Kimberley, South Africa
Kimberley, South Africa

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Bezuidenhout A.F.,Stellenbosch University | Hurter D.,Kimberley Hospital | Maydell A.T.,Stellenbosch University | van Niekerk F.,Kimberley Hospital | And 4 more authors.
South African Medical Journal | Year: 2013

Background. The indications for urgent computed tomography of the brain (CTB) in the acute setting are controversial. While guidelines have been proposed for CTB in well-resourced countries, these are not always appropriate for resource-limited environments. Furthermore, no unifying guideline exists for trauma-related and non-trauma-related acute intracranial pathology. Adoption by resource-limited countries of more conservative scanning protocols, with outcomes comparable to well-resourced countries, would have significant benefit. A multidisciplinary team from Kimberley Hospital in the Northern Cape Province of South Africa adopted the principles defined in the National Institute for Health and Care Excellence (NICE) guideline for the early management of head injury and drafted the Kimberley Hospital Rule (KHR), a proposed unifying guideline for the imaging of acute intracranial pathology in a resource-limited environment. Objective. To evaluate the sensitivity and specificity of the KHR. Methods. A prospective cohort study was conducted in the Northern Cape Province between 1 May 2010 and 30 April 2011. All patients older than 16 years presenting to emergency departments with acute intracranial symptoms were triaged according to the KHR into three groups, as follows: group 1 - immediate scan (within 1 hour); group 2 - urgent scan (within 8 hours); and group 3 - no scan required. Patients in groups 1 and 2 were studied. The primary outcome was CTB findings of clinically significant intracranial pathology requiring acute change in management. Results. Seven hundred and three patients were included. The KHR achieved 90.3% sensitivity and 45.5% specificity, while reducing the number of immediate CTBs by 36.0%. Conclusion. The KHR is an accurate, unifying clinical guideline that appears to optimise the utilisation of CTB in a resource-limited environment.


Adland E.,University of Oxford | Paioni P.,University of Oxford | Thobakgale C.,University of KwaZulu - Natal | Laker L.,Kimberley Hospital | And 28 more authors.
PLoS Pathogens | Year: 2015

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression. © 2015 Adland et al.


Matthews P.C.,University of Oxford | Beloukas A.,University of Liverpool | Malik A.,University of Oxford | Carlson J.M.,Microsoft | And 19 more authors.
PLoS ONE | Year: 2015

There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care. © 2015 Matthews et al.


Muenchhoff M.,University of Oxford | Muenchhoff M.,University of KwaZulu - Natal | Muenchhoff M.,Ludwig Maximilians University of Munich | Muenchhoff M.,German Center for Infection Research | And 44 more authors.
Science Translational Medicine | Year: 2016

Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-Age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.


PubMed | University of Liverpool, University of KwaZulu - Natal, Royal Berkshire Hospital, Kimberley Hospital and 6 more.
Type: Journal Article | Journal: PloS one | Year: 2015

There is progressive concern about the evolving burden of morbidity and mortality caused by coinfection with HIV-1 and hepatitis B virus (HBV) in sub-Saharan Africa, but the epidemiology and impact of this problem are not well defined. We therefore set out to assimilate more information about the nature of HBV/HIV coinfection in this region by undertaking a retrospective observational study of southern African adult women. We used samples from previously recruited HIV-1 positive women attending antenatal clinics in three settings in South Africa and Botswana (n = 950) and added a small cohort of HIV-negative antenatal South African women for comparison (n = 72). We tested for HBsAg and followed up HBsAg-positive samples by testing for HBeAg, HBV DNA, HBV genotype, presence of drug-resistance associated mutations (RAMs) and HDV. We identified HBsAg in 72 individuals (7% of the whole cohort), of whom 27% were HBeAg-positive, and the majority HBV genotypes A1 and A2. We did not detect any HDV coinfection. HBV prevalence was significantly different between geographically distinct cohorts, but did not differ according to HIV status. Among adults from South Africa, HBV/HIV coinfected patients had lower CD4+ T cell counts compared to those with HIV-monoinfection (p = 0.02), but this finding was not replicated in the cohort from Botswana. Overall, these data provide a snapshot of the coinfection problem at the heart of the HIV/HBV co-epidemic, and are important to inform public health policy, resource allocation, education, surveillance and clinical care.


