- ItemAssessment of Epstein-Barr virus in blood from patients with multiple sclerosis(2012) Hon G.M.; Hassan M.S.; Rensburg S.J.V.; Erasmus R.T.; Matsha T.E.Viruses such as Epstein-Barr virus (EBV) which can establish latent infections in the central nervous system or the immune system have been associated with chronic neurological disorders, including multiple sclerosis. Results vary, therefore the aim of this study was to investigate the presence of EBV using both viral DNA and antibody screening techniques, using PCR and ELISA assays respectively, to evaluate viral presence in blood from control subjects and patients with multiple sclerosis. Viral gene sequences for latent proteins EBNA-1 and LMP-1 and lytic gene BamH1- W were present equally in both patients and controls (<7%). Anti-EBV-VCA IgG positive cases were present in >99% of all study subjects, and anti-EBV-VCA IgG immune status ratio showed a near-significant positive correlation with the EDSS in patients with multiple sclerosis. In contrast, Anti- EBV-VCA IgM positive cases were significantly increased in patients (controls: 23.3%; patients; 41.9%; P00.046). The IgM to IgG immune status ratio was near-significantly higher in patients with relapse episodes in the year preceding blood sampling (P00.058). Results from this and previous studies have shown higher prevalence rates for EBV evaluating anti-EBV IgM positive cases against viral DNA positive cases. Also, IgM, an innate immune response, showed an association with relapse episodes, suggesting viral re-activation as a contributing factor to these relapses. © Springer Science+Business Media, LLC 2012.
- ItemA diffusion tensor imaging and neuropsychological study of prospective memory impairment in South African HIV positive individuals(2012) Jacqueline H.; Jenny W.-T.; Jean-Paul F.; Bruce S.; Robert P.; Kevin T.; Dan S.; John J.HIV-associated prospective memory (ProM) impairment has emerged, in earlier studies as a significant predictor of medication management and independence in activities of daily living. The relationship between ProM and white matter integrity in HIV has not previously been investigated. Participants, including 128 HIV-infected individuals and 32 healthy controls, were assessed using a comprehensive neuropsychological evaluation and both objective and subjective measures of ProM. Diffusion tensor imaging (DTI) was utilized to investigate the relationship of white matter integrity to ProM in a randomly selected subsample of 40 HIV positive subjects, using a whole brain voxel-based approach to define fractional anisotrophy (FA) and mean diffusion (MD). Total prospective memory was significantly poorer in the HIV positive group when compared with healthy controls (p00.023). Timebased ProM was poorer in the HIV group compared to healthy controls both without prompts (p00.001) and with prompts (p00.001). Poor Total ProM score correlated with performance on neuropsychological tests of executive functioning, information processing speed, learning, and working memory (p<0.05). Those HIV positive participants with poor ProM had significantly decreased FA in the regions of superior corona radiata (p00.0035), the corpus collosum (p00.006) and the cingulum (p00.0033) when compared to those who were HIV positive with good ProM. This study reinforces the importance of ProM assessment in HIV. © Springer Science+Business Media, LLC 2012.
