Flubendazole as a macrofilaricide: History and background
Bibliographic record
Abstract
Benzimidazole anthelmintics have long been employed for the control of soil-transmitted helminth infections.Flubendazole (FBZ) was approved in 1980 for the treatment of gastrointestinal nematode infections in both veterinary and human medicine.It has also long been known that parenteral administration of FBZ can lead to high macrofilaricidal efficacy in a variety of preclinical models and in humans.As part of an effort to stimulate the discovery and development of new macrofilaricides, particularly for onchocerciasis, research has recently been devoted to the development of new formulations that would afford high oral bioavailability of FBZ, paving the way for potential clinical development of this repurposed drug for the treatment of human filariases.This review summarizes the background information that led to this program and summarizes some of the lessons learned from it.Elimination of the human filarial diseases lymphatic filariasis (LF) and onchocerciasis is a formal objective of the global health community [1,2].Decades-long control programs leading to elimination rely primarily on annual or semiannual mass drug administration (MDA) campaigns using drugs that kill the microfilarial stages of Onchocerca volvulus and Wuchereria bancrofti, the primary causative agents of these diseases; the chemotherapeutic regimens also induce prolonged suppression of microfilarial production by female parasites.The long-lasting reduction of the microfilarial burden effectively prevents transmission and, in onchocerciasis patients, the development of dermal and ocular pathology.Elimination can be attained if transmission is blocked until all adult worms in a locale have died (5 to 15 years).The drugs used in MDA campaigns include ivermectin in onchocerciasis areas and diethylcarbamazine in areas in which only LF is present; both agents are combined with albendazole for use in LF control.The use of ivermectin or diethylcarbamazine in areas coendemic with Loa loa is problematic due to the danger of severe adverse neurologic sequelae in patients harboring high loads of L. loa microfilariae [3,4].Because the regimens used for MDA are not rapidly macrofilaricidal, there is general agreement that availability of a macrofilaricide would significantly accelerate progress toward elimination of filariases, in particular onchocerciasis [5][6][7].Macrofilaricidal regimens
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".