PMID- 19197365
OWN - NLM
STAT- MEDLINE
DCOM- 20090320
LR  - 20240326
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 2
DP  - 2009
TI  - CLSI-derived hematology and biochemistry reference intervals for healthy adults 
      in eastern and southern Africa.
PG  - e4401
LID - 10.1371/journal.pone.0004401 [doi]
LID - e4401
AB  - 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.
FAU - Karita, Etienne
AU  - Karita E
AD  - Projet San Francisco (PSF), Kigali, Rwanda.
FAU - Ketter, Nzeera
AU  - Ketter N
FAU - Price, Matt A
AU  - Price MA
FAU - Kayitenkore, Kayitesi
AU  - Kayitenkore K
FAU - Kaleebu, Pontiano
AU  - Kaleebu P
FAU - Nanvubya, Annet
AU  - Nanvubya A
FAU - Anzala, Omu
AU  - Anzala O
FAU - Jaoko, Walter
AU  - Jaoko W
FAU - Mutua, Gaudensia
AU  - Mutua G
FAU - Ruzagira, Eugene
AU  - Ruzagira E
FAU - Mulenga, Joseph
AU  - Mulenga J
FAU - Sanders, Eduard J
AU  - Sanders EJ
FAU - Mwangome, Mary
AU  - Mwangome M
FAU - Allen, Susan
AU  - Allen S
FAU - Bwanika, Agnes
AU  - Bwanika A
FAU - Bahemuka, Ubaldo
AU  - Bahemuka U
FAU - Awuondo, Ken
AU  - Awuondo K
FAU - Omosa, Gloria
AU  - Omosa G
FAU - Farah, Bashir
AU  - Farah B
FAU - Amornkul, Pauli
AU  - Amornkul P
FAU - Birungi, Josephine
AU  - Birungi J
FAU - Yates, Sarah
AU  - Yates S
FAU - Stoll-Johnson, Lisa
AU  - Stoll-Johnson L
FAU - Gilmour, Jill
AU  - Gilmour J
FAU - Stevens, Gwynn
AU  - Stevens G
FAU - Shutes, Erin
AU  - Shutes E
FAU - Manigart, Olivier
AU  - Manigart O
FAU - Hughes, Peter
AU  - Hughes P
FAU - Dally, Len
AU  - Dally L
FAU - Scott, Janet
AU  - Scott J
FAU - Stevens, Wendy
AU  - Stevens W
FAU - Fast, Pat
AU  - Fast P
FAU - Kamali, Anatoli
AU  - Kamali A
LA  - eng
GR  - MC_U950080930/MRC_/Medical Research Council/United Kingdom
GR  - MC_U950097145/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090206
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hemoglobins)
RN  - 0 (Immunoglobulin G)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - RFM9X3LJ49 (Bilirubin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Africa, Eastern
MH  - Africa, Southern
MH  - Bilirubin/metabolism
MH  - Biochemistry
MH  - Blood Cell Count
MH  - *Chemistry, Clinical/standards
MH  - *Clinical Laboratory Techniques
MH  - Eosinophils/metabolism
MH  - Female
MH  - *Health
MH  - *Hematology/standards
MH  - Hemoglobins/metabolism
MH  - Humans
MH  - Immunoglobulin G/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Middle Aged
MH  - National Institute of Allergy and Infectious Diseases (U.S.)
MH  - Neutrophils/metabolism
MH  - Reference Values
MH  - United States
PMC - PMC2632744
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/02/07 09:00
MHDA- 2009/03/21 09:00
PMCR- 2009/02/06
CRDT- 2009/02/07 09:00
PHST- 2008/09/09 00:00 [received]
PHST- 2008/11/24 00:00 [accepted]
PHST- 2009/02/07 09:00 [entrez]
PHST- 2009/02/07 09:00 [pubmed]
PHST- 2009/03/21 09:00 [medline]
PHST- 2009/02/06 00:00 [pmc-release]
AID - 08-PONE-RA-06306 [pii]
AID - 10.1371/journal.pone.0004401 [doi]
PST - ppublish
SO  - PLoS One. 2009;4(2):e4401. doi: 10.1371/journal.pone.0004401. Epub 2009 Feb 6.