title: Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, Toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag.
abstract: OBJECTIVE
  To determine the proportion of patients with evidence of an acute infection due to Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), Toxoplasma, or human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag, and to develop a cost-effective testing algorithm for managing such heterophile-negative patients.
  
  
  METHODS
  We conducted a prospective investigation of 70 selected outpatients who tested negative for heterophile antibody in association with an absolute lymphocytosis or instrument-generated atypical lymphocyte flag. The control population consisted of 50 patients who were heterophile negative and had a normal absolute lymphocyte count and no instrument-generated atypical lymphocyte flag.
  
  
  METHODS
  A large outpatient laboratory system.
  
  
  METHODS
  Viral serology for HHV-6 was performed by immunofluorescence, and all other serologies were performed by enzyme-linked immunoassay. All testing was for immunoglobulin (Ig) M antibodies, except in the case of HIV.
  
  
  RESULTS
  The proportion of study patients positive for EBV was 40% (28/70); for CMV, 39% (27/70); for HHV-6, 25% (16/65); for Toxoplasma, 3% (2/70); and for HIV, 0% (0/70). All 50 control patients were negative for EBV IgM antibodies. When patients with more than 1 positive viral test were excluded from analysis, positivity was 20% (9/45) for EBV, 22% (10/45) for CMV, 9% (4/45) for HHV-6, and 2% (1/45) for Toxoplasma. Utilizing hypothesis-generating logistic regression models, Downey type II atypical lymphocytes were significantly associated with EBV positivity (P =.006), while Downey type III lymphocytes were significantly associated with HHV-6 positivity (P =.016), and there was a trend for the association of Downey type I lymphocytes with CMV positivity (P =.097).
  
  
  CONCLUSIONS
  A positive viral serology was identified in 70% of study patients. Multiple positive serologies complicate establishing a definitive diagnosis. Potential cost savings may be associated with the use of an appropriate testing algorithm.
authors.affiliation: University of Calgary Medical School, Calgary, Alberta, Canada.
authors.forename: Y F
authors.initials: YF
authors.lastname: Tsaparas
authors.forename: M L
authors.initials: ML
authors.lastname: Brigden
authors.forename: R
authors.initials: R
authors.lastname: Mathias
authors.forename: E
authors.initials: E
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Raboud
authors.forename: P W
authors.initials: PW
authors.lastname: Doyle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000818:Animals; D000910:Antibodies, Heterophile / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003363:Cost Control; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D007223:Infant; D016014:Linear Models; D008214:Lymphocytes / Q000473:pathology; D008218:Lymphocytosis / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014122:Toxoplasma / Q000276:immunology; D014777:Virus Diseases / Q000175:diagnosis*
chemical_list: D000910:Antibodies, Heterophile; D000914:Antibodies, Viral; D007075:Immunoglobulin M