Treatment outcomes and tolerability of the revised WHO anti-tuberculosis drug dosages for children

Int J Tuberc Lung Dis. 2018 Feb 1;22(2):151-157. doi: 10.5588/ijtld.17.0535. Epub 2017 Dec 20.

Abstract

Background: In 2010, the World Health Organization (WHO) revised the paediatric dosages of anti-tuberculosis drugs, increasing rifampicin to 15 mg/kg, isoniazid to 10 mg/kg and pyrazinamide to 35 mg/kg. We assessed treatment outcomes, safety and adherence among children treated with the new recommended dosages.

Methods: Prospective cohort of children started on anti-tuberculosis treatment in Uganda with 12 months of follow-up, including alanine aminotransferase (ALT) monitoring. Treatment intake was observed.

Results: Of 144 treated children, 81 were male (56.3%), 106 (73.6%) were aged <5 years, 30 (22%) had moderate to severe malnutrition and 48 (33.3%) had human immunodeficiency virus infection. Treatment outcomes were as follows: 117 (81.3%) successes, 3 (2.1%) failures, 4 (2.8%) lost to follow-up, 19 (13.2%) deaths and 1 (0.7%) transferred out. There was no relapse. Severe malnutrition (adjusted hazard ratio 8.76, 95% confidence interval [CI] 1.59-48.25) was the only predictor of death. Two serious adverse events were attributed to treatment: one case of increased ALT and one with peripheral neuropathy. Median ALT values at baseline and at weeks 2, 4 and 8 were respectively 24 (interquartile range [IQR] 16-39), 26 (IQR 18-38), 28 (IQR 21-40) and 27 (IQR 19-38) international units/l. Treatment adherence was above 85% on all visits.

Conclusion: We confirm the good tolerability of and adherence to the new treatment recommendations. The increased risk of fatal outcome among severely malnourished children requires attention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • Child, Preschool
  • Cohort Studies
  • Female
  • HIV Infections / complications*
  • Humans
  • Infant
  • Infant, Newborn
  • Isoniazid / administration & dosage
  • Male
  • Malnutrition*
  • Patient Compliance*
  • Practice Guidelines as Topic
  • Prospective Studies
  • Pyrazinamide / administration & dosage
  • Rifampin / administration & dosage
  • Treatment Outcome
  • Tuberculosis, Pulmonary / complications
  • Tuberculosis, Pulmonary / drug therapy*
  • Uganda
  • World Health Organization

Substances

  • Antitubercular Agents
  • Pyrazinamide
  • Isoniazid
  • Rifampin