Bacterial MeningitisBacterial Meningitis

Ziad Elnasser, MD, Ph.DZiad Elnasser, MD, Ph.D

Anatomical considerationsAnatomical considerations

CNS parts.CNS parts.Blood brain barrier.Blood brain barrier.CSF and its circulation.CSF and its circulation.HydrocephalusHydrocephalus..

Routes of infectionRoutes of infection

Blood borne.Blood borne.Occult or overt.Occult or overt.Remote focus.Remote focus.Venous spread.Venous spread.Direct.Direct.Congenital.Congenital.Surgery complications.Surgery complications.

Neisseria Neisseria meningitidismeningitidis

General characteristicsGeneral characteristics

G –ve diplococci, size variations.G –ve diplococci, size variations.Polysaccharides capsule.Polysaccharides capsule.Colonial morphology.Colonial morphology.Growth conditions and media.Growth conditions and media.Carbohydrates fermentation.Carbohydrates fermentation.Oxidase positive.Oxidase positive.Significance of iron.Significance of iron.

Antigenic structureAntigenic structure

Capsular polysaccharidesCapsular polysaccharides..Quellung reaction, group A and C.Quellung reaction, group A and C.13 serotypes: A, B, C, D, X, Y, Z, E, W135, 13 serotypes: A, B, C, D, X, Y, Z, E, W135,

H, I, K and L.H, I, K and L.A, B, C, X, Y, Z, W135, and L has been A, B, C, X, Y, Z, W135, and L has been

purified.purified.Group C divided into Neuraminidase R or S.Group C divided into Neuraminidase R or S.Serogrouping and antibiotics resistance?Serogrouping and antibiotics resistance?Group B not immunogenic.Group B not immunogenic.

Noncapsular Cell wall AntigensNoncapsular Cell wall Antigens

Like other G –ve bacteria.Like other G –ve bacteria.Lipo-oligosaccharide (12 serotypes).Lipo-oligosaccharide (12 serotypes).Similar to human Glycosphingolipid Similar to human Glycosphingolipid

Antigens.Antigens.Lipo-oligosaccharides as future vaccines.Lipo-oligosaccharides as future vaccines.OMP typing.OMP typing.Classification based on Serotyping, OMP Classification based on Serotyping, OMP

and Lipo-oligosaccharides.and Lipo-oligosaccharides.

PiliPili

Phase and antigenic variation.Phase and antigenic variation.

Attachment to nasopharyngeal cells.Attachment to nasopharyngeal cells.

Colonies of Piliated and nonpiliated are Colonies of Piliated and nonpiliated are the same not as that of Gonococci.the same not as that of Gonococci.

PathogenesisPathogenesis

Nasopharyngeal surface.Nasopharyngeal surface. Ciliated or nonciliated.Ciliated or nonciliated. Mucus.Mucus. Pili and attachment to MCPs (CD46).Pili and attachment to MCPs (CD46). Opa and Opc role.Opa and Opc role. Only non encapsulated strains invade?Only non encapsulated strains invade? Actin rearrangement and porin protein.Actin rearrangement and porin protein. IgAase and Pil C role and BB barrier.IgAase and Pil C role and BB barrier.

Immune responseImmune response

Immune responseImmune response

Group A antigen and Bacillus pumilis.Group A antigen and Bacillus pumilis.E. coli K1 antigen and Group B.E. coli K1 antigen and Group B.Neonatal tissue and group B.Neonatal tissue and group B.Some times not protective.Some times not protective. IgAase only in pathogenic strains.IgAase only in pathogenic strains.

Carrier stateCarrier state

Presence of the meningococci in healthy Presence of the meningococci in healthy individuals.individuals.

Parameningococci.Parameningococci. Carrier state and epidemic status, >20%.Carrier state and epidemic status, >20%. Carrier to carrier via respiratory route.Carrier to carrier via respiratory route. Normal flora role.Normal flora role. Group B is the most common (9.6months).Group B is the most common (9.6months). Invasion and newly infected patients.Invasion and newly infected patients. Upper respiratory tract infection and Upper respiratory tract infection and

carriage.carriage.

EpidemiologyEpidemiology

Worldwide epidemics.Worldwide epidemics.5 – 19 years old during epidemic.5 – 19 years old during epidemic.Fatality rate 2 – 10% and in septicemia Fatality rate 2 – 10% and in septicemia

up to 70%.up to 70%.Low socioeconomic status and poverty.Low socioeconomic status and poverty.Serotypes and different epidemic Serotypes and different epidemic

potential.potential.School children, military recruits and School children, military recruits and

medical personnel. medical personnel.

