Detection of coxsackievirus A6 in formalin-fixed, paraffin-embedded skin biopsy specimens using immunohistochemistry and real-time reverse-transcriptase PCR.

Amy M Denison, Julu Bhatnagar, Richard R Jahan-Tigh, Pamela Fair, Gillian L Hale

Open access · goldAbstract read

In one paragraph

Article in Journal of clinical virology plus, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

0.2field-weighted citation impact, top 50% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

Comprehensive Review on Viral RNA Extraction Strategies for Enhanced Molecular Diagnostics.Interdisciplinary perspectives on infectious diseases · 2025
Review

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

5 authors at 2 institutions in 1 country.

Amy M DenisonInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Julu BhatnagarInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Richard R Jahan-TighUniversity of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA.

Pamela FairInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Gillian L HaleInfectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Centers for Disease Control and Prevention · USThe University of Texas Health Science Center at Houston · US

Funding

Intramural CDC HHS CC999999

6 · The paper itself

Abstract

Background: Hand, foot, and mouth disease (HFMD), classically a childhood viral infection, has an atypical and severe clinical presentation in adults. Coxsackievirus A6 is a leading cause of atypical HFMD, but current diagnostic methods utilizing formalin-fixed, paraffin-embedded skin biopsy specimens often lack sensitivity and specificity. Methods: Formalin-fixed, paraffin-embedded skin biopsies from seven case patients with clinical and histopathological suspicion of atypical HFMD were evaluated by coxsackievirus A6 (CVA6) immunohistochemistry, enterovirus-specific conventional reverse transcriptase-PCR with subsequent Sanger sequencing targeting the 5'UTR, and CVA6-specific real-time PCR targeting the VP1 gene. Results: The CVA6-specific antibody demonstrated appropriate antigen distribution and staining intensity in keratinocytes in all cases. Conventional RT-PCR and sequencing also detected the presence of enterovirus, and CVA6-specific real-time RT-PCR analysis identified CVA6. Conclusion: Applying these immunohistochemistry and molecular techniques to formalin-fixed, paraffin-embedded tissues, CVA6 was determined to be the causative infectious agent in seven cases of atypical hand, foot, and mouth disease.

Indexed as

Atypical HFMDCoxsackievirus A6 (CVA6) real-timeEnterovirusFormalin-fixedHand, foot, and mouth disease (HFMD)Immunohistochemistry (IHC)Paraffin-embedded (FFPE) tissuereaction (rRT-PCR)reverse-transcriptase polymerase chain

Identifiers

PMID38481773

DOI10.1016/j.jcvp.2021.100018

PMCPMC10936323

OpenAlexW3158623144

What OpenQuestion holds

Textmetadata

LicenceCC BY-NC-ND

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.