ParvovirusSatoko Ugai, MD,a Yuta Aizawa, MD, PhD,B19:b Tetsuya Kanayama, A Cause MD,a Akihiko Saitoh, of MD, PhDb
Sepsislike Syndrome in anabstract Infant Parvovirus B19 (PB19) is an important human pathogen that results in a wide spectrum of clinical outcomes, from mild, self-limiting erythema infectiosum in immunocompetent children and arthralgia in adults to lethal cytopenia in immunocompromised patients and intrauterine – fetal death. However, there have been few reports of PB19 infection in neonates or young infants (aged 28 90 days), and no previous reports contained descriptions of PB19 infection as a cause of sepsislike syndrome in this age group. We report a case of sepsislike syndrome caused by PB19 infection in a 56-day-old infant whose mother had polyarthralgia at the time of his admission. PB19 infection was diagnosed on the basis aDepartment of Pediatrics, Tokamachi Prefectural Hospital, of positive polymerase chain reaction results for PB19 DNA in the Tokamachi, Niigata, Japan; and bDepartment of Pediatrics, serum and cerebrospinal fluid. Positive immunoglobulin M and negative Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan immunoglobulin G for PB19 suggested acute infection. He was admitted to the ICU because of poor peripheral circulation, but fully recovered without Dr Ugai conceived and designed the study and antibiotic administration. After excluding other possible pathogens, PB19 drafted the initial manuscript; Drs Aizawa and Kanayama critically reviewed the manuscript; should be suspected as a cause of sepsislike syndrome in young infants, Dr Saitoh supervised the study and revised and especially those who have close contact with PB19-infected individuals. critically reviewed the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Parvovirus B19 (PB19) infection young infants. Herein, we report a case DOI: https://doi.org/10.1542/peds.2017-1435 is common in childhood, but of sepsislike syndrome caused by PB19 Accepted for publication Feb 21, 2018 its clinical manifestations vary infection in a young infant. Address correspondence to Satoko Ugai, MD, Department of Pediatrics, Tokamachi Prefectural considerably in relation to patient1,2 CASE PRESENTATION age and immunologic status. Hospital, Takayama, Tokamachi, Niigata 948-0055, Japan. E-mail: [email protected] PB19 infection typically presents as erythema infectiosum in healthy, A term 56-day-old boy with a birth PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). immunocompetent school-aged weight of 3072 g was admitted to our children. Arthralgia is the most hospital in January 2016 because of Copyright © 2018 by the American Academy of Pediatrics common manifestation in adults, high fever and poor sucking. Perinatal particularly in women. PB19 can cause history was unremarkable. He had FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships fetal hydrops when mothers3 develop close contact with sick family members relevant to this article to disclose. intrauterine infections. Less common who had clinical symptoms of PB19 FUNDING: Supported by a grant from the National manifestations of PB19 infection in infections, namely a 12-year-old cousin – Center for Child Health and Development, Japan neonates and young infants (aged and 8-year-old cousin with erythema 4 ’ (24-11) to Dr Saitoh. 28 90 days)5 include meningitis, 6 infectiosum 10 and 6 days before POTENTIAL CONFLICT OF INTEREST: The authors hepatitis, leukoerythroblastosis,7 our patient s admission, respectively. have indicated they have no potential conflicts of interest to disclose. transient myeloproliferation,8 In addition, his mother reported encephalitis, and hemophagocytic9 systemic joint pain, a sign of PB19 lymphohistiocytosis. However, PB19 infection, on the day of his admission. To cite: Ugai S, Aizawa Y, Kanayama T, et al. infection in this population is rare, and However, they were not tested for Parvovirus B19: A Cause of Sepsislike Syndrome no researchers of previous reports PB19-specific antibodies or viral in an Infant. Pediatrics. 2018;141(6):e20171435 described PB19 infection as a cause DNA by immunoassay or quantitative of sepsislike syndrome in neonates or polymerase chain reaction (PCR) assay.
Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 141, number 6, June 2018:e20171435 CASE REPORT DISCUSSION
In the emergency department, parechoviruses, and adenovirus, but ° – his vital signs were as follows: all tests yielded negative results. This is the first case report of a body temperature, 39.0 C; pulse young infant (aged 28 90 days) rate, 210 beats per minute; blood As stated above, the boy had close with a sepsislike illness caused by pressure, 95/45 mmHg; and contact with family members with PB19. This age group is susceptible respiratory rate, 45 breaths per erythema infectiosum. His mother to numerous pathogens; thus, when minute. Peripheral oxygen saturation developed rash on her extremities bacterial infection is ruled out, viral was 97% in room air. Physical a few days after she developed etiologies should be considered, examination revealed significant arthritis. Because we suspected an including herpes simplex– virus, abdominal distension. Capillary outbreak of PB19 among his family enterovirus, human12 14 parechoviruses, refilling time was prolonged members, PB19 was considered as a and adenovirus. We diagnosed (up to 5 seconds), and his possible cause of his condition. PB19 PB19 infection after real-time PCR extremities were cold. He had DNA was detected in serum and CSF detection of PB19 in serum and no bulging anterior fontanelle, on admission, when he presented CSF samples and exclusion of other rash, petechiae, vesicular lesions, with symptoms of sepsislike × possible pathogens. hepatosplenomegaly, or abnormal syndrome, and viral load was high on × × 10 PB19 DNA viral load in serum was neurologic signs. real-time PCR (1.6 10 copies/mL 10 × 7 extremely high (>1.0 10 copies/mL) Laboratory findings on admission in serum and 1.6 10 copies/mL – × 10 in our patient. Researchers of a in CSF). Sequence analysis of the were9 a white blood cell count of 3.1 previous study reported that PB19 × 10 /L (normal range: 6.0 14.0 NS1-VP1 overlapping region (from DNA viral load in the serum was high 9 – × –6 × 10 /L), hemoglobin of 97 g/L nt 1765 to nt 112672) of PB19 showed (median: 7.63 103 genomes/mL;6 (normal range: 98 116 g/L), mean genotype 1A. The presence of – range: 4.48 10 8.31 10 ) corpuscular volume of 88 fL (normal positive immunoglobulin M (IgM) – among patients10 with acute erythema range: 72 88 fL), reticulocyte count results and negative immunoglobulin × infectiosum. The researchers of of 3.0% (normal range: 0.1% 2.9%), G (IgG) results indicated acute – × that report also found that PB19 DNA and9 a platelet count of 218 infection. Ultimately, sepsislike viral load in serum during the acute 10 /L (normal range: 84 478 syndrome due to PB19 infection phase of aplastic crisis in chronic 9 × – × 10 /L). A blood smear revealed no was diagnosed. hemolytic anemia was10 extremely13 evidence of atypical lymphocytes or high (range: 1.0 10 1.0 10 ). abnormal red blood cell morphology. During hospitalization, fever The extremely high viral load in Biochemistry testing revealed an – persisted for 2 days but resolved our patient suggests that PB19 aspartate aminotransferase level of with supportive care. He was well infection was the cause of severe 57 U/L (normal range: 22 63 U/L), – enough to be transferred from sepsislike syndrome. The patient an alanine aminotransferase level of the ICU to the pediatric ward on had leukopenia at admission, which 38 U/L (normal range: 12 45 U/L), – hospital day 2 and was discharged suggests the possibility of viral lactate dehydrogenase of 237 U/L from the hospital on day 6 without infection, including PB19 infection, as × (normal range: 170 580 U/L), total sequelae. At the time of discharge, a cause. However, leukopenia was not – × 9 bilirubin level of 0.94 mg/dL (normal white blood cell count (13.2 10 /L; reported by researchers in previous 9 – – range: <1.0 mg/dL), and a C-reactive × – normal range: 6.0 14.0 109/L) case studies of young infants (aged4 7, 9 protein level of 21.9 nmol/L (normal – × and platelet count (532 109 /L; 28 90 days) with PB19 infection. range: 7.6 150.5 nmol/L). No normal range: 84 478 10 /L) had Therefore, it is uncertain whether – abnormal findings were observed in improved, and hemoglobin level leukopenia is a characteristic of PB19 cerebrospinal fluid (CSF) or urine. (90 g/L, normal range: 98 116 g/L) infection in young infants. The patient did not present with was close to normal range. No The prevalence of antibodies against additional measurement of viral any obvious source of fever on PB19 in pregnant women was 15 admission. He was critically ill with load was performed during his reported to be 55.4% in Japan, – poor circulation and was admitted hospitalization. Findings of a 2-month which is similar to prevalences to an ICU. Bacterial infection was follow-up examination were all normal. reported in other countries (30% excluded on the basis of negative 50%), including the Netherlands,16 results for blood, urine, and Written informed consent was Denmark, and the United States. CSF cultures. Real-time reverse obtained from his parents, and they Therefore, approximately half of transcription PCR was used to test were informed that the case would neonates and young infants are at serum and CSF samples for herpes be submitted for publication as a case risk for primary PB19 infection in simplex virus, enteroviruses, human report. Japan. However, sepsislike syndrome Downloaded from www.aappublications.org/news by guest on October 1, 2021 2 UGAI et al 7 8 9 6 8 5 4 in young infants has not been possible pathogen in such cases. In reported. A possible explanation for addition, we suspected that PB19 the lack of such reports is that young might be the pathogen responsible infants with PB19 infection might not for sepsislike syndrome in the Died
Outcome Ref No. present with rash, which is the most present patient because he had close Improved Improved Improved Improved Improved Improved common sign of PB19 infection in contact with family members who children. A literature search revealed had developed erythema infectiosum. only 7 cases of PB19 infection Obtaining a history of sick contacts confirmed by positive anti-PB19– IgM can be helpful for identifying the
and/or PB19 DNA by PCR of serum4 9 or pathogen in cases without an CSF in young infants (Table 1). The apparent source. clinical presentations included fever,
Treatment CONCLUSIONS poor feeding, and vomiting; rash was observed in only 1 patient. Although the number of reported cases is We reported a case of sepsislike IVIG Cefotaxime Prednisone, cyclosporine A small, existing data suggest that PB19 syndrome caused by PB19 infection infection can present without rash in a young infant. After excluding in young infants. Therefore, many other possible pathogens, PB19 pediatricians might not consider +
− should be considered as a cause NA None NA IVIG NA IVIG
+ (CSF) IVIG, methylprednisolone PB19 as the pathogen– responsible of sepsislike syndrome in this for sepsislike syndrome4 9 presenting age group, especially when infants