Clinical manifestationsClinical manifestations

Ranges from mild fever to septicemia Ranges from mild fever to septicemia and fulminant death.and fulminant death.

Bacteremia without sepsis, upper Bacteremia without sepsis, upper respiratory tract infection.respiratory tract infection.

Meningococcemia, leukocytosis, skin Meningococcemia, leukocytosis, skin rash, headache and hypotention.rash, headache and hypotention.

Meningitis with or without septicemia.Meningitis with or without septicemia.Meningoencephalitic manifestation.Meningoencephalitic manifestation.Children vs adults.Children vs adults.

Laboratory DiagnosisLaboratory Diagnosis

CSF and Blood.CSF and Blood.Synovial, pleural, petechial skin and Synovial, pleural, petechial skin and

mucosal lesions and pericardial.mucosal lesions and pericardial.Chemical and cytological examination.Chemical and cytological examination.CIE, latex agglutination, CIE, latex agglutination,

coagglutination.coagglutination.Lactate dehydrogenase and Lactate dehydrogenase and

neuraminidase detection.neuraminidase detection.PCR value if antibiotics were usedPCR value if antibiotics were used..

TreatmentTreatment

Antibiotics reduced mortality and Antibiotics reduced mortality and supportive care improved prognosis.supportive care improved prognosis.

Sulfonamides.Sulfonamides. Penicillin.Penicillin. Chloramphenicol.Chloramphenicol. First generation cephalosporins?.First generation cephalosporins?. Second and third generation Second and third generation

cephalosporins.cephalosporins. Value of early treatment.Value of early treatment.

Supportive careSupportive care

Treat complications caused by LPS.Treat complications caused by LPS. TNF alpha and other cytokines as TNF alpha and other cytokines as

indicators of shock.indicators of shock. Complement level.Complement level. Recombinant proteins.Recombinant proteins. Steroids? Low dose.Steroids? Low dose. Heparin?Heparin? Plasmin activator with fibrinolysis for DICPlasmin activator with fibrinolysis for DIC..

ChemoprophylaxisChemoprophylaxis

Sulfonamides reduced the carrier state.Sulfonamides reduced the carrier state.Penicillin proved to be ineffective.Penicillin proved to be ineffective.Rifampin and minocycline.Rifampin and minocycline.Ciprofloxacin.Ciprofloxacin.Ceftriaxone.Ceftriaxone.House hold contacts, medical House hold contacts, medical

personnel, nursery schools, military personnel, nursery schools, military barracksbarracks

ImmunoprophylaxisImmunoprophylaxis

Capsular polysaccharides A and C.Capsular polysaccharides A and C. Erythema and irritability in some.Erythema and irritability in some. Not effective before 24 months of age.Not effective before 24 months of age. Day care centers.Day care centers. Hyporesponsiveness.Hyporesponsiveness. Now quadrivalent of A, C, Y and W135 is Now quadrivalent of A, C, Y and W135 is

avialable.avialable. Detoxified LOS and OMP, Capsule protein Detoxified LOS and OMP, Capsule protein

conjugate, anti-idiotype antibodies.conjugate, anti-idiotype antibodies.

CRYPTOCOCCOSISCRYPTOCOCCOSIS

Cryptococcus neoformans.Cryptococcus neoformans.Yeast , large capsue unique, Yeast , large capsue unique,

polysaccharidepolysaccharideUrease positive.Urease positive.Bacterial like colonies.Bacterial like colonies.Pigeon and birds droppings in soil.Pigeon and birds droppings in soil.No human to human transmission.No human to human transmission.

PATHOGENESISPATHOGENESIS

Inhalation of yeast or conidia.Inhalation of yeast or conidia.Minimal signs and symptoms.Minimal signs and symptoms.CNS is the primary target.CNS is the primary target.Common complication of AIDS.Common complication of AIDS.Phagocytosis?Phagocytosis?Humoral and CMI role.Humoral and CMI role.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

Meningitis, skin, pneumonia.Meningitis, skin, pneumonia.Slow insidious onset.Slow insidious onset.Headache, irritability, dizziness and Headache, irritability, dizziness and

behavioural changes.behavioural changes.Seizures, cranial nerves, papillidema, Seizures, cranial nerves, papillidema,

and dementia.and dementia. In AIDS 5 - 15% becomes infected.In AIDS 5 - 15% becomes infected.

