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Ethambutol in tuberculosis: time to reconsider?
  1. S M Grahama,
  2. H M Daleya,
  3. A Banerjeeb,
  4. F M Salaniponic,
  5. A D Harriesa,c
  1. aCollege of Medicine, University of Malawi, Chichiri, Blantyre 3, Malawi, bDistrict Health Officer, Ntcheu District Hospital, Malawi, cNational TB Programme, Malawi
  1. Dr S M Graham, Department of Paediatrics, College of Medicine, Private Bag 360, Chichiri, Blantyre 3, Malawi. email:sgraham{at}

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In the wake of the worsening tuberculosis (TB) situation in young African adults, the number of clinically diagnosed cases of childhood TB is also steadily increasing.1 The recent and proposed introduction into Malawi of new anti-TB regimens, which include ethambutol has prompted us to reconsider the safety of using this drug in young children.

Key messages

  • Ethambutol toxicity is generally dose related

  • There is no confirmed report of ethambutol toxicity in children, except perhaps in TB meningitis

  • In the context of co-infection with HIV in African children, there are significant advantages to ethambutol usage over thiacetazone and streptomycin

  • Uncertainties include appropriate dosage schedules and whether malnutrition may increase the risk of toxicity

Revision of treatment regimens in Malawi

Table 1 shows the regimens used in Malawi for new cases of TB. Having used thiacetazone for approximately 12 years, the Malawi National TB Programme removed it from its essential drug list in January 1997 and substituted ethambutol. Most paediatric cases of TB fall into the category of smear negative pulmonary TB. The proposed new regimen consists of a two month initial phase (with the first two weeks spent in hospital) of supervised rifampicin, isoniazid, and pyrazinamide given three times a week, followed by a six month continuation phase of daily unsupervised isoniazid and ethambutol. For those children with smear positive pulmonary TB and serious forms of extrapulmonary TB, ethambutol is added to the two month initial supervised phase of treatment. Patients with TB meningitis are an exception to the proposed changes and will continue to be given the current regimen.

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Table 1

Treatment regimens in Malawi for new cases of tuberculosis

Reasons for change and potential risks

From the viewpoint of TB management in Malawi, the advantages of these changes are as follows.

The risk of nosocomial transmission of human immunodeficiency virus (HIV) and hepatitis B associated with the use of intramuscular streptomycin in overcrowded wards and those with poor resources is removed.
The danger of thiacetazone induced cutaneous reactions in HIV positive patients is removed.
The duration of hospital admission which accompanied the initial phase is decreased from two months (for injections) to around two weeks, the time required for patient education.
The cost of treatment is reduced as the overall cost of intramuscular injections (drugs, syringes, needles, water for injections, sterilisation) exceeds that of ethambutol.2
The staff time needed for the preparation and administration of intramuscular injections is reduced.

 These advantages apply in treating TB in adults and children. There is also the added attraction of using the same regimen …

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