viral diseases
● Pneumotropic viral diseases
○ Coughing sneezing and upper and lower respiratory tract infections
● Dermotropic viral diseases
● Viscerotropic viral diseases
Influenza
● Acute, contagious disease of upper resp tract
● Transmitted by resp droplets
● Enveloped ssRNA virus
● Not a retrovirus(viral proteins produced directly from viral RNA)
● 3 types of influenza
○ Type A: divided into subtypes ex(H5N1)
■ Infected humans, birds, pigs
○ Type B
■ No subtypes
■ Infects humans
○ Type c
■ Rare, mild disease in humans
● Concerns about pandemics: TYPE A & B most likely, C less likely(not as virulent)
● Viral envelope contains spikes
● 2 proteins
○ Hemagglutinin (H)
■ Helps virus attachment to host cell
■ 16 different ‘ subtypes’
■ ANTIGENIC
○ Neuraminidase (N)
■ Entry and exit of virions in/out of host cell
■ 9 different ‘ subtypes’
■ ( drugs that block this enzyme?)
■ ANTIGENIC
● Virions constantly undergo genetic changes in H and N ( as well as other proteins/ carbohydrates)
○ Antigenic drift( small, annually)
■ Minor mutations
■ Year-year variations
■ Some immunity from previous strain
○ Antigenic shift(big)
■ Major mutations
■ Reassortments as virus crosses species( animals to humans)
■ Pandemic possibility (no or little immunity)
■ Ex. H2N3 mutates to H1N1
● Manifestations
○ Abrupt onset( acute)
○ Chills, fatigue, headache, pain in chest..
○ Severe, hacking cough
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○ Increased body temp 40 degrees
○ Short- lived, 1-2 weeks complete resolution (acute)
○ Risk of vary infection in young and old
Serious complication
○ Guillain- barre syndrome
■ Neurological symptoms, polio-like paralysis
■ Usually reversible
■ May involve NEUROMUSCULAR DISRUPTION BY IMMUNE SYSTEM
○ Reye's syndrome
■ Neurological symptoms
■ In children following flu or chickenpox
■ Child experiences repeated vomiting, lethargy, disoriented, combativeness
■ Associated with ASA
■ May involve NEUROMUSCULAR DISRUPTION BY IMMUNE SYSTEM
Death rate
○ Approx 40,000/ year
○ 90% death are 65 +
Prevention
○ Vaccine
■ What is in the vaccine?
● WHO decides yearly (health canada approves)
● 3-6 strains of whole, destroyed virus including: Top 3 strains from last
year and new prominent strains
● This years 2021:
○ Tetravalent: H1N1, H3N2 and 2 influenza B viruses (victoria
and yamagata)
○ Trivalent (high dose for 65+): H1N1, H3N2 and 1 influenza B
viruses ) (victoria)
■ Approx 80% of influenza burden in 65+ is H3N2
■ Trivalent has 60 ug hemagglutinin antigen versus 15 ug
in tetra
■ More potent and effective for 65+
■ Does it work?
● Estimated prevention= ⅔, up to 60%
● Success of Ontario vaccinations since 1999?
■ How is it made
● Embryonated chicken eggs
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First time in ontario,one supplier of tetravalent used mammalian cells
(K9 kidney cells)
Myths and realities
● Can u get the flue from the flu vaccine- YES
● Flu vaccine takes about 2 weeks to works and last 1 year
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No scientific study showing alzheimer's arthritis, autism(long term side
effects)
Can u get sick from flu vaccine
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May feel sick: soreness, body ache, headache, low grade fever
Small chance of allergic rxn (only concern with anaphylaxis)
Rhinoviruses
● 30% of all common colds
● Non Enveloped ssRNA viruses
● Life cycle similar to flu virus
● About 100 diff strains
● Mutate often
○ Vaccines?
