OpenUCT :: Browsing by Subject "Adults"

Browsing by Subject "Adults"

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Open Access
Acute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults
(2016) Kenteu, Bernold; Noubiap, Jean Jacques N; Etoa, Martine Claude; Azabji-Kenfack, Marcel; Dehayem, Mesmin; Sobngwi, Eugène
Abstract Background Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults. Methods We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m 2 with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test. Results During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893). Conclusion Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.
Open Access
Alignment between chronic disease policy and practice: case study at a primary care facility
(Public Library of Science, 2014) Draper, Claire A; Draper, Catherine E; Bresick, Graham F
BACKGROUND: Chronic disease is by far the leading cause of death worldwide and of increasing concern in low- and middle-income countries, including South Africa, where chronic diseases disproportionately affect the poor living in urban settings. The Provincial Government of the Western Cape (PGWC) has prioritized the management of chronic diseases and has developed a policy and framework (Adult Chronic Disease Management Policy 2009) to guide and improve the prevention and management of chronic diseases at a primary care level. The aim of this study is to assess the alignment of current primary care practices with the PGWC Adult Chronic Disease Management policy. METHODS: One comprehensive primary care facility in a Cape Town health district was used as a case study. Data was collected via semi-structured interviews (n = 10), focus groups (n = 8) and document review. Participants in this study included clinical staff involved in chronic disease management at the facility and at a provincial level. Data previously collected using the Integrated Audit Tool for Chronic Disease Management (part of the PGWC Adult Chronic Disease Management policy) formed the basis of the guide questions used in focus groups and interviews. RESULTS: The results of this research indicate a significant gap between policy and its implementation to improve and support chronic disease management at this primary care facility. A major factor seems to be poor policy knowledge by clinicians, which contributes to an individual rather than a team approach in the management of chronic disease patients. Poor interaction between facility- and community-based services also emerged. A number of factors were identified that seemed to contribute to poor policy implementation, the majority of which were staff related and ultimately resulted in a decrease in the quality of patient care. CONCLUSIONS: Chronic disease policy implementation needs to be improved in order to support chronic disease management at this facility. It is possible that similar findings and factors are present at other primary care facilities in Cape Town. At a philosophical level, this research highlights the tension between primary health care principles and a diseased-based approach in a primary care setting.
Open Access
Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis
(Public Library of Science, 2012) Suthar, Amitabh B; Lawn, Stephen D; Del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R; Chaisson, Richard E; Williams, Brian G; Harries, Anthony D
In a systematic review and meta-analysis, Amitabh Suthar and colleagues investigate the association between antiretroviral therapy and the reduction in the incidence of tuberculosis in adults with HIV infection.
Open Access
Antiretroviral treatment outcomes amongst older adults in a large multicentre cohort in South Africa
(Public Library of Science, 2014) Fatti, Geoffrey; Mothibi, Eula; Meintjes, Graeme; Grimwood, Ashraf
Introduction Increasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25-54 years) in routine care settings in South Africa. METHODS: A multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models. RESULTS: 4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29-1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26-1.64), particularly for the period 7-60 months of treatment, asHR = 1.73 (95% CI: 1.44-2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78-0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23-1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56-0.85) and 0.64 (95% CI: 0.47-0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3-33.2) lower in older adults. CONCLUSIONS: Although older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies.
Open Access
Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients
(Public Library of Science, 2012) Pepper, Dominique J; Marais, Suzaan; Bhaijee, Feriyl; Wilkinson, Robert J; De Azevedo, Virginia; Meintjes, Graeme
Setting: A South African township clinic where loss to follow-up during TB treatment may prevent HIV-infected TB patients from receiving life-saving ART. Objective: To determine factors associated with loss to follow-up during TB treatment. Design: Regression analyses of a cohort of ART-eligible TB patients who commenced TB treatment and were followed for 24 weeks. RESULTS: Of 111 ART-eligible TB patients, 15 (14%) died in the ensuing 24 weeks. Of the remaining 96 TB patients, 11 (11%) were lost to follow-up. All TB patients lost to follow-up did not initiate ART. Of 85 TB patients in follow-up, 62 (73%) initiated ART 56 days after TB diagnosis (median, IQR 33-77 days) and 31 days after initial assessment at an ART clinic (median, IQR: 18-55 days). The median duration from TB diagnosis to initial assessment at an ART clinic was 19 days (IQR: 7-48 days). At 24 weeks, 6 of 85 (7%) TB patients who presented to an ART clinic for assessment were lost to follow-up, compared to 5 of 11 (45%) TB patients who did not present to an ART clinic for assessment. Logistic regression analysis (adjusted odds ratio = 0.1, 95% confidence interval [95% CI]: 0.03-0.66) and our Cox proportional hazards model (hazard ratio = 0.2, 95% CI: 0.04-0.68) confirmed that assessment at an ART clinic during TB treatment reduced loss to follow-up. CONCLUSION: Assessment at antiretroviral clinics for HIV care by trained health-care providers reduces loss to follow-up among HIV-infected patients with TB.
