = slapped cheek fever: A mild, febrile disease with facial rash followed by lacy body rash Linked to aplastic crises in Sickle Cell anemia patients B-19 infects only immature red cells causing lysis, hence the anemia, which is only clinically significant in Sickle Cell Disease Potential cause of hydrops fetalis 131585 >>> 0:00:51.2 SLIDE 2 of 53 Parvoviridae ssDNA (linear) Naked icosahedral B-19 Virus Fifth disease = erythema infectiosum = slapped cheek fever: A mild, febrile disease with facial rash followed by lacy body rash Linked to aplastic crises in Sickle Cell anemia patients B-19 infects only immature red cells causing lysis, hence the anemia, which is only clinically significant in Sickle Cell Disease Potential cause of hydrops fetalis 131590 >>> 0:01:38.2 SLIDE 3 of 53 Papovaviridae Circular ds DNA Naked icosahedral Human Papilloma Virus Contact Plantar warts: HPV 1 & 4 Anogenital (condyloma acuminatum) and laryngeal papillomas; HPV types 6 and 11 are most common (considered benign) Cervical intraepithelial neoplasia (HPV 98%) HPV 16 and 18 are most common 131595 >>> 0:02:25.2 SLIDE 4 of 53 Papovaviridae Circular ds DNA Naked icosahedral Human Papilloma Virus Contact Plantar warts: HPV 1 & 4 Anogenital (condyloma acuminatum) and laryngeal papillomas; HPV types 6 and 11 are most common (considered benign) Cervical intraepithelial neoplasia (HPV 98%) HPV 16 and 18 are most common 131600 >>> 0:02:37.2 SLIDE 5 of 53 Papovaviridae Circular ds DNA Naked icosahedral Human Papilloma Virus Contact Plantar warts: HPV 1 & 4 Anogenital (condyloma acuminatum) and laryngeal papillomas; HPV types 6 and 11 are most common (considered benign) Cervical intraepithelial neoplasia (HPV 98%) HPV 16 and 18 are most common 131605 >>> 0:02:50.2 SLIDE 6 of 53 Adenoviruses Upper respiratory disease in kids Pharyngoconjunctivitis (“pink eye” or “Swimming pool” conjunctivitis), non-purulent (unlike Haemophilus aegyptius) Epidemic keratoconjunctivitis (“shipyard” conjunctivitis: patients having foreign particles removed acquired these viruses from equipment used on the eyes) Acute respiratory disease (ARD) and pneumonia: Major problem in young military recruits Serotypes 4, 7; and 21 Three separate vaccines are used by the US military: o live non-attenuated; o serotypes 4, 7, and 21; o administered separately by enteric- coated capsules. Adenovirus 40 and 41 cause infantile diarrhea. 131606 >>> 0:03:56.2 SLIDE 7 of 53 Herpesviridae Enveloped icosahedral nucleocapsids with ds DNA DNA is synthesized in the nucleus Can enter the latent state in the host: HSV in neurons, EBV in B-lymphocytes Acyclovir (the prodrug form of a nucleoside analog) is effective only in Herpes virus infected cells because the herpes thymidine kinase is required to activate it; then it inhibits only the herpes polymerase, leaving the host polymerase functioning. No current drug can remove the latent DNA. Form intranuclear inclusion bodies Produce distinctive cytopathology 131610 >>> 0:05:15.2 SLIDE 8 of 53 Herpesviridae Enveloped icosahedral nucleocapsids with ds DNA DNA is synthesized in the nucleus Can enter the latent state in the host: HSV in neurons, EBV in B-lymphocytes Acyclovir (the prodrug form of a nucleoside analog) is effective only in Herpes virus infected cells because the herpes thymidine kinase is required to activate it; then it inhibits only the herpes polymerase, leaving the host polymerase functioning. No current drug can remove the latent DNA. Form intranuclear inclusion bodies Produce distinctive cytopathology 131615 >>> 0:05:49.2 SLIDE 9 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131620 >>> 0:06:14.2 SLIDE 10 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131625 >>> 0:06:31.2 SLIDE 11 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131630 >>> 0:06:35.2 SLIDE 12 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131635 >>> 0:06:39.2 SLIDE 13 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131640 >>> 0:06:52.2 SLIDE 14 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131645 >>> 0:07:28.2 SLIDE 15 of 53 Herpes Simplex type I (HSV-1) Gingivostomatitis and recurrent cold sores (skin or lip); latent in trigeminal root ganglion Keratoconjunctivitis generally with lid swelling and vesicles; dendritic ulcers may be seen; untreated repeated attacks may result in visual impairment Meningoencephalitis Herpetic Whitlow Eczema Herpeticum 131650 >>> 0:07:47.2 SLIDE 16 of 53 Herpes Simplex Type II (HSV-2) Herpes genital infections-painful vesicular lesions of genitals and anal area; latent in sacral nerve ganglia Neonatal herpes may be one of three presentations: 1. Disseminated with liver involvement; high mortality 2. Encephalitis; high mortality 3. Skin, eyes, or mouth The Tzanck smear (Giemsa stain to show multinucleated giant cells) has been largely replaced by immunofluorescent staining, which can distinguish HSV-1 from HSV-2 131655 >>> 0:08:17.2 SLIDE 17 of 53 Herpes Simplex Type II (HSV-2) Herpes genital infections-painful vesicular lesions of genitals and anal area; latent in sacral nerve ganglia Neonatal herpes may be one of three presentations: 1. Disseminated with liver involvement; high mortality 2. Encephalitis; high mortality 3. Skin, eyes, or mouth The Tzanck smear (Giemsa stain to show multinucleated giant cells) has been largely replaced by immunofluorescent staining, which can distinguish HSV-1 from HSV-2 131660 >>> 0:08:22.2 SLIDE 18 of 53 Herpes Simplex Type II (HSV-2) Herpes genital infections-painful vesicular lesions of genitals and anal area; latent in sacral nerve ganglia Neonatal herpes may be one of three presentations: 1. Disseminated with liver involvement; high mortality 2. Encephalitis; high mortality 3. Skin, eyes, or mouth The Tzanck smear (Giemsa stain to show multinucleated giant cells) has been largely replaced by immunofluorescent staining, which can distinguish HSV-1 from HSV-2 131665 >>> 0:08:29.2 SLIDE 19 of 53 Herpes Simplex Type II (HSV-2) Herpes genital infections-painful vesicular lesions of genitals and anal area; latent in sacral nerve ganglia Neonatal herpes may be one of three presentations: 1. Disseminated with liver involvement; high mortality 2. Encephalitis; high mortality 3. Skin, eyes, or mouth The Tzanck smear (Giemsa stain to show multinucleated giant cells) has been largely replaced by immunofluorescent staining, which can distinguish HSV-1 from HSV-2 131670 >>> 0:08:37.2 SLIDE 20 of 53 Herpes Simplex Type II (HSV-2) Herpes genital infections-painful vesicular lesions of genitals and anal area; latent in sacral nerve ganglia Neonatal herpes may be one of three presentations: 1. Disseminated with liver involvement; high mortality 2. Encephalitis; high mortality 3. Skin, eyes, or mouth The Tzanck smear (Giemsa stain to show multinucleated giant cells) has been largely replaced by immunofluorescent staining, which can distinguish HSV-1 from HSV-2 131675 >>> 0:09:05.2 SLIDE 21 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with VaricellaZoster Immunoglobulin 131680 >>> 0:09:37.2 SLIDE 22 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with Varicella-Zoster Immunoglobulin 131685 >>> 0:09:44.2 SLIDE 23 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with VaricellaZoster Immunoglobulin 131690 >>> 0:09:56.2 SLIDE 24 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with Varicella-Zoster Immunoglobulin 131695 >>> 