Adenoviruses
● Family of non enveloped dsDNA viruses
● 15% of common upper respiratory tract infections
○ Common cold
● Symptoms can be severe
● Spread by resp or ocular secretion
○ Can cause conjunctivitis (pink eye)
● Cause of viral (aseptic) meningitis
● Spikes with adhesions on end
● Viral DNA injected into nucleus of host cell for viral protein production
● Good candidate for ‘ gene therapy’- adding genes
○ Attenuated virus is infectious but not contagious
○ Double strand DNA for gene insertion/ ready for protein production
○ Candidates for gene therapy= single gene disease
■ Hemophilia
■ Cystic fibrosis
■ Muscular dystrophy
Sars cov1 vs sars cov2
● 80% genetic similarity between strains
● 96.2% genetic similarity between sars cov2 and bat coronavirus
Sars cov2
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Severe acute respiratory syndrome coronavirus 2
ssRNA, enveloped virus
Relatively large ss RNA virus 120nm
Large genome with 30 kilobases (flu is 13.5 kilobases)
Replication slower than most human rna enveloped virus
Slow mutation rate due to exonuclease proofreading- take nucleic acid and pulls out to replace if sequence
is wrong
Symptoms
○ Non- specific (cough, sore throat, fever, lethargy, myalgia)
○ Shortness of breath/ breathing difficulties
○ Elevated temp above 38 degrees
○ Loss of smell/taste
○ GI symptoms- abdominal pain, vomiting, diarrhea
Host target receptor= ACE-2
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ACE-2 located primarily in upper respiratory tract epithelium (lower levels in conjunctiva and GI
tract)
Since ACE-2 degrades angiotensin 2, viral infection with ACE-2 may contribute to heart effects of
infection
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Underlying conditions as risk factors
○ Hypertension
○ Cardiovascular disease
○ Chronic obstructive pulmonary disorder COPD
○ Obesity
○ Malignancy
○ Diabetes
○ OLD AGE #1
● Death rate
○ Varies greatly by age
○ 80+ has a high death rate - 15%
● Treatments for severe disease
○ Corticosteroids have an anti- inflammatory action
● Steroid treatment
○ Severely ill patient may experiencing an exaggerated immune response (cytokine storm)
○ Promote immune response and inflammatory response
○ Corticosteroids have an anti-inflammatory action
○ those on supplemental oxygen or mechanical ventilation, corticosteroids reduce death and length
of hospitalization by 10-20%
● Vaccines
○ Pfizer- bioNTech (comirnaty): 95% after two doses
○ Moderna (spikevax): 94% after two doses
○ Above 2 vaccines use mRNA technology
○ Works by introducing mRNA into body cells via lipid nanoparticle
■ Ribosomes in body cells use mRNA to produce CoV2 spike protein antigen = antibody
production
○ astraZeneca( vaxevria): 67% after two doses
○ Johnson and johnson (janssen): covid 19 vaccine: 67% after 1 dose
○ Above 2 vaccines based on recombinant adenovirus vector to introduce DNA gene for spike
protein antigen
○ ALL 3RD GENERATION VACCINE
Dermotropic viral diseases (skin virus)
● Herpes viruses
○ ‘To creep’
○ Large family of viruses
■ Abt 100 species known (including all animal)
■ 8 human herpes viruses known
● Herpes simplex (HSV-1,HSV-2)
● Varicella zoster (VZV)- CHICKEN POX
● CYTOMEGALOVIRUS (CMV)
● Epstein- barr(EBV)
● Human herpesvirus (HHV) -6, -7, -8
○ Family of herpesviridae
● Common features of herpes
○ dsDNA, enveloped viruses
○ Icosahedral capsid, spherical envelope with spikes
○ Latency periods( usually in nervous tissue
○ Occasional recurrence
○ Incurable
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Herpes simplex virus
○ 2 strains (HSV-1 & HSV-2)
○ 50% genetically identical
○ Common to both strains:
■ Infect mucosa (mouth/ genitals)
■ Most are asymptomatic
■ Viral shedding approx 5% of time dure latency
○ Characteristic episode both strains:
■ Formation of painful vesicle blisters
■ Often proceed by tingling and itching
■ Vesicles ulcerate, releasing virus-laden fluid
■ Sores crust & heal completely
○ Primary difference between strains
■ Where the virus prefers to establish latency
■ HSV-1 prefers trigeminal ganglion (near ear)
■ HSV-2 prefers sacral ganglion (near base of spine)
○ HSV-1= 50-80% population
○ HSV-2= about 1 in 5 ppl infected - 1 in 40 acc know
○ What affects outbreak frequency?
