title: Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya.
abstract: BACKGROUND
  In resource-limited settings, such as Kenya, access to CD4 testing is limited. Therefore, evaluation of less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children.
  
  
  OBJECTIVE
  To evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected children.
  
  
  METHODS
  This was a hospital based retrospective study conducted in three HIV clinics in Kisumu and Nairobi in Kenya. TLC, CD4 count and CD4 percent data were abstracted from hospital records of 487 antiretroviral-naïve HIV-infected children aged 1 month--12 years.
  
  
  RESULTS
  TLC and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest correlation seen in children with severe immuno-suppression (r = 0.72, p < 0.001) and children >59 months of age (r = 0.68, p < 0.001). Children were considered to have severe immuno-suppression if they met the following WHO set CD4 count thresholds: age below 12 months (CD4 counts < 1500 cells/mm(3)), age 12-35 months (CD4 count < 750 cells/mm(3)), age 36-59 months (CD4 count < 350 cells/mm(3), and age above 59 months (CD4 count < 200 cells/mm(3)). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm(3) for age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%, 33% and 62% respectively in predicting severe immuno-suppression using CD4 count as gold standard. Raising TLC thresholds to 7000, 6000, 4500 and 3000 cells/mm3 for each of the stated age categories increased sensitivity to 71%, 64%, 56% and 86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but reduced specificity to 73%, 62%, 54% and 68% with negative predictive values of 54%, 65%, 71% and 87% respectively.
  
  
  CONCLUSIONS
  TLC is positively correlated with absolute CD4 count in children but current WHO age-specific thresholds had low sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity and therefore utility of TLC to identify immuno-suppressed children may be improved by raising the TLC cut off levels across the various age categories.
authors.affiliation: Department of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya.
authors.forename: Nyawira
authors.initials: N
authors.lastname: Githinji
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.forename: Moses
authors.initials: M
authors.lastname: Nderitu
authors.forename: Dalton C
authors.initials: DC
authors.lastname: Wamalwa
authors.forename: Dorothy
authors.initials: D
authors.lastname: Mbori-Ngacha
mesh_terms: D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000302:isolation & purification*; D006761:Hospitals; D006801:Humans; D007223:Infant; D007630:Kenya; D018655:Lymphocyte Count; D008297:Male; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers