title: CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.
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.
  
  
  RESULTS
  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.
authors.affiliation: Projet San Francisco (PSF), Kigali, Rwanda.
authors.forename: Etienne
authors.initials: E
authors.lastname: Karita
authors.forename: Nzeera
authors.initials: N
authors.lastname: Ketter
authors.forename: Matt A
authors.initials: MA
authors.lastname: Price
authors.forename: Kayitesi
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authors.lastname: Kayitenkore
authors.forename: Pontiano
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authors.lastname: Kaleebu
authors.forename: Annet
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authors.lastname: Nanvubya
authors.forename: Omu
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authors.lastname: Anzala
authors.forename: Walter
authors.initials: W
authors.lastname: Jaoko
authors.forename: Gaudensia
authors.initials: G
authors.lastname: Mutua
authors.forename: Eugene
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authors.lastname: Ruzagira
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Eduard J
authors.initials: EJ
authors.lastname: Sanders
authors.forename: Mary
authors.initials: M
authors.lastname: Mwangome
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Agnes
authors.initials: A
authors.lastname: Bwanika
authors.forename: Ubaldo
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authors.lastname: Bahemuka
authors.forename: Ken
authors.initials: K
authors.lastname: Awuondo
authors.forename: Gloria
authors.initials: G
authors.lastname: Omosa
authors.forename: Bashir
authors.initials: B
authors.lastname: Farah
authors.forename: Pauli
authors.initials: P
authors.lastname: Amornkul
authors.forename: Josephine
authors.initials: J
authors.lastname: Birungi
authors.forename: Sarah
authors.initials: S
authors.lastname: Yates
authors.forename: Lisa
authors.initials: L
authors.lastname: Stoll-Johnson
authors.forename: Jill
authors.initials: J
authors.lastname: Gilmour
authors.forename: Gwynn
authors.initials: G
authors.lastname: Stevens
authors.forename: Erin
authors.initials: E
authors.lastname: Shutes
authors.forename: Olivier
authors.initials: O
authors.lastname: Manigart
authors.forename: Peter
authors.initials: P
authors.lastname: Hughes
authors.forename: Len
authors.initials: L
authors.lastname: Dally
authors.forename: Janet
authors.initials: J
authors.lastname: Scott
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.forename: Pat
authors.initials: P
authors.lastname: Fast
authors.forename: Anatoli
authors.initials: A
authors.lastname: Kamali
mesh_terms: D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D000353:Africa, Southern; D001663:Bilirubin / Q000378:metabolism; D001671:Biochemistry; D001772:Blood Cell Count; D002624:Chemistry, Clinical / Q000592:standards; D019411:Clinical Laboratory Techniques; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D006262:Health; D006405:Hematology / Q000592:standards; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054579:National Institute of Allergy and Infectious Diseases (U.S.); D009504:Neutrophils / Q000378:metabolism; D012016:Reference Values; D014481:United States
chemical_list: D006454:Hemoglobins; D007074:Immunoglobulin G; D007770:L-Lactate Dehydrogenase; D001663:Bilirubin