Evidence Based Practice Infectious Mononuclosis Biology Essay

Infectious glandular fever is a womb-to-tomb clinical disease, chiefly associated with the Epstein-Barr virus.

In the USA, there is an estimated 500 instances per 100,000 persons diagnosed each twelvemonth ( 1,2 ) . Common symptoms include sore pharynx, weariness, febrility and lymphadenopathy. Although seldom fatal, IM can take to other serious complications including splenetic rupture and external respiration troubles ( 2 ) .

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In the hematology research lab at Victoria Hospital in Fife, the current pattern for IM diagnosing is to execute a full blood count ( FBC ) and blood movie ( BF ) followed by a monospot ( heterophile antigen trial ) . Over recent months, it has been noticed that the figure of petitions for monospots has risen although the figure of positive consequences remains low.Due to laboratory fiscal restraints and the possible debut of vetting standards for monospot testing, an audit ( Appendix A ) was performed to find the figure of monospots performed in one month, along with the clinical inside informations and consequences. Findingss showed that merely 10 of the 99 petitions had a positive monospot trial. In add-on, it was highlighted that 70 % of the petitions did non hold any of the typical FBC and BF findings associated with IM, such as lymphocytosis and the presence of untypical lymph cells severally. Although the audit showed that a big per centum of monospot trials are requested for the inappropriate grounds, for illustration as portion of a unease screen with no other important symptoms, the negative findings may be associated with the restrictions of the monospot instead than due to being requested unnecessarily.The vetting standards will include the FBC and BF findings and depending upon the consequences, the monospot trial may non be performed ( Figure 1 ) . However, monospots, every bit good as FBC and BF ‘s, may give false negative consequences in a one-fourth of instances with early disease ( 1st hebdomad of symptoms ) ( 3 ) and in the bulk of kids less than 4 old ages old.

Additionally, 10-20 % of IM infected grownups fail to bring forth IM heterophile antibodies, which would besides take to a negative monospot trial ( Appendix B ) . These instances are referred to as heterophile negative EBV induced IM. Furthermore, monospot trials are unable to separate between primary disease, reactivated IM and relentless antibody presence, as heterophile antibodies can prevail for many old ages at low degrees, along with a normal FBC and BF ( 1,2,4 ) . It is besides deserving observing that other serious conditions including human immunodeficiency, CMV, infection with Toxoplasma gondii and some malignances may show with symptoms of IM and bring forth positive monospots ( false positive ) ( 3, Appendix B )Therefore, it is deserving sing utilizing other IM diagnostic methods such as EBV serological surveies, including viral mirid bug antigen ( VCA ) trials ( EBV Anti-VCA IgM and IgG-antibodies ) and IgG-antibodies to EBV atomic antigen 1 ( EBNA-1 ) , for an definite diagnosing of IM, along with the stage of disease ( 1,3,4 ) ( Table 1 ) .Figure 1 – Potential Vetting Criteria for IM Testing and Diagnosis ( adapted from 3 )* It is assumed that a monospot trial would give a non-specific consequenceTable 1 – EBV Serological Trials and their Association with IM ( adapted from 2 )

EBV Serological Test

Association with IM

EBV Anti-VCA IgM-antibodiesDetected in early disease, vanishing within 4-8 hebdomads. Diagnostic of primary infection.EBV Anti-VCA IgG-antibodiesDetected in early disease and stay in system for life.

Diagnostic of primary and chronic infection.IgG-antibodies to EBNA-1Detected several hebdomads after showing symptoms. Diagnostic of past infection.


Population: Persons with suspected EBV induced IMIntervention: EBV serological surveiesComparison: MonospotResult: Valid replacing trial ( improved sensitiveness and specificity byset uping presence of infection and phase of disease at diagnosing )

Make EBV serological surveies provide a valid replacing for the monospot trial and better sensitiveness and specificity of diagnosing in patients with suspected EBV induced IM?

Search Scheme

Potential words / phrases to utilize for hunt:Infectious glandular feverEpstein-Barr virusMonospotHeterophile antigen trialEBV serologyAntibod* ( antibody, antibodies )Viral mirid bug antigen trial ( VCA )EBV atomic antigen 1 ( EBNA-1 )ComparedDiagnosisThe hunt scheme began by working through each database, utilizing the hunt footings deemed most of import, before contracting them down ( where required ) utilizing filters or altering hunt words. Table 2 demonstrates the order of resources used and search footings.

