Viral meningitis: an overview

May combine two claims.

PCR is the gold standard for diagnosing viral meningitis, detecting and quantifying viral DNA or RNA in the patient's CSF.

“The gold standard tool for diagnosis of viral meningitis is the polymerase chain reaction (PCR), which detects and quantifies viral DNA or RNA in the patient’s CSF [41].”

• cites [41] Verstrepen WA et al (2001) Rapid detection of enterovirus RNA in cerebrospinal fluid specimens with a novel single-tube real-time reverse transcription-PCR assay. J Clin Microbiol 39(11):4093–4096 sourceDisputed

  The paper’s introductory passage explicitly calls viral culture the “gold standard” for diagnosing enteroviral infections in CSF and describes RT-PCR as an alternative. Its assay detects and quantifies enterovirus RNA, but it does not establish PCR as the gold standard for viral meningitis generally. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

In bacterial meningitis, CSF typically shows a WBC count of at least 500 cells/μl with more than 80% neutrophils, glucose not exceeding 300 mg/dL, a decreased CSF/blood glucose ratio below 0.4, and an elevated protein level of 1 g/l.

“For instance, a high WBC count (≥ 500 cells/μl) with a large proportion of neutrophils (>80%) is usually observed in bacterial meningitis. Furthermore, in bacterial meningitis, the CSF glucose level typically does not exceed (300 mg/dL), but a decreased glucose CSF/blood ratio (< 0.4), and an elevated protein level (1 g/l) are indications of bacterial meningitis [2].”

• cites [2] Hoffman O, Weber JR (2009) Pathophysiology and treatment of bacterial meningitis. Ther Adv Neurol Disord 2(6):401–412 sourceDisputed

  The Laboratory tests passage (Introduction; page not available) gives the opposite inequalities for three cited thresholds: WBC <500 cells/μl, protein <1 g/l, and CSF/blood glucose ratio >0.4. It supports predominant neutrophils but gives no >80% threshold or CSF glucose limit of 300 mg/dL. The verdict follows the inequalities as printed in our copy. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

EV-D68 binds to the N-acetylneuraminic acid α2,6-galactose receptor on epithelial cells, which is predominant in the upper respiratory tract, and this could explain the limited spread of the virus and its rare progression to neurological complications such as meningitis.

“As the virus enters the upper respiratory tract (URT), it binds to the N-acetylneuraminic acid α2,6-galactose receptor found on the surface of the epithelial cells. This receptor is predominant in the upper respiratory tract (URT) [73], which could explain the limited spread of the virus and its rare progression to neurological complications, such as meningitis.”

• cites [73] Esposito S et al (2015) Enterovirus D68 infection. Viruses 7(11):6043–6050 sourceDisputed

  Split into 2 atoms — 1 confirmed, 0 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In Egypt, 573 of 1337 meningitis cases (42.86%) from 2013 to 2015 were due to viral infections.

“Additionally, a three-year study (2013-2015) in Egypt indicated that 573 out of 1337 meningitis cases (42.86%) were due to viral infections [18].”

• cites [18] Abdelkader MM et al (2017) Prevalence of MDR pathogens of bacterial meningitis in Egypt and new synergistic antibiotic combinations. PLoS ONE 12(2):e0171349–e0171349 sourcePartly supported

  The Results > Data analysis section reports 573 of 1,337 specimens (42.86%) as *possibly* viral meningitis. It describes a two-year study from September 2013 to September 2015, not a three-year study, and includes specimens classified as potentially misdiagnosed cases. The source therefore does not establish that 573 confirmed meningitis cases were due to viral infections. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In South Africa, children under 10 years of age made up 87.3% of those affected in an aseptic meningitis outbreak caused by coxsackievirus A9.

“In South Africa, children less than 10 years of age constituted 87.3% of those affected by an aseptic meningitis outbreak in which the responsible pathogen was coxsackievirus A9 [12].”

• cites [12] Smuts H et al (2018) Molecular characterization of an outbreak of enterovirus-associated meningitis in Mossel Bay, South Africa, December 2015-January 2016. BMC Infect Dis 18(1):709–709 sourcePartly supported

  The Abstract Results report that 55 of 63 patients (87.3%) were under 10, and the Conclusions identify coxsackievirus A9 as responsible for the South African outbreak. But the Results distinguish those 63 enterovirus-positive patients from the 43 cases classified as part of the outbreak. The paper does not establish that 87.3% of the outbreak cases were under 10. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Viral meningitis is the most frequent form of aseptic meningitis and usually affects young children.

“Viral meningitis is the most common type of aseptic meningitis and usually affects young children [1].”

• cites [1] Logan SA, MacMahon E (2008a) Viral meningitis. BMJ 336(7634):36–40 sourcePartly supported

  The ‘How common is viral meningitis?’ section says viral meningitis is most common in young children. The paper defines aseptic meningitis and discusses viral causes, but does not say that viral meningitis is the most common type of aseptic meningitis. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the United Arab Emirates between 2000 and 2005, 37% of meningitis cases were viral, with a mortality rate of 3%, and children and young adults were the most affected age group.

“Based on earlier studies in the Gulf region between 2000 and 2005, 37% of meningitis cases in the United Arab Emirates (UAE) were caused by viral infections, with a mortality rate of 3%. The same study also showed that children and young adults are the most affected age group [15].”

• cites [15] Dash N et al (2007) Epidemiology of meningitis in Al-Ain, United Arab Emirates, 2000–2005. Int J Infect Dis 11(4):309–312 sourcePartly supported

  The Abstract and Results report that 37% of 92 meningitis cases in Al-Ain Medical District were viral; the Results give a 3% case-fatality rate for viral meningitis. The claim extends this district-level finding to the UAE as a whole. The Results say viral cases occurred mainly among children and young adults, but the highest rate of meningitis overall was in children aged 0–5, not children and young adults collectively. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In Kuwait, 387 patients, mainly pediatric, had aseptic meningitis, with echovirus 9, E-11, and E-30 accounting for 24% of cases.

“In another study from Kuwait, it was shown that 387 patients (mainly pediatric patients) had aseptic meningitis, with the most common viral agents being echovirus 9 (E-9), E-11 and E-30, accounting for 24% of the cases [16].”

• cites [16] Dalwai A, Ahmad S, Al-Nakib W (2010) Echoviruses are a major cause of aseptic meningitis in infants and young children in Kuwait. Virol J 7(1):236 sourcePartly supported

  The Patient’s data section reports 387 children under 12 with aseptic meningitis, and Table 3 identifies E9, E11 and E30 as the most common detected enterovirus genotypes. But the Abstract’s Results assign 24% to all enterovirus-positive cases (92 of 387), not to those three echoviruses. Table 3 lists 60 cases with those genotypes, about 16% of the 387 cases. (LLM, conf=0.93)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In England between 2011 and 2014, the incidence of viral meningitis was 2.73 per 100,000, with most cases caused by non-polio enteroviruses.

“A study conducted in England between 2011 and 2014 showed that the incidence of viral meningitis was 2.73 per 100,000, with the largest number of cases caused by non-polio enteroviruses [8].”

