Browsing by Author "Levin, Michael"
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- ItemOpen AccessAntigenic and immunological determinants of acute allergic susceptibility to meat in a uniquely defined cohort in the Eastern Cape(2023) Murangi, Tatenda; Levin, Michael; Horsnell WilliamAllergic sensitization can occur after allergen exposure through the oral-mucosal or cutaneous route. Allergic remission is associated with a decrease in total and specific IgE levels to allergens. Ascaris lumbricoides is a potent inducer of IgE through the establishment of a strong Th2 environment. IgE induction following A. lumbricoides infection is a risk for allergic sensitization. Tick disruption of host skin during feeding has a systemic effect resulting in the induction of a Th2 phenotype with elevated IgE production. Raised IgE can be driven by exposure to parasite proteins and lipids with complex glycosylation patterns. Our study demonstrates the presence of alpha-gal in both adult and larval developmental stages of A. lumbricoides, Amblyomma hebraeum and Rhipicephalus evertsi. Alpha-gal glycosylation was prominent on 100kDa and 130-250kDa protein bands. A. hebraeum and R. evertsi showed differential expression of alpha-gal glycosylated proteins during feeding with band intensity increasing proportionally to an increase in feeding time in the salivary glands. Immunolocalization of alpha-gal in A. lumbricoides adult worms showed staining in the lining of the gastrointestinal tract while in A. hebraeum and R. evertsi, staining was prominent in the salivary glands. Screening for IgE demonstrated elevated IgE to A. lumbricoides in human research participants with challenge-proven alpha-gal allergy which positively correlated to alpha-gal IgE. Furthermore, non-alpha gal glycosylated A. lumbricoides antigens caused significant activation of a humanized rat basophil RS-ATL8 IgE reporter cell system after incubation with sera from alpha-gal allergic individuals. Interestingly, serum IgG4 from alphagal allergic individuals showed surface labelling of A. lumbricoides larvae invitro. Alpha-gal positive participants also demonstrated raised IgE and IgG4 towards A. hebraeum proteins. Proteomic analysis suggests alpha-gal glycosylation to be present on alpha-2-macroglobulin found in lysates from both A. lumbricoides and A. hebraeum. These findings present A. lumbricoides, A. hebraeum and R. evertsi as potential sources of sensitization to alpha-gal and hypersensitivity reactions including anaphylaxis in humans after the consumption of red meat or use of pharmaceutical products from a mammalian source
- ItemOpen AccessBetter recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy: iMAP—an international interpretation of the MAP (Milk Allergy in Primary Care) guideline(BioMed Central, 2017-08-23) Venter, Carina; Brown, Trevor; Meyer, Rosan; Walsh, Joanne; Shah, Neil; Nowak-Węgrzyn, Anna; Chen, Tong-Xin; Fleischer, David M; Heine, Ralf G; Levin, Michael; Vieira, Mario C; Fox, Adam TCow’s milk allergy (CMA) is one of the most common presentations of food allergy seen in early childhood. It is also one of the most complex food allergies, being implicated in IgE-mediated food allergy as well as diverse manifestations of non-IgE-mediated food allergy. For example, gastrointestinal CMA may present as food protein induced enteropathy, enterocolitis or proctocolitis. Concerns regarding the early and timely diagnosis of CMA have been highlighted over the years. In response to these, guideline papers from the United Kingdom (UK), Australia, Europe, the Americas and the World Allergy Organisation have been published. The UK guideline, ‘Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy—a UK primary care practical guide’ was published in this journal in 2013. This Milk Allergy in Primary Care (MAP) guideline outlines in simple algorithmic form, both the varying presentations of cow’s milk allergy and also focuses on the practical management of the most common presentation, namely mild-to-moderate non-IgE-mediated allergy. Based on the international uptake of the MAP guideline, it became clear that there was a need for practical guidance beyond the UK. Consequently, this paper presents an international interpretation of the MAP guideline to help practitioners in primary care settings around the world. It incorporates further published UK guidance, feedback from UK healthcare professionals and affected families and, importantly, also international guidance and expertise.
