Assistant Prof./ Tamer Ata MD, PhD MEDICAL MICRIBIOLIOGY AND IMMUNOLOGY FACULTY OF MEDICINE AL-MAAREFA COLLEGES

Meningitis Definition Causes Classifications Septic meningitis 1. Epidemiology (organisms & risk factors & source and mode of transmission of the infection) 2. Pathogenesis 3. Virulence factors 4. Clinically 5. Complication 6. Investigation 7. Diagnosis 8. Treatment 9. Prevention

MENINGITIS Definition: is a disease caused by the inflammation of the protective membranes (meninges) covering the brain and spinal cord and subarachnoid space. Causes: InfectiousNon infectious -Bacterial (pyogenic) -Viral -Fungal -Tuberculous -Parasitic -Drugs -Cancer -Trauma & brain surgery -Autoimmune as SLE

Classifications Septic = pyogenic bacterial meningitis Aseptic meningitis = clinical and laboratory CSF evidence for meningeal inflammation with negative routine bacterial cultures. It includes Infectious (viral, fungal, parasitic, mycobacteria, spirochates) Non infectious Gram positive (G+ve)Gram negative (G-ve) Strept. Pneumoniae (pneumococci) Group B strept. (GBS) Listeria monocytogenes Neisseria meningitides (meningiococci) Haemophilus influenzae B(HiB) Escherichia coli

SEPTIC MENINGITIS = pyogenic bacterial meningitis It is Sever, life threatening infection which considered as medical emergency requiring immediate medical diagnosis and treatment. Epidemiology: Causes: varies according to age group Age GroupCauses Newborns GBS (the commonest), E. coli, Listeria monocytogenes 5month – 5 years Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae 5 years – 18 years Strept. Pneumoniae, N. meningitidis Adults Streptococcus pneumoniae Neisseria meningitidis, Elderly Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes

Epidemiology GBS is the commonest cause of neonatal meningitis Strept. pneumoniae is the most common cause of meningitis in adult N. meningitidis usually affect 2—18 year. Meningiococci group A the most common in African belt(subsharan) while meningiococci group B is the most common in US. HiB mainly affect children 5 months to 2 years as HiB vaccine reduces its rate. Untreated cases give mortality 100%

Epidemiology Risk Factors: Age Infants and elderly are at higher risk for bacterial meningitis Community setting Infectious diseases tend to spread more quickly in outbreaks Overcrowdings as in military personnel and pilgrims are at increased risk for meningococcal meningitis (caused by Neisseria meningitidis). Pregnant females with listeriosis or vaginal colonization of GBS → ↑ risk of neonatal meningitis Certain medical conditions asplenia, alcoholism, viral infections as influenza, heart failure, chemotherapy and surgical

Epidemiology Risk Factors: Health care workers and Microbiologists: Working with meningitis-causing pathogens Travelers to the meningitis belt in sub-Saharan Africa (meningiococci group A) and travelers to Mecca during Hajj and Umrah pilgrimage. So vaccination is a must. Source of the infection : Exogenous: human case and incubatory carrier Endogenous: patient own flora (e.g. Strept. Pneumoniae and H. influenzae)

Epidemiology Transmission : Droplet or inhalation and contact. In neonatal meningitis: A. GBS and E. coli are acquired through passage in birth canal so prophylactic antibiotic during labor is important B. Listeria is a food born pathogen which infect pregnant females then infect the fetus

Pathogenesis Pathogens transmitted by droplet or inhalation colonize and multiply in nasopharynx and draining lymph nodes → bacteremia → CNS cross BBB → invade meninges causing meningitis with ↑ CSF production → ↑ intracranial tension → pressure on brain tissue and blood vessels supplying nerves → possible neurological damage.

Virulence factors Adherence and colonization with epithelium: in G+ve bacteria by techoic acid & in G-ve bacteria by pili IgA protease Polysaccharide CapsuleAg: antiphagocytic & antigenic N. menigitidis (meningiococci) Strept. Pneumoniae (pneumococci) H. influenza (HiB) different serogroups (A&B&C&Y&W135) but group B capsule is less antigenic -80 different serotypes → only 23 serotype infect human -Poly-ribitol phosphate polysaccharide -Weak immunogen (T independent Ag)

Virulence factors Inflammation and toxins: G-ve bacteria : Lipopolysaccharides → toxic effect and skin rash. G+ve bacteria: Techoic acid & pneumolysin (pneumococci)

Clinically Fever, headache Altered mental state Vomiting Neck rigidity Ophthalmoplegia, photophobia Abnormal reflexes as Kernig’s sign and Brudzinski ‘s sign Bulged fontanelles in infants Hypotonia Purpura (meningiococci)

Complications brain damage hearing loss Loss of vision learning disabilities Convulsions Subdural empyema and brain abscess septicemia, septic shock, DIC death

Investigations CBC Blood culture CSF analysis (protein, cells, glucose) CSF direct smear stained by Gram CSF Ag detection (serological) CSF bacteriological culture Radiological as CT & MRI

Diagnosis (according CDC case definition ) Suspected caseProbable caseConfirmed case Clinical picture Ag detection in CSF (latex agglutination) -Rapid methods -Using specific Antibodies against different bacterial Ag which could be detected in CSF PCR: detect nucleic acid in CSF by using specific primer for each organism CSF: turbid - ↑ protein & ↓ glucose & PMN -Gram stained smear: 1.G+ve cocci in pairs (pneumococci) 2.G-ve cocci in pairs (meningiococci) 3.Pleomorphic G-ve bacilli (hemophilus) 4.G+ve cocci in long chain (GBS) Culture (gold standard): -CSF or blood culture -On blood & chocolate agar with ↑ CO2 (5-10%) -Identification of growth by Biochemical reactions 1.Pneumococci: catalase –ve & optochain sensitive 2.Meningiococci: oxidase +ve & ferment maltose 3.Hemophilus: Quelling reaction (serotyping)

Treatment Any delay in empirical antibiotic will ↑ risk of brain damage and death For G+ve bacteria (pneumococci & GBS) : amoxicillin/clavulanic or ampicillin/sulbactam (can cross inflamed BBB) if resistance anticipated vancomycin For G-ve bacteria: ceftriaxone Single dose of cortisone could be given with 1 st dose of antibiotic to ↓ inflammation in meninges

Prevention Active immunization: Pediatric pneumococcal conjugate vaccine (13 serotype capsule polysaccharide Ag conjugated with DT as adjuvant) Adult pneumococcal polysaccharide vaccine (23 serotype capsule polysaccharide Ag) HiB vaccine: conjugate polyribitol capsule polysaccharide with DT or OMP of meningiococci group B Capsule polysaccharide of meningiococci group A,C,Y, W135 & OMP of meningiococci group B

Prevention Chemoprophylaxis: rifampin OR ciprofloxacin ( ↓ meningiococci &HiB colonization in pharynx) → given for susceptible person whom in close contact with case or carrier with septic meningitis. NB: Patient should be isolated in separate room with negative ventilation and using PPE on dealing with the patients with hand hygiene.

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