Tari et al.

, Int J Med Lab Res 2016, 1(2): 48-54

ISSN 2456-4400

REVIEW ARTICLE INTERNATIONAL JOURNAL OF MEDICAL LABORATORY RESEARCH

PARVOVIRUS B19 INFECTION AND TRANSIENT APLASTIC CRISIS

Kaveh Tari 1, Amir Atashi1*, Hamid Reza Ghafari2,Mohammad Shahjahani1.

1
Department of Hematology, Faculty of Medical Sciences, TarbiatModares University, Tehran, Iran
2
Department of Hematology, Faculty of Medical, Bushehr University of Medical Sciences, Bushehr, Iran.
Received:14 Nov, 2016/Accepted:30 Nov, 2016
ABSTRACT: Parvovirus B19, also called erythrovirus, is a small DNA virus of parvoviridae family. It
causes diseases such as erythematous infection or fifth disease, transient aplastic crisis, pure red cell
aplasia, hydrops fetalis and fetal death. Disease symptoms are mainly observed in children and not in
adults; however, the symptoms also appear in adults with immune deficiency. Respiratory secretions,
blood and plasma derived products are the major transmission routes of Parvovirus B19.Serological
methods, measurement of IgG and IgM against Parvovirus B19 as well as histopathological and
immunohistochemical approaches are diagnostic methods of Parvovirus B19. In newborns, PCR as well
as DNA and RNA analysis in amniotic fluid or umbilical cord blood are used for diagnosis of Parvovirus
B19infection. In this review article, we reviewed the main concept of the parvovirus b19 and its disease,
fifth disease, and sympthoms, finally we have discussion about its diagnosis.
KEYWORDS: Parvovirus B19, Fifth Disease, Diagnosis

INTRODUCTION:

Humanparvovirus B19 (HPV - B19)is a small crisis induced by it in10%of cases in children
virus that was discovered in 1975. Thestructure under10 years,70% in children 5-15 years and
of this virus, which belongs to Parvoviridae 20% in people over15 years3. Parvovirus B19 is
family,consists of asingle stranded DNA prevalent around the world, and
surrounded by capsid. It is a human pathogen serorpidemiological studies have shown that 40-
capable of causing a range of clinical symptoms 60% of population in the worldbear specific IgG
fromself-limited infectious erythema in children antibody against B19virus, including IgG
with intact immune system to lethal cytopeniain againstVP1 capsid, which is the most common
patients with immunodeficiency and intrauterine antibody4.The main transmission routes ofthis
fetal death in pregnant women infected with virus includerespiration,blood products and
HIV.The virus canalsobe established and cause transmissionfrom mother to child5.
autoimmuneinflammatory disorder 1, 2. Infection
bythisvirusis mainlyseeninlatewinter and early
spring,and is observed duringthe

*Corresponding Author:
Department of Hematology, Faculty of Medical Sciences, Tarbiat Modarres University,
Tehran, Iran P.O.Box: 14115-331
incidence of erythematous infection oraplastic

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TRANSMISSION OF VIRUS BY BLOOD

AND BLOOD PRODUCTS:

As noted, blood, its products and respiratory concerning the prevalence of antibodies against
secretions are the major transmission routes of B19 among blood donors around the world.The
B19. Factors such asthe level of B19 virus prevalence of this virus among volunteer blood
antigen or Anti B19 IgG in blood products as donors has been reported 39.9% in India4, 60%
well as immune status of patients are involved in inGreat Britain8,16.2% in Singapore9 and 32.8%
virus transmission by blood product6. The in Taiwan10.The most sensitive people at risk of
virusis also transmitted by plasma and plasma- Parvovirus B19 infection include
derived products.Virus inactivation techniques multitransfusion recipients particularly
like the use of organic solvents and detergents, thalassemia major patients. In the study
filters and filtration methods as well as liquid- ofJanaket al on thalassemia major patients
heat treatment are not effective upon this virus7. receiving blood,ahigh prevalence ofanti B19 IgG
With regard to transmission of B19 Parvovirus (81%)andanti B19 IgM (41%)was reported11.
through blood and blood products,several
studies have been conducted