■ Stimulation (stress, UV)
■ Immune suppression
■ How long subject has been infected- longer been affected= less frequence outbreak
■ Site of infection (HSV-1 mouth, HSV-2 genitals)
■ Infection with on strain protects against second strain
● Ex. HSV during childhood= HSC-2 less likely in adolescence
■ 99% of oral= HSV-1
■ 30% of gential= HSV-1
■ 70% gential= HSV-2
○ Comparison of strains
■ Both cause same disease
■ Different complications
● HSV-1=
○ Herpes whitlow( finger infection)- seen in children or nail biting
○ Complication of HSV-1
■ Ocular herpes- pink eye
● Herpes encephalitis- (potentially deadly)
○ Complication HSV-2
■ Neonatal herpes
■ Transmitted from mother to baby during birth
■ 50-80% mortality rate
■ Careful monitoring of mother for viral shedding, especially in last 4 weeks of pregnancy
○ TREATMENT
■ Antivirals
● vidarabine(vira-A): block adhesions
● acyclovir(zovirax): nucleotide analogue
○ HSV-1 and HSV-2 destroyed viruses do not elicit strong immune response
○ HSV-2 vaccines directed against viral DNA envelope protein and spikes in phases 1 and 3
clinical trials
○ Vaccines may reduce outbreak frequency/ severity
Varicella- zoster virus
● CHICKEN POX
● SHINGLES
● Transmitted via respiratory secretions
● More than 95% prevalence
● Incubation period usually 14-21 days
● Not life threatening unless immunocompromised
○ Ex. pneumonia, liver failure, encephalitis
● VACCINE
○ Live, attenuated chickenpox vaccine
○ Given between 1-2 years of age
○ Boosters at 4-6 years of age
○ May decrease shingles incidence
Herpes zoster (shingles)
● Occurs in 15% of infected population
● Not new infection
● Characteristic distribution of painful vesicles following sensitization of skin
● About 20% develop post- herpetic neuralgia (pain persists for months- years)
● Antivirals given early enough = decreasing pain, duration of lesions & post herpetic neuralgia
● VACCINE
○ New vaccine= shingrix( antigen encapsulated in liposome)
○ Free 65-70 yr old
Human herpes virus 6 *HHV-6)
● Discovered in 1986
● Almost all children exposed by 2yrs old 90%
● Causes roseola (body trunk rash and fever)
○ 1in 5 of all ER visits under 2
○ Spread by oral route- no treatment
● HHV6 caused by multiple sclerosis (MS)
○ MS involves autoimmune destruction of myelin sheaths around neurons (sclerosis)
○ Associated between MS and HHV6 antibodies
Human herpes virus 8 HHV7
● Very little is known
● Very prevaeltn (over 90% pop )
● Infects t- lymphocytes
● May be cause of pityriasis rosea
○ Skin rash most common in 10-35 age group
Human herpes virus 8 HHV8
● Least prevalent of herpes - 3%
● Transmitted by sex semen and orally
● Thought to be a cause of kaposi's sarcoma( skin lesions)
○ Purple tumor on skin or mouth
○ An angiogenic tumors● How is HHV8 involved in kaposi sarcoma?
