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PLoS Negl Trop Dis. 2019 Jul 17;13(7):e0007541. doi: 10.1371/journal.pntd.0007541. eCollection 2019 Jul.

Dosing pole recommendations for lymphatic filariasis elimination: A height-weight quantile regression modeling approach.

Author information

1
Washington University, St. Louis, Missouri, United States of America.
2
Centers of Disease Control and Prevention, Atlanta, Georgia, United States of America.
3
Murdoch Children's Research Institute, Melbourne, Australia.
4
The University of Melbourne, Melbourne, Australia.
5
ICMR-Vector Control Research Centre, Puducherry, India.
6
Case Western Reserve University, Cleveland, Ohio, United States of America.
7
Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
8
Ministère de la Santé Publique et de la Population (MSPP), Port au Prince, Haiti.
9
Burnet Institute, Melbourne, Australia.
10
Fiji Ministry of Health and Medical Services, Suva, Fiji.
11
Universitas Indonesia, Jakarta, Indonesia.

Abstract

BACKGROUND:

The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios.

METHODOLOGY/PRINCIPAL FINDINGS:

Age, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the "gold standard" for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing.

CONCLUSIONS/SIGNIFICANCE:

Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing.

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