Download General Virology

Epidemiology versus
Pathogenesis
• Pathogenesis:
Concerns the processes by which viruses infect
individuals.
• Epidemiology:
Studies the transfer and persistence of viruses in
populations.
Routs of virus transmission
Individuals
Mother
Individuals
Individuals
Individuals
Offspring
Viral zoonoses
(Arboviruses)
• Multiply in both arthropods (mainly ticks and
mosquitoes) and vertebrates
• Animals are the main reservoirs and humans are only
occasionally infected.
Portals of entry and exit
for
Horizontal Transmission
• Three large epithelial surfaces:
Skin
Respiratory mucosa
Alimentary tract
• Two lesser surfaces:
Genital tract
Conjunctiva
Portals of entry and exit
(continued)
• Breach the surface
- Bite of an arthropod or mammal (all Flaviviridae viruses,
Colorado tick fever virus from Reoviridae, Sandfly fever virus from
Bunyaviridae; Rabies virus)
- Trauma (HBV, Papillomavirus, HSV-1 and -2,
Molluscum contagiosum virus)
- Injection (medical procedures or social practices): HBV,
Cytomegalovirus, Epstein-Barrvirus (EBV), HIV
-
Transfusion
Transplantation
Minor surgical procedures (tattooing, dentistry, ear piercing)
Arm to arm vaccination
Are the entry and exit portals for each
virus always the same ?
• Measles and chickenpox viruses infect via
respiratory tract but shed from lesions of
oral mucosa and skin.
• Mumps virus infects humans via
respiratory tract but sheds from infected
salivary glands.
Infection via
Respiratory tract
(The most common route of viral infection)
Type of multiplication and infection in
respiratory tract infections
1. Local infection in respiratory tract
(cause ifluenza, colds, pharyngitis, bronchiolitis, and
pneumonia. e.g. Influenza A and B viruses; Parainfluenza virus,
respiratory syncytial virus; Rhinoviruses, many Corona- and
Adenoviruses).
2. Initiation of infection via the respiratory tract but can
also produce generalized infection usually without
respiratory symptoms.
(Herpesviruses:
EBV,
Cytomegalovirus;
some
enteroviruses;
Paramyxoviridae: mumps, measles; rubella virus from Togaviridae)
Infection via
Alimentary tract
• Stomach and duodenum are protected by:
- Acid
- Bile salts
- Enzymes
• Virus multiplication in the cells of small intestine
and excretion in the feces : water- and food-borne
epidemics.
Viruses that initiate infection via
Alimentary tract
• In mouth or oropharynx:
(HSV, EBV, Cytomegalovirus)
• In intestinal tract : Producing enteritis
(Rotaviruses, several Adenoviruses, Narwalk virus from
Calciviridae)
• In intestinal tract : Producing generalized disease
• (many enteroviruses from picornaviridae including
poliovirus and HAV)
Infection via
Genital tract
•
•
•
•
Molluscum contagiosum virus from poxviridae
HSV-2 and Cytomegalovirus from Herpesviridae
HIV and HTLV-1 from retroviridae
HBV
Virus shedding in urine: Cytomegalovirus, Rubella virus,
measles virus, mumps virus, HBV
Arena virus in rodent urine
Human infection: e.g.
