Abstract
BackgroundIn 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.ObjectivesTo evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected children.MethodsThis 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.ResultsTLC 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/mm3), age 12-35 months (CD4 count < 750 cells/mm3), age 36-59 months (CD4 count < 350 cells/mm3, and age above 59 months (CD4 count < 200 cells/mm3). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm3 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.ConclusionTLC 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.
Highlights
In resource-limited settings, such as Kenya, access to CD4 testing is limited
All HIV infected children aged between one month and twelve years on follow-up in the comprehensive HIV care clinics (CCC) at the three hospitals who had medical records on CD4 count and total lymphocyte at enrollment into care prior to initiation of antiretroviral therapy (ART) were eligible for inclusion in the study
We found the World Health Organization (WHO) 2006 total lymphocyte count (TLC) thresholds defining immuno-suppression to have low sensitivity but high specificity for detecting severely depressed CD4 count in these Kenyan children, and sensitivity was lowest among young children under 5 years (
Summary
In resource-limited settings, such as Kenya, access to CD4 testing is limited. evaluation of less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children. The mortality of these children in Kenya and similar resource-poor settings approaches 50% by the age of 2 years, with most predicting clinical progression of pediatric HIV-1 is well described [11,12,13]. There are an estimated 100 machines for CD4 testing (FACSCount ® or FACSCalibre ®) in Kenya of which only 35 are located in public health facilities which serve the majority of HIV-1 infected children, while the remainder are found in large private hospitals and clinics, largely in urban settings. In 2006 the World Health Organization (WHO) recommended the use of total lymphocyte count (TLC) as a guide for initiating ART in children with WHO clinical stage 2 who are aged 8 years and below in settings where CD4 counts are not available [14]. Correlation between the TLC and CD4 counts ranged from 0.64 to 0.78, and appeared to be stronger for patients with advanced disease [15,16,17,18]
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