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      Complete blood count reference intervals from a healthy adult urban population in Kenya

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          Abstract

          Background

          There are racial, ethnic and geographical differences in complete blood count (CBC) reference intervals (RIs) and therefore it is necessary to establish RIs that are population specific. Several studies have been carried out in Africa to derive CBC RIs but many were not conducted with the rigor recommended for RI studies hence limiting the adoption and generalizability of the results.

          Method

          By use of a Beckman Coulter ACT 5 DIFF CP analyser, we measured CBC parameters in samples collected from 528 healthy black African volunteers in a largely urban population. The latent abnormal values exclusion (LAVE) method was used for secondary exclusion of individuals who may have had sub-clinical diseases. The RIs were derived by both parametric and non-parametric methods with and without LAVE for comparative purposes.

          Results

          Haemoglobin (Hb) levels were lower while platelet counts were higher in females across the 4 age stratifications. The lower limits for Hb and red blood cell parameters significantly increased after applying the LAVE method which eliminated individuals with latent anemia and inflammation. We adopted RIs by parametric method because 90% confidence intervals of the RI limits were invariably narrower than those by the non-parametric method. The male and female RIs for Hb after applying the LAVE method were 14.5–18.7 g/dL and 12.0–16.5 g/dL respectively while the platelet count RIs were 133–356 and 152–443 x10 3 per μL respectively.

          Conclusion

          Consistent with other studies from Sub-Saharan Africa, Hb and neutrophil counts were lower than Caucasian values. Our finding of higher Hb and lower eosinophil counts compared to other studies conducted in rural Kenya most likely reflects the strict recruitment criteria and healthier reference population after secondary exclusion of individuals with possible sub-clinical diseases.

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          Most cited references27

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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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              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.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: Supervision
                Role: InvestigationRole: MethodologyRole: Project administrationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: Resources
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 June 2018
                2018
                : 13
                : 6
                : e0198444
                Affiliations
                [1 ] Department of Pathology, Aga Khan University Hospital Nairobi, Nairobi, Kenya
                [2 ] Division of Chemical Pathology, Department of Pathology, Stellenbosch University, Cape Town, South Africa
                [3 ] PathCare Kenya Limited, Nairobi, Kenya
                [4 ] Karen Hospital, Nairobi, Kenya
                [5 ] Department of Pathology, Maseno University, Maseno, Kenya
                [6 ] Formerly of Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
                [7 ] Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan
                Inselspital Universitatsspital Bern, SWITZERLAND
                Author notes

                Competing Interests: Authors JW, CW and KR are employees of PathCare Kenya Limited which is a privately owned commercial laboratory. However, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                http://orcid.org/0000-0002-3866-5118
                Article
                PONE-D-18-03505
                10.1371/journal.pone.0198444
                5991659
                29879171
                7d85a253-e6e5-4600-a350-1bf050e22e11
                © 2018 Omuse 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
                : 7 February 2018
                : 18 May 2018
                Page count
                Figures: 6, Tables: 3, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100007607, University Research Council, Aga Khan University;
                Award ID: 1420088A
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001322, South African Medical Research Council;
                Award ID: 94261
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001322, South African Medical Research Council;
                Award ID: 004_94479
                Award Recipient :
                Part of this study was funded by an Aga Khan University Research Council grant (URC Project ID: 1420088A to GO) and Medical research council South Africa grants (Grant 94261 to RE and 004_94479 to MH). PathCare Kenya Limited provided support in the form of salaries for authors JM, CW and KR, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the author contributions’ section.
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                Custom metadata
                All complete blood count data files are available from the DRYAD database (DOI: https://doi.org/10.5061/dryad.pf1gt).

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