Browsing by Department "Department of Clinical Laboratory Science"
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- ItemOpen AccessAdolescent immunisation in Africa in the decade of vaccines(2019) Abdullahi, Leila Hussein; Hussey, Gregory D.; Wiysonge,Charles S.; Kagina, Benjamin M.N.Rationale: There are many public health benefits of targeting adolescent for immunisation. However, and in many settings, adolescents do not get optimal benefits from immunisation. In the decade of vaccines (2011-2020), adolescent immunisation is a topical subject. An up-to-date and synthesized research on adolescent immunisation is lacking. Overall purpose: The purpose of the PhD thesis was to characterize adolescent immunisation in the decade of vaccines. Research methods: First, we conducted a comprehensive narrative review of the literature (chapter 2) on adolescent immunisation. Then, we conducted systematic reviews (chapters 3 and 4). One of the systematic reviews assessed the strategies to improve uptake of vaccines among adolescents. The other systematic review assessed the knowledge, attitudes and practices of adolescents and their parents and teachers towards immunisation. Finally (chapter 5), we conducted a cross-sectional study to describe the challenges experienced, and lessons learnt during the introduction of national human papillomavirus (HPV) vaccination programmes in Africa. Findings: Adolescents are an important group to target with primary, booster or catch up immunisation. Some global initiatives have advocated for adolescent immunisation. Multiple reasons, among them, lack of knowledge and access to immunisation services are barriers to adolescent immunisation. There exist multiple strategies to improve uptake of vaccines among adolescents. For example, health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. The evidence suggests that a combination of strategies may be more effective than one strategy alone in enhancing uptake of vaccines by adolescents. Knowledge of vaccines, immunisation and vaccine preventable diseases was found to be suboptimal among key stakeholders of adolescent immunisation in Africa. We found a disconnect between the level of knowledge on immunisation and the uptake of vaccines, an interesting finding that warrants further research in Africa. Six African countries shared the lessons learnt and experiences during the national introduction of HPV vaccination programmes that targeted adolescent girls. There were similarities in the results among the participating countries. The challenges included: logistical coordination, identification of the target population, obtaining political support, integration with other school programmes and stakeholder engagement. A lesson learnt was that schools are a convenient site to access and vaccinate adolescents. Conclusion: Adolescent immunisation is not routinely practiced in many countries. The introduction of HPV vaccines has created an ideal opportunity to build platforms for adolescent immunisation. Research on adolescent immunisation is limited, more so in low and middle-income countries. Existing research shows a combination of strategies can be used to enhance uptake of vaccines among adolescents. Strong advocacy programmes are required to drive the global agenda of adolescent immunisation, particularly in Africa.
- ItemOpen AccessAssessment of the effectiveness of electronic gatekeeping as a utilization management tool at Groote Schuur Hospital(2018) Bosman, Michelle; van der Watt, George; Omar, Fierdoz; Vreede, HelenaBACKGROUND: Utilization management ensures the appropriateness of laboratory testing by reducing the performance of tests which can be reasonably avoided with no adverse effects for the patient. Electronic gatekeeping, a utilization management tool, was introduced at Groote Schuur in 2010. Criteria were based on the minimum retesting interval, healthcare location, level of experience and discipline of the requesting clinician and specific ICD-10 codes. METHODS: A retrospective observational study assessing the effectiveness of electronic gatekeeping at Groote Schuur Hospital (Cape Town, South Africa), by comparing the test request volumes by using absolute test numbers and pre-defined ratios in the year prior to gatekeeping, to the two years following implementation. A secondary aim is to apply selected ratios to the other national academic hospitals to determine the potential for cost saving. RESULTS: At the medical wards of Groote Schuur Hospital there was an overall decrease in number and cost of tests of 24% per inpatient day for 2011. The most dramatic difference in cost is seen for chloride (91%) followed by HbA1c (90%), FT3 (89%) and CRP (82%). The application of ratios to Groote Schuur Hospital show a decrease in 2011 in all ratios apart from PCT: FBC+WCC (0.003 vs 0.002) and Mg: Ca (0.86 vs 0.84). AST: ALT remained the same at 0.55. This suggests overall effectiveness of the eGK rules although there is ongoing panel requesting. If the GSH eGK rules were to be applied at all other national academic hospitals, it could translate into a potential cost saving of $13 411 873.96 (R103 196 838.80) per annum. CONCLUSIONS: Electronic gatekeeping is an effective utilization management tool at Groote Schuur Hospital. It is relatively easy to implement and manage, and when combined with additional tools has the potential to result in larger reductions of unnecessary tests, cost savings and improved patient outcome.
- ItemOpen AccessCharacterization of Mycobacterium tuberculosis isolates with discordant rifampicin susceptibility test results(2018) Ghebrekristos, Yonas; Beylis, Natalie; Nicol, Mark PBackground: The Xpert MTB/RIF assay was adopted as the initial diagnostic test for patients with presumptive tuberculosis (TB) by the South African National TB Control programme in December 2010. Rifampicin (RIF) resistance detected by the Xpert MTB/RIF (Xpert) is confirmed by a line probe assay (LPA) (GenoType MTBDRplus) and/or phenotypic (culture-based) drug susceptibility testing (DST) by MGIT (Mycobacterial Growth Indicator Tube) on the culture isolate from a 2nd specimen. Although both the Xpert and LPA target the rifampicin resistance determining region (RRDR) of the rpoB gene, discordant RIF results (Xpert RIF resistant (RIFR ), LPA RIF susceptible (RIFS )) have been reported. In addition, in cases where genotypic tests detect an rpoB mutation, inferring RIF resistance, routine phenotypic DST may report a RIF susceptible result. This is usually due to disputed rpoB mutations. Aim: The aims of this study are to determine 1) whether the discordance between Xpert and LPA is due to false RIFR by Xpert or false RIFS by LPA and to elucidate the causes of false results and 2) the frequency and types of rpoB mutations expected to test susceptible on routine phenotypic DST and their corresponding RIF MIC (minimum inhibitory concentration). Methods: Consecutive isolates with discordant Xpert RIFR and LPA RIFS results were selected during routine review. For the Xpert, parameters including bacterial DNA load and cycle threshold (Ct) of the probes were evaluated. In addition, isolates with a pattern of any absent rpoB WT band and absent MUT band on the LPA strip (“miscellaneous rpoB mutations”) were selected for MIC testing using the MGIT 960 system and EpiCenter TB eXiST software. Sanger sequencing of the rpoB gene from codon 462 to 591 was performed on all selected isolates. Results and discussion: Discordant Xpert/LPA results: From the total of 1542 patients with RIFR results by Xpert, 106 (6.9%) had a discordant LPA RIFS result. Sequencing results were available for 101 isolates of which 78 (77.2%) had no rpoB mutation detected and these were categorized as false RIFR by Xpert. Mutations were detected by sequencing in the remaining 23 (22.8%); these were categorized as false RIFS by LPA. Probe delay occurred in 56/76 (73.7%) cases compared with 104/1436 (7.2%) controls (p 4 and there is a Very Low bacterial load has a positive predictive value (PPV) of 64.2 % of being false and where the Ct max is between 4.1 and 4.9 with Very Low bacterial load, the PPV of a false result increases to 85.7%. For the false RIFS results by LPA, the majority 11/23 (47.8%) were due to technical errors. In 6/23 (26.1%) it was due to mixed infection and in 2/23 (8.7%) there was laboratory mix up. In the remaining 4/23 (17.4%) the cause could not be determined and mixed infection or a laboratory mix up could not be excluded. Discordant genotypic/phenotypic results: RIF resistance was detected in 1502 patients by LPA, of which 169 (11.3%) had a miscellaneous mutation. In addition, a further 21 isolates were selected from “Part 1” of the study, where sequencing confirmed that the rpoB mutation was not one of the high level / high confidence rpoB mutations. A total of 178 isolates had both MIC and rpoB sequencing results. In our study 140/178 (78.7%) isolates with miscellaneous rpoB mutations (n=158) or previously described disputed rpoB mutations (n=20) had MIC values ranging from ≤0.0625 µg/ml to 1.0 µg/ml. An MIC >1.0 µg/m was determined for 38/178 (21.3%) that would have tested RIFR by MGIT DST. Conclusion: Arising from this study is a laboratory based guideline that is now used within NHLS TB laboratories detailing steps on how to detect possible false RIFR results by Xpert MTB/RIF and on how to troubleshoot discordant Xpert RIFR and LPA RIFS results. A database has been created from the results obtained in this study that lists specific rpoB mutations and their corresponding MIC value and has the potential to assist clinicians in individualizing the patient TB treatment regimen.