hemorrhagic fever
Inhalation of dust containing
viruses in dried urine
Infection via
Conjuctiva
(Conjunctivitis)
• Direct infection of the conjunctiva
(e.g. HSV-1)
• Caused by generalized disease
(e.g. measles and Newcastle disease virus from
Paramyxoviridae)
Routs for
Vertical Transmission
• The ovum (some retroviruses)
• The placenta (Rubella virus, Cytomegalovirus, HIV,
HBV)
• Vagina during birth (Herpes simplex virus)
• Mother’s milk (Cytomegalovirus)
• Salivary contamination (Cytomegalovirus, herpes
simplex virus)
Epidemiological features of viral infections
• Mode of transmission (as told before)
1. Respiratory
2. Alimentary
3. Bite (Animal, mosquito, tick)
4. Sexual contact
5. Congenital
6. Contact
Epidemiological features of viral
infections
(continued)
• Mode of transmission
• Incubation period (1 day to 15 years)
• Period of Communicability
• Incidence of subclinical infections
• Season of maximum incidence
Incubation period and season of
maximum incidence
•
•
•
•
•
•
•
•
•
•
•
Influenza : 1-2 days/ Winter
Common cold: 1-3 days/ Spring, autumn
Herpes simplex: 5-8 days/ Nil
Enterovirus diarrhea: 6-12 days/ Summer
Rotavirus diarrhea: 2-4 days/ Winter
Measles: 9-12 days/ Spring
Chikenpox: 13-17 days/ Spring
Mumps: 16-20 days/ Spring
Rubella: 17-20 days/ Spring
HAV: 15-40 days/ Summer
Warts: 50-150 days/ Nil
Variables that determine the
transmissibility
• Excretion (manner, duration, quantity of virus,
infectivity).
• Environment (Stability of the virus and the
chance of contact with a new host).
• Immunity (the level of herd immunity)
So, to control or eradicate viral infections, we
must manipulate these variables
Viral infection control
•
•
•
•
•
Immunoprophylaxis
Vector control
Sanitation
Interferons
Antiviral agents
Immunoprophylaxis
Active immunity:
• Vaccines
Passive immunity:
• Antibody-containing preparations (e.g. Gamma
globulin)
Vaccines classification
Based on:
• The technology of production
(Vaccine generation)
• Being attenuated or inactivated
• The route of administration (Oral, Subcutaneous “SC”,
Intramuscular “IM”)
Vaccine production
• First Generation:
Prepared in the tissues of an inoculated animal.
(e.g. small-pox vaccine from the skin of a calf).
• Second Generation:
Products from the inoculation of embryonated eggs (e.g.
inactivated influenza virus vaccine)
Vaccine production
(continued)
• Third Generation:
Tissue culture-propagated vaccines
(e.g. poliomyelitis, measles, mumps, and rubella vaccines)
• Fourth Generation:
Using nucleic acid recombinant technology (e.g. HBV
Subunit vaccine)
Attenuated (live) or inactivated
(killed) vaccines
Attenuated (Live) vaccines
(advantages and disadvantages)
• Lifelong immunity (usually after one dose)
• A chance of reversion to pathogenic form
Inactivated (killed) vaccines
(Structure)
• Whole virus particles (e.g. Rabies vaccine)
OR
• Some component(s) of the virus (e.g. HBV vaccine
based on HBsAg)
Inactivated (killed) vaccines
(Advantages and Disadvantages)
• Not reversible to pathogenic form
• For lifelong immunoprophylaxy multiple doses are
required.
• Needs large concentration of viral antigens.
• Chance of allergic reactions
(Recombinant vaccines is a help!)
Enhancing immune response to vaccine
• Adjuvant substances (e.g. aluminum salts in hepatitis B
vaccine).
• Route of vaccine administration (Oral, subcutaneous,
Intra muscular).
• Age of vaccine administration (e.g. when MMR is
administrated less than 15 months, lower response rates
can be seen).
Vaccine assessment
• Should be compared with the immunity conferred by
natural disease.
• Vaccine-induced immunity can be defined by:
_ Percentage of recipients protected.
_ The duration of protection.
_ The degree of protection.
• Upon reactivation or re-infection, a boost in IgG
antibodies is observed with little or no detectable IgM
response, suggesting prior protection.
Passive immunoprophylaxis
Immunoglobulins: Gama globulin
When?
- Exposure has occurred and time does
not allow for vaccination.
- No effective vaccine exists.
Other methods for control
• Avoidance of viral exposure
• Control of viral reservoirs
• Vector control
• Improving sanitation, especially in case of
viruses with fecal-oral transmission.
Papova viruses
(Papilloma polyoma vacoulating)
• Structure:
DNA virus, double strand, circular, Icosahedral
nucleocapsid, small size (45-55nm).
• Papillomaviruses
• Polyoma viruses
Oncogenic in some animals (e.g. in rodents)
Human Papilloma virus (HPV)
• 60 to 70 different types.
• It replicates only in the nucleus of epithelial cells.
• HPV are species-specific.
HPV
• Some cause warts (condylomata accuminata or skin
papillomas) and some others are associated with
cancer
• They involve keratinizing and mucosal
epithelium:
Causing mucocutaneous lesions
• They are transmitted by both direct and indirect
contact.
Human Papilloma virus (Continued)
• HPV2, 3 and 10: Common wart (on knees and
fingers)
• HPV1 and HPV4: plantar wart
• HPV6, 11, 16, 18 and 32: Genital warts
(Condylomata accuminata) on penis, vulva and
perianal regions
Genital warts
• Can blossom into cauliflower-like
protuberances.
• In the cervix the lesion may be a flat area of
dysplasia.
HPV16 and HPV18
• Associated with
cervical cancer which starts with a flat area
of dysplasia (visible as a white plaque).
HPV Pathogenesis
• Infects cells in the basal layers of the skin or mucosa
(abortive infection)
• Viral antigen and infectious virus is produced when the
cells begin to become squamifed and keratinized.
• The mass of infected cells, 1-6 months after initial
infection protrude from the body surface to form a visible
papilloma. Several months after infection, the wart
regresses.
HPV
• CMI responses are more important in recovery.
• In immunocompromised patients (e.g. post transplant),
there may be crops of warts as a result of reactivation.
Diagnosis
• Diagnosis is clinical
• HPV cannot be cultivated in the laboratory
• Serological tests are neither useful nor available
Treatment
• Post-hypnotic suggestion has at times been successful.
• The application of Keratolytic agents, such as salicylic
acid to soften and cause desquamation of epithelium or
horny layer of skin.
• Destruction of wart tissue by freezing with dry ice (solid
CO2) or with liquid nitrogen.
• Podophyllin
HPV, an oncogenic virus
HPV viral genes, “E6 and E7”
Tumor suppressor genes
(e.g. P53 )
Protein
Proteins
Regulating
cell cycle
Uncontrolled DNA duplication and cell division
Parvoviruses
• Structure
- Nonenveloped, icosahedral particle,
Single and Positive DNA strand.
- Very small viruses (18-26 nm in
diameter) and ubiquitous.
- Infect many species of animals.
Parvoviruses
- unusual requirements for replication:
either a helper virus (a helper adenovirus)or
rapidly dividing cells.
Two types of these viruses:
Dependovirus and parvovirus. B19 virus is
a parvovirus replicating in erythroid
precursor cells.
B19
• A human virus cannot pass to animals.
• Erythema infectiosum, (fifth disease), is the commonest
clinical manifestation of B19 virus infection.
• In children (age 5-15) and sometimes adults (up to 30).
40-60% infectionsare asymptomatic.
Fifth disease pathogenesis
• The virus is transmitted by the respiratory route.
• The virus infects erythroid precursor cells in the bone
marrow and leads to anemia.
• It leads to erythroid aplasia (Aplastic crisis) in patients
with hemolytic anemia or immune deficiency.
• Anemia and aplastic crisis is self-limiting.
Fifth disease
(Erythema infectiosum)
• First stage:
7-8 days after infection, a prodromal influenza-like illness,
characterized by headache, malaise, chills.
• Second stage:
17 to 18 days after infection, the development of a mild
feverish illness and a maculopapular rash. It starts with
erythema of the cheeks followed by a rash (resembling the
rash of rubella) on the trunk and limbs. These symptoms
disappeared 1-3 weeks.
Fifth disease
• Acute symptoms: Severe anemia in blood disorders
(e.g. in Sickel cell anemia, Leukemia or hemolytic anemia)
• Bone marrow examination shows an absence of erythroid
precursors.
Diagnosis
• Detecting viral DNA in serum
• A rise in parvovirus-specific IgM or IgG.
Control and treatment
• There is no antiviral therapy or vaccine.
• Most infections are asymptomatic when there is
viral shedding.
• The anemia is self-limiting, but blood transfusion
support is required until the bone marrow
recovers.