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Cns infections

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Cns infections

  1. 1. CNS Infections Dr Kamran Afzal Asst Prof Microbiology
  2. 2. Classification <ul><li>Classification by organ involvement </li></ul><ul><ul><li>Meningitis </li></ul></ul><ul><ul><li>Encephalitis </li></ul></ul><ul><ul><li>Myelitis </li></ul></ul><ul><li>Classification by pathogen </li></ul><ul><ul><li>Bacteria </li></ul></ul><ul><ul><li>Viruses </li></ul></ul><ul><ul><li>TB bacilli </li></ul></ul><ul><ul><li>Fungi </li></ul></ul><ul><ul><li>Spirochetes </li></ul></ul><ul><ul><li>Parasites </li></ul></ul>
  3. 3. Definitions <ul><li>Meningitis </li></ul><ul><ul><li>Inflammation of the leptomeninges </li></ul></ul><ul><ul><li>Usually caused by bacteria </li></ul></ul><ul><li>Encephalitis </li></ul><ul><ul><li>Inflammation of the brain itself </li></ul></ul><ul><ul><li>Usually caused by viruses </li></ul></ul><ul><li>Myelitis </li></ul><ul><ul><li>Inflammation of the spinal cord </li></ul></ul><ul><li>Meningoencephalitis </li></ul><ul><li>Meningomyelitis </li></ul><ul><li>Encephalomyelitis </li></ul><ul><li>Meningo-encephalomyelitis </li></ul><ul><li>Brain abscess </li></ul>
  4. 4. Meningitis
  5. 5. Meninges
  6. 6. Meningitis Classification - I <ul><li>Acute </li></ul><ul><ul><li>Pyogenic </li></ul></ul><ul><ul><ul><li>usually bacterial meningitis </li></ul></ul></ul><ul><ul><li>Aseptic </li></ul></ul><ul><ul><ul><li>usually viral meningitis </li></ul></ul></ul><ul><li>Chronic </li></ul><ul><ul><li>Usually TB, spirochetes, cryptococcus </li></ul></ul>
  7. 7. Meningitis Classification - II <ul><li>Purulent meningitis </li></ul><ul><ul><li>- polymorphonuclear cell </li></ul></ul><ul><ul><li>- WBC >1000 cells/mm 3 </li></ul></ul><ul><ul><li>- pyogenic bacteria </li></ul></ul><ul><li>Lymphocytic meningitis </li></ul><ul><ul><li>Viral </li></ul></ul><ul><ul><li>Chronic </li></ul></ul><ul><li>Eosinophilic meningitis </li></ul><ul><ul><li>- eosinophils > 5% </li></ul></ul><ul><ul><li>- parasitic </li></ul></ul>
  8. 8. Routes of Spread <ul><li>Hematogenous spread </li></ul><ul><li>Parameningeal structures </li></ul><ul><ul><li>sinusitis, mastoiditis, otitis media, dental caries </li></ul></ul><ul><li>Direct infection to the subarachnoid space </li></ul><ul><ul><li>fracture base of skull, ruptured meningocele </li></ul></ul><ul><li>Direct infection </li></ul><ul><ul><li>surgery, lumbar puncture </li></ul></ul>
  9. 9. Etiology of Acute Bacterial Meningitis Escherichia coli Group B streptococci <ul><li>Neonates </li></ul>Listeria monocytogenes
  10. 10. Hemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae >1 months to 5 years
  11. 11. Mycobacterium tuberculosis >5 years and Adults Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae
  12. 12. Immunocompromised Patients Enterobacteriaceae Hemophilus influenzae Pseudomonas aeruginosa
  13. 13. Post surgical procedures OR Post cranial/spinal trauma Enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Streptococcus pneumoniae Persistant CSF leak Streptococcus pneumoniae
  14. 14. Ventriculo - Peritoneal shunt Staphylococcus epidermidis Enterobacteriaceae Diphtheroids
  15. 15. Viral Meningitis (Aseptic meningitis) <ul><li>Etiological Agents </li></ul><ul><ul><li>Enteroviruses (Coxsackie and Echovirus) </li></ul></ul><ul><ul><li>Adenovirus </li></ul></ul><ul><ul><li>Arbovirus </li></ul></ul><ul><ul><li>Measles virus </li></ul></ul><ul><ul><li>Herpes Simplex virus </li></ul></ul><ul><ul><li>Varicella Zoster virus </li></ul></ul>
