The Epidemiology of viruses

1. The Epidemiology of viruses

2. Epidemiology versus Pathogenesis • Pathogenesis: Concerns the processes by which viruses infect individuals. • Epidemiology: Studies the transfer and persistence of viruses in populations.

3. Routs of virus transmission Mother Individuals Individuals Individuals Individuals Offspring

4. Viral zoonoses(Arboviruses) • Multiply in both arthropods (mainly ticks and mosquitoes) and vertebrates • Animals are the main reservoirs and humans are only occasionally infected.

5. Portals of entry and exit for Horizontal Transmission • Three large epithelial surfaces: Skin Respiratory mucosa Alimentary tract • Two lesser surfaces: Genital tract Conjunctiva

6. 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, Molluscumcontagiosum 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

7. 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.

8. Infection via Respiratory tract(The most common route of viral infection)

9. 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)

10. 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.

11. 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)

12. 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 Inhalation of dust containing viruses in dried urine Human infection: e.g. hemorrhagic fever

13. 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)

14. 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)

15. Epidemiological features of viral infections • Mode of transmission (as told before) • Respiratory • Alimentary • Bite (Animal, mosquito, tick) • Sexual contact • Congenital • Contact

16. 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

17. 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

18. 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

19. Viral infection control • Immunoprophylaxis • Vector control • Sanitation • Interferons • Antiviral agents

20. Immunoprophylaxis Active immunity: • Vaccines Passive immunity: • Antibody-containing preparations (e.g. Gamma globulin)

21. Vaccines classification Based on: • The technology of production (Vaccine generation) • Being attenuated or inactivated • The route of administration (Oral, Subcutaneous “SC”, Intramuscular “IM”)

22. 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)

23. 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)

24. Attenuated (live) or inactivated (killed) vaccines

25. Attenuated (Live) vaccines(advantages and disadvantages) • Lifelong immunity (usually after one dose) • A chance of reversion to pathogenic form

26. 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)

27. 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!)

28. 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).

29. 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.

30. Passiveimmunoprophylaxis Immunoglobulins: Gama globulin - Exposure has occurred and time does not allow for vaccination. - No effective vaccine exists. When?

31. 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.

32. 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)

33. Human Papilloma virus (HPV) • 60 to 70 different types. • It replicates only in the nucleus of epithelial cells. • HPV are species-specific.

34. HPV • Some cause warts (condylomata accuminata or skin papillomas) andsome others are associated with cancer • They involve keratinizing and mucosal epithelium: Causing mucocutaneous lesions • They are transmitted by both direct and indirect contact.

35. 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

36. Genital warts • Can blossom into cauliflower-like protuberances. • In the cervix the lesion may be a flat area of dysplasia.

37. HPV16 and HPV18 • Associated with cervical cancer which starts with a flat area of dysplasia (visible as a white plaque).

38. 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.

39. 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.

40. Diagnosis • Diagnosis is clinical • HPV cannot be cultivated in the laboratory • Serological tests are neither useful nor available

41. Treatment • Post-hypnotic suggestion has at times been successful. • The application of Keratolytic agents, such as salicylic acid to soften and causedesquamation of epithelium or hornylayer of skin. • Destruction of wart tissue by freezing with dry ice (solid CO2) or with liquid nitrogen. • Podophyllin

42. HPV, an oncogenic virus Protein HPV viral genes, “E6and E7” Regulating cell cycle Tumor suppressor genes (e.g. P53 ) Proteins Uncontrolled DNA duplication and cell division

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.

49. Diagnosis • Detecting viral DNA in serum • A rise in parvovirus-specific IgM or IgG.

50. 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.