MMI 133 Session 2 Lecture PDF

MMI 133 Session 2  Diagnosis Unknown Edmonton Alberta Diagnosis Unknown: Sudden Death (9th video in series) https://www.kanopy.com/en/ualberta/video/ 119074/82661 (the link is in eclass as well)  Neisseria meningitidis One cause of: meningitis and sepsis  Objectives ❑ Define meni...

MMI 133 Session 2  Diagnosis Unknown Edmonton Alberta Diagnosis Unknown: Sudden Death (9th video in series) https://www.kanopy.com/en/ualberta/video/ 119074/82661 (the link is in eclass as well)  Neisseria meningitidis One cause of: meningitis and sepsis  Objectives ❑ Define meningitis and explain what the meninges are ❑ Describe Neisseria meningitidis in terms of its Gram stain reaction and physical attributes ❑ Identify the mode of transmission for N. meningitidis ❑ List some virulence factors of N. meningitidis ❑ Identify symptoms characteristic of meningitis and sepsis ❑ Recognize the importance of a rapid diagnosis for treatment and survival  So what is meningitis? ❑ Meningitis is inflammation of the meninges. ❑ Meninges are coverings of the brain and spinal cord (protect and enclose) ❑ Meningitis is usually caused by microbes infecting the cerebral spinal fluid (CSF) ©NIH, US govt. Our Bacterium: Neisseria meningitidis ❑ One of the microbial causes of meningitis ❑ Gram negative diplococcus, capsule (layer of sugars outside of the bacterial cell wall) important for disease ❑ >12 serotypes based on capsule carbohydrates (polysaccharides or sugars) ❑ Only 6 subtypes called serotypes are responsible for most of the epidemics in the world (A,B,C, W-135, X, Y) ❑ Serotype B most common in developed nations ❑ Only affects humans: no animal reservoir  Transmission » Droplet transmission (coughs, sneezes, saliva) (range ~1 m) © J. Gnarpe, U of A Virulence and Pathogenicity ❑ Attaches to epithelial cells in the throat ❑ Invades and can go to the bloodstream and/or CSF ❑ Contains “endotoxin” anchored in the cell wall – this causes inflammation ❑ Endotoxin = (LOS)(lipo-oligopolysaccharide) has Lipid A as part of the molecule – this is the endotoxin) ❑ Endotoxin activates blood clotting, leads to DIC (disseminated intravascular coagulation), hemorrhage (petichiae, purpura) and shock ❑ Bacteria evade phagocytosis (being eaten) by white blood cells (possible due to presence of a polysaccharide coating around the outside of the bacterial cell wall – the “capsule”) ❑ This allows the bacteria to survive and reproduce in the CSF Clinical Disease Ecchymoses or purpura © U of A, Infectious Disease Digital Repository  5 year old: result of this is the need for amputation © Andreas Eliades, DermAtlas, Johns Hopkins University This bacterium is sometimes called “meningococcus (sing.) (pl. meningococci)” which are nicknames for Neisseria meningitidis  2 types of disease: meningitis and sepsis ❑ Meningococcal meningitis ❑ Meningococcal sepsis (inflammation/infection of (replication of bacteria in the the meninges) bloodstream) Increased pressure to brain, disseminated infection, can influx of inflammatory cells occur quickly, Gram negative (white blood cells) to CSF sepsis , intravascular (cerebral spinal fluid) coagulation (clotting), need for amputation death if untreated - if treated early has very good death if untreated, or if prognosis treated too late Disease: mortality high if untreated, but… 90-95% chance of survival if diagnosed early and treated early Symptoms and Disease ❑ Meningitis ❑ Sepsis headache, stiff neck, fever, petichiae/purpura, photosensitivity, nausea, shock, hemorrhage, DIC - sore throat, petichiae, internal organ meltdown finally coma and eventual and eventual death death © PHIL 6548 CDC Diagnosis » aspirate CSF (cerebral spinal fluid) and/or blood » Gram stain CSF and report to physician » culture and/or EIA or PCR » serogroup for epidemiology (public health) » ascertain susceptiblity to antibiotics Treatment must be immediate! » Administer antibiotics directly after taking the culture specimens (NOT BEFORE) » Empirical antibiotic treatment: best guess before culture confirmation » Best to use third generation cephalosporin, e.g. ceftriaxone (good CSF penetration) » Antibiotic susceptibility testing will be done on bacterial isolate growing from the cultures  Vaccine ❑ Three types: Polysaccharide (antibodies will be made to capsule): -effective against 4/15 types (A,C,Y, W135) -90% protection for 2-5 years -cannot be used for pediatric patients , < 2 yrs Conjugated: polysaccharide combined with a protein good for children < 2 yr and immunosuppressed individuals who can’t make antibodies efficiently. Serogroups A,C,W,Y) Type B vaccine based on proteins in the cell wall NOT the capsule! (new vaccine spring 2014 but varying activity in different populations – here maybe 50-60% effective) » Changing epidemiology ˃ Serogroup A used to be the most common invasive infection in Sub-Saharan Africa until 2010 when the population there were vaccinated ˃ Serogroups have shifted to W,X and C in this area  So what happened in Alberta? ❑ First cases in Dec 1999 – outbreak lasted to June 2001 with serogroup C ❑ 61 cases ❑ 2 deaths ❑ Total of 56 isolates: 50/56 typed by lab as Serogroup C (unique clone) ❑ Resulted in a mass vaccination program, stopping the outbreak ❑ Outcome for patients: ❑ 70.5% full recovery Do not need to ❑ 3.3% died (2) know this! ❑ 6.6% (4) amputations ❑ 11.5% (7) severe scars ❑ 14.5% other sequalae (neurological problems mostly) Recent outbreaks (global) ❑ Nigeria ❑ 108/1364 fatal (8%) ❑ Chad ❑ ~150/1650 fatal (11%) Do not need to ❑ Burkina Faso know this! ❑ 718/5118 fatal (14%) ❑ African Meningitis Belt ❑ 57 deaths/923 cases (A) fatal (6.2%) ❑ African Meningitis Belt ❑ 639 deaths/6685 case (W-135) fatal (9.6%)  Public Health Issues ❑ Rapid ID of disease ❑ Rapid ID of contacts ❑ Prophylactic antibiotics ❑ Vaccination of susceptible individuals ❑ Health prevention information ❑ Reportable disease