Open Access
The association between hypertension and depression and anxiety disorders: results from a nationally-representative sample of South African adults
(Public Library of Science, 2009) Grimsrud, Anna; Stein, Dan J; Seedat, Soraya; Williams, David; Myer, Landon
Objective: Growing evidence suggests high levels of comorbidity between hypertension and mental illness but there are few data from low- and middle-income countries. We examined the association between hypertension and depression and anxiety in South Africa. METHODS: Data come from a nationally-representative survey of adults (n = 4351). The Composite International Diagnostic Interview was used to measure DSM-IV mental disorders during the previous 12-months. The relationships between self-reported hypertension and anxiety disorders, depressive disorders and comorbid anxiety-depression were assessed after adjustment for participant characteristics including experience of trauma and other chronic physical conditions. RESULTS: Overall 16.7% reported a previous medical diagnosis of hypertension, and 8.1% and 4.9% were found to have a 12-month anxiety or depressive disorder, respectively. In adjusted analyses, hypertension diagnosis was associated with 12-month anxiety disorders [Odds ratio (OR) = 1.55, 95% Confidence interval (CI) = 1.10-2.18] but not 12-month depressive disorders or 12-month comorbid anxiety-depression. Hypertension in the absence of other chronic physical conditions was not associated with any of the 12-month mental health outcomes (p-values all <0.05), while being diagnosed with both hypertension and another chronic physical condition were associated with 12-month anxiety disorders (OR = 2.25, 95% CI = 1.46-3.45), but not 12-month depressive disorders or comorbid anxiety-depression. CONCLUSIONS: These are the first population-based estimates to demonstrate an association between hypertension and mental disorders in sub-Saharan Africa. Further investigation is needed into role of traumatic life events in the aetiology of hypertension as well as the temporality of the association between hypertension and mental disorders.
Open Access
Better antiretroviral therapy outcomes at primary healthcare facilities: an evaluation of three tiers of ART services in four South African provinces
(Public Library of Science, 2010) Fatti, Geoffrey; Grimwood, Ashraf; Bock, Peter
BACKGROUND: There are conflicting reports of antiretroviral therapy (ART) effectiveness comparisons between primary healthcare (PHC) facilities and hospitals in low-income settings. This comparison has not been evaluated on a broad scale in South Africa. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was conducted including ART-naïve adults from 59 facilities in four provinces in South Africa, enrolled between 2004 and 2007. Kaplan-Meier estimates, competing-risks Cox regression, generalised estimating equation population-averaged models and logistic regression were used to compare death, loss to follow-up (LTFU) and virological suppression (VS) between PHC, district and regional hospitals. 29 203 adults from 47 PHC facilities, nine district hospitals and three regional hospitals were included. Patients at PHC facilities had more advanced WHO stage disease when starting ART. Retention in care was 80.1% (95% CI: 79.3%-80.8%), 71.5% (95% CI: 69.1%-73.8%) and 68.7% (95% CI: 67.0%-69.7%) at PHC, district and regional hospitals respectively, after 24 months of treatment ( P <0.0001). In adjusted regression analyses, LTFU was independently increased at regional hospitals (aHR 2.19; 95% CI: 1.94−2.47) and mortality was independently elevated at district hospitals (aHR 1.60; 95% CI: 1.30−1.99) compared to PHC facilities after 12 months of ART. District and regional hospital patients had independently reduced probabilities of VS, aOR 0.76 (95% CI: 0.59−0.97) and 0.64 (95% CI: 0.56−0.75) respectively compared to PHC facilities over 24 months of treatment. Conclusions/Significance: ART outcomes were superior at PHC facilities, despite PHC patients having more advanced clinical stage disease when starting ART, suggesting that ART can be adequately provided at this level and supporting the South African government's call for rapid up-scaling of ART at the primary level of care. Further prospective research is required to determine the degree to which outcome differences are attributable to either facility level characteristics or patient co-morbidity at hospital level.