HEMATOLOGICAL COMPLICATIONS:
2
Transientaplasia of RBC progenitors is one of patients with accelerated blood cell destruction
themost important hematological complications in whom Parvovirus B19 infection can lead to
of Parvovirus B19.This virus directlyaffects aplasticcrisis15. Sickle cell anemia in adults and
hematopoiesis (especially erythropoiesis) and pregnant women is among the diseases
results in anemia12, 13 In fact, infection with associated with transient aplastic crisis in case of
Parvovirus B19 can lead to erythroblastopenia infection with Parvovirus B19, which is
and reticulocytopeniain healthy people but does associated with reticulocytopenia, mild
not cause anemia because ofthe long lifespan neutropenia in some cases thrombocytopenia 16-
19
ofred blood cells. However, in patients with . Anemia due to membrane defects such as
hemolytic anemia, it can decrease hemoglobin elliptocytosis, erythrocyte enzyme deficiencies,
concentration and life spanof red blood cells, thalassemia and acquired hemolytic diseases are
which ultimately exacerbates anemiaand is other diseases associated with transient aplastic
known as transient aplastic crisis14. Transient crisis by Parvovirus B19 20, 21. Chronic cases of
aplastic crisis, in fact, refers to sudden self- aplastic crisis can be seen in patients with
limiting cease of erythropoies is characterized primary and secondary membrane
by reticulocytopenia, which leads to aggravation deficiencywho are not capable of producing
of anemia5. Two main groups of patients are at neutralizing antibodies against Parvovirus B19
risk of severe and even life-threatening anemia: 1 22, 23
.
fetus that can contract anemia and myocarditis
through infection transmission via placenta,
which can lead tohydrops fetalisand fetal death;

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PARVOVIRUS B19 INFECTION IN

CHILDREN:
children with thalassemia major was
Infection with Parvovirus B19, which is a virus reported 41% and 81%, respectively11.
specific to RBC precursors, is seen in children Furthermore, a high prevalence of this infection
around the world. Acute infection with his virus has been reported in children with leukemia and
can lead to cease of erythropoiesis for 5-7 days lymphoma undergoing chemotherapy. Children
as well as increased apoptosis of RBC, which with leukemia and lymphoma under
can eventually lead to reduced hemoglobin chemotherapy have been recommended to be
concentration for 1-2 weeks 24. Studies have screened for Parvovirus B19 infection before
shown that the prevalence of infection with changing the chemotherapy protocol in case of
Parvovirus is higher in children with blood developing anemia 26. In addition, Jitschin et al
disorders, which can lead to anemia 25. In one showed that the prevalence of Parvovirus B19
study, the prevalence of IgM and infection in healthy children, children with
IgG antibodies against Parvovirus B19 in benign hematologic malignancy and children
with malignant lymphoma was43.6%, 38.5%
and 52%, respectively 27.

PARVOVIRUS INFECTION IN
PREGNANT WOMEN:
approximately 65% of women in North America
Parvovirus B19 is potentially dangerous for the show evidence of previous infection with B19,
fetus during pregnancy because it can infect and about 1-2% have acute B19 viral infection,
embryonic erythroid precursor cells and tissues. which may reach up to 10%. Infection in
It has broad complications in the fetus, including pregnant women with a sound immune system is
transient embryonic anemia, non-immune usually without symptoms 1. Moreover, in 30%
hydrops fetalis and abortion (intrauterine death). of pregnant women, the infection manifests as
In addition, symptoms such as myocarditis, poly-arthralgia, 30-90% with skin rashes
endothelial lesions, fetal brain damage, especially on face and 30-50% have no
thrombocytopenia secondary to B19 infection, symptoms 30, 31.
chronic anemia and congenital heart disease may
be seen 28, 29. Studies have indicated that

FIFTH DISEASE:

As noted, varied clinical symptoms from no sign The rashes appearing on the skin of these
to severe infections can be seen in patients 32. In children can be transient or appear with higher
children, infection with this virus manifests as intensity, depending on other factors, including
erythematous infection or fifth disease, which is environmental factors such as exposure to
also referred to as slapcheek 33, 34. sunlight 35.