PubMed | Peter Medawar Building, Foundation Medicine, University of Oxford, University of the Free State and Kimberley Hospital
Type: | Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2016

In South Africa, the first HBV vaccine dose is administered at age 6 weeks, leaving a potential window for vertical transmission. Insights into HBV seroprevalence in the vulnerable HIV-infected group are important to drive improvements in surveillance, treatment and prevention.We set out to implement a screening program for HBV among HIV-infected children and adolescents in Kimberley, South Africa. Our aims were to demonstrate that screening is feasible and sustainable, to establish the prevalence of HBV, to characterise the HBV cases we identified, and to inform discussion about the infant vaccination schedule.We tested all HIV positive children (age 0-16) for Hepatitis B surface antigen (HBsAg), delivering this testing as part of routine state-funded care. We followed up HBsAg-positive cases with an extended panel of HBV serology tests, and HBV DNA viral load quantification.Our screening campaign was successfully incorporated into routine out-patient care. Among 625 patients tested, we found five positive for HBsAg (0.8%), of whom three were Hepatitis B e-antigen positive. Two additional children initially tested HBsAg-positive but were negative on repeat testing. Antiviral therapy in the HBsAg children was reviewed and adjusted if required.The results testify to the overall success of the HBV vaccine campaign. However, we have demonstrated that ongoing vigilance is required to detect cases and prevent transmission events. Further evaluation of the optimum timing of the first vaccine HBV vaccine dose is required; a vaccine dose at birth could reduce prevalence further.


PubMed | Massachusetts Institute of Technology, University of KwaZulu - Natal, Great Ormond St Hospital for Children, Kimberley Hospital and 6 more.
Type: Journal Article | Journal: PLoS pathogens | Year: 2015

HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC) of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-nave, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004). The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001), but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007). Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002). In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.


Limburgh C.M.,Kimberley Hospital | Van Schalkwyk G.I.,Yale University | Lee K.-H.,Kimberley Hospital | Buys C.,Kimberley Hospital | And 4 more authors.
AIDS Care - Psychological and Socio-Medical Aspects of AIDS/HIV | Year: 2013

Following the adoption of key national policy, several campaigns aimed at increasing the number of adult males receiving circumcisions have been implemented across South Africa. Evidence as to the likely effectiveness of such interventions comes predominantly from three large randomized-controlled trials. However, little has been written about how these campaigns are perceived by the participants. This is significant given the importance of the social issues that are implicit in determining both the ethical acceptability, and effectiveness of these campaigns. We report on a study aimed at identifying and exploring motivating factors for participation, behavioral effects, and cultural attitudes of participants towards a circumcision campaign undertaken in the Northern Cape Province. For this interpretive sociological research project, semi-structured interviews were conducted with 29 participants. These were recorded, transcribed, and qualitatively analyzed. The main reasons given for participation included that of reducing the risk of acquiring HIV and other sexually transmitted infections (STIs), as well as the enhancement of sexual experience. Participants insisted that they would continue to use condoms after the circumcision, although felt that other community members receiving circumcisions would not do so. Several advantages were described when receiving a circumcision at a public health facility, as opposed to the manner more traditional to the participant's culture. Whilst they did not report intentions for risk compensation, the reasons given for participation and their willingness to attribute this problem to other community members casts doubt on the veracity of their reported intentions. Furthermore, participants did not appear to have a complete understanding as to how circumcision is protective. Participants shared the belief that circumcisions as performed in the context of this campaign were safer than the traditional circumcision occurring in the area, which represents an important area for further research. © Taylor and Francis.


PubMed | National Health Research Institute, Copenhagen University, University of KwaZulu - Natal, Imperial College London and 10 more.
Type: Journal Article | Journal: Science translational medicine | Year: 2016

Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-nave children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.


Bidmos M.A.,University of Toronto | Joubert S.,Kimberley Hospital | Van Jaarsveld M.F.P.C.,Universitas Hospital | Louw V.J.,Universitas Hospital
International Journal of Hematology | Year: 2013

Plasma cell leukaemia (PCL) is a rare condition with high mortality. HIV-positive patients have a propensity to develop malignancy; however, the occurrence of PCL with HIV infection in South Africa has not been documented. We describe patients with PCL in Universitas Hospital in Bloemfontein, South Africa, and report two new cases of HIV infection concurrent with PCL. A retrospective case series of PCL patients (2006-2012) seen at our Clinical Haematology unit is reported. Patient files were used to obtain information. The median age of patients (n = 9) was 51 years, and 66.7 % of cases were of African ethnicity. The condition was equally distributed between genders. Two patients were HIV positive. Both received combination antiretroviral therapy. The diagnosis of PCL was usually made as an incidental finding, subsequently confirmed on bone marrow aspirate and trephine. Deranged haematological and biochemical parameters, including severe anaemia, hypoalbuminaemia, and hyper-cellular bone marrow, were observed. Only one patient improved markedly on treatment, and remains alive at the time of writing. PCL shows poor response to treatment and predominates among Africans. The small sample size made it difficult to determine whether co-infection with HIV was a coincidental finding or the two diseases are pathophysiologically linked. © 2013 The Japanese Society of Hematology.

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