Chapter 4.7.2 Tuberculosis

Most children infected with M. tuberculosis do not develop TB. The only evidence of infection may be a positive skin test. The development of TB depends on the competence of the immune system to resist multiplication of the M. tuberculosis infection. This competence varies with age, being least in the very young. HIV infection and malnutrition lower the body’s defenses, and measles and whooping cough temporarily impair the strength of the immune system. In the presence of any of these conditions, TB can develop more easily.

TB is most often severe when it is located in the lungs, meninges or kidney. Cervical lymph nodes, bones, joints, abdomen, ears, eyes and skin may also be affected. Many children present only with failure to grow normally, weight loss or prolonged fever. Cough for > 14 days can also be a presenting sign; in children, however, sputum-positive pulmonary TB is rarely diagnosed.

Diagnosis

The risk for TB is increased when there is an active case (infectious, smear-positive pulmonary TB) in the same house or when the child is malnourished, has HIV/AIDS or had measles in the past few months. Consider TB in any child with:

A history of:

  • unexplained weight loss or failure to grow normally
    unexplained fever, especially when it continues for longer than 2 weeks 
  • chronic cough (i.e. cough for > 14 days, with or without a wheeze)
    exposure to an adult with probable or definite infectious pulmonary TB. 
  • On examination:
    fluid on one side of the chest (reduced air entry, stony dullness to percussion) 
  • enlarged non-tender lymph nodes or a lymph node abscess, especially in the neck
    signs of meningitis, especially when these develop over several days and the spinal fluid contains mostly lymphocytes and elevated protein
    abdominal swelling, with or without palpable lumps
  • progressive swelling or deformity in the bone or a joint, including the spine

Investigations

Try to obtain specimens for microscopic examination of acid-fast bacilli (Ziehl-Neelsen stain) and for culture of tubercle bacilli. Possible specimens include three consecutive early-morning, fasting gastric aspirates, CSF (if clinically indicated) and pleural fluid and ascites fluid (if present). As the detection rates with these methods are low, a positive result confirms TB, but a negative result does not exclude the disease.

New rapid diagnostic tests are more accurate and may be more widely available in future.
Obtain a chest X-ray. A diagnosis of TB is supported when a chest X-ray shows a miliary pattern of infiltrates or a persistent area of infiltrate or consolidation, often with pleural effusion, or a primary complex.
Perform a purified protein derivative skin test (PPD or mantoux test). The test is usually positive in children with pulmonary TB (reactions of > 10 mm suggest TB; < 10 mm in a child previously vaccinated with BCG is equivocal). The purified protein derivative test may be negative in children with TB who have HIV/AIDS, miliary disease, severe malnutrition or recent measles.
Xpert MTB/RIF should be used as the initial diagnostic test in children suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB.
Routine HIV testing should be offered to all children suspected of TB.

Treatment

  • Give a full course of treatment to all confirmed or strongly suspected cases.
  • When in doubt, e.g. in a child with strongly suspected TB or who fails to respond to treatment for other probable diagnoses, give treatment for TB.

Treatment failures for other diagnoses include antibiotic treatment for apparent bacterial pneumonia (when the child has pulmonary symptoms), for possible meningitis (when the child has neurological symptoms) or for intestinal worms or giardiasis (when the child fails to thrive or has diarrhoea or abdominal symptoms).

  • Suspected or confirmed childhood TB should be treated with a combination of anti-TB drugs, depending on the severity of disease, HIV status and level of isoniazid resistance.
  • Follow the national TB programme guidelines for recommended treatment.
  • To reduce the risk for drug-induced hepatotoxicity in children, follow the recommended dosages:
    • Isoniazid (H):10mg/kg (range,10–15mg/kg); maximum dose, 300mg/day
    • Rifampicin (R):15mg/kg (range,10–20mg/kg); maximum dose, 600mg/ kg per day
    • Pyrazinamide (Z): 35 mg/kg (range, 30–40 mg/kg)
    • Ethambutol (E): 20 mg/kg (range, 15–25 mg/kg).

