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Recent Submissions

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Genetic characterisation of epidermolysis bullosa in South African patients
(University of the Witwatersrand, Johannesburg, 2024) Vania, Ashira; Dillon, Bronwyn
Background: Epidermolysis bullosa (EB) is a clinically and genetically heterogeneous inherited skin condition, characterised by the formation of blistering skin lesions in response to minimal abrasive skin trauma, with variable additional clinical complications. EB is divided into four subtypes based on histological characteristics: simplex EB (EBS), junctional EB (JEB), dystrophic EB (DEB) and Kindler syndrome (KS). EB is diagnosed on the basis of family history, and clinical signs and symptoms, in conjunction with histological examination, immunofluorescence mapping and transmission electron microscopy to determine subtype. Where available, molecular genetic testing can identify the causative genetic pathogenic variant/s. There is little recently published research on EB and its genetic aetiology in South African cohorts. The aim of this study was to design a multigene EB panel to investigate the pathogenic genetic variant/s responsible for EB in a group of South African patients, thereby providing information for targeted symptomatic treatment, medical surveillance, and to allow for more accurate genetic counselling and future reproductive options. Methods: Thirteen South African patients with clinically-diagnosed EB were recruited from the genetic clinic in four local State hospitals in Gauteng, South Africa. They were phenotypically characterised in terms of family history of the disorder, clinical features, and histological subtype. Whole exome sequencing was performed and a virtual panel of 11 of the commonly implicated EB-associated genes to screen for pathogenic variants. Genetic variants detected were analysed and classified according to American College of Medical Genetics and Genomics guidelines. Results: The 13 patients all had similar clinical characteristics of generalised skin blistering from birth. Skin biopsy with histopathology examination was available for 7/13 (54%). Histological and electron microscopy investigations correlated with molecular findings in only three cases. A genetic result that either confirmed the clinical diagnosis or supported the clinical diagnosis of EB was found in over half of the study cohort (8/12 (67%)). Three recurring variants were identified; COL7A1 (c.3265C>T), LAMB3 (c.958_1034dup) and LAMB3 (c.1034_1035insGGG; previously unreported). Of the eight patients with a confirmed/supported genetic diagnosis, 50% had JEB and 13% had EBS Conclusion: Of the 13 clinically diagnosed EB patients, 8/13 (67%) could be genetically characterised and three parents had confirmed carrier status; allowing for accurate genetic counselling, in terms of inheritance and recurrence risk information. JEB was seen in a higher frequency and EBS in a lower frequency than would be expected, reflecting a possible ascertainment bias. This study validates the clinical utility of an EB multigene panel for South African patients with EB, with particular focus on COL7A1 and LAMB3
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The relationship between increased Body Mass Index and primary headache disorders in a group of Antiretroviral therapy induced overweight and obese patients
(University of the Witwatersrand, Johannesburg, 2023) Ganesh, Annsureeka
Introduction: Primary headache disorders are highly prevalent and may be found co-morbid with other diseases, including Human Immunodeficiency Virus (HIV). Recent literature has suggested a relationship between increased Body Mass Index (BMI) and primary headaches, although the exact mechanisms are largely unknown and likely diverse. Weight gain following initiation of Antiretroviral therapy (ART) has recently emerged as a complication amongst people living with HIV. This unique population with primary headaches may exhibit an artificially-induced state of obesity, which forms the basis of this study in order to describe the relationship between increased BMI and primary headache disorders. Methods: This was a cross-sectional study involving HIV positive patients on ART who had primary headaches. Participants who fulfilled inclusion criteria were enrolled in the study during their routine clinic visits. An anonymous interviewer-based questionnaire was used to record clinical and demographic data. Participants’ height and weight were measured in order to calculate BMI. Fischer’s exact test was used to investigate the association between the presence of primary headache, severity and frequency of headache and increased BMI. A p- value of less than 0.05 was considered evidence for statistical significance. Results: There was a statistically significant association between female gender and increased BMI (OR 6.02, 95% CI, 1.32-26.21, p-value <0.02). Multivariate regression analysis demonstrated a higher risk of increased BMI amongst participants with features of tension type headache when compared to those with migraine, however this was not statistically significant (OR 2.47, 95% CI, 0.25-24.88, p-value 0.44). There was no statistically significant relationship between increased BMI and the presence of primary headache, type of primary headache, severity, or frequency of headache in this study. Conclusion: This study did not find any statistically significant relationship between increased BMI and primary headache disorders, nor any of their associated characteristics. This may be due to the small sample size, and further studies are needed to corroborate these findings
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Laboratory Evaluation of Aspergillus Galactomannan Lateral Flow Assays
(University of the Witwatersrand, Johannesburg, 2023) Ubbink, Anja; Chibabhai, Vindana
Invasive aspergillosis diagnosis is based on a combination of clinical, radiological, and mycological factors, including the detection of Aspergillus galactomannan antigen in serum and bronchoalveolar lavage fluid (BALF). Lateral flow assays (LFA) introduced for rapid detection of galactomannan in serum and BALF include the IMMY sōna Aspergillus LFA (IMMY LFA) and the Dynamiker QuicGMTM Aspergillus Galactomannan Ag LFA (QuicGM LFA). Objective To evaluate the performance of the IMMY LFA and QuicGM LFA in South Africa. Methods Serum and BALF samples previously tested by Platelia BioRad Aspergillus GM-EIA were analysed using the two different LFAs. Percentage agreement and precision was assessed. Results Forty-six serum- and 13 BALF samples were tested using the IMMY GM LFA and 48 serum- and 6 BALF samples were tested using the QuicGM LFA. Using an optical density ≥0.5 as positive, results were compared to the BioRad Aspergillus GM-EIA. For the IMMY LFA, serum samples had a positive percent agreement (PPA) of 0% (0/1); negative percent agreement (NPA) of 91% (41/45) and overall percent agreement (OPA) of 89% (41/46). BALF samples had a PPA of 75% (3/4), NPA 50% (5/10) and OPA of 57% (8/14). For the QuicGM LFA, serum samples had a PPA 0% (0/3), NPA of 96% (43/45) and OPA of 90% (43/48). BALF samples had a PPA of 100% (1/1), NPA of 100% (5/5) and OPA of 100% (6/6). For the IMMY LFA, between-day reproducibility for 72% (13/18) and 63% (5/8) for serum and BALF samples, respectively. Between-batch reproducibility was 89% (16/18) and 50% (4/8), respectively for serum and BALF samples. For the QuicGM LFA, between-day reproducibility was 75% (9/12) and 75% (3/4) for the serum and BALF samples, respectively. The between-batch reproducibility was 100% (8/8) for serum and 100% (3/3) for BALF. Conclusion A follow-up evaluation with a larger sample size utilizing clinical, radiological, and laboratory data is warranted to determine the assays’ clinical utility. What this study adds Invasive aspergillosis is a life-threatening disease, where a prompt diagnosis improves outcome. Currently there is no Aspergillus galactomannan assay available in the South African state sector. This study evaluates two lateral flow assays for the detection of Galactomannan in South Africa