Parvoviruses are the smallest DNA viruses, including human parvovirus B19. B19 is pathogenic in humans, infecting erythroid progenitor cells and causing fifth disease in children characterized by a rash. It can also cause aplastic crisis, hydrops fetalis in fetuses, and chronic anemia in immunocompromised patients. Diagnosis involves detecting IgG and IgM antibodies by ELISA or PCR to detect the virus. There is no treatment, though a vaccine is in clinical trials.

1. Parvoviruses
A Presentation By
G. Prashanth Kumar
Department of Microbiology & Parasitology,
International Medical & Technological University,
Dar-Es-Salaam, Tanzania.

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.

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.

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.

5. Human infections caused by B19 virus

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.

7. Viral replication
• B 19 virus shows tropism for (a) bone marrow cells, (b)
erythroid cells from fetal liver, and (c) erythroid
leukemia cells.
• Replication of virus occurs in the nucleus.
• The single- stranded DNA genome has hairpin loops at
both of its ends which facilitate double-stranded areas
for the cellular DNA polymerase to start synthesis of
the progeny genomes.
• The cellular RNA polymerase synthesizes viral mRNA
from the double-stranded DNA intermediate.
• This is followed by assembly of virions in the nucleus.
• Viral replication results in the cell death.

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.

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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. Gloves and sock syndrome

18. 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.

19. 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.

20. 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.

21. Epidemiology
• The infected patient is contagious from 24 to 48 hours
before developing prodromal syndrome till the
appearance of rash.
• The infection is transmitted by
• (a) vertical transmission during birth,
• (b) respiratory route through respiratory secretions,
• (c) percutaneous exposure to blood and transfusion of
blood and blood products (pooled RBCs, platelets,
intravenous immunoglobulins, etc.).

22. 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.

23. 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.