69
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references32

          • Record: found
          • Abstract: not found
          • Article: not found

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

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Population-based hematologic and immunologic reference values for a healthy Ugandan population.

            To assess the validity of the reference values for hematologic and immunologic indices currently used in Africa, we evaluated blood samples from 3,311 human immunodeficiency virus (HIV)-negative Ugandans aged 1 week to 92 years. Erythrocyte, hemoglobin, and hematocrit levels and mean corpuscular volume all significantly increased with age (P < 0.001) and were independent of gender until the age of 13 years, after which the levels were higher in males than in females (P < 0.001). White blood cell, neutrophil, lymphocyte, basophil, and monocyte counts significantly declined with age until the age of 13 years (P < 0.001), with no differences by gender, while platelet counts declined with age (P < 0.001) and showed differences by gender only among adults older than age 24 years. CD4+- and CD8+-cell counts declined with age until the age of 18 years; thereafter, females had higher counts than males. The absolute values for many of these parameters differed from those reported for populations outside Africa, suggesting that it may be necessary to develop tables of reference values for hematologic and immunologic indices specific for the African population. This may be particularly important with regard to CD4+-cell counts among children because significant differences in absolute and percent CD4+-cell counts exist between the values for Western populations and the values for the population evaluated in our study. These differences could influence the decision to initiate antiretroviral therapy among children infected with HIV.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Immunohematological reference ranges for adult Ethiopians.

              A cross-sectional survey was carried out with 485 healthy working adult Ethiopians who are participating in a cohort study on the progression of human immunodeficiency virus type 1 (HIV-1) infection to establish hematological reference ranges for adult HIV-negative Ethiopians. In addition, enumeration of absolute numbers and percentages of leukocyte subsets was performed for 142 randomly selected HIV-negative individuals. Immunological results were compared to those of 1,356 healthy HIV-negative Dutch blood donor controls. Immunohematological mean values, medians, and 95th percentile reference ranges were established. Mean values were as follows: leukocyte (WBC) counts, 6.1 x 10(9)/liter (both genders); erythrocyte counts, 5.1 x 10(12)/liter (males) and 4.5 x 10(12)/liter (females); hemoglobin, 16.1 (male) and 14.3 (female) g/dl; hematocrit, 48.3% (male) and 42.0% (female); platelets, 205 x 10(9)/liter (both genders); monocytes, 343/microl; granulocytes, 3, 057/microl; lymphocytes, 1,857/microl; CD4 T cells, 775/microl; CD8 T cells, 747/microl; CD4/CD8 T-cell ratio, 1.2; T cells, 1, 555/microl; B cells, 191/microl; and NK cells, 250/microl. The major conclusions follow. (i) The WBC and platelet values of healthy HIV-negative Ethiopians are lower than the adopted reference values of Ethiopia. (ii) The absolute CD4 T-cell counts of healthy HIV-negative Ethiopians are considerably lower than those of the Dutch controls, while the opposite is true for the absolute CD8 T-cell counts. This results in a significantly reduced CD4/CD8 T-cell ratio for healthy Ethiopians, compared to the ratio for Dutch controls.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2009
                6 February 2009
                : 4
                : 2
                : e4401
                Affiliations
                [1 ]Projet San Francisco (PSF), Kigali, Rwanda
                [2 ]Uganda Virus Research Institute (UVRI), Entebbe, Uganda
                [3 ]Kenya AIDS Vaccine Initiative (KAVI), Nairobi, Kenya
                [4 ]MRC/UVRI Uganda Virus Research Unit on AIDS, Masaka Site, Masaka, Uganda
                [5 ]Zambia Emory HIV Research Project (ZEHRP), Lusaka, Zambia
                [6 ]Centre for Geographic Medicine Research-Coast (CGMRC), Kenya Medical Research Institute (KEMRI), Kilifi, Kenya
                [7 ]Emory University, Atlanta, Georgia, United States of America
                [8 ]International AIDS Vaccine Initiative - New York, New York, United States of America
                [9 ]Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom
                [10 ]The EMMES Corporation, Rockville, Maryland, United States of America
                [11 ]University of the Witwatersrand, Johannesburg, South Africa and National Health Laboratory Services, Johannesburg, South Africa
                [12 ]Johnson and Johnson, New Brunswick, New Jersey, United States of America
                [13 ]University of Oxford, Oxford, United Kingdom
                [14 ]El Cerrito, California, United States of America
                University of Louisville, United States of America
                Author notes

                Conceived and designed the experiments: NK MAP PK JG GS PF AK. Performed the experiments: EK KK PK AN OA WJ GM ER JM EJS MM SA AB UB KA GO BF JB ES OM PH AK. Analyzed the data: EK MAP KK PNA SY LD JS. Contributed reagents/materials/analysis tools: BF LSJ JG GS OM PH JS WS. Wrote the paper: EK MAP KK OA EJS SA PNA LSJ LD WS PF AK.

                Article
                08-PONE-RA-06306
                10.1371/journal.pone.0004401
                2632744
                19197365
                dedb71c2-fa12-40fc-8daa-4c38cd03fb40
                Karita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 9 September 2008
                : 24 November 2008
                Page count
                Pages: 14
                Categories
                Research Article
                Public Health and Epidemiology/Epidemiology
                Public Health and Epidemiology/Global Health
                Public Health and Epidemiology/Infectious Diseases

                Uncategorized
                Uncategorized

                Comments

                Comment on this article