Evidence map›Paper›PMID 27667983›Full record

ArticleFrontiers in microbiology2016

Detection of Low Frequency Multi-Drug Resistance and Novel Putative Maribavir Resistance in Immunocompromised Pediatric Patients with Cytomegalovirus.

Charlotte J Houldcroft, Josephine M Bryant, Daniel P Depledge, Ben K Margetts, Jacob Simmonds, Stephanos Nicolaou, Helena J Tutill, Rachel Williams, Austen J J Worth, Stephen D Marks and 3 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

42 citing papers in PubMed, 85 citations in OpenAlex.

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  11. Observational
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  15. Alphaherpesvirus Genomics: Past, Present and Future.Current issues in molecular biology · 2021
    Review
  16. Antiviral Drugs Against Herpesviruses.Advances in experimental medicine and biology · 2021
    Article
  17. Article
  18. Article
  19. Article
  20. 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

13 authors at 2 institutions in 1 country.

Charlotte J HouldcroftInfection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College LondonLondon, UK; Division of Infection and Immunity, University College LondonLondon, UK.
Josephine M BryantDivision of Infection and Immunity, University College London London, UK.
Daniel P DepledgeDivision of Infection and Immunity, University College London London, UK.
Ben K MargettsInfection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College LondonLondon, UK; Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College LondonLondon, UK.
Jacob SimmondsGreat Ormond Street Hospital for Children NHS Foundation Trust London, UK.
Stephanos NicolaouDivision of Infection and Immunity, University College London London, UK.
Helena J TutillDivision of Infection and Immunity, University College London London, UK.
Rachel WilliamsDivision of Infection and Immunity, University College London London, UK.
Austen J J WorthGreat Ormond Street Hospital for Children NHS Foundation Trust London, UK.
Stephen D MarksInfection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College LondonLondon, UK; Great Ormond Street Hospital for Children NHS Foundation TrustLondon, UK.
Paul VeysGreat Ormond Street Hospital for Children NHS Foundation Trust London, UK.
Elizabeth WhittakerGreat Ormond Street Hospital for Children NHS Foundation Trust London, UK.
Judith BreuerInfection, Immunity, Inflammation and Physiological Medicine, Institute of Child Health, University College LondonLondon, UK; Division of Infection and Immunity, University College LondonLondon, UK; Great Ormond Street Hospital for Children NHS Foundation TrustLondon, UK.
University College London · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human cytomegalovirus (HCMV) is a significant pathogen in immunocompromised individuals, with the potential to cause fatal pneumonitis and colitis, as well as increasing the risk of organ rejection in transplant patients. With the advent of new anti-HCMV drugs there is therefore considerable interest in using virus sequence data to monitor emerging resistance to antiviral drugs in HCMV viraemia and disease, including the identification of putative new mutations. We used target-enrichment to deep sequence HCMV DNA from 11 immunosuppressed pediatric patients receiving single or combination anti-HCMV treatment, serially sampled over 1-27 weeks. Changes in consensus sequence and resistance mutations were analyzed for three ORFs targeted by anti-HCMV drugs and the frequencies of drug resistance mutations monitored. Targeted-enriched sequencing of clinical material detected mutations occurring at frequencies of 2%. Seven patients showed no evidence of drug resistance mutations. Four patients developed drug resistance mutations a mean of 16 weeks after starting treatment. In two patients, multiple resistance mutations accumulated at frequencies of 20% or less, including putative maribavir and ganciclovir resistance mutations P522Q (UL54) and C480F (UL97). In one patient, resistance was detected 14 days earlier than by PCR. Phylogenetic analysis suggested recombination or superinfection in one patient. Deep sequencing of HCMV enriched from clinical samples excluded resistance in 7 of 11 subjects and identified resistance mutations earlier than conventional PCR-based resistance testing in 2 patients. Detection of multiple low level resistance mutations was associated with poor outcome.

Indexed as

antiviralsherpesvirusesimmune deficiencyimmune suppressionnext-generation sequencing

Identifiers

PMID27667983
PMCPMC5016526
OpenAlexW2516420403

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.