A negatively stained preparation of parvovirus seen by transmission electron microscope. www.wadsworth.org

Properties of Parvoviruses Structure Icosahedral 18-26 nm diameter Single-stranded DNA, 5.6 kb Two proteins Nonenveloped

Human parvoviruses B19 Bocavirus Adeno-associated viruses (AAVs) can cause acute respiratory disease, which may become severe in young children Adeno-associated viruses (AAVs) infect humans replicate with a second “helper” virus, usually an adenovirus

B19 Replication in human cells restricted to erythroid progenitor cells Adult bone marrow Fetal liver Transmission by close contact Airborne droplets 50% of a household may become infected 10-60% of students in school outbreaks

Virologic, immunologic, and clinical course following B19 infection. Virologic, immunologic, and clinical course following B19 infection. Data from references 8 and 254. Heegaard E D , and Brown K E Clin. Microbiol. Rev. 2002;15:485-505

Parvovirus B-19 Infections in Humans Diseases Fifth disease (cutaneous rash) Transient aplastic crisis (severe acute anemia) Pure red cell aplasia (chronic anemia) Hydrops fetalis (fatal fetal anemia) Fifth Disease (parvovirus B19)

Fifth Disease Six separate childhood exanthems were defined from what was once called the “measles” (Early 20th Century) 1st Measles (rubeola) Morbillivirus 2nd Scarlet fever (Streptococcus pyogenes ) 3rd Rubella (German measles) 4th Atypical scarlet fever Duke Filatow's disease staph 5th Erythema infectiosum 6th Roseola herpesviruses (HHV-6 and HHV-7) Exanthem = rash Fifth disease is the only one still called by this name

Symptoms – Fifth Disease Incubation 7-10 days Lasts 5-7 days Three Phases First phase –peak level of virus and RBC destruction Fever Malaise Chills Bright red, raised “slap cheek” rash

Symptoms – Fifth Disease Second phase – rash and arthralgia Virus has disappeared – no longer infectious Caused by immune complexes in the capillaries of the skin Appears at presence of parvovirus IgM Erythematous maculopapular rash on arms and trunk Fades into a lace-like reticular pattern Third phase Frequent clearing and recurrences for weeks Due to stimuli such as exercise, irritation, or overheating of skin from bathing or sunlight.

Erythema infectiosum “Slap cheek” rash on the face, lacy rash on the extremities.

Parvovirus Infections in Humans Transient aplastic crisis (TAC) B19 infection of those with other hemolytic anemias Sickle cell disease Thalassemias Can complicate crises Sometimes fatal

Symptoms – Aplastic Crisis Anemic patients Pallor, fatigue, drop in hemoglobin >1g/dL Destroys infected red blood cells No reticulocytes to replace aging or damaged erythrocytes This normally happens in disease but is symptomatic in anemic patients Thrombocytopenic patients Bruising Typical giant proerythroblast (arrow) seen in parvovirus B19-associated pure red cell aplasia with highly uncondensed chromatin and pale purple intranuclear inclusions. Bone marrow aspirate.

Parvovirus Infections in Humans Pure Red Cell Anemia (PRCA) Can cause persistent infection in bone marrow Suppress red cell maturation Leads to anemia Hydrops Fetalis: Infection during pregnancy Can cause fetal anemia Usually not fatal to fetus

Laboratory Diagnosis PCR is most sensitive Most useful during viremia Otherwise, requires tissue biopsy or bone marrow tap Serological testing for IgM Determines recent infection IgG testing is not informative