Meningitis, Tuberculous (TBM) In Children

Description

Diagnostic criteria

General and supportive measures

Medicine treatment

Referral

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ICD-10 code: A17.0

*Notifiable condition.

DESCRIPTION

Tuberculous meningitis is an infection of the meninges caused by M. tuberculosis. Early diagnosis and treatment improves the prognosis.

Differentiation from acute bacterial meningitis may be difficult. If in any doubt, treat for both conditions.

Complications may be acute or long term:

• Acute:
  • raised intracranial pressure,
  • hydrocephalus,
  • cerebral oedema,
  • brain infarcts,
  • hemi/quadriplegia, 
  • convulsions,
  • hyponatraemia due to inappropriate antidiuretic hormone (ADH) secretion or cerebral salt wasting.
    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral salt wasting both present with hyponatraemia; the former responding to fluid restriction and the latter to fluid replacement, i.e. sodium chloride 0.9%.
    SIADH has lower serum uric acid and low urine output. Cerebral salt wasting has a normal serum uric acid and high urine output.
  • Long term neurological sequelae include: mental handicap, blindness and deafness.

DIAGNOSTIC CRITERIA

Clinical

• History of contact with an infectious tuberculosis case.
• Onset may be gradual with vague complaints of drowsiness (or fatigue), vomiting, fever, weight loss, irritability and headache.
• Later symptoms such as convulsions and neurological fall-out may occur.
• Older children may present with behavioural changes.
• Examination may reveal signs of meningeal irritation and raised intracranial pressure, convulsions, cranial nerve palsies, localising signs (such as hemiparesis), altered level of consciousness or coma and choroidal tubercles.
• The degree of involvement is classified into 3 stages. Prognosis relates to the stage of the disease.
  • Stage 1: Non-specific signs, conscious, rational, no focal neurological signs, no hydrocephalus.
  • Stage 2: Signs of meningeal irritation, confusion and/or focal neurological signs.
  • Stage 3: Stupor, delirium, coma and/or neurological signs, i.e. hemiplegia.

Investigations

• CSF findings:
  • May vary depending on the stage.
  • Protein is usually raised.
  • Chloride and glucose are moderately low.
  • Lymphocytes usually predominate.
  • Gram stain is negative and acid-fast bacilli are seldom found.
  • A rapid TB molecular test (e.g. GeneXpert®) should be done on CSF. It is helpful where it is positive, but a negative rapid TB molecular test (e.g. GeneXpert®) does not exclude TBM.
  • A negative result does not exclude TB and CSF cultures must still be done. Bacilli may be cultured from the CSF but may take up to 4–6 weeks. If culture is positive, drug susceptibility testing will be done. Always send for culture, do not perform a stain as there is a low diagnostic yield from low concentration of organisms and wastes the CSF sample.
• A TST and chest X-ray must be done, but are often unhelpful.
• If depressed level of consciousness or focal neurological signs are present, a CT scan is useful to determine if safe to LP (do CT first before LP in such cases).
• Electrolytes: check for hyponatraemia.

GENERAL AND SUPPORTIVE MEASURES

• Monitor neurological status on a regular basis. If rapid deterioration in level of consciousness, consider neurosurgical referral for a ventriculoperitoneal shunt (VP shunt).
• Ensure optimal nutrition. Initially naso-gastric feeding is usually needed. Refer for nutrition support.
• Rehabilitative measures: most patients need physiotherapy and occupational therapy.
• Surgical treatment (VP shunt) is needed for a non-communicating hydrocephalus, diagnosed by air-encephalogram.
• Communicating hydrocephalus with severely raised pressure may be managed with medicines once hydration status is stable and/or with serial lumbar puncture with specialist consultation (tertiary hospital care).

MEDICINE TREATMENT

Differentiation from acute bacterial meningitis may be difficult. If in doubt, treat for both conditions.

Anti-tuberculosis treatment

• Requires therapy with a combination of 4 drugs as a special regimen.
• All treatment should be directly observed therapy.
• Single drugs may form part of the regimen to provide the total daily required dose for each medicine by supplementing the combination to give the necessary therapeutic dose per kilogram.

A 6-month regimen of all 4 of the following drugs:

• Rifampicin, oral, 20 mg/kg as a single daily dose.
  • Maximum daily dose: 600 mg.

PLUS

• Isoniazid, oral, 20 mg/kg as a single daily dose.
  • Maximum daily dose: 400 mg.

PLUS 

• Pyrazinamide, oral, 40 mg/kg as a single daily dose.
  • Maximum daily dose: 2000 mg.

PLUS

• Ethionamide, oral, 20 mg/kg as a single daily dose.
  • Maximum daily dose: 1000 mg.

The 75/50 RH and 75/50/150 RHZ formulations are not suitable for achieving the required doses in disseminated TB & TBM, so the 60/60 RH formulation should be used for such children.

