1. Herpetic Stomatitis & Infectious Esophagitis Flashcards
HSV Structure
Large
Linear dsDNA
No polymerase
Icosahedral core > Nucleocapsid > Tegument > Lipoprotein envelope
Tegument: regulatory proteins (transcription & translation)
- used for viral replication
HSV Properties
Replicates in nucleus > intranucleur inclusions
Obtains envelope by budding from nuclear membrane
Causes latent infections:
- Asymptomatic period (latent state) > Acute disease
- Provoking agent/immunosuppression > reactivates HSV replication > disease
After HSV infects > latency-associated transcripts (noncoding & regulatory RNAs) are synthesised > suppresses viral replication > initiates & maintains latent state
HSV family members
Alpha: (1ry - Epithelial / Latent - Neurons)
- HSV1 (cranial) - HSV2 (lumbar/sacral) - VZV (cranial/thoracic)
Beta: (1ry & Latent - variety of tissue)
-CMV (Monocytes)
Gamma: (1ry & Latent - Lymphoid cells)
- EBV (B Lymphocytes) - HV8 (uncertain)
HSV1 Primary infection
Ginivostomatitis
HSV1 Usual latency site
cranial sensory ganglia
HSV1 Recurrent infection [3]
- Herpes labialis
- Encephalitits
- Keratitis
HSV1 Route of transmission
- Respiratory secretions & saliva
- Direct contact with virus vesicle
- Oral-genital sex
HSV1 giant cell [Yes/No]
Yes
HSV1 Fetal/Neonatal [Yes/No]
No
VZV Primary infection
Varicella
VZV Usual latency site
Cranial/thoracic sensory ganglia
VZV Recurrent infeciton
Zoster
VZV Route of transmission
Respiratory secretions
VZV giant cell [Yes/No]
Yes
VZV Fetal/Neonate [Yes/No]
No
CMV Primary infection
- Congenital infection ( in utero)
- Mononucelosis
CMV Usual latency site
Monocytes
CMV Recurrent infection
Asymptomatic shedding
CMV Route of transmission [4]
- Intrauterine infection
- Transfusions
- Sexual contact
- Secretions (e.g. saliva & urine)
CMV giant cell [Yes/No]
Yes
CMV Fetal/Neonate [Yes/No]
Yes
EBV Primary infection
Infectious mononucleosis
EBV Usual latency site
B lymphocytes
EBV Recurrent infection
Asymptomatic shedding
EBV Route of transmission
Respiratory secretions & saliva
EBV giant cell [Yes/No]
No
EBV Fetal/Neonatal [Yes/No]
No
HSV1 Pathogenesis
Initial: (childhood)
Replicates in skin/mucous membranes > Retrograde axonal flow > Latent in Trigemnial ganglia (viral DNA in cytoplasm)
Reactivated by
-Sunlight, Hormonal changes, Trauma, Stress, Fever
Migrates down neuron > replicates in skin > lesions
- Lesions = vesicle (infectious) w/serous fluid filled w/virus particles & cell debris
- Multinucleated giant cells: base of herpesvirus lesions
- Cell-mediated immunity
HSV1 Clinical Findings
1- Gingivostomatitis 2- Herpes labialis 3- Keratoconjunctivitis 4- Encephalitits 5- Herpetic whitlow 6- Herpes gladiatorum 7- Eczema herpeticum 8- Disseminated infections 9- Erythema multiforme
1- Gingivostomatitis
- 1rily in children
- fever, irritability & vesicular lesions in mouth
- 1ry disease is more sever & lasts longer than recurrences
- lesions heal spontaneosly in 2-3 weeks
- many children are asymptomatic
2- Herpes labialis (fever blisters/cold sores)
- Crops of vesicles at mucocutaneous junction of lips/nose
- Milder & recurrences appear at same sites
3- Keratoconjunctivitis
- Corneal ulcers & lesions of conjunctival epithelium
- Recurrences > scarring & blindness
4- Encephalitis
-fever, headache, nausea, & vomiting
-focal neurological defects - medial temporal lobe:
(smell, vision, memory, hemiparesis, ataxia, hyperreflexia)
