Rural and urban exposures shape early life immune development in South African children with atopic dermatitis and nonallergic children.

BACKGROUND: Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long-term impacts. METHODS: We performed RNA-Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. RESULTS: A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). CONCLUSIONS: This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways.

Skin and nasal colonization of coagulase-negative staphylococci are associated with atopic dermatitis among South African toddlers.

BACKGROUND: Skin colonization with coagulase-negative staphylococci (CoNS) is generally beneficial, but recent investigations suggest its association with flares and atopic dermatitis (AD) severity. However, this relationship remains unclear. OBJECTIVE: To assess patterns of staphylococcal colonization and biofilm formation in toddlers with and without AD from rural and urban South African settings. METHODS: We conducted a cross-sectional study of AD-affected and non-atopic AmaXhosa toddlers from rural Umtata and urban Cape Town, South Africa. CoNS isolates were recovered from lesional, nonlesional skin samples and the anterior nares of participants. Identification of the staphylococci was achieved by MALDI-TOF mass spectrometry. The microtiter plate assay assessed in-vitro biofilm formation. RESULTS: CoNS and S. aureus commonly co-colonized nonlesional skin among cases (urban: 24% vs. 3%, p = 0.037 and rural 21% vs. 6%, p<0.001), and anterior nares in urban cases (24% vs. 0%, p = 0.002) than the control group. S. capitis colonization on nonlesional skin and anterior nares was positively associated with more severe disease in rural (48.3±10.8 vs. 39.7±11.5, P = 0.045) and urban cases (74.9±10.3 vs. 38.4±13, P = 0.004), respectively. Biofilm formation was similar between cases and controls, independent of rural-urban living. CONCLUSION: CoNS colonization is associated with AD and disease severity and may be implicated in AD exacerbations. Studies are needed to understand their underlying pathological contribution in AD pathogenesis.

Environment-dependent alterations of immune mediators in urban and rural South African children with atopic dermatitis.

BACKGROUND: In order to improve targeted therapeutic approaches for children with atopic dermatitis (AD), novel insights into the molecular mechanisms and environmental exposures that differentially contribute to disease phenotypes are required. We wished to identify AD immunological endotypes in South African children from rural and urban environments. METHODS: We measured immunological, socio-economic and environmental factors in healthy children (n = 74) and children with AD (n = 78), in rural and urban settings from the same ethno-linguistic AmaXhosa background in South Africa. RESULTS: Circulating eosinophils, monocytes, TARC, MCP-4, IL-16 and allergen-specific IgE levels were elevated, while IL-17A and IL-23 levels were reduced, in children with AD regardless of their location. Independent of AD, children living in a rural environment had the highest levels of TNFα, TNFß, IL-1α, IL-6, IL-8, IL-21, MCP-1, MIP-1α, MIP-1ß, MDC, sICAM1, sVCAM1, VEGFA, VEGFD and Tie2, suggesting a generalized microinflammation or a pattern of trained immunity without any specific TH polarization. In contrast, IL-15, IL-22, Flt1, PIGF and ßFGF were highest in urban children. Rural healthy children had the lowest levels of food allergen-specific IgG4. Early life nutritional factors, medications, animal exposures, indoor environment, sunlight exposure, household size, household income and parental education levels were associated with differences in circulating cytokine levels. CONCLUSIONS: This study highlights the immunological impact of environmental exposures and socio-economic status in the manifestation of immune endotypes in children with AD living in urban and rural areas, which are important in selecting appropriately matched immunological therapies for treatment of AD.

Molecular epidemiology of Staphylococcus aureus in African children from rural and urban communities with atopic dermatitis.

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.

House dust microbiota and atopic dermatitis; effect of urbanization.

BACKGROUND: Previous studies have shown that a child's risk of developing atopic disease is impacted by both genetic and environmental factors. Because small children spend the majority of their time in their homes, exposure to microbial factors in their home environment may be protective or risk factors for development of atopic diseases, such as atopic dermatitis. METHODS: Dust samples from the homes of 86 Black South African children 12 to 36 months old were collected for analysis of the bacterial microbiome. This case-control study design included children with and without atopic dermatitis from rural and urban environments. RESULTS: Significant differences in bacterial composition and diversity were found when comparing children with and without atopic dermatitis. Furthermore, house dust microbiota was significantly different in rural and urban areas. Differences were best accounted for by higher relative abundance of Ruminococcaceae, Lachnospiraceae, and Bacteroidaceae families in rural compared with urban houses. Levels of Ruminococcaceae were also found to be significantly depleted in the house dust of rural children with atopic dermatitis as compared to control children. CONCLUSIONS: House dust composition may be an important risk factor for the development of atopic disease, and this association may be driven in part by the gut microbiome. Low levels of the Ruminococcaceae family from Clostridia class in particular may explain the association between urban living and atopy. However, further research is needed to elucidate these links.

Associations between Environmental dust composition and Atopic Dermatitis in urban and rural settings.

BACKGROUND: Environmental exposures are involved in the pathogenesis of the allergic phenotype and in determining which individual triggers a person becomes sensitized to. Atopic dermatitis (AD) may modulate these effects through increased penetration through the skin modifying the immune system and AD may be triggered or intensified by environmental exposures. These exposures and immune-modulating factors may differ in urban and rural environments. OBJECTIVES: To compare house dust composition in urban and rural settings and correlate them with AD outcomes. METHODS: Dust samples were collected from the beds of 156 children aged 6 months to 3 years. 42% of participants had atopic dermatitis. Samples were analyzed for bacterial endotoxin, fungal (ß-1,3-glucan) levels, and house dust mite, cockroach, dog, cat, mouse, and peanut allergen. Exposures were compared in urban and rural environments and in participants with and without AD. RESULTS: Endotoxin but not fungal ß-glucan exposure is higher in the environment of healthy controls than children with AD in both urban and rural settings. House dust mite allergen exposure is high in urban and rural settings with Dermatophagoides detected in 100% of samples. Cat and dog allergen exposure mirrors pet ownership patterns which differ slightly between groups and environments. Mouse allergen exposure is higher in urban homes. CONCLUSION: Environmental endotoxin may be protective against AD in both urban and rural settings. There are marked differences in allergen exposure in urban and rural settings, but these are unlikely to be important protective or risk factors.

Molecular IgE sensitization profiles of urban and rural children in South Africa.

BACKGROUND: Allergens can act as disease-triggering factors in atopic dermatitis (AD) patients. The aim of the study was to elucidate the molecular IgE sensitization profile in children with and without AD living in urban and rural areas of South Africa. METHODS: Specific IgE reactivity was assessed in 166 Black South African children aged 9-38 months using a comprehensive panel of microarrayed allergens. According to clinical characterization children fell in four groups, urban AD cases (n = 32), urban controls (non-AD, n = 40), rural cases (n = 49) and rural controls (non-AD, n = 45). RESULTS: IgE reactivity to at least one of the allergens was detected in 94% of urban and 86% of rural AD children. House dust mite (HDM; 81% urban, 74% rural AD) and animal-derived allergens (50% urban, 31% rural AD) were the most frequently recognized respiratory allergens, whereas IgE to pollen allergens was almost absent. Urban AD children showed significantly higher frequency of IgE reactivity (50%) to mouse lipocalin, Mus m 1, than rural AD children (12%). The most frequently recognized food allergens were from egg (63% urban, 43% rural AD), peanut (31% vs 41%), and soybean (22% vs 27%), whereas milk sensitization was rare. α-gal-specific IgE almost exclusively occurred in rural children (AD: 14%, non-AD: 49%). CONCLUSION: Molecular allergy diagnosis detects frequent IgE sensitization to HDM, animal but not pollen allergens and to egg, peanut, and soy, but not milk allergens in African AD children. Urban AD children reacted more often to Mus m 1, whereas α-gal sensitization is more common in rural children likely due to parasite exposure.