Treatment regimens

If national recommendations are not available, follow the WHO guidelines according to the regimens given below:

  • Four-drug regimen: HRZE for 2 months, followed by a two-drug (HR) regimen for 4 months for all children with suspected or confirmed pulmonary TB or peripheral lymphadenitis living in an area of high HIV prevalence or where resistance to H is high or children with extensive pulmonary disease living in areas of low HIV prevalence or low H resistance;
  • Three-drug regimen: HRZ for 2 months, followed by a two-drug (HR) regimen for 4 months for children with suspected or confirmed pulmonary TB or tuberculous peripheral lymphadenitis living in areas of low HIV prevalence or low H resistance or HIV-negative;
  • In cases of suspected or confirmed tuberculous meningitis, spinal TB with neurological signs or osteo-articular TB, treat for 12 months with a four- drug regimen (HRZE) for 2 months, followed by a two-drug (HR) regimen for 10 months;
  • In infants (aged 0–3 months) with suspected or confirmed pulmonary TB or tuberculous peripheral lymphadenitis, treat promptly with the standard regimens described above, with adjustment of doses to reconcile the effect of age and possible toxicity in young infants.

ntermittent regimens: In areas with well-established directly observed therapy, thrice-weekly regimens can be considered for children known to be HIV-negative. They should not be used in areas with a high HIV prevalence, because there is a high risk of treatment failure and development of multidrug-resistant TB.

Precautions: Streptomycin should not be used as part of first-line treatment regimens for children with pulmonary TB or tuberculous peripheral lymphadenitis. It should be reserved for the treatment of multidrug-resistant TB in children with known susceptibility to this medicine.

Multidrug-resistant TB

In cases of MDR TB, treat children with proven or suspected pulmonary TB or tuberculous meningitis with a fluoroquinolone or other second-line TB drug. An appropriate MDR TB treatment regimen in the context of a well- functioning MDR TB control programme should be used. The decision to treat should be taken by a clinician experienced in managing paediatric TB.

Monitoring

Confirm that the medication is being taken as instructed, by direct observation of each dose. Monitor the child’s weight gain daily and temperature twice a day in order to check for resolution of fever. These are signs of response to therapy. When treatment is given for suspected TB, improvement should be seen within 1 month. If this does not occur, review the patient, check compliance, re-investigate and reconsider the diagnosis.

Public health measures

  • Notify the case to the responsible district health authorities. Ensure that treatment is monitored as recommended by the national TB programme. Check all household members of the child (and, if necessary, school contacts) for undetected cases of TB, and arrange treatment for any that are found.
  • Children < 5 years of age who are household or close contacts of people with TB and who, after an appropriate clinical evaluation, are found not to have active TB should be given 6 months of isoniazid preventive therapy (10 mg/ kg/day, range 7–15 mg/kg, maximum dose 300 mg/day).

Follow-up

A programme of ‘active’ follow-up, in which a health worker visits the child and his or her family at home, can reduce default from TB treatment. During follow-up at home or in hospital, health workers can:

  • Check whether medications for TB are being taken regularly.
  • Remind the family and the treatment supporter about the importance of taking medications regularly, even if the child is well, for the full duration of treatment.
  • Screen family contacts, including other children in the family, by inquiring about cough, and start these children on isoniazid preventive therapy.
  • Suggest how the family’s home environment might be made healthier for children, such as eliminating smoking inside the house, good ventilation and hand-washing.
  • Discuss with the parents the importance of nutrition in recovery from TB and any problems in providing good nutrition for their children.
  • Check the child for growth, nutritional state and signs of TB and other treat- able conditions. If problems are found, the health worker should recommend how these can be treated or refer the family to a paediatrician.
  • Check the child’s health record, and tell the parents when and where they should bring the child for doses of vaccine.
  • Ask the parents if they have any questions or concerns, and answer or discuss these, or refer the family to a paediatrician.
  • Record their observations on the TB treatment card.