Open Access
Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha, South Africa: a quality of care assessment
(Public Library of Science, 2014) Green, Ann; de Azevedo, Virginia; Patten, Gabriela; Davies, Mary-Ann; Ibeto, Mary; Cox, Vivian
Introduction To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. METHODS: A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. RESULTS: Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95-100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. CONCLUSIONS: Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings.
Open Access
A comparative analysis of polyfunctional T cells and secreted cytokines induced by Bacille Calmette-Guerin immunisation in children and adults
(Public Library of Science, 2012) Ritz, Nicole; Strach, Madeleine; Yau, Carmen; Dutta, Binita; Tebruegge, Marc; Connell, Tom G; Hanekom, Willem A; Britton, Warwick J; Robins-Browne, Roy; Curtis, Nigel
BCG vaccine is one of the most commonly-administered vaccines worldwide. Studies suggest the protective efficacy of BCG against TB is better for children than for adults. One potential explanation is that BCG induces a better protective immune response in children. Twenty six children and adults were immunised with BCG. The proportion of Th1-cytokine-producing mycobacterial-specific T cells, and the concentrations of secreted cytokines, were measured before and 10 weeks after BCG immunisation. A significant increase in the proportion of mycobacterial-specific cytokine-producing T cells was observed in both age groups. After BCG immunisation, children and adults had comparable proportions of mycobacterial-specific polyfunctional CD4 T cells when measured relative to the total number of CD4 T cells. However, relative to the subset of Th-1-cytokine-producing CD4 T cells, the proportion of polyfunctional cells was greater in children. Concentrations of secreted cytokines were comparable in children and adults. These findings suggest that the mycobacterial-specific cell-mediated immune response induced by BCG immunisation in children and adults is similar. The implication of a shift to a more polyfunctional immune response within the Th1-cytokine-producing CD4 T cells in children is uncertain as this aspect of the immune response has not been assessed as a potential correlate of protection against TB.
Open Access
Comparison of mantoux and tine tuberculin skin tests in BCG-vaccinated children investigated for tuberculosis
(Public Library of Science, 2009) Pan, Wenli; Matizirofa, Lyness; Workman, Lesley; Hawkridge, Tony; Hanekom, Willem; Mahomed, Hassan; Hussey, Gregory; Hatherill, Mark
Background: Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result. Methodology/Principal Findings: 1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result. Conclusions/Significance: The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.
Open Access
Density-dependent natal dispersal patterns in a leopard population recovering from over-harvest
(Public Library of Science, 2015) Fattebert, Julien; Balme, Guy; Dickerson, Tristan; Slotow, Rob; Hunter, Luke
Natal dispersal enables population connectivity, gene flow and metapopulation dynamics. In polygynous mammals, dispersal is typically male-biased. Classically, the ‘mate competition’, ‘resource competition’ and ‘resident fitness’ hypotheses predict density-dependent dispersal patterns, while the ‘inbreeding avoidance’ hypothesis posits density-independent dispersal. In a leopard ( Panthera pardus ) population recovering from over-harvest, we investigated the effect of sex, population density and prey biomass, on age of natal dispersal, distance dispersed, probability of emigration and dispersal success. Over an 11-year period, we tracked 35 subadult leopards using VHF and GPS telemetry. Subadult leopards initiated dispersal at 13.6 ± 0.4 months. Age at commencement of dispersal was positively density-dependent. Although males (11.0 ± 2.5 km) generally dispersed further than females (2.7 ± 0.4 km), some males exhibited opportunistic philopatry when the population was below capacity. All 13 females were philopatric, while 12 of 22 males emigrated. Male dispersal distance and emigration probability followed a quadratic relationship with population density, whereas female dispersal distance was inversely density-dependent. Eight of 12 known-fate females and 5 of 12 known-fate male leopards were successful in settling. Dispersal success did not vary with population density, prey biomass, and for males, neither between dispersal strategies (philopatry vs. emigration). Females formed matrilineal kin clusters, supporting the resident fitness hypothesis. Conversely, mate competition appeared the main driver for male leopard dispersal. We demonstrate that dispersal patterns changed over time, i.e. as the leopard population density increased. We conclude that conservation interventions that facilitated local demographic recovery in the study area also restored dispersal patterns disrupted by unsustainable harvesting, and that this indirectly improved connectivity among leopard populations over a larger landscape.