• cites [8] McGill F et al (2018) Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study. Lancet Infect Dis 18(9):992–1003 sourcePartly supported

  The Results report enrollment across England from September 2011 to September 2014 and identify enteroviruses as the most frequent cause of confirmed viral meningitis (127 of 231 cases). The Discussion gives an estimated annual incidence of 2.73 per 100,000, but specifies UK adults with confirmed viral meningitis; it does not identify the enteroviruses as non-polio. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Lebanon, 82.7% of study subjects were diagnosed with viral meningitis and 17.3% with bacterial meningitis.

“Furthermore, a study in Lebanon showed that 82.7% of study subjects were diagnosed with viral meningitis, while only 17.3% were diagnosed with bacterial meningitis [22].”

• cites [22] Haydar SM et al (2019) Adherence to international guidelines for the treatment of meningitis infections in Lebanon. Saudi Med J 40(3):260–265 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Viral meningitis occurs throughout the year but is most common in summer and autumn.

“Viral meningitis occurs throughout the year, but it is most commonly seen in summer and autumn [7].”

• cites [7] Logan SAE, MacMahon E (2008b) Viral meningitis. BMJ (Clinical research ed.) 336(7634):36–40 sourcePartly supported

  The “Who gets it?” section says enterovirus infection is highest in summer and autumn in temperate climates, but remains high year-round in tropical and subtropical climates. Enteroviruses are the most common cause of viral meningitis, yet the paper does not state that viral meningitis overall follows this year-round pattern or that its summer–autumn peak applies across climates. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

The SARS-CoV-2 case report suggests that SARS-CoV-2 may be neuroinvasive and may cause central nervous system complications such as meningitis.

“This case report indicates the possible neuroinvasive potential of SARS-CoV-2 and its potential to cause CNS complications such as meningitis [14] (Tables 1 and 2).”

• cites [14] Moriguchi T et al (2020) A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 94:55–58 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

According to the Palestinian Ministry of Health, aseptic meningitis incidence is 6.8 per 100,000 in the West Bank and 247 per 100,000 in the Gaza Strip.

“According to the Palestinian Ministry of Health, the incidence of aseptic meningitis is 6.8 per 100,000 in the West Bank and 247 per 100,000 in the Gaza Strip [21].”

• cites [21] Dumaidi K, Al-Jawabreh A (2017) Molecular detection and genotyping of enteroviruses from CSF samples of patients with suspected sepsis-like illness and/or aseptic meningitis from 2012 to 2015 in West Bank, Palestine. PLoS ONE 12(2):e0172357–e0172357 sourcePartly supported

  The Introduction reports the same rates for the West Bank and Gaza Strip in 2014, and the Discussion figure caption identifies the incidence data as Ministry of Health-reported. But the source describes the rates as covering “sepsis-like illness and/or viral meningitis,” not aseptic meningitis alone. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Enterovirus infection can lead to different clinical outcomes, including respiratory illness, hepatitis, pancreatitis, myocarditis, and hand, foot, and mouth disease.

“Infection with EVs can lead to different clinical outcomes, such as respiratory illness, hepatitis, pancreatitis, myocarditis, and hand, foot, and mouth (HFM) disease [52, 53].”

• cites [52] Wells AI, Coyne CB (2019) Enteroviruses: a gut-wrenching game of entry, detection, and evasion. Viruses 11(5):460 sourceSupported
• cites [53] Akuzawa N et al (2014) Myocarditis, hepatitis, and pancreatitis in a patient with coxsackievirus A4 infection: a case report. Virol J 11:3–3 sourcePartly supported

  The Background and Discussion identify coxsackieviruses as enteroviruses associated with myocarditis and pancreatitis; the Case report describes liver dysfunction in a patient with coxsackievirus A4 infection. The Case report also mentions earlier cough and sore throat, but does not establish respiratory illness as an enterovirus outcome, and our copy does not address hand, foot, and mouth disease. No page numbers are available in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Other manifestations of meningitis include short and fast breathing, loss of appetite, neck stiffness and pain, and sensitivity to bright light.

“Other manifestations of the disease include short and fast breathing, loss of appetite, neck stiffness and pain, and sensitivity to bright light [28].”

• cites [28] Parikh V, Tucci V, Galwankar S (2012) Infections of the nervous system. Int J Crit Illn Inj Sci 2(2):82 sourcePartly supported

  The Meningitis > Neisseria meningitides section (page unavailable) lists a stiff neck and radicular pain; the Listeria section also reports poor feeding, but specifically in infants. The St. Louis encephalitis section lists photophobia with a viral meningitis presentation. Our copy does not identify short, fast breathing as a meningitis manifestation, and its support for loss of appetite is limited to infant poor feeding. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Children are usually less likely to present with meningeal complications and often present with nonspecific illness, making meningitis more likely to be misdiagnosed in children.

“Children are usually less likely to present with meningeal complications and usually present with nonspecific illness, which makes meningitis more likely to be misdiagnosed in children [31].”

• cites [31] Shukla B et al (2017) Aseptic meningitis in adults and children: diagnostic and management challenges. J Clin Virol 94:110–114 sourcePartly supported

  The Discussion (page unavailable) says children in this aseptic-meningitis cohort were less likely than adults to present with meningeal complaints and notes that children often present with nonspecific febrile illness. Neither the Discussion nor the Results (page unavailable) establishes that meningitis is more likely to be misdiagnosed in children; the paper's diagnostic-challenge conclusion concerns unknown etiologies, not a higher pediatric misdiagnosis rate. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Most viral meningitis cases go undetected, and fatal cases manifest as severe encephalitic syndrome rather than meningitis.

“Moreover, it is made harder by the fact that most viral meningitis cases go undetected, and fatal cases manifest as severe encephalitic syndrome rather than meningitis [29].”

• cites [29] Irani DN (2008) Aseptic meningitis and viral myelitis. Neurol Clin 26(3):635 sourcePartly supported

  The Clinical Features section (page not supplied) reports that some viral infections with a more encephalitic presentation have adverse outcomes, while aseptic meningitis is typically self-limited. It does not establish that fatal cases generally present as severe encephalitis, or that most viral meningitis cases go undetected. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Next-generation sequencing has been used in studies to detect a wide variety of pathogens including viruses, but its possible application as a diagnostic tool in meningitis is not yet clear.

“Next-generation sequencing (NGS) was recently used in a number of studies to detect a wide variety of pathogens, including viruses, the possible application of this technique as a diagnostic tool in meningitis cases is not yet clear, and more studies are required [45].”

• cites [45] Poplin V, Boulware DR, Bahr NC (2020) Methods for rapid diagnosis of meningitis etiology in adults. Biomark Med 14(6):459–479. https://doi.org/10.2217/bmm-2019-0333 sourceSupported

May combine two claims.

EV-D68 strains were able to infect and replicate in a human neuroblastoma cell line and a postnatal cortical neuron culture, whereas non-neurotropic strains were not.

“In addition, EV-D68 strains were able to infect and replicate in a human neuroblastoma cell line and a postnatal cortical neuron culture, but non-neurotropic strains were not [60].”