○ HHV8 promotes blood vessel formation needed for tumor growth
○ Combines with immune compromised to promote tumors
Measles (rubeola)
● Rub- red
● ssRNA (helica), enveloped virus
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Rubella
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Mumps
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○ Hemagglutinin & cell fusion glycoprotein spikes
Highly contagious, transmitted by resp droplets
1-2 week incubation period
SYMPTOMS
○ Fever, sore throat, hacking cough
○ Headache, sneezing, conjunctivitis (pink eye)
○ Koplik's spots
■ Small white lesions in oral cavity mucosa near molars
Death rate= 1or 2/ 1000
Skin rash appears 1-2 days after oral lesions- begin in head then to trunk
○ Reed patches turn brown and disappear without complications
MOST INFECTIOUS
rubella= little red
Small 60nm, enveloped ssRNA virus
Transmitted via respiratory secretions
2-3 week incubation period
Relatively mild disease
○ Slight fever, mild cold symptoms
○ Enlarged lymph nodes
○ Faint rash over face, chest, abdomen
○ Painful joints in adults
Can be contagious up7 days before and after rash
Pathogenesis
○ Replicated both resp tract and lymph nodes
○ Viremia results in formation of antigen- antibody complexes
○ antigen- antibody complexes responsible for joint pain (immunopathology)
MAJOR CONCERN
○ Threat to fetus
○ Congenital rubella syndrome (CRS)
○ First trimester vulnerable
■ Still births, miscarriage
■ Fetal malformations
● Cataracts
● deafness/ blind
● Heart defects
● Mental deficiencies
○ Major reason for vaccination
Live attenuated vaccine
Administered with measles mumps
Given at 12-18 months then 5-6 years of age
Acute viral disease attacking primary parotid gland(parotitis)
ssRNA, enveloped virus
Transmission resp droples, contact, fomites
Swelling of one or both parotid glands
Pathogenesis
○ 15-21 day incubation
○ Initial reproduction in resp tract epithelium- blood stream- salivary glands
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Inflammation- blockage- swelling
Testes may also be involves (orchitis; orchis= testicle)
Parotid glands not always involved= may develop meningitis
Viscerotropic viruses
● Viral hepatitis
● EBola
● HIV
Hepatitis
● Effects the liver
● Causes
○ viral -80-90%
○ Hepatitis ABC (DEFG)
○ Epstein- barr virus
○ Herpes simplex virus, CMV
○ Other enterovirus
○ Entamoeba histolytica (protozoa infection)
○ Drugs, alcohol, acetaminophen, ischemic injury
● Common viruses
○ Hepatitis A- HAV-mild- vaccine- easites to get
○ Hepatitis B - HBV- severe- vaccine
○ Hepatitis C- HCV- most severe- no vaccine
● Hepatitis A
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Non enveloped, ssRNA
Used to be called infectious hepatitis
How do you get it?■ FECAL- ORAL ROUTE
■ Sexual transmission
■ Eating. Drinking contaminated food
Incubation period- 15-50 days
Symptoms
■ Flu like
■ Fever, fatigue
■ Nauseous, anorexia
■ Dark coloured urine, clay coloured poop
■ Jaundice in 10% patients
Self limiting disease
No complication
Epidemiology
■ Epidemic 10 yr period or sporadic
■ Low incidence ( previous exposure to hepa A)
■ Contracted in area of poor sanitation
■ About 20,000 currenyl infection, 2,000/ year in Canada
■ 150,000 curren and 28,00 new NA
Exposure
■ About 3# of preadolescents, less 60 of those over 60yr
■ Greats increase 20-39 yr old
Who is at risk?????
■ Contact with new illness
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Travelers in developing countries
● 3-5 infection/1000 travelers= 0.5% to get infected
Prevention
■ Wash hands
■ Extra care around infected ppl
■ Immunizations
Immunizations
■ Inactivated (dead) virus vaccine
■ First does provide with protection less than year
■ Booster at 6 months,less than 3yr old
TREATMENT
■ Avoid liver toxins
■ 0 alcohol consumptions
■ Interferon for severe cases
● HEP B
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Currently most prevalent reported strain of hep virus
dsDNA enveloped virus
Used to be called- serum hepatitis
Several mutants - non clinically relevant
3 forms
■ Full viron (Dane particle)
■ Capsomeres without genome
● Spheres and tubes
Incubation- 1-4 months
Symptoms■ Range from mild flu like symptoms to life threatening liver failure
■ Jaundice in 30% of patients
Transmission
■ Parenteral route
■ Found in blood, semen, breast milk, vaginal secretion, saliva