- ItemOpen AccessCorrection to: Better recognition, diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy: iMAP—an international interpretation of the MAP (Milk Allergy in Primary Care) guideline(BioMed Central, 2018-01-25) Venter, Carina; Brown, Trevor; Meyer, Rosan; Walsh, Joanne; Shah, Neil; Nowak-Węgrzyn, Anna; Chen, Tong-Xin; Fleischer, David M; Heine, Ralf G; Levin, Michael; Vieira, Mario C; Fox, Adam TAbstract In the original version of this article [1], published on 23 August 2017, an incorrect version of Additional file 4 has been used. The corrected version of Additional file 4 is given in this correction.
- ItemOpen AccessCorrelation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans(2016) Laurence, Craig; Levin, MichaelBackground: Asthma and allergic disease are the result of a complex interaction between genetic predisposition and environmental exposure. It is likely that multiple genes are involved in the progression from allergen exposure to the development of signs and symptoms of allergic disease. Although advances in genetic research have progressed exponentially in the past twenty years, and a growing body of evidence from the developed world has yielded several promising candidate polymorphisms, the precise nature of the genetic basis for allergic disease remains to be elucidated. In addition, there is a paucity of literature in this field from the developing world, and for people of African origin in particular. Several studies suggest that the prevalence of asthma and allergic disease in South Africa has increased significantly over the past forty years, at a rate that is too rapid to be explained by genetic modification. A likely explanation for this trend is that an increasing number of genetically susceptible individuals are being exposed to environmental stimuli that are critical to the formation of allergic disease. It is possible, although unproven, that evolutionary adaptation of inflammatory immune responses may increase the genetic predisposition to allergic disease amongst people of Black African origin. This thesis represents the first analysis of several single nucleotide polymorphisms (SNPs) with regards to their prevalence in the Xhosa population, as well as the correlation between these SNPs and clinical and laboratory markers of allergic disease in this population. Methods: A cross-sectional sample of about 300 unrelated Xhosa school children was obtained from a local high school. Phenotypic data was collected in the form of a symptom questionnaire, blood samples for total IgE as well as IgE to Ascaris lumbricoides, skin prick tests to common local food and aeroallergens, as well as a modified methacholine challenge to establish the prevalence of bronchial hyper-reactivity. In addition, genotyping was performed to investigate the prevalence of twenty-seven SNPs in this population. We aimed to establish a baseline of the prevalence of potential pro-inflammatory alleles (PIAs), as well as to investigate the relationship between these PIAs and clinical and laboratory markers of asthma and allergic disease. Results: We found several significant associations between several SNPs and allergic disease, specifically in genes relating to the development of immune tolerance (IL-10), genes relating to TH1 inflammation (IL-12 and IFNGR1) and genes relating to TH2 inflammation (IL-4, IL- 4R, IL-13). Unfortunately, the generalizability of our findings is limited by, amongst others, the selection of pupils from a single school and the use of self-reported end points as markers of clinical phenotypes rather than physician diagnosed allergic illnesses. Conclusion: This is the first trial of its kind in the Xhosa population. Despite the limitations described above, we feel that this study has provided valuable baseline prevalence data, and unearthed some interesting associations between PIAs and allergic disease. We would welcome further research in this population to confirm or refute our findings.
- ItemOpen AccessDiscordant definitions of medical terminology and their impact on communication between English-speaking doctors and Xhosa-speaking parents at a paediatric hospital(2005) Levin, Michael; Weinberg, Eugene[page 312 missing] This thesis falls into the broad area of applied linguistics, in the field of medical communication. The central problem which I investigate is the imperfect communication that takes place between largely English-speaking doctors and largely Xhosa-speaking parents. Some of the problems result from lack of bilingualism or asymmetrical bilingualism; however, even if bilingualism were to be achieved, communication difficulties might still persist in relation to what I call discordant terminology between the two languages.
- ItemOpen AccessEnvironmental and occupational respiratory diseases - 1040. Associations between asthma and bronchial hyper-responsivness with allergy and atopy phenotypes in urban black South African teenagers(BioMed Central Ltd, 2013) Levin, Michael; Muloiwa, Rudzani; Motala, CassimEpidemiological studies in South Africa show increasing prevalence rates of asthma and allergic sensitisation in both urban and rural Black African communities, and narrowing of the urban-rural gradient. There is a paucity of current data on bronchial hyper-responsiveness (BHR) in urban Black African children, associations between asthma and BHR and the relationship between BHR, allergen sensitisation and other atopic diseases.