• cites [60] Brown DM et al (2018) Contemporary circulating enterovirus D68 strains have acquired the capacity for viral entry and replication in human neuronal cells. mBio 9(5):e01954-e2018 sourcePartly supported

  The Results report that US/MO/47 replicated in the SH-SY5Y neuroblastoma cell line and primary human neurons, whereas US/TN and VR1197 did not. Materials and Methods identifies the latter culture as human postnatal brain neurons, but our copy does not identify them as cortical neurons. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

Echoviruses such as E-6, E-9, E-11, E-13, E-19, and E-30 belong to the species Enterovirus B and are commonly associated with viral meningitis in children.

“Echoviruses, such as E-6, E-9, E-11, E-13, E-19, and E-30 also belong to the species Enterovirus B and are commonly known to be associated with viral meningitis in children [69].”

• cites [69] Kim H-J et al (2012) Epidemics of viral meningitis caused by echovirus 6 and 30 in Korea in 2008. Virol J 9:38–38. https://doi.org/10.1186/1743-422X-9-38 sourceSupported

May combine two claims.

Neutrophilic pleocytosis usually indicates bacterial rather than viral meningitis, but 25% of patients with central nervous system abnormalities caused by viral agents have neutrophilic pleocytosis.

“The presence of neutrophilic pleocytosis is usually indicative of bacterial meningitis rather than viral meningitis. However, it has been found that 25% of patients with CNS abnormalities caused by viral agents have neutrophilic pleocytosis [39].”

• cites [39] Jaijakul S et al (2017) The clinical significance of neutrophilic pleocytosis in cerebrospinal fluid in patients with viral central nervous system infections. Int J Infect Dis 59:77–81 sourceSupported

May combine two claims.

In viral meningitis, the WBC count typically ranges from 80 to 100 cells/μl with a large proportion of lymphocytes (>80%), and glucose and protein levels usually remain normal.

“In viral meningitis, the WBC count typically ranges between 80 and 100 cells/μl (pleocytosis), with a large proportion of lymphocytes (>80%) [21]. Also, glucose and protein levels usually remain normal [35].”

• cites [21] Dumaidi K, Al-Jawabreh A (2017) Molecular detection and genotyping of enteroviruses from CSF samples of patients with suspected sepsis-like illness and/or aseptic meningitis from 2012 to 2015 in West Bank, Palestine. PLoS ONE 12(2):e0172357–e0172357 sourcePartly supported

  The Introduction (page not provided) describes CSF pleocytosis as a feature of aseptic meningitis, supporting that limited part of the cited clause. It gives age-dependent WBC thresholds, not a typical count of 80–100 cells/μl, and does not report lymphocytes exceeding 80%. The Results (page not provided) also report that many enterovirus-positive patients lacked pleocytosis. The separate statement about glucose and protein cites [35], not this source. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [35] Seehusen DA, Reeves M, Fomin D (2003) Cerebrospinal fluid analysis. Am Fam Physician 68(6):1103–1108Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Gram staining and bacterial culture are key diagnostic tools for identifying bacterial infections, and viral meningitis is suspected when both are negative.

“Gram staining and bacterial culture are the key diagnostic tools for identifying bacterial infections [2], and viral meningitis is suspected when Gram staining and culture of CSF are negative.”

• cites [2] Hoffman O, Weber JR (2009) Pathophysiology and treatment of bacterial meningitis. Ther Adv Neurol Disord 2(6):401–412 sourceSupported

May combine two claims.

Viral meningitis pathogenesis begins when the causative agent enters the host through respiratory secretions or the fecal-oral route, causing primary infection in the respiratory or gastrointestinal tract, followed by secondary central nervous system infection that causes meningitis or other neurological problems.

“The pathogenesis of viral meningitis begins when the causative agent enters the host through respiratory secretions or by the fecal-oral route to cause primary infection in the respiratory or gastrointestinal (GI) tract. This is followed by secondary infection of the CNS, causing meningitis or other neurological problems.”

• cites [46] Kim JV et al (2009) Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 457(7226):191–195 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites [47] Wolinsky JS, Klassen T, Baringer JR (1976) Persistence of neuroadapted mumps virus in brains of newborn hamsters after intraperitoneal inoculation. J Infect Dis 133(3):260–267 sourceNot checked — no full text of the source
• cites [48] Wong KT et al (2008) The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol 67(2):162–169 sourceNot checked — no full text of the source
• cites [49] Munster VJ et al (2012) Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route. Sci Rep 2(1):736 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Difficulty focusing or concentrating and double vision can be associated with meningitis and may continue after recovery.

“In addition, difficulty in focusing or concentrating as well as double vision can also be associated with meningitis and may continue after recovery [29].”

• cites [29] Irani DN (2008) Aseptic meningitis and viral myelitis. Neurol Clin 26(3):635 sourceCould not verify

  The Aseptic Meningitis Clinical Features section says that symptoms in adults with enteroviral meningitis may persist for several weeks. It does not identify difficulty concentrating or double vision, or say that either continues after recovery. Searches for focusing, concentration, double vision, and diplopia found no passage addressing those symptoms. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

May combine two claims.

Risk factors that increase susceptibility to viral meningitis include compromised immunity, age, travel history, and HIV infection.

“There are a number of risk factors that are known to increase one's susceptibility to contracting viral meningitis, including compromised immunity, age, travel history, and HIV infection [7].”

• cites [7] Logan SAE, MacMahon E (2008b) Viral meningitis. BMJ (Clinical research ed.) 336(7634):36–40 sourcePartly supported

  “How common is viral meningitis?” reports that incidence is highest in young children, and “What causes it?” (box 1) links immunocompromised hosts and travel history to particular viral causes. The “Human immunodeficiency virus” section identifies primary HIV infection as a cause of aseptic meningitis. The paper does not establish that all four factors generally increase susceptibility to contracting viral meningitis; travel history, in particular, is presented as a clue to the possible cause of an existing case. (LLM, conf=0.85)

  Experimental — accuracy not yet measured

May combine two claims.

Viral infection of the central nervous system can occur through infection of the choroid plexus epithelium, infection of lymphoid tissue, induction of inflammation and blood-brain barrier breakdown, and infection of peripheral sensory neural pathways.

“Viral infection of the CNS can occur through different mechanisms, such as infection of the choroid plexus epithelium, infection of the lymphoid tissue, induction of inflammation and blood-brain barrier (BBB) breakdown, and infection of peripheral sensory neural pathways [46–49] (Fig. 1).”

