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Canterbury Health
Laboratories
Meningococcal septicaemia
Rachel C Hutton, PhD
Medical Laboratory Scientist
Canterbury Health
Laboratories
Diagnosis Meningococcus
• Disease
• Transmission
• Symptoms
• Diagnosis
• Treatment
• Prevention
• Case Study
Canterbury Health
Laboratories
Meningococcal Disease
• Contagious bacterial disease
• Neisseria meningitidis
– Fastidious aerobe
– Gram Negative Diplococci (GNDC)
– 12 serogroups
• 6 can cause epidemic (A, B, C, W135, X, Y) (WHO)
• Humans only natural carriers
• Meningitis
• Meningococcemia
• Pneumonia
• Arthritis
• Urethritis
Canterbury Health
Laboratories
Transmission
– Exchange of respiratory/throat secretions
– Cough/sneeze
– Close contact – household members
– 10% population are carriers (nose/throat)
– Carriers are crucial to disease transmission
Canterbury Health
Laboratories
Symptoms
• Meningitis
– Nausea
– Vomiting
– Photophobia
– Altered mental status
• Meningococcemia
– Fatigue
– Vomiting
– Cold hands and feet
– Cold chills
– Severe aches or pain
– Rapid breathing
– Diarrhoea
– Petechial rash (dark purple)
Source: CDC online
Canterbury Health
Laboratories
Disease
• 5-10% of patients die within 24-48H
• Meningitidis
– Brain damage
– Hearing loss
– Learning disability
• Septicaemia
– Haemorrhagic rash
– Rapid circulatory collapse
Canterbury Health
Laboratories
Diagnosis
• Clinical Examination
• Gram Stain
• Culture
• Agglutination
• PCR
• MALDI-TOF
– Susceptibility testing
– Serogroups
Canterbury Health
Laboratories
Treatment & Prevention
• Medical Emergency
• Antibiotics immediately ( after LP/Blood)
– Penicillin
– Ampicillin
– Chloramphenicol
– Ceftriaxone
• Vaccination
– Polysaccharide
• Bivalent (A&C), Trivalent (A,C,W), Tetravalent (A,C,Y,W135)
– Outer Membrane Protein (OML)
– Group B
– Conjugate Vaccines
• Tetravalent (A,C,Y,W135)
Canterbury Health
Laboratories
CASE STUDY:
MENINGOCOCCAL
DISEASE
Case Study:
Meningococcal disease
Canterbury Health
Laboratories
Case Study:
Meningococcal disease
Day Event Tests/Results Treatment
0 Presents to GP Diagnosed as EBV
No bloods
None – sent home
Canterbury Health
Laboratories
Day Event Tests/Results Treatment
0 Presents to GP Diagnosed as EBV
No bloods
None – sent home
1 Found by mother Unresponsive Ambulance called
Ambulance GCS 8/15 (E2V2M4)
Skin cool & mottled
Rash (Non-blanching erythematous
confluent)
HR 76
BP not palpable
Airway patient – sat not recorded (NR)
IV ceftriaxone
Canterbury Health
Laboratories
Day Event Tests/Results Treatment
1 ED GCS 9/15
CT head Scan = No pathological
changes
IV Dexamethasone
IV fluids
Adrenalin
ICU LP not performed due to coagulopathy
Low BP
Blood tests
-INR 3.1
-No evidence of DIC
-Raised blood glucose
IV Vancomycin
IV Acyclovar
2 u FFP
Noradrenalin
Insulin infusion
Serology EBV IgG Positive
EBV IgM Negative
EBV EBNA Positive
Evidence of PAST
infection with EBV
Microbiology Blood Cultures = Negative
-Blood, Arterial, CVC
IV Acyclovar Stopped
IV Dexamethasone
Stopped
Canterbury Health
Laboratories
Day Event Tests/Results Treatment
1 ED GCS 9/15
CT head Scan = No pathological
changes
IV Dexamethasone
IV fluids
Adrenalin
ICU LP not performed due to coagulopathy
Low BP
Blood tests
-INR 3.1
-No evidence of DIC
-Raised blood glucose
IV Vancomycin
IV Acyclovar