Open Access
Factors associated with excessive body fat in men and women: cross-sectional data from Black South Africans living in a rural community and an urban township
(Public Library of Science, 2015) Okop, Kufre Joseph; Levitt, Naomi; Puoane, Thandi
Objective To determine the factors associated with excessive body fat among black African men and women living in rural and urban communities of South Africa. METHODS: This is a cross-sectional analysis of data from the Prospective Urban and Rural Epidemiology (PURE) study, Cape Town, South Africa conducted in 2009/2010. The study sample included 1220 participants (77.2% women) aged 35-70 years, for whom anthropometric measurements were obtained and risk factors documented through face-to-face interviews using validated international PURE study protocols. Sex-specific logistic regression models were used to evaluate socio-demographic, lifestyle and psychological factors associated with three excessive body fat indicators, namely body mass index (BMI), waist circumference (WC) and body fat percent (BF%). RESULTS: The prevalence of excessive body fat based on BF%, WC and BMI cut-offs were 96.0%, 86.1%, and 81.6% for women respectively, and 62.2%, 25.9%, and 36.0% for men respectively. The significant odds of excessive body fat among the currently married compared to unmarried were 4.1 (95% CI: 1.3-12.5) for BF% and 1.9 (95% CI: 1.3-2.9) for BMI among women; and 4.9 (95% CI: 2.6-9.6), 3.2 (95% CI: 1.6-6.4) and 3.6 (95% CI: 1.9-6.8) for BF%, WC and BMI respectively among men. Age ≤50 years (compared to age >50 years) was inversely associated with excessive BF% in men and women, and less-than-a-college education was inversely associated with excessive BMI and WC in men. Tobacco smoking was inversely associated with all three excessive adiposity indicators in women but not in men. Unemployment, depression, and stress did not predict excessive body fat in men or women. CONCLUSION: The sex-differences in the socio-demographic and lifestyle factors associated with the high levels of excessive body fat in urban and rural women and men should be considered in packaging interventions to reduce obesity in these communities.
Open Access
Factors associated with retention to care in an HIV clinic in Gabon, Central Africa
(Public Library of Science, 2015) Janssen, Saskia; Wieten, Rosanne Willemijn; Stolp, Sebastiaan; Cremers, Anne Lia; Rossatanga, Elie Gide; Klipstein-Grobusch, Kerstin; Belard, Sabine; Grobusch, Martin Peter
BACKGROUND: Retention to HIV care is vital for patients' survival, to prevent onward transmission and emergence of drug resistance. Travelling to receive care might influence adherence. Data on the functioning of and retention to HIV care in the Central African region are limited. METHODS: This retrospective study reports outcomes and factors associated with retention to HIV care at a primary HIV clinic in Lambaréné, Gabon. Adult patients who presented to this clinic between January 2010 and January 2012 were included. Outcomes were retention in care (defined as documented show-up for clinical visits, regardless of delay) or LTFU (defined as a patient not retained in care; on ART or ART naïve, not returning to care during the study period with a patient delay for scheduled visits of more than 6 months), and mortality. Cox regression analysis was used to assess factors associated with respective outcomes. Qualitative data on reasons for LTFU were obtained from focus-group discussions. RESULTS: Of 223 patients included, 67.3% were female. The mean age was 40.5 (standard deviation 11.4) years and the median CD4 count 275 (interquartile range 100.5-449.5) cells/μL. In total, 34.1% were lost to follow up and 8.1% died. Documented tuberculosis was associated with increased risk of being LTFU (adjusted hazard ratio (aHR) 1.80, 95% confidence interval (95% CI) 1.05-3.11, P = 0.03), whereas early starting anti-retroviral therapy (ART) was associated with a decreased risk of LTFU (aHR 0.43, 95%CI 0.24-0.76, P = 0.004), as was confirmed by qualitative data. CONCLUSIONS: Retention to HIV care in a primary clinic in Gabon is relatively poor and interventions to address this should be prioritized in the HIV program. Early initiation of ART might improve retention in care.
