Related Experiment Video
Updated: Jul 30, 2025
An Automated Culture System for Use in Preclinical Testing of Host-Directed Therapies for Tuberculosis
Published on: August 16, 2021
A model-based approach for a practical dosing strategy for the short, intensive treatment regimen for paediatric
Roeland E Wasmann1, Tiziana Masini2, Kerri Viney2
1Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Insights
A new dosing strategy for the 6-month tuberculosis meningitis (TBM) treatment regimen in children was developed. This strategy aims to simplify drug administration using globally available formulations, improving TBM management for pediatric patients.
Area of Science:
- Pediatric infectious diseases
- Pharmacokinetics and pharmacodynamics
- Global health
Background:
- Tuberculosis meningitis (TBM) poses a severe risk to young children, leading to high morbidity and mortality.
- The World Health Organization (WHO) recommended a shorter, 6-month TBM treatment regimen for children and adolescents.
- Previous dosing schemes were complex, relying on locally available fixed-dose combinations (FDCs).
Purpose of the Study:
- To develop a simplified dosing strategy for the 6-month TBM treatment regimen.
- To facilitate the implementation of the short TBM regimen using newer, globally available drug formulations.
- To inform WHO guidelines for managing TBM in children and adolescents.
Main Methods:
- Population pharmacokinetic (PK) modeling was used to simulate various dosing options in a virtual pediatric population.
- Dosing strategies were designed to align with exposure targets from a previously implemented TBM regimen in South Africa.
- Results were presented to a WHO-convened expert meeting for review and feedback.
Main Results:
- Achieving simple dosing with the globally available RH 75/50 mg FDC proved challenging.
- An expert panel favored targeting slightly higher rifampicin exposure while maintaining isoniazid exposure levels similar to South African practices.
- The developed dosing strategy was incorporated into the WHO operational handbook for TB management in children.
Conclusions:
- A new, simplified dosing strategy for the short TBM treatment regimen in children has been developed.
- This strategy enhances the feasibility of implementing the WHO-recommended 6-month TBM treatment.
- The work supports improved global management of TBM in pediatric populations.
Abstract:
Following infection with Mycobacterium tuberculosis, young children are at high risk of developing severe forms of tuberculosis (TB) disease, including TB meningitis (TBM), which is associated with significant morbidity and mortality. In 2022, the World Health Organization (WHO) conditionally recommended that a 6-month treatment regimen composed of higher doses of isoniazid (H) and rifampicin (R), with pyrazinamide (Z) and ethionamide (Eto) (6HRZEto), be used as an alternative to the standard 12-month regimen (2HRZ-Ethambutol/10HR) in children and adolescents with bacteriologically confirmed or clinically diagnosed TBM. This regimen has been used in South Africa since 1985, in a complex dosing scheme across weight bands using fixed-dose combinations (FDC) available locally at the time. This paper describes the methodology used to develop a new dosing strategy to facilitate implementation of the short TBM regimen based on newer globally available drug formulations. Several dosing options were simulated in a virtual representative population of children using population PK modelling. The exposure target was in line with the TBM regimen implemented in South Africa. The results were presented to a WHO convened expert meeting. Given the difficulty to achieve simple dosing using the globally available RH 75/50 mg FDC, the panel expressed the preference to target a slightly higher rifampicin exposure while keeping isoniazid exposures in line with those used in South Africa. This work informed the WHO operational handbook on the management of TB in children and adolescents, in which dosing strategies for children with TBM using the short TBM treatment regimen are provided.
More Related Videos
Related Concept Videos
01:28Pulmonary Tuberculosis V
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the...
01:24Rational Dosage Regimen: Maintenance Dose and Loading Dose
In most cases, drugs are administered repetitively or infused continuously to maintain a steady-state concentration in the body. At a steady...
01:01Dosage Regimen: Fixed Dose
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...
01:15Drug Dosage Regimen: Overview
Typically, the starting dose and dosing interval are guided by the manufacturer's recommendations based on clinical trials conducted during and after drug...
01:26Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
01:19One-Compartment Open Model for IV Bolus Administration: General Considerations
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...