TB

Question 1

Define

Answer 1

Close proximity, infectious load and underlying immunodeficiency all ENHANCE risk of transmission

IMPORTANT: there is a distinction between latent TB (asymptomatic infection state) and TB disease (active)

NOTE: Latent TB is more likely to progress to active TB in infants and young children compared to adults

Children usually acquire TB from an infected adult in the household

Question 2

Symptoms and Signs

Answer 2

Diagnosis in children is particularly difficult

Clinical features are often non-specific:

• Prolonged fever
• Malaise
• Anorexia
• Weight loss

Focal signs of infection (e.g. lymph node swelling)

NOTE: extra-pulmonary disease is relatively uncommon (e.g. TB lymphadenitis, osteoarticular TB, genitourinary TB, TB meningitis)

Question 3

Investigation

Answer 3

1. Sputum samples are UNOBTAINABLE in children < 8 years old (unless specialist techniques are used)
2. Gastric washings on 3 consecutive mornings are required to identify acid-fast bacilli and mycobacterial cultures using Ziehl-Neelsen or auramine stains
   * This is obtained by passing an NG tube and washing out secretions in the stomach with saline before food
3. Urine, lymph node excision, CSF and other radiological examinations should be performed where appropriate.
4. PCR-based methods are increasingly being used in parallel with mycobacterial cultures but these methods provide limited information about drug resistance

Tuberculin Skin Test (TST)/ Mantoux Test

This is done by injecting purified protein derivative intradermally into the forearm and observing 48-72 hours later and measuring the induration in millimetres

NOTE: PPD is a mixture of proteins, some of which are expressed by M. tuberculosis and the BCG, so a positive test result may be because of past BCG vaccination rather than latent TB and active TB.

NEW GUIDELINES: state that an induration ≥ 5mm should be considered POSITIVE regardless of prior BCG vaccination

Interferon-Gamma Release Assay (IGRAs)

• New blood-based test
• Assess the response of T cells to stimulation in vitro with a small number of antigens found in TB but not in the BCG
• A positive result will indicate TB infection rather than BCG
• HOWEVER, a negative result does NOT reliably rule out TB infection

IMPORTANT: neither the IGRA or the TST can reliably distinguish between latent TB and active TB so need to correlate with signs and symptoms

NOTE: with advanced immunocompromise (e.g. HIV), both TST and IGRA can produce false negatives

BEWARE: Do NOT attempt to diagnose TB based on CXR alone in HIV patients because lymphoid interstitial pneumonitis can have a similar appearance and occur in 20% of HIV-infected children

IMPORTANT: ALL individuals with TB should be tested for HIV and vice versa

Question 4

Management

Answer 4

• Arrange hospital admission if the patient has suspected active TB and is unwell
• If hospital admission is not needed, arrange urgent referral to specialist TB service for confirmation of diagnosis and ongoing management

It is a NOTIFIABLE DISEASE

Medical Management

1. Rifampicin + Isoniazid – 6 months
2. Pyrazinamide + Ethambutol – first 2 months only
   (RIPE for 2 months, then RI for another 4 months)

• Pyridoxine (Vitamin B6)- given weekly to prevent peripheral neuropathy due to isoniazid
• In tuberculous meningitis, dexamethasoneis given initially to reduce the risk of long-term sequelae

IMPORTANT: asymptomatic children who are Mantoux or IGRA positive (i.e. latently infected) should also be treated as it will DECREASE the risk of reactivation later in life

Risk assessment for drug-resistant TB

• An MDT approach should be taken, including a key worker who should monitor the patient’s adherence to treatment, clinical response and any adverse effects
• TB Alert is a good website with information about TB

PREVENTION and CONTACT TRACING

• BCG does reduce the incidence of TB but its protective effect is incomplete
• UK RECOMMENDATION: BCG is given at birth for high-risk groups
• IMPORTANT: BCG should NOT be given to HIV-positive or other immunocompromised children due to risk of severe local reactions and dissemination (as it is a live vaccination)
• As most children are infected by a household contact, it is important to screen other family members
• Children exposed to individuals with pulmonary TB should be assessed for evidence of latent TB (by TST and IGRA)

NICE Guidelines: children <2 years who had close contact with a sputum smear positive pulmonary TB person(where organisms are visualised on sputum) should be started on prophylactic isoniazid

If TST and IGRA are negative at 6 weeks, isoniazid should be discontinued and BCG should be given (unless previously immunised with BCG)