- ItemOpen AccessEosionphilic oesophagitis in Cape Town, South Africa(BioMed Central Ltd, 2011) Levin, Michael; Motala, CassimEosinophilic oesophagitis has been described in patients from all ethnic backgrounds in studies originating in all continents apart from Africa. A cohort of 8 patients (3 boys, 5 girls) identified at Red Cross Hospital during 2009-2010 is described. Average age 7 years (1yr 11 months to 15 years 10 months). Ethnicity 2 caucasian, 5 mixed, 1 Black African. Age of onset: mean 3 years, median 1 year 4 months. Age of diagnosis mean 6years 3 months, median 3 years 9 months. Time to diagnosis: mean 3 years 3 months, median 6 months, IQ range 5 months to 6 years. Presenting symptoms in order of prevalence are reflux (7/8), long time to eat (6/8), difficult swallowing (6/8), growth failure (5/8), food refusal (5/8) and painful swallowing (4/8).
- ItemOpen AccessEvaluating the implementation of a paediatric allergy-training programme in urban primary care centres in Cape Town, South Africa(2022) Ortel, Randall Shane; Levin, Michael; Ras, TasleemBackground: Approximately a third of South Africans have suffered from some allergic disease during their life, with the highest burden of morbidity occurring in childhood. Despite the incidence and prevalence of allergic diseases steadily increasing worldwide in the past few years, it has not yet been met with an increased capacity to treat these conditions. Inappropriate management in primary care, for instance, impacts patient quality of life and leads to increased health care costs, compounded by limited relevant learning opportunities for primary care practitioners (PCP). Studies in a South African context have demonstrated that inadequate management of allergic disorders in children results in unscheduled hospital visits, preventable admissions and a heavy reliance on tertiary allergy services. To address this, the Allergy Foundation of South Africa (AFSA) and Red Cross Children's hospital Allergy unit designed a hybrid in-service training programme in paediatric allergies for PCP's. The training consists of online modules, face-to-face seminars, in reach and outreach support. The aim of this study was to evaluate the implementation of this paediatric allergy training programme. Methods: A cross-sectional observational descriptive design with an analytical component was used. The study population were all staff members who registered for the training programme, with voluntary recruitment into the survey arm of the study. As this is programme-level data, exclusion criteria were not applied. Descriptive data were collected from registration and attendance registers, and survey data in the form of an online self-administered questionnaire which explored three domains: accessibility; relevance to practice and acceptability. Results: Three hundred and forty staff members registered for the training programme, and 89 participated in the survey by completing the self-administered questionnaire. Of the staff enrolled in the training programme, 215 were doctors, 66 were nurses, 2 were facility managers, and 2 were pharmacists. Job categories of 55 staff who registered could not be determined. The throughput rate for the online component was 35.3% (120/340), and for the practical's, it was 49.2% (59/120), with an overall throughput rate of 17.4% (59/340). Medical officers were more likely to complete the training programme (online component: OR 5.4, (95% CI) 1.54 – 21.3, p = 0.011; practical component: OR 4.37, (95% CI) 1.33 – 15.5, p = 0.18) when compared to the nurses in this study. Having easy access to the training programme (OR 2.42; 95% CI 1.48 – 4.39; p= 0.001), senior or mentor support (OR 1.54; 95% CI 1.05 – 2.29, p= 0.035), having enough allocated time to complete the programme (OR 5.34; 95% CI 2.88 – 11.8, p 0.9) for the training of this nature requiring regular coursework was not associated with the completion of the training programme. The roll-out of the training programme was significantly impacted by the COVID-19 pandemic, which prevented any further training from March 2020. Conclusions: This study showed that significant contextually relevant factors impact the implementation of innovations aimed at improving clinical quality in primary care. Developing a deep understanding of these barriers is essential in implementing sustainable quality improvement projects. The study achieved its key outcomes of describing the implementation of the training programme, measuring the accessibility, relevance to practice, the overall acceptability domains of the programme and identifying factors that were enablers or barriers to its implementation.
