1. Parvovirus & Rubella Virus Robert Seese, MD Assistant Professor, Clinical Pediatrics Nationwide Children’s Hospital The Ohio State University Robert.Seese@nationwidechildrens.org

2. Learning Objectives  Recognize the structure and microbial physiology of Parvovirus and Rubella virus and integrate this information with the human pathophysiologic correlates  Describe physical and chemical properties of Parvovirus and Rubella viruses  Describe the replication of Parvovirus and Rubella viruses  Describe the underlying genetic mechanisms of Parvovirus and Rubella viruses  Recognize the molecular basis of pathogenesis and physiology of Parvovirus and Rubella virus infections  Identify the normal human immune response to Parvovirus and Rubella virus infection

3. Learning Objectives  Recognize the epidemiology and ecology of Parvovirus and Rubella virus infections  Describe and differentiate the principles of laboratory diagnosis for Parvovirus and Rubella virus infections  Describe the treatment, prevention and control of Parvovirus and Rubella virus infections  Apply principles of immunology in select clinical settings: Vaccine  Describe the mechanisms by which Rubella virus vaccine is used to induce a protective adaptive immune response without overt infection.

4. Parvoviridae  The smallest of the DNA viruses  Small size makes them dependent on the host cell or the presence of a helper virus to replicate  Parvovirus B19 and bocavirus are the only parvoviridae known to cause human disease

5. Parvovirus B19: Structure & Replication

6.  Parvoviruses MUST infect mitotically active cells  They do not encode for polymerase or a method to stimulate cell growth  B19 virus prefers cells of erythroid lineage for this reason (bone marrow cells, fetal liver erythroid cells, etc.)

7. Parvovirus B19: Structure & Replication

8. Parvovirus B19: Pathogenesis, Disease Mechanisms & Immunity

10. Parvovirus B19: Epidemiology  The virus has a worldwide distribution  Infection is most common in late winter and spring  65% of the adult population is seropositive for antibodies  Children aged 4 – 15 y/o are the most common source of contagion  Viral Factors:  Capsid is resistant to inactivation  Contagious period precedes symptoms  Virus can cross placenta  Transmission via respiratory droplets and oral secretions

11. Parvovirus B19: Clinical Syndromes Erythema Infectiosum (“Fifth Disease”)

12. Parvovirus B19: Clinical Syndromes  Adult infections  Polyarthritis with or without rash that can lasts for weeks to months  Joints involved usually include hands, wrists, ankles, and knees  Rash may precede the arthritis, but is often absent  Immunocompromised patients may have chronic disease  Aplastic Crisis  Potentially fatal reticulocytopenia due to transient drops in erythropoeisis  Depletion of erythrocyte precursors combined with shortened RBC life span  Occurs in patient with underlying hemoglobinopathies  Accompanied by fever and flu-like symptoms

13. Parvovirus B19: Clinical Syndromes  Infection in seronegative pregnancy  Can infect the fetus and kills its erythrocyte precursors  This causes congestive heart failure due to severe anemia Non-immune “Hydrops Fetalis”  The virus does not cause congenital anomalies in and of itself  Seropositive mothers have no ill effects library.med.utah.edu

14. Parvovirus B19: Laboratory Diagnosis, Treatment, Prevention & Control  “Erythema infectiosum” is usually a clinical diagnosis  ELISA assays for IgM and IgG  DNA PCR (very sensitive!!)  No specific antiviral treatments available  Vaccines are available for the canine and feline forms of the disease, but not for the human forms

15. Summary  Parvovirus B19  Smallest DNA virus  Infects mitotically active cells of the bone marrow  Mostly yields mild illness with rash  In special cases can lead to aplastic crises  Can infect in utero and lead to fetal demise

16. Rubivirus (Rubella virus)  Member of Togaviridae  Several subgroups  The only member of the Rubivirus group is Rubella  Enveloped, single-stranded positive-sense RNA  It has an icosahedral capsid surrounded by an envelope (“toga”) CDC/ Dr. Erskine Palmer

17. Rubella: Structure & Replication

19. Rubella: Pathogenesis & Immunity  Respiratory virus that does not cause cytopathological effects  Infects the upper respiratory tract and then spreads to lymph nodes  Viremia and the characteristic rash result  This prodromal period lasts for 2 weeks and is associated with viral shedding

20. Rubella: Pathogenesis & Immunity

21. Rubella: Epidemiology  Humans are the only host for rubella and asymptomatic disease is possible  Spread by respiratory secretions and usually acquired early in life  Spreads rapidly in crowded conditions  Children have a milder disease course than adults

22. Rubella: Clinical Syndromes  Children  Normally benign  14 – 21 day incubation period, then… 3 day maculo-papular rash Swollen glands  More severe events can occur: Bone and joint pain Thrombocytopenia or post-infectious encephalopathy Centers for Disease Control and Prevention

23. Rubella: Clinical Syndromes  Adults  Approximately 20% escape infection during childhood  Adults have more severe joint and hematological manifestations of illness  Pregnant women without immunity risk transmission to the fetus!!

24. Rubella: Clinical Syndromes http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v5/v5c033.html From Damjanov, 2000. 1 2 3 Amer. Acad. Pediatrics Congenital Rubella Syndrome (CRS)

25. Rubella: Laboratory Diagnosis  Isolation of the virus is difficult and rarely attempted  Viral RNA can be detected by PCR  Diagnosis confirmed by rubella-specific IgM assay  ≥ 4-fold rise in IgG titers from acute and convalescent sera  Antibodies to rubella are assayed early in pregnancy  Testing for pregnant women is legally mandated in many states

26. Rubella: Treatment, Prevention & Control  No treatment available  Best means of prevention is vaccination  Live-attenuated vaccine usually administered with the mumps and measles vaccines (MMR vaccine)  Vaccine promotes both humoral and cellular immunity

27. Rubella: Treatment, Prevention & Control

28. Summary  Rubella virus  Togavirus  Enveloped icosahedral virus  Usually causes benign illness in children  Congenital Infection is devastating  Is vaccine preventable

30. Thank you for completing this module I hope that I was able to teach the subject clearly. If you have any questions, write to me.

31. References  Murray, Rosenthal & Pfaller. Medical Microbiology, 7 th Ed. 2013. Chapters 53, pages 490 – 494 and Chapter 60, pages 556 – 560.