128-131 Human Parvovirus

Türkiye Tıp Dergisi 2000; 7(3): 128-131
Human Parvovirus B19 Seroprevalence in Children
with Idiopathic Thrombocytopenic Purpura
Etem ÖZKAYA*, Nam›k ÖZBEK**, Orhan AKTEPE*, Engin GÜVENER*, Çiğdem ALTAY*
* Department of Microbiology, Refik Saydam Institute of Hygiene
** Department of Pediatric Hematology, School of Medicine, Hacettepe University, Ankara, TURKEY
SUMMARY
Objective: The association between idiopathic thrombocytopenic purpura (ITP) and certain viral diseases in
childhood has been well established. However, the role of Human Parvovirus B19 (HPV-B19) in ITP has yet to
be defined. We herein compare the results of parvovirus HPV-B19 antibody response in 19 patients with ITP in
comparison with the antibody response in healthy children.
Method: In this study, we analyzed patients with ITP and 29 normal controls in order to determine the prevalence of HPV-B19 IgM and IgG antibodies using enzyme-linked immunosorbent assay (ELISA).
Results: We found that HPV-B19 IgM was positive in 5 of 19 patients with ITP, whereas it was positive in 1
of 29 children in the control group.
Conclusion: Our findings in patients with ITP provides support for the hypothesis that HPV-B19 may be a role
for HPV-B19 infection with HPV-B19-associated ITP.
Key Words: HPV-B19, seroprevalence, idiopathic thrombocytopenic purpura
ÖZET
İdiopatik Trombositopenik Purpural› Çocuklarda Human Parvovirüs B19 Seroprevalans›
Amaç: İdiopatik trombositopenik purpura (İTP) ile bazı çocukluk çağı viral hastalıklarının birlikteliği iyi bir
şekilde tanımlanmıştır. Bununla birlikte Human parvovirus B19’un (HPV-B19) İTP’deki rolü henüz tam olarak
aydınlatılamamıştır. Biz burada sağlıklı çocuklarla İTP’li 19 hastadaki HPV-B19 antikor yanıtlarını
kıyasladık.
Yöntem: Bu çalışmada “enzyme-linked immunosorbent assay” (ELISA) yöntemini kullanarak HPV-B19 IgM
ve IgG antikorlarının varlığını saptamak için İTP’li 19 hasta ve 29 sağlıklı bireyi analiz ettik.
Bulgular: İTP’li hastadan 5’inde ve kontrol grubunda 29 hastadan 1’inde HPV-B19 IgM’i pozitif olarak bulduk.
Yorum: İTP’li hastalardaki bulgularımız, HPV-B19 enfeksiyonu ile İTP’nin ilişkili olabileceği yönündeki
hipotezleri destekler niteliktedir.
Anahtar Kelimeler: HPV-B19, seroprevalans, idiopatik trombositopenik purpura
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Türkiye Tıp Dergisi 2000; 7(3): 128-131
INTRODUCTION
Childhood acute idiopathic thrombocytopenic purpura (ITP) is usually a self-limited disease characterized by spontaneous bruising and isolated severe
thrombocytopenia in an otherwise healthy child.
Chronic ITP refers to the same disease if the duration of symptoms maintains more than six months (1).
The association between ITP and certain viral diseases in childhood including rubella, cytomegalovirus, varicella and Epstein Barr virus infections has
been well established. Thrombocytopenia is one of
the hematologic manifestations with which HPVB19 infection is associated (2). Additionally, several
cases have been reported associating ITP and HPVB19 (3-5), a virus the role of which has been established in the etiology of many other diseases (2,6,7).
We herein report the results of parvovirus HPV-B19
antibody response in 19 patients with ITP in comparison with the antibody response in healthy children.
PATIENTS and METHODS
Serum samples of 19 patients (8 months to 14 years
of age) who were diagnosed to have ITP between
February and October 1994 were analyzed and there
was no known outbreak of viral infection (f.i. fifth
disease). Twenty-nine serum samples drawn in the
same period from healthy and age-matched controls
having no rash, fever, thrombocytopenia or viral infection, were also tested. Anti-HPV-B19 IgM and
IgG antibodies were determined using the ELISA
(IBL Immuno Biological Laboratories, Hamburg,
Germany).
Chi-square test was used for statistical analysis.
RESULTS
Antibody response to HPV-B19 in acute and chronic
ITP is summarized in Table 1. Anti-HPV-B19 IgM
was positive in 4 and anti-HPV-B19 IgG was positive in 7 of 14 patients with acute ITP. The overall
HPV-B19 IgM seropositivity was 5/19 (4 acute and 1
chronic) in ITP patients. Four of the patients with acu-
te ITP had both anti-HPV-B19 IgM and anti-HPVB19 IgG. In the serum samples of 5 patients with
chronic ITP, IgM was detected only in one and IgG in
three samples. Anti-HPV-B19 IgM positivity rate
(1/29) was lower in the control group than the rate of
IgM positivity in patients with ITP (5/19). Anti-HPVB19 IgG seroprevalence was 10/19 and 11/29 in patients and control group, respectively (p>0.05).