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ARTHROPATHY:

Less than 10% of children infected with virus 36. In adults, arthralgia and arthritis are the
erythematous infection show arthralgia. In most common manifestations of primary B19
addition, 19% of children who develop arthritis infection while skin symptoms are less common
16, 37, 38
show evidence of recent infection with B19 .

PARVOVIRUS INFECTION AND

SYSTEMIC LUPUS ERYTHEMATOSUS:
exacerbate the disease conditions. B19 virus
Parvovirus B19 infection is associated with infection in children can show similar clinical
various types of rheumatoid diseases, including symptoms with SLE, including symptoms such
rheumatoid arthritis, systemic lupus as red rash, fatigue and arthritis 31. Studies have
erythematosus and vasculitis. B19 infection may also indicated that infection with B19 in both
showclinical and laboratory signs of SLE, which adults and children is similar with SLE in terms
can be helpful in early diagnosis of SLE and can of signs and serological results. Therefore, B19
infection may predispose the patient to lupus 39.

PARVOVIRUS B19 DIAGNOSIS:

Parvovirus B19 cannot replicate in culture normoblasts can indicate B19 infection.
systems. Therefore, viral capsid is isolated from Visualizing the virus under electron microscope,
patients bearing high titers of virus in serum and ELISA for detection of B19 antigen and even
is used for antibody tests. In addition, since the hemagglutination are among the methods to
virus is difficult to grow and cannot be cultured, diagnose infection as well as PCR and
it is diagnosed using several approaches hybridization to detect viral DNA. Hybridization
including serological tests and PCR as well as is a proper approach to detect B19 in transient
immunohistochemistry and histopathological plastic crisis and pure red cell aplasia due to B19
methods 40. B19 infection in pregnant women infection. Patients with low viremia usually
and in people with immune deficiency is remain undiagnosed. PCR has a higher
diagnosed using molecular methods. sensitivity than hybridization and detects the
Furthermore, neonatal infection diagnosis is cases with low viremia but there is likelihood of
based on PCR and detection of viral DNA in contamination during PCR for the technician.
amniotic fluid or umbilical cord blood 41, 42. Detection of anti B-19 IgM indicates recent
Overall, we can mention different diagnostic infection in patients with a sound immune
procedures depending on their complications. system.Nearly 85% of patients with
For example, in conditions that cause transient erythematous infection or aplastic crisis caused
aplastic crisis, presence of large and giant by B19 bear IgM antibody that is detectable for
2-3 months.

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REFERENCES:

1. Broliden K, Tolfvenstam T, Norbeck O. Epidemiology and infection.

Clinical aspects of parvovirus B19 1994;113(03):537-40.
infection. Journal of internal medicine.
2006;260(4):285-304. 10. Poovorawan Y, Theamboonlers A,
Suandork P, Hirsch P. Prevalence of
2. Parsyan A, Candotti D. Human antibodies to parvovirus B 19in
erythrovirus B19 and blood transfusion– Thailand. Southeast Asian J Trop Med
an update. Transfusion Medicine. Public Health. 2000;31:422-4.
2007;17(4):26.78-3
11. Kishore J, Srivastava M, Choudhury N.
3. ANDERSON LJ. Role of parvovirus Serological study on parvovirus B19
B19 in human disease. The Pediatric infection in multitransfused thalassemia
infectious disease journal. major patients and its transmission
1987;6(8):711-8. through donor units. Asianjournal of
transfusion science. 2011;5(2):140.
4. Kishore J, Srivastava M, Choudhary N.
Standardization of B19 IgG ELISA to 12. Yetgin S, Elmas SA. Parvovirus-B19
study the seroepidemiology of and hematologic disorders. Turk J
parvovirus B19 in North Indian Hematol. 2010;27(4):224-33.
voluntary blood donors. Asian journal of
transfusion science. 2010;4(2):86. 13. Pattison J, Jones S, Hodgson J, Davis L,
White J, Stroud C, et al. Parvovirus
5. Heegaard ED, Brown KE. Human infections and hypoplastic crisis in
parvovirus B19. Clinical microbiology sickle-cell anaemia. The Lancet.
reviews. 2002;15(3):485-505. 1981;317(8221):664-5.