- ItemRates and predictors of failure of first-line antiretroviral therapy and switch to second-line ART in South Africa(2012) Fox M.P.; Cutsem G.V.; Giddy J.; Maskew M.; Keiser O.; Prozesky H.; Wood R.; Hernan M.A.; Sterne J.A.C.; Egger M.; Boulle A.Objectives: To measure rates and predictors of virologic failure and switch to second-line antiretroviral therapy (ART) in South Africa. Design: Observational cohort study. Methods: We included ART-naive adult patients initiated on public sector ART (January 2000 to July 2008) at 5 sites in South Africa who completed ≥6 months of follow-up. We estimated cumulative risk of virologic failure (viral load ≥400 copies/mL with confirmation above varying thresholds) and switching to second-line ART. Results: Nineteen thousand six hundred forty-five patients (29,935 person-years) had a median of 1.3 years of study follow-up (1.8 years on ART) and a median CD4 count of 93 (IQR: 39-155) cells per microliter at ART initiation. About 9.9% (4.5 per 100 person-years) failed ART in median 16 (IQR: 12-23) months since ART initiation, with median 2.7 months (IQR: 1.6-4.7) months between first elevated and confirmatory viral loads. By survival analysis, using a confirmatory threshold of 400 copies per milliliter, 16.9% [95% confidence interval (CI): 15.4% to 18.6%] failed by 5 years on ART, but only 7.8% (95% CI: 6.6% to 9.3%) using a threshold of 10,000. CD4 <25 versus 100-199 (adjusted HR: 1.60; 95% CI: 1.37 to 1.87), ART initiation viral load ≥1,000,000 versus <10,000, (1.32; 0.91 to 1.93), and 2+ gaps in care versus 0 (95% CI: 7.25; 4.95 to 10.6) were predictive of failure. Overall, 10.1% (95% CI: 9.0% to 11.4%) switched to second-line by 5 years on ART. Lower CD4 at failure and higher rate of CD4 decline were predictive of switch (decline 100% to 51% versus 25% to-25%, adjusted HR: 1.96; 95% CI: 1.35 to 2.85). Conclusions: In resource-limited settings with viral load monitoring, virologic failure rates are highly sensitive to thresholds for confirmation. Despite clear guidelines there is considerable variability in switching failing patients, partially in response to immunologic status and postfailure evolution. © 2012 by Lippincott Williams & Wilkins.
- ItemChanges in pediatric HIV-related hospital admissions and mortality in Soweto, South Africa, 1996-2011: Light at the end of the tunnel?(2012) Meyers T.; Dramowski A.; Schneider H.; Gardiner N.; Kuhn L.; Moore D.Background: With widespread availability of pediatric antiretroviral therapy and improved access to prevention of mother-to-child transmission (PMTCT), it is important to monitor the impact on pediatric HIV-related hospital admissions and in-hospital mortality in South Africa. Methods: Over a 15-year period, 4 independent surveillance studies were conducted in the pediatric wards at Chris Hani Baragwanath Hospital in Soweto, South Africa (1996, 2005, 2007, and late 2010 to early 2011). Trends in HIV prevalence and HIV-related mortality were evaluated. Results: HIV prevalence was similar during the first 3 periods: 26.2% (1996), 31.7% (2005), and 29.5% (2007) P > 0.10, but was lower in 2010-2011 (19.3%; P = 0.0005). Median age of the children admitted with HIV increased in the latter periods from 9.13 (interquartile range 3.6-28.8) months to 10.0 (3.0-44.5) months (P > 0.10) and 18.0 (6.2-69.8) months (P = 0.048). Median admission weight-for-age z-scores were similar (<-3 SD) for the latter 3 periods. Admission CD4 percentage increased from 0.0% (0.0-9.4) in 2005 to 15.0% (8.2-22.8) in 2007 (P < 0.0001) and was 18.7% (9.6-24.7) in 2010-2011 (P > 0.10). Mortality among all vs. HIV-infected admissions was 63 of 565 (11.2%) and 43 of 179 (24.0%) in 2005, 91 of 1510 (6.0%) and 53 of 440 (12.0%) in 2007, and 18 of 429 (4.2%) and 9 of 73 (12.3%) in 2010-2011. Conclusions: HIV prevalence and mortality among pediatric admissions is decreasing. This is likely a result of improved PMTCT and wider antiretroviral therapy coverage. Continued effort to improve PMTCT coverage and identify and treat younger and older HIV-infected children is required to further reduce HIV-related morbidity and mortality. © 2012 by Lippincott Williams & Wilkins.
- ItemDopamine transporter binding in social anxiety disorder: The effect of treatment with escitalopram(2012) Warwick, James M.; Carey P.D.; Cassimjee N.; Lochner C.; Hemmings, Sian M. J.; Moolman-Smook H.; Beetge E.; Dupont P.; Stein D.J.Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using 123I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects' Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration. © Springer Science+Business Media, LLC 2012.