2 u FFP
Noradrenalin
Insulin infusion
Serology EBV IgG Positive
EBV IgM Negative
EBV EBNA Positive
Evidence of PAST
infection with EBV
Primary diagnosis
=
meningococcal
meningitis
Blood Cultures = Negative
-Blood, Arterial, CVC
EDTA – N. meningitidis PCR = Positive
IV Acyclovar Stopped
IV Dexamethasone
Stopped
Canterbury Health
Laboratories
Day Event Tests/Results Treatment
2 Extubated Continued improvement
Mild headache & photophobia
3 Transferred to Ward Ceftriaxone 2g Q12H
TEDS
7 Discharged
Canterbury Health
Laboratories
This is not the end of the story…
Canterbury Health
Laboratories
Diagnosis Arthritis
Day Event Tests/Results Treatments
9 Increasing unwell
Painful knee + elbow
Lines present L hand + R groin
Admitted to orthopaedic ward
CRP 102
WCC elevated
Pyretic
R Knee = swollen, effusion,
good ROM
Groin = visible scab from line,
no erythema, tender, able to
weight bare
Wash out elbow + knee
(under GA)
IV ceftriaxone
IV flucloxacillin
12 Washout L elbow CRP 32
Full ROM Hip & Knee
Limitation at extremes of left
elbow extension
R hip joint aspirated & washed out N. meningitidis DNA detected
18 Discharged
Canterbury Health
Laboratories
Blood Tests: Trends
WBC
Neutrophils
Platelets
INR Fibrinogen
Canterbury Health
Laboratories
CRP
pH Blood Base Excess
Canterbury Health
Laboratories
EDTA
N. meningitidis DNA detected
Canterbury Health
Laboratories
Samples Sent to Microbiology
Day Sample Results
9 L Elbow Aspirate BC bottle NG
9 L Elbow Aspirate Pottle
Anti co-ag tube
NOS
WBC 175600 x106/L– predom polynucleated
RBC 12700 x106
No Crystals
NG
9 R Knee Aspirate BC bottle GPC
NG
9 R Knee Aspirate Pottle
Anti co-ag tube
Occasional GPC
WBC 5950 x106/L– predom polynucleated
RBC 1520 x106/L
No Crystals
NG
16S rRNA PCR: Bacterial DNA not detected
10 R Knee Aspirate Syringe NOS
Scanty leucocytes
NG
12 Hip Aspirate Pottle
Anti co-ag tube
NOS
WBC 51650 x106/L– predom polynuecleated
RBC 2800 x106/L
N. meningitidis PCR = Detected
Canterbury Health
Laboratories
The Value of PCR
Day Sample Results
9 L Elbow Aspirate BC bottle NG
9 L Elbow Aspirate Pottle
Anti co-ag tube
NOS
WBC 175600 x106/L– predom polynucleated
RBC 12700 x106
No Crystals
NG
9 R Knee Aspirate BC bottle GPC
NG
9 R Knee Aspirate Pottle
Anti co-ag tube
Occasional GPC
WBC 5950 x106/L– predom polynucleated
RBC 1520 x106/L
No Crystals
NG
16S rRNA PCR: Bacterial DNA not detected
10 R Knee Aspirate Syringe NOS
Scanty leucocytes
NG
12 Hip Aspirate Pottle
Anti co-ag tube
NOS
WBC 51650 x106/L– predom polynuecleated
RBC 2800 x106/L
N. meningitidis PCR = Detected
Canterbury Health
Laboratories
Request Forms
Canterbury Health
Laboratories
Canterbury Health
Laboratories
The Value of PCR
Day 12: Hip Aspirate
Test Add N. meningitidis PCR
Result = Positive
Canterbury Health
Laboratories
Meningococcal Burdon
Canterbury Health
Laboratories
Meningococcal Burden
• Meningococcal disease causes life-threatening meningitis and sepsis
conditions
• Patient's health can change from good to mortally ill within hours
• As the antibiotics kill the bacteria, they release more toxin. It can take
several days for the toxin to be neutralized from the body
• Despite antibiotic therapy ~ 1/10 will die
• ~ 1/10 survivors will lose a limb, loose their hearing or suffer
permanent brain damage
Canterbury Health
Laboratories
Thank you