6. Tsukada Y, Yokoyama K, Ishida A, 14. Cauff BE, Quinn CT. Transient

Handa M, Mori T, Kizaki M, et al. parvovirus‐ associated hypoplasia of
Erythroid crisis caused by parvovirus multiple peripheral blood cell lines in
B19 transmitted via red blood cell children with chronic hemolytic anemia.
transfusion. Internal Medicine. Pediatric blood & cancer.
2011;50(20):2379-82. 2008;50(4):8.4-61

7. Slavov SN, Kashima S, Pinto ACS, 15. Juhl D, Görg S, Hennig H. Persistence
Covas DT. Human parvovirus B19: of Parvovirus B19 (B19V) DNA and
general considerations and impact on humoral immune response in
patients with sickle‐ cell disease and B19V‐ infected blood donors. Vox
thalassemia and on blood transfusions. sanguinis. 2014;107(3):226-32.
FEMS Immunology & Medical
Microbiology. 2011;62(3):247-62. 16. Cossart Y, Cant B, Field A, Widdows D.
Parvovirus-like particles in human sera .
8. Cohen B, Buckley MM. The prevalence The Lancet. 1975;305(7898):72-3.
of antibody to human parvovirus B 19 in
England and Wales. Journal of Medical 17. Cohen B, Beard S, Knowles W, Ellis J,
Microbiology. 1988;25(2):151-3. Joske D, Goldman J, et al. Chronic
anemia due to parvovirus B19 infection
9. Matsunaga Y, Goh K, Utagawa E, in a bone marrow transplant patient after
Muroi N. Low prevalence of antibody to platelet transfusion. Transfusion.
human parvovirus B19 in Singapore. 1997;37(9):947-52.

