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Herpesvirus
- Large, enveloped, dsDNA virus
- Icosahedral capsid containing 162 capsomeres
- Linear dsDNA genomes that can vary in size
- Grouped into three subfamilies based on viral characteristics
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Human Herpes Simplex Stucture
- Two distinct epidemiologic and antigenic types, HSV-1 and HSV-2
- 50% sequence homology between the two
- Linear dsDNA genome
- Capsid surrounds DNA core and over capsid is tegument (protein filled region
- Envelope contains glycoproteins
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HSV disease syndrome
- HSV-1 and HSV-2 often infect the same tissue
- Acute and latent infections
- Cause painful but benign lesions – clear vesicle on an erythematous base
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HSV-1
clinical disease
- Gingivostomatitis
- Labialis (cold sores)
- Keratoconjunctivitis
- Encephalitis
- Mild or fulminant
- Herpatic whilow
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HSV-1
clinical disease
Gingivostomatitis
- Most common in children 1-6 years, fever, oral blisters on buccal mucosa, tongue, and gums
- Vesicles which ulcerate 7-10 days in duration
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HSV-1
clinical disease
Labialis (cold sores)
- Vesicles at mucocutaneous junction of lips
- Recurrent (latent)
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HSV-1
clinical disease
Keratoconjunctivitis
- Corneal ulceration, usually limited to one eye
- Recurrent, leading to permanent scarring and blindness
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HSV-1
clinical disease
Encephalitis
Limited to temporal lobe, high mortality
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HSV-1
clinical disease
Herpatic whilow
- Tips of fingers and nails
- Occurs in nurses/physicians who attend patients with HSV infection, thumbsucking children, people who have genital HSV
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HSV-1
clinical disease
Mild or fulminant
- Mild or fulminant
- Acquired by children with active eczema
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HSV-2
- Usually causes genital herpes (10% cause by HSV-1)
- 80% of patients develop recurrent infections within 12 months
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HSV-2
Clinical disease
- VulvoganitisProgenitalisAseptic meningitis
- Neonatal herpes
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HSV-2
Vulvoganitis
- Mucous membranes of skin of labia, lower vagina, cervix
- Lesions become ulcerated, painful
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HSV-2
Progenitalis
Ulcers on penis and/or skin in groin or perianal area
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HSV-2
Neonatal herpes
- Contracted during delivery
- Widespread organ involvement
- High mortality – more than 60%
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HSV latency
- All herpes viruses establish latent infections
- Site of latency and feature of reactivation disease is different for each virus
- HSV Reactivation – same site as primary infection
- DNA resides in ganglia (trigeminal root ganglion, sacral root ganglion)
- Reactivation: trauma, fever, sunlight, excitement, emotional stress
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HSV Diagnosis
- Isolation of virus – definitive assay
- Stain biopsy material (immunofluorescence)
- DNA detection by PCR in tissue sample (latent infection)
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HSV Treatment
- Acyclovir and closely related drugs (Valtrex)
- Eye infections (topical) – trifluridine, penciclovir, acylcovir
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Varicella-Zoster Virus (VZV)
- ¢Human Herpesvirus 3
- Clinical chicken pox (primary infection)
- Virus entry through inhalation
- Replicates in respiratory tract and invades lymph nodes
- Viremia: spreads to liver spleen, reticuloendothelial system
- Secondary viremia : spreads to the skin
- Latency in neurons
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Chicken pox
- Maculopapular rash appears first on head, neck and trunk
- Vesicles contain clear fluid (itch)
- Vesicle will become pustular and begin to crust
- Recovery in about 2 weeks
- Adult infection more severe: 20-30% develop pneumonia
- Neonatal infections – encephalitis
- Immunosuppressed – severe progressive infection
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VZV - Shingles
- Shingles: reactivation of varicella-zoster
- DNA remains latent in ganglia
- Occurrence increases with age (50% over 50 yrs)
- Onset of pain occurs before appearance of vesicles
- Usually unilateral
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VZV - Shingles
Treatment
- Supportive
- Acyclovir for extreme cases
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VZV - Shingles
Diagnosis
- Clinical picture
- Immunofluorescent antibody staining
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VZV - Shingles
Prevention
- Vaccine:
- Varivax – live attenuated vaccine, administered between 12-18 months of age
- Zostavax –stronger formulation of Varivax, recommended to adults 60 or older
- 50% reduction in shingles occurrence
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Epstein-Barr Virus (EBV)
- Human herpesvirus 4
- Etiologic agent of infectious mononucleosis (mono) and Burkitt’s Lymphoma
- Linked with Hodgkins lymphoma
- Infects B cells and epithelial cells
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EBV
Diagnosis
¢Infects B
cells and epithelial cells
- Clinical presentaion
- Complete blood cell count – atypical lymphocytes
- Heterophile – positive antibodies
- Hetrophile antibodies (sheep erythocyte agglutinins; used as monospot test)
- Activation of B cells by EBV produces a wide range of antibodies
- Positive in 50% on presentation and 90% at some point
- Serology: expensive, but can be useful
- Demonstrate antibody to viral capsid antigen (VCA) which rises quickly and persists for life
- Antibodies to EB nuclear antigens (EBNA) rise later and decreases in about 1 month
- A high titer of VCA and titer of EBNA suggest recent infection
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EBV – Burkitt’s lymphoma
Epidemiology
- Central and East Africa - tumor in jaw area
- China and Southeast Asia – nasopharyngeal carcinoma
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EBV – Burkitt’s lymphoma
Treatment and Prevention
- Supportive
- Acyclovir can suppress the replication
- No vaccine
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EBV – Hairy oral leukoplakia
- Unusual manifestation of a productive EBV infection of epithelial cells
- Characterized by lesions of the tongue and mouth