DISCUSSION
Seroprevalence studies have shown that HPV-B19
infections are common in childhood (2). It is well
known that HPV-B19 is the primary cause of several
manifestations including erythema infectiosum in
children (8), transient aplastic crisis in patients with
hemolytic anemia, and chronic anemia in immunocompromised patients (7). In recent years, parvovirus
has been associated with a number of different hematologic manifestations, including transient erythroblastopenia of childhood, Diamond-Blackfan anemia
and ITP (6,8), but the role of parvovirus as an etiologic agent in ITP has yet to be clarified. One of the reliable ways to diagnose acute or recent infections in
immunologically normal individuals is the HPV-B19
IgM antibody assay (2,7,9,10). Also, HPV-B19 IgG
antibody assay is one of the most reliable methods
for past infection (7). In a comparative study of commercial kits in terms of HPV-B19 IgM sensitivity
and specifity, the commercial kit we’ve used was found to be ≥97% sensitive and 96% spesific (11).
HPV-B19 IgM seropositivity in ITP has been shown
in some case reports (3-5,12). Although some authors suggest that HPV-B19 is probably an uncommon cause of ITP (2,6), Inoue et al (12), suggested
that this virus may be an etiologic agent of ITP more
commonly than the literature indicated. Murray et al
(13) detected HPV-B19 DNA in 17 (48.5%) and
HPV-B19 IgM antibodies in 6 (17%) of 35 patients
with ITP and they suggested that HPV-B19 may be
associated with ITP. HPV B19 IgM positivity rates
in our study and in the study of Murray et al were similar. Lefrere et al (14) detected specific anti-parvovirus IgM, suggesting recent infection in 3 (5%) of
Table 1. Anti-HPV-B19 IgM and IgG positivity in ITP patients and the control group.
IgM+/IgG+
IgM+/IgG-
IgM-/IgG+
IgM-/IgG-
Total
Acute ITP
4
0
3
7
14
Chronic ITP
0
1
3
1
5
Controls
0
1
11
17
29
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Özkaya E, Özbek N, Aktepe O, Güvener E, Altay Ç
61 serum samples from patients with ITP in the Paris
area. They suggested that parvovirus serology should
be included in virological investigations in ITP. Our
results were relatively high in comparison with the
HPV-B19 IgM seropositivity rate in their study. In a
patient with chronic ITP, despite lack of IgG, the positivity of anti-HPV-B19 IgM has surprised us, too.
But it’s reported that anti-HPV-B19 IgM antibodies
may persist in some persons up to 6 months after the
onset of illness (8). But a different conclusion was reached by investigators using both serologic and DNA
detection methods. There was a poor correlation with
serologic results and DNA positivity (9). In one
study (16), serum samples of 41 with acute ITP and
19 with chronic ITP patients were tested for HPVB19 spesific IgM and IgG, and for HPV-B19 DNA.
All patients were adult and only in one patient was
evidence of recent HPV-B19 infection found. In this
study they suggested that there may well be correlation in pediatric ITP cases and HPV-B19 infection.
Polymerase chain reaction (PCR) is the most sensitive method for detecting HPV-B19 DNA (9). Heegaard et al (17) examined serum samples of 47 children
with newly diagnosed ITP for HPV-B19 DNA by
PCR. HPV-B19 DNA was demonstrated in 6 of 47
serum samples (13 %). Their study indicates that there is a significant prevalence of HPV B19 infections
in association with childhood ITP.
HPV-B19 IgM positive serum samples should have
been examined for HPV-B19 DNA by PCR method
for to show recent infection in our study. But unfortunately we could not examined the serum samples
using by PCR method.
HPV-B19 IgG prevalence was high both in the patient and the control groups (p>0.05, Table 1). In a
comparative study from Turkey on thalassemia patients and healthy age-matched controls, HPV-B19
IgG positivity was found 26.7% under 5 years and
86.5% between 6 and 17 years of age in the control
group (15). The results of this study are similar with
those of ours. Our findings in patients with ITP provides support for the hypothesis that HPV-B19 may
be a role for HPV-B19 infection with HPV-B19-associated ITP. We consider wider series should be
studied to determine the role of HPV-B19 infection
in ITP as well as the other viral agents.
130
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Beardsley DS. Platelet abnormalities in infancy and
childhood. In: Nathan DG, Oski FA (eds). Hematology of Infancy and Childhood. Philadelphia. WB Saunders. 1993: 1561-1604.
Török TJ. Parvovirus B19 and human disease. Adv
Intern Med 1992; 37: 431-455.
