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Parvoviruses
By,
Maneesha M Joseph
Assistant Professor
Baby Memorial College
Kozhikode
Video Class uploaded in YouTube Channel “Mallu Medicos Lounge”
Maneesha M Joseph 1
INTRODUCTION
• Parvoviruses are the smallest of the DNA viruses
belonging to the family Parvoviridae.
• They are icosahedral, nonenveloped viruses containing a
single-stranded DNA.
• Human parvovirus B 19 (B 19) is the only known
parvovirus that is pathogenic for humans, and it shows
tropism for erythroid progenitor cells.
• History: In 1974, Cossart et al. first identified B19 while
evaluating tests for hepatitis B virus surface antigen. The
name originates from the coding of a serum sample,
number 19 in panel B, that gave anomalous results when
tested by counterimmunoelectrophoresis and
radioimmunoassay.
Maneesha M Joseph 2
Classification
• The family Parvoviridae consists of three genera:
• Dependo-virus, Parvovirus, and Erythrovirus.
• The genus Dependovirus consists of poxviruses which are
defective and replicate only in association with a second
helper virus.
• They neither cause illness by themselves nor alter the
infection caused by helper viruses.
• These are usually found in association with an adenovirus,
hence are known as adeno-associated viruses.
• These viruses do not cause any disease in humans.
• The genus Parvovirus includes the viruses which include
animal viruses of veterinary importance such as feline
panleukopenia virus and canine parvovirus.
• The genus Erythrovirus consists of B 19, the only member
of the Parvoviridae family known to cause disease in
humans.
Maneesha M Joseph 3
PARVOVIRUS B19
• Parvovirus B19, or B19 virus, is the causative agent of
erythema infectiosum ('fifth disease'-it was fifth of the
six classified exanthematous diseases of childhood), a
mild viral illness of children, and polyarthralgia-arthritis
syndrome in immunocompetent adults.
Maneesha M Joseph 4
Human infections caused by B19 virus
Maneesha M Joseph 5
Morphology
• B 19 viruses are extremely small
viruses, measuring 18-26 nm in
diameter.
• They possess a nonenveloped,
icosahedral capsid.
• The viral genome contains a single-
stranded DNA measuring 4000-6000
bases in length.
• The genome is negative-strand DNA.
• The genome encodes for many
proteins which include three
structural, one major nonstructural,
and several smaller proteins.Maneesha M Joseph 6
Epidemiology
• Geographical distribution
• B 19 virus is distributed worldwide.
• The exact data on sero-positivity in population world
over is not known.
• Approximately, 90% of adults older than 60 years are
seropositive in the United States.
• Similar data from other parts of the world are lacking.
• Reseruoir, source, and transmission of infection
• B 19 virus infection is strictly a human disease.
• Humans are the only reservoir of infections. Viruses are
excreted in respiratory samples which are the primary
source of infection. Maneesha M Joseph 7
Antigenic properties
• Only one serotype of B 19 virus is known to occur.
Other properties
• B 19 virus is highly resistant to inactivation but can be
inactivated by formalin, beta propiolactone, and
oxidizing agents.
• The viruses withstand heating at 56°C for 30 minutes
and are stable between pH 3 and 9.
Maneesha M Joseph 8
Pathogenesis and Immunity
• B 19 virus shows a tropism for two types of cells:
• (a) red blood cell (RBC) precursors and
• (b) endothelial cells in the blood vessels.
• The virus infects rapidly dividing erythrocyte precursors
such as bone marrow cells, erythroid cells from fetal liver,
and erythroid leukemia cells and destroys these cells after
infection, thereby causing aplastic anemia.
• Infection of the endothelial cells in the blood vessels leads
to erythema infectiosum.
• It has been demonstrated that the B19 virus first enters
through the nasopharynx or upper respiratory tract and
then spreads to the blood, causing viremia.
• The virus then infects mitotically active erythroid precursor
cells in bone marrow and establishes the infection.
Maneesha M Joseph 9
Pathogenesis and Immunity
• The virus enters susceptible cells through the P blood
antigen receptors on the erythrocyte precursors.
• Inside the red cells the virus enters the nucleus, starts
replicating, followed by killing of the red cells.
• The production of RBCs is stopped for approximately 1
week due to killing of the erythroid precursor cells by
the viruses.
