Parvovirus and Poxvirus

• Parvoviruses


  • Non-enveloped, icosahedral, small (18-26 nm diameter) in size
  • Genome linear ssDNA
  • Proteins one major (VP2) and one minor (VP1)
  • No virion polymerase
  • Virions contain either positive or negative-sense strands
  • Need help from other viruses or rapidly dividing host cells to replicate
  • Human pathogen: Parvovirus B19 has tropism for RBC progenitors

  
• Parvovirus transmission


  Respiratory route (droplets), blood transfusion, vertically from mother to fetus (vertical transmission rate is more than 30%)
• Parvovirus B19 replication


  Highly tropic to human erythroid cells, cellular receptor is blood group P antigen (globoside)
• Childhood exanthems


  • Measles (Rubeola) Morbillivirus
  • Scarlet fever (Streptococcus pyogenes)
  • Rubella (German measles)
  • Atypical scarlet fever Duke Filatow's disease staph
  • Erythema infectiosum
  • Roseola herpesviruses (HHV-6 and HHV-7)

  
• Fifth disease is the only one still called by this name
• Epidemiology of Parvovirus B19

  • Transmission: respiratory or through blood and blood products
  • Seasonal: commonly as outbreaks of erythema infectiosum in schools during winter and spring months
  • Rate of infection: Common, 60% of adults possess serum antibodies

  
• Pathogenesis of Parvovirus B19

  • Infects red blood cell precursors (erythroblasts) in the bone marrow → aplastic anemia
  • Infects endothelial cells in the blood vessels → accounts in part for rash associated with erythema infectiosum
  • Immune complexes (virus & IgM or IgG) deposition → rash & arthritis in some adults infected with B19 virus

  
• Diseases caused by Parvovirus B19

  • Erythema infectiosum (Slapped Check syndrome, Fifth disease)
  • Aplastic anemia (transient aplastic crisis-TAC)
  • Infection in immunodeficient patients (pure red cell aplasia-PRCA)
  • Fetal infection (fetal death, hydrops fetalis)

  
• Symptoms of Fifth Disease

  • Erythema Infectiosum, Polyarthralgia arthritis syndrome
  • Children: Erythema Infectiosum (skin rash)
  • Adults: Polyarthralgia arthritis syndrome (joints)
  • Endothelial cell destruction → rash
  • Immune complex deposition
  • Incubation period is 4-14 days
  • Entry: respiratory tract
  • Spread: one week, viremia is started and persist for about 5 days
  • Shedding is the pharynx and nasal secretion
  • Biphasic illness with symptoms during viremic and immune complex mediated stage

  
• Pure red cell aplasia (PRCA)

  • B19 infection in patients with immunodeficiency diseases
  • Patients unable to eliminate B19 infection, because they cannot produce adequate levels of virus-specific antibodies
  • Results in persistent infection with destruction of erythroid precursor cells in the BM and chronic anemia
  • Cured or controlled by immunoglobulin therapy
• Transient Aplastic Crisis (TAC)


  • Occurs in patients with chronic hemolytic disease
  • The infection lowers the production erythrocytes, causing reduction in the hemoglobin level of peripheral blood
  • Clinically: anemia (pallor, weakness), may need blood transfusion
• Fetal and Congenital Infection


  • Maternal infections pose serious risk to the fetus
  • Infected fetus may be severely affected due to high red blood cell turnover and deficient immune response
  • Infection during 1st trimester: fetal death
  • Infection during 2nd trimester: hydrops fetalis and fetal death due to severe anemia
• Diagnosis of Parvovirus B19


  • Most sensitive tests detect viral DNA in respiratory secretions, serum, and tissue sample (B.M)
  • PCR (most sensitive), probe hybridization
  • Serological assays by detecting B19 IgM antibodies in recent infections (up to 2-3 months)
  • B19 IgG antibodies against VP1 and VP2 persists for years
  • Antigen detection can identify high titer virus in clinical samples
  • Immunohistochemistry can detect B19 antigens in fetal tissue and bone marrow
  • Culture failed to grow in conventional cell culture lines, replicates only in human erythroid progenitor cells

  
• Treatment, Prevention and control of Parvovirus B19

  • No specific treatment, transient aplastic crisis can be treated symptomatically by blood transfusion
  • Commercial immunoglobulin preparations contain neutralizing antibodies given for immunodeficient patients and anemic
  • No vaccine available

  
• Poxviruses


  • Largest and most complex of viruses
  • Infections characterized by a rash, although lesions induced by some members are markedly proliferative
  • Include variola virus, the etiologic agent of smallpox
• Poxviridae


  • Orthopoxvirus (Variola virus, Monkeypox, Cowpox)
  • Molluscum Contagiosum virus (MCV)
• Properties of Poxviruses


  • Largest viruses
  • Enveloped with Complex capsid
  • Double-stranded Linear DNA
  • Replicate in cytoplasm (Encode enzymes necessary for replication: DNA and RNA polymerases)
  • Very resistant to inactivation
  • Virus-encoded proteins help evade host immune defense system

  
• Smallpox was the first viral disease eradicated from the world
• Pathogenesis of Variola virus

  • Infects upper respiratory tract and then spreads to regional lymph-nodes and small blood vessels in the skin
  • After 5 days, skin rashes developed, reaching maximum at 7 days
  • 30% of the infected individuals die from bleeding and cardiovascular collapse
  • Rash started on the face then arms & legs then hands and feet

  
• Immunity against Smallpox


  • An attack of smallpox gave complete protection against reinfection
  • Vaccination with vaccinia induced immunity against variola virus for at least 5 years and sometimes longer
• Laboratory Diagnosis of Smallpox

  • Isolation and Identification of Virus (skin lesions are the specimen of choice)
  • Antibody assays can be used to confirm a diagnosis

  
• Treatment of Smallpox


  Vaccinia immune globulin is prepared from blood from persons vaccinated with the vaccinia virus
• Time of Vaccination


  • Complications of vaccination occur most commonly under the age of 1 year, therefore vaccinating between 1 and 2 years of age is preferable
  • Revaccination has been done at 3-year intervals
• Causes of successful eradication of Smallpox

  • Man is the only host, and there is no animal reservoir of infection
  • There is only one stable serotype of the virus
  • There is no carrier state or subclinical infection
  • Effective vaccine that is highly immunogenic and was used world wide
  • A surveillance-containment program was used by the WHO
  • Smallpox cases are easily recognized clinically, cases were traced and all susceptible contacts were identified and vaccinated
• Monkeypox


  • Can infect both monkey and humans and may resemble smallpox clinically
  • Human infections were discovered in 1970 in Africa after eradication of smallpox from the region
  • Acquired by contact with wild animals killed for food or for their skins
  • Affects all ages but mainly children below 15 years
  • Symptoms are similar to smallpox, but differ in occurrence of lymphadenopathy, lower mortality and transmissibility
  • Complications are common and serious, mainly pulmonary distress and secondary bacterial infections
  • Recently has reemerged on a greater scale than previously seen
  • Antigenically distinct and produces different lesions on the chorioallantoic membrane of chick embryo
  • PCR is used for diagnosis
• Molluscum contagiosum


  • Causes human soft warts (benign skin nodules)
  • Umbilicated papules (Umbilicated cheesy material)
  • Transmitted by close contact and sexually
  • Common in children and immunocompromised persons
  • Virus resembles smallpox in morphology but is not antigenically related
  • Diagnosis is clinical, PCR or electron microscopy may be used
  • Treatment is surgical removal