0:10:09.2 SLIDE 25 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with Varicella-Zoster Immunoglobulin 131700 >>> 0:10:21.2 SLIDE 26 of 53 Varicella-Zoster Chickenpox: Asynchronous rash Latent in dorsal root ganglia shingles in adults (severe nerve pain) Associated with Reye’s syndrome Disseminated infections in immunocompromised hosts Attenuated vaccine Passive transfer of immunity with VaricellaZoster Immunoglobulin 131705 >>> 0:10:38.2 SLIDE 27 of 53 Epstein-Barr Virus (EBV) Many inapparent infections; common, worldwide 90% of the population seropositive Infectious mononucleosis - “Kissing disease” Heterophile positive mononucleosis, fatigue, fever, sore throat, Lymphadenopathy, and splenomegaly Positive for heterophile antibodies that cross-react with Paul-Bunnell antigen on sheep and bovine RBC; (only mono that is heterophile antibody positive) 131710 >>> 0:11:58.2 SLIDE 28 of 53 Cytomegalovirus (CMV) Herpesviridae infecting fibroblasts; common 80% worldwide Owl’s eyes = CMV (Sightomegalovirus?) basophilic intranuclear inclusion bodies with smaller eosinophilic cytoplasmic inclusion bodies Dangerous in HIV+ patients Treat with gangcyclovir 131711 >>> 0:13:25.2 SLIDE 29 of 53 Human Herpesvirus 6 Exanthem subitum (Roseola) - common infant disease: fever followed by rash Human Herpesvirus 8 Probable cofactor in Kaposi's sarcoma 131715 >>> 0:13:57.2 SLIDE 30 of 53 RNA Viruses 131720 >>> 0:18:14.2 SLIDE 31 of 53 131721 >>> 0:20:01.2 SLIDE 32 of 53 Caliciviridae Small (slightly larger than Picornaviridae) but similar to Picornaviridae Hepatitis E Norwalk Agent Described as Calicivirus-like Naked icosahedral Epidemic viral gastroenteritis in school-age kids and adults 131725 >>> 0:20:50.2 SLIDE 33 of 53 Picornaviridae Small ss(+) RNA viruses Naked Enteroviruses (group) Fecal-oral transmission but do not cause diarrhea Polio Virus Most infections are asymptomatic; small % cause fever (viremia) Vaccines: both are trivalent: Sabin (live/oral/best gut immunity), Salk (killed/injectable) Coxsackie A Herpangina (vesicles on soft palate and fauces) Hand-foot-and-mouth disease (oral lesions primarily in the anterior buccal mucosa) Aseptic meningitis Coxsackie B Aseptic meningitis Myocarditis Hepatitis A Virus ss (+) RNA Infectious hepatitis Inactivated vaccine Non-entero Viruses (group) Rhinoviruses The common cold 131730 >>> 0:23:17.2 SLIDE 34 of 53 Picornaviridae Small ss(+) RNA viruses Naked Enteroviruses (group) Fecal-oral transmission but do not cause diarrhea Polio Virus Most infections are asymptomatic; small % cause fever (viremia) Vaccines: both are trivalent: Sabin (live/oral/best gut immunity), Salk (killed/injectable) Coxsackie A Herpangina (vesicles on soft palate and fauces) Hand-foot-and-mouth disease (oral lesions primarily in the anterior buccal mucosa) Aseptic meningitis Coxsackie B Aseptic meningitis Myocarditis Hepatitis A Virus ss (+) RNA Infectious hepatitis Inactivated vaccine Non-entero Viruses (group) Rhinoviruses The common cold 131735 >>> 0:23:25.2 SLIDE 35 of 53 Picornaviridae Small ss(+) RNA viruses Naked Enteroviruses (group) Fecal-oral transmission but do not cause diarrhea Polio Virus Most infections are asymptomatic; small % cause fever (viremia) Vaccines: both are trivalent: Sabin (live/oral/best gut immunity), Salk (killed/injectable) Coxsackie A Herpangina (vesicles on soft palate and fauces) Hand-foot-and-mouth disease (oral lesions primarily in the anterior buccal mucosa) Aseptic meningitis Coxsackie B Aseptic meningitis Myocarditis Hepatitis A Virus ss (+) RNA Infectious hepatitis Inactivated vaccine Non-entero Viruses (group) Rhinoviruses The common cold 131736 >>> 0:24:57.2 SLIDE 36 of 53 Flaviviridae ss (+) RNA icosahedral capsid with envelope Yellow Fever Virus Mosquito-borne (Aedes) Liver, kidney, heart, and gastrointestinal mucosa damage Attenuated vaccine St. Louis Encephalitis Virus Mosquito-borne (summer) Elderly (especially blacks or individuals with hypertension): Most likely to have severe disease Dengue Virus Dengue (break bone disease): mild disease with rash and joint or muscle pain Mosquito-borne Hepatitis C 131740 >>> 0:26:15.2 SLIDE 37 of 53 Togaviridae ss (+) RNA viruses H, no P Alpha viruses (group) Equine Encephalitis Viruses: Western, Eastern, and Venezuelan All mosquito-borne Wild birds are reservoirs Horses are dead end hosts Rubella Crosses placenta and is teratogenic Congenital rubella = patent ductus arteriosis, pulmonary stenosis, cataracts, microcephaly, deafness Attenuated vaccine; single strain—part of MMR 131741 >>> 0:27:43.2 SLIDE 38 of 53 Coronaviridae ss (+)RNA, enveloped helical virus Second most common cause of common cold (peak winter and early spring) 131742 >>> 0:28:14.2 SLIDE 39 of 53 Human Immunodeficiency Virus (HIV) Positive sense (ss) RNA virus, diploid, non-segmented Lentivirus in the Retrovirus family (not oncogenic) The other retrovirus group, the oncogenic group, contains tumor-causing virus (HTLV) The HIV virion contains: Enveloped truncated conical capsid (type D retrovirus) Two copies of the ss (+) RNA RNA-dependent DNA polymerase (reverse transcriptase) Integrase Protease 131745 >>> 0:32:18.2 SLIDE 40 of 53 131750 >>> 0:34:18.2 SLIDE 41 of 53 HIV Life Cycle 1. Surface gp120 of HIV binds to CD4 of T helper cells, macrophages, and microglia. 2. HIV is taken into the cell, losing the envelope; the RNA is uncoated. 3. The RNA is copied using the virion-associated reverse transcriptase;ultimately ds DNA with long terminal repeats is made. 4. The DNA and integrase migrate to nucleus and the DNA is integrated into host DNA forming the provirus. The provirus remains in the host DNA. The rate of viral replication is regulated by the activity of the regulatory proteins (tat /rev, nef, etc). Tat up regulates transcription. Rev regulates transport of RNAs to cytoplasm. Coinfections (e.g., mycobacterial) stimulate the HIV-infected cells to produce more virus. 5. Transcription produces ss (+) RNAs, some spliced and some remain intact. Spliced RNAs will be used as mRNA. Whole RNA is used as genomic RNA. 6. Translation produces the proteins some of which are polyproteins that are cleaved by the HIV protease. 7. Assembly, and maturation/release of virus 131755 >>> 0:37:06.2 SLIDE 42 of 53 Table V-11. CDC Categories* CD4+ T- Category A (excludes cells/µL conditions in B &C) Acute (primary) or asymp-tomatic HIV infection Persistent generalized lymphadenopathy >500 A1 200-499 A2 <200 A3 Category B Symptomatic but not conditions in C) Condition attributed to HIV infection (list below) or are indicative of a defect in cellmediated immunity B1 B2 B3 Category C AIDS defining conditions(See list below) C1 C2 C3 AIDS = A3, B3, or C1-3 Acute phase has high level of viral production and mononucleosis-like symptoms: Fever, sore throat, rash, malaise, lymphadenopathy, diarrhea, etc. * 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS among Adolescents and Adults. MMWR December 18, 1992/41(RR-17) 131756 >>> 0:38:05.2 SLIDE 43 of 53 Conditions Included in the 1993 AIDS Surveillance Case Definition Encephalopathy, HIV-related Pneumonia, recurrent (leading cause of death) Fungal Infections Candidiasis of esophagus, bronchi, trachea, or lungs Coccidioidomycosis, disseminated, or extrapulmonary Cryptococcosis, extrapulmonary Histoplasmosis, disseminated, or extrapulmonary Pneumocystis carinii pneumonia Viral