What viruses can cause meningitis

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. In addition, EV-D68 can reach the CNS through binding to the functional receptors of the olfactory nerve in the nasal cavity [ 76 ].

The neuropathogenesis of EV-D68 and its ability to infect neuron cells may highlight the potential link between EV-D68 infection and aseptic meningitis. HPeV can be transmitted from person to person through respiratory secretions and saliva, leading primarily to respiratory infections [ 77 ]. However, it can also cause neurological diseases, such as meningitis and encephalitis, particularly in children [ 78 ].

Moreover, it has been found that HPeV-3 utilizes an RBS-receptor binding site other than the arginine-glycine-glutamic acid sequence motif at the carboxyl terminus of VP capsid protein that is utilized by the other serotypes of HPeV [ 80 ]. To date, no receptor has been identified for HPeV-3 [ 81 ] that would explain its different tropism. 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.

The major neurological consequences of HSV are encephalitis and meningitis [ 83 , 84 ]. All of these viruses are known to cause meningitis and can establish a latent infection in neurons, which can be reactivated [ 82 ]. 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 ].

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. 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. The virus can also infect the endothelial cells of blood vessels in the brain, causing latent infection. 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 ].

Studies have shown that the influenza virus enters the CNS by the olfactory route [ 90 ] and other cranial nerves [ 91 ]. 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. Several arboviruses of different families have been associated with CNS infection and development of meningitis.

These include members of the families Flaviviridae e. Most of these viruses are zoonotic and are transmitted to humans through arthropods such as mosquitoes, ticks, and sandflies.

In the case of the arboviruses, viral entry can occur through skin bites from infected arthropods, which results in regional lymph node infection, viremia, and spread to the CNS, leading to meningitis [ 29 ]. 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. Therefore, WNV infection can trigger the development of various neurologica1 complications, including meningitis.

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 ]. Although corticosteroids are commonly given in cases of suspected bacterial meningitis to reduce the inflammatory effect that accompanies the disease, there is a lack of evidence of their efficacy against viral meningitis, and more studies are still needed [ 97 ].

Pleconaril is an antiviral drug that acts as an inhibitor of enterovirus replication by targeting the viral capsid structure [ 98 ].

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 ].

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 [ ]. The FDA did not approve the oral usage of the drug because it induces CYP3A enzyme activity, resulting in a drug interaction, especially with oral contraceptives [ ].

In a study done in the UK, researchers found that the median length of hospital stay was 4 days for patients with viral meningitis and nine days for those under antiviral therapy. They also concluded that delays in performing lumbar puncture and unnecessary treatments were associated with prolonged hospital stays and long-term morbidity [ 8 ]. 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 ].

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 [ ]. The use of acyclovir against HSVinduced 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 [ ].

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 [ ]. 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 [ , ].

Clinical trials showed a high efficacy of the vaccine [ ]. 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 [ ]. Viral meningitis is considered one of the most common clinical conditions affecting different age groups. 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.

Many viral causative agents are found to be associated with aseptic meningitis, such as enterovirus, parechovirus, and herpesviruses. Therefore, knowing the most common causative agents responsible for aseptic meningitis will help in better understanding the disease, and hence provide the basis for the development of preventative and control programs.

Molecular epidemiology studies of viral meningitis are scarce in many countries, including the MENA region. Accordingly, more studies should be conducted to understand the etiology and pathogeneses of this illness to develop new therapeutic interventions that will help in improving outcome. HMY developed the concept. AK and SJ wrote the initial draft. MKS revised the first draft and supervised students.

All authors read and approved the last version. This work was supported by funding from Qatar University, Grant Nos. Publisher's Note. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. National Center for Biotechnology Information , U. Arch Virol. Smatti , 2 and Hadi M. Yassine 2. Maria K. Hadi M. Author information Article notes Copyright and License information Disclaimer. Yassine, Email: aq. Corresponding author.

Received Jun 24; Accepted Oct 4. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. This article has been cited by other articles in PMC. Abstract Meningitis is a serious condition that affects the central nervous system.

Introduction Meningitis is an inflammation that affects the three protective membrane layers that cover the brain and spinal cord, called the meninges [ 1 ]. Epidemiology Viral meningitis occurs throughout the year, but it is most commonly seen in summer and autumn [ 7 ]. Table 1 Epidemiology of viral meningitis in children worldwide. Open in a separate window. Table 2 Epidemiology of viral meningitis in adults worldwide.

Clinical manifestations and diagnosis Although the etiology of meningitis can vary, the symptoms are usually similar. Pathogenesis 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.

Schematic presentation of the general features of viral meningitis pathogenesis. Family Picornaviridae Enteroviruses EVs 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 ].

Human parechovirus HPeV HPeV can be transmitted from person to person through respiratory secretions and saliva, leading primarily to respiratory infections [ 77 ]. Family Orthomyxoviridae 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 ].

Arboviruses Several arboviruses of different families have been associated with CNS infection and development of meningitis. Management 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.

Table 4 The most common types of vaccines developed against EV Conclusion Viral meningitis is considered one of the most common clinical conditions affecting different age groups.

Author contributions HMY developed the concept. Compliance with ethical standards Conflict of interest Authors declare no conflict of interest. Footnotes Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Viral meningitis. Hoffman O, Weber JR. Pathophysiology and treatment of bacterial meningitis.

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Vaccines can protect against some diseases, such as measles, mumps, chickenpox, and influenza, which can lead to viral meningitis. Make sure you and your child are vaccinated on schedule. Control mice and rats. If you have a rodent in or around your home, follow appropriate cleaning and control precautions. Top of Page. Skip directly to site content Skip directly to page options Skip directly to A-Z link.

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Request an Appointment at Mayo Clinic. Meningitis Open pop-up dialog box Close. Meningitis Meningitis is an infection and inflammation of the fluid and three membranes meninges protecting your brain and spinal cord. Share on: Facebook Twitter.

Show references Meningitis and encephalitis fact sheet. National Institute of Neurological Disorders and Stroke. Accessed Sept. Bacterial meningitis. Centers for Disease Control and Prevention. Bartt R. Acute bacterial and viral meningitis. Continuum Lifelong Learning in Neurology. Viral meningitis. Fungal meningitis. Derber CJ, et al. Head and neck emergencies: Bacterial meningitis, encephalitis, brain abscess, upper airway obstruction, and jugular septic thrombophlebitis.

Medical Clinics of North America. Longo DL, et al. Acute meningitis. In: Harrison's Principals of Internal Medicine. McGraw Hill; Acute bacterial meningitis. Merck Manual Professional Version. Prevention — Listeriosis.

Subacute and chronic meningitis. Van de Beek D, et al. Advances in treatment of bacterial meningitis. The Lancet.