Immunohaematological reference values for HIV-negative healthy adults in Botswana

BACKGROUND: Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers' kits and textbooks. OBJECTIVES: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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

Timing Constraints of In Vivo Gag Mutations during Primary HIV-1 Subtype C Infection

Background: Aiming to answer the broad question “When does mutation occur?” this study examined the time of appearance, dominance, and completeness of in vivo Gag mutations in primary HIV-1 subtype C infection. Methods: A primary HIV-1C infection cohort comprised of 8 acutely and 34 recently infected subjects were followed frequently up to 500 days post-seroconversion (p/s). Gag mutations were analyzed by employing single-genome amplification and direct sequencing. Gag mutations were determined in relation to the estimated time of seroconversion. Time of appearance, dominance, and completeness was compared for different types of in vivo Gag mutations. Results: Reverse mutations to the wild type appeared at a median (IQR) of 62 (44;139) days p/s, while escape mutations from the wild type appeared at 234 (169;326) days p/s (p<0.001). Within the subset of mutations that became dominant, reverse and escape mutations appeared at 54 (30;78) days p/s and 104 (47;198) days p/s, respectively (p<0.001). Among the mutations that reached completeness, reverse and escape mutations appeared at 54 (30;78) days p/s and 90 (44;196) days p/s, respectively (p = 0.006). Time of dominance for reverse mutations to and escape mutations from the wild type was 58 (44;105) days p/s and 219 (90;326) days p/s, respectively (p<0.001). Time of completeness for reverse and escape mutations was 152 (100;176) days p/s and 243 (101;370) days p/s, respectively (p = 0.001). Fitting a Cox proportional hazards model with frailties confirmed a significantly earlier time of appearance (hazard ratio (HR): 2.6; 95% CI: 2.3–3.0), dominance (4.8 (3.4–6.8)), and completeness (3.6 (2.3–5.5)) of reverse mutations to the wild type Gag than escape mutations from the wild type. Some complex mutational pathways in Gag included sequential series of reversions and escapes. Conclusions: The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion. Overall, the in vivo reverse mutations to the wild type occurred significantly earlier than escape mutations from the wild type. This shorter time to incidence of reverse mutations remained in the subsets of in vivo Gag mutations that reached dominance or completeness

Evidence for cross rift structural controls on deformation and seismicity at a continental rift caldera

In continental rifts structural heterogeneities, such as pre-existing faults and foliations, are thought to influence shallow crustal processes, particularly the formation of rift faults, magma reservoirs and surface volcanism. We focus on the Corbetti caldera, in the southern central Main Ethiopian Rift. We measure the surface deformation between 22nd June 2007 and 25th March 2009 using ALOS and ENVISAT SAR interferograms and observe a semi-circular pattern of deformation bounded by a sharp linear feature cross-cutting the caldera, coincident with the caldera long axis. The signal reverses in sign but is not seasonal: from June to December 2007 the region south of this structure moves upwards 3 cm relative to the north, while from December 2007 until November 2008 it subsides by 2 cm. Comparison of data taken from two different satellite look directions show that the displacement is primarily vertical. We discuss potential mechanisms and conclude that this deformation is associated with pressure changes within a shallow (<1 km) fault-bounded hydrothermal reservoir prior to the onset of a phase of caldera-wide uplift. Analysis of the distribution of post-caldera vents and cones inside the caldera shows their locations are statistically consistent with this fault structure, indicating that the fault has also controlled the migration of magma from a reservoir to the surface over tens of thousands of years. Spatial patterns of seismicity are consistent with a cross-rift structure that extents outside the caldera and to a depth of ∼30 km, and patterns of seismic anisotropy suggests stress partitioning occurs across the structure. We discuss the possible nature of this structure, and conclude that it is most likely associated with the Goba–Bonga lineament, which cross-cuts and pre-dates the current rift. Our observations show that pre-rift structures play an important role in magma transport and shallow hydrothermal processes, and therefore they should not be neglected when discussing these processes

Immunohaematological reference values for HIV-negative healthy adults in Botswana

Background: Clinical laboratories in Botswana have relied entirely on the reference intervals for normal immunohaematological values provided by manufacturers’ kits and textbooks. Objectives: 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. Method: 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. Results: 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. Conclusion: 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