Y›ld›rmak Y, Kemahl› S, Akar N, Uysal Z, Cin Ş, Arcasoy A. A case of severe thrombocytopenia due to
parvovirus B19 virus. Pediatr Hematol Oncol 1996;
13: 183-185.
Mortimer PP, Cohen JJ, Rossiter MA, Fairhead SM,
Rahman AFMS. Human parvovirus and purpura.
Lancet 1985; 2: 730-731.
Foreman NK, Oakhill A, Caul EO. Parvovirus-associated thrombocytopenic purpura. Lancet 1988; 2:
1426-1427.
Mustafa MM, McClain KL. Diverse hematologic effects of Parvovirus B19 infection. Pediatr Hematol
1996; 43: 809-821.
Anderson LJ. Human Parvoviruses. J Infect Dis
1990; 161: 603-608.
Heegaard ED, Hornsleth A. Parvovirus: The expanding spectrum of disease. Acta Pediatr 1995; 84:
109-117.
Anderson LJ, Young NS. Monographs in Virology.
Human Parvovirus B19. Switzerland, 1997.
Erdman DD, Usher MJ Tsou C, Caul EO, Gary GW,
Kajigaya S, Young NS, Anderson LJ. Human parvovirus B19 spesific IgG, IgA, and IgM antibodies and
DNA in serum specimens from persons with erythema
infectiosum. J Med Virol 1991; 35: 110-115.
Sloots T, Devine PL. Evaluation of four commercial
enzyme immunoassays for detection of immunoglobulin M antibodies to human parvovirus B19. Eur J
Clin Microbiol Infect Dis 1996; 15: 758-761.
Inoue S, Kinra NK, Mukkamala SR, Gordon R. Parvovirus B-19 Infection: Aplastic crisis, erythema infectiosum and idiopathic thrombocytopenic purpura.
Pediatr Inf Dis J 1991; 10: 251-253.
Murray JC, Kelley PK, Hogrefe WR, McClain KL.
Childhood idiopathic thrombocytopenic purpura: Association with human parvovirus B19 infection. Am J
Pediatr Hematol Oncol 1994; 16: 314-319.
Lefrere JJ, Courouce AM, Kaplan C. Parvovirus and
idiopathic thrombocytopenic purpura. Lancet 1989;
1: 279.
Akar N, Sipahi T, Eğin Y, Cin Ş, Arcasoy A. Incidence of parvovirus B19 infection among thalassemia
major patients from Ankara, Turkey. Pediatr Hematol Oncol 1995; 12: 507-509.
Türkiye Tıp Dergisi 2000; 7(3): 128-131
16. Van Elsacker-Niele AMW, Weiland HT, Kroes ACM,
Kappers-Klunne MC. Parvovirus B19 infection and
idiopathic thrombocytopenic purpura. Ann Hematol
1996; 72: 141-144.
17. Heegaard ED, Rosthoj S, Petersen BL, Nielsen S, Karup Pedersen F, Hornsleth A. Role of parvovirus B19
infection in childhood idiopathic thrombocytopenic
purpura. Acta Paediatr 1999; 88: 614-617.
ADDRESS FOR CORRESPONDENCE:
Uzm. Dr. Etem ÖZKAYA
Refik Saydam H›fz›ss›hha Merkezi Başkanl›ğ›
Viroloji Laboratuvar›
Cemal Gürsel Caddesi No: 16
S›hhiye-ANKARA
DÜZETME
Dergimizin 2000 y›l› 7. cilt 1. say›s›nda “Diabetik S›çanlar›n İzole Sağ Atriyum Preparat›nda Klonidinin Adenozin Antagonisti Etkisi” başl›kl› makalede metin içinde belirtilen ancak bas›lmayan Şekil
1 ve 2 aşağ›daki gibidir.
Türkiye T›p Dergisi
Kontrol
Diabet
40
Kontraksiyon güc
% inhibisyon
a
b
c
d
30
20
10
0
-6 -5.5 -5 -4.5 -4
-6 -5.5 -5 -4.5 -4
-6 -5.5 -5 -4.5 -4
-6 -5.5 -5 -4.5 -4
Log adenozin (M)
Şekil 1. Kontrol ve diabetik s›çanlar›n sağ atriyum kontraksiyon gücünde adenozinin oluşturduğu inhibisyona klonidinin etkisi.
70
60
Kontrol
Diabet
a
b
c
d
At›m say›s›
% inhibisyon
50
40
30
20
10
0
-6 -5.5 -5 -4.5 -4
-6 -5.5 -5 -4.5 -4 -6 -5.5 -5 -4.5 -4
Log adenozin (M)
-6 -5.5 -5 -4.5 -4
Şekil 2. Kontrol ve diabetik s›çanlar›n sağ atriyum at›m say›s›nda adenozinin oluşturduğu inhibisyona
klonidinin etkisi.
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