- ItemOpen AccessLanguage differences as an access barrier for Xhosa speaking patients at a children's hospital in Cape Town(2004) Levin, Michael; Motala, CasThe research documented in this thesis was conducted between November 2002 and March 2003. Rationale for the study. A problem faces many health professionals - that of communication between ourselves and patients who may differ from us in terms of the language spoken, educational level, medical knowledge, models of illnesses, socio-economic status, race and power.
- ItemOpen AccessPolymorphic variation in TIRAP is not associated with susceptibility to childhood TB but may determine susceptibility to TBM in some ethnic groups(Public Library of Science, 2009) Dissanayeke, Shobana Rebecca; Levin, Samuel; Pienaar, Sandra; Wood, Kathryn; Eley, Brian; Beatty, David; Henderson, Howard; Anderson, Suzanne; Levin, MichaelHost recognition of mycobacterial surface molecules occurs through toll like receptors (TLR) 2 and 6. The adaptor protein TIRAP mediates down stream signalling of TLR2 and 4, and polymorphisms in the TIRAP gene ( TIRAP ) have been associated with susceptibility and resistance to tuberculosis (TB) in adults. In order to investigate the role of polymorphic variation in TIRAP in childhood TB in South Africa, which has one of the highest TB incidence rates in the world, we screened the entire open reading frame of TIRAP for sequence variation in two cohorts of childhood TB from different ethnic groups (Xhosa and mixed ancestry). We identified 13 SNPs, including seven previously unreported, in the two cohorts, and found significant differences in frequency of the variants between the two ethnic groups. No differences in frequency between individual SNPs or combinations were found between TB cases and controls in either cohort. However the 558C→T SNP previously associated with TB meningitis (TBM) in a Vietnamese population was found to be associated with TBM in the mixed ancestry group. Polymorphisms in TIRAP do not appear to be involved in childhood TB susceptibility in South Africa, but may play a role in determining occurrence of TBM.
- ItemOpen AccessThe prevalence and patterns of IgE-mediated food allergy and sensitisation in South African children with atopic dermatitis(2014) Gray, Claudia Liesel; Levin, Michael; Du Toit, GeorgeBackground: The prevalence of food allergy in South Africa is unknown, but previously thought to be low, particularly in black South Africans. We hypothesised that food allergies would be low in Xhosa patients, even those at increased risk of food allergy such as children with atopic dermatitis (AD). This study aimed to determine the prevalence of, patterns and risk factors for, IgE-mediated food allergy in South African children with moderate to severe AD. It is the first food allergy prevalence study in South Africa to utilise controlled food challenges and component analysis, and is unique for its comparison of food allergy patterns between ethnic groups in the same geographical area. Methodology: This was a prospective, observational study in a paediatric university hospital in Cape Town. Children with moderate to severe AD, aged 6 months to 10 years, were randomly recruited from the dermatology clinic. They were assessed for sensitisation and allergy by questionnaire, skin prick tests (SPT), Immuno Solid Phase Allergen Chip (ISAC) test and incremental food challenges. Sensitised patients were also tested for specific IgE by ImmunoCAP test. Results: One hundred participants (59 black Africans and 41 of mixed race) were enrolled, median age 42 months. There were high overall rates of food sensitisation (66%) and food allergy (40%). Egg (25%) and peanut (24%) were the most common allergies. Black participants had comparable sensitisation (69% vs 61%) but lower allergy rates (34% vs 46%) than mixed race participants. This was especially evident for peanut allergy (15% vs 37%, p=0.01). Early onset AD (< 6 months), severe eczema, and young age < 2 years were significant risk factors for food allergy. The ISAC test was less sensitive than SPT and ImmunoCAP tests. Only 42% of cases of perceived food allergy were confirmed as true food allergy.
