Parvovirus B19 Causes Fetal Loss

Another example of how confounding by infection leads to false blame of smoking; and of how investigation of "lifestyle" factors (even including video display terminals!) has had priority over the role of infection.

Parvovirus B19 in pregnancy

Infectious causes of hydrops fetalis. SD Barron, RF Pass. Semin Perinatol 1995 Dec;19(6):493-501. "A variety of infectious agents have been associated with nonimmune hydrops fetalis, most notably parvovirus B19, cytomegalovirus, herpes simplex virus, Toxoplasma gondii, and Treponema pallidum. These agents produce hydrops through effects on fetal bone marrow, myocardium, or vascular endothelium...."

Parvovirus B19 infection in pregnancy. AM Eis-Hubinger, D Dieck, R Schild, M Hansmann, KE Schneweis. Intervirology 1998;41(4-5):178-184. "Transplacental transmission of human parvovirus B19 (B19 virus) to the fetus is an important cause of intrauterine death, abortion, stillbirth, and nonimmune hydrops fetalis. Adverse outcome of pregnancy can occur after symptomatic and asymptomatic maternal infection. Only rare cases of congenital malformations and fetal disease in live-born infants have been associated with intrauterine B19 virus infection. Laboratory results obtained from paired maternal and fetal cord blood samples indicate that a reliable diagnosis of fetal B19 virus infection should be based on detection of parvovirus B19 DNA."

Feto-placentary pathology in human parvovirus B19 infection. AG Garcia, CS Pegado, Rd Cubel, ME Fonseca, I Sloboda, JP Nascimento. Rev Inst Med Trop Sao Paulo 1998 May-Jun;40(3):145-150. In six autopsies, "All fetuses showed a similar pathology--hydrops, hepato-splenomegaly, lung hypoplasia and erythroblastemia, the specific histological feature being the presence of intranuclear inclusions in the erythroid progenitors, in the erythropoietic visceral tissue and in blood marrow. Complex cardiopathy allied to abnormal lung lobulation and polisplenia were observed once; in 2 cases endocardial fibroelastosis was diagnosed. The pulmonary lesions were represented by dysmaturity allied to interstitial mononuclear infiltration. The hepatic consisted of cholestasis, portal fibrosis, canalicular proliferation, hemossiderosis, focal necroses and giant cell transformation. The central nervous system lesions were predominantly anoxic although the autolysis impaired a correct diagnosis."

Risk factors for parvovirus B19 infection in pregnancy. AK Valeur-Jensen, CB Pedersen, T Westergaard, IP Jensen, M Lebech, PK Andersen, P Aaby, BN Pedersen, M Melbye. JAMA 1999 Mar 24-31;281(12):1099-1105. "Based on 30 946 serum samples, 65.0% of pregnant women had evidence of past infection. Annual seroconversion rates among susceptible women during endemic and epidemic periods were 1.5% (95% confidence interval [CI], 0.2%-1.9%) and 13.0% (95% CI, 8.7%-23.1 %), respectively. Baseline seropositivity was significantly correlated with increasing number of siblings, having a sibling of the same age, number of own children, and occupational exposure to children. Risk of acute infection increased with the number of children in the household as follows: 0 children odds ratio (OR), 1 (reference); 1 child OR, 3.17 (95% CI, 2.24-4.49); 2 children OR, 5.47 (95% CI, 3.55-8.45); 3 or more children OR, 7.54 (95% CI, 3.80-14.94). Having children aged 6 to 7 years resulted in the highest rate of seroconversion among mothers (6.8%; OR, 4.07; 95% CI, 1.89-8.73). Compared with other pregnant women, nursery school teachers had a 3-fold increased risk of acute infection (OR, 3.09; 95% CI, 1.62-5.89). Population-attributable risk of seroconversion was 55.4% for number of own children and 6.0% for occupational exposure.... Nursery school teachers have the highest occupational risk, but most infections seem to be the result of exposure to the woman's own children."

