NEISSERIA MENINGITIDIS: A GUIDE TO CLINICAL FEATURES, LAB DIAGNOSIS AND TREATMENT
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NEISSERIA MENINGITIDIS: A GUIDE TO CLINICAL FEATURES, LAB DIAGNOSIS AND TREATMENT
- 1. NEISSERIA MENINGITIDIS Dr. K V CHAKRADHAR Assistant professor Department of Microbiology NRIIMS
- 2. Morphology • Capsulated Gram negative cocci in pairs (diplococci) • 0.5 – 1 µm in size • Kidney shaped, flat sides adjacent • Intracellular, usually • Non motile • Non spore forming.
- 3. Virulence factors • Antigens • Capsular polysaccharide • 13 serogroups (A, B, C, D, W 135, X, Y, Z, H, K & L) • Used in vaccine • Serogroups A, B, C, Y, W 135 for about 90% of the epidemics • Antiphagocytic in nature • Outer membrane proteins • 5 classes • Serogroups further subdivided into 20 serotypes
- 4. • Pili – helps in meningeal invasion • Toxin • Endotoxin • Lipid A part of lipopolysaccharide • Induces septicemic shock • Enzyme • IgA protease – cleaves the IgA antibodies present in the respiratory mucosa.
- 5. Epidemiology • Reservoir and habitat • Upper respiratory tract of humans • Transmission • Direct contact and air borne droplets • Close contact with infectious person • Family members • Day care centers • Military barracks • Prisons and • Other institutional settings • Incubation period – 1 to 7 days • Carriage • 5 – 30% of normal persons may harbor meningococci in nasopharynx
- 6. Diseases caused • Meningitis • Meningococcemia • Pneumonia • Arthritis • urethritis
- 7. Meningitis • Meningitis is an inflammation of leptomeninges within the subarachnoid space.
- 10. Bacterial Meningitis • Bacterial meningitis can be classified as • Acute • Chronic • Acute meningitis: Onset of meningeal symptoms over the course of hours to days. • Chronic meningitis: Onset in weeks to months. • Acute Pyogenic Meningitis: Infectious inflammatory infiltration of leptomeninges caused by bacteria
- 11. Bacterial Causes Related to Age Age Group Pathogen 0 – 4 Weeks Streptococcus agalactiae Escherichia coli Listeria monocytogenes Streptococcus pneumoniae 1 – 3 Months Haemophilus influenzae Listeria monocytogenes Neisseria meningitidis Streptococcus pneumoniae 3 Months – 18 Years Haemophilus influenzae Neisseria meningitidis Streptococcus pneumoniae 18 – 50 Years Neisseria meningitidis Streptococcus pneumoniae > 50 Years Listeria monocytogenes Streptococcus pneumoniae
- 12. Bacterial Causes Related to Clinical Condition Clinical Condition Pathogen Healthy, Immunocompetent (Community Acquired) Neisseria meningitidis Streptococcus pneumoniae Post Neurosurgical or Post traumatic (Nosocomial) Staphylococcus aureus Enterobacteriaceae Pseudomonas aeruginosa Immunosuppressed or older patients Listeria monocytogenes Enterobacteriaceae Pseudomonas aeruginosa Streptococcus pneumoniae
- 13. Predisposing factors • Immunoglobulin deficiencies. • Complement deficiencies. • Splenectomy and asplenic conditions. • Acute viral infections. • Head trauma.
- 14. Epidemiology • Accounts for an estimated annual 1,70,000 deaths worldwide. • S pneumoniae and N meningitidis causes approximately 6.5 and 4 cases per 1,00,000 children aged 1-23 months respectively. • In 1996, the biggest meningococcal meningitis outbreaks recorded in West Africa. An estimated 250,000 cases and 25,000 deaths occurred. • In 1985, in Delhi 6133 cases with 799 deaths (13%) were reported. All the isolates of N. meningitidis belonged to subgroup A.
- 15. Transmission • Although dangerous disease, not easily spread. • Through droplets from mouth and nose. • Transmission not necessarily gives rise to disease. • 15% adults carry disease causing strains in nose and throat.
- 16. Pathogenesis • Bacteria reach the intracranial structures in one of the 3 ways • Hematogenous spread. • Extension from the juxtacranial structures. • Iatrogenic source.
- 18. Nasopharyngeal Colonization Local Invasion Bacteremia Meningeal Invasion Bacterial Replication Release of bacterial components
- 20. Immune Response Pathogenic Event Host factors Bacterial evasion mechanism Mucosal Colonization Mucosal epithelium, large amount of secretory IgA, Ciliary activity IgA protease secretion, ciliostasis, adhesive pili Intravascular survival Complement system Blockage of alternative pathway Meningeal invasion Blood brain barrier Passage through tight junctions Survival within CSF Poor opsonic activity Rapid replication
- 21. Clinical features • Meningitis and meningococcal septicaemia may not always be easy to detect, in early stages the symptoms can be similar to flu. • They may develop over one or two days, but sometimes develop in a matter of hours. • It is important to remember that symptoms do not appear in any particular order and some may not appear at all.