Open Access
Gender differences in survival among adult patients starting antiretroviral therapy in South Africa: a multicentre cohort study
(Public Library of Science, 2012) Cornell, Morna; Schomaker, Michael; Garone, Daniela Belen; Giddy, Janet; Hoffmann, Christopher J; Lessells, Richard; Maskew, Mhairi; Prozesky, Hans; Wood, Robin; Johnson, Leigh F
Morna Cornell and colleagues investigate differences in mortality for HIV-positive men and women on antiretroviral therapy in South Africa.
Open Access
High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa
(Public Library of Science, 2014) Schaftenaar, Erik; Verjans, Georges M G M; Getu, Sarah; McIntyre, James A; Struthers, Helen E; Osterhaus, Albert D M E; Peters, Remco P H
Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa.
Open Access
ICU-Associated Acinetobacter baumannii Colonisation/Infection in a High HIV-Prevalence Resource-Poor Setting
(Public Library of Science, 2012) Ntusi, Ntobeko B A; Badri, Motasim; Khalfey, Hoosain; Whitelaw, Andrew; Oliver, Stephen; Piercy, Jenna; Raine, Richard; Joubert, Ivan; Dheda, Keertan
BACKGROUND: There are hardly any data about the incidence, risk factors and outcomes of ICU-associated A.baumannii colonisation/infection in HIV-infected and uninfected persons from resource-poor settings like Africa. METHODS: We reviewed the case records of patients with A.baumannii colonisation/infection admitted into the adult respiratory and surgical ICUs in Cape Town, South Africa, from January 1 to December 31 2008. In contrast to colonisation, infection was defined as isolation of A.baumannii from any biological site in conjunction with a compatible clinical picture warranting treatment with antibiotics effective against A.baumannii . RESULTS: The incidence of A.baumannii colonisation/infection in 268 patients was 15 per 100 person-years, with an in-ICU mortality of 26.5 per 100 person-years. The average length of stay in ICU was 15 days (range 1-150). A.baumannii was most commonly isolated from the respiratory tract followed by the bloodstream. Independent predictors of mortality included older age (p = 0.02), low CD4 count if HIV-infected (p = 0.038), surgical intervention (p = 0.047), co-morbid Gram-negative sepsis (p = 0.01), high APACHE-II score (p = 0.001), multi-organ dysfunction syndrome (p = 0.012), and a positive blood culture for A.baumannii (p = 0.017). Of 21 A.baumannii colonised/infected HIV-positive persons those with clinical AIDS (CD4<200 cells/mm 3 ) had significantly higher in-ICU mortality and were more likely to have a positive blood culture. Conclusion In this resource-poor setting A.baumannii infection in critically ill patients is common and associated with high mortality. HIV co-infected patients with advanced immunosuppression are at higher risk of death.
Open Access
Impaired CD4 T cell memory response to Streptococcus pneumoniae precedes CD4 T cell depletion in HIV-infected Malawian adults
(Public Library of Science, 2011) Glennie, Sarah J; Sepako, Enoch; Mzinza, David; Harawa, Visopo; Miles, David J C; Jambo, Kondwani C; Gordon, Stephen B; Williams, Neil A; Heyderman, Robert S
Objective Invasive pneumococcal disease (IPD) is a leading cause of morbidity and mortality in HIV-infected African adults. CD4 T cell depletion may partially explain this high disease burden but those with relatively preserved T cell numbers are still at increased risk of IPD. This study evaluated the extent of pneumococcal-specific T cell memory dysfunction in asymptomatic HIV infection early on in the evolution of the disease. METHODS: Peripheral blood mononuclear cells were isolated from asymptomatic HIV-infected and HIV-uninfected Malawian adults and stained to characterize the underlying degree of CD4 T cell immune activation, senescence and regulation. Pneumococcal-specific T cell proliferation, IFN-γ, IL-17 production and CD154 expression was assessed using flow cytometry and ELISpot. RESULTS: We find that in asymptomatic HIV-infected Malawian adults, there is considerable immune disruption with an increase in activated and senescent CD4 + CD38 + PD-1 + and CD4 + CD25 high Foxp3 + Treg cells. In the context of high pneumococcal exposure and therefore immune stimulation, show a failure in pneumococcal-specific memory T cell proliferation, skewing of T cell cytokine production with preservation of interleukin-17 but decreased interferon-gamma responses, and failure of activated T cells to express the co-stimulatory molecule CD154. CONCLUSION: Asymptomatic HIV-infected Malawian adults show early signs of pneumococcal- specific immune dysregulation with a shift in the balance of CD4 memory, T helper 17 cells and Treg. Together these data offer a mechanistic understanding of how antigen-specific T cell dysfunction occurs prior to T cell depletion and may explain the early susceptibility to IPD in those with relatively preserved CD4 T cell numbers.