Seroprevalence of parvovirus B19 NS1-specific IgG in B19-infected and uninfected individuals and in infected pregnant women. A Hemauer, A Gigler, K Searle, K Beckenlehner, U Raab, K Broliden, H Wolf, G Enders, S Modrow. J Med Virol 2000 Jan;60(1):48-55. "IgG against the NS1 protein was present in 22% of healthy individuals with past B19 infection. In cases of persistent or prolonged B19 infections, the prevalence of NS1-specific antibodies was as high as 80%. It is concluded that NS1-specific IgG may be used as an indicator of chronic or more severe courses of parvovirus B19 infections."

Parvovirus B19 infection: association with third-trimester intrauterine fetal death. L Skoldebrand-Sparre, T Tolfvenstam, N Papadogiannakis, B Wahren, K Broliden, M Nyman. BJOG 2000 Apr;107(4):476-480. 5/7 cases of third trimester intrauterine fetal death without hydrops had delayed or absent IgG responses; 2 "had unusual infection patterns; persistent viraemia for at least five months before birth in one case and likely persistence or re-infection by B19 in the other."

Frequency of human parvovirus B19 infection in intrauterine fetal death. T Tolfvenstam, N Papadogiannakis, O Norbeck, K Petersson, K Broliden. Lancet 2001 May 12;357(9267):1494-1497. "Of 14147 deliveries in three hospitals in the major Stockholm area of Sweden, all cases of intrauterine fetal death (>22 gestational weeks) that occurred between January, 1998, and May, 1999 (n=47), referred cases of miscarriage (<22 gestational weeks, n=37), and induced abortions (n=29), were included in the study," plus 53 normal pregnancies at term. "Significantly more cases of intrauterine fetal death were positive for parvovirus B19 DNA (seven [15%]) than were normal pregnancies at term (zero, p=0.049). Furthermore, parvovirus B19 DNA was found in two (5%) of the miscarriages but not in any of the cases of induced abortion. Only three of nine DNA-positive cases had parvovirus-B19-associated inclusions and stained positive for viral proteins. All but one of the DNA-positive cases of intrauterine fetal death were non-hydropic."

Etiology and outcome of hydrops fetalis. KM Ismail, WL Martin, S Ghosh, MJ Whittle, MD Kilby. J Matern Fetal Med 2001 Jun;10(3):175-181. A retrospective review of 63 consecutive cases of hydrops fetalis. "Of the pregnancies, 12.7% (n = 8) were associated with an 'immune' etiology. Of these, 62.5% (n = 5) had fetal anemia due to anti-D, 25% (n = 2) anti-Kell and 12.5% (n = 1) anti-c antibodies. The remaining 55 cases (87.3%) had a non-immune cause. Eight (14.5%) were due to human parvovirus B19 infection. Fourteen cases (25.5%) were associated with aneuploidy and, in four (7.3%), a primary hydrothorax was the cause of the non-immune hydrops fetalis. A cardiac cause was found in five (9.1%) cases. Three of these had supraventricular tachycardia and one had congenital complete heart block. Cystic hygroma was associated with hydrops fetalis in six cases. Twin-twin transfusion syndrome was the cause for hydrops in two cases. Massive transplacental hemorrhage was identified in one case. Fetal akinesia and muscular dystrophy caused hydrops in one case each. In 14.5% (8/55) of cases no obvious cause was identified and these were classified as 'idiopathic'. Three other cases could not be classified because parents declined investigations (unclassified). In the pregnancies with non-immune hydrops fetalis, the outcome was favorable in 27.3% (15/55) of cases."