• cites [46] Kim JV et al (2009) Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis. Nature 457(7226):191–195 sourcePartly supported

  The main text reports blood–brain barrier breakdown and inflammatory cell recruitment during LCMV infection of the murine CNS. But the Methods (Virus; page unavailable) say the mice were infected intracerebrally, and the paper treats barrier breakdown as injury following infection—not as a route by which virus enters the CNS. Our copy does not support the listed choroid plexus, lymphoid-tissue, or sensory-neural pathways. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [47] Wolinsky JS, Klassen T, Baringer JR (1976) Persistence of neuroadapted mumps virus in brains of newborn hamsters after intraperitoneal inoculation. J Infect Dis 133(3):260–267 sourceNot checked — no full text of the source
• cites [48] Wong KT et al (2008) The distribution of inflammation and virus in human enterovirus 71 encephalomyelitis suggests possible viral spread by neural pathways. J Neuropathol Exp Neurol 67(2):162–169 sourceNot checked — no full text of the source
• cites [49] Munster VJ et al (2012) Rapid Nipah virus entry into the central nervous system of hamsters via the olfactory route. Sci Rep 2(1):736 sourcePartly supported

  The Results (Entry of Nipah virus into the CNS) directly document entry along olfactory neurons, supporting the peripheral sensory neural pathway. The Discussion describes blood–brain barrier disruption as a proposed route but says it was unlikely to be the initial route in these hamsters; it also discusses inflammation as a possible cause of barrier breakdown, not as a demonstrated entry mechanism. Our copy does not describe CNS entry through infection of the choroid plexus epithelium or lymphoid tissue. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Four glycoproteins in HSV-1 and HSV-2 are important for viral entry (gB, gD, gH, and gL), but cell binding is mediated by only two glycoproteins, gB and/or gC, that bind to cell-surface heparan sulfate.

“Four glycoproteins in HSV-1 and HSV-2 are important for viral entry (gB, gD, gH, and gL); however, cell binding is mediated by only two glycoproteins, gB and/or gC, that bind to cell-surface heparan sulfate [82].”

• cites [82] Spear PG, Longnecker R (2003) Herpesvirus entry: an update. J Virol 77(19):10179–10185 sourceSupported

May combine two claims.

EBV can infect endothelial cells of blood vessels in the brain, causing latent infection; when the brain undergoes stress, the virus can be activated and expression of cytokines and chemokines such as IL-1, TNF-α, IL-12, and IL18 increases, resulting in an inflammatory response.

“The virus can also infect the endothelial cells of blood vessels in the brain, causing latent infection. When the brain undergoes stress, the virus can be activated and the expression of different cytokines and chemokines, such as IL-1, TNF-α, IL-12 and IL18 increases, resulting in an inflammatory response [86].”

• cites [86] Koyuncu OO, Hogue IB, Enquist LW (2013) Virus infections in the nervous system. Cell Host Microbe 13(4):379–393. https://doi.org/10.1016/j.chom.2013.03.010 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

EV-D68 is the most common member of the species Enterovirus D associated with aseptic meningitis and can cause central nervous system complications in children, commonly meningitis and flaccid paralysis.

“Enterovirus D68 (EV-D68) is the most common member of the species Enterovirus D found to be associated with the development of aseptic meningitis. EV-D68 can cause CNS complications in children, commonly meningitis and flaccid paralysis [72].”

• cites [72] González-Sanz R et al (2019) Enterovirus D68-associated respiratory and neurological illness in Spain, 2014–2018. Emerg Microbes Infect 8(1):1438–1444 sourcePartly supported

  The non-respiratory-disease results (p. 4) report EV-D68 in children with meningitis or meningoencephalitis and acute flaccid paralysis. But the paper calls EV-D68 the most frequently detected enterovirus in its respiratory samples (Abstract, p. 2), not the most common member of species Enterovirus D associated with aseptic meningitis. The Discussion (p. 7) also says the association with paralysis is accepted but causality has not been proven, so “can cause” is stronger than its conclusion. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Valacyclovir was tested in clinical trials for antiviral suppression of recurrence of meningitis, but treatment with valacyclovir twice daily did not prevent recurrent meningitis and was not recommended for this purpose.

“Valacyclovir was also tested in clinical trials for its antiviral suppression ability on recurrence of meningitis. However, treatment with valacyclovir (twice daily) did not prevent recurrent meningitis and was not recommended for this purpose [105, 106].”

• cites [105] Aurelius E et al (2012) Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial. Clin Infect Dis 54(9):1304–1313 sourceSupported
• cites [106] Kato K et al (2015) Recurrent neonatal herpes simplex virus infection with central nervous system disease after completion of a 6-month course of suppressive therapy: case report. J Infect Chemother 21(12):879–881 sourceNot checked — no full text of the source

May combine two claims.

Psoromic acid, a bioactive lichen-derived compound, has been found to inhibit replication of both HSV-1 and HSV-2 by inhibiting proteases and DNA polymerases, making it a possible drug for treating meningitis caused by HSV.

“Recently, a promising drug called psoromic acid (a bioactive lichen-derived compound) has been found to inhibit the replication of both HSV-1 and HSV-2 by inhibiting proteases and DNA polymerases, which makes it a possible drug for treating meningitis caused by HSV [104].”

• cites [104] Hassan STS et al (2019) Psoromic acid, a lichen-derived molecule, inhibits the replication of HSV-1 and HSV-2, and inactivates HSV-1 DNA polymerase: shedding light on antiherpetic properties. Molecules (Basel, Switzerland) 24(16):2912 sourcePartly supported

  Results and Discussion §2.1 reports that psoromic acid inhibits HSV-1 and HSV-2 replication, and §2.2 links its anti-HSV-1 activity to inhibition of HSV-1 DNA polymerase. Section 2.4 suggests HSV-2 protease inhibition from molecular docking, rather than demonstrating that protease inhibition causes reduced replication. The paper does not assess psoromic acid as a treatment for HSV meningitis. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Infection of the central nervous system by West Nile virus activates Toll-like receptor 3, increases the concentration of TNF-α and other pro-inflammatory factors, which in turn increases the permeability of the blood-brain barrier and leads to neural death.

“Infection of the CNS by WNV activates Toll-like receptor 3, increases the concentration of TNF-α and other pro-inflammatory factors, which in turn increases the permeability of the BBB and leads to neural death [96].”

• cites [96] Lim SM et al (2011b) West Nile virus: immunity and pathogenesis. Viruses 3(6):811–828 sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

A recent systematic analysis showed that most viral meningitis cases have a good long-term clinical outcome and that patients with viral meningitis have a better outcome after hospital discharge than patients with viral encephalitis.

“A recent systematic analysis showed that most viral meningitis cases have a good long-term clinical outcome and that patients with viral meningitis have a better outcome after hospital discharge than patients with viral encephalitis [109].”

• cites [109] Hudson JA et al (2020) Outcomes beyond hospital discharge in infants and children with viral meningitis: a systematic review. Rev Med Virol 30(2):e2083 sourcePartly supported

  The Discussion reports good clinical outcomes in the majority of cases, but the review covers infants and children, not patients of all ages. It also says its results “suggest” children with viral meningitis “may have better outcomes” than children with viral encephalitis; the citing sentence presents that comparison as established. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

EBV pathogenesis starts when the virus infects oropharyngeal epithelium cells, then spreads to lymphoid tissue and infects lymphoid cells, mainly B cells; in the infected B cell population the virus can be latent or, less frequently, lytic, and in the latent stage it mainly expresses EBNAs and LMPs.

