VIRAL MENINGITIS FOR MICROBIOLOGY, APURWA SHASRTI

Viral meningitis in apurwa Shastri

1. VIRAL MENINGITIS PRESENTED BY: KOMAL AGRAWAL (53) KRISHN KUMAR PATEL (54) GUIDED BY : DR. DEBASHISH SAMAL SIR

2. CONTENTS: INTRODUCTION ETIOLOGY AND AGENTS CAUSING VIRAL MENINGITIS EPIDEMIOLOGY CLINICAL MANIFESTATIONS LABORATORY DIAGNOSIS TREATMENT

3. INTRODUCTION: Viral meningitis involves inflammation of subarachnoid space. It is the second most common type of meningitis, next to acute bacterial meningitis less severe than bacterial meningitis has a better prognosis

4. ETIOLOGY: Enteroviruses are the most common cause of viral meningitis (accounts for more than 85% of cases) Enteroviruses belong to picornaviruses (family Picornaviridae ) transmitted by feco -oral route

5. They comprise of the following viruses which further divide into several (>115) human serotypes Polioviruses —cause myelitis Coxsackieviruses, echoviruses, parechoviruses and Enterovirus 71— cause aseptic meningitis

6. Other less common viral agent (causing acute meningitis) are: Herpes viruses : herpes simplex virus(HSV), varicella-zoster virus (VZV), Epstein-Barr virus ,etc. Arbovirus : The encephalitis group of arboviruses can also occasionally cause meningitis, especially in people having travel history

7. LCM Virus : Lymphocytic choriomeningitis virus affects people with history of contact with rodent droppings or urine Other causes : Mumps virus, measles virus, influenza virus and human immunodeficiency virus (HIV).

8. AGENTS CAUSING VIRAL MENINGITS : Non-polio enteroviruses : most common cause of viral meningitis (accounting for >85% of cases). It can affecting any age especially in children Majority cases occur in the summer and rainfall,

9. Examples : Coxsackieviruses echoviruses parechoviruses Enterovirus 71

10. Coxsackieviruses: can be divided into two groups : A and B (based on their pathogenic potentials) Serotypes : 1. Group A: typed into serotypes 1–24 (except 15, 18 and 23) 2. Group B: typed into serotypes 1–6.

11. can spread through an infected person’s nasal and throat secretions, fluid from blisters or scabs. incubation period - 2 to 9 days.

12. Clinical Manifestations Aseptic meningitis : a. caused by all types of group B coxsackieviruses and by many group A coxsackieviruses ( most commonly A7 and A9 ) Herpangina : a. It is a severe febrile vesicular pharyngitis that is caused by certain group A viruses ( type 2–6, 8, 10 )

13. Hand-foot-and-mouth disease : It is characterized by oral and pharyngeal ulcerations and vesicular rashes of the palms and soles which heal without crusting. It is particularly associated with coxsackievirus A1 Pleurodynia (also known as Bornholm disease or epidemic myalgia): It is caused by coxsackie B viruses. It is characterized by fever and abrupt onset of stabbing chest

14. Cardiac : Myocarditis and pericarditis are caused by coxsackievirus B types 1–5 Respiratory : Coxsackieviruses A and B have been associated with common colds. Pneumonia may be caused by coxsackieviruses B4 and 5 Acute hemorrhagic conjunctivitis : It is caused by coxsackievirus A24 and enterovirus 70

15. Generalized disease of infants : It is an extremely serious disease involving multiple organs, caused by group B coxsackieviruses Pancreatitis leading to juvenile diabetes mellitus is caused by coxsackievirus B4.

16. Laboratory Diagnosis : specimens : throat swabs, stool and CSF Isolation of the virus Inoculating into tissue culture : Cytopathic effect can be observed within 5–14 days .

17. PCR targeting specific genes (e.g. VP1 )is highly useful as it is rapid, more sensitive and serotype-specific Serology: to detect neutralizing antibodies

18. Echoviruses (enteric cytopathogenic human orphan viruses) Echoviruses are further typed into serotypes 1–33 (there are no types—8, 10, 22, 23 or 34), cause aseptic meningitis other than that they also cause : encephalitis, rashes, common cold, and ocular disease They can cause outbreaks in summer especially among children.

19. Parechoviruses : Parechoviruses have 16 serotypes: 1. Serotype 1 and 2 were previously classified as echoviruses 22 and 23 respectively 2. Their capsid consists of three viral proteins (in contrast to four proteins in most picornaviruses) 3. They rarely cause aseptic meningitis, respiratory and neonatal diseases

20. Enterovirus 71: has caused large epidemic of meningitis in Southeast Asia In addition to meningitis, it can also cause encephalitis, hand-foot-and-mouth disease and herpangina (similar to coxsackieviruses) and paralysis resembling poliomyelitis

21. Herpesvirus Meningitis: A number herpesviruses can cause meningitis: The common agents are : herpes simplex viruses, varicella zoster virus (VZV) and Epstein-Barr virus (EBV) Rare causes include cytomegalovirus and human herpesvirus 6

22. HSV Meningitis Herpes simplex viruses (HSV): second most common cause of viral meningitis, next to enteroviruses (accounts for 5% of cases). Adults are commonly affected than children. History of genital herpes may be an important clue as HSV meningitis can occur in ~25–35% of women and ~ 10–15% of men at the time of an initial (primary) episode of genital herpes

23. Mollaret meningitis : HSV typically produces a chronic recurrent lymphocytic meningitis , called as Mollaret meningitis. It is characterized by repeated episodes of meningitis , typically lasting two to five days; occurring weeks to years apart. It can also be caused by EBV

24. VZV meningitis : should be suspected in the presence of concurrent chickenpox or shingles cases of VZV meningitis can occur in patients without history of rash EBV meningitis : Patients may have history of associated infectious mononucleosis and may demonstrate presence of atypical lymphocytes in the CSF or peripheral blood.

