Epidemiology:

Pathogenesis:

Concerns the processes by which viruses infect individuals.

Studies the transfer and persistence of viruses in populations.

Epidemiology

versus

Pathogenesis

1

2

3

Mode of transmission

4

Incubation period (1 day to 15 years)

Period of Communicability

Incidence of subclinical infections

5Season of maximum incidence

Epidemiological features of viral infections

Routs of virus transmission

Offspring

Individuals Individuals

Individuals Individuals

Mother

Reservoir Biological vector Accidental host

Multiply in both arthropods (mainly ticks and mosquitoes) and vertebrates

Animals are the main reservoirs and humans are only occasionally infected.

Viral zoonoses(Arboviruses)

Two lesser surfaces:

Skin Respiratory mucosa Alimentary tract

Genital tract Conjunctiva

Portals of entry and exit

for Horizontal Transmission

Three large epithelial surfaces:

1 Arm to arm vaccination

2 Minor surgical procedures (tattooing, dentistry, ear piercing)

3 Transplantation

4 Transfusion

5 Trauma (HBV, Papillomavirus, HSV-1 and -2, Molluscum contagiosum virus)

6 Injection (medical procedures or social practices): HBV, Cytomegalovirus, Epstein-Barrvirus (EBV), HIV

7 Bite of an arthropod or mammal (all Flaviviridae viruses, Colorado tick fever virus from Reoviridae, Sandfly fever virus from Bunyaviridae; Rabies virus)

Bre

ach

the

surf

ace

Portals of entry and exit (continued)

Mumps virus

infect via respiratory tract but shed from lesions of oral

mucosa and skin.

infects humans via respiratory tract but sheds from infected

salivary glands.

Are the entry and exit portals for each virus

always the same ?

Measles and chickenpox viruses

Infection via Respiratory tract

(The most common route of viral infection ?)

2

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)

Initiation of infection via the respiratory tract but can also produce generalized infection usually without respiratory symptoms.(e.g: Herpesviruses: EBV, ytomegalovirus; some enteroviruses; Paramyxoviridae: mumps, measles; rubella (German measles) virus from Togaviridae)

Type of multiplication and infection in respiratory tract

infections

1

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.

Infection via Alimentary tract

1In mouth or oropharynx

Example text

HSV, EBV, Cytomegalo

virus

1

2

3

2In intestinal

tract : Producing enteritis

Example text

Rotaviruses, several

Adenoviruses, Narwalk virus

from Calciviridae

1

2

3

3In intestinal

tract : Producing generalized

disease

Example text

many enteroviruses

from picornaviridae

including poliovirus and

HAV

1

2

3

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URGENT but NOT IMPORTANT

HIV and HTLV-1 from retroviridae HBV

NOT URGENT but IMPORTANT

Virus shedding in urine

Cytomegalovirus, Rubella virus, measles virus, mumps virus, HBV

Systemic infectionLocal Infections

Molluscum contagiosum virus from poxviridae HSV-2 and Cytomegalovirus from Herpesviridaes

Arena virus in rodent urine

Inhalation of dust containing viruses in

dried urineHuman infection: e.g.

hemorrhagic fever

Infection via

Genital tract

Direct infection of the conjunctiva (e.g. HSV-1)

Caused by generalized disease (e.g. measles and Newcastle disease virus from Paramyxoviridae)

Infection via Conjuctiva

(Conjunctivitis)

1

2

3

The ovum: some Retroviruses

4

Salivary contamination: (Cytomegalovirus, HSV virus)

Mother’s milk: (Cytomegalovirus)

Vagina during birth: (Herpes simplex virus)

5The placenta: Rubella (German measles) virus, Cytomegalovirus, HIV, HBV)

Routs for Vertical Transmission

Common cold: 1-3 days/ Spring, autumn 2

1 Influenza: 1-2 days/ Winter

3 Herpes simplex: 5-8 days/ Nil

Enterovirus diarrhea: 6-12 days/ Summer 4

Measles: 9-12 days/ Spring 6

5 Rotavirus diarrhea: 2-4 days/ Winter

7 Chikenpox: 13-17 days/ Spring

Mumps: 16-20 days/ Spring 8

9 Rubella: 17-20 days/ Spring

HAV: 15-40 days/ Summer 10

11 Warts: 50-150 days/ Nil

Incu

bat

ion

per

iod

an

d s

easo

n o

f m

axim

um

inci

den

ce

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URGENT but NOT

IMPORTANT

NOT URGENT but IMPORTANT

Stability of the virus and the

chance of contact with a

new host

Immunity

the level of herd

immunity

EnvironmentExcretion

manner, duration,

quantity of virus,

infectivityVariables

that

determ

ine the

transm

issibilit

y

So, to control or eradicate viral infections, we must manipulate these variables

541

Immunoprophylaxis

Interferons

2Vector control

Antiviral agents

3Sanitation

Viral infection control

Passive immunity

Vaccines Antibody-containing preparations (e.g. Gamma

globulin)