“EBV pathogenesis starts when the virus infects oropharyngeal epithelium cells. It then spreads to the lymphoid tissue and infects lymphoid cells, mainly B cells. In the infected B cell population, the virus can be latent or, less frequently, lytic. In the latent stage, the virus mainly expresses EBNAs (Epstein-Barr nuclear antigens) and LMPs (latent membrane proteins) [85].”

• cites [85] Akkoc G et al (2016) Epstein-Barr virus encephalitis in an immunocompetent child: a case report and management of Epstein-Barr virus encephalitis. Case Rep Infect Dis 2016 sourceCould not verify

  Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

These herpesviruses are known to cause meningitis and can establish a latent infection in neurons that can be reactivated.

“All of these viruses are known to cause meningitis and can establish a latent infection in neurons, which can be reactivated [82].”

• cites [82] Spear PG, Longnecker R (2003) Herpesvirus entry: an update. J Virol 77(19):10179–10185 sourcePartly supported

  The opening section says HSV-1 and HSV-2 can cause meningitis and that they, along with VZV, establish latent infections in neurons and can reactivate from neurons. It does not say VZV causes meningitis, so the claim's 'all of these viruses' wording is not fully supported. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Human influenza viruses often cause pneumonia and acute respiratory distress syndrome, but on rare occasions they can cause extra-respiratory illnesses including meningitis, encephalitis, meningoencephalitis, and myelitis.

“Human influenza viruses often cause pneumonia and acute respiratory distress syndrome (ARDS) [87], but on rare occasions, they can cause extra-respiratory illnesses, including meningitis [87], encephalitis [88], meningoencephalitis, and myelitis [89].”

• cites [87] Liang C-Y, Yang C-H, Lin J-N (2018) Focal encephalitis, meningitis, and acute respiratory distress syndrome associated with influenza A infection. Med Princ Pract 27(2):193–196 sourcePartly supported

  The Introduction lists pneumonia and meningitis among influenza complications, and the Conclusion says neurologic complications are infrequent compared with respiratory symptoms. The Conclusion also reports one patient with acute respiratory distress syndrome (ARDS), but the paper does not establish that influenza often causes ARDS; a single case cannot support that frequency claim. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [88] Sejvar JJ, Uyeki TM (2010) Neurologic complications of 2009 influenza A (H1N1). Neurology 74(13):1020 sourceNot checked — no full text of the source
• cites [89] Xia J-B et al (2014) H7N9 influenza A-induced pneumonia associated with acute myelitis in an adult. Intern Med 53(10):1093–1095 sourcePartly supported

  Citation [89] follows “meningoencephalitis, and myelitis.” The Introduction says influenza-associated nervous-system symptoms are uncommon and lists myelitis among reported complications; the Abstract describes a patient with H7N9-associated acute myelitis. Our copy does not mention meningoencephalitis, so that part of the attributed claim is unsupported. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Because HVEM is present on various cell types including epithelial cells and neurons, viral entry through this receptor is suggested in meningitis.

“HVEM is present on the surface of various cell types, including epithelial cells and neurons. Accordingly, viral entry through this receptor is suggested in meningitis.”

• cites [82] Spear PG, Longnecker R (2003) Herpesvirus entry: an update. J Virol 77(19):10179–10185 sourcePartly supported

  The HSV entry section (page not specified) identifies HVEM as an entry receptor and says it is expressed in various cell types, including epithelial cells. It attributes neuronal expression and potential entry into neurons to nectins, not HVEM, and does not suggest HVEM-mediated entry in meningitis. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Three known cellular receptors have been identified for HSV: herpesvirus entry mediator, members of the immunoglobulin superfamily, and heparan sulfate generated by certain isoforms of 3-O-sulfotransferases.

“Three known cellular receptors have been identified for HSV: 1) herpesvirus entry mediator (HVEM), 2) members of the immunoglobulin superfamily, and 3) heparan sulfate generated by certain isoforms of 3-O-sulfotransferases [82].”

• cites [82] Spear PG, Longnecker R (2003) Herpesvirus entry: an update. J Virol 77(19):10179–10185 sourceSupported

May combine two claims.

The pathogenesis of West Nile virus depends mainly on replication of virus in the host's lymph nodes and skin keratinocytes, resulting in primary viremia; the virus can then spread to secondary locations such as the central nervous system after penetrating the blood-brain barrier.

“The pathogenesis of the virus depends mainly on the replication of virus in the host's lymph nodes and skin keratinocytes [95], resulting in primary viremia. The virus can then spread to secondary locations such as CNS after penetrating the BBB [96].”

• cites [95] Lim P-Y et al (2011a) Keratinocytes are cell targets of West Nile virus in vivo. J Virol 85(10):5197–5201 sourceNot checked — no full text of the source
• cites [96] Lim SM et al (2011b) West Nile virus: immunity and pathogenesis. Viruses 3(6):811–828 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Some vaccines have been developed for viruses such as EV-71.

“Some vaccines have been developed for some viruses such as EV-71 [107], considering its clinical significance, and the different types of EV-71 vaccines are summarized in Table 4.”

• cites [107] Yi E-J et al (2017) Enterovirus 71 infection and vaccines. Clin Exp Vaccine Res 6(1):4–14 sourceSupported

May combine two claims.

E-30 can cause neural damage by modulating TRIO protein function: it affects guanine exchange factor domain 2, activating RhoA, which activates ROCK and MLC signaling pathways, leading to actin formation and elevated nitric oxide levels, resulting in central nervous system complications.

“E-30 can cause neural damage by modulating the function of the TRIO protein. In the first pathway, the virus affects the function of guanine exchange factor domain 2 (GEFD2), which results in the activation of Ras homology family member A (RhoA), a GTPase signaling protein. This activates both the ROCK and MLC signaling pathways. This cascade of events leads to actin formation and elevation of the”

• cites [71] Lee J-W et al (2012) Echovirus 30 induced neuronal cell death through TRIO-RhoA signaling activation. PLoS ONE 7(5):e36656–e36656 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

V-7404 (a viral polymerase inhibitor) and DAS181 (a sialidase) are newly developed drugs against EV-D68.

“Moreover, V-7404 (viral polymerase inhibitor) and DAS181 (sialidase) are newly developed drugs against EV-D68 [73, 76].”

• cites [73] Esposito S et al (2015) Enterovirus D68 infection. Viruses 7(11):6043–6050 sourcePartly supported

  Section 5 (Diagnosis, Treatment and Prevention; page not provided) reports strong inhibitory activity against EV-D68 for both compounds and identifies DAS181 as a sialidase fusion protein. But it calls V-7404 a protease inhibitor, not a polymerase inhibitor, and says the drugs are being developed for other infections while remaining possible candidates for EV-D68 outbreaks. (LLM, conf=0.90)

  Experimental — accuracy not yet measured
• cites [76] Messacar K et al (2018) Enterovirus D68 and acute flaccid myelitis-evaluating the evidence for causality. Lancet Infect Dis 18(8):e239–e247 sourceCould not verify

  The Introduction (page unavailable) calls for further research to inform treatment, but does not identify V-7404 or DAS181 as drugs against EV-D68. Searches for both drug names and their proposed roles found no passage addressing the claim. (LLM, conf=0.75)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Jordan, viral meningitis accounted for 83% of all meningitis cases between 2001 and 2004 and 81% in 2014.