25. Arboviral Meningitis: The encephalitic arboviruses can sometime cause meningitis, especially in individuals who have recently travelled to the areas where these viruses are endemic. examples: 1.West Nile virus 2.Saint Louis encephalitis virus 3.Tick-borne encephalitis 4.California encephalitis virus

26. Non-encephalitic arboviruses which can cause meningitis are Zika virus (Brazil) and Oropouche virus

27. HIV MENINGITIS: Meningitis in HIV infection may occur following primary infection in 5–10% of cases and less commonly at later stages of illness. Cranial nerve palsies — especially involves cranial nerves V, VII, or VIII, are more common in HIV meningitis than in other viral infections .

28. Mumps meningitis: Meningitis in mumps may occur secondary to parotitis, or rarely in about 10% of cases, patients may directly develop meningitis without an underlying history of parotitis (called as atypical mumps). Mumps meningitis is more common in the late winter or early spring, especially in unvaccinated children with a male preponderance

29. LCM Virus Meningitis: Lymphocytic choriomeningitis (LCM) virus affects people with history of contact with rodent droppings or urine. Some patients have an associated rash, pulmonary infiltrates, alopecia, parotitis, orchitis, or myopericarditis.

30. EPIDEMIOLOGY: People at risk: Children(< 5 years old) old age Immunocompromised individuals, chemotherapy or transplant recipients.

31. Transmission : Close contacts with infected patients is necessary for the transmission to set in seasonality : Most cases of viral meningitis occur from nonwinter months (from late spring to fall), the time when enteroviruses and arbovirus spread most often

32. CLINICAL MANIFESTATIONS: Common symptoms : Fever headache (frontal or retro-orbital) stiff neck (milder than bacterial meningitis) Photophobia sleepiness or trouble in waking up from sleep Nausea

33. Irritability Vomiting lack of appetite (poor eating in babies) lethargy

34. Seizures or focal neurologic signs , or profound alterations in consciousness such as coma, or marked confusion does not occur in viral meningitis and suggest the presence of encephalitis or other alternative diagnoses.

35. LABORATORY DIAGNOSIS: CSF Analysis (Cytological and Biochemical): Examination of CSF reveals the following : Normal or slightly elevated protein level (20–80 mg/dL) Normal glucose level (rarely low glucose level may occur, as in cytomegalovirus meningitis)

36. Normal or mildly elevated CSF pressure (100–350 mm H2 O) Cell count is typically 25–500/ μL , although in some viral meningitis (e.g. LCM virus and mumps) the cell counts of several thousands/ μL may be seen Pleocytosis : Lymphocytes are typically the predominant cell type, although neutrophils may predominate in the first 48 h of illness in some viral meningitis (e.g. West Nile virus) Organisms are not seen on Gram staining of CSF

37. Molecular Methods : Molecular methods have become the gold standard method for diagnosing viral meningitis, appears to be more sensitive than viral cultures. Amplification of specific viral DNA or RNA from CSF by PCR based method provides definitive diagnosis

38. PCR of throat washings or stool specimen may assist in the diagnosis of enterovirus infections Formats: Multiplex PCR and multiplex real-time PCR can be used for simultaneous detection of common agents of viral meningitis

39. BioFire FilmArray is an automated nested multiplex PCR commercially available that can simultaneously detect 14 common agents of meningitis in CSF , which includes agents of pyogenic and viral meningitis. It is extremely sensitive and specific, with a turnaround time of 1 hour.

40. Viral Culture The sensitivity of CSF cultures for the diagnosis of viral meningitis is generally poor. In addition to CSF, specific viruses may also be isolated from throat swabs, stool, blood, and urine isolation of enteroviruses from stool is not diagnostic as it may also result from residual fecal shedding from a previous infection.

41. Antibody Detection Antibody detection is important for the diagnosis of less prevalent arboviruses such as West Nile virus, however it is of less useful for viruses that have a high seroprevalence in the general population, such as HSV and VZV

42. Oligoclonal Gamma Globulin Bands They may be detected in CSF in a number of viral infections; although can also be raised in other conditions such Lyme disease and multiple sclerosis .

43. TREATMENT: primarily symptomatic: includes - use of 1.analgesics, 2.antipyretics, 3.antiemetics 4.fluid and electrolyte replacement Antivirals may be useful for certain viral agents

44. Examples: Oral or i /v acyclovir used in 1. meningitis caused by HSV-1 or 2 2. EBV or VZV infection highly active antiretroviral therapy is used in patients with HIV Meningitis .