TY - JOUR
T1 - Efficacy and safety of single 40 mg/kg oral praziquantel in the treatment of schistosomiasis in preschool-age versus school-age children
T2 - An individual participant data meta-analysis
AU - Olliaro, Piero L.
AU - Coulibaly, Jean T.
AU - Garba, Amadou
AU - Halleux, Christine
AU - Keiser, Jennifer
AU - King, Charles H.
AU - Mutapi, Francisca
AU - N’goran, Eliézer K.
AU - Raso, Giovanna
AU - Scherrer, Alexandra U.
AU - Sousa-Figueiredo, José Carlos
AU - Stete, Katarina
AU - Utzinger, Jürg
AU - Vaillantid, Michel T.
N1 - Funding Information:
The Special Programme for Research and Training in Tropical Diseases (TDR) supported this work and the clinical trial reported in Olliaro et al, 2013 with core funding. The Luxembourg Institute of Health supported the analyses with core funding. The data from Zimbabwe was collected during a research project funded by the World Health Organization (FM) and Thrasher Research Fund (FM). This research was commissioned in part by the National Institute for Health Research (NIHR) Global Health Research programme (16/ 136/33) using UK aid from the UK Government (FM). JK and JC are grateful to the European Research Council for financial support (ERC-2013-CoG 614739-A_HERO). CHK is supported by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE), funded by the University of Georgia Research Foundation through a grant from the Bill & Melinda Gates Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2020 Olliaro et al.
PY - 2020/6
Y1 - 2020/6
N2 - Background Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in pre-school-age children is required, should preventive chemotherapy programs for schistosomi-asis be expanded to include this age group. Methodology We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6–14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs). Principal findings Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool-and school-age children using a general linear model of individual-par-ticipant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up. Conclusions/Significance There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety.
AB - Background Better knowledge of the efficacy and safety of single 40 mg/kg oral praziquantel in pre-school-age children is required, should preventive chemotherapy programs for schistosomi-asis be expanded to include this age group. Methodology We analyzed individual participant-level data from 16 studies (13 single-arm or cohort studies and three randomized trials), amounting to 683 preschool-age children (aged <6 years) and 2,010 school-age children (aged 6–14 years). Children had a documented Schistosoma mansoni or S. haematobium infection, were treated with single 40 mg/kg oral praziquantel, and assessed between 21 and 60 days post-treatment. Efficacy was expressed as arithmetic mean and individual egg reduction rate (ERR) and meta-analyzed using general linear models and mixed models. Safety was summarized using reported adverse events (AEs). Principal findings Preschool-age children had significantly lower baseline Schistosoma egg counts and more losses to follow-up compared to school-age children. No difference in efficacy was found between preschool-and school-age children using a general linear model of individual-par-ticipant ERR with baseline log-transformed egg count as covariate and study, age, and sex as fixed variables, and a mixed model with a random effect on the study. Safety was reported in only four studies (n = 1,128 individuals); few AEs were reported in preschool-age children 4 and 24 hours post-treatment as well as at follow-up. Three severe but not serious AEs were recorded in school-age children during follow-up. Conclusions/Significance There is no indication that single 40 mg/kg oral praziquantel would be less efficacious and safe in preschool-age children compared to school-age children, with the caveat that only few randomized comparisons exist between the two age groups. Preventive chemotherapy might therefore be extended to preschool-age children, with proper monitoring of its efficacy and safety.
UR - https://www.scopus.com/pages/publications/85087354072
U2 - 10.1371/journal.pntd.0008277
DO - 10.1371/journal.pntd.0008277
M3 - Article
C2 - 32569275
AN - SCOPUS:85087354072
SN - 1935-2727
VL - 14
SP - 1
EP - 23
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 6
M1 - e0008277
ER -