Evidence map›Paper›PMID 30653499›Full record

ArticlePLoS neglected tropical diseases2019

Development of a preliminary in vitro drug screening assay based on a newly established culturing system for pre-adult fifth-stage Onchocerca volvulus worms.

Denis Voronin, Nancy Tricoche, Shabnam Jawahar, Michael Shlossman, Christina A Bulman, Chelsea Fischer, Michael T Suderman, Judy A Sakanari, Sara Lustigman

Open access · goldAbstract read
In one paragraph

Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  4. Comparative development of human filariaeFrontiers in tropical diseases · 2024
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  7. Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Denis VoroninMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
Nancy TricocheMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
Shabnam JawaharMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
Michael ShlossmanMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.
Christina A BulmanDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
Chelsea FischerDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.ORCID 0000-0002-6402-5886
Michael T SudermanCell Systems-3D, LLC, Kemah, Texas, United States of America.
Judy A SakanariDept. of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, California, United States of America.
Sara LustigmanMolecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America.ORCID 0000-0003-2389-6113
New York Blood Center · USUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe human filarial parasite Onchocerca volvulus is the causative agent of onchocerciasis (river blindness). It causes blindness in 270,000 individuals with an additional 6.5 million suffering from severe skin pathologies. Current international control programs focus on the reduction of microfilaridermia by annually administering ivermectin for more than 20 years with the ultimate goal of blocking of transmission. The adult worms of O. volvulus can live within nodules for over 15 years and actively release microfilariae for the majority of their lifespan. Therefore, protracted treatment courses of ivermectin are required to block transmission and eventually eliminate the disease. To shorten the time to elimination of this disease, drugs that successfully target macrofilariae (adult parasites) are needed. Unfortunately, there is no small animal model for the infection that could be used for discovery and screening of drugs against adult O. volvulus parasites. Here, we present an in vitro culturing system that supports the growth and development of O. volvulus young adult worms from the third-stage (L3) infective stage. METHODOLOGY/PRINCIPAL

findingsIn this study we optimized the culturing system by testing several monolayer cell lines to support worm growth and development. We have shown that the optimized culturing system allows for the growth of the L3 worms to L5 and that the L5 mature into young adult worms. Moreover, these young O. volvulus worms were used in preliminary assays to test putative macrofilaricidal drugs and FDA-approved repurposed drugs.

conclusionThe culture system we have established for O. volvulus young adult worms offers a promising new platform to advance drug discovery against the human filarial parasite, O. volvulus and thus supports the continuous pursuit for effective macrofilaricidal drugs. However, this in vitro culturing system will have to be further validated for reproducibility before it can be rolled out as a drug screen for decision making in macrofilaricide drug development programs.

Indexed as

AnimalsDrug Evaluation, PreclinicalFemaleFilaricidesMaleOnchocerca volvulusParasitic Sensitivity TestsFilaricides

Identifiers

PMID30653499
PMCPMC6353222
OpenAlexW2910424110

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.