Johannesburg, South Africa
Johannesburg, South Africa

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Fitzgibbon J.E.,National Institute of Allergy and Infectious Diseases | Wallis C.L.,Lancet Laboratories
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

There are many challenges to performing clinical research in resource-limited settings. Here, we discuss several of the most common laboratory issues that must be addressed. These include issues relating to organization and personnel, laboratory facilities and equipment, standard operating procedures, external quality assurance, shipping, laboratory capacity, and data management. Although much progress has been made, innovative ways of addressing some of these issues are still very much needed. Copyright © 2013 by Lippincott Williams & Wilkins.


George J.A.,University of Witwatersrand | Norris S.A.,University of Witwatersrand | van Deventer H.E.,Lancet Laboratories | Crowther N.J.,University of Witwatersrand
PLoS ONE | Year: 2013

Introduction: Though inconsistent, a number of studies have shown an association between vitamin D (25(OH)D) status, parathyroid hormone (PTH) and the metabolic syndrome (Met S). These have largely been carried out in Caucasians or black subjects living in high income countries. There no data on the relationship of 25(OH)D and PTH status with Met S in populations resident in Africa. The aims of this study were to evaluate if there was an association of 25(OH)D or PTH with Met S in non-Caucasian populations in South Africa, and whether these molecules explained ethnic differences in the prevalence of Met S and its individual components. Methods: We measured anthropometry, serum 25(OH)D and PTH levels and the components of Met S, plus related metabolic variables, in 374 African and 350 Asian Indian healthy adults from the greater Johannesburg metropolitan area. Results: Met S was diagnosed in 29% of the African and 46% of the Asian Indian subjects (p<0.0001). Subjects with Met S had higher PTH than those without Met S, (p<0.0001), whilst 25(OH)D levels were not significantly different (p = 0.50). In multivariate analysis, 25(OH)D was not associated with any components of the Met S however PTH was shown to be positively associated with systolic (p = 0.018) and diastolic (p = 0.005) blood pressures and waist circumference (p<0.0001) and negatively associated with HOMA (p = 0.0008) levels. Logistic regression analysis showed that Asian Indian ethnicity (OR 2.24; 95% CIs 1.57, 3.18; p<0.0001) and raised PTH (OR 2.48; 95% CIs 1.01, 6.08; p = 0.04; adjusted for 25(OH)D) produced an increased risk of Met S but 25(OH)D did not (OR 1.25; 95% CI 0.67, 2.24; p = 0.48). Conclusions: Plasma PTH but not 25(OH)D is an independent predictor of the Met S in African and Asian Indians in South Africa. © 2013 George et al.


George J.A.,University of Witwatersrand | Norris S.A.,University of Witwatersrand | Van Deventer H.E.,Lancet Laboratories | Pettifor J.M.,University of Witwatersrand | Crowther N.J.,University of Witwatersrand
British Journal of Nutrition | Year: 2014

Vitamin D deficiency has been implicated in the aetiology of infectious diseases and metabolic syndrome. These diseases are prevalent in the African and Asian-Indian populations of South Africa; however, there is limited data on 25-hydroxyvitamin D (25(OH)D) concentrations in these populations. The aim of the present study was to assess the vitamin D status and its predictors in healthy adults in Johannesburg. We assessed the vitamin D status of 730 adult African and Asian-Indian subjects residing in Johannesburg. The contributions of sun exposure, season, dietary intake of Ca and vitamin D, total body fat and body fat distribution to 25(OH)D concentrations were assessed. The concentrations of 25(OH)D were measured by HPLC. The contribution of 25(OH)D3 to total 25(OH)D concentrations was assessed. The mean age of the subjects was 42·6 (sd 13·1) years (range: 18-65). Concentrations of 25(OH)D < 30 nmol/l were found in 28·6 % of the Asian-Indian subjects in comparison with 5·1 % of the African subjects (P< 0·0001). Parathyroid hormone (PTH) concentrations were negatively associated with 25(OH)D concentrations, while season and sun exposure were positive predictors explaining 16 % of the variance in 25(OH)D concentrations (P< 0·0001) in the African subjects. In the Asian-Indian subjects, PTH concentrations were negatively associated with 25(OH)D concentrations, while male sex, season and Ca supplementation were positive predictors and explained 17 % of the variance in 25(OH)D concentrations (P< 0·0001). In the multivariate regression analysis, neither total body fat nor body fat distribution was predictive of 25(OH)D concentrations in either group. In conclusion, factors such as sun exposure, dietary supplement use and ethnicity are important determinants of plasma 25(OH)D concentrations. © 2014 The Authors.


