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

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

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

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

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 4/28/2017

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

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. 4/28/2017

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 4/28/2017

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? 4/28/2017

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 4/28/2017

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? 4/28/2017

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 4/28/2017

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

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

Listeria monocytogenes Normally causes Listeriosis Listeria monocytogenes

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.

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

Neisseria meningitidis

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

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

This inflammation puts pressure on the brain.

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

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

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%.

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

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

Rashes

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

CSF with meningococcus

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

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

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

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

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

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

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

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

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

Meningitis Viral &Fungal

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

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

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

Acute Meningitis

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

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

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

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

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

Chronic Meningitis

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

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

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)

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

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

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

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

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

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