How an ivermectin study that didn’t mention COVID-19 fell under scrutiny

A PLOS journal has issued an expression of concern for a 2018 paper which claimed that ivermectin could be useful as a way to control dengue fever. 

In fact, the reason the journal re-examined the article was because the hype about the use of ivermectin for Covid-19 led at least one skeptic to take a closer look at the study – and he didn’t like what he saw. 

The article, “Antivirus effectiveness of ivermectin on dengue virus type 2 in Aedes albopictus,” was written by a group in China led by Tie-Long Xu, of the National Institute of Parasitic Diseases at the  Chinese Center for Disease Control and Prevention. According to the study, which appeared on PLOS Neglected Tropical Diseases: 

Ivermectin can directly or indirectly inhibit DENV-2 multiplication in Aedes albopictus.

However, in 2020, Kyle Sheldrick, a researcher in Australia, saw the study and had doubts – doubts that, as he relayed on Twitter, included whether the reported findings were the result of an experiment: 

Sheldrick, who told PLOS about the problems in May 2020, long before he made them public, told us that he found the 2018 article by chance:

I saw a comment in another paper on ivermectin for covid about how ivermectin had some efficacy in treating dengue, so that’s why I looked it up.

He added that:

I’m a bit surprised about how long it took for action.

By early April 2021, after Sheldrick had reported his concerns to the journal but nine months before it took action, the paper had been cited by at least two research groups as at least partial justification for clinical trials of ivermectin in people with Covid-19.

The expression of concern, dated January 11, states: 

After this article [1] was published, a concern was raised that for each experimental treatment (group), the triplicate data reported in Table 1 align quite closely with the group average, with low deviation and no outliers. In response, the authors noted that that they had repeatedly performed preliminary experiments to optimize conditions that yielded consistent results. The authors provided PCR data (S1 File) and analysis results (S2 File) to support Table 1.

In reviewing this issue, PLOS Neglected Tropical Diseases obtained input from multiple members of our Editorial Board. All consulted editors questioned the feasibility of the Table 1 results. They advised that the table and supporting dataset report infection rates that are more consistent within and across cohorts for each dose than are expected; while the results are theoretically possible, the probability of obtaining the reported values is exceedingly low for this assay and biological system.

The notice adds that:

Overall, the consulted editors advised that there are concerns about the feasibility, integrity, and reliability of the Table 1 results which were not resolved by the data and comments received in post-publication discussions. Therefore, the PLOS Neglected Tropical Diseases Editors issue this Expression of Concern.

The senior author of the study did not respond to requests for comment.

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