how to distinguish bacterial meningitis from cerebral...
TRANSCRIPT
How to distinguish bacterial meningitis from cerebral
malaria ?
02.09.16
Prof Alain Gervaix Dre Noémie Wagner
1. Definitions
2. Bacterial meningitis
3. Cerebral malaria
4. Common features and differences
5. Clinical cases
6. Take home messages
Objectives
• Bacterial Meningitis in children:
Definitions
o Infection of the meninges (membranes that envelop the central nervous system)
o Mainly due to S. pneumoniae, N. meningitidis,
H. influenzae type b and Salmonella sp.
• Cerebral malaria:
o Severe form of malaria with neurological signs due to the sequestration of RBC in the brain vessels by cytoadherence, and excessive cytokine production
o Mainly due to Plasmodium falciparum (rarely P. vivax)
Clinical presentation
Convulsion, lethargy and unconsciousness can be the clinical presentation of meningitis and cerebral malaria.
“Pocket book of hospital care for children” WHO, 2013
→ A differential diagnosis must be performed
NOTE: for severe malaria: blood glucose< 2.2
mmol/L
Children
Bacterial meningitis: main clinical signs
Newborns/infants ü Abrupt onset of fever
ü Nonspecific symptoms
o Headache (81-100%)
o Nausea
o Vomiting (70-92%)
ü Neurologic symptoms o Nuchal rigidity (39-70%)
o Photophobia
o Convulsions
o Coma
ü Others o Kernig and Brudzinski signs
o Purpura
ü Abrupt onset of fever
ü Nonspecific symptoms o Thermal instability o Poor feeding o Vomiting o Diarrhea o Rash
ü Neurologic symptoms o None o High pitched cry o Irritability and lethargy o Nuchal rigidity o Bulging fontanelle o Convulsion
Bacterial meningitis: main clinical signs
Bulging fontanelle
Nuchal rigidity
Bacterial meningitis: diagnosis
For the diagnosis of a bacterial meningitis a lumbar puncture is required
CSF Normal values Bacterial meningitis
Pressure < 8cm H2O increased ++
Aspect clear, colorless yellowish, turbid
Cell count/mm3 < 5 leuko > 100 leuko
neonate < 25 > 80 % neutrophils
Protein < 0.4 g/L 0.5 - 6.0 g/L
neonate < 1.5 g/L
CSF Glucose CSF / blood glucose
> 2.2 mmol/L
> 60%
low
< 60%
Gram stain negative Gram: positive
Culture negative positive
Leukocytes < 100 /mm3 in CSF reasonably rule out a bacterial meningitis in immunocompetent children
Cause: Plasmodium falciparum (rarely P. vivax)
Cerebral malaria
Montgomery ,Blood (2016)
• Severe P. falciparum malaria with impaired consciousness
(Glasgow coma score < 11 in children ≥ 2 years of age
or Blantyre coma score < 3 in children < 2 years of age)
AND
• If malaria with seizure: coma persisting for > 30 min after the seizure.
• --> Other treatable causes of coma should be
excluded before diagnosing cerebral malaria (e.g. hypoglycemia, bacterial meningitis).
