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      Population-Based Biochemistry, Immunologic and Hematological Reference Values for Adolescents and Young Adults in a Rural Population in Western Kenya

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          Abstract

          Background

          There is need for locally-derived age-specific clinical laboratory reference ranges of healthy Africans in sub-Saharan Africa. Reference values from North American and European populations are being used for African subjects despite previous studies showing significant differences. Our aim was to establish clinical laboratory reference values for African adolescents and young adults that can be used in clinical trials and for patient management.

          Methods and Findings

          A panel of 298, HIV-seronegative individuals aged 13–34 years was randomly selected from participants in two population-based cross-sectional surveys assessing HIV prevalence and other sexually transmitted infections in western Kenya. The adolescent (<18 years)-to-adults (≥18 years) ratio and the male-to-female ratio was 1∶1. Median and 95% reference ranges were calculated for immunohematological and biochemistry values. Compared with U.S-derived reference ranges, we detected lower hemoglobin (HB), hematocrit (HCT), red blood cells (RBC), mean corpuscular volume (MCV), neutrophil, glucose, and blood urea nitrogen values but elevated eosinophil and total bilirubin values. Significant gender variation was observed in hematological parameters in addition to T-bilirubin and creatinine indices in all age groups, AST in the younger and neutrophil, platelet and CD4 indices among the older age group. Age variation was also observed, mainly in hematological parameters among males. Applying U.S. NIH Division of AIDS (DAIDS) toxicity grading to our results, 40% of otherwise healthy study participants were classified as having an abnormal laboratory parameter (grade 1–4) which would exclude them from participating in clinical trials.

          Conclusion

          Hematological and biochemistry reference values from African population differ from those derived from a North American population, showing the need to develop region-specific reference values. Our data also show variations in hematological indices between adolescent and adult males which should be considered when developing reference ranges. This study provides the first locally-derived clinical laboratory reference ranges for adolescents and young adults in western Kenya.

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          Most cited references46

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          Better Bootstrap Confidence Intervals

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            Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values.

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              CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa

              Background Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. Methods and Findings Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S.-derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. Conclusions To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                21 June 2011
                : 6
                : 6
                : e21040
                Affiliations
                [1 ]U.S. Centers for Disease Control and Prevention (CDC-Kenya), Kisumu, Kenya
                [2 ]Centre for Global Health Research, Kenya Medical Research Institute/U.S. CDC Research and Public Health, Kisumu, Kenya
                [3 ]Department of Internal Medicine, Center for Infection and Immunity (CINIMA), Center for Poverty-Related Communicable Diseases (CPCD), Academic Medical Center, Amsterdam Institute for Global Health and Development (AIGHD), University of Amsterdam, Amsterdam, The Netherlands
                [4 ]Institute of Tropical Medicine (ITM), Antwerp, Belgium
                [5 ]Global AIDS Program, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                University of Toronto, Canada
                Author notes

                Conceived and designed the experiments: TT PNA CZ DMM HV KMD JN. Performed the experiments: CZ SI BO. Analyzed the data: CH CZ AG JW PO KL. Contributed reagents/materials/analysis tools: TT KL KMD JN PNA HV. Wrote the paper: CZ JN SI. Read and reviewed the manuscript: CZ PNA SI PO BO DMM HV AG JW TT KMD CH JN KL.

                [¤a]

                Current address: International AIDS Vaccine Initiative, San Francisco, California, United States of America

                [¤b]

                Current address: Department of Medical Microbiology, College of Health Sciences, University of Nairobi, Nairobi, Kenya

                [¤c]

                Current address: Arctic Investigations Program, U.S. Centers for Disease Control and Prevention, Anchorage, Alaska, United States of America

                [¤d]

                Current address: Centre for Global Health, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America

                Article
                PONE-D-11-04304
                10.1371/journal.pone.0021040
                3119664
                21713038
                6f2d0588-1bb4-4ee6-a1f1-0376dcce6627
                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
                History
                : 4 March 2011
                : 17 May 2011
                Page count
                Pages: 10
                Categories
                Research Article
                Biology
                Biochemistry
                Blood Chemistry
                Immunochemistry
                Immunology
                Immune Cells
                Molecular Cell Biology
                Cellular Types
                Blood Cells
                Population Biology
                Medicine
                Diagnostic Medicine
                Clinical Laboratory Sciences
                Hematology
                Red Cells
                Public Health
                Health Screening

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                Uncategorized

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