Fetal parvovirus B19 infection. CS Von Kaisenberg, W Jonat. Ultrasound Obstet Gynecol 2001 Sep;18(3):280-288. ""Parvovirus B19 infection during pregnancy causes up to 27% cases of non-immune hydrops in anatomically normal fetuses. The virus is believed to cause arrest of maturation of red blood cell precursors at the late normoblast stage and also causes a decrease in the number of platelets. Fetal anemia is presently thought to be responsible for the development of skin edema and effusions. Myocarditis leading to heart failure may contribute to the development of fetal hydrops." In a review of 82 studies involving 230 invasively and 435 conservatively managed pregnancies, "the proportion of seronegative susceptible mothers ranged from 19 to 65%, seroconversion with an incubation time of up to 20 days occurred in 5.7-12.1%, and 188/230 (82%) who were transfused infected fetuses had a normal outcome as opposed to only 239/435 (55%) in the conservatively managed group."

Relevance of parvovirus B19, herpes simplex virus 2, and cytomegalovirus virologic markers in maternal serum for diagnosis of unexplained recurrent abortions. M el-Sayed Zaki, H Goda. Arch Pathol Lab Med 2007 Jun;131(6):956-960. "There was a statistically significant difference between the RSA group and the pregnant women without RSA group in frequency of parvovirus IgM (84% and 16.7%, respectively) (P < .001) and herpes simplex IgM (40% for RSA) (P = .001). Parvovirus B19 viremia was positive in 48% RSA, herpes simplex virus 2 was positive in 32% RSA, and cytomegalovirus was positive in 12% RSA patients. For RSA patients with parvovirus viremia, the mean +/- SD of IgM value was 78.5 +/- 30.12 IU/mL, and for RSA patients with negative viremia it was 30.02 +/- 17.64 IU/mL with statistically significant difference between both levels (P < .001)."

Parvovirus B19 and other illness

Human parvovirus B19: relevance in internal medicine. AM van Elsacker-Niele, AC Kroes. Neth J Med 1999 Jun;54(6):221-230. Acute and chronic arthritis and anemias.

Clinical and laboratory findings in immunocompetent patients with persistent parvovirus B19 DNA in bone marrow. A Lundqvist, T Tolfvenstam, J Bostic, M Soderlund, K Broliden. Scand J Infect Dis. 1999;31(1):11-6. "The clinical relevance of parvovirus B19 DNA persistence in bone marrow was examined in 10 immunocompetent individuals undergoing examinations for unexplained fever, arthralgia or chronic leukopenia. Common causes of these symptoms had been ruled out and bone marrow aspiration was indicated at this stage of investigation. In addition to morphological analysis of the bone marrow, a test for B19 DNA was performed with 2 nested PCRs. Five of these 10 selected patients had detectable B19 DNA in their bone marrow, whereas no viraemia was observed. Additional bone marrow samples were collected at least 6 months after the first sample from the B19 DNA-positive patients, of whom 3 were found to be still positive. Indeed, 2 of the patients have been positive for more than 5 y of follow-up. Sera from all patients with persistent B19 DNA in bone marrow could neutralize the virus. One patient responded to treatment with immunoglobulin but later relapsed. No other cause of the symptoms was found, despite extensive investigations, and at least some of the prolonged disease manifestations may be due to parvovirus B19."

Evidence for persistence of parvovirus B19 DNA in livers of adults. AM Eis-Hubinger, U Reber, T Abdoul-Nour, U Glatzel, H Lauschke, U Putz. J Med Virol 2001 Oct;65(2):395-401. "B19 was detected in the livers of 4/17 (24%) anti-B19 IgG-positive individuals, three of whom had also B19 DNA in their bone marrow... Further studies are needed to address whether B19 is an innocent bystander in the liver or whether the presence of B19 in liver is of biological and clinical significance." (News) Human parvovirus B19 persists in adult livers. M Greener, Doctor's Guide 2001 Oct 11.

Human Parvovirus B19. ED Heegaard, KE Brown. Clinical Microbiology Reviews 2002 Jul; 15(3):485-505. Review Article

[Research on Parvovirus B19 infections and chronic articular manifestations in a Tunisian hospital]. F Regaya, R Khelifa, R Zouari, M Kchir, M Karoui, R Essid. Arch Inst Pasteur Tunis 2003;80(1-4):9-15. 100 patients with different chronic inflammatory rheumatismal affections vs 100 controls. specific anti-Parvovirus B19 IgG was detectable in the sera of 80.7% of patients and 43% of controls. No synovial fluid samples were positive.

