Optimal regimens of praziquantel for schistosomiasis in young children
10 affiliations
- 1Department of Pharmacology and Therapeutics, University of Liverpool
- 2MRC/UVRI and LSHTM Uganda Research Unit
- 3Department of Clinical Research, London School of Hygiene and Tropical Medicine
- 4MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine
- 5Department of Infection Biology, London School of Hygiene and Tropical Medicine
- 6Leiden University Center for Infectious Diseases, Leiden University Medical Center
- 7Department of Women’s and Children’s Health, University of Liverpool
- 8Infectious Diseases Institute, Makerere University College of Health Sciences
- 9Department of Pediatrics, Alpert Medical School of Brown University
- 10Center for International Health Research, Brown University Health
Abstract
Praziquantel (PZQ) is the drug of choice for control and treatment of schistosomiasis. Pharmacokinetic (PK) data for establishing a safe and effective PZQ dose in preschool-aged children are limited. We characterized PZQ pharmacokinetics in children aged 1–4 years with intestinal schistosomiasis. PZQ was administered at either 40 mg/kg or 80 mg/kg (split into two doses of 40 mg/kg, 3 h apart), and plasma concentrations were quantified. These data were pooled with pre-existing PK data from children aged 3–8 years, who received PZQ 40 mg/kg or 60 mg/kg. A population PK model was fitted to the pooled data, and individual drug exposure was estimated. Pharmacodynamic outcomes were egg reduction rate, and both parasitological and antigenic cure at 4 weeks post-treatment. The relationship between PZQ exposure and cure was established using regression analysis. Monte Carlo simulations were performed to assess the adequacy of weight-based PZQ dosing. A two-compartment model, with first-order absorption and elimination, best described PZQ disposition. Total body weight was allowed to influence clearance and the central compartment volume, with fixed allometric exponents 0.75 and 1, respectively. Simulations indicated that both weight-banded fixed-dose regimens and individual weight-based dosing achieved comparable drug exposures. The area under the concentration-time curve (AUC 0–24 ) of the total drug was a strong predictor of parasitological cure. PZQ 80 mg/kg achieved parasitological cure rates >85% but may still be insufficient for complete worm elimination, as demonstrated by the lower rate (69.5%) of antigen clearance. Further optimization of anti-schistosomiasis treatments may be required to achieve complete worm elimination in mass treatment programs.
IMPORTANCE: Schistosomiasis is a neglected tropical disease of significant global health concern, disproportionately affecting children in endemic areas. Praziquantel (PZQ) is the only drug currently recommended by the WHO, as a single 40 mg/kg dose for treatment of schistosomiasis. However, pharmacokinetic-pharmacodynamic (PK/PD) data to support optimal dosing of PZQ for children <5 years are limited. In this study, we evaluated the PK/PD of PZQ, administered at 80 mg/kg (split into two doses of 40 mg/kg, 3 h apart), vs the standard 40 mg/kg regimen, in children aged 1–4 years. Our results indicate that PZQ exposure following 80 mg/kg achieves parasitological cure more effectively than the current standard 40 mg/kg single-dose regimen. In children with a heavy infection intensity, the 80 mg/kg dose may still be insufficient to achieve complete worm clearance. These results highlight the need for further optimization of PZQ regimens and the discovery and development of new antiparasitic agents.
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BibTeX
@article{obura2026optimal,
title = {{Optimal regimens of praziquantel for schistosomiasis in young children}},
author = {Bonniface Obura and Andrew Edielu and Jennifer Unsworth and Ana Jimenez-Valverde and Gloria K. Ayebazibwe and Emily L. Webb and Patrice A. Mawa and Pytsje T. Hoekstra and Govert J. van Dam and Catriona Waitt and Jennifer Friedman and Amaya L. Bustinduy and Shampa Das and William Hope},
journal = {mBio},
year = {2026},
month = nov,
doi = {10.1128/mbio.02512-26},
url = {https://journals.asm.org/doi/10.1128/mbio.02512-26},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Optimal regimens of praziquantel for schistosomiasis in young children
AU - Bonniface Obura
AU - Andrew Edielu
AU - Jennifer Unsworth
AU - Ana Jimenez-Valverde
AU - Gloria K. Ayebazibwe
AU - Emily L. Webb
AU - Patrice A. Mawa
AU - Pytsje T. Hoekstra
AU - Govert J. van Dam
AU - Catriona Waitt
AU - Jennifer Friedman
AU - Amaya L. Bustinduy
AU - Shampa Das
AU - William Hope
PY - 2026
DA - 2026/11/05
JO - mBio
DO - 10.1128/mbio.02512-26
UR - https://journals.asm.org/doi/10.1128/mbio.02512-26
AB - Praziquantel (PZQ) is the drug of choice for control and treatment of schistosomiasis. Pharmacokinetic (PK) data for establishing a safe and effective PZQ dose in preschool-aged children are limited. We characterized PZQ pharmacokinetics in children aged 1–4 years with intestinal schistosomiasis. PZQ was administered at either 40 mg/kg or 80 mg/kg (split into two doses of 40 mg/kg, 3 h apart), and plasma concentrations were quantified. These data were pooled with pre-existing PK data from children aged 3–8 years, who received PZQ 40 mg/kg or 60 mg/kg. A population PK model was fitted to the pooled data, and individual drug exposure was estimated. Pharmacodynamic outcomes were egg reduction rate, and both parasitological and antigenic cure at 4 weeks post-treatment. The relationship between PZQ exposure and cure was established using regression analysis. Monte Carlo simulations were performed to assess the adequacy of weight-based PZQ dosing. A two-compartment model, with first-order absorption and elimination, best described PZQ disposition. Total body weight was allowed to influence clearance and the central compartment volume, with fixed allometric exponents 0.75 and 1, respectively. Simulations indicated that both weight-banded fixed-dose regimens and individual weight-based dosing achieved comparable drug exposures. The area under the concentration-time curve (AUC 0–24 ) of the total drug was a strong predictor of parasitological cure. PZQ 80 mg/kg achieved parasitological cure rates >85% but may still be insufficient for complete worm elimination, as demonstrated by the lower rate (69.5%) of antigen clearance. Further optimization of anti-schistosomiasis treatments may be required to achieve complete worm elimination in mass treatment programs. IMPORTANCE: Schistosomiasis is a neglected tropical disease of significant global health concern, disproportionately affecting children in endemic areas. Praziquantel (PZQ) is the only drug currently recommended by the WHO, as a single 40 mg/kg dose for treatment of schistosomiasis. However, pharmacokinetic-pharmacodynamic (PK/PD) data to support optimal dosing of PZQ for children <5 years are limited. In this study, we evaluated the PK/PD of PZQ, administered at 80 mg/kg (split into two doses of 40 mg/kg, 3 h apart), vs the standard 40 mg/kg regimen, in children aged 1–4 years. Our results indicate that PZQ exposure following 80 mg/kg achieves parasitological cure more effectively than the current standard 40 mg/kg single-dose regimen. In children with a heavy infection intensity, the 80 mg/kg dose may still be insufficient to achieve complete worm clearance. These results highlight the need for further optimization of PZQ regimens and the discovery and development of new antiparasitic agents.
SN - 2150-7511
ER -