How to distinguish bacterial meningitis from cerebral...

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

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


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:


White blood cell count Leukocytes: 15 500 /mm3 Hemoglobin: 8.2 g/dl

Blood electrolytes Glycemia: Not done




Leukocytes: 0

Glucose: 3.7 mmol/L

Gram stain: negative

Culture: negative

⇒  Diagnosis: Cerebral malaria

Attitude: •  Artesunate IV •  Rule out hypoglycemia

Results:


•  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



Cerebral malaria

Fever ü  ü 

Convulsion (>1) ü  ü 

Generalized weakness ü  ü 

Impaired consciousness ü  ü 



WBC count Leukocytes: 12 000 /mm3 Hemoglobin: 9.0 g/dl

Blood electrolytes Glycemia: not done




Leukocytes : 3/mm3

Glucose: Not done

Gram: negative

Culture: negative

Results:


⇒  Diagnosis:


Blood electrolytes Glycemia: not done




Leukocytes : 3/mm3

Glucose: Not done

Gram: negative

Culture: negative

Results:


⇒  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 



•  Malaria test (Thick and thin blood film and/or RDT) •  Blood culture •  NO Lumbar puncture because of contraindication

(Pupillary asymmetry)


WBC count Not done

Glycemia 5.0 mmol/l

RDT malaria Positive


Lumbar puncture (CSF) Not done

⇒  Diagnosis:

Results:


WBC count Not done

Glycemia 5.0 mmol/l

RDT malaria Positive


Lumbar puncture (CSF) Not done

⇒  Diagnosis: Cerebral malaria Bacterial Meningitis possible

Attitude:

•  Artesunate IV •  Ceftriaxone

Results:


•  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:


Cerebral malaria

Fever ü  ü 

Convulsion (1) ü 

Neck stiffness ü 

Vomiting ü 

Clinical case: Omar



WBC count Leukocytes: 18.200 /mm3 Hemoglobin: not done

Blood electrolytes Not done

Malaria RDT positive


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


Malaria RDT positive


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


Cerebral malaria

Fever ü  ü 







Thin blood smear P falciparum +++

Blood culture -

Lumbar puncture (CSF) Leukocytes: 11/mm3

Glucose: not done

Gram: negative

Culture: not done

⇒ Diagnosis:

Results:




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:


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

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