Main clinical presentation
Cerebral malaria
• Clinical signs and symptoms • Malaria blood tests positive
– Microscope (Thick or thin blood film) – Rapid diagnostic test for malaria parasite
Cerebral malaria
Diagnosis
Always investigate other causes of prostration/coma/convulsion
ü Hypoglycemia ü Meningitis
Resemblance - difference
Bacterial Meningitis Cerebral malaria
Coma
Convulsions
Prostration
Vomiting
Nuchal rigidity *
Bulging of the fontanelle Lumbar puncture: Leukocytes > 100/mm3
Malaria test: positive
(Thick blood film, thin
blood film, rapid
diagnostic test)
Hypoglycemia
* Very frequent in meningitis in children > 18 months - rare in cerebral malaria
Cerebral malaria Bacterial meningitis
Generalized weakness Always Always
Prostration Frequent Frequent
Coma Always Possible
Vomiting Possible Possible
Convulsions Frequent Possible
Nuchal rigidity Rare Fréquent
Purpura Very rare Rare
Bulging fontanelle (< 1 an) Very rare Possible
Lumbar puncture (CSF) Leukocytes > 100/mm3 Very rare Always
Thick / thin blood film or RDT Always Rare (only if concomitant malaria)
Hypoglycemia Frequent Rare
Cerebral malaria Bacterial meningitis
Generalized weakness Always Always
Prostration Frequent Frequent
Coma Always Possible
Vomiting Possible Possible
Convulsions Frequent Possible
Nuchal rigidity Rare Fréquent
Purpura Very rare Rare
Bulging fontanelle (< 1 an) Very rare Possible
Lumbar puncture (CSF) Leukocytes > 100/mm3 Very rare Always
Thick / thin blood film or RDT Always Rare (only if concomitant malaria)
Hypoglycemia Frequent Rare
In practice…
• If clinical signs do not differentiate a bacterial meningitis (BM)
from a cerebral malaria (CM) you must do lab tests to help you with the diagnosis following national guidelines.
1) Thick/thin blood film or RDT for malaria parasite: Negative : no cerebral malaria, look for another diagnosis (see slide 4)
Positive : possible CM, not rule out bacterial meningitis, do a LP 2) Lumbar puncture (LP) if no contraindication: o Direct examination
Leukocytes < 100 mm3 : no bacterial meningitis Gram stain: negative, proteinorachia < 0.4g/L, glycorachia > 2.2mmol/L: very low risk of bacterial meningitis in immunocompetent children
o Culture
Pending for the lumbar puncture start treating with Ceftriaxone and Artesunate
Lumbar puncture (LP): reminder
Contraindication to LP
• Signs of increased intracranial pressure
- Pupillary asymmetry/dilatation - Papilledema - Irregular breathing
• Presence of infected skin over the needle entry site
If LP is contraindicated, treat the patient against bacterial meningitis and cerebral malaria
Treatment for bacterial meningitis:
As soon as possible
• Ceftriaxone : 100 mg/kg once a day for 7 to 10 days (IM or IV)
or • Cefotaxime : 50 mg/kg every 6 hours for 7 to
10 days (IM or IV)
Treatment
• Artesunate 2,4 mg/kg IV or IM Repeat at 12h, at 24h, then 1x/d until the child is able to take the treatment orally
• Monitor hypoglycemia, and treat if needed • Diazepam if seizures
Treatment
Treatment for cerebral malaria
Can LP be abnormal in cerebral malaria? ü YES Rarely, moderate increase of leukocytes in CSF
CSF cell count in cerebral malaria Leukocytes < 100/mm3
CSF cell count in bacterial meningitis Leukocytes ≥ 100/mm3
Frequently asked question (FAQ)
Can a child have a bacterial meningitis AND a malaria concomitantly? ü YES
• Concomitant bacterial infection and severe malaria is possible (meningitis, bacteremia, typhoid fever)
• In many malaria endemic area, children have a positive malaria test. A malaria positive test does not rule out a meningitis
Frequently asked question (FAQ)
Clinical cases
• Zackaria, 18 months old boy
– Day before consultation: • Fever (40.5°C) • Vomiting
– Day 0: • 2 episodes of seizure • Coma (score Blantyre: 2/5)for 45 min.
– No neck stiffness, no purpura
Clinical case: Zackaria
Clinical case: Zackaria
Signs and symptoms Bacterial meningitis
Cerebral malaria
Fever ü ü Convulsion (>1) ü ü Generalized weakness ü ü Impaired consciousness ü ü Vomiting ü ü
→ Additional exams to distinguish CM from BM!