- ItemOpen AccessSevere allergic reactions at a tertiary paediatric service 2014 - 2016(2018) Chippendale, Sa-Eeda; Levin, MichaelIntroduction: Anaphylaxis is a severe, life-threatening generalized hypersensitivity reaction. The European Anaphylaxis Registry was established to review and improve medical management of these patients, facilitate accurate comparisons between centres, highlight public health implications, and examine trends in treatment over time. This is replicated here in a South African setting. Methods: Participants comprised patients treated at Red Cross War Memorial Children’s Hospital (RCWMCH) for severe allergic reactions between January 2014 and August 2016. Recruitment was by applying relevant ICD- 10 coding to the hospital’s clinical summary system of admissions and discharges, the pharmacy’s records of adrenaline autoinjector dispensing, and referrals from the allergy department’s clinical staff. Participants who were screened but did not meet inclusion criteria after preliminary questioning and/or folder review were excluded. 156 episodes were analyzed. A local web-based registry was established, and used to capture data collected via a questionnaire in interviews at the RCWMCH Allergy Clinic. Results: Males, younger children, and participants of coloured ethnicity were more frequently affected. Skin and mucosa was most commonly involved, followed by respiratory and gastrointestinal upset, with cardiovascular and other systemic involvement occurring infrequently. More than 40% of episodes were graded as severe. Specific IgE was the most frequently requested testing. Nearly two-thirds of patients were seen with a recurrent episode. Food-related triggers predominated and decreased with age: particularly peanut, hen’s egg, fish, cashew nuts and cows’ milk. There was a strong correlation with atopic conditions, in excess of international trends. 3 Adrenaline was rarely used, by both lay persons when previously prescribed, and by professional attenders. Hospital admissions were infrequent, and no deaths were recorded. Prophylactic measures were almost universally instituted, but the success thereof could be improved. Conclusion: This is the first local comprehensive description of anaphylactic trends. Further areas of research are suggested: to investigate the propensity for allergic reactions in the coloured population, our much higher rate of association with other atopic disorders compared to international patterns, comparison of our baseline comorbid conditions for contextual analysis, and a review of barriers to care. Ongoing education and training to patients, parents, teachers, and health care workers is identified as a major area requiring intensification.
- ItemOpen AccessThe biodiversity and description of microbiota in traditionally fermented milk products: a study in rural South Africa(2020) de Waal, Pieter Johannes; Levin, MichaelThe rapid rise in allergic diseases has been linked to urbanization and Westernization. Recent observational studies indicate a significantly lower prevalence of allergic disease in children exposed to farming environments during the ante- and postnatal period. Consumption of unpasteurized and fermented cow's milk have been hypothesized as independent protective factors against allergy. Lack of microbial diversity and low levels of lactic acid producing bacteria (LAB) in infant diets may be predisposing factors to developing atopic eczema, allergic sensitisation and asthma. In South Africa, rural communities with a low prevalence of allergy consume unpasteurized and traditional fermented milk products on a regular basis. The objective of this study was to characterize and compare the microbiome of differently sourced cow's milk samples. Raw, unpasteurized cow's milk was collected from farms in an urban and rural setting, respectively. Another sample, collected from a cow on a rural farm, was left to naturally ferment (amasi) while three different brands of commercially fermented milk samples were obtained from a local retail shop. The variable V3 and V4 regions of the 16S rRNA gene were amplified and diversity and abundance plots were constructed and analyzed. Clear differences in the diversity and abundance of especially LAB in the differently sourced samples were demonstrated. Urban, and rural fresh cow's milk samples were the most diverse, and commercially bought products, the least. The commercially fermented products were similarly dominated by LAB, belonging to the phylum Firmicutes (more than 98% abundance) and the phylum Proteobacteria (less than 2% abundance). The homemade fermented milk (amasi) comprised approximately 50% Firmicutes and approximately 50% Proteobacteria. At the family member level, Leuconostocaceae dominated in all three the commercially bought samples. At the species level, Lactococcus lactis (AB100803) dominated in all the milk products, with less abundance in the fresh cow's milk samples. Lactobacillus paracasei (D79212) and Streptococcus infantis (AY485603) were abundant in amasi and absent in the commercially fermented products. Statistically significant difference between fermented and unfermented cow's milk samples at species level were demonstrated. Lactococcus chungangensis (EF694028), Leuconostococcus mesenteroides (AB023247) and Leuconostococcus pseudomesenteroides (AB023237) were abundant in the commercially fermented products, but absent in amasi. Important pathogens were identified in fresh cow's milk and amasi. We concluded that commercially fermented milk, although of low diversity, may be utilized as a safe allergy protective weaning food in infant diets. The microbiome of homemade amasi is more diverse than commercially fermented products and important allergy protective lactic acid producing organisms were identified in this study. However, the safety of amasi remains a concern. This information can be used in future research to produce important allergy protective ‘starter cultures' and to appropriately shape the gut microbiome early in life.