- 22. In infants and young children: -High temperature, fever, possibly with cold hands and feet -Vomiting or refusing feeds -High pitched moaning, whimpering cry -Blank, staring expression -Pale, blotchy complexion -Stiff neck -Arched back -Baby may be floppy, may dislike being handled, be fretful -Difficult to wake or lethargic -The fontanelles may be tense or bulging.
- 24. In older children and adults: -High temperature, fever, possibly with cold hands and feet. -Vomiting, sometimes diarrhoea. -Severe headache. -Joint or muscle pains, sometimes stomach cramps. -Neck stiffness (unable to touch the chin to the chest) -Dislike of bright lights. -Drowsiness. -The patient may be confused or disorientated. Seizures may also be seen. -A rash may develop.
- 26. Signs • Neck and back stiffness • Positive Kernig’s and Brudzinski’s signs • In infants, there is usually presence of neck rigidity with bulging fontanelle.
- 27. • Severe stiffness of the hamstrings causes an inability to straighten the leg when the hip is flexed to 90 degrees.
- 28. • Severe neck stiffness causes a patient's hips and knees to flex when the neck is flexed.
- 29. • One sign of meningococcal septicaemia is a rash that does not fade under pressure (see ‘Glass test’) • This rash is caused by blood leaking under the skin. It starts anywhere on the body. It can spread quickly to look like fresh bruises. • This rash is more difficult to see on darker skin. Look on the paler areas of the skin and under the eyelids.
- 30. Laboratory diagnosis • Specimen • Cerebrospinal fluid (CSF) and blood • Nasopharyngeal swab for carrier state • CSF is collected through lumbar puncture, subdural tap or ventricular aspiration • Collected preferably before instillation of antibiotics
- 31. CSF Macroscopy Centrifuge Specimen and take deposits for bacteriological analysis Direct examination Gram Stain Initial Report Culture Examination Rapid Diagnostic Test Inoculate BA CA MA Incubate 37oC, 24 hours. (BA & CA @ 5 – 10 % CO2) Examine colonies, Gram stain, biochemical, Serology. AST and Final report • • • • • Latex agglutination Quellung test Limulus amoebocyte lysate assay Coagglutination test PCR
- 32. Differential Diagnosis of Meningitis based on Cerebrospinal Fluid Findings Diagnosis CSF Pressure (mm H2O) (WBC /mm3) Neutrophils(%) Glucose (Ratio) Protein (g/l) Normal <200 1-2 <1 >0.5 <0.45 Acute Bacterial >200 >1000 >50 <0.4 >1 Chronic Bacterial (TB) Variable >1000 Variable <0.4 >0.45 Aseptic (Viral) <200 <1000 <50 >0.4 Variable
- 33. • Culture media • Blood agar • Chocolate agar • Selective medium – Modified Thayer-Martin medium with vancomycin, colistin and nistatin to avoid contamination.
- 34. Growth characteristics • Oxygen requirement • Aerobic and facultative anaerobic • Temperature • Optimum growth at 370C • Growth promoted by 5 – 10% CO2 • Colony morphology • 1 – 2 mm diameter, convex, grey, translucent, non pigmented and non hemolytic • After 48 hours, colonies are larger with opaque raised center and transparent margins.
- 35. Biochemical reactions • Oxidase positive and catalase positive • Ferments glucose and maltose with production of gas but not sucrose or lactose
- 36. Serology • Latex agglutination test • CSF sample • Antibodies to meningococcal polysaccharide capsule can be detected • Results within 20 – 30 minutes • High sensitivity but lacks specificity
- 37. Treatment • Empiric therapy • Ceftriaxone/ cefotaxime • Vancomycin until S pneumoniae is ruled out • Ampicillin to be added if Listeria is suspected • If severe penicillin allergies, Meropenem is used instead • Acyclovir is to be added if viral infection is suspected. • Definitive therapy • As per antimicrobial sensitivity test pattern.
- 38. Chemoprophylaxis • Rifampicin is the drug of choice for 2 days • A single dose of oral ciprofloxacin or iv ceftriaxone is also effective • Given to close contacts of suspected patients
- 39. Immunization • Infants – passive immunity from mothers • Under 2 years of age – no reliable antibody production • Quadrivalent meningococcal polysaccharide vaccine (A, C, Y and W 135) • Use of vaccine is strongly advised during outbreaks.
- 40. Meningococcemia • Intravascular multiplication of Neisseria meningitidis • Abrupt onset of spiking fever, chills, arthralgia and muscle pains • Abrupt onset of hypotension and tachycardia • Rapidly enlarging petechial lesions • Wide spread purpura coalesce into hemorrhagic bullae • Shock • DIC • Coma and death ensues within hours
- 41. Fulminant meningococcemia • The most severe form of meningococcemia is the life threatening WATERHOUSE FRIDERICHSEN SYNDROME • Septic shock with vascular collapse and multisystem failure • Bilateral hemorrhages into the adrenal glands leading to adrenal insufficiency • Increased prothrombin time, raised fibrin dimers, reduced fibrinogen levels and low platelet count indicating disseminated intravascular coagulation • Commonly seen in individuals with C5, C6 and C7 deficiency disorders.