• Malaria test (Thick and thin blood film and/or RDT) • Blood culture • Lumbar puncture if no contraindication
White blood cell count Leukocytes: 15 500 /mm3 Hemoglobin: 8.2 g/dl
Blood electrolytes Glycemia: Not done
Thin blood smear P falciparum positive +++
Blood culture Not done
Lumbar puncture (CSF) Aspect: clear
Leukocytes: 0
Glucose: 3.7 mmol/L
Gram stain: negative
Culture: negative
⇒ Diagnosis:
Results:
Clinical case: Zackaria
White blood cell count Leukocytes: 15 500 /mm3 Hemoglobin: 8.2 g/dl
Blood electrolytes Glycemia: Not done
Thin blood smear P falciparum positive +++
Blood culture Not done
Lumbar puncture (CSF) Aspect: clear
Leukocytes: 0
Glucose: 3.7 mmol/L
Gram stain: negative
Culture: negative
⇒ Diagnosis: Cerebral malaria
Attitude: • Artesunate IV • Rule out hypoglycemia
Results:
Clinical case: Zackaria
• Ambroise, 13 months old boy – Treated for a meningitis and severe malaria 3 months ago
(Artesunate, ampicilline, metronidazol, diazepam, artemether-lumefantrine)
– Since 2 days: • Fever • Decline in general condition
– Day 0: • 2 episodes of generalized convulsion • Coma > 1 hour (score Blantyre: 2) • Prostration
– No neck stiffness, no purpura
Clincal case: Ambroise
Clincal case: Ambroise
Signs and symptoms Bacterial meningitis
Cerebral malaria
Fever ü ü
Convulsion (>1) ü ü
Generalized weakness ü ü
Impaired consciousness ü ü
→ Additional exams to distinguish CM from BM!
• Malaria test (Thick and thin blood film and/or RDT) • Blood culture • Lumbar puncture if no contraindication
WBC count Leukocytes: 12 000 /mm3 Hemoglobin: 9.0 g/dl
Blood electrolytes Glycemia: not done
Thin blood smear P falciparum positive +++
Blood culture Not done
Lumbar puncture (CSF) Aspect: clear
Leukocytes : 3/mm3
Glucose: Not done
Gram: negative
Culture: negative
Results:
Clincal case: Ambroise
⇒ Diagnosis:
WBC count Leukocytes: 12 000 /mm3 Hemoglobin: 9.0 g/dl
Blood electrolytes Glycemia: not done
Thin blood smear P falciparum positive +++
Blood culture Not done
Lumbar puncture (CSF) Aspect: clear
Leukocytes : 3/mm3
Glucose: Not done
Gram: negative
Culture: negative
Results:
Clincal case: Ambroise
⇒ Diagnosis: Cerebral malaria
Attitude: • Artesunate IV • Rule out hypoglycemia
• Thérèse, 16 months old girl – Treated for a cerebral malaria, enteritis and a candidiasis
4 mo ago (Quinine, metronidazol, diazepam, nystatine)
– Since 5 days: • Low grade fever (37.5°C) • Impaired general condition
– Day 0: • Multiple generalized convulsions • Coma > 1 hour • Pupillary asymmetry
– No neck stiffness, no purpura, no vomiting
Clinical case: Thérèse
Signs / Symptoms Bacterial meningitis
Cerebral malaria
Fever ü ü
Convulsion (>1) ü ü
→ Additional exams to distinguish CM from BM!
• Malaria test (Thick and thin blood film and/or RDT) • Blood culture • NO Lumbar puncture because of contraindication
(Pupillary asymmetry)
Clinical case: Thérèse
WBC count Not done
Glycemia 5.0 mmol/l
RDT malaria Positive
Blood culture Not done
Lumbar puncture (CSF) Not done
⇒ Diagnosis:
Results:
Clinical case: Thérèse
WBC count Not done
Glycemia 5.0 mmol/l
RDT malaria Positive
Blood culture Not done
Lumbar puncture (CSF) Not done
⇒ Diagnosis: Cerebral malaria Bacterial Meningitis possible
Attitude:
• Artesunate IV • Ceftriaxone
Results:
Clinical case: Thérèse
• Omar, 36 months old boy
² Since 2 days: • Impaired general condition
Clinical case: Omar
• Fever (max 39.8°C) • Vomiting • Nuchal rigidity • 1convulsion < 5 min
² No purpura
² Day 0:
Signs and symptoms Bacterial meningitis
Cerebral malaria
Fever ü ü
Convulsion (1) ü
Neck stiffness ü
Vomiting ü
Clinical case: Omar
→ Additional exams to distinguish CM from BM!