ww.ijmlr.com/IJMLR© All right are reserved

52
 Tari et al., Int J Med Lab Res 2016, 1(2): 48-54
ISSN 2456-4400

18. Azzi A ,Macchia P, Favre C, Nardi M, hematological disorders. The Egyptian

Zakrzewska K, Corsi OB. Aplastic crisis Journal of Haematology.
caused by B19 virus in a child during 2013;38(3):115.
induction therapy for acute
lymphoblastic leukemia. 26. Kishore J, Sen M, Kumar A, Kumar A.
Haematologica. 1988;74(2):191-4. A pilot study on parvovirus B19
infection in paediatric haematological
19. Yates AM, Hankins JS, Mortier NA, malignancies. The Indian journal of
Aygun B, Ware RE. Simultaneous acute medical research. 2011;133(4):407.
splenic sequestration and transient
aplastic crisis in children with sickle cell 27. Jitschin R, Peters O, Plentz A, Turowski
disease. Pediatric blood & cancer. P, Segerer H, Modrow S. Impact of
2009;53(3):479-81. parvovirus B19 infection on paediatric
patients with haematological and/or
20. Green L, De Lord C, Clark B, Cadet E, oncological disorders. Clinical
Rochette J, Thein SL. Transient aplastic Microbiology and Infection.
crisis as presentationof a previously 2011;17(9.42-1336:)
unknown G6PD deficiency with iron
overload. British journal of 28. Bonvicini F, Puccetti C, Salfi NC,
haematology. 2011;154(3):288.- Guerra B, Gallinella G, Rizzo N, et al.
Gestational and fetal outcomes in B19
21. Kapavarapu PK, Paul A, Lalitha A, Shet maternal infection: a problem of
AS. Transient Aplastic Crisis in diagnosis. Journal of clinical
Hereditary Elliptocytosis. The Indian microbiology. 2011;49(10):3514-8.
Journal of Pediatrics. 2012;79-1666:)12(
.8 29. Segata M, Chaoui R, KhalekN, Bahado-
Singh R, Paidas MJ, Mari G. Fetal
22. Cotmore SF, Christensen J, Nüesch J, thrombocytopenia secondary to
Tattersall P. The NS1 polypeptide of the parvovirus infection. American journal
murine parvovirus minute virus of mice of obstetrics and gynecology.
binds to DNA sequences containing the 2007;196(1):61. e1-. e4.
motif [ACCA] 2-3. Journal of virology.
1995;69(3):1652-60. 30. Enders M, Weidner A, Enders G.
Current epidemiological aspects of
23. Chorba T, Coccia P, Holman RC, human parvovirusB19 infection during
Tattersall P, Anderson LJ, Sudman J, et pregnancy and childhood in the western
al. The role of parvovirus B19 in part of Germany. Epidemiology and
aplastic crisis and erythema infectiosum infection. 2007;135(04):563-9.
(fifth disease). Journal of Infectious
Diseases. 1986;154(3):383-93. 31. Aslanidis S, Pyrpasopoulou A,
Kontotasios K, Doumas S, Zamboulis C.
24. Singhal L, Mishra B, Trehan A, Varma Parvovirus B19 infection and systemic
N, Marwaha R, RathoRK. Parvovirus lupus erythematosus :Activation of an
B19 infection in pediatric patients with aberrant pathway? European journal of
hematological disorders. Journal of internal medicine. 2008;19(5):314-8.
global infectious diseases.
2013;5(3):124. 32. Woolf AD, Campion GV, Chishick A,
Wise S, Cohen BJ, Klouda PT, et al.
25. Azzazy EA, Shaheen AA, Mousaad AA, Clinical manifestations of human
Abdel Salam M, Ibrahim RA. The parvovirus B19 in adults. Archives of
prevalence of human parvovirus B19 internal medicine.6-1153:)5(149;1989 .
infection in children with a variety of

ww.ijmlr.com/IJMLR© All right are reserved

53
 Tari et al., Int J Med Lab Res 2016, 1(2): 48-54
ISSN 2456-4400

33. Naides SJ. Erythema infectiosum (fifth 39. Moore TL, Bandlamudi R, Alam SM,
disease) occurrence in Iowa. American Nesher G, editors. Parvovirus infection
journal of public health. mimicking systemic lupus
1988;78(9):1230-1. erythematosusin a pediatric population.
Seminars in arthritis and rheumatism;
34. Anderson M, Lewis E, Kidd I, Hall S, 1999: Elsevier.
Cohen B. An outbreak of erythema
infectiosum associated with 40. Lamont RF, Sobel J, Vaisbuch E,
humanparvovirus infection. Journal of Kusanovic JP, Mazaki Tovi S, Kim SK,
hygiene. 1984;93(01):85-93. et al. Parvovirus B19 infection in human
pregnancy. BJOG: An International
35. Naides SJ. Infection with parvovirus Journal of Obstetrics & Gynaecology.
B19. Current infectious disease reports. 2011;118(2):175-86.
1999;1(3):273-8.
41. Dieck D, Schild RL, Hansmann M, Eis
36. Moore TL. Parvovirus-associated Hübinger AM. Prenatal diagnosis of
arthritis. Current opinion in congenital parvovirus B19 infection:
rheumatology. 2000;12(4):289.94- value of serological and PCR techniques
in maternal and fetal serum. Prenatal
37. Joseph P. Fifth disease: the frequency of diagnosis. 1999;19(12):1119-23.
joint involvement in adults. New York
state journal of medicine. 42. Skjöldebrand-Sparre L, Nyman M,
1986;86(11):560-3. Broliden K, Wahren B. All cases of
intrauterine fetal death should be
38. Yee T, Cohen B, Pasi K, Lee C. evaluated for parvovirusB19 viral
Transmission of symptomatic deoxyribonucleic acid. American
parvovirus B19 infection by clotting journal of obstetrics and gynecology.
factor concentrate .British journal of 1999;180(6):1595-6.
haematology. 1996;93(2):457-9.

CONFLICT OF INTEREST: Authors declared no conflict of interest

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