“Moreover, higher percentages of viral meningitis were reported in Jordan, reaching 83% of all meningitis cases between 2001 and 2004, and 81% in 2014 [19].”

• cites [19] Alzein K (2016) Revision of meningitis surveillance system in Jordan during 2001 and 2014 years. Epidemiol (sunnyvale) 6:220. https://doi.org/10.4172/2161-1165.100022 sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S4 (based).

The pathogenesis of viral meningitis is not clearly defined.

“The pathogenesis of viral meningitis is not clearly defined, and more studies are needed to improve the health care of patients in terms of early diagnosis and management.”

May combine two claims.

In Gaza during 2013-2014, 72% of meningitis cases were viral, mainly caused by enterovirus infection (35%).

“In a two-year study in Gaza (2013–2014), 72% of meningitis cases were classified as viral meningitis, caused mainly by an EV infection (35%) [20].”

• cites [20] Ghuneim N, Dheir M, AbuAli K (2016) Epidemiology of different types of meningitis cases in gaza governorates, occupied Palestinian Territory, December 2013–January 2014. J Antivir Antiretrovir 8(1):26–34 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Denmark, non-polio enteroviruses were the most common causative agent of aseptic meningitis, and incidence decreased with age from 58.7 per 100,000 after birth to 38.7 per 100,000 at 6 months and 15.6 per 100,000 at 5 years.

“In addition, a study done in Denmark showed similar findings, with non-polio enteroviruses being the most common causative agent. They also showed that the incidence of aseptic meningitis decreases with increasing age (58.7 per 100,000 after birth, 38.7 per 100,000 in 6-month-old infants, and 15.6 per 100,000 in 5-year-old children) [10] (Table 1).”

• cites [10] Hviid A, Melbye M (2007) The epidemiology of viral meningitis hospitalization in childhood. Epidemiology 18(6):695–701 sourceNot checked — no full text of the source

May combine two claims.

In Austria from 2001 to 2004, 56% of study patients had viral meningitis, with E-30, coxsackievirus-B, and EV-71 being the most frequent viruses.

“In Austria (2001-2004), 56% of the patients included in a study had viral meningitis, where E-30 (36.4%), coxsackievirus-B (19.6%), and EV-71 (13.1%) were the viruses that were most frequently found [13].”

• cites [13] Ortner B et al (2009) Epidemiology of enterovirus types causing neurological disease in Austria 1999–2007: detection of clusters of echovirus 30 and enterovirus 71 and analysis of prevalent genotypes. J Med Virol 81(2):317–324 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In China, viral meningitis caused by EV-71 accounted for about 55.2% of neurological disorders.

“Also, a study conducted in China found that viral meningitis caused by EV-71 accounted for approximately 55.2% of neurological disorders [11].”

• cites [11] Hu Y, Jiang L, Peng H-L (2015) Clinical analysis of 134 children with nervous system damage caused by enterovirus 71 infection. Pediatr Infect Dis J 34(7):718–723 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Egypt, among 250 confirmed meningitis cases, 17 were caused by viral agents, most commonly EV, HSV, and VZV.

“In Egypt, out of 250 confirmed cases of meningitis, 17 were caused by viral agents, and the most commonly encountered viruses were EV, herpes simplex virus (HSV), and varicella zoster virus (VZV) [23].”

• cites [23] Selim HS et al (2007) Microbial study of meningitis and encephalitis cases. J Egypt Public Health Assoc 82(1–2):1–19Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Qatar, the incidence of viral meningitis from 2011 to 2015 was estimated at 6.4 per 100,000, with most cases being children infected with enterovirus.

“In Qatar, it has been estimated that the incidence of viral meningitis from 2011 to 2015 was 6.4 per 100,000, with most cases being children infected with EV [17].”

• cites [17] Abid FB et al (2018) Epidemiology and clinical outcomes of viral central nervous system infections. Int J Infect Dis 73:85–90 sourceNot checked — no full text of the source

May combine two claims.

Clinical manifestations and symptoms of viral meningitis are largely similar across causative agents, which makes early diagnosis difficult.

“With few exceptions, the clinical manifestations and symptoms associated with viral meningitis are similar for the different causative agents, which makes it difficult to diagnose the disease at early stages.”

May combine two claims.

Coxsackievirus replicates in monocytes, T cells, and B cells during the viremia phase, and the susceptibility of immune cells to infection determines the severity of secondary organ damage.

“Another study demonstrated that this virus replicates in monocytes, T cells, and B cells during the viremia phase and that the level of susceptibility of immune cells to infection determines the severity of secondary organ damage [67], such as causing severe meningitis after reaching the CNS.”

• cites [67] Hwang JY et al (2012) Characterization of infections of human leukocytes by non-polio enteroviruses. Intervirology 55(5):333–341 sourceNot checked — no full text of the source

May combine two claims.

Patients with meningitis usually suffer from fever, chills, abdominal pain, nausea, and headache.

“Patients with meningitis usually suffer from fever, chills, abdominal pain, nausea, and headache [5].”

• cites [5] Kumar R (2005) Aseptic meningitis: diagnosis and management. Indian J Pediatr 72(1):57–63 sourceNot checked — no full text of the source

May combine two claims.

Analysis of brain tissues from mice born to mothers inoculated with coxsackievirus B4 showed signs of meningitis, accumulation of immune cells mainly T cells, and increased secretion of inflammatory cytokines and chemokines.

“Moreover, analysis of brain tissues obtained from mice born to mothers inoculated with coxsackievirus B4 showed signs of meningitis and accumulation of immune cells (mainly T cells) and increased secretion of inflammatory cytokines and chemokines (IL6, TNF-α, IFNα and MCP-1) [68].”

• cites [68] Jmii H et al (2020) Immunopathology in the brain of mice following vertical transmission of Coxsackievirus B4. Microb Pathog 103965 sourceNot checked — no full text of the source

May combine two claims.

Jolt accentuation of headache can be used in emergency settings to exclude meningitis, but its pooled sensitivity of 65.3% and specificity of 70.4% are considered low.

“A systematic review done by Iguchi and colleagues showed that jolt accentuation can be used in emergency settings to exclude meningitis. However, the pooled sensitivity and specificity of this test (65.3%, 70.4% respectively) are considered low, and more research is needed to assess its usefulness [32].”

• cites [32] Iguchi M et al (2020) Diagnostic test accuracy of jolt accentuation for headache in acute meningitis in the emergency setting. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD012824 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Enteroviruses can undergo vertical transmission from an infected mother to her infant by crossing the placenta or through breastfeeding.

“They can also undergo vertical transmission from an infected mother to her infant by crossing the placenta or through breastfeeding [55].”

