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PLOS ‘expression of concern’ over study punting Ivermectin for dengue fever

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

Retraction Watch reports that the reason the journal re-examined the article was because the hype about the use of Ivermectin for COVID-19 led at least one sceptic to take a closer look at the study – and he didnʼt 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. 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 optimise 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.

“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.

Study details

Antivirus effectiveness of Ivermectin on dengue virus type 2 in Aedes albopictus

Tie-Long Xu, Yin Han, Wei Liu, Xing-Ya Pang, Bin Zheng, Yi Zhang, Xiao-Nong Zhou.

Published in PLOS Neglected Tropical Diseases on 19 November 2018

Abstract

Background
Dengue fever is the most rapidly spreading mosquito-borne viral disease over the past 50 years, with a 30-fold increase in global incidence. Dengue vector control is a key component for the dengue control strategy, since no absolutely effective vaccine or drug is available yet. However, the rapid rise and spread of mosquito insecticide resistance have become major threats to the efficiency of insecticide-based vector control activities. Thus, innovative vector control tools are badly needed. This study aims to confirm the antivirus effectiveness of Ivermectin on dengue virus type 2 (DENV-2) in Aedes albopictus (Skuse, 1894), then to explore its potential use in the combating to the dengue epidemics.

Methods
Aedes albopictus were first infected with DENV-2 in human whole blood, and at the fourth day after infectious blood feeding, they were divided into eight groups. Seven of them were held for six days with access to 0, 2, 4, 8, 16, 32 and 64 ng/ml Ivermectin, respectively, and the last one was set as a historical control group, which was stored at -80°C until being detected at the same time with the other groups. Each mosquito was detected using real-time fluorescent RT-PCR kit. DENV-2 RNA concentration (copies/ml) and infection rate in each group were compared.

Results
Both of quantitatively and qualitatively inhibiting effects of Ivermectin have been detected in this study. Generally, DENV-2 replicated well in Aedes albopictus without Ivermectin intervention, whose virus loads exhibited significantly higher when the mosquitoes were holding from 4 days to 10 days after infectious blood feeding. In contrast, with the treatment of Ivermectin, the infection rate was reduced by as much as 49.63%. The regression equation between infection rates (Y2) and Ivermectin concentration log2 values (X2) was obtained as Y2 = 91.41–7.21*X2 with R2 = 0.89.

Conclusion
Ivermectin can directly or indirectly inhibit DENV-2 multiplication in Aedes albopictus. Moreover, the actual concentration for application in zooprophylaxis needs to be confirmed in the further field trials.

 

Retraction Watch article – How an ivermectin study that didn’t mention COVID-19 fell under scrutiny (Open access)

 

PLOS journal article with Expression of Concern – Antivirus effectiveness of Ivermectin on dengue virus type 2 in Aedes albopictus (Open access)

 

See more from MedicalBrief archives:

 

Another key pro-Ivermectin meta-analysis is retracted

 

Ivermectin papers show limitations of ‘inherently unreliable’ summary data

 

First evidence of what most attracts the mosquitos that carry dengue and chikungunya

 

Insect-borne diseases more than triple in the US

 

 

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