Parvovirus B19 Parvovirus B19 InfectionsInfections

PathogenesisPathogenesis Autonomous parvoviruses are highly parasitic Autonomous parvoviruses are highly parasitic

because of their molecular simplicity.because of their molecular simplicity.

Parvovirus B19 replicates in mitotically active cells Parvovirus B19 replicates in mitotically active cells and prefers cells of the erythroid lineage.and prefers cells of the erythroid lineage.

The human parvovirus B19 receptor has been The human parvovirus B19 receptor has been identified as globoside, the blood group identified as globoside, the blood group “’“’PP”” antigen. antigen.

Major sites of replication have been assumed to be Major sites of replication have been assumed to be adult marrow and fetal liver (sites of adult marrow and fetal liver (sites of erythropoiesis).erythropoiesis).

The absence of lipid envelope and the The absence of lipid envelope and the small DNA content contribute to the high small DNA content contribute to the high heat stability of parvoviruses.heat stability of parvoviruses.

B19 virus has been transmitted in B19 virus has been transmitted in pasteurized blood products and the virus pasteurized blood products and the virus resists solvent detergent treatment.resists solvent detergent treatment.

The major route of transmission is The major route of transmission is probably the upper airway, but can be probably the upper airway, but can be transmitted by contaminated blood transmitted by contaminated blood products and transplacentally. products and transplacentally.

Spread is by viremia which starts at day 5 Spread is by viremia which starts at day 5 to 6 and peaks at 8 to 9 days. to 6 and peaks at 8 to 9 days.

High titers (10High titers (101414/ml) are reached and virus /ml) are reached and virus is released into oral and respiratory is released into oral and respiratory secretions.secretions.

Viremia is accompanied by nonspecific flu-Viremia is accompanied by nonspecific flu-

like symptoms. like symptoms.

Bone marrow suppression coincides with Bone marrow suppression coincides with viremia. viremia.

The illness is biphasic and the second phase The illness is biphasic and the second phase coincides with antibody production coincides with antibody production

Manifestations are immune- mediated mainly Manifestations are immune- mediated mainly in the form of skin rash, and joint in the form of skin rash, and joint involvement. involvement.

Virus is rarely detected in patients with fifth Virus is rarely detected in patients with fifth disease because the clinical manifestations disease because the clinical manifestations are secondary to immune complex formationare secondary to immune complex formation

Patients present to medical attention after Patients present to medical attention after the period of viremia has passed.the period of viremia has passed.

Consistent pathologic changes have been Consistent pathologic changes have been restricted to hematopietic tissuerestricted to hematopietic tissue

Giant pronormoblasts, depletion of later Giant pronormoblasts, depletion of later erythroid precursor cells and more occasionally erythroid precursor cells and more occasionally dysplastic changes in myeloid and dysplastic changes in myeloid and megakaryocytic cells. megakaryocytic cells.

Protective, long- lasting antibody is produced. Protective, long- lasting antibody is produced.

Cessation of erythropoiesis lasts 5-7 days.Cessation of erythropoiesis lasts 5-7 days.

Cases of ITP and HSP have apparently followed Cases of ITP and HSP have apparently followed acute parvovirus infection. acute parvovirus infection.

Transient Aplastic CrisisTransient Aplastic Crisis An abrupt cessation of red blood cell An abrupt cessation of red blood cell

production in the bone marrow in persons production in the bone marrow in persons with underlying hemolysis.with underlying hemolysis.

It is characterized by reticulocytopenia, It is characterized by reticulocytopenia, absent erythroid precursors in marrow, and absent erythroid precursors in marrow, and precipitous worsening of anemia. precipitous worsening of anemia.

Transient aplastic crisis results when failed Transient aplastic crisis results when failed erythropoiesis is combined with a much erythropoiesis is combined with a much shortened red blood cell life span. shortened red blood cell life span.

Although the illness is self Although the illness is self –– limited, the limited, the patient is acutely ill.patient is acutely ill.

Symptoms may include dyspnea, fatigue, Symptoms may include dyspnea, fatigue, extreme lassitude, confusion, and extreme lassitude, confusion, and congestive heart failure. congestive heart failure.

The crisis can precipitate cerebrovascular The crisis can precipitate cerebrovascular accidents in patients with sickle cell accidents in patients with sickle cell diseasedisease

Death can occur from profound anemia Death can occur from profound anemia and heart failure. and heart failure.

The anemia of TAC is readily treated by The anemia of TAC is readily treated by blood transfusion. It is rarely complicated blood transfusion. It is rarely complicated by bone marrow necrosis.by bone marrow necrosis.

TAC occurs in :TAC occurs in : - Sickle cell disease - Sickle cell disease

- Congenital erythrocyte membrane - Congenital erythrocyte membrane defectsdefects

- Enzymopathies- Enzymopathies

- Thalassemia - Thalassemia

- Acquired hemolytic anemia in adults. - Acquired hemolytic anemia in adults.

- Conditions of erythroid stress: - Conditions of erythroid stress: - hemorrhage and iron deficiency - hemorrhage and iron deficiency - myelofibrosis- myelofibrosis - after bone marrow transplantation. - after bone marrow transplantation.

It may be followed by pancytopenia with It may be followed by pancytopenia with hemophagocytosis.hemophagocytosis.

TAC is often associated with variable TAC is often associated with variable degrees of neutropenia and degrees of neutropenia and thrombocytopenia. thrombocytopenia.

Persistent infectionPersistent infection

Pure red cell aplasia.Pure red cell aplasia.

Failure to mount a neutralizing antibody Failure to mount a neutralizing antibody response to the virusresponse to the virus

No immune complex mediated symptoms No immune complex mediated symptoms of fifth disease; fever, rash, and of fifth disease; fever, rash, and polyarthralgia/ polyarthritis.polyarthralgia/ polyarthritis.

Documented in four patient populations:Documented in four patient populations:

- Congenital immunodeficiency (Nezelof- Congenital immunodeficiency (Nezelof ’’’’s s Syndrome)Syndrome)

- Children with lymphoblastic leukemia and - Children with lymphoblastic leukemia and

other malignancies in remission after or other malignancies in remission after or during chemotherapyduring chemotherapy

- patients with AIDS- patients with AIDS

- Recipients of solid organ transplants.- Recipients of solid organ transplants.

Clinically, the anemia is severe, and the Clinically, the anemia is severe, and the patient becomes dependent on patient becomes dependent on transfusions. transfusions.

There may be intermittent neutropenia.There may be intermittent neutropenia.

The bone marrow contains giant The bone marrow contains giant pronormoblasts.pronormoblasts.

The anemia may be intermittent, with The anemia may be intermittent, with periods of relapse and remissionperiods of relapse and remission

DiagnosisDiagnosis Virus IsolationVirus Isolation Human erythroid progenitors remain the most Human erythroid progenitors remain the most

convenient productive tissue culture system.convenient productive tissue culture system. Bone marrow, peripheral blood, fetal liver, and Bone marrow, peripheral blood, fetal liver, and

a few leukemic cells or cell lines have been a few leukemic cells or cell lines have been used to reproduce virus.used to reproduce virus.

SerologySerology IgM and IgG. IgM and IgG.

PCR PCR most specific most specific