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Intensive short course chemotherapy in the management of tuberculous meningitis
P R Donald1, J F Schoeman, L E Van Zyl
1Department of Paediatrics and Child Health, University of Stellenbosch and Tygerberg Hospital, South Africa. aec1@maties.sun.ac.za
Insights
This study shows that a six-month chemotherapy regimen for childhood tuberculous meningitis (TBM) using high-dose isoniazid, rifampicin, ethionamide, and pyrazinamide is safe and effective, with minimal hepatotoxicity and low relapse rates.
Area of Science:
- Pediatric Infectious Diseases
- Tuberculosis Research
- Pharmacology
Background:
- Short-course chemotherapy for tuberculous meningitis (TBM) is recommended but lacks extensive pediatric data.
- Evaluating the safety and efficacy of a 6-month treatment regimen in children with TBM is crucial.
Observation:
- A prospective study involved 95 children with TBM (Stages I-III) treated with isoniazid (INH), rifampicin (RMP), ethionamide (ETH), and pyrazinamide (PZA) for 6 months.
- Children were followed for one year post-discharge. Treatment involved high daily doses of these agents.
- Adverse events included transient elevated bilirubin in 20% and one case of hepatitis A; no overt hepatotoxicity was observed.
Findings:
- The 6-month regimen demonstrated a low risk of relapse and was generally well-tolerated.
- Mortality occurred primarily in Stage III TBM patients before or shortly after therapy completion.
- The study suggests that high-dose, 6-month chemotherapy is a viable option for pediatric TBM.
Implications:
- This research supports the use of a standardized 6-month chemotherapy regimen for TBM in children.
- Findings provide evidence for safe and effective TBM treatment, potentially reducing long-term complications.
- Further research could explore optimizing dosages and monitoring for rare adverse events in pediatric TBM management.
Setting:
Short course chemotherapy for tuberculous meningitis (TBM) is advocated by several groups, but relatively few children have been so treated and followed up.
Methods:
A prospective, observational study of isoniazid (INH), rifampicin (RMP) and ethionamide (ETH) in a dosage of 20 mg/kg, and pyrazinamide (PZA) 40 mg/kg, all given once daily in hospital for 6 months. Surviving children were followed up for a year after discharge.
Results:
Ninety five children, 39 (41%) at stage III, 52 (55%) at stage II and 4 (4%) at stage I TBM were studied. Ten (26%) at stage III and 3 (6%) at stage II died before completion of therapy. Five surviving children (6%) moved on discharge and were untraceable; seven children (9%) were lost during follow up and three were inadvertently restarted on antituberculosis therapy. Two children with severe stage III disease died after discharge. One child experienced a probable disease recrudescence 1 month after discharge. Eighteen children (20%) developed a mildly elevated serum bilirubin concentration during the first month of treatment. In five of these children INH, RMP, ETH and PZA were stopped and streptomycin (SM) and ethambutol substituted. In all cases the original treatment was restarted without incident. One child developed overt jaundice after 5 months of treatment due to hepatitis A infection.
Conclusions:
Our experience suggests that young children with TBM can be safely treated for 6 months with high doses of antituberculosis agents without overt hepatotoxicity and with a low risk of relapse.