+ (leukocytes, plasma) in a young infant. A second reason have close contact with PB19- for the lack of previous reports is infected individuals. Serological PB19 Diagnostic Tests that, for viral diagnosis of sepsis testing for PB19 (IgM and IgG +/+ +/+ +/+ +/+ +/+ − /+ in neonates and young infants, we IgM/IgG DNA by PCR antibodies) should be the first usually test for herpes viruses, assessment. If serological testing enteroviruses, and parechoviruses, cannot exclude PB19 infection, but not for PB19. PCR testing for PB19 should be performed in suspected cases. A review of the clinical records for Obtaining a history of sick contacts NA NA Mother NA 11 infants aged 3 to 11 months who was also essential in identifying were confirmed to be infected with PB19 as the cause of sepsislike PB19 by positive IgM and/or PB19 syndrome in our patient. DNA revealed– that no patient had ABBREVIATIONS presented 2,with17 24 sepsis or sepsislike syndrome. One patient with dilated cardiomyopathy caused by
Signs and Symptoms Sick Contact CSF: cerebrospinal fluid Seizure Rash, fever Fever Fever Fever, poor feedingFever, brother Mother, +/+ PB19 met the definition of systemic IgG: immunoglobulin G inflammatory response syndrome IgM: immunoglobulin M (SIRS). He had a respiratory rate ° PB19: parvovirus B19 of 56 breaths per minute and a PCR: polymerase chain reaction temperature of 39 C, and sepsis 24 SIRS: systemic inflammatory was thus diagnosed. Four cases response syndrome Diagnosis
vovirus Infection in Neonates and Young Infants did not18, 20,meet22, 23 the definition of SIRS, and the reports of the REFERENCES lymphohistiocytosis remaining 6 cases had no clinical2,17, 19, 21 1. Heegaard ED, Brown KE. Human information on SIRS diagnosis. parvovirus B19. Clin Microbiol Rev. Therefore, existing evidence is 2002;15(3):485–505 insufficient for determining how 2. Yoto Y, Kudoh T, Haseyama often sepsis or sepsislike syndrome ∼
Literature Review of Par K, Suzuki N, Chiba S. Human develops in infants. A previous report parvovirus B19 infection associated showed that 55% of pathogens with acute hepatitis. Lancet. 67 2 mo 2 mo M M Encephalitis Hemophagocytic 5 2 mo F myeloproliferation Transient vomiting Fever, NA 4 2 mo M Leukoerythroblastosis Vomiting, poor feeding NA 3 2 mo M Meningitis 1 20 d F Meningitis Case Age Sex 2 1 mo M Hepatitis
TABLE 1 female; IVIG, intravenous immunoglobulin; M, male; NA, not available. F, responsible for infantile sepsis could 1996;347(9005):868–869 not be identified25 even after thorough investigation. PB19 might be a Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 141, number 6, June 2018 3 3. Carrington D, Gilmore DH, Whittle infectiosum and aplastic crisis. J Med and high cytokine levels: report of MJ, et al. Maternal serum alpha- Virol. 2014;86(12):2102–2106 3 cases and review. Clin Infect Dis. fetoprotein—a marker of fetal 11. Candotti D, Etiz N, Parsyan A, Allain JP. 2000;31(1):65–69 aplastic crisis during intrauterine Identification and characterization 19. Kerr JR, Barah F, Chiswick ML, et al. human parvovirus infection. Lancet. of persistent human erythrovirus Evidence for the role of demyelination, 1987;1(8530):433–435 infection in blood donor samples. HLA-DR alleles, and cytokines in the 4. Suzuki N, Terada S, Inoue M. Neonatal J Virol. 2004;78(22):12169–12178 pathogenesis of parvovirus B19 meningitis with human parvovirus B19 12. Amel Jamehdar S, Mammouri G, Sharifi meningoencephalitis and its sequelae. infection. Arch Dis Child Fetal Neonatal Hoseini MR, et al. Herpes simplex J Neurol Neurosurg Psychiatry. Ed. 1995;73(3):F196–F197 virus infection in neonates and young 2002;73(6):739–746 5. Nobili V, Vento S, Comparcola D, infants with sepsis. Iran Red Crescent 20. Papadogiannakis N, Tolfvenstam T, Sartorelli MR, Luciani M, Marcellini M. Med J. 2014;16(2):e14310 Fischler B, Norbeck O, Broliden K. Autoimmune hemolytic anemia and 13. Kliegman R, Nelson WE. Nelson Textbook Active, fulminant, lethal myocarditis autoimmune hepatitis associated with of Pediatrics. 19th ed. Philadelphia, PA: associated with parvovirus B19 parvovirus B19 infection. Pediatr Infect Elsevier/Saunders; 2011 infection in an infant. Clin Infect Dis. Dis J. 2004;23(2):184 185 2002;35(9):1027 1031 – 14. Colvin JM, Muenzer JT, Jaffe DM, et al. – 6. Ozdemir N, Akı H, Hakyemez HT, Detection of viruses in young children 21. Chatproedprai S, Boonsuk P, Cokuğraş FÇ, Apak H. Parvovirus with fever without an apparent source. Wananukul S, Poovorawan Y, B19 infection mimicking juvenile Pediatrics. 2012;130(6). Available at: Thisyakorn U. Purpuric-like rash as myelomonocytic leukemia. Int J Infect www.pediatrics.org/cgi/content/full/ cutaneous eruptions in parvovirus Dis. 2010;14(suppl 3):e379–e380 130/6/e1455 B19 infection in Thai infant. Southeast Asian J Trop Med Public Health. 7. Gupta N, Gupta R, Bakhshi S. Transient 15. Takemoto K, Nishimura N, Kozawa K, 2006;37(5):911 914 myeloproliferation mimicking JMML et al. Time-series analysis comparing – associated with parvovirus infection the prevalence of antibodies against 22. Ozbek OY, Onay OS, Kinik ST, Ozbek of infancy. Pediatr Blood Cancer. nine viral species found in umbilical N. Laryngitis and neutropenia from 2009;52(3):411–413 cord blood in Japan. Jpn J Infect Dis. parvovirus-B19. Indian J Pediatr. 8. Barah F, Vallely PJ, Chiswick ML, 2016;69(4):314–318 2007;74(10):950–952 Cleator GM, Kerr JR. Association of 16. Lamont RF, Sobel JD, Vaisbuch E, et al. 23. Kim BJ, Yoo KH, Li K, Kim MN. human parvovirus B19 infection with Parvovirus B19 infection in human Parvovirus B19 infection associated acute meningoencephalitis. Lancet. pregnancy. BJOG. 2011;118(2):175–186 with acute hepatitis in infant. Pediatr Infect Dis J. 2009;28(7):667 2001;358(9283):729–730 17. Sokal EM, Melchior M, Cornu 9. Kishore J, Kishore D. Fatal missed case C, et al. Acute parvovirus B19 24. Jain P, Jain A, Khan DN, Kumar M. of hemophagocytic lymphohistiocytosis infection associated with fulminant Human parvovirus B19 associated co-infected with parvovirus B19 and hepatitis of favourable prognosis dilated cardiomyopathy. BMJ Case Rep. Epstein-Barr virus in an infant: test in young children. Lancet. 2013;bcr2013010410 hyperferritinaemia early. Indian J Med 1998;352(9142):1739–1741 25. Byington CL, Enriquez FR, Hoff C, et al. Microbiol. 2014;32(2):181–183 18. Nigro G, Bastianon V, Colloridi V, et al. Serious bacterial infections in febrile 10. Ishikawa A, Yoto Y, Tsugawa T, Human parvovirus B19 infection in infants 1 to 90 days old with and Tsutsumi H. Quantitation of human infancy associated with acute and without viral infections. Pediatrics. parvovirus B19 DNA in erythema chronic lymphocytic myocarditis 2004;113(6):1662–1666
Downloaded from www.aappublications.org/news by guest on October 1, 2021 4 UGAI et al Parvovirus B19: A Cause of Sepsislike Syndrome in an Infant Satoko Ugai, Yuta Aizawa, Tetsuya Kanayama and Akihiko Saitoh Pediatrics 2018;141; DOI: 10.1542/peds.2017-1435 originally published online May 31, 2018;
Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/141/6/e20171435 References This article cites 23 articles, 6 of which you can access for free at: http://pediatrics.aappublications.org/content/141/6/e20171435#BIBL Subspecialty Collections This article, along with others on similar topics, appears in the following collection(s): Infectious Disease http://www.aappublications.org/cgi/collection/infectious_diseases_su b Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml
Downloaded from www.aappublications.org/news by guest on October 1, 2021 Parvovirus B19: A Cause of Sepsislike Syndrome in an Infant Satoko Ugai, Yuta Aizawa, Tetsuya Kanayama and Akihiko Saitoh Pediatrics 2018;141; DOI: 10.1542/peds.2017-1435 originally published online May 31, 2018;
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/141/6/e20171435
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2018 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.
Downloaded from www.aappublications.org/news by guest on October 1, 2021