• cites [55] Mereaux J et al (2017) Enterovirus infection during pregnancy: Underestimated cause of fetal and neonatal complications? Gynecologie, obstetrique, fertilite & senologie 45(4):231–237 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The pathogenesis of aseptic meningitis is not well understood and is difficult to study because of limited data.

“However, the pathogenesis of aseptic meningitis is not well understood, and it is difficult to study due to limited data.”

May combine two claims.

Diagnosis of mumps virus, herpesvirus, arboviruses, and HIV infections can be achieved using serological assays, but results might be negative at early stages, so a second sample should be obtained after two weeks and tested again.

“On the other hand, diagnosis of mumps virus, herpesvirus, arboviruses, and human immunodeficiency virus (HIV) infections can be achieved using serological assays, although the results might be negative at early stages of the disease. Hence, a second sample should be obtained after two weeks and tested again for the presence of viral agents [5].”

• cites [5] Kumar R (2005) Aseptic meningitis: diagnosis and management. Indian J Pediatr 72(1):57–63 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Enteroviruses can be transmitted through respiratory secretions or by the fecal-oral route.

“Enteroviruses can be transmitted through respiratory secretions or by the fecal-oral route [54].”

• cites [54] Burrell CJ, Howard CR, Murphy FA (2017) Chapter 32—picornaviruses. In: Burrell CJ, Howard CR, Murphy FA (eds) Fenner and White’s Medical virology (Fifth Edition). Academic, London, pp 447–463 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Skin rash is observed with certain types of meningitis and is considered a late sign of bacterial meningitis, where the pathogen in the blood targets capillary cells and damages them.

“Skin rash is also observed with certain types of meningitis and is considered a late sign of bacterial meningitis, where the pathogen in the blood targets the capillary cells, leading to their damage [30].”

• cites [30] Tsai J, Nagel MA, Gilden D (2013) Skin rash in meningitis and meningoencephalitis. Neurology 80(19):1808–1811 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Because obtaining CSF is difficult, alternative specimens such as blood, throat or nasal swabs, or stool samples might be used, particularly in suspected EV infections.

“However, since obtaining CSF is difficult, alternative specimens, such as blood, throat or nasal swabs, or stool samples might be used instead, particularly in cases of suspected EV infections [44].”

• cites [44] Kupila L et al (2005) Diagnosis of enteroviral meningitis by use of polymerase chain reaction of cerebrospinal fluid, stool, and serum specimens. Clin Infect Dis 40(7):982–987 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

A case report diagnosed a 9-day-old newborn with EV E-25 viral meningitis using RT-PCR and sequencing.

“A recent case report described a 9-day-old newborn admitted to the emergency department with nonspecific symptoms of fever and irritability. Molecular analysis (RT-PCR and sequencing) showed that the patient was positive for EV (specifically, E-25) and viral meningitis was diagnosed [43].”

• cites [43] Alhazmi A et al (2020) Repeated viral meningitis in a newborn. J NeuroVirol 1–3 sourceNot checked — no full text of the source

May combine two claims.

The virus can reach the bloodstream by infecting immune cells and cause secondary infections at other sites, such as the heart and central nervous system.

“Also, the virus could reach the bloodstream by infecting immune cells and cause secondary infections at other sites, such as the heart and CNS [61].”

• cites [61] Palacios G, Oberste M (2005) Enteroviruses as agents of emerging infectious diseases. J Neurovirol 11(5):424–433 sourceNot checked — no full text of the source

May combine two claims.

In most cases, enterovirus enters through the oral-fecal route, reaches the lower gastrointestinal tract, binds to a receptor on enterocytes, crosses the intestinal lining, reaches Peyer's patches, and continues replication.

“In most cases, the virus enters the body through the oral-fecal route until it reaches the lower gastrointestinal (GI) tract, where it binds to a specific receptor on the surface of enterocytes and crosses the lining of the intestine, reaching the Peyer’s patches, where it continues its replication [57].”

• cites [57] Rotbart HA (2000) Viral meningitis. In: Seminars in neurology. Copyright© 2000 by Thieme Medical Publishers, Inc sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In Egypt, 56% of pediatric aseptic meningitis cases were due to enterovirus.

“Another study in Egypt done on pediatric patients with aseptic meningitis found that 56% of cases were due to EV [24].”

• cites [24] Shaker OG, Abdelhamid N (2015) Detection of enteroviruses in pediatric patients with aseptic meningitis. Clin Neurol Neurosurg 129:67–71 sourceNot checked — no full text of the source

May combine two claims.

In HPeV-positive meningitis cases, RT-PCR achieved 100% sensitivity while viral culture failed to detect the virus.

“Similarly, in a study of HPeV-positive meningitis cases, 100% sensitivity was achieved with RT-PCR, while viral culture failed to detect the virus [42].”

• cites [42] De Crom S et al (2013) Prospective comparison of the detection rates of human enterovirus and parechovirus RT-qPCR and viral culture in different pediatric specimens. J Clin Virol 58(2):449–454 sourceNot checked — no full text of the source

May combine two claims.

Meningitis symptoms can resemble those of encephalitis or brain abscess, so viral meningitis can be misdiagnosed.

“In fact, signs and symptoms of meningitis can be similar to those of other diseases such as encephalitis or brain abscesses, and hence, viral meningitis can be misdiagnosed [25].”

• cites [25] Visintin C et al (2010) Management of bacterial meningitis and meningococcal septicaemia in children and young people: summary of NICE guidance. BMJ 340:c3209 sourceNot checked — no full text of the source

May combine two claims.

Pleocytosis is generally considered an important criterion for diagnosing viral meningitis, but it is often not observed in EV meningitis cases involving infants (38%) or children (39%), or when lumbar puncture is performed early.

“Pleocytosis generally is considered an important criterion for diagnosis of viral meningitis. However, a number of studies have shown that pleocytosis is often not observed in EV meningitis cases involving infants (38%) or children (39%), or when a lumbar puncture is performed at an early stage of disease [36, 37].”

• cites [36] de Crom SC et al (2012) Characteristics of pediatric patients with enterovirus meningitis and no cerebral fluid pleocytosis. Eur J Pediatr 171(5):795–800 sourceNot checked — no full text of the source
• cites [37] Alhazmi A et al (2019) Paediatric enterovirus meningitis without cerebrospinal fluid pleocytosis. J Infect 79(6):612–625 sourceNot checked — no full text of the source

May combine two claims.

A strong inflammatory immune response is induced during aseptic meningitis and plays an important role in the pathogenesis of the disease.

“Therefore, a strong inflammatory immune response is induced during aseptic meningitis and plays an important role in the pathogenesis of the disease.”

May combine two claims.

Although patients with viral meningitis usually do not need to be hospitalized, treatment such as antipyretics, antiemetics, and analgesics can be taken at home; some patients, such as those who suffer from seizures, need to be under medical supervision.

“Although patients with viral meningitis usually do not need to be hospitalized, treatment should be provided, such as antipyretics, antiemetics, and analgesics, which can be taken at home. However, some patients, such as those who suffer from seizures, need to be under medical supervision [5].”

• cites [5] Kumar R (2005) Aseptic meningitis: diagnosis and management. Indian J Pediatr 72(1):57–63 sourceNot checked — no full text of the source

May combine two claims.

