Date Published: December 15, 2011
Publisher: AOSIS OpenJournals
Author(s): Madisa Mine, Sikhulile Moyo, Penny Stevens, Kurt Michael, Vladimir Novitsky, Kgomotso Makhaola, Aida Asmelash, S’khatele Molefhabangwe, Elias Woldegabriel, Gaseboloke Mothowaeng, Talkmore Maruta, Charity Kamhukamwe, Phibeon M. Mangwendeza, Molly Holmes-Pretorius, Isaac Mtoni, Modisa Motswaledi, Rosemary Musonda, Ndwapi Ndwapi, Joseph Makhema, Richard Marlink, Khumo Seipone, Tendani Gaolathe, Max Essex.
Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers’ kits and textbooks.
The aim of this study was to determine the means, medians, 2.5th and 97.5th percentile reference intervals, for normal immunohaematological values in healthy adults in Botswana.
A total of 261 healthy participants comprising 126 men (48%) and 135 (52%) women were enrolled in the southern part of Botswana, and immunological and haematological laboratory parameters were measured.
The mean age was 28.8 (95% Confidence Interval [CI] 27.7–29.8) years, with a median of 27 years and a range 18–66 years. The mean haemoglobin level was significantly lower for women (12.4 g/dL; 95% CI 12.1% – 12.7%) than men (15.1 g/dL; 95% CI 14.9% – 15.3%). The women’s haemoglobin reference values (9.0 g/dL – 15.0 g/dL) levels were lower than observed in predominantly White populations (12.0 g/dL – 16.0 g/dL), but comparable with regional consensus reference intervals (9.5 g/dL – 15.8 g/dL) recently defined for East and Southern Africa.
The established values provide an important tool for patient management and could influence decisions on inclusion of participants and adverse events in clinical trials conducted locally.
The human immunodeficiency virus (HIV) constitutes a major public health problem in Botswana with a prevalence of 17.6%1 in the general population and 31.8% amongst pregnant woman.2,3 Botswana is one of the countries in Africa that has led a very high response to the epidemic through a range of multilevel interventions, including the widespread access to antiretrovirals (ARVs),4,5 and has built capacity to conduct international prevention, treatment and vaccine trials.6 A valid scientific safety evaluation of ARVs and HIV vaccines relies on the availability of locally defined reference values for parameters of clinical interest.7
The study was approved by the Health Research and Development Committee (HRDC) of the Ministry of Health in Botswana. Written informed consent was obtained from participants prior to their enrollment. Those people found to be HIV-positive were excluded from the study, and referred for HIV care and treatment clinics for further management. CD4 and haematology results that were obtained, were offered free of charge as per the Botswanan guidelines.
Screening and enrollment started in May 2008 and ended in June 2008. A total of 294 individuals were screened: 145 men (49%) and 149 women (51%). A total of 33 (11.2%) of screened volunteers were excluded, following enrollment based on defined exclusion criteria. The remaining 261 participants’ samples were included in the study, and comprised 135 women (51%) and 126 men (49%). The mean age was 28.8 (95% CI, 27.7–29.8) years, with a median of 27 and a range 18–66 years.
The reference intervals for immunohaematological and clinical chemistry parameters, which may serve as Botswanan standards for the interpretation of laboratory results, were established from 260 HIV-negative participants (134 women [52%] and 126 men [48%]) aged 18–66 years, from around Gaborone. As expected, the percentage CD4+ and CD8+ T-lymphocytes varied less between women and men. Malone et al.31 reported large fluctuations in repeated CD4+ cell counts in HIV-positive patients and can be explained, in part, by CD4+ cell count diurnal cycle, and also by high variability in total lymphocyte counts. HIV-negative women have a higher average CD4+ T-lymphocytes count than men, which confirms the findings of Bussmann et al.32 The CD4 cell counts are lower in Botswana than those observed in East Africa and USA. This has obvious implications on the clinical staging of AIDS and the assessment for disease progression.
This is the first study in Botswana to document haematological reference intervals for healthy adults. Our study shows that clinical reference values developed within the region are more appropriate for the Botswanan population than those adopted from developed countries. The established values provide an important tool for patient management and could influence decisions on the inclusion of participants, as well as the management of adverse events. It could also improve scientific validity in clinical trials that are conducted locally and regionally.