Reference Ranges for the Clinical Laboratory Derived from a Rural Population in Kericho, Kenya

Rukia S Kibaya,Paul T Scott,Merlin L Robb,Deborah L Birx,Warren B Sateren,Mark S De Souza,Nelson L Michael,Douglas N Shaffer,Christian T Bautista,Frederick K Sawe,Beatriz Grinsztejn

doi:10.1371/journal.pone.0003327

Abstract

The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrolment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9∶1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/µl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7–11.1) and neutrophil counts (1850 cells/µl; range 914–4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment.

Highlights

Many human immunodeficiency virus (HIV-1) vaccine trials are slated for Phase I–III trials in Africa[1].The inception of the US President’s Emergency Plan for AIDS Relief in 2004[2], with a mandate to treat 2 million HIV infections with anti-retroviral therapy (ART) by 2008 has accelerated the implementation of lymphocyte immunophenotyping in urban and rural areas in Africa as initiation of therapy is often predicated by absolute CD4+ T- lymphocyte counts
Lower CD4 T-cell numbers have been reported in Asians and Ethiopians compared to Caucasians [6,11,19], absolute CD4 T cell counts in Africans from the Central African Republic have been reported to be similar to Europeans [10]
Our data collection method was in accordance with the rigorous Clinical and Laboratory Standards Institute (CLSI) guidelines for determining laboratory reference ranges, which recommends a minimum of 153 subjects for a 95th percentile clinical reference range determination with 95% confidence [17]

Summary

Introduction

Many human immunodeficiency virus (HIV-1) vaccine trials are slated for Phase I–III trials in Africa[1].The inception of the US President’s Emergency Plan for AIDS Relief in 2004[2], with a mandate to treat 2 million HIV infections with anti-retroviral therapy (ART) by 2008 has accelerated the implementation of lymphocyte immunophenotyping in urban and rural areas in Africa as initiation of therapy is often predicated by absolute CD4+ T- lymphocyte counts. Central to any HIV vaccine and/or care and treatment program is the capability to measure absolute CD4 counts. CD4 counts are important in the context of breakthrough infections during HIV vaccine trials and informing treatment. Phase I/II vaccine trials rely on the clinical laboratory for assessing safety, with particular emphasis on assays monitoring hematology, liver and kidney function. The treatment of HIV infection requires monitoring of drug toxicity on renal, hepatic and hematologic parameters. The majority of immunohematological and clinical chemistry reference ranges are based on North American or European data. Dietary patterns, sex, age and altitude can affect immunohematology and clinical chemistry reference ranges [17,18]. Lower CD4 T-cell numbers have been reported in Asians and Ethiopians compared to Caucasians [6,11,19], absolute CD4 T cell counts in Africans from the Central African Republic have been reported to be similar to Europeans [10]

Methods

Results

Conclusion