- Mass drug administration campaigns for several neglected diseases could improve results and simplify logistics with a fixed-dose approach based on age groups, rather than current weight- or height-based strategies, according to a new Individual Participant Data meta-analysis published in PLOS NTDs with data from over 700.000 people
Ivermectin is an antiparasitic drug used by roughly 500 million people every year in mass drug administration (MDA) programs. It is a cornerstone treatment for neglected tropical diseases like onchocerciasis (river blindness), lymphatic filariasis (elephantiasis), scabies, and strongyloidiasis. Currently, health workers must measure each person’s weight or height to determine the proper dose, often using a color-coded “dose pole” to estimate weight from height. This process is time-consuming and logistically challenging in large parasite control campaigns, and it can lead to dosing errors.
An Individual Participant Data meta-analysis published in the journal em>PLOS Neglected Tropical Diseases, with anthropometric data of 741,700 people from 53 endemic countries, suggest a superior alternative: a fixed-dose regimen based on age group. With this method, children aged 2–4 years would receive a 3 mg dose (one ivermectin tablet), children 5–15 years get 9 mg (three tablets), and those over 16 years get 18 mg (six tablets). With this strategy, instead of calculating an exact dose for each person, health workers could simply give a set number of pills based on the patient’s age bracket.
The study, led by Argentinian physicians Dr. Adriana Echazú and Dr. Alejandro Krolewiecki, of Fundación Mundo Sano, shows that an age-based fixed-dose regimen can simplify logistics and bring more patients within the recommended therapeutic ranges (between 200µg/kg and 400µg/kg), without compromising safety.
More People Treated Correctly, Fewer Underdosed
The results show a significant improvement in dosing accuracy with the fixed-dose regimen. Nearly 80% of participants would receive the target range of ivermectin when using the age-based fixed doses, compared to only about one-third with current weight-based (32.7%) or height-based (37.3%) methods. In other words, most people treated by age-group dosing would get an effective amount of the drug, whereas the existing approaches leave a large share of people under-treated.Underdosing was dramatically reduced – only 8.7% of people would get less than the recommended dose with fixed-age dosing, versus 32.6% under the weight-based system and 46.3% under the height-based “dose pole” system.
Importantly, the age-based fixed-dose approach only slightly increased the number of people who would get a dose above the 400 µg/kg target and even those higher doses remained within safe limits. The analysis found that the vast majority of participants would stay below about 600 µg/kg with the alternative strategy, well under levels known to be tolerated in humans. Previous clinical studies have shown ivermectin as safe at single doses up to 800 µg/kg or higher. In practical terms, the study suggests the simpler regimen reduces systematic underdosing without a significant increase in risk. By hitting that therapeutic “sweet spot” for a much larger proportion of the population, the fixed-dose-by-age strategy could improve the efficacy of MDA campaigns in controlling diseases.
A Simpler, Scalable Strategy for Mass Campaigns
Beyond individual dosing benefits, a key advantage of the age-based schedule is operational simplicity. Mass preventive chemotherapy programs for diseases like river blindness often involve treating tens of thousands of people in remote areas. Removing the need for scales or dose poles means the distribution of the treatment can proceed much faster, and be achieved with less effort.
“While it might now take a team one day to treat all the children in a single school, age-based fixed dosing might allow for going through several schools in the same timeframe” said Dr. Krolewiecki, the study’s senior author and Director of Innovation at Fundación Mundo Sano. “It could greatly simplify logistics, which hopefully could lead to more people being treated.”
The researchers point out that streamlined logistics can also translate to cost savings in drug distribution and administration. Fewer staff may be needed, training becomes easier, and the risk of dosage mistakes drops. All improvements that could boost the overall efficiency of MDA programs. In resource-limited health systems, these efficiencies are not trivial and can mean more people covered, bringing countries closer to their disease control or elimination targets.
With over 500 million people receiving ivermectin annually through MDA programs, recommended by WHO, the gains suggested by the study can have significant public health benefits.
Reaching More People, Including Young Children
Crucially, the fixed-dose strategy makes a point about expanding treatment to a group that is currently left out under existing dosing guidelines. Right now, children below 90 cm in height or under 15 kg in weight (roughly under 5 years old) are generally excluded from ivermectin MDA campaigns due to an absence of evidence regarding its safety. However, the new analysis supports bringing these preschool-age children (PSAC, ages 2–4) into treatment with a low fixed dose (1 tablet of 3mg). The analysis showed a median dose of 236 µg/kg in this age group, with only 0.26% exceeding 400 µg/kg and none above 600 µg/kg, i.e. drug levels under known safety thresholds while providing therapeutic coverage.
“With the weight-based dosing strategy, over 80% of PSAC are excluded from ivermectin treatment”, explains Dr. Echazú. “But our results show that a 3mg tablet would hit the sweet spot in 80% of them while staying below 600µg/kg for the rest. Therefore, with a wide safety margin”.
The study insights also support the development of fixed-dose combination treatments like the coformulation of albendazole and ivermectin currently under phase IV clinical trials by the STOP2030 Consortium, that already received a positive scientific opinion by EMA. This approach can further streamline drug delivery by allowing a one-tablet-per-person strategy, which has been shown to improve treatment adherence and coverage, while targeting a wider spectrum of parasites.
Next Steps and Clinical Trials
While this study makes a case for the inclusion of preschool-aged children in ivermectin-based MDA campaigns, further evidence is needed. In a timely development, IVM-KIDS, a multi-year, multi-country project that will evaluate the safety of ivermectin in children below 15 kg through clinical trials is about to start its work this September. The consortium, formed by 9 African and European research institutions led by the London School of Hygiene and Tropical Medicine (LSHTM), funded by Global Health EDCTP3 and the Swiss Government, will conduct this clinical evaluation during the next 48 months.
Mundo Sano is also part of this consortium and will participate in the clinical design and evaluation while leading the internal and external communications of the project.