-Seizures, Altered mental status, Behavioral changes
-Meningeal signs (nuchal rigidity & photphobia)
-CSF analysis:
(high protein, lymphocytic pleocytosis, normal glucose)
5- Herpetic whitlow
- Pustular lesion of slin/finger/hand
- In medical personnel (lesion contact)
6- Herpes gladiatorum
- Vesicular lesions on head/neck/trunk
- Wrestlers & other close body contact people
7- Eczema herpeticum (Kaposi’s varicelliform eruption)
Vesicular lesions at site of atopic dermatitis (eczema) in children
8- Disseminated infections
Esophagitis & pneumonia in immunocompromised w/ depressed T-cell function
9- Ereythema multiforme
-Rash (target/bull’s eye lesion)
-Macular/papular lesions occur symmetrically on trunk/hands/feet
(Rash due to immune reaction)
Lab diagnosis
1- Cell culture 2- Tzanck smear 3- PCR 4- Neonatal Diagnosis 5- Serologic tests
1- Cell culture
- Isolation of virus from lesion > Cytopathic effect (1-3 days)
- Virus is identified by:
1) Fluorescent antibody staining of infected cells
2) ELISA - virus glycoproteins - Monoclonal antibody against glycoprotein G for HSV1 vs HSV2
2- Tzanck smear
- Rapid presumption diagnosis of skin lesions
- Detect multinucleated giant cells using Giemsa stain
3- PCR
-Rapid diagnosis of herpes encephalitis
-Detect HSV DNA in spinal fluid
(more sensitive than viral culture)
4- Diagnosis of neonatal herpes
- Viral culture
- PCR
5- Serological test
Neutralisation test (for 1ry - increase in titer) (not for recurrent since antibodies are available/rarely increase)
CMV Properties
- Similar to other HV
- Antigenically different
- Single serotype
- Natural host: human
- Forms giant cells (cytomegalo)
CMV Transmission
- Early in life: aross placenta, bith canal, & breast milk
- Young children: saliva
- Later in life: sexually, blood transfusions, & organ transplant
CMV Pathogenesis
- Fetal infection can cause cytomegalic inclusion disease > multinucleated giant cells w/intranuclear inclusions.
- Many organs affected & widespread congenital abnormalities
- Fetus infected if virus isn’t neutrailised by mother w/ 1ry infection
- Congenital abnormalities if during trimester
- Enters latent in monocytes > reactivated in immunocomprimisation
- Can persist in kidney for years
- Reactivation of CMV in cervical > fetal infections
CMV mechanisms for longer latent period state
1- Unstable MHC I > viral antigens aren’t displayed > not killed by Tc cells
2- Micro RNAs prevent MHC I synthesis > …
3- Synthesise chemokine receptor > prevent signalling
4- Infection inhibit T cells > immunsuppresion
CMV Clinical findings
1- CMID: microcephaly, seizures, deafness, jaundice, & purpura (blueberry muffin)
2- Hepatosplenomegaly
3- Excrete CMV in urine for years
4- Immunocompetent adults > heterophil(-ve) mononucleosis fever, lethargy, & abnormal lymphocytes in peripheral blood smears
5- Immunicomprimised > (renal/bone marrow transplants) systemic infection e.g. pneumonitis, esophagitis, & hepatitis
6- AIDS: intestinal tract > colitis w/diarrhea / retinitis > blindness
CMV Lab diagnosis
1- Culturing w/immunofluorescent antibody > 72 hrs
(to test susceptibility to ganciclovir)
2- Flourescent antibody & Histologic staining (basophilic owl’s eye in giant cells/urine/tissue)
3- Fourfold or greater in antibody titer
4- PCR of CMV DNA/RNA
5- CMV antigenemia (pp65 protein from CMV nucleocapsid in blood leukocytes via immunofluorescence assay)