Immunoprophylaxis

Active immunity

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URGENT but NOT

IMPORTANT

NOT URGENT but IMPORTANT

Being attenuated or inactivated

3

The route of administration

Oral, Subcutaneous

“SC”, Intramuscular

“IM”

21

The technology of production (Vaccine generation)

Vaccines classification

Based on

Example text

Prepared in the tissues of an inoculated

animal. (e.g. small-pox vaccine from the skin of a calf)

Vaccine production

1

1

2

3

4

First Generation

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Products from the inoculation of

embryonated eggs(e.g. inactivated influenza virus

vaccine)

Vaccine production 1

2

3

4

2Second Generation

Example text

Tissue culture-propagated vaccines(e.g. poliomyelitis,

measles, mumps, and rubella vaccines)

Vaccine production

3

1

2

3

4

Third Generation

Example text

Using nucleic acid recombinant technology

(e.g. HBV, HIV Subunit vaccine)

Vaccine production

4

1

2

3

4

Fourth Generation

Attenuated (live) vaccines(Structure)

Whole virus particles (e.g. Rabies vaccine)OR

Some component(s) of the virus (e.g. HBVvaccine based on HBsAg or recombinant subunits)

1

2

3

Not reversible to pathogenic form

4

For lifelong immunoprophylaxy multiple doses are required.

Needs large concentration of viral antigens.

Chance of allergic reactions

Inactivated (killed) vaccines (Advantages and Disadvantages)

1

2

3

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).

Enhancing immune response to vaccine

2

In general it should be compared with the immunity conferred by natural disease.

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.

Vaccine assessment

1

Attenuated (Live) vaccines(advantages and disadvantages)

Lifelong immunity (usually after one dose)

A chance of reversion to pathogenic form

Passive immunoprophylaxis

Exposure has occurred and time does not allow for vaccination.

No effective vaccine exists.

Immunoglobulins: Gama globulin

When?

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URGENT but NOT

IMPORTANT

NOT URGENT but IMPORTANT

Developing oral vaccines

by using transgenic

plants expressing

virulent viral antigenes

3

Developing DNA vaccines (Gene

vaccines): Injecting recombinant plasmids including certain gene

to the host and then expression of protective proteins by the host cell

itselfe

21

Entering a gene into a

non-virulent virus and then using

the virus as a vaccine

The future view for vaccines

1

2

3

Avoidance of viral exposure

4

Control of viral reservoirs

Vector control

Improving sanitation, especially in case of viruses with fecal-oral transmission.

Other methods for control

History

The first known

cytokine

Classification

: IFN-α, IFN-β, IFN-γ

IFN synthesis

by all vertebrates but only in cell induction conditions

Inducers for IFN-α, IFN-β: Viruses, dsRNA, endotoxins, some polysacharids. Inducers for IFN-γ: mitogens

Specificity: for the hosts but not to the viruses

Interferons (IFNs)

The mechanism of IFNs (1)

Attachment of IFN to the second cell (non-infected cell)

Tyrozin phosphorilation

Activation of transcription factors (TFs) in cytoplasm

Transportation of activated TFs to the nuclous

Transcription of the genes induced by IFN

The mechanism of IFNs (2)

Inducing synthesis of at least these enzymes:dsRNA dependent Protein kinase (PKR)

Phosphorylation and inactivation of initiation factor (eIF2) viral mRNA cannot bind to ribosome Inhibition of translationOligonucleotide synthetase (2’-5’ oligo A synthetase)

Activating Endonuclease degradation of viral mRNAPhosphodiestrase

Inhibition of polypeptide elongation

IFNs as antiviral drugs

Strongness:

< 50 IFNs molecules in each cell is enough for antiviral activity

Limitation:

It can affect if added to the cell before viral cell infection

Usable in some viral infections:

HBV, HCV, HSV

Viral mechanisms for IFNs nutralization and resistance: Inhibition of protein kinase (PKR) by viral proteins. Filling the site of IFN receptors on the cell by viruses

Antiviral drugs

Introduction

Nucleoside analogs(Non-Nucleoside) Revers transcriptase

inhibitors

Protease inhibitors

Acyclovir (HSV),Gancycleovir (CMV), Lamivudien (HBV, HIV), Ribavirin (B Influenza virus, RSV, Congo fever), Vidarabin (HSV), Didanosine (HIV), Zidovudin (HIV)

Nevirapin (HIV)

Saquinavir, Indinavir, Ritonavir (HIV)

Fuzeon (HIV)

Fusion inhibitor (The fusion of virus and cell/nucleus membrane)

Amantadine and Rimantadine (A Influenza virus)

Inhibiting virus uncoating

Antiviral drugs mechanisms