• Malaria test (Thick and thin blood film and/or RDT) • Blood culture • Lumbar puncture if no contraindication
WBC count Leukocytes: 18.200 /mm3 Hemoglobin: not done
Blood electrolytes Not done
Malaria RDT positive
Blood culture Not done
Lumbar puncture (CSF) Aspect: turbid
Leukocytes: 900/mm3
Glucose: 1.5 mmol/L
Gram stain: positive (gram neg. diplococcus )
Culture: Not done
⇒ Diagnosis:
Results:
Clinical case: Omar
WBC count Leukocytes: 18.200 /mm3 Hemoglobin: not done
Blood electrolytes Not done
Malaria RDT positive
Blood culture Not done
Lumbar puncture (CSF) Aspect: turbid
Leukocytes: 900/mm3
Glucose: 1.5 mmol/L
Gram stain: positif (gram neg. diplococcus )
Culture: Not done
⇒ Diagnosis: Bacterial meningitis Malaria
Attitude: • Continue ceftriaxone • Artesunate IV • Assess blood glucose
Results:
Clinical case: Omar
• Abdel, 2 years old boy
– Day 0: • Fever (40.3°C) • Convulsions (3 episodes)
– No neck stiffness, no purpura, no vomiting
Clinical case: Abdel
Signs and symptoms Bacterial meningitis
Cerebral malaria
Fever ü ü
Convulsion (>1) ü ü
Clinical case: Abdel
→ Additional exams to distinguish CM from BM!
• Malaria test (Thick and thin blood film and/or RDT) • Blood culture • Lumbar puncture if no contraindication
WBC count Leukocytes: 15 700 /mm3 Hemoglobin: 2.6 g/dl
Blood electrolytes Not done
Thin blood smear P falciparum +++
Blood culture -
Lumbar puncture (CSF) Leukocytes: 11/mm3
Glucose: not done
Gram: negative
Culture: not done
⇒ Diagnosis:
Results:
Clinical case: Abdel
WBC count Leukocytes: 15 700 /mm3 Hemoglobin: 2.6 g/dl
Blood electrolytes Not done
Thin blood smear P falciparum +++
Blood culture -
Lumbar puncture (CSF) Leukocytes: 11/mm3
Glucose: not done
Gram: negative
Culture: not done
⇒ Diagnosis: Severe malaria Severe anemia
Attitude: • Artesunate IV • Blood transfusion • Assess blood glucose
Results:
Clinical case: Abdel
o Signs and symptoms of cerebral malaria (CM) and bacterial meningitis (BM) often overlap
o In a child presenting with convulsion, lethargy and unconsciousness a differential diagnosis must be thought, including cerebral malaria, bacterial meningitis and hypoglycemia
o Coma score evaluation should be performed after compensation of hypoglycemia or post-ictal convulsion
Take home message
Take home message
o Lumbar puncture (LP) allows to distinguish CM from BM and must be performed whenever it is possible, when not contraindicated
o LP must not delay initiation of treatment against CM and BM pending of the laboratory results
References
• WHO, « Pocket book oh hospital care for children » – 2nd ed. (2013)
• WHO, « Management of severe malaria - A practical handbook » - 3rd ed. (2013)
• Jakka SR and Al, Characteristic abnormalities in cerebrospinal fluid biochemistry in children with cerebral malaria compared to viral encephalitis. Cerebrospinal Fluid Research 2006, 3:8
• Laman M, Manning L, Siba P, and Davis T. Am. J. Trop. Med. Hyg., 89(5), 2013, pp. 866–868
• Laman M and al., Predictors of Acute Bacterial Meningitis in Children from a Malaria-Endemic Area of Papua New Guinea. Am. J. Trop. Med. Hyg., 86(2), 2012, pp. 240–245
• Berklay and al, Cerebral malaria versus bacterial meningitis in children with impaired consciousness. Q J Med 1999; 92:151–157
Thank you !!!
Prof Alain Gervaix Dre Noémie Wagner