Human Parechovirus as an Important Cause of Central Nervous System Infection in Childhood

Hyun Joo Jung; Eun Hwa Choi; Hoan Jong Lee

doi:10.14776/piv.2016.23.3.165

Journal List > Pediatr Infect Vaccine > v.23(3) > 1095925

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Jung, Choi, and Lee: Human Parechovirus as an Important Cause of Central Nervous System Infection in Childhood

Original Article

Pediatr Infect Vaccine 2016;23(3):165-171.

Published online: 21 January 2016

DOI: https://doi.org/10.14776/piv.2016.23.3.165

Human Parechovirus as an Important Cause of Central Nervous System Infection in Childhood

Hyun Joo Jung^1,², Eun Hwa Choi^2,, Hoan Jong Lee²

¹Department of Pediatrics, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea

²Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea

Correspondence: Eun Hwa Choi Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea Tel: +82-2-2072-3624, Fax: +82-2-766-7283 E-mail: eunchoi@snu.ac.kr

Received 20 April 201613 May 2016 Accepted 14 105 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Human parechovirus (HPeV) is an increasingly recognized pathogenic cause of central nervous system (CNS) infection in neonates. However, HPeV infections have not been studied in older children. This study determined the prevalence and clinical features of HPeV CNS infection in children in Korea.

Methods

Reverse transcription polymerase chain reaction assays were performed using HPeV-specific, 5' untranslated, region-targeted primers to detect HPeV in cerebrospinal fluid (CSF) samples from children presenting with fever or neurologic symptoms from January 1, 2013, to July 31, 2014. HPeV genotyping was performed by sequencing the viral protein 3/1 region. Clinical and laboratory data were retrospectively abstracted from medical records and compared with those of enterovirus (EV)-positive patients from the same period.

Results

Of 102 CSF samples, six (5.9%) were positive for HPeV; two of 21 EV-positive samples were co-infected with HPeV. All samples were genotype HPeV3. Two HPeV—positive patients were <3 months of age and four others were over 1 year old. While HPeV—positive infants under 1 year of age presented with sepsis-Iike illness without definite neurologic abnormalities, HPeV—positive children over 1 year of age presented with fever and neurologic symptoms such as seizures, loss of consciousness, and gait disturbance. The CSF findings of HPeV-positive patients were mostly within the normal range, whereas most (73.7%) EV—positive patients had pleocytosis.

Conclusions

Although HPeV is typically associated with disease in young infants, the results of this study suggest that HPeV is an emerging pathogen of CNS infection with neurologic symptoms in older childhood.

Keywords: Parechovirus, Central nervous system infections, Korea

REFERENCES

1. Wigand R, Sabin AB. Properties of ECHO types 22, 23 and 24 viruses. Arch Gesamte Virusforsch. 1961; 11:224–47.

2. Oberste MS, Maher K, Pallansch MA. Specific detection of echoviruses 22 and 23 in cell culture supernatants by RT-PCR. I Med Virol. 1999; 58:178–81.

3. Mayo MA, Pringle CR. Virus taxonomy: 1997. I Gen Virol. 1998; 79(Pt 4):649–57.

4. Chuchaona W, Khamrin P, Yodmeeklin A, Saikruang W, Kongsricharoern T, Ukarapol N, et al. Detection and characterization of a novel human parechovirus genotype in Thailand. Infect Genet Evol. 2015; 31:300–4.

5. van der Linden L, Wolthers KC, van Kuppeveld FJ. Replication and inhibitors of enteroviruses and parechoviruses. Viruses. 2015; 7:4529–62.

6. Levorson RE, Jantausch BA. Human parechoviruses. Pediatr Infect Dis I. 2009; 28:831–2.

7. Harvala H, Robertson 1, Chieochansin T, McWilliam Leitch EC, Templeton K, Simmonds P. Specific association of human parechovirus type 3 with sepsis and fever in young infants, as identified by direct typing of cerebrospinal ﬂuid samples. I Infect Dis. 2009; 199:1753–60.

8. Wolthers KC, Benschop KS, Schinkel J, Molenkamp R, Ber-gevoet RM, Spijkerman I], et al. Human parechoviruses as an important Viral cause of sepsislike illness and meningitis in young children. Clin Infect Dis. 2008; 47:358–63.