  16. 16. Chronic Meningitis <ul><li>Mycobacterium tuberculosis </li></ul><ul><li>Treponema pallidum </li></ul><ul><li>Cryptococcus neoformans </li></ul><ul><li>Toxoplasma gondii </li></ul>
  17. 18. <ul><li>Seed and traverse blood brain barrier </li></ul><ul><li>Organism multiplication, liberation of endotoxin and </li></ul><ul><li>teichoic acid </li></ul><ul><li>Release of TNF-α, IL-1 </li></ul><ul><li>Activation and release of prostaglandins, </li></ul><ul><li>leukotreines, PAF and other cytokines </li></ul>
  18. 19. Symptoms
  19. 20. Symptoms
  20. 21. Signs <ul><li>Kernig’s sign </li></ul><ul><ul><li>Flexion of hip, extension of knee hamstrings contract </li></ul></ul><ul><li>Brudzinski’s sign </li></ul><ul><ul><li>Passive neck flexion hips and knees flex </li></ul></ul><ul><ul><li>Skin </li></ul></ul><ul><ul><ul><li>Purpura </li></ul></ul></ul><ul><ul><ul><li>Petechial hemorrhages </li></ul></ul></ul>
  21. 22. <ul><li>Signs of meningococcaemia with or without meningitis </li></ul><ul><ul><li>prominent rash on extremities </li></ul></ul><ul><ul><li>Waterhouse-Friedrichsen syndrome </li></ul></ul>
  22. 23. Laboratory Diagnosis <ul><li>Acute Bacterial Meningitis </li></ul><ul><li>CSF Routine Examination </li></ul><ul><li>CSF Culture </li></ul><ul><li>CSF Immunological Tests </li></ul><ul><li>Polymerase Chain Reaction </li></ul><ul><li>Blood Culture </li></ul>
  23. 24. Collection and Transportation of CSF <ul><li>Must be collected by an experienced medical officer </li></ul><ul><li>L-3, L-4 space (L-4, L-5 in new-born) </li></ul><ul><li>Strict aseptic measures </li></ul><ul><li>Ideally two screw capped sterile tubes, each containing 1 ml of CSF </li></ul><ul><li>CSF for C/S should not be refrigerated </li></ul><ul><li>Must be transported to the lab without delay </li></ul>
  24. 25. CSF Routine Examination Appearance in acute meningitis <ul><ul><ul><li>Cloudy, viscid or purulent </li></ul></ul></ul><ul><ul><ul><li>Elevated pressure </li></ul></ul></ul>
  25. 26. CSF Routine Examination <ul><li>Cell Count >1000/Cmm </li></ul><ul><li>Neutrophils predominantly </li></ul><ul><li>Glucose <2.2mmol/L </li></ul><ul><li>Proteins >200 mg/Dl </li></ul><ul><li>CSF : PLASMA GLUCOSE RATIO <40% </li></ul>
  26. 27. CSF Routine Examination GRAM NEGATIVE COCCI GRAM POSITIVE COCCI GRAM NEGATIVE RODS GRAM POSITIVE RODS GRAM STAIN
  27. 28. CSF Evaluation Normal Bacterial Viral TB Cells 0-5 >1000 <1000 <500 Polymorphs 0 Predominate Early +/- increased Lymphocytes 5 Low Predominate Increased Glucose 60-80 Decreased ++ Normal Decreased+ CSF : plasma Glucose ratio 66% <40% Normal < 30% Protein 5-40 Increased+++ +/- Increased Increased+ Culture Negative Positive Negative Positive (MTB)
  28. 29. CSF Culture <ul><li>Specimens </li></ul><ul><ul><ul><li>Blood and CSF for smear and culture </li></ul></ul></ul><ul><ul><ul><li>Nasophyrangeal swab for carrier state </li></ul></ul></ul><ul><li>Culture media </li></ul><ul><ul><ul><li>Blood agar </li></ul></ul></ul><ul><ul><ul><li>Chocolate agar </li></ul></ul></ul><ul><ul><ul><li>Selective medium </li></ul></ul></ul><ul><ul><li>(Modified Thayer-Martin medium) </li></ul></ul><ul><ul><ul><ul><li>To avoid contamination, add vancomycin amphotericin B and colistin </li></ul></ul></ul></ul>
  29. 30. Antibiotic Sensitivity Testing <ul><li>Ampicillin/Penicillin </li></ul><ul><li>Ceftriaxone </li></ul><ul><li>Chloramphenicol </li></ul><ul><li>Rifampicin </li></ul><ul><li>Meropenem </li></ul>
