Reference Intervals in Healthy Adult Ugandan Blood Donors and Their Impact on Conducting International Vaccine Trials

BACKGROUND: Clinical trials are increasingly being conducted internationally. In order to ensure enrollment of healthy participants and proper safety evaluation of vaccine candidates, established reference intervals for clinical tests are required in the target population. METHODOLOGY/PRINCIPAL FINDINGS: We report a reference range study conducted in Ugandan adult blood bank donors establishing reference intervals for hematology and clinical chemistry parameters. Several differences were observed when compared to previously established values from the United States, most notably in neutrophils and eosinophils. CONCLUSIONS/SIGNIFICANCE: In a recently conducted vaccine trial in Uganda, 31 percent (n = 69) of volunteers screened (n = 223) were excluded due to hematologic abnormalities. If local reference ranges had been employed, 83% of those screened out due to these abnormalities could have been included in the study, drastically reducing workload and cost associated with the screening process. In addition, toxicity tables used in vaccine and drug trial safety evaluations may need adjustment as some clinical reference ranges determined in this study overlap with grade 1 and grade 2 adverse events

Sex and Urbanicity Contribute to Variation in Lymphocyte Distribution across Ugandan Populations.

Management of patient care and interpretation of research data require evaluation of laboratory results in the context of reference data from populations with known health status to adequately diagnose disease or make a physiological assessment. Few studies have addressed the diversity of lymphocyte subsets in rural and urban Ugandan populations. Here, 663 healthy blood bank donors from semi-urban centers of Kampala consented to participate in a study to define lymphocyte reference ranges. Whole blood immunophenotyping was performed to determine the frequency and absolute counts of T, B, and NK cells using clinical flow cytometry. Results from blood bank donors were compared to a rural cohort from the district of Kayunga and more urban clinical trial participants from the capital city, Kampala. Relationships between hematological and lymphocyte parameters were also explored. In the semi-urban blood donors, females were significantly different from males in all parameters except the frequency of CD8 T and B cells. Females had higher absolute counts of CD4 T, CD8 T and B cells, whereas males had higher NK cell counts. NK cell frequency and counts were significantly higher in semi-urban blood donors, regardless of sex, compared to more urban study participants. CD8 T cell frequency and counts were significantly higher in the blood donors compared to the rural participants, irrespective of sex. Interestingly, basophil counts were positively associated with overall T cell counts. These findings suggest that both sex and level of cohort urbanicity may influence lymphocyte subset distributions in Ugandans

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<p>Box and whisker plots showing median and 2.5–97.5 percentiles of (A) neutrophils in semi-urban blood bank donors [SU] and vaccine trial [U]; (B) eosinophils; (C) lymphocytes; (D) basophils; (E) B monocytes; and (F) hemoglobin levels and RBC counts. The non-parametric Mann Whitney U test was used to determine any statistically significant differences between cohorts; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.</p

Large-Scale Human Immunodeficiency Virus Rapid Test Evaluation in a Low-Prevalence Ugandan Blood Bank Population▿

The use of rapid tests for human immunodeficiency virus (HIV) has become standard in HIV testing algorithms employed in resource-limited settings. We report an extensive HIV rapid test validation study conducted among Ugandan blood bank donors at low risk for HIV infection. The operational characteristics of four readily available commercial HIV rapid test kits were first determined with 940 donor samples and were used to select a serial testing algorithm. Uni-Gold Recombigen HIV was used as the screening test, followed by HIV-1/2 STAT-PAK for reactive samples. OraQuick HIV-1 testing was performed if the first two test results were discordant. This algorithm was then tested with 5,252 blood donor samples, and the results were compared to those of enzyme immunoassays (EIAs) and Western blotting. The unadjusted algorithm sensitivity and specificity were 98.6 and 99.9%, respectively. The adjusted sensitivity and specificity were 100 and 99.96%, respectively. This HIV testing algorithm is a suitable alternative to EIAs and Western blotting for Ugandan blood donors

95% Chemistry Reference Intervals

*<p>indicates parameters with statistically significant gender differences.</p

Associations between lymphocyte and basophil counts.

<p>Correlation graphs of (A) basophil and CD8 T cell counts; (B) basophil and CD4 T cell counts; and (C) basophil and B cell counts. The Spearman’s rank correlation was used to assess associations between parameters, with rho ≥ 0.25 and p values < 0.05 considered statistically significant.</p

Vaccine Trial Exclusions

<p>Vaccine Trial Exclusions</p

Association between age, lymphocytes and hematological parameters.

<p>Correlation graphs of (A) Age and CD4 T cell frequency; (B) Age and RBC count; (C) Age and hemoglobin levels; (D) eosinophil and CD3 T cell counts; and (E) basophil and CD3 T cell counts. The Spearman’s rank correlation was used to assess associations between parameters, with rho ≥ 0.25 and p values < 0.05 considered statistically significant.</p