9. Selvarangan R, Nzabi M, Selvaraju SB, Ketter P, Carpenter C, Harrison C]. Human parechovirus 3 causing sepsislike illness in children from midwestern United States. Pediatr Infect Dis I. 2011; 30:238–42.

10. Sec IH, Yeom IS, Youn HS, Han TH, Chung IY. Prevalence of human parechovirus and enterovirus in cerebrospinal ﬂuid samples in children in Iinju, Korea. Korean I Pediatr. 2015; 58:102–7.

11. Verboon-Maciolek MA, Krediet TG, Gerards L}, de Vries LS, Groenendaal F, van Loon AM. Severe neonatal parechovirus infection and similarity with enterovirus infection. Pediatr Infect Dis I. 2008; 27:241–5.

12. Mizuta K, Kuroda M, Kurimura M, Yahata Y, Sekizuka T, Aoki Y, et al. Epidemic myalgia in adults associated with human parechovirus type 3 infection, Yamagata, Japan, 2008. Emerg Infect Dis. 2012; 18:1787–93.

13. Mizuta K, Yamakawa T, Kurokawa K, Chikaoka S, Shimizu Y, Itagaki T, et al. Epidemic myalgia and myositis associated with human parechovirus type 3 infections occur not only in adults but also in children: findings in Yamagata, Iapan, 2014. Epidemiol Infect. 2016; 144:1286–90.

14. Figueroa IP, Ashley D, King D, Hull B. An outbreak of acute ﬂaccid paralysis in Jamaica associated with echovirus type 22. I Med Virol. 1989; 29:315–9.

15. Harvala H, Robertson 1, McWilliam Leitch EC, Benschop K, Wolthers KC, Templeton K, et al. Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol. 2008; 46:3446–53.

16. Renaud C, Harrison CI. Human parechovirus 3: the most common Viral cause of meningoencephalitis in young infants. Infect Dis Clin North Am. 2015; 29:415–28.

17. Esposito S, Rahamat-Langendoen I, Ascolese B, Senatore L, Castellazzi L, Niesters HG. Pediatric parechovirus infections. I Clin Virol. 2014; 60:84–9.

18. Han TH, Chung JY, You SI, Youn IL, Shim GH. Human pa-rechovirus-3 infection in children, South Korea. J Clin Virol. 2013; 58:194–9.

19. Zhang DL, Jin Y, Li DD, Cheng WX, Xu ZQ, Yu IM, et al. Prevalence of human parechovirus in Chinese children hospitalized for acute gastroenteritis. Clin Microbiol Infect. 2011; 17:1563–9.

20. Pajkrt D, Benschop KS, Westerhuis B, Molenkamp R, Span-jerberg L, Wolthers KC. Clinical characteristics of human parechoviruses 4-6 infections in young children. Pediatr Infect Dis J. 2009; 28:1008–10.

21. Felsenstein S, Yang S, Eubanks N, Sobrera E, Grimm JP, A1-drovandi G. Human parechovirus central nervous system infections in southern California children. Pediatr Infect Dis1. 2014; 33:e87–91.

22. Sharp 1, Harrison C], Puckett K, Selvaraju SB, Penaranda S, Nix WA, et al. Characteristics of young infants in whom human parechovirus, enterovirus or neither were detected in cerebrospinal ﬂuid during sepsis evaluations. Pediatr Infect Dis I. 2013; 32:213–6.

23. Cabrerizo M, Trallero G, Pena MJ, Cilla A, Megias G, noz—Almagro C, et al. Comparison of epidemiology and clinical characteristics of infections by human parechovirus vs. those by enterovirus during the first month of life. Eur J Pediatr. 2015; 174:1511–6.

24. Pineiro L, Vicente D, Montes M, Hernandez-Dorronsoro U, Cilla G. Human parechoviruses in infants with systemic infection. J Med Virol. 2010; 82:1790–6.

Table 1.