The spectrum of skin diseases in a black population in Durban, KwaZulu-Natal, South Africa.

BACKGROUND: Precise knowledge of the prevalence and spectrum of skin diseases in a population allows for effective planning for provision of dermatology services and distribution of resources. There are no published data on the epidemiology of skin disorders in Durban, KwaZulu-Natal. OBJECTIVE: We investigated the prevalence of skin diseases in black African patients attending a predominantly black private healthcare facility and profiled the patients. METHODS: Clinical charts of all black African patients seen between January 2003 and December 2010 in a private practice in Durban were reviewed. The diseases seen were described and the prevalence calculated. RESULTS: A total of 6664 patient charts were reviewed. The five most common conditions were acne, eczemas, dyschromias, infections, and hair disorders. These data agree with reports from other parts of the world. LIMITATIONS: Selection bias was presented by a single private practice, thus data may not be fully representative of our population. CONCLUSION: Acne, eczemas, dyschromias, infections, and hair disorders are, in that order, the five most common disorders encountered.

HIV infection predisposes skin to toxic epidermal necrolysis via depletion of skin-directed CD4⁺ T cells.

BACKGROUND: A greater incidence of adverse cutaneous drug eruptions, including toxic epidermal necrolysis (TEN), occurs among HIV-infected patients. OBJECTIVE: We sought to determine if immunophenotypical differences exist in the inflammatory infiltrates of TEN lesions from HIV-infected individuals versus noninfected individuals. METHODS: The inflammatory infiltrates in 12 cases of TEN from HIV-positive patients were characterized and compared with the infiltrates present in 12 cases of TEN from HIV-negative patients. RESULTS: TEN infiltrates consisted of CD3, CD4, and CD8 immunoreactive T lymphocytes in both the dermis and epidermis. HIV infection was associated with an 8-fold increase in the ratio of CD8(+) to CD4(+) T cells infiltrating the dermis (P = .006) and a decrease in the number of dermal CD4(+) cells (P = .044). There was also a significant decrease in the ratio of CD25(+) to CD4(+) cells in the epidermis of HIV-infected skin (P = .011). LIMITATIONS: This study is limited by small sample sizes. CONCLUSION: A decrease in the number of skin-directed CD4(+) cells and an increase in the ratio of CD8(+) to CD4(+) cells exists in TEN lesions among HIV-infected individuals and likely contribute to an increased risk of developing drug reactions because of the loss of skin-protective CD4(+)CD25(+) regulatory T cells.

Common skin conditions in children with HIV/AIDS.

The most recent Joint United Nations Programme on HIV/AIDS (UNAIDS) data inform us that approximately 2.3 million children were infected with HIV at the end of 2009. The greatest burden of this infection is thrust squarely on the most impoverished healthcare systems in the world. Sub-Saharan Africa is home to at least 68% of the global total of HIV infection of 22.5 million. Although a scale up of antiretrovirals has been one of the UNAIDS priorities, and access to services to prevent mother-to-child transmission has increased, an estimated 370,000 children were newly infected in 2009. Hence, infected mothers continue giving birth to HIV-infected children who require appropriate healthcare to diagnose and treat their underlying immunodeficiency and related disorders. Skin lesions are common in these children as they present with infections common in the general population, albeit more severe. Those lesions that are markers of HIV or AIDS are important signs heralding an improving or declining immune system and the success of antiretrovirals. Cutaneous manifestations of HIV/AIDS can be classified broadly as infections and infestations, inflammatory conditions, tumors, and antiretroviral related. This manuscript discusses the more common skin conditions seen in children infected with HIV so as to improve the diagnosis and therapy administered by healthcare professionals especially in sub-Saharan Africa.