Infections Cytomegalovirus retinitis (with loss of vision) or disease (other than liver, spleen, or nodes) Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis Parasitic Infections Cryptosporidiosis, chronic intestinal (greater than 1 month's duration) Isosporiasis, chronic intestinal (greater than 1 month's duration) Toxoplasmosis of brain Bacterial Infections Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary) Mycobacterium avium complex or M. kansasii or other species or unidentified species, disseminated, or extrapulmonary 131757 >>> 0:38:50.2 SLIDE 44 of 53 Diagnosis: HIV Infection Screening: ELISA (most commonly done) to detect HIV antibodies in patient’s serum. (Most tests include the antigens p24, p17, gp160, gp120, and gp41.) Confirmation (Using a Second Blood Sample) Western Blot for antibodies specific for HIV (electrophoretically separated HIV antigens react with the patient’s antibody; detection by enzyme-labeled anti human IgG) Immunofluorescence HIV DNA PCR Qualitative to detect HIV infection in newborns whose mothers are HIV positive Quantitative HIV DNA PCR to determine viral load to assess treatment 131760 >>> 0:41:08.2 SLIDE 45 of 53 131765 >>> 0:43:14.2 SLIDE 46 of 53 131770 >>> 0:44:17.2 SLIDE 47 of 53 Paramyxoviridae ss(-) RNA strand Enveloped helical nucleocapsids Parainfluenza Virus (Types 1-4) Single HN glycoprotein, also fusion protein (F) Croup (laryngotracheobronchitis) Common cold, bronchitis 131775 >>> 0:45:57.2 SLIDE 48 of 53 Paramyxoviridae Mumps Single HN glycoprotein, also F protein Live vaccine Parotitis Pancreatitis Orchitis in adult males Meningoencephalitis 131780 >>> 0:46:55.2 SLIDE 49 of 53 Paramyxoviridae Measles (Rubeola) H glycoprotein and fusion protein, no neuraminidase Measles: Presentation generally the three C’s and photophobia: Cough, coryza, and conjunctivitis with photophobia Koplik spots maculopapular rash from the ears down Giant cell Pneumonia (Warthin-Finkeldy cells) Live vaccine (single strain) 131785 >>> 0:47:29.2 SLIDE 50 of 53 Paramyxoviridae Measles (Rubeola) H glycoprotein and fusion protein, no neuraminidase Measles: Presentation generally the three C’s and photophobia: Cough, coryza, and conjunctivitis with photophobia Koplik spots maculopapular rash from the ears down Giant cell Pneumonia (Warthin-Finkeldy cells) Live vaccine (single strain) 131790 >>> 0:47:39.2 SLIDE 51 of 53 Paramyxoviridae Measles (Rubeola) H glycoprotein and fusion protein, no neuraminidase Measles: Presentation generally the three C’s and photophobia: Cough, coryza, and conjunctivitis with photophobia Koplik spots maculopapular rash from the ears down Giant cell Pneumonia (Warthin-Finkeldy cells) Live vaccine (single strain) 131795 >>> 0:47:47.2 SLIDE 52 of 53 Paramyxoviridae Respiratory Syncytial Virus No H nor N glycoproteins; only F protein Major cause of bronchiolitis and pneumonia in infants Common cold 131800 >>> 0:48:58.2 SLIDE 53 of 53 Paramyxoviridae ss(-) RNA strand Enveloped helical nucleocapsids Parainfluenza Virus (Types 1-4) Single HN glycoprotein, also fusion protein (F) Croup (laryngotracheobronchitis) Common cold, bronchitis Mumps Single HN glycoprotein, also F protein Live vaccine Parotitis Pancreatitis Orchitis in adult males Meningoencephalitis Measles (Rubeola) H glycoprotein and fusion protein, no neuraminidase Measles: Presentation generally the three C’s and photophobia: Cough, coryza, and conjunctivitis with photophobia Koplik spots maculopapular rash from the ears down Giant cell Pneumonia (Warthin-Finkeldy cells) Live vaccine (single strain) Respiratory Syncytial Virus No H nor N glycoproteins; only F protein Major cause of bronchiolitis and pneumonia in infants Common cold