Open Access
Linkage to HIV care and antiretroviral therapy in Cape Town, South Africa
(Public Library of Science, 2010) Kranzer, Katharina; Zeinecker, Jennifer; Ginsberg, Philip; Orrell, Catherine; Kalawe, Nosindiso N; Lawn, Stephen D; Bekker, Linda-Gail; Wood, Robin
BACKGROUND: Antiretroviral therapy (ART) has been scaled-up rapidly in Africa. Programme reports typically focus on loss to follow-up and mortality among patients receiving ART. However, little is known about linkage and retention in care of individuals prior to starting ART. METHODOLOGY: Data on adult residents from a periurban community in Cape Town were collected at a primary care clinic and hospital. HIV testing registers, CD4 count results provided by the National Health Laboratory System and ART registers were linked. A random sample (n = 885) was drawn from adults testing HIV positive through antenatal care, sexual transmitted disease and voluntary testing and counseling services between January 2004 and March 2009. All adults (n = 103) testing HIV positive through TB services during the same time period were also included in the study. Linkage to HIV care was defined as attending for a CD4 count measurement within 6 months of HIV diagnosis. Linkage to ART care was defined as initiating ART within 6 months of HIV diagnosis in individuals with a CD4 count ≤200 cells/µl taken within 6 months of HIV diagnosis. FINDINGS: Only 62.6% of individuals attended for a CD4 count measurement within 6 months of testing HIV positive. Individuals testing through sexually transmitted infection services had the best (84.1%) and individuals testing on their own initiative (53.5%) the worst linkage to HIV care. One third of individuals with timely CD4 counts were eligible for ART and 66.7% of those were successfully linked to ART care. Linkage to ART care was highest among antenatal care clients. Among individuals not yet eligible for ART only 46.3% had a repeat CD4 count. Linkage to HIV care improved in patients tested in more recent calendar period. CONCLUSION: Linkage to HIV and ART care was low in this poor peri-urban community despite free services available within close proximity. More efforts are needed to link VCT scale-up to subsequent care.
Open Access
Missed opportunities for retention in pre-ART care in Cape Town, South Africa
(Public Library of Science, 2014) du Toit, Elizabeth; van Schalkwyk, Cari; Dunbar, Rory; Jennings, Karen; Yang, Blia; Coetzee, David; Beyers, Nulda
BACKGROUND: Few studies have evaluated access to and retention in pre-ART care. Objectives To evaluate the proportion of People Living With HIV (PLWH) in pre-ART and ART care and factors associated with retention in pre-ART and ART care from a community cohort. METHODS: A cross sectional survey was conducted from February - April 2011. Self reported HIV positive, negative or participants of unknown status completed a questionnaire on their HIV testing history, access to pre-ART and retention in pre-ART and ART care. RESULTS: 872 randomly selected adults who reported being HIV positive in the ZAMSTAR 2010 prevalence survey were included and revisited. 579 (66%) reconfirmed their positive status and were included in this analysis. 380 (66%) had initiated ART with 357 of these (94%) retained in ART care. 199 (34%) had never initiated ART of whom 186 (93%) accessed pre-ART care, and 86 (43%) were retained in pre-ART care. In a univariable analysis none of the factors analysed were significantly associated with retention in care in the pre-ART group. Due to the high retention in ART care, factors associated with retention in ART care, were not analysed further. CONCLUSION: Retention in ART care was high; however it was low in pre-ART care. The opportunity exists, if care is better integrated, to engage with clients in primary health care facilities to bring them back to, and retain them in, pre-ART care.
Open Access
Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer
(Public Library of Science, 2009) Blum, Roy; Gupta, Rashmi; Burger, Patricia E; Ontiveros, Christopher S; Salm, Sarah N; Xiong, Xiaozhong; Kamb, Alexander; Wesche, Holger; Marshall, Lisa; Cutler, Gene
BACKGROUND: The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-β has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg. Conclusions/Significance Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors.