Usmle step 1 Web Prep — Medically Important Viruses, Part 3




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USMLE Step 1 Web Prep — Medically Important Viruses, Part 3

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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






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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






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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






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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






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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






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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:

    • live non-attenuated;

    • serotypes 4, 7, and 21;

    • administered separately by enteric-coated capsules.

  • Adenovirus 40 and 41 cause infantile diarrhea.




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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





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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





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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






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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






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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






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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






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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






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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






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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






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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





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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





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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





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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





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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





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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





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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





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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





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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





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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





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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





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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)






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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





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Human Herpesvirus 6

 Exanthem subitum (Roseola) - common infant disease: fever followed by rash




Human Herpesvirus 8

 Probable cofactor in Kaposi's sarcoma






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RNA Viruses




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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




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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





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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





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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





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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






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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





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Coronaviridae

 ss (+)RNA, enveloped helical virus

 Second most common cause of common cold (peak winter and early spring)





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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

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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. Co-infections (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






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Table V-11. CDC Categories*

CD4+ T-cells/µL

Category A (excludes conditions in B &C)
Acute (primary) or asymp-tomatic HIV infection
Persistent generalized lymphadenopathy

Category B 
Symptomatic but not conditions in C)
Condition attributed to HIV infection (list below) or are indicative of a defect in cell-mediated immunity

Category C
AIDS defining conditions(See list below)

>500

A1

B1

C1

200-499

A2

B2

C2

<200

A3

B3

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)







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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

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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

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Paramyxoviridae

 ss(-) RNA strand

 Enveloped helical nucleocapsids

Parainfluenza Virus (Types 1-4)

 Single HN glycoprotein, also fusion protein (F)

 Croup (laryngotracheobronchitis)

 Common cold, bronchitis





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Paramyxoviridae

Mumps


 Single HN glycoprotein, also F protein

 Live vaccine

 Parotitis

 Pancreatitis

Orchitis in adult males

 Meningoencephalitis






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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)




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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)




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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)




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Paramyxoviridae

Respiratory Syncytial Virus

 No H nor N glycoproteins; only F protein

 Major cause of bronchiolitis and pneumonia in infants

 Common cold





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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







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