Frequent infection with a viral pathogen, parvovirus B19, in rheumatic diseases of childhood. HW Lehmann, A Knöll, RM Küster, S Modrow. Arthritis Rheum 2003 Jun;48(6):1631-1638. 74 children with rheumatic disease vs. 124 controls. "Twenty-six of the 74 patients (35%) had detectable amounts of parvovirus B19 DNA in the serum (n = 22 [30%]) and/or the synovial fluid (n = 16 [22%]), whereas only 9 of the 124 control sera (7%) were positive for the viral DNA (P < 0.0001). Forty-six patients (62%) had serum IgG against the structural proteins, indicating past infection with B19. NS1-specific antibodies were detected in sera from 29 patients (39%) and 27 controls (22%) (P < 0.001)."

High frequency of parvovirus B19 DNA in bone marrow samples from rheumatic patients. A Lundqvist, A Isa, T Tolfvenstam, G Kvist, K Broliden. J Clin Virol 2005 May;33(1):71-74. "B19 IgG was found in 41 of 50 patients (82%) whereas none was B19 IgM positive. The serologic evaluation showed that none of the patients had acute B19 infection. However, B19 DNA was detected by PCR in 13 of 50 (26%) bone marrow samples from these patients indicating a high frequency of persistent infection compared with previous reports of patient groups and healthy controls. In the study, 22 patients had rheumatoid arthritis (RA) and 7 of these RA patients were B19 DNA positive in bone marrow. Rheumatoid factor was positive in 4 of the 7 B19 DNA positive RA patients as compared with Rheumatoid factor positivity in all of the 15 B19 DNA negative RA patients. Erosive arthritis in X-ray was less common in the B19 DNA positive group than in the B19 DNA negative group."

Epidemiology of parvovirus B19

The prevalence of antibody to parvovirus B19 in hemophiliacs and in the general population. AM Eis-Hubinger, J Oldenburg, HH Brackmann, B Matz, KE Schneweis. Zentralbl Bakteriol 1996 Jul;284(2-3):232-240. Rates of infection rose rapidly during childhood, to 61% at age 12 years; then increased more slowly to 77% at age 60 and over. 98% of hemophiliacs were positive, indicating that it can be transmitted by clotting factors.

Prolonged activation of virus-specific CD8+ T cells after acute B19 infection. A Isa, V Kasprowicz, O Norbeck, A Loughry, K Jeffery, K Broliden, P Klenerman, T Tolfvenstam, P Bowness. PLoS Med 2005 Dec;2(12):e343.

New Parvoviruses

New DNA viruses identified in patients with acute viral infection syndrome. MS Jones, A Kapoor, VV Lukashov, P Simmonds, F Hecht, E Delwart. J Virol. 2005 Jul;79(13):8230-6. A parvovirus and two viruses related to TT virus (TTV) were discovered among 25 individuals with acute viral syndrome of unknown etiology.

Novel Parvovirus and Related Variant in Human Plasma. JF Fryer, A Kapoor, PD Minor, E Delwart, SA Baylis. Emerg Infect Dis 2006 Jan;12(1):05-0916. 5% of human plasma pools tested positive for the parvovirus found by Jones, which was named PARV4. "As yet, nothing is known about the prevalence of PARV4, its possible role in human disease, or whether PARV4 was transmitted to the original patient from an unidentified animal host."

Human bocavirus: clinical significance and implications. J Kahn. Curr Opin Pediatr 2008 Feb;20(1):62-66. Review. "Human bocavirus (HBoV), a parvovirus, was discovered in 2005 with the use of nonspecific genome amplification techniques. Since its discovery, HBoV has been identified worldwide.... HBoV is not confined to the respiratory tract as evidence of the virus has been detected in serum and stool, the significance of which remains unclear. Presence of the virus in respiratory secretions, serum and stool suggests that this virus may cause systemic illness."

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cast 02-10-08