• The initial stage is associated with flu-like illness caused
by large viremia.
• The viruses are shed in the oral and respiratory
secretions and even cross the placenta.
• Subsequently, viremia is controlled by the production
of specific antibodies against B 19 virus.Maneesha M Joseph 10
Pathogenesis and Immunity
• The rash and arthralgia present the second stage of the
disease, and is believed to be immunologically mediated.
• This stage coincides with the disappearance of B 19 virus from
the circulation, appearance of B19 virus-specific IgM and IgG
antibodies, and finally the formation of immune complexes.
Host immunity
• “The disease exhibits two stages: initial stage is flu-like
illness and second stage is appearance of rash and
arthralgia.
• Host immunity to B 19 virus infection is primarily antibody
mediated.
• The circulating antibodies stop the viremia and are
important for resolution of the disease.
• The role of cell-mediated immunity in conferring immunity to B
19 virus is unknown.
Maneesha M Joseph 11
Clinical Syndromes
• B19 virus causes following clinical syndromes:
• (a) Flu like illness, (b) erythema infectiosum or fifth disease,
(c) infection in pregnant women, and (d) chronic B 19
infection.
Flu-like illness
• B 19 virus most commonly causes a flu-like illness.
• Malaise, headache, myalgia, and rhinorrhea are the
common symptoms.
Erythema infectiosum or fifth disease
• B 19 virus is an additional causative agent of erythema
infectiosum or fifth disease, the condition seen most
commonly in children.
• The infection begins with nonspecific symptoms, followed
by appearance of a distinctive rash on 5th day of infection.Maneesha M Joseph 12
Clinical Syndromes
• A bright red rash develops
on both cheeks that
appear as they have been
slapped.
• The rash then appears on
the trunk, which spreads
gradually toward the arms
and legs.
• The condition usually
subsides within 1-2 weeks.
Maneesha M Joseph 13
Clinical Syndromes
Aplastic anemia
• Transient but severe aplastic anemia
can occur in children with chronic
anemia such as sickle cell anemia,
thalassemia, and spherocytosis
(aplastic crisis) after infection with B
19 virus. Gloves and sock syndrome
is another serious complication
caused by B19 virus.
• In this syndrome, erythematous
exanthema appears on the hands
and feet, with a well-defined margin
on the wrist and ankle joints.
Maneesha M Joseph 14
Gloves and sock syndrome
Maneesha M Joseph 15
Clinical Syndromes
Infection in pregnant women
• If the B 19 virus causes reinfection in a pregnant mother
who is infected earlier by the same virus, and is already
immune to the virus (showing positive B19 antibodies),
then no adverse effects are seen in the fetus.
• In non immune seronegative pregnant mothers, B19 virus
infection is increasingly associated with risk for fetal death.
• The infection may cause severe anemia in the fetus, and
subsequently, the fetus may develop signs of high-output
cardiac failure (hydrops fetalis).
• B19 virus, however, does not cause any congenital
anomalies in the fetus.
Maneesha M Joseph 16
Clinical Syndromes
Chronic B19 infection
• This infection occurs in immunocompromised
patients such as patients with HIV, those receiving
immunosuppressive therapy, and transplant patients.
• Chronic anemia, leukopenia, and thrombocytopenia
are the common manifestations.
Maneesha M Joseph 17
Laboratory Diagnosis
• Demonstration of specific IgG and IgM antibodies in the
serum is useful for diagnosis of erythema infectiosum
caused by B19 virus.
• ELISA (enzyme-linked immunosorbent assay), RIA
(radioimmunoassay), and IFA (indirect fluorescent
antibody) for demonstration of IgG and IgM antibodies are
available.
• In pregnant women, the serum positive for IgG and IgM
antibodies indicates B19 virus infection within 7 days to 4
months, and a possible risk to fetus.
• Positive IgG but negative IgM result indicates only past
infection, hence no risk to fetus.
• Furthermore, polymerase chain reation (PCR) is available to
demonstrate B19 virus genome in the blood.
• The positive result suggests viremia or infection.Maneesha M Joseph 18
Treatment
• No specific antiviral therapy is available for treatment
of B 19 virus infection.
Prevention and Control
• No specific measures are available for prevention of
the infection.
• Development of a vaccine against B 19 virus is
undergoing phase I clinical trial.
Maneesha M Joseph 19
Maneesha M Joseph 20

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Parvovirus

  • 1. Parvoviruses By, Maneesha M Joseph Assistant Professor Baby Memorial College Kozhikode Video Class uploaded in YouTube Channel “Mallu Medicos Lounge” Maneesha M Joseph 1
  • 2. INTRODUCTION • Parvoviruses are the smallest of the DNA viruses belonging to the family Parvoviridae. • They are icosahedral, nonenveloped viruses containing a single-stranded DNA. • Human parvovirus B 19 (B 19) is the only known parvovirus that is pathogenic for humans, and it shows tropism for erythroid progenitor cells. • History: In 1974, Cossart et al. first identified B19 while evaluating tests for hepatitis B virus surface antigen. The name originates from the coding of a serum sample, number 19 in panel B, that gave anomalous results when tested by counterimmunoelectrophoresis and radioimmunoassay. Maneesha M Joseph 2
  • 3. Classification • The family Parvoviridae consists of three genera: • Dependo-virus, Parvovirus, and Erythrovirus. • The genus Dependovirus consists of poxviruses which are defective and replicate only in association with a second helper virus. • They neither cause illness by themselves nor alter the infection caused by helper viruses. • These are usually found in association with an adenovirus, hence are known as adeno-associated viruses. • These viruses do not cause any disease in humans. • The genus Parvovirus includes the viruses which include animal viruses of veterinary importance such as feline panleukopenia virus and canine parvovirus. • The genus Erythrovirus consists of B 19, the only member of the Parvoviridae family known to cause disease in humans. Maneesha M Joseph 3
  • 4. PARVOVIRUS B19 • Parvovirus B19, or B19 virus, is the causative agent of erythema infectiosum ('fifth disease'-it was fifth of the six classified exanthematous diseases of childhood), a mild viral illness of children, and polyarthralgia-arthritis syndrome in immunocompetent adults. Maneesha M Joseph 4
  • 5. Human infections caused by B19 virus Maneesha M Joseph 5
  • 6. Morphology • B 19 viruses are extremely small viruses, measuring 18-26 nm in diameter. • They possess a nonenveloped, icosahedral capsid. • The viral genome contains a single- stranded DNA measuring 4000-6000 bases in length. • The genome is negative-strand DNA. • The genome encodes for many proteins which include three structural, one major nonstructural, and several smaller proteins.Maneesha M Joseph 6
  • 7. Epidemiology • Geographical distribution • B 19 virus is distributed worldwide. • The exact data on sero-positivity in population world over is not known. • Approximately, 90% of adults older than 60 years are seropositive in the United States. • Similar data from other parts of the world are lacking. • Reseruoir, source, and transmission of infection • B 19 virus infection is strictly a human disease. • Humans are the only reservoir of infections. Viruses are excreted in respiratory samples which are the primary source of infection. Maneesha M Joseph 7
  • 8. Antigenic properties • Only one serotype of B 19 virus is known to occur. Other properties • B 19 virus is highly resistant to inactivation but can be inactivated by formalin, beta propiolactone, and oxidizing agents. • The viruses withstand heating at 56°C for 30 minutes and are stable between pH 3 and 9. Maneesha M Joseph 8
  • 9. Pathogenesis and Immunity • B 19 virus shows a tropism for two types of cells: • (a) red blood cell (RBC) precursors and • (b) endothelial cells in the blood vessels. • The virus infects rapidly dividing erythrocyte precursors such as bone marrow cells, erythroid cells from fetal liver, and erythroid leukemia cells and destroys these cells after infection, thereby causing aplastic anemia. • Infection of the endothelial cells in the blood vessels leads to erythema infectiosum. • It has been demonstrated that the B19 virus first enters through the nasopharynx or upper respiratory tract and then spreads to the blood, causing viremia. • The virus then infects mitotically active erythroid precursor cells in bone marrow and establishes the infection. Maneesha M Joseph 9
  • 10. Pathogenesis and Immunity • The virus enters susceptible cells through the P blood antigen receptors on the erythrocyte precursors. • Inside the red cells the virus enters the nucleus, starts replicating, followed by killing of the red cells. • The production of RBCs is stopped for approximately 1 week due to killing of the erythroid precursor cells by the viruses. • The initial stage is associated with flu-like illness caused by large viremia. • The viruses are shed in the oral and respiratory secretions and even cross the placenta. • Subsequently, viremia is controlled by the production of specific antibodies against B 19 virus.Maneesha M Joseph 10
  • 11. Pathogenesis and Immunity • The rash and arthralgia present the second stage of the disease, and is believed to be immunologically mediated. • This stage coincides with the disappearance of B 19 virus from the circulation, appearance of B19 virus-specific IgM and IgG antibodies, and finally the formation of immune complexes. Host immunity • “The disease exhibits two stages: initial stage is flu-like illness and second stage is appearance of rash and arthralgia. • Host immunity to B 19 virus infection is primarily antibody mediated. • The circulating antibodies stop the viremia and are important for resolution of the disease. • The role of cell-mediated immunity in conferring immunity to B 19 virus is unknown. Maneesha M Joseph 11
  • 12. Clinical Syndromes • B19 virus causes following clinical syndromes: • (a) Flu like illness, (b) erythema infectiosum or fifth disease, (c) infection in pregnant women, and (d) chronic B 19 infection. Flu-like illness • B 19 virus most commonly causes a flu-like illness. • Malaise, headache, myalgia, and rhinorrhea are the common symptoms. Erythema infectiosum or fifth disease • B 19 virus is an additional causative agent of erythema infectiosum or fifth disease, the condition seen most commonly in children. • The infection begins with nonspecific symptoms, followed by appearance of a distinctive rash on 5th day of infection.Maneesha M Joseph 12
  • 13. Clinical Syndromes • A bright red rash develops on both cheeks that appear as they have been slapped. • The rash then appears on the trunk, which spreads gradually toward the arms and legs. • The condition usually subsides within 1-2 weeks. Maneesha M Joseph 13
  • 14. Clinical Syndromes Aplastic anemia • Transient but severe aplastic anemia can occur in children with chronic anemia such as sickle cell anemia, thalassemia, and spherocytosis (aplastic crisis) after infection with B 19 virus. Gloves and sock syndrome is another serious complication caused by B19 virus. • In this syndrome, erythematous exanthema appears on the hands and feet, with a well-defined margin on the wrist and ankle joints. Maneesha M Joseph 14
  • 15. Gloves and sock syndrome Maneesha M Joseph 15
  • 16. Clinical Syndromes Infection in pregnant women • If the B 19 virus causes reinfection in a pregnant mother who is infected earlier by the same virus, and is already immune to the virus (showing positive B19 antibodies), then no adverse effects are seen in the fetus. • In non immune seronegative pregnant mothers, B19 virus infection is increasingly associated with risk for fetal death. • The infection may cause severe anemia in the fetus, and subsequently, the fetus may develop signs of high-output cardiac failure (hydrops fetalis). • B19 virus, however, does not cause any congenital anomalies in the fetus. Maneesha M Joseph 16
  • 17. Clinical Syndromes Chronic B19 infection • This infection occurs in immunocompromised patients such as patients with HIV, those receiving immunosuppressive therapy, and transplant patients. • Chronic anemia, leukopenia, and thrombocytopenia are the common manifestations. Maneesha M Joseph 17
  • 18. Laboratory Diagnosis • Demonstration of specific IgG and IgM antibodies in the serum is useful for diagnosis of erythema infectiosum caused by B19 virus. • ELISA (enzyme-linked immunosorbent assay), RIA (radioimmunoassay), and IFA (indirect fluorescent antibody) for demonstration of IgG and IgM antibodies are available. • In pregnant women, the serum positive for IgG and IgM antibodies indicates B19 virus infection within 7 days to 4 months, and a possible risk to fetus. • Positive IgG but negative IgM result indicates only past infection, hence no risk to fetus. • Furthermore, polymerase chain reation (PCR) is available to demonstrate B19 virus genome in the blood. • The positive result suggests viremia or infection.Maneesha M Joseph 18
  • 19. Treatment • No specific antiviral therapy is available for treatment of B 19 virus infection. Prevention and Control • No specific measures are available for prevention of the infection. • Development of a vaccine against B 19 virus is undergoing phase I clinical trial. Maneesha M Joseph 19