Viruses can cause damage to host tissues in several ways (3)
- Virus replication = Host cell lysis (Dmg to tissue -> Inflammation)
- Virus infection = altered host cell metabolism ( Host cell/tissue lose function)
- Viral proteins inserted into host cell membrane (host cell surface looks foreign = immune response to attack host cell)
Tissue dmg by virus = increased susceptibility to infection by other microbes
Viruses can infect almost every body system
- Different classes of viruses infect same organ/tissue
Nose/throat:
- Adenovirus
- Influenza
- Rhinovirus
Viruses don’t stay at site of first contact always
- Spread via lymphatic or blood system
- Can infect other sites if cell receptors present
-site where symptoms happen isn’t always where virus entered
Why is it important to identify the specific virus causing an infection?
3
- Rules out other microbes (different microbes = different therapeutic approaches)
- Optimizes patient management (will anti-viral work, supportive care needed)
- Infection Control (Patient with same infection stay together)
Diagnostic Challenges:
3
- Symptoms of Viral diseases mimic other diseases (viral vs bacterial sore throat)
- Viruses produce very similar symptoms, one can produce different symptoms
- Viruses cant be grown (need host, aka tissue culture which is hard)
Diagnostic Approaches:
3
- Assess the clinical picture
- Symptoms (Virus vs bacteria)(Virus A or B) (history suggest a virus?) - Collect an appropriate specimen
- (lung bacteria needs a lung specimen)
3.Lab testing (direct test = virus itself) vs Indirect test (body immune response to virus)
Viral diagnosis: Nucleic Acid Amplification tests (NAAT)
Direct test 1
- Looks at DNA/RNA
- Polymerase chain reaction (PCR) tech
- Rapid (3-4h), sensitive
- Complex and expensive
- FULL SERVICE CLINICAL LABS IN HOSPITALS
Viral diagnosis: Rapid Antigen Tests
Direct test 2
Virus = antigen
Recognized by antibodies
Antibodies detect antigens
- minutes/ not sensitive
- Positive= Reliable, Negative = Retest with more sensitive test (PCR)
-Point of care tests or remote locations
Viral diagnosis: Serology test (Indirect)
-Not useful in early stages
- Look for ANTI-VIRUS ANTIBODIES in blood(plasma/serum)
- Presence indicates current infection or previous (persist months to years)(days-weeks for antibodies to appear after virus)
-Serum antibodies against a virus can be detected with “ELISA” test (Enzyme-Linked Immunosorbent Assay)
Viruses that infect skin
- Rashes, fluid filled blisters or warts
- Direct contact (blister) or inhaling respiratory secretions (migrates to skin)
- Herpes, Varicella can migrate to CNS
Herpes Simplex Virus (HSV) (Skin disease) HOW DOES IT SPREAD 3
- Large enveloped DNA virus (HSV-1 & HSV-2 closely related)
- Viral Gene can be reactivated by external stimuli (Stress, trauma, fever)*HSV reappears and causes lytic infection at original site
HSV infection for life switching between latent and lytic stages
- starts at mucosal surfaces or skin that has a opening(cut,break)
- Acquired after direct contact with active HSV - HSV enters epithelial cells -> replication = cell death (lytic infection)
- 100,000 viruses released from each cell
- turns into vesicular lesions (fluid blisters)
- Re-transmission - During infection, HSV can enter into nearby sensory nerves
- Viral DNA inserted into cell chromosome = LATENT infection
* Viral genes not expressed= no new virus = no dmg to cell = no symptoms of disease = hidden from immune system
Types of Herpes Infections 3
*Mostly caused by HSV-1 Very Common (65% adults have antibodies)
-Oral Herpes (mucosal lesions/cold sores)
- Herpes Keratitis (infection of eyes/corneas due to autoinoculation*
- > corneal scarring, blindness
- Herpetic Whitlow (fingers after contact with lesions)
- Occupational hazard of nurses, doctors, dentists
Genital Herpes
(mostly 2,but 1 is high in young adults)
*common sti (1/4 W, 1/5M)