- ItemOpen AccessExploring the Medico-legal death scene investigation of sudden unexpected death of infants admitted to Salt River mortuary, Cape Town, South Africa(2018) Bennett, Tracy; Heathfield, Laura; Martin, LornaA death scene investigation (DSI) forms an integral part of the inquiry into death, particularly for sudden unexpected death of infants (SUDI). Global guidelines exist for DSI, however, it is unclear how many countries adhere to them, and to what extent they are followed. Therefore, a systematic literature review was undertaken to assess the scope of SUDI DSI performed internationally. It was found that national protocols have been established in some countries, and have shown value in guiding medico-legal examinations. Further, South Africa did not routinely perform DSI for SUDI cases, nor was there a protocol. This was largely attributed to the burden of SUDI cases as well as the lack of resources. Therefore, this study aimed to suggest realistic and feasible ways to improve DSI for local SUDI cases. This research study consisted of three phases: 1) A twoyear review of medico-legal case files from SUDI cases investigated at Salt River Mortuary; 2) The prospective observation of DSI for ten SUDI cases, using a semi-structured checklist; and 3) he distribution and analysis of a survey regarding SUDI DSI to all registered, qualified forensic pathologists in South Africa. The results showed that the SUDI death scenes were assessed in 59.2% of cases at Salt River Mortuary, with inconsistent levels of documentation or photography. Death scenes were never investigated in cases where the infant was pronounced dead on arrival at a medical facility. In both scene observations (n=10) and retrospective analysis (n=454) only one case incorporated a re-enactment, but the majority of infants were moved prior to DSI. The findings support the need for a standardised approach to DSI, coupled with specialised training for staff. Based on the available resources, this should focus on the establishment of guidelines pertaining to photography, handling medicine and scene reconstruction, as well as accurate use of relevant documentation.
- ItemOpen AccessExpression levels of miRNA-127 in a cohort of HIV-positive and HIV-negative Diffuse Large B-Cell Lymphoma.(2018) Olivier, Chera; Naidoo, Richard; Govender, DhirenDiffuse Large B Cell Lymphoma is one of the most common Non-Hodgkin’s Lymphomas. It is prevalent in older age patients but as of late there has been a rise in the younger population in South Africa due to the rise of HIV. DLBCL is quite an aggressive cancer but can be treated, however the relapse rate is high. There are prognostic indicators which can be seen as factors which can be indicative of a poor outcome for patients. Micro-RNA(miRNA) are small non-coding RNA which can remain stable to be tested. There are several miRNAs which may be linked to prognosis, including miRNA-21 whose upregulated expression has been associated with bad prognosis. However, this is not specific to DLBCL and some studies done have indicated that there may be other miRNAs which are better suited to be biomarkers for DLBCL. Studies have pointed to the direction of miRNA127 as a more reliable microRNA in its association with prognosis in breast, cervical and gastric cancer as well as DLBCL. Objective: The primary aim of this study was to determine the association between miRNA127 and prognostic markers including immunohistochemical stains, survival status and the IPI factor to determine its significance as a prognostic indicator. An additional aim was to determine the correlation between HIV status and expression level of miRNA-127. Design: A total of 42 DLBCL cases were collected from the archive of Division of Anatomical Pathology, University of Cape Town/NHLS Groote Schuur. The H&E slides were assessed before RNA was extracted from FFPE tissue and converted to cDNA. Real time quantitative RT-qPCR was used to assess the expression of the microRNA. Normal tissue as well as reactive lymph node tissue were used as controls. The expression patterns were also correlated to the clinical information to determine if there was any relationship. Results: Out of the 42 cases used, 10 cases were silenced, and 31 cases had high miRNA-127 expression. The expression levels were correlated with the IPI factors and the other clinicopathologic features however no significant conclusion were determined. Conclusion: We found high expression of miRNA-127 cases in the majority of the DLBCL cases. There was no correlation between HIV status and the expression of miRNA-127, nor between the expression and any of the clinicopathological feature. For future studies it is advised that more equally distribution of samples (both HIV status and gender) are obtained, this will allow for a better comparative study.