Table 2 – Search Schemes for placing the relevant literature

Resource ( database )

Search Footings **

Filters Applied

Entire Number of Hits

Irrelevant Hits

Relevant Hits

BandolierInfectious glandular feverNone110Epstein-Barr virusNone110BestBETsInfectious glandular feverNone000Epstein-Barr virusNone000TripInfectious glandular feverNone1389N/AN/AInfectious glandular fever and monospotNone40N/AN/AInfectious glandular fever and monospot and EBV serologyNone16N/AN/AInfectious glandular fever and monospot and EBV serologyEvidence based outlines101NHS EvidenceInfectious glandular feverNone201N/AN/AInfectious glandular fever and monospotNone000Infectious glandular fever and diagnosingNone146N/AN/AInfectious glandular fever and diagnosingDiagnosis35N/AN/AInfectious glandular fever and diagnosing and EBV serologyDiagnosis330Infectious glandular fever and diagnosing and EBV serologyRemoved “ diagnosing ” filter901Epstein-Barr virus and diagnosing and EBV serologyNone13130CochraneInfectious glandular feverNone330Epstein-Barr virusNone110Infectious glandular fever and diagnosingNone752PubMedInfectious glandular feverNone7888N/AN/AInfectious glandular fever and EBV serologyNone965N/AN/AInfectious glandular fever and EBV serology and comparingNone31N/AN/AInfectious glandular fever and EBV serology and heterophileNone85N/AN/AInfectious glandular fever and EBV serology and heterophileWorlds81N/AN/AInfectious glandular fever and EBV serology and heterophile and diagnosingWorlds69N/AN/AInfectious glandular fever and EBV serology and heterophile and diagnosing and comparingWorlds431Infectious glandular fever and EBV serology and monospotWorlds14113EBNA-1 and viral mirid bug antibody and heterophileWorlds743Antibod* and infective glandular feverN/A2144N/AN/AAntibod* and infective glandular fever and diagnosingN/A1475N/AN/AAntibod* and infective glandular fever and diagnosingWorlds1395N/AN/AAntibod* and infective glandular fever and diagnosingWorlds and 5 old ages72N/AN/AAntibod* and infective glandular fever and diagnosing and comparedWorlds and 5 old ages16151** Search footings have been entered into tabular array in order they were input into each database. N/A = non applicable ( used in irrelevant/relevant column when hunt hit is excessively high )

Consequences of Search


Date and Country

Title of Paper

Beginning of Evidence

Lattimore K A2001, USAAccurate diagnosing of EBV mono with rapid heterophile latex agglutination depends on the trial usedTrip – University of Michigan Department of Pediatrics.

Evidence -based paediatricss websiteHealth protection bureau ( Standards unit, Microbiology services divison )2012, UKUK criterions for microbiology probes. Epstein-Barr virus serologyNHS Evidence – Virology ( V26, 4 )Andersson A, Vetter V, Kreutzer L and Bauer G1994Eagernesss of IgG directed against viral mirid bug antigen or early antigen: utile markers for important Epstein-Barr virus serologyCochrane – Journal of medical virologyTamaro G, Donato M, Princi T and Parco S2009, ItalyCorrelation between the immunological status and the consequences of immunoenzymatic trials in naming infective glandular feverCochrane – Acta bio-medica: Atenei ParmensisSiennicka J and TrzciA„ska A2007, PolandLaboratory diagnosing of Epstein-Barr virus infectionPubMed – Med Dosw MikrobiolVouloumanou E K, Rafailidis P I and Falagas M E2012, GreeceCurrent diagnosing and direction of infective glandular feverPubMed – Current Opinion HematololgyPapesch M and Watkins R2001, UKEpstein-Barr virus infective glandular feverPubMed – Clinical Otolaryngology and Allied SciencesSeviA‡ S1997, CroatiaSerologic diagnosing of acute infective glandular feverPubMed – med PreglKlutts J S, Ford B A, Perez N R and Gronowski A M2009, USAEvidence-based attack for reading of Epstein-Barr virus serological formsPubMed – Journal of Clinical MicrobiologyDe Paschale M, Agrappi C, Manco M T, Mirri P, Vigano E F and Clerici P2009, ItalySeroepidemiology of EBV and reading of the “ stray VCA IgG ” formPubMed – Journal of Medical VirologyNystad T W and Myrmel H2007, NorwayPrevalence of primary versus reactivated Epstein-Barr virus infection in patients with VCA IgG- , VCA IgM- and EBNA-1-antibodies and suspected infective glandular feverPubMed – Journal of Clinical VirologyLlor C, Hernandez M, Hernandez S, Martinez T and Gomez F F2012, SpainCogency of a point-of-care based on heterophile antibody sensing for the diagnosing of infective glandular fever in primary attention.PubMed – European Journal of General Practice


I researched assorted databases, looking for relevant literature to assist reply my inquiry on whether EBV serological surveies are a valid replacing for the monospot trial. I found my inquiry to be both relevant to my workplace and specific plenty to obtain adequate literature to assist come to a generalized decision.

I prepared before get downing my hunt by making background reading around my inquiry which gave me a good penetration to the general countries I need to concentrate on, nevertheless, as I had no old experience of this type of database searching, I found it rather hard to cognize which cardinal words to utilize. I wrote a list of relevant words in order of importance to assist maintain me on the right path.In the beginning, I found this undertaking rather dashing as my hunts produced “ hits ” with either an highly high figure ( 7000 in PubMed ) or a really low figure ( 0 in BestBETs ) and I found it hard to cognize when to use filters, add extra hunt footings or usage wildcards.I performed rather a batch of single hunts, merely altering one word or filter at a clip to do it easier for myself since it was a new experience. Besides, on this juncture, I did non utilize any Boolean operators and I later realised that I could hold saved myself some hunt clip ab initio by seeking for “ infective glandular fever ” OR “ Epstein-Barr virus ” alternatively of seeking for these footings separately. This pattern will alter in the hereafter as I feel more confident in my abilities to execute database hunts every bit good as experiencing more confident utilizing wildcards, which I did towards the terminal of my hunts ( e.g. antibod* ) .

I besides found that utilizing some basic filters such as ‘humans ‘ and publication day of the month ( e.g. ‘last 5 old ages ‘ ) at the beginning may besides salvage me some search clip right at the beginning.When executing this type of database hunt in the hereafter, I think I will get down with the database I found to be most utile, which was PubMed. I found it produced the most relevant documents and I found it rather easy to utilize. I have significantly developed my cognition and accomplishments in this country and my ability to hunt databases will be used during the remainder of my MSc and in my current pattern in the research lab when required.


Vouloumanou E K, Rafilidis P I and Falagas M E. Current diagnosing and direction of infective glandular fever. Myeloid Biology. 2012 ; 1:14-20Luzuriaga K and Sullivan J L. Infectious glandular fever. The New England Journal of Medicine. 2010 ; 362 ( 21 ) :1993-2000Hurt C and Tammaro D.

Diagnostic rating of monocucleosis-like unwellness. The Americal Journal of Medicine. 2007 ; 120 ( 10 ) :911, e1-911.

e8Nystad T W and Myrmel H. Prevalence of primary versus reactivated Epstein-Barr virus infection with VCA IgG- , VCA IgM- and EBNA-1-antibodies and suspected infective glandular fever. Journal of Clinical Virology. 2007 ; 38:292-297

Appendix A

Horizontal Audit of IM Screening Tests Sept 2012

Entire Trials = 99, age scope 3 months – 77 old ages, most petitions as expected in the teens – mid-twentiess. 96 were GP petitions, merely three IM testing petitions were added by BMS staff, all holding lymphocytosis. All were reported on the same twenty-four hours the petition was received by the lab.Entire Positives = 10 ( 10.

1 % ) , all except one of the positives had typical IM characteristics, lymphocytosis and reactive lymph cells in the movie. The individual positive without IM characteristics had a normal FBC and blood movie and no legible clinical inside informations.Entire Negative =89 ( 89.

9 % )Clinical Details both groups ( ruddy = IM slide positive )FBC Results for the negative group.The Diagnosis of IM is characterised by sore throat, lymphadenopathy and unease. This diagnosing is supported by typical FBC consequences ( lymphocytosis and atypicals in the movie ) . The FBC has a sensitiveness of 75 % and specificity of 92 % for the diagnosing of IM. The IM slide trial for the heterophil antibody has a reported sensitiveness of about 85 % and specificity of 94 % . ( reappraisal by Luzuriaga and Sulivan, Infectious Monomucleosis NEJM, 2010, 263 21, pages 1993-2000.

) .More that 70 % of FAL petitions fail to run into any of the above diagnostic or research lab standards. In some instances it appears as though the IM slide trial is use as portion of a ‘Tired/Malaise ‘ testing procedure.

This is supported as 9 of the IM slide trial petitions besides had a Ferritin petition.Using our current trial cards it costs about ?1.00 per trial, if we introduced even the most basic degree of petition control i.e. normal FBC without Lymphocytosis, Atypicals in the movie )Brian H Little BMS 2


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