DIAGNOSISDIAGNOSIS

CSF pleocytosis, lymphocytes CSF pleocytosis, lymphocytes predominance, Sugar, protein.predominance, Sugar, protein.

Microscopy, negative staining.Microscopy, negative staining.Culture, urease.Culture, urease.Serology.Serology.

TREATMENTTREATMENT

Amphotericin B + Flucytosine.Amphotericin B + Flucytosine.Fluconazole.Fluconazole.Relapse is a problem, chronic.Relapse is a problem, chronic.Residual neurological damage.Residual neurological damage.

Viral MeningitisViral Meningitis

Self limiting to severe.Self limiting to severe.Meningitis vs encephalitis and clinical Meningitis vs encephalitis and clinical

course.course.Viral infections in the immune suppressed.Viral infections in the immune suppressed.Slow viral infections.Slow viral infections.Unconventional infections.Unconventional infections.

Aetiological agentsAetiological agents

Acute Aseptic Meningitis SyndromeAcute Aseptic Meningitis SyndromeMumps.Mumps.Coxsakie.Coxsakie.Echo.Echo.HSV-2HSV-2HIVHIVPolioPolioLymphocytic choriomeningitis virus.Lymphocytic choriomeningitis virus.

Acute lymphocytic pleocytosis in the CSF.Acute lymphocytic pleocytosis in the CSF.No involvement of the brain paranchyma.No involvement of the brain paranchyma.Normal sugar and slight protein increase.Normal sugar and slight protein increase.Clinical course is usually mild.Clinical course is usually mild.Trimethoprim, Ibubrufin, Carbamazipine.Trimethoprim, Ibubrufin, Carbamazipine. IV Immunoglobulin injection.IV Immunoglobulin injection.Treatment is supportive.Treatment is supportive.

Acute encephalitidesAcute encephalitides

Parenchymal affection.Parenchymal affection. Like viral meningitis but more severe Like viral meningitis but more severe

symptoms, seizures to coma.symptoms, seizures to coma. Togaviruses, mosquitoes, summer to fall. Togaviruses, mosquitoes, summer to fall. St. Louis encephalitis.St. Louis encephalitis. Eastern Equine Encephalitis.Eastern Equine Encephalitis. Western Equine Encephalitis.Western Equine Encephalitis. California Encephalitis.California Encephalitis. Supportive care.Supportive care.

HSV-2 some times HSV-1.HSV-2 some times HSV-1.Acute widespread necrotizing infection of the Acute widespread necrotizing infection of the

newborne. Cervical infection and the baby.newborne. Cervical infection and the baby.Very high mortality or sever retardation.Very high mortality or sever retardation.HSV-1 and cold sores, frontal and temporal.HSV-1 and cold sores, frontal and temporal.Acyclovir is effective mortality drops from 70 Acyclovir is effective mortality drops from 70

to 40%.to 40%.Steroids use.Steroids use.

Viral infections in the immune Viral infections in the immune suppressedsuppressed

PML and the JC virus.PML and the JC virus.Chronic demyelinating disease.Chronic demyelinating disease.Hodgkin's, Lymphoma, Leukemia and HIV.Hodgkin's, Lymphoma, Leukemia and HIV.CSF studies are completely normal.CSF studies are completely normal.

HIV and AIDS.HIV and AIDS.Opportunistic infections.Opportunistic infections.Double infection.Double infection.

Slow Viral diseasesSlow Viral diseases

SSPE and mealses.SSPE and mealses. PRPE and Rubella.PRPE and Rubella. Unconventional Agents:Unconventional Agents:

Cretzfeldt-Jacob disease (prog. Dementia).Cretzfeldt-Jacob disease (prog. Dementia).Kuru.Kuru.Gerstmann–Straussler-Scheinker Syndrome.Gerstmann–Straussler-Scheinker Syndrome.Familial Fatal Insomnia.Familial Fatal Insomnia.Bovine Spongiform encephalopathy.Bovine Spongiform encephalopathy.Scrapie, Transmissible Mink encephalopathy, Scrapie, Transmissible Mink encephalopathy,

chronic wasting disease.chronic wasting disease.