  30. 31. CSF Antigen Screening <ul><li>Bacterial antigen screening detect </li></ul><ul><ul><li>S. pneumoniae </li></ul></ul><ul><ul><li>N. meningitidis </li></ul></ul><ul><ul><li>Klebsiella pneumoniae </li></ul></ul><ul><ul><li>S. agalactiae </li></ul></ul><ul><ul><li>Hib </li></ul></ul><ul><li>Crypto antigen screening detects C. neoformans </li></ul><ul><ul><li>+ in 90-95% of pts with crypto meningitis </li></ul></ul>
  31. 32. Treatment <ul><li>Empiric Antibiotics </li></ul><ul><ul><li>Ceftriaxone </li></ul></ul><ul><ul><li>Add Vancomycin (till possibility of Penicillin-resistant Strep pneumoniae has been ruled out) </li></ul></ul><ul><ul><li>Add Ampicillin (for Listeria infections) </li></ul></ul><ul><ul><li>For patients with serious Penicillin allergies, Meropenem </li></ul></ul><ul><ul><li>Ceftazidime + Vancomycin for neurosurgical patients </li></ul></ul><ul><ul><li>Add Acyclovir in case of viral infection </li></ul></ul><ul><ul><li>Add Amphotericin B in case of fungal infections </li></ul></ul><ul><li>Definitive Therapy </li></ul><ul><ul><li>As per C/S report </li></ul></ul>
  32. 33. Chemoprophylaxis <ul><li>Household/school/daycare contacts last 7 days </li></ul><ul><li>Direct exposure to secretions </li></ul><ul><ul><li>Kissing, sharing utensils/toothbrushes, mouth to mouth, intubation without a mask </li></ul></ul><ul><li>First line: Rifampicin x 4 doses </li></ul><ul><li>Alternative: Ceftriaxone, ciprofloxacin </li></ul>
  33. 34. Encephalitis
  34. 35. Viral Encephalitis <ul><li>Parenchymal infection </li></ul><ul><ul><ul><li>sometimes spinal cord involvement (encephalomyelitis) </li></ul></ul></ul><ul><li>Most characteristic features </li></ul><ul><ul><ul><li>perivascular and parenchymal mononuclear cell infiltration </li></ul></ul></ul><ul><li>Slowly progressive degenerative disease may occur many years after viral illness </li></ul><ul><ul><ul><li>Post-encephalitic parkinsonism </li></ul></ul></ul>
  35. 36. HSV Encephalitis <ul><li>In adult most caused by HSV-1 </li></ul><ul><li>Primary infection in oropharyngeal or intranasal mucosa </li></ul><ul><li>Latent ganglionic infection </li></ul><ul><li>Reactivation leads to encephalitis </li></ul><ul><li>Headache, fever, alteration of conciousness </li></ul><ul><li>VZV Encephalitis </li></ul><ul><li>Develops after varicella, VZV remain within the ganglia </li></ul><ul><li>Reactivation, spread to spinal cord and brain </li></ul>
  36. 37. Japanese Encephalitis <ul><li>Flavivirus, Culex- borne, Southeast Asia /China </li></ul><ul><li>Symptoms: headache and alteration of consciousness </li></ul><ul><li>Rabies Encephalitis </li></ul><ul><li>Rhabdovirus family, transmission through dog bites </li></ul><ul><li>CMV Encephalitis </li></ul><ul><li>Opportunistic infection in organ transplant, HIV </li></ul>
  37. 38. Diagnosis of Viral Encephalitis <ul><li>CSF studies </li></ul><ul><ul><li>CSF usually colorless </li></ul></ul><ul><li>- slightly  pressure </li></ul><ul><li>- initially may be a neutrophilic pleocytosis, which rapidly converts to lymphocytes </li></ul><ul><li>- proteins are slightly  </li></ul><ul><li>- glucose is normal </li></ul><ul><li>Virus isolation from CSF by PCR </li></ul>
  38. 39. Treatment <ul><li>Acyclovir for HSV and VZV </li></ul><ul><ul><li>given IV reduces mortality in 55% </li></ul></ul><ul><li>Gancyclovir for CMV </li></ul>
  39. 40. Chronic CNS infections