■ Transfusion, needle sticks, IV drug abuse
■ Sexual transmission
■ Mother-child during birth
■ Toothbrush/ Razor transmission
Pathogenesis
■ Severe acute hepatitis- rapid destruction of liver= 0.1-0.5 of patients
■ Chronic hepatitis- 10-20%
● Asymptomatic carrier
● Never develop antibodies
● Has virus with no liver injury
● Chronic persistent hepatitis- low grade’ smoldering’ hepatitis
● Chronic active hepatitis
○ Severe liver damage,6-12 months without recovery
complete recovery 80-90% with immunity
Epidemiology
■ 10-15% carrier rate in asia & sub saharan africa (3ndemic area)
■ Canada 20,000 cases/yr= 0.5% pop
Vaccine
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Old vaccine
● Made from plasma of pll with hep B
● Still used but no in canada
■ protein vaccine
● Immunization with HBsAg
■ New vaccine= recombinant
● HBV s gene put into yeast- HBsAg purified from yeast
Therapy for chronic hepatitis
■ Therapy with interferon
● Decreased viral level and improved appearance of liver microscopically in 3350% of patients
■ Therapy For end-stage liver disease
● Liver transplant
● HEP C
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ssrNA enveloped virus
Has protein which prevent host cell death= chronicity
Never been cultured
Clinical illness
■ Incubation starts ½ - 5 months after initial infection
Transmission
■ Blood (sexual transmission rare)
■ Blood transfusion before 1992
● 1.5% blood donors infected before 1992
■ Sharing needles ½ cases
■ Tattooing, body piercing
■ Needles stick- occupational exposure
■ Tooth brush, razer
Epidemiology
■ 80,000 reported cases
■ 250,000 probable infection = less than 1% of adults
■ 50% prevalence among IV drug abusers
■ 50% prevalence among hemophiliacs transfused before 1992
Prognosis
■ 10% recover
■ 90% carry for life
● Liver damage- cirrhosis, cancer, profound fatigue, jaundice
■ Of those with cirrhosis=
● 30% progress to end stage liver disease
● 15% develop hepatocellular carcinoma
● Alcohol consumption accelerates disease
● New drug combinations may be a cure
Combination drug
■ Including nucleotide analogue and assembly inhibitor
■ 99% effecting for genotype 1 chronic hepatitis, 70% for chronic hepatitis
NO VACCINATION
Prevention
■ Screen blood supply
■ Avoid high risk behavior
■ Universal precautions as nurses
Ebola virus vaccines
● Viral family filoviridae(filamentous virions)
● ssRNA, encoding 7 proteins
● Currently 6 different vaccine trials
● Canadian vaccine in phase 3 trials
○ Based on vesicular stomatitis virus(VSV) expression of Ebola Gps (VSV-EBOV)
○ April 2015: vaccine is safe and effective
● Is a filamentous virus
● Incubation period
○ 2 week - 3 weeks
● Progression of disease
○ Fever, sore throat,muscle ache, vomiting, diarrhea, rash, intern, external bleeding, organ failure
○ Fluid resuscitation and symptom reduction(fever) has decreased death rate from 90% to 40%
AIDS
Prevalence of HIV infection in
● AFRICA= 5-20%
● INDIA= 1%
● CANADA=0.2%
● The effect of HIV on immune system = non healing wounds and promotes other infections
AIDS- clinical definition
● Severe immunodeficiency disease arising from infection with HIV
● Possible symptoms
○ Life threatening opportunistic infections- pneumonia
○ Persistent fever
○ Cancers
○ Chronically swollen lymph nodes
○ Extensive weight loss
○ Chronic diarrhea
○ Neurological disorders
● Transmissions
○ Sex
○ Blood transfer
○ Breast milk
○ Small viral #s in other body fluid, may not be sufficient for transmission
○ Not transmissible through touch (fomites, saliva)
● Pathogenesis
○ Initial infections
■ First 2-3 weeks
■ Mononucleosis- like symptoms
■ Disappear on their own in 1-4 weeks
○ Asymptomatic (latent) infection
■ Varies considerably in length (2-15 years)
■ Silent struggle going on between HIV and CD4 cells
■ Intermittent symptoms throughout this period
○ Normal CD4 count - 1000 cells/ microliter
○ AIDS symptoms- CD4 COUNT = less than 200 cells/ uL
HIV
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Enveloped, ssRNA virus
Retrovirus- converts RNA to DNA
Reverse transcriptase, protease
Lipid envelope contains glycoproteins as spikes and knobs( GP41, GP120)
○ Facilitate attachment and penetration of host cells
Cause immunodeficiency
Target cells of immune system (CD4 cells)
○ CD= cluster of differentiation)
○ Primary CD4 cells= helper T- cells