Differences in Clinical and Laboratory Features in Patients with Human Parechovirus or Enterovirus

Variable	HPeV∗ (n=6)	EV^† (n=19)	P-value
AGE	33.5 mo	2 mo	NS
	(1 mo—15yr)	(13 day-7yr)
Hospltal days (day)	3.8(1-11)	3.5(1-6)	NS
Clinical symptoms
Days of fever (day)	3.2 (2-4)	2.9 (1-5)	NS
Tmax hospital (“C)	38.8 (38-40.4)	38.7 (38.2-39.4)	NS
Neurologic symptoms (%)'	66.7 (n=4)	5.3 (n=1)	0.001
Gastrointestinal symptoms (%)	66.7(n=2)	5.3(n=2)	0.001
Respiratory symptoms (%)	33.3 (n=2)	10.5 (n=2)	NS
Cerebrospinal fluid
Pleocytosis (%)“	16.7(n=1)	73.7(n=14)	0.001
Glucose level (mg/dL)	72.7 (64-95)	57.2 (45-74)	0.020
Protein level (mg/d L)	32.2 (15-60	60.9 (19-116)	0.030
Blood
WBC counts (/μL)	9.205 (7,680-23,740)	11.580 (6,280-15,140)	NS
Neutrophlls (%)	61.2(33.7-82.6)	60.5(26.0-91.0)	NS
Lymphocytes (%)	29.0 (13.5-51.8)	29.1 (5.3-55.3)	NS
Platelet counts (x10³/μL)	308.8 (238-364)	330.1 (187-516)	NS
C-reactlve protein (mg/dL)	0.51 (0.09-7.64)	0.48 (003-2.72)	NS
AST (IU/L)	28.4(16-47)	38.6(17-81)	NS
ALT (IU/L)	16.4(11-26)	23.5 (8-48)	NS

Values are presented as medlan (range). ∗Two cerebrospinal fluid samples were positive for both HPeV and EV. Patients with EV not HPeV. Neurologic symptoms except headache. P<o.05. Age-adjusted results. Abbreviations: HPeV, human parechovirus; EV, enterovirus; NS, not significant; Tmax, maximum body temperature; WBC, white blood cell; AST, aspartate transaminase; ALT, alanine transaminase.

Table 2.

Characteristics of the Six Positive Human Parechovirus Cases

Patient	Age	Sex	Fever		Symptom	CSF			Peripheral blood						Brain MRI	HPeV genotyping	GXEA
Patient	Age	Sex	Initial impression	Duration (day)	Symptom	Tmax (C)	Cell counts (/mm³)	Glucose (mg/dL)	Protein mg/dL)	WBC COUHIS (/L)	Neut (%)	Lym ph (%)	PLT counts (x10³/pL)	CRP mg/dL)	Brain MRI	HPeV genotyping	GXEA
1	6yr	F	Febrile convulsion	2	40.4	Headache, seizure abdominal pain, diarrhea, cough, coryza, sore throat	0	95	20	23,240	69.6	21.4	364	7.64	NO specfic flndlngs	HPeV3	(+)
2	15yr	M	Aseptic meningitis	4	38.9	Headache, loss of consciousness, vomiting	132	65	50	8,970	71.2	16.9	298	0.71	Slightly prominent meningeal enhancement	HPeV3	(+)
3	1mo	M	Aseptic meningitis	1	38.2	Fever without focus	7	71	15	9,440	33.7	51.8	325	0.09	ND	HPeV3	(-)
4	19 mo	M	Acute cerebellar ataxia	11	38	Gait disturbance, vomiting, cough, coryza	3	74	23	7,680	68.8	20.1	238	2.19	No specific findings	HPeV3	(-)
5	3mo	M	Sepsis	1	38.4	Lethargy	0	64	18	9,890	41.2	50.3	331	0.15	ND	HPeV3	(-)
6	4yr	F	Common cold, known Sturge—Weber syndrome	4	38.6	Selzure aggravation, headache, vomiting	0	67	67	8,300	82.6	13.5	297	0.3	More prominent sulcal hyperintensity and leptomeningeal enhancement of temporo-occipital Iobr (aggravated chronic ischemia suggested)	HPeV3	(-)

Abbreviations: Tmax. Maximum body temperature; CSF, cerebrospinal fluid; WBC. white blood cell; Neut, neutrphil; Lymph, lymphocyte; PLT, platelet; CRP, C-reactive protein; MRI, magnetic resonance imaging; HPeV, human parechovirus; GXEA, GeneXpert enterovirus assay; ND, not done.

TOOLS

Similar articles