Peanut-specific IgE antibodies in asymptomatic Ghanaian children possibly caused by carbohydrate determinant cross-reactivity.

BACKGROUND: The prevalence of peanut allergy has increased in developed countries, but little is known about developing countries with high peanut consumption and widespread parasitic infections. OBJECTIVE: We sought to investigate peanut allergy in Ghana. METHODS: In a cross-sectional survey among Ghanaian schoolchildren (n = 1604), data were collected on reported adverse reactions to peanut, peanut sensitization (serum specific IgE and skin reactivity), consumption patterns, and parasitic infections. In a subset (n = 43) IgE against Ara h 1, 2, 3, and 9 as well as cross-reactive carbohydrate determinants (CCDs) was measured by using ImmunoCAP. Cross-reactivity and biological activity were investigated by means of ImmunoCAP inhibition and basophil histamine release, respectively. RESULTS: Adverse reactions to peanut were reported in 1.5%, skin prick test reactivity in 2.0%, and IgE sensitization (≥0.35 kU/L) in 17.5% of participants. Moreover, 92.4% of those IgE sensitized to peanut (≥0.35 kU/L) had negative peanut skin prick test responses. Schistosoma haematobium infection was positively associated with IgE sensitization (adjusted odds ratio, 2.29; 95% CI, 1.37-3.86). In the subset IgE titers to Ara h 1, 2, 3, and 9 were low (<1.3 kU/L), except for 6 moderately strong reactions to Ara h 9. IgE against peanut was strongly correlated with IgE against CCDs (r = 0.89, P < .0001) and could be almost completely inhibited by CCDs, as well as S haematobium soluble egg antigen. Moreover, IgE to peanut showed poor biological activity. CONCLUSIONS: Parasite-induced IgE against CCDs might account largely for high IgE levels to peanut in our study population of Ghanaian schoolchildren. No evidence of IgE-mediated peanut allergy was found.

Food allergy in Ghanaian schoolchildren: data on sensitization and reported food allergy.

BACKGROUND: Epidemiological data on food allergy are scarce in African countries. We studied the prevalence of food sensitization in Ghanaian schoolchildren. METHODS: Children (5-16 years; n = 1,714) from 9 Ghanaian schools were given parental consent to participate in the study. Adverse reactions and food consumption were determined by a questionnaire and atopy by skin prick testing (SPT) to peanut and 6 fruits. Subjects with positive SPTs were considered cases (n = 43) and matched with at least 1 control (n = 84), using age, sex, and school as matching criteria. Serum samples from case-control sets were analyzed for specific IgE (sIgE) to foods that elicited a positive SPT response in cases. RESULTS: Overall, 11% of 1,407 children reported adverse reactions to foods, and 5% of 1,431 children showed a positive SPT reaction mostly directed against peanut and pineapple (both 2%). Although there was a positive association between adverse reactions and SPT responses to any food allergen in the urban children (adjusted OR = 3.6, 95% CI 1.2-10.8), most of the reported adverse reactions were not in children showing an SPT reaction to the specific food item. sIgE sensitization was very variable for the different foods, ranging from 0 to 100% in cases, and from 0 to 25% among controls. High IgE levels for a food item significantly increased the risk of SPT positivity to any food item in the urban, but not in the rural, schoolchildren. CONCLUSIONS: Specific foods were identified to be allergenic in Ghana. We show a good association between SPT and sIgE in urban, but not in rural, schoolchildren. However, there was no clear association between reported adverse reactions to food and SPT or sIgE.

High body mass index is not associated with atopy in schoolchildren living in rural and urban areas of Ghