Background Ivermectin (IVM) is widely used in mass drug administration (MDA) programs for the control of neglected tropical diseases (NTDs). Current regimens rely on weight- or height-based dosing, which lead to operative challenges. This study evaluates an age-based fixed-dose regimen for IVM.

Methodology This is an individual participant data (IPD) meta-analysis including anthropometric data from over 700,000 individuals, across 53 NTD-endemic countries. Fixed-dose regimens were developed based on weight distribution by age. The proportion of individuals achieving the target range dose (200–400 µg/kg) was assessed and compared to traditional dosing regimens.

Principal Findings Fixed-doses of 3 mg for pre-school children (PSAC), 9 mg for school-aged children (SAC), and 18 mg for women of reproductive age (WRA) resulted in a higher proportion of participants receiving the target dose compared to weight- and height-based regimens (79.9% vs. 32.7% and 37.3%, respectively, p < 0.001). Underdosed individuals were fewer with fixed-dose (8.7%) compared to weight-based (32.6%) and height-based (46.3%) regimens. Although doses above the target range increased slightly, most remained within 600 µg/kg.

Conclusions An age-based fixed-dose regimen for IVM could improve treatment coverage and simplify MDA activities. Simplified logistics could lead to cost savings in drug distribution and administration, improving the overall efficiency of MDA programs. These findings support the inclusion of currently excluded PSAC in IVM-based MDA interventions. More broadly, this paper provides evidence for considering the potential policy and programmatic implications of fixed-dose IVM. This Individual Participant Data Meta-analysis (IPD-MA) is registered in PROSPERO (CRD42024521610).

AUTHOR SUMMARY Ivermectin is an essential drug with proven safety and effectiveness against several parasitic infections. It plays a key role in Mass Drug Administration (MDA) programs targeting prevalent Neglected Tropical Diseases. Currently, ivermectin dosing is based on weight or height, which can be difficult to measure in the field during MDA campaigns and adds complexity and workload for health workers. These methods also carry a risk of underdosing.

In this study, we analyzed data from more than 700,000 participants across 53 countries to explore whether a fixed-dose approach could simplify MDA implementation while maintaining doses within the therapeutic range. We found that fixed-dose regimens provide more accurate treatment for a larger proportion of individuals, reduce the likelihood of underdosing, and only occasionally result in doses above the recommended levels, typically by small margins and in a limited proportion of participants. This simplified approach could ease treatment delivery in community settings and improve coverage and operational efficiency. Our findings provide practical evidence to inform policy discussions on how to streamline and strengthen ivermectin - based MDA programs.

Alejandro Krolewiecki, a co-author of this manuscript, is the Principal Investigator of the EDCTP-funded STOP2030 project, which is coordinated by Liconsa Laboratories. In this role, he holds an ad-hoc consultancy with Liconsa Labs. Adriana Echazu, as the corresponding author, declares no conflict of interest. All other authors also declare no conflict of interest.

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024521610

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This retrospective observational study did not require ethical approval, as it involved the analysis of de-identified data from previously conducted studies. All data were fully anonymized, ensuring that individual participants could not be identified and that confidentiality was maintained. The study relied on simulated ivermectin doses applied to hypothetical scenarios no actual medication was administered, eliminating risks to any participants. Additionally, the study was conducted in accordance with established ethical standards, including the guidelines of the Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the WHO, and the principles outlined in the Declaration of Helsinki

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