Browsing by Author "Lunjani, Nonhlanhla"

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    Mechanisms of atopic dermatitis and allergy development in African (AmaXhosa) children between 12-36 months of age
    (2024) Lunjani, Nonhlanhla; Maitin, Thabi
    Atopic dermatitis is a highly complex multifactorial inflammatory skin disease that disproportionately affects children and has increased rapidly during recent years in South Africa. Current data suggest that the changing diversity of environmental exposures, diet, and lifestyle factors across African societies might provide unique disease promoting effects in populations where a low risk of developing AD and allergic disease was previously documented. To identify novel immunological endotypes and responsible environmental exposures in South African children with AD, we collected data on environmental exposures, lifestyle factors, and conducted clinical assessments in 217 children (Urban AD, n=56; Rural AD, n=60; Urban Healthy Controls, n=49; Rural Healthy Controls, n=52). Detailed immunological analysis (cell counts, cytokine levels, serology and RNA-Seq) were performed on 152 of these children. Participants were from the same ethno-linguistic AmaXhosa background. Strong evidence for persistent TH2 responses (elevated circulating eosinophils, allergen-specific IgE, TARC, MCP-4, and IL-16 levels) with reduced TH17 responses (IL-17A and IL-23 levels) were seen in South African children with AD regardless of whether they lived in urban or rural communities. However, independent of AD, a vast array of circulating immune mediators (including proinflammatory cytokines, chemokines, soluble adhesion molecules and growth factors) were associated with early life nutrition, medications, animal exposures, indoor environment, sunlight exposure and household size. RNA sequencing of peripheral blood mononuclear cells corroborated the TH2 cytokine profile identified. Furthermore, multiple immunological pathways (including immunoregulatory factors, aryl hydrocarbon receptor and G protein-coupled receptors) were discovered to be differentially expressed in rural and urban children, regardless of atopic status. The study results address knowledge gaps on the immune interactions between atopic dermatitis and environmental exposures in South African children and clarify population-specific AD endotypes. Overall, protective exposures (e.g., animal) and potentially detrimental (e.g., pollutant) exposures shape the early life innate and adaptive immune response. Lastly, when immune-mediated disorders do occur in children, living environment is worth considering and its effects on background immune profile that can potentially interact with immune-targeting therapies and consequently impact treatment efficacy.
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    Molecular epidemiology of Staphylococcus aureus in African children from rural and urban communities with atopic dermatitis
    (2021-04-13) Ndhlovu, Gillian O N; Abotsi, Regina E; Shittu, Adebayo O; Abdulgader, Shima M; Jamrozy, Dorota; Dupont, Christopher L; Mankahla, Avumile; Nicol, Mark P; Hlela, Carol; Levin, Michael E; Lunjani, Nonhlanhla; Dube, Felix S
    Abstract Background Staphylococcus aureus has been associated with the exacerbation and severity of atopic dermatitis (AD). Studies have not investigated the colonisation dynamics of S. aureus lineages in African toddlers with AD. We determined the prevalence and population structure of S. aureus in toddlers with and without AD from rural and urban South African settings. Methods We conducted a study of AD-affected and non-atopic AmaXhosa toddlers from rural Umtata and urban Cape Town, South Africa. S. aureus was screened from skin and nasal specimens using established microbiological methods and clonal lineages were determined by spa typing. Logistic regression analyses were employed to assess risk factors associated with S. aureus colonisation. Results S. aureus colonisation was higher in cases compared to controls independent of geographic location (54% vs. 13%, p < 0.001 and 70% vs. 35%, p = 0.005 in Umtata [rural] and Cape Town [urban], respectively). Severe AD was associated with higher colonisation compared with moderate AD (86% vs. 52%, p = 0.015) among urban cases. Having AD was associated with colonisation in both rural (odds ratio [OR] 7.54, 95% CI 2.92–19.47) and urban (OR 4.2, 95% CI 1.57–11.2) toddlers. In rural toddlers, living in an electrified house that uses gas (OR 4.08, 95% CI 1.59–10.44) or utilises kerosene and paraffin (OR 2.88, 95% CI 1.22–6.77) for heating and cooking were associated with increased S. aureus colonisation. However, exposure to farm animals (OR 0.3, 95% CI 0.11–0.83) as well as living in a house that uses wood and coal (OR 0.14, 95% CI 0.04–0.49) or outdoor fire (OR 0.31, 95% CI 0.13–0.73) were protective. Spa types t174 and t1476, and t272 and t1476 were dominant among urban and rural cases, respectively, but no main spa type was observed among controls, independent of geographic location. In urban cases, spa type t002 and t442 isolates were only identified in severe AD, t174 was more frequent in moderate AD, and t1476 in severe AD. Conclusion The strain genotype of S. aureus differed by AD phenotypes and rural-urban settings. Continued surveillance of colonising S. aureus lineages is key in understanding alterations in skin microbial composition associated with AD pathogenesis and exacerbation.