Peirano G.,University of Calgary | Moolman J.,Lancet Laboratories | Pitondo-Silva A.,University of Sao Paulo | Pitout J.D.D.,University of Calgary
Scandinavian Journal of Infectious Diseases | Year: 2012

A study was designed to characterize a carbapenem-resistant Klebsiella pneumoniae (KPSA01) isolated from a patient in Gauteng, South Africa without recent travel outside South Africa. Molecular characterization was done using isoelectric focusing, polymerase chain reaction and sequencing for blaVIM, blaIMP, blaNDM, blaCTX-Ms, blaOXAs, blaTEMs, and blaSHV, plasmid-mediated quinolone resistance determinants, multilocus sequencing typing, plasmid replicon typing, and addiction factors. KPSA01 produced VIM-1 and belonged to the newly described sequence type ST569. The plasmid that harboured blaVIM typed within the narrow host range IncF replicon group, contained the aadA1 gene cassette, and tested positive for the vagCD and ccdAB addiction systems. This is the first report of VIM-1-producing K. pneumoniae outside Europe. It is important that surveillance studies be undertaken in Africa to determine if VIM-1-producing K. pneumoniae are present in significant numbers. © 2012 Informa Healthcare.


Rubin J.E.,University of Calgary | Rubin J.E.,University of Saskatchewan | Peirano G.,University of Calgary | Peer A.K.,Lancet laboratories | And 2 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2014

We describe 4 patients infected with NDM-1 Enterobacter cloacae, Citrobacter freundii, and Serratia marcescens from South Africa that co-produced SHV-12, CTX-M-3, and CTX-M-15 and were positive for qnrS, qnrA, aac(6')-Ib-cr, rmtF, rmtC, and armA. Plasmids belonged to IncN, IncA/C replicon types with ccdAB and vagC/D addiction factors. Local and imported cases of NDM-producing bacteria co-exist within South Africa. © 2014 Elsevier Inc.


Masenya M.,Lancet Laboratories
Obstetrics and Gynaecology Forum | Year: 2011

The human papilloma virus has been shown to play a significant aetiological role in invasive cervical cancer. The changes caused by human papilloma virus can be evaluated using Pap smear. The discovery of Pap smears has led to an unprecedented dramatic decline in the incidence of cervical cancer over the past five decades. This has been the case in high income countries due to effective cervical cancer screening programmes. The effectiveness of this simple cost-effective tool has led to attempts at improving the quality of the Pap smear sample as well as the processing technique in the laboratory. This has led to the introduction of Liquid based cytology, a technique slowly replacing conventional cytology in the world due to its advantages. Although initially thought to be more sensitive and specific than conventional cytology, recent studies suggest that there are no significant differences in this aspect. The main advantage is that Liquid based cytology is less likely to be unsatisfactory or limited. Liquid based cytology has also reduced the screening time leading to improved turn-around time. The specimen submitted for liquid based cytology can be used to perform further tests such as molecular and microbiological studies. The Pap smear still plays an integral part in cervical cancer screening, despite recent advances in detection of human Papilloma virus using molecular techniques. The implementation of cervical screening programmes in low and middle income countries will assist in reducing the mortality related to invasive cervical cancer.


Moolman J.,Lancet Laboratories | Pitout J.,University of Calgary
South African Medical Journal | Year: 2012

We describe the first known report of a VIM1 metallo-betalactamase- producing Klebsiella pneumonia outside Europe -confirmed by our colleagues in Canada. The patient had no travel history, and surveillance failed to identify additional cases. The importance of healthcare professionals being diligent in identifying these multi-drug resistant isolates is emphasised.


Van Deventer H.E.,Lancet Laboratories | Soldin S.J.,U.S. National Institutes of Health
Advances in Clinical Chemistry | Year: 2013

This review discusses the state-of-the-art measurement of free and total thyroid hormones in clinical laboratories. We highlight some of the limitations of currently used immunoassays and critically discuss physical separation methods for the measurement of free thyroid hormone. Physical separation methods, such as equilibrium dialysis or ultrafiltration, followed by tandem mass spectrometry for the measurement of free thyroid hormones offer many advantages, which we feel, can deepen our understanding of thyroid hormone metabolism and improve patient diagnosis and care. Problems with direct analogue immunoassay methods for FT4/FT3 as well as immunoassay methods for total T3 at low T3 concentrations and during pregnancy are highlighted. Improved diagnosis and patient management can be achieved utilizing tandem mass spectrometry for these measurements. © 2013 Elsevier Inc.


Cheuk W.,Queen Elizabeth Hospital | Beavon I.,Lancet Laboratories | Chui D.T.Y.,Queen Elizabeth Hospital | Chan J.K.C.,Queen Elizabeth Hospital
International Journal of Gynecological Pathology | Year: 2011

Solid pseudopapillary neoplasm, an uncommon, intriguing, low-grade malignant tumor of the pancreas, can exceptionally occur in extrapancreatic sites. We report 1 such case occurring as an ovarian primary in a 25-year-old woman, who presented with abdominal fullness. She remained well 12 years after resection of the 1.7-kg right ovarian tumor. Histologically, the tumor showed a solid, dehiscent, and pseudopapillary growth, traversed by fibrous septa and arborizing blood vessels. The polygonal tumor cells had round nuclei, fine chromatin, and lightly eosinophilic granular cytoplasm. In certain areas, eosinophilic hyaline globules were present. On immunostaining, the tumor cells were positive for β-catenin (nuclear translocation), CD10, CD56, and synaptophysin (focal), and were negative for cytokeratin, E-cadherin, and chromogranin. The morphologic and immunohistochemical features were compatible with those of solid pseudopapillary neoplasm. Review of the literature uncovered 10 cases of extrapancreatic solid pseudopapillary neoplasm with adequate data for analysis. They were seen to occur predominantly in young female patients, who presented with a large tumor mass, similar to their pancreatic counterparts. The most common sites of occurrence were the mesocolon (with ectopic pancreatic tissue) and ovary. Awareness of the existence of this tumor in various extrapancreatic sites is essential to avoid misdiagnosis. © 2011 International Society of Gynecological Pathologists.


Patel V.B.,University of KwaZulu - Natal | Singh R.,University of KwaZulu - Natal | Connolly C.,Biostatistics Unit | Coovadia Y.,University of KwaZulu - Natal | And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Current tools for the rapid diagnosis of tuberculous meningitis (TBM) are suboptimal. We evaluated the clinical utility of a quantitative RD-1 IFN-γ T-cell enzyme-linked immunospot (ELISPOT) assay (T-SPOT.TB), using cerebrospinal fluid cells for the rapid immunodiagnosis of TBM. Objectives: To evaluate the diagnostic utility of the RD1 antigen-specific ELISPOT assay for the diagnosis of tuberculous meningitis. Methods: The ELISPOT assay was evaluated in 150 patients with suspected TBM who were categorized as definite-TBM, probable-TBM, and non-TBM. Culture or polymerase chain reaction positivity for Mycobacerium tuberculosis served as the reference standard. To determine the diagnostic value of the ELISPOT assay, a clinical prediction rule was derived from baseline clinical and laboratory parameters using a multivariable regression model. Measurements and Main Results: A total of 140 patients (81% HIV-infected; median CD4 count, 160 cells/mm3) were included in the final analysis. When comparing the definite-TBM (n = 38) and non-TBM groups (n = 48), the ELISPOT assay (cut point of ≥228 spot-forming cells per 1 million mononuclear cells) was a useful rule-in test: sensitivity 58% (95% confidence interval [CI], 41-74); specificity 94% (95% CI, 83-99). However, ELISPOT outcomes improved when other rapid tests were concurrently used to exclude bacterial (Gram stain) and cryptococcal meningitis (latex-agglutination test) within the non-TBM group. Using this approach, the ELISPOT assay (cut point of ≥46 spot-forming cells) was an excellent rule-in test: sensitivity 82% (95% CI, 66-92); specificity 100% (95% CI, 78-100); positive predictive value, 100% (95% CI, 89-100); negative predictive value, 68% (95% CI, 45-86); area under the curve, 0.90. The ELISPOT assay had incremental diagnostic value compared with the clinical prediction rule. Conclusions: The RD-1 ELISPOT assay, using cerebrospinal fluid mononuclear cells and in conjunction with other rapid confirmatory tests (Gram stain and cryptococcal latex-agglutination test), is an accurate rapid rule-in test for TBM in a TB and HIV endemic setting.

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