  40. 41. Tuberculous Meningitis <ul><li>Low grade fever </li></ul><ul><li>Headaches </li></ul><ul><li>Malaise and confusion </li></ul><ul><li>Vomiting </li></ul><ul><li>CSF: </li></ul><ul><ul><li>moderate pleocytosis </li></ul></ul><ul><li>- PMN initially then lymphocytes </li></ul><ul><ul><li>proteins  </li></ul></ul><ul><ul><li>glucose slightly  or normal </li></ul></ul>
  41. 42. Lab Diagnosis <ul><li>CSF routine examination – AFB on ZN smear </li></ul><ul><li>CSF Culture for M. tuberculosis </li></ul><ul><li>PCR for M. tuberculosis </li></ul><ul><li>Serological tests for tuberculosis </li></ul>
  42. 43. Treatment <ul><li>3 IRZS + 6IRZ </li></ul><ul><li>Dexamethasone IV </li></ul>
  43. 44. Neurosyphilis <ul><li>Tertiary stage of syphilis </li></ul><ul><ul><ul><li>~ 10% of untreated patients </li></ul></ul></ul><ul><li>Major forms of meningovascular neurosyphilis </li></ul><ul><ul><ul><li>Paretic neurosyphilis caused by invasion of the brain by T. pallidum </li></ul></ul></ul><ul><ul><ul><li>Tabes dorsalis is a result of damage to the sensory nerves in dorsal roots, causing locomotor ataxia and loss of pain sensation </li></ul></ul></ul>
  44. 45. Lab Diagnosis <ul><li>VDRL/RPR positive </li></ul><ul><li>CSF reactive FTA-ABS or TPHA </li></ul><ul><li>Treatment </li></ul><ul><li>Penicillin G IV 4 mU q 4 h 14d </li></ul><ul><li>Then benzathine penicillin G 2.4 mU IM x3 </li></ul>
  45. 46. Fungus <ul><li>Candidia albicans </li></ul><ul><li>Cryptococcus neoformans </li></ul><ul><li>Aspergillus fumigatus </li></ul><ul><li>Coccidiodes imitis </li></ul><ul><li>Lab Diagnosis </li></ul><ul><li>Gram stain, Indian ink preparation </li></ul><ul><li>Candida, Cryptococcal Ag </li></ul>
  46. 47. Treatment Disease Dose Duration HIV neg. Amphotericin 0.7MKD +flucytosine 100MKD +fluconazole 400mg/d 2 wk 10 wk Amphotericin 0.7MKD +flucytosine 100MKD 10 wk HIV pos. induction Amphotericin 0.7MKD +flucytosine 100MKD +fluconazole 400mg/d 2 wk 10 wk maintanance Fluconazole 400 mg/d
  47. 48. Protozoa Protozoan Disease Toxoplasma gondii Associated with congenital defects and AIDS African Trypanosomes African Sleeping Sickness Plasmodium falciparum Cerebral Malaria Entamoeba histolytica Rare invasion of the brain Acanthamoeba Rare cases
  48. 49. Helminths
  49. 50. Prions <ul><li>“ Small proteinaceous infectious particles without nucleic acids which resist inactivation by procedures that modify nucleic acids&quot; </li></ul><ul><li>Prion diseases are often called spongiform encephalopathies because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum </li></ul>
  50. 52. Examples of Prion Diseases That Affects the Brain <ul><li>Kuru </li></ul><ul><li>CJD: Creutzfeld-Jacob Disease </li></ul><ul><li>Variant Creutzfield-Jacob Disease </li></ul><ul><li>(Mad Cow Disease) </li></ul><ul><li>FFI: Fatal familial Insomnia </li></ul>􀂄
  51. 53. Aetiology <ul><li>Acquired infection </li></ul><ul><ul><li>diet and following medical procedures such as surgery, growth hormone injections, corneal transplants </li></ul></ul><ul><li>Apparent hereditary transmission </li></ul><ul><ul><li>autosomal dominant trait </li></ul></ul><ul><ul><li>this is not consistent with an infectious agent </li></ul></ul>
  52. 54. Lab Diagnosis <ul><li>Western blotting </li></ul><ul><li>Brain biopsy - characteristic spongy change </li></ul><ul><li>EEG studies </li></ul><ul><li>MRI </li></ul><ul><li>Treatment </li></ul><ul><li>Amphotericin </li></ul>

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