- vesicular lesions in genital area (itching, tingling, burning)
- spread via sexual contact during recurrence of lesions
Central Nervous System Infections HSV
15% of encephalitis (brain inflammation) due to HSV
70% mortality if untreated
Adult encephalitis (mainly HSV-1) (CNS disease 1)
- reactivated latent infection-> HSV migrates up into brain
- elderly and immunocompromised
-altered mental state, decreased consciousness
Neonatal encephalitis (mainly HSV-2) (CNS disease 2)
- Primary infection->newborn infected in mom has HSV lesions during birth
- lethargy, fever, seizures, permanent neurological dmg or death
- consider caesarean if genital lesions present
Diagnosis of HSV
Nucleic acid amplification tests for HSV-1/2
-highly sensitive and rapid
- To confirm HSV or if other virus and for early diagnosis of encephalitis
- vesicular skin lesion present = test for HSV first (and varicella Zoster virus)
- Sample appropriate site
- nero symptoms = CSF collected via spinal tap
- Lesions = fluid from blister
Treatment and control 5
- Acyclovir(cyclovir)
- not cure, shortens lesion time
- effective against encephalitis if given early
- Prophylactic use= suppressive treatment (>6 outbreaks per year)
- Abreva(docosanol topical cream)
- blocks entry of HSV into cell(works best <12 hrs after symptoms)
- reduces symptoms (pain, tingling and shortens healing by 1-2days
- NOT A CURE
- Topical Anesthetics(benzocaine)
- no anti-viral activity
- only used to reduce discomfort
-Avoid contact with active lesions
- Virus easily destroyed by soap and water (same for other enveloped viruses)
- detergent destroys lipid envelope and removes spike (attachment) protein
Human Papilloma Virus (HPV) Oncogenic virus
- Naked DNA virus made of >100 different genotypes
- different genotypes produce different types of clinical disease
- Most common HPV infection-> abnormal growth of skin cells that project outward (papillomas = warts)
- Less common -> abnormal uncontrolled growth of cells in cervical and genital areas (leads to invasive cancer)
Life Cycle of HPV (Oncogenic virus) 6
- Transmission requires direct skin-to-skin contact (enters abrasions)
- Virus enters into basal epithelial cells of skin epidermis
- HPV causes basal cells to grow and divide more rapidly than normal and to continue growing after they normally should have stopped (HPV can only replicate if host alive)
- Infected basal cells migrate upward to surface of skin
(Migration of basal cells trigger production and assembly of new HPV)
(1000s of HPV particles per cell when they reach the surface) - Infected epithelial cells on the skin surface divide faster than the non infected cells (Form papilloma/can take weeks)
- Infected epithelial cells eventually die, releasing HPV onto skin surface
Treatment of cutaneous warts
home remedy prob involves localized killing of cells
-no effective anti-viral agents
-killing/removing infected tissue eliminates HPV
(caustic chemicals/duofilm, Cryogenic/liquid nitrogen, laser, surgical)
50% disappear after 6-18 months without treatment due to immune response
How does HPV cause cervical Dysplasia (cancer)
- HPV types (6, 11, 16, 18) have preference for infecting epithelial cells of genital area
- types 6, 11 (low risk) = genital warts
- types 16, 18 (high risk) = genital warts, cervical cancer (rare penile cancer)
Why do high risk 16, 18 hpv stimulate progression to cancer
- More rapid basal cell replication
- Greater ability to interfere with host cell proteins that regulate cell growth and repair mutated DNA
Cells infected 16, 18 replicate fast and get lots of mutations (cancerous cell growth)
Formation of cancerous cells and CIN scale
Cancerous cells form over years
Require continuous presence of high risk HPV and other factors
Presence of HPC is need but not enough to cause cancer
Cervical Intraepithelial neoplasia -> (1-3 score)
*indicates how deep and progression
