Human Parechoviruses as an Important Viral Cause of Sepsislike Illness and Meningitis in Young Children

Wolthers, Katja C.; Benschop, Kimberley; Schinkel, Janke; Molenkamp, Richard; Bergevoet, Rosemarijn M.; Spijkerman, Ingrid J. B.; Kraakman, H. Carlijn; Pajkrt, Dasja

doi:10.1086/589752

Cited by 234 publications

(202 citation statements)

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“…The associated spectrum of diseases is not fully understood and probably has been underestimated. Recent data indicate that HPeVs may cause severe clinical conditions, such as infant sepsis and meningitis, in addition to acute diarrhea (10). Prevalence in young children with diarrhea was >16% in previous studies; more important, <8% of meningitis Figure 1.…”

Section: Discussionmentioning

confidence: 87%

“…The molecular ecology of HPeV seems especially relevant in view of their diversifi ed and strain-dependent pathogenesis (10,11).…”

Section: Discussionmentioning

confidence: 99%

“…Predominantly in infants, HPeVs can cause a variety of clinical symptoms, including diarrhea, and respiratory infection (8,9). Recent data point toward substantial involvement in severe conditions, such as meningitis and infant sepsis, for which HPeV may constitute the second most frequent causative virus after enterovirus in young children (10). Different HPeV types may cause different clinical diseases (10,11).…”

mentioning

confidence: 99%

“…Recent data point toward substantial involvement in severe conditions, such as meningitis and infant sepsis, for which HPeV may constitute the second most frequent causative virus after enterovirus in young children (10). Different HPeV types may cause different clinical diseases (10,11). Unconnected diseases might be caused by yet unrecognized HPeVs.…”

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confidence: 99%

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Novel Human Parechovirus from Brazil

Drexler¹,

Grywna²,

Stöcker³

et al. 2009

Emerg. Infect. Dis.

103

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Section: Discussionmentioning

confidence: 87%

“…The molecular ecology of HPeV seems especially relevant in view of their diversifi ed and strain-dependent pathogenesis (10,11).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Novel Human Parechovirus from Brazil

Drexler¹,

Grywna²,

Stöcker³

et al. 2009

Emerg. Infect. Dis.

103

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“…For example, two members of the family Picornaviridae, Enterovirus (EV) and Parechovirus (PeV), have been shown to induce seizures in infected children; however, the available diagnostic tests for EVs do not detect PeVs (2,3). A recent retrospective study, using pediatric cerebrospinal fluid samples previously screened for EV, demonstrated that the inclusion of a novel PeV-specific PCR assay led to a 31% increase in the detection of viruses causing virally induced CNS symptoms and neonatal sepsis (4). Therefore, the role of viral infection in the induction of seizures has not been fully recognized, possibly due to the sensitivity and specificity of currently available viral diagnostic tests.…”

mentioning

confidence: 99%

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Cusick

Libbey

Patel

et al. 2013

J Virol

101

173

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b Viral infections of the central nervous system (CNS) can trigger an antiviral immune response, which initiates an inflammatory cascade to control viral replication and dissemination. The extent of the proinflammatory response in the CNS and the timing of the release of proinflammatory cytokines can lead to neuronal excitability. Tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), two proinflammatory cytokines, have been linked to the development of acute seizures in Theiler's murine encephalomyelitis virus-induced encephalitis. It is unclear the extent to which the infiltrating macrophages versus resident CNS cells, such as microglia, contribute to acute seizures, as both cell types produce TNF-␣ and IL-6. In this study, we show that following infection a significantly higher number of microglia produced TNF-␣ than did infiltrating macrophages. In contrast, infiltrating macrophages produced significantly more IL-6. Mice treated with minocycline or wogonin, both of which limit infiltration of immune cells into the CNS and their activation, had significantly fewer macrophages infiltrating the brain, and significantly fewer mice had seizures. Therefore, our studies implicate infiltrating macrophages as an important source of IL-6 that contributes to the development of acute seizures.

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Human Parechoviruses: Biology and Infection

Fischer

Harvala

Midgley

2017

Encyclopedia of Life Sciences

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Infections with human parechoviruses (HPeVs) are highly prevalent, particularly in neonates, where they may cause substantial morbidity and mortality. The clinical presentation of HPeV infection in neonates is indistinguishable from that of enterovirus (EV) infection and may vary from mild disease involving gastrointestinal and/or respiratory symptoms to more severe illness with sepsis‐like symptoms such as fever, seizures, irritability, rash and/or feeding problems. HPeV is among the most common single causes of aseptic meningitis/meningoencephalitis in infants <90 days old worldwide. The mainstay of diagnosis for HPeV infections involves the use of molecular diagnostic techniques for detection of virus RNA (ribonucleic acid) in various materials (e.g. faeces, cerebrospinal fluid (CSF), nasopharyngeal, bronchial and autopsy materials). Despite the relatedness of HPeV and EV both at the genomic and clinical presentation levels, routine nucleic acid detection methods for EV will not detect HPeV. Laboratory diagnosis of these viral infections is important not only for differential diagnostic purposes and determining a patient's prognosis but also for guidance of clinical management. Clinical disease varies somewhat among genotypes; while HPeV1 mostly causes gastrointestinal illness, HPeV3 prominence is due to sepsis syndromes and central nervous system (CNS) infections in preterm and term infants. Of diagnostic importance, HPeV3 CNS infections usually lack CSF pleocytosis, and despite ‘unremarkable’ CSF, HPeV3 RNA can be amplified from CSF, nasopharyngeal and rectal swabs in an infected individual. Taking the global incidence of reported laboratory‐confirmed HPeV cases into consideration, mortality and sequelae are overall uncommon and usually accompanying initially severe or neurologically complicated acute illnesses. However, underreporting due to lack of testing and/or appropriate diagnostic methodology likely means gross underestimation of the true incidence of HPeV disease. Currently, neither effective treatment nor vaccines are available in the control of these common viruses with the potential to cause severe harm in neonates and young children worldwide. Key Concepts HPeV infections are common among infants and children worldwide. HPeV infections are underdiagnosed, and HPeV disease burden underestimated. Nineteen HPeV types identified so far – their role/significance in human infections unclear except for HPeV3. HPeV3 is a major cause of neonatal infections including severe meningoencephalitis. Genomic differences between EV and HPeV. Diagnostics: HPeV required specific PCR for detection, not that easy to culture. Majority of children with HPeV3 infection lack pleocytosis in CSF/have normal CSF. Having older siblings are associated with higher risk for an infant to be hospitalised with severe HPeV infection. HPeV infection should always be ruled out when caring for infants with sepsis‐like illness and/or CNS infection.

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Human Parechoviruses as an Important Viral Cause of Sepsislike Illness and Meningitis in Young Children

Cited by 234 publications

References 32 publications

Novel Human Parechovirus from Brazil

Novel Human Parechovirus from Brazil

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Human Parechoviruses: Biology and Infection

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