An EV-D68 virus-like particle vaccine has been developed; it is composed of a recombinant baculovirus expressing 3CD protease and P1 precursor, and clinical trials showed high efficacy.

“Recently, an EV-D68 virus-like particle vaccine (VLP) has been developed [108]. The VLP is composed of a recombinant baculovirus expressing 3CD protease and P1 precursor. Clinical trials showed a high efficacy of the vaccine [108].”

• cites [108] Dai W et al (2018) A virus-like particle vaccine confers protection against enterovirus D68 lethal challenge in mice. Vaccine 36(5):653–659 sourceNot checked — no full text of the source

May combine two claims.

Antiviral therapy in immunocompromised patients with HSV-induced meningitis should be started immediately, and any delay in administration can result in adverse complications.

“Regarding to HSV treatment, one study showed that antiviral therapy in immunocompromised patients with HSV-induced meningitis should be started immediately and that any delay in the administration of treatment can result in the development of adverse complications [102].”

• cites [102] Momméja-Marin H et al (2003) Herpes simplex virus type 2 as a cause of severe meningitis in immunocompromised adults. Clin Infect Dis 37(11):1527–1533 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

The lack of a receptor in the respiratory tract might explain why HPeV-3 commonly causes meningitis and neonatal sepsis, while HPeV-1 causes respiratory and gastrointestinal illness.

“In fact, the lack of a receptor in the respiratory tract might explain why HPeV-3 commonly causes meningitis and neonatal sepsis, while HPeV-1 causes respiratory and gastrointestinal illness.”

May combine two claims.

Several arboviruses of different families have been associated with central nervous system infection and development of meningitis, including members of Flaviviridae (e.g., West Nile virus), Togaviridae (e.g., Eastern equine encephalitis virus), and Peribunyaviridae (e.g., La Crosse virus); most are zoonotic and transmitted to humans through arthropods such as mosquitoes, ticks, and sandflies.

“Several arboviruses of different families have been associated with CNS infection and development of meningitis. These include members of the families Flaviviridae (e.g., West Nile virus [WNV]), Togaviridae (e.g., Eastern equine encephalitis virus), and Peribunyaviridae (e.g., La Crosse virus). Most of these viruses are zoonotic and are transmitted to humans through arthropods such as mosquitoes,”

• cites [94] Miller BR (2008) Arboviruses. In: Mahy BWJ, Van Regenmortel MHV (eds) Encyclopedia of virology (Third Edition). Academic Press, Oxford, pp 170–176 sourceNot checked — no full text of the source

May combine two claims.

Several studies have shown that pleconaril shortens the course of symptoms, especially headache, but other studies have shown no significant difference between treatment and placebo groups.

“Several studies have shown that pleconaril plays an important role in shortening the course of symptoms, especially headache [6, 99]. However, other studies have shown that there was no significant difference between treatment and placebo groups [100].”

• cites [6] Desmond R et al (2006) Enteroviral meningitis: natural history and outcome of pleconaril therapy. Antimicrob Agents Chemother 50(7):2409–2414 sourceNot checked — no full text of the source
• cites [99] Romero JR (2001) Pleconaril: a novel antipicornaviral drug. Expert Opin Investig Drugs 10(2):369–379 sourceNot checked — no full text of the source
• cites [100] Abzug MJ et al (2003) Double blind placebo-controlled trial of pleconaril in infants with enterovirus meningitis. Pediatr Infect Dis J 22(4):335–341 sourceNot checked — no full text of the source

May combine two claims.

Collectively, these findings can explain the spread of influenza virus to the central nervous system, where it has the potential to cause various neurological syndromes such as meningitis.

“Collectively, this can explain the spread of influenza virus to the CNS, where it has the potential to cause various neurological syndromes, such as meningitis.”

May combine two claims.

HPeV can be transmitted from person to person through respiratory secretions and saliva, leading primarily to respiratory infections.

“HPeV can be transmitted from person to person through respiratory secretions and saliva, leading primarily to respiratory infections [77].”

• cites [77] Romero JR, Modlin JF (2015) 175—human parechoviruses. In: Bennett JE, Dolin R, Blaser MJ (eds) Mandell, Douglas, and Bennett's principles and practice of infectious diseases (Eighth Edition). Content Repository Only!: Philadelphia, pp 2091–2094.e2. sourceNot checked — no full text of the source

May combine two claims.

Pleconaril is licensed as intranasal therapy for the common cold, but it attains several-fold higher concentrations in the central nervous system, making it a potential treatment for brain-related diseases such as meningitis.

“It is licensed as intranasal therapy for the common cold, but it attains several-fold higher concentrations in the CNS, making it a potential treatment for brain-related diseases such as meningitis [99].”

• cites [99] Romero JR (2001) Pleconaril: a novel antipicornaviral drug. Expert Opin Investig Drugs 10(2):369–379 sourceNot checked — no full text of the source

May combine two claims.

The use of acyclovir against HSV-2-induced meningitis was evaluated, with better outcomes observed in treated patients; however, one patient developed concentration difficulties as a meningitis symptom that lasted for approximately three months.

“The use of acyclovir against HSV-2-induced meningitis was also evaluated, with better outcomes observed in treated patients. However, one patient developed concentration difficulties as a meningitis symptom that lasted for approximately three months [103].”

• cites [103] Bergström T, Alestig K (1990) Treatment of primary and recurrent herpes simplex virus type 2 induced meningitis with acyclovir. Scand J Infect Dis 22(2):239–240 sourceNot checked — no full text of the source

May combine two claims.

No specific treatment is prescribed for aseptic meningitis cases, and supportive medications are usually given to minimize disease complications such as fever and headache; full recovery takes from 5 to 14 days in the majority of cases.

“No specific treatment is prescribed for aseptic meningitis cases, and supportive medications are usually given to minimize disease complications such as fever and headache, and full recovery takes from 5 to 14 days in the majority of cases [5].”

• cites [5] Kumar R (2005) Aseptic meningitis: diagnosis and management. Indian J Pediatr 72(1):57–63 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Viral meningitis often goes undetected or leads to a self-limited disease in adults, but severe complications can develop in infants and children, including high fever, mental retardation, and even death in some cases.

“It often goes undetected or leads to a self-limited disease in adults. However, severe complications can develop in infants and children, including high fever, mental retardation, and even death in some cases.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Viral meningitis is considered one of the most common clinical conditions affecting different age groups.

“Viral meningitis is considered one of the most common clinical conditions affecting different age groups.”

Probably not a substantial claim: may not pass S4 (based).

Molecular epidemiology studies of viral meningitis are scarce in many countries, including the MENA region.

“Molecular epidemiology studies of viral meningitis are scarce in many countries, including the MENA region.”

Probably not a substantial claim: may not pass S4 (based).

Many viral causative agents are associated with aseptic meningitis, such as enterovirus, parechovirus, and herpesviruses.

“Many viral causative agents are found to be associated with aseptic meningitis, such as enterovirus, parechovirus, and herpesviruses.”