- Opportunistic manifestation of AIDS patients
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Cytomegalovirus
(CMV)
- HHV-5
- Largest genome of herpes virus (~240 kb)
- Similar to HSV but highly regulated – slow replication and slow disease effects
- Nuclear and cytoplasmic inclusion bodies, induction of giant cell
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CMV
Clinical Disease
Transmission
- Close contact, sexually transmitted, virus can be recovered from all body fluids:
- saliva, urine, semen, and cervical secretions
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CMV
Clinical Disease
- High infection rates in early childhood and early adulthood
- Usually asymptomatic
- Heterophil negative mononucleosis
- Systemic CMV infection, pneumonia and hepatitis in immunosuppressed patients (transplant)
- In AIDS patients: diarrhea, retinitis
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CMV
clinical disease
Congential
- Most infants appear normal at birth
- May develop hearing loss or some mental retardation often later
- Infants with sympotmatic illness at birth demonstrate hepatosplenomegaly, jaundice, anemia, rash
- Neonatal– usually asymptomatic
- Immunosuppressed –pneumonia, hepatitis
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CMV Diagnosis
- Culture in diploid fibroblast, serology, PCR
- Hallmark is cytomegalic cell (large cell with basophilic nuclear inclusion body – “owls eye”)
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CMV Treatment
Ganciclovir, valganciclovir
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Human Herpes 6
- Genetically distinct but morpholically similar to other herpes virus
- Replicates in lymphoid tissue – preferentially in T lymphocytes
- Cytopathic for T lymphocytes in cell culture
- Serologic studies indicate that almost all children are infected by age 5.
- Most communicable of all herpes virus
- Spread by close personal contact or by respiratory route
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Human Herpes 6
Treatment
Acyclovir
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HHV-7
- Closely related to HHV-6
- Causes exanthem subitum (roseola) – one of the five classical childhood exanthems
- Recover without complications
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HHV-8
- STD
- Kaposi’s sarcoma-associated herpesvirus, KSHV
- Isolated in culture and closely related to EBV
- Infects B lymphocytes
- Immunosuppression, genetic predisposition are cofactors
- Interferon-alpha can be effective as treatment
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HHV-8
Treatment
Interferon-alpha can be effective
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Pharyngitis
Streptococcus pyogenes
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Sinusitis
- Streptococcus pneumoniaeHaemophilus influenzaeMoraxella catarrhalis
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Otitis externa
- Pseudomonas aeruginosaStaphylococcus aureus
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Otitis media (inner/middle)
- Streptococcus pneumoniaeHaemophilus influenzaeMoraxella catarrhalis
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Conjunctivitis
- Staphylococcus aureus
- Streptococcus
pneumoniaeHaemophilus aegyptius
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Keratitis
- Staphylococcus aureus
- Streptococcus
pneumoniae- Pseudomonas
aeruginosa
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Bronchitis
- Haemophilus influenzae
- Streptococcus
pneumoniae
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Empyema (pus in body cavity)
- Staphylococcus aureus
- Streptococcus
pneumoniae, group A
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Pneumonia
- Streptococcus pneumoniae
- Staphylococcus
aureusKlebsiella pneumoniaeother EnterobacteriaceaeMycoplasma pneumoniaeLegionella species
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Cystitis and Pyelonephritis
- Escherichia coli
- Proteus mirabilis
otherEnterobacteriaceae
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Renal abscess
Staphylococcus aureus
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Prostatitis
Escherichia coli
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Endocarditis
Viridans Streptococcus
coagulase-negative Staphylococcus
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Myocarditis
- Corynebacterium diphtheriaeClostridium perfringens
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Pericarditis
- Streptococcus pneumoniaeStaphylococcus aureus
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Sepsis
- Staphylococcus aureuscoagulase-negative Staphylococcus
- Escherichia coli
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Meningitis
- Group B Streptococcus
- Streptococcus
pneumoniaeNeisseria meningitidis
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Encephalitis
- Listeria monocytogenesTreponema pallidum
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Impetigo
- Group A Streptococcus
- Staphylococcus
aureus
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Folliculitis
- Staphylococcus aureus
- Pseudomonas
aeruginosa
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Cellulitis
- Group A Streptococcus
- Staphylococcus
aureus
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Necrotizing cellulitis and fasciitis
- Group A Streptococcus
- Clostridium
perfringens
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Burn infection
Pseudomonas aeruginosa
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Skin Infection
Surgical wounds
Staphylococcus aureus
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Gastroenteritis
- Salmonella speciesShigella speciesCampylobacter jejuni
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Food Intoxication
- Staphylococcus aureus
- Bacillus cereus
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Osteomyelitis
- Staphylococcus aureus
- Salmonella
species
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Arthritis
- Staphylococcus aureusNeisseria gonorrhoeae
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Genital Ulcers
- Treponema pallidumHaemophilus ducreyi
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Urethritis
- Neisseria gonorrhoeae
- Chlamydia
trachomatis
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Vaginitis
- Mycoplasma hominisMobiluncus species
- Gardnerella
vaginalis
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Cervicitis
- Neisseria gonorrhoeae
- Chlamydia
trachomatis
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Granulomatous Infections
- Mycobacterium tuberculosis and
- other species
Nocardia speciesTreponema pallidum
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