Single phase of treatment, 6–9 months Once daily; 7 days a week

Body weight	Rifampicin/ Isoniazid (RH)*  60/60 mg dispersible tablet (scored)	Pyrazinamide (Z)  500 mg tablet (scored) OR 500 mg/8 mL suspension**	Ethionamide (Eto)  250 mg tablet (scored) OR 250 mg/8 mL suspension***
< 2	Obtain Expert Advice
2–2.9	3⁄4 tablet or 3 mL	1 mL	1.5 mL
3–3.9	1 tablet or 4 mL	2 mL	2 mL
4–4.9	1 1⁄2 tablets or 6 mL	2.5 mL	2.5 mL
5–5.9	1 3⁄4 tablets or 7 mL	3 mL	3 mL
6–6.9	2 tablets or 8 mL	1⁄2 tablet or 4 mL	1⁄2 tablet or 4 mL
7–8.9	2 1⁄2 tablets or 10 mL
9–9.9	3 tablets or 12 mL	3⁄4 tablet or 6 mL	3⁄4 tablet or 6 mL
10–11.9	3 1⁄2 tablets or 14 mL
12–12.9	4 tablets or 16 mL	1 tablet or 8 mL	1 tablet or 8 mL
13–14.9	4 1⁄2 tablets or 18 mL
15–16.9	5 tablets or 20 mL		1 1⁄4 tablet or 10 mL
17–17.9	5 1⁄2 tablets or 22 mL	1 1⁄4 tablets or 18–19.9
18–19.9			1 1⁄2 tablets or 12 mL
20–24.9	6 tablets or 24 mL	1 1⁄2 tablets or 12 mL

 

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Note:
Children should be taught and encouraged to swallow whole tablets or, if required, fractions of tablets so as to avoid large volumes of liquid medication if possible.

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*If oral suspension required, for each dose, disperse 1 x RH 60/60 mg tablet in 4 mL of water, administer required dose as indicated in above chart, discard unused suspension.

**If oral suspension is required, crush 1 x 500 mg pyrazinamide tablet to a fine powder, disperse in 8 mL water to prepare a concentration of 500 mg/8 mL (62.5 mg/mL), administer required dose as indicated in above chart, discard unused suspension.

***If oral suspension is required, crush 1 x 250 mg ethionamide tablet to a fine powder, disperse in 8 mL of water to prepare a concentration of 250 mg/8 mL (31.3 mg/mL); administer required dose as indicated in above chart; discard unused suspension.

Consider prolonging treatment for another 3 months if there are concerns about ongoing disease. Consult with a specialist.

In case of suspected/confirmed multidrug-resistant TBM, refer immediately for admission and treatment.

Steroid therapy:

• Prednisone, oral, 2 mg/kg as a single daily dose for 4 weeks.
  • Maximum daily dose: 60 mg.
  • Taper to stop over further 2 weeks.

Hydrocephalus

Avoid low sodium IV fluids in these patients, i.e. < 60 mmol/L. To differentiate communicating from non-communicating hydrocephalus an air-encephalogram is usually required. Communicating hydrocephalus is more common in this condition. In children with a sudden deterioration of level of consciousness and other comatose children with TBM, inform the neurosurgeon before doing the airencephalogram so that shunt surgery can immediately be done if the hydrocephalus is non-communicating. Air-encephalogram procedure: do a lumbar puncture, inject 5 mL of air with a syringe and do an immediate lateral X-ray of the skull. Air in the lateral ventricles on skull X-ray indicates communicating hydrocephalus; air at the base of the brain (not in lateral ventricles), indicates non-communicating hydrocephalus.

Communicating hydrocephalus
If dehydrated, rehydrate with sodium chloride 0.9%, IV.
Start diuretics as soon as patient is well hydrated and serum electrolytes are within the normal range.

• Acetazolamide, oral, 20 mg/kg/dose 8 hourly.
  • Maximum daily dose: 1 000 mg.
  • Monitor for metabolic acidosis and serum potassium derangements.

PLUS

• Furosemide, oral, 0.3 mg/kg/dose 8 hourly for the first month of treatment.
  • Taper slowly over 2 weeks if the intracranial pressure has normalised, as indicated by clinical response or resolution of hydrocephalus on follow-up scan.
  • Do not restrict fluids once on diuretics.

Sudden deterioration of level of consciousness:

• Mannitol, IV, 250 mg/kg administered over 30–60 minutes.

REFERRAL

• TBM not responding to adequate therapy.
• TBM with complications.
• Suspicion of non-communicating hydrocephalus.
• Suspected drug-resistant TB (contact with drug-resistant TB case).

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Standard Treatment Guidelines And Essential Medicines List For South Africa, Hospital Level, Paediatrics, 2023 Edition

Chapter 10: Tuberculosis,  10.4 Meningitis, Tuberculous (TBM) In Children