• Dr Sophie Wen
• Jen Fahey
• Elaine Keith
• CHL

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Meningococcal septicaemia

  • 1. Canterbury Health Laboratories Meningococcal septicaemia Rachel C Hutton, PhD Medical Laboratory Scientist
  • 2. Canterbury Health Laboratories Diagnosis Meningococcus • Disease • Transmission • Symptoms • Diagnosis • Treatment • Prevention • Case Study
  • 3. Canterbury Health Laboratories Meningococcal Disease • Contagious bacterial disease • Neisseria meningitidis – Fastidious aerobe – Gram Negative Diplococci (GNDC) – 12 serogroups • 6 can cause epidemic (A, B, C, W135, X, Y) (WHO) • Humans only natural carriers • Meningitis • Meningococcemia • Pneumonia • Arthritis • Urethritis
  • 4. Canterbury Health Laboratories Transmission – Exchange of respiratory/throat secretions – Cough/sneeze – Close contact – household members – 10% population are carriers (nose/throat) – Carriers are crucial to disease transmission
  • 5. Canterbury Health Laboratories Symptoms • Meningitis – Nausea – Vomiting – Photophobia – Altered mental status • Meningococcemia – Fatigue – Vomiting – Cold hands and feet – Cold chills – Severe aches or pain – Rapid breathing – Diarrhoea – Petechial rash (dark purple) Source: CDC online
  • 6. Canterbury Health Laboratories Disease • 5-10% of patients die within 24-48H • Meningitidis – Brain damage – Hearing loss – Learning disability • Septicaemia – Haemorrhagic rash – Rapid circulatory collapse
  • 7. Canterbury Health Laboratories Diagnosis • Clinical Examination • Gram Stain • Culture • Agglutination • PCR • MALDI-TOF – Susceptibility testing – Serogroups
  • 8. Canterbury Health Laboratories Treatment & Prevention • Medical Emergency • Antibiotics immediately ( after LP/Blood) – Penicillin – Ampicillin – Chloramphenicol – Ceftriaxone • Vaccination – Polysaccharide • Bivalent (A&C), Trivalent (A,C,W), Tetravalent (A,C,Y,W135) – Outer Membrane Protein (OML) – Group B – Conjugate Vaccines • Tetravalent (A,C,Y,W135)
  • 10. Canterbury Health Laboratories Case Study: Meningococcal disease Day Event Tests/Results Treatment 0 Presents to GP Diagnosed as EBV No bloods None – sent home
  • 11. Canterbury Health Laboratories Day Event Tests/Results Treatment 0 Presents to GP Diagnosed as EBV No bloods None – sent home 1 Found by mother Unresponsive Ambulance called Ambulance GCS 8/15 (E2V2M4) Skin cool & mottled Rash (Non-blanching erythematous confluent) HR 76 BP not palpable Airway patient – sat not recorded (NR) IV ceftriaxone
  • 12. Canterbury Health Laboratories Day Event Tests/Results Treatment 1 ED GCS 9/15 CT head Scan = No pathological changes IV Dexamethasone IV fluids Adrenalin ICU LP not performed due to coagulopathy Low BP Blood tests -INR 3.1 -No evidence of DIC -Raised blood glucose IV Vancomycin IV Acyclovar 2 u FFP Noradrenalin Insulin infusion Serology EBV IgG Positive EBV IgM Negative EBV EBNA Positive Evidence of PAST infection with EBV Microbiology Blood Cultures = Negative -Blood, Arterial, CVC IV Acyclovar Stopped IV Dexamethasone Stopped
  • 13. Canterbury Health Laboratories Day Event Tests/Results Treatment 1 ED GCS 9/15 CT head Scan = No pathological changes IV Dexamethasone IV fluids Adrenalin ICU LP not performed due to coagulopathy Low BP Blood tests -INR 3.1 -No evidence of DIC -Raised blood glucose IV Vancomycin IV Acyclovar 2 u FFP Noradrenalin Insulin infusion Serology EBV IgG Positive EBV IgM Negative EBV EBNA Positive Evidence of PAST infection with EBV Primary diagnosis = meningococcal meningitis Blood Cultures = Negative -Blood, Arterial, CVC EDTA – N. meningitidis PCR = Positive IV Acyclovar Stopped IV Dexamethasone Stopped
  • 14. Canterbury Health Laboratories Day Event Tests/Results Treatment 2 Extubated Continued improvement Mild headache & photophobia 3 Transferred to Ward Ceftriaxone 2g Q12H TEDS 7 Discharged
  • 15. Canterbury Health Laboratories This is not the end of the story…
  • 16. Canterbury Health Laboratories Diagnosis Arthritis Day Event Tests/Results Treatments 9 Increasing unwell Painful knee + elbow Lines present L hand + R groin Admitted to orthopaedic ward CRP 102 WCC elevated Pyretic R Knee = swollen, effusion, good ROM Groin = visible scab from line, no erythema, tender, able to weight bare Wash out elbow + knee (under GA) IV ceftriaxone IV flucloxacillin 12 Washout L elbow CRP 32 Full ROM Hip & Knee Limitation at extremes of left elbow extension R hip joint aspirated & washed out N. meningitidis DNA detected 18 Discharged
  • 17. Canterbury Health Laboratories Blood Tests: Trends WBC Neutrophils Platelets INR Fibrinogen
  • 20. Canterbury Health Laboratories Samples Sent to Microbiology Day Sample Results 9 L Elbow Aspirate BC bottle NG 9 L Elbow Aspirate Pottle Anti co-ag tube NOS WBC 175600 x106/L– predom polynucleated RBC 12700 x106 No Crystals NG 9 R Knee Aspirate BC bottle GPC NG 9 R Knee Aspirate Pottle Anti co-ag tube Occasional GPC WBC 5950 x106/L– predom polynucleated RBC 1520 x106/L No Crystals NG 16S rRNA PCR: Bacterial DNA not detected 10 R Knee Aspirate Syringe NOS Scanty leucocytes NG 12 Hip Aspirate Pottle Anti co-ag tube NOS WBC 51650 x106/L– predom polynuecleated RBC 2800 x106/L N. meningitidis PCR = Detected
  • 21. Canterbury Health Laboratories The Value of PCR Day Sample Results 9 L Elbow Aspirate BC bottle NG 9 L Elbow Aspirate Pottle Anti co-ag tube NOS WBC 175600 x106/L– predom polynucleated RBC 12700 x106 No Crystals NG 9 R Knee Aspirate BC bottle GPC NG 9 R Knee Aspirate Pottle Anti co-ag tube Occasional GPC WBC 5950 x106/L– predom polynucleated RBC 1520 x106/L No Crystals NG 16S rRNA PCR: Bacterial DNA not detected 10 R Knee Aspirate Syringe NOS Scanty leucocytes NG 12 Hip Aspirate Pottle Anti co-ag tube NOS WBC 51650 x106/L– predom polynuecleated RBC 2800 x106/L N. meningitidis PCR = Detected
  • 24. Canterbury Health Laboratories The Value of PCR Day 12: Hip Aspirate Test Add N. meningitidis PCR Result = Positive
  • 26. Canterbury Health Laboratories Meningococcal Burden • Meningococcal disease causes life-threatening meningitis and sepsis conditions • Patient's health can change from good to mortally ill within hours • As the antibiotics kill the bacteria, they release more toxin. It can take several days for the toxin to be neutralized from the body • Despite antibiotic therapy ~ 1/10 will die • ~ 1/10 survivors will lose a limb, loose their hearing or suffer permanent brain damage
  • 27. Canterbury Health Laboratories Thank you • Dr Sophie Wen • Jen Fahey • Elaine Keith • CHL

Notas del editor

  1. Contagious bacterial diseaseCausative organisim = Meningitis – Infection of the meninges : SwellingSepticaemia – Blood stream Infection: Damages blood vessel walls causing bleeding into the skin & organs
  2. Exposure to asymptomatic carriers
  3. Meningitis develops3-7 post exposureEarly symptoms = generalLate symptoms = disease specific
  4. MALDI-TOF Matrix assisted laser desorbtion ionisationTime of flight – mass spec = mass:charge ration measured (ions accelerated by electric field)Susceptibility = appropriate ABxImportant to ID serotypes = Epidemiology
  5. Treat with ABXPrevent with vaccine3 types – cover epidemic strainsIf cant grow cant test susceptibility/ serogroup? ALL LISCENCED IN nz
  6. 16yr old femaleRenalimpaiment
  7. Table showingThe Day, Event, Test & resultsClassic presentation – early non-specific symptoms16yr old femaleRenal impairment
  8. DIC = Diseminated Intravascular Co-agulation
  9. INR =DIC =
  10. Day 9 = re-admitted due to the onset of an oligoarthristis
  11. Red = AbnormalBlood Count:WBC + Neutrophils High due to immune responsePlatelets (circulating) Low due to consumption the increase as a result of the inflammatory processCo-Aggulation Tests: DIC indicator: Low grade DIC is common with sepsisINRInternational Normalised rate = Clotting time, hi for a pt not on WarfarinNot really useful if the patient is NOT on WarfarinFibrinogen Low/falling indicates DIC High indicates sepsis/CALow fibrinogen lads to prolonged reaction times for other factorsIf fibrinogen Decreased  Prolongs others
  12. CRP:marker for inflammation, part of complement systemnormal <4Remains high probably due to oligoarthritisCRP V ESR: CRP immediate (ESR much slower to increase and to drop again)Blood Gases: AcidosispH & Base Excess Acidosis due to metabolic disturbance (CO2 = respiratory disturbance)Physiological pH = 7.365
  13. Primers = Target CTR A geneEnzyme = TM It is a rapid real time PCR test based on Taqmanchemisty and involves amplifying a section of the CTR A gene.This gene is exclusive to meningococcus and forms part of the capsual biosynthesis locus. The 3 prime end of the CTR A gene is highly conserves amoungstmeningococcus irrespective of serogroupThe PCR test is able to detect less than 1 organism/ml of sampleSample types that can be tested by PCR include EDTA whole blood, CSF, Tissue biopsy and lesion aspirations
  14. Remember N.meningo PCR pos 12 days ago!
  15. Remember N.meningo PCR pos 12 days ago!
  16. No mention of prev meningococcal diseaseOnly 1 sample request N.meningo PCR
  17. Finally on 12th December somebody thinks a PCR for n. meningitidis would be a good idea
  18. This was a very good outcome, most cases are not detected &/or treated so earlyMeningococcus is a very serious disease Sepsis: body.bacterial toxins rupture blood vessels and can rapidly shut down vital organs.
  19. Meningococcus is a very serious disease This was a very good outcome, most cases are not deteted/treated so earlySepsis: bacterial toxins rupture blood vessels and can rapidly shut down vital organs. Largest burdon in an area of sub-saharanafrica – the meningitidis beltAfrica 1996 largest outbreak in historyover 250,000 cases reported25,000 deaths registeredIn NZ – Epidemic began in mid 1991 Group B 96 cases in 2010 (2.4/100,000) Maori 43.8% European 36.5% Case-fatality rate 6.3%