1. Dr. Hani Masaadeh, MD, PhD Lecture 6&7
Meningitis
Dr. Hani Masaadeh, MD, PhD
Lecture 6&7

2. Objectives Define meningitis Describe prevalence of meningitis
Explain pathophysiology
Identify clinical manifestations
Know the appropriate antibiotic treatment per age group

3. Definition Meningitis: inflammation of the leptomeninges (the tissues
surrounding the brain and spinal cord)
Bacterial meningitis
Aseptic meningits: infectious or noninfectious
Viral, Rickettsiae, Mycoplasma Fungal, spirochetes: syphilis, Lyme
Protozoa: malaria
Malignancy
Lupus erythematous
Lead or mercury poisoning
The meninges consist of three parts: the pia, arachnoid, and dura maters. Meningitis reflects infection of the arachnoid mater and the cerebrospinal fluid (CSF) in both the subarachnoid space and in the cerebral ventricles
Aseptic meningits: etiology can be infectious or noninfectious
Virus- enteroviruses, Epstein-Barr, CMV, VZV, herpes simplex, Arbovirus
Rickettsiae- Rocky Mt. Spotted fever
Spirochetes- syphilis, Lyme disease
Mycoplasma- Ureaplasma urealyticum
Fungi- Candida albicans, C. neoformans
Protozoa- malaria
Malignancy- primary neuroblastoma, metastatic leukemia, Hodgkin disease
Lupus erythematous
Sarcoidosis
Lead, mercury poisoning

4. RISK FACTORS OF MENINGITIS
Age-Viral meningitis occur in children younger than age 5
Bacterial meningitis most commonly occurs in pre-teens and young adults
Community Setting: this infection spreads quickly in large groups such as college
students living in dormitories, military personnel, and children in childcare
facilities are at high risk
Pregnancy- increased risk of listeriosis, which this bacteria can also cause
meningitis.
Working with animals- dairy farmers, ranchers, or others who work with domestic
animals have an increased risk of listeriosis which can cause meningitis
Weakened immune system-diseases, medications and surgical procedure can
increase the risk of meningitis

5. Symptoms can be the same for Viral and Bacterial
Fever and chills
Mental status changes
Nausea and vomiting
Sensitivity to light (photophobia)
Severe headache
Stiff neck
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6. Causes of Meningitis Bacteria Viruses Fungi TB
Community-acquired - S. pneumoniae, N. meningitidis, gp B streptococcus
Post-op or hospital acquired – MRSA, Ps. Aeruginosa
In the very young and very old Listeria monocytogenes
Viruses
Enterovirus, coxsackie virus, echovirus, HSV-2, etc
Fungi
Coccidioides, cryptococcus TB

7. Clinical description
Meningitis is a disease caused by the inflammation of the protective membranes covering the brain and spinal cord known as the meninges. The inflammation is usually caused by an infection of the fluid surrounding the brain and spinal cord. Meningitis is also referred to as spinal meningitis.
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8. Bacterial Meningitis- Outbreaks Local Health Departments
Investigate cases immediately
Report cases to Regional Epidemiologist and Infectious Disease Epidemiology
Determine who is at risk by interviewing physician, family or possibly the case
Organize notes and respond as though this will be an outbreak
Send isolates to OLS
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9. So…you get a call from a Hospital ER at 4:00 on Thursday
A patient has been intubated and the doctor believes that the symptoms are consistent with Meningitis Spinal fluid cultures are incomplete What should you do first?
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10. Causes of Meningitis Bacterial - Haemophilus influenzae - Listeria
- Meningococcus  
- Mumps
- Pneumococcus
- Group A Streptococcus 
- Group B Streptococcus
Viral
- Arboviral (mosquito-borne) diseases
- Influenza
- LaCrosse Encephalitis virus
- West Nile Virus
- Also enteroviral
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11. Bacterial Meningitis
What types are important in Public Health Response? 1. Neisseria meningitidis (also called meningococcal meningitis) 2. Haemophilus influenzae Serotype b (Hib) Why are they important?
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12. Viral Meningitis
Clinical description: A syndrome characterized by acute onset of meningeal symptoms- fever, and cerebrospinal fluid pleocytosis (white cells in the spinal fluid) with bacteriologically sterile cultures. Confirmed: a clinically compatible illness diagnosed as aseptic meningitis, with no laboratory evidence of bacterial or fungal meningitis
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13. Age Group
Causes
Newborns
Group B Streptococcus, Escherichia coli, Listeria monocytogenes
Infants and Children
Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b
Adolescents and Young Adults
Neisseria meningitidis, Streptococcus pneumoniae
Older Adults
Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes

14. Streptococcus pneumoniae
One of the top contributors ear infections and can cause  Pneumococcal pneumonia.

15. Listeria monocytogenes
Normally causes Listeriosis
Listeria monocytogenes

16. How is Bacterial Meningitis diagnosed?
Early diagnosis is very important
If symptoms occur, patient should
seek medical help immediately
Diagnosis is made by retrieving
growing bacterial from a sample
of the spinal fluid
By performing a spinal tap, spinal
fluid is obtained through a needle
The needle is inserted in the
lower back where the fluid in the
spinal canal can be retrieved.

17. CT Scan- a type of x-ray Other Testing Procedures
that uses a computer to
make pictures of
structures inside the
body.
Other Cultures- testing of
samples of blood, urine,
mucous, and/or pus from
skin infections
MRI Scan- test that uses
magnetic waves to take
pictures of structures of
inside of body (to clarify
that inflammation is not
some other cause such as a
tumor

18. Neisseria meningitidis

19. Clincal Presentation Acute meningitis Abrupt or rapid onset
“flu-like” prodrome – myalgias
Fever
Headache
Nucal stiffness
Altered sensorium (meningo-encephalitis)
Rash

20. Clinical Presentation
Chronic meningitis
Insidious, gradual onset
Weeks of headache
Low grade fever
Sweats, chills
Weight loss

21. This inflammation puts pressure on the brain.

22. Sudden onset of Headaches, neck stiffness, fear, confusion, vomiting, irritability, skin rashes, inability to tolerate light or loud noises

23. These bacteria can be spread through nose and throat body fluids.

24. The body cannot handle this disease on its own
The body cannot handle this disease on its own. Untreated bacterial meningitis has a mortality rate of 50%.

25. Blood cultures are used to determine signs of inflammation and a lumbar puncture is used to definitively test for the presence of bacteria in the CSF

26. The bacteria cultures are grown an are tested with gram staining.

27. Rashes

28. Lab CT head – r/o cerebritis, brain abscess, brain edema
Lumbar puncture
Pleocytosis
High protein
Low glucose (CSF:serum glucose < 50%)
Bacterial antigens – more sensitive in children
Gram stain and culture

29. CSF with meningococcus

30. Prevention Vaccines Exposure to meningococcus Pneumovax
Meningicoccal vaccine
Both should be administered to any asplenic patient
Exposure to meningococcus
Rifampin 600 mg PO BID x 4 doses
Only for intimate contacts: spouse, boyfriend/girlfriend, household contacts

31. Differential Dx Viral - 40 % of meningitis Fungal Tuberculous
Spirochete
Chemical / Drug induced
Collagen Vascular Disease
Parameningeal infection: brain abscess, epidural abscess
Subarachnoid hemorrhage
Neuroleptic Malignant Syndrome

32. LABORATORY FEATURES
Most often the WBC count is elevated with a shift toward immature forms
Platelets may be reduced if disseminated intravascular coagulation is present or in the face of meningococcal bacteremia
Blood cultures are often positive, and can be very useful in the event that CSF cannot be obtained before the administration of antimicrobials
At least one-half of patients with bacterial meningitis have positive blood cultures

34. Complications of Meningitis
One of the most common problems resulting from meningitis is hearing loss. Anyone who has had meningitis should take a hearing test.
Young children:
Babyish behavior
Forgetting recently learned skills
Reverting to bed-wetting

35. Older people:
Lethargy
Recurring headaches
Difficulty in concentration
Short-term memory loss
Clumsiness
Balance problems
Depression

36. Serious complications
Other serious complications can include:
Brain damage
Epilepsy
Changes in eye sight

37. Choice of agent
Selected third generation cephalosporins such as cefotaxime and ceftriaxone, have emerged as the beta-lactams of choice in the empiric treatment of meningitis
These drugs have potent activity against the major pathogens of bacterial meningitis with the notable exception of listeria

38. PRECAUTIONS Antibiotic - Prophylaxis Prophylaxis is for
household contacts of
someone with the Hib
Disease
Recommended the entire
household should receive
this to protect them

39. A 9-month-old Baby in Septic Shock with Purpuric Neisseria meningitidis Skin Lesions.

40. Meningitis Viral &Fungal

41. Causes of Meningitis Viruses Fungi TB
Enterovirus, coxsackie virus, echovirus, HSV-2, etc
Fungi
Coccidioides, cryptococcus TB

42. Clincal Presentation Acute meningitis Abrupt or rapid onset
“flu-like” prodrome – myalgias
Fever
Headache
Nucal stiffness
Altered sensorium (meningo-encephalitis)
Rash

43. Clinical Presentation
Chronic meningitis
Insidious, gradual onset
Weeks of headache
Low grade fever
Sweats, chills
Weight loss

44. Acute Meningitis

45. Lab CT head – r/o cerebritis, brain abscess, brain edema
Lumbar puncture
Pleocytosis
High protein
Low glucose (CSF:serum glucose < 50%)
Bacterial antigens – more sensitive in children
Gram stain and culture

46. Viral Meningitis 75% caused by enteroviruses Other viruses Enterovirus
Coxsackie virus
Echo virus
Other viruses
HSV2 (HSV1 causes encephalitis)
HIV
Lymphocytic choriomeningitis virus
Mumps
Varicella Zoster

47. Viral Meningitis
Cannot distinguish initially from bacterial meningitis
Severe HA, photophobia, nucal rigidity, fever
May be preceded by a few weeks by viral gastroenteritis
Ask pt is he/she had the “stomach flu” some time in the past couple weeks
Disease is self-limited, resolves after 7 to 10 days without treatment

48. CSF Low numbers of WBCs : 10 to 500
PMNs predominate early, Monos or Lymphocytes later
CSF to serum glucose ratio usually = 50%
Protein may be high
Gram stain, culture and bacterial antigens negative
Enteroviral PCR positive about 70% of time

49. Approach to Viral Meningitis
Treat like bacterial meningitis until the 72 hr culture comes back negative, or…
Enteroviral PCR comes back positive
Consider acyclovir if CSF HSV PCR positive
HSV meningitis is self-limited

50. Chronic Meningitis

51. Causes Cryptococcus Coccidioides immitis Mycobacterium tuberculosis
Other fungal – histoplasmasma, blastomyces, sporotrix
Other bacteria – brucella, francisella, nocardia, borellia
Non-infectious – Wegener’s, sarcoid, malignanacy

52. Presentation Insidious onset Low grade fever
Persistant, worsening headache
Photophobia and nucal rigidty usually absent
Symptoms have usually lasted several weeks by the time diagnosis is made

53. Diagnosis History CSF Exposure to bird droppings (crypto)
Contacts with TB pts
CSF
Modest pleocytosis
Glucose may be normal, but protein usually high (very high if coccidioma causes CSF obstruction)

54. Diagnosis TB Cryptococcus CSF AFB smear usually negative
AFB culture takes 6 weeks
Positive PPD
CSF PCR not standardized yet, but may be helpful;
Cryptococcus
India ink
Cryptococcal Ag in CSF

55. Diagnosis Coccidioidomycosis Difficult diagnosis to make
CSF fungal smear and cultures usually negative
Titers have high false negativity rate even from CSF
Any pt with history of pulmonary cocci who develops HA with pleocytosis should be treated for cocci meningitis

56. Treatment TB Crytpococcus
Treat like pulmonary TB: INH, Rif, Eth, PZA for two months, then INH, Rif to comlete 12 months
Steroids – improves mortality, reduces adverse events (infarcts)
Crytpococcus
Amphotericin plus flucytosine for 6 weeks followed by fluconazole to complete 6 months
High toxicity rate (renal failure, pancytopenia)
High dose fluconazole (400 to 800 mg QD) if can’t tolerate ampho + 5FC
Serial LPs to reduce CSF pressure and assure clearing of infection
In AIDS pts – continue Fluconazole until CD4 >100

57. Treatment Coccidioidomycosis Intrathecal amphotericin now rarely used
Chemical arachnoiditis
High dose fluconazole (800 to 1200 mg QD)
Serial LPs to assure improvement of infection
Incurable – symptoms may resolve, but patient can never stop fluconazole
Taper down to no lower than 400 to 600 mg QD

58. Recurrent meningitis Mollaret’s meningitis Most common cause is HSV2
Many other poorly defined causes as well
Leaking arachnoid cyst
Cryptogenic
May respond to acyclovir

59. Conclusion
Acute meningitis is most commonly caused by viruses, then bacteria
Chronic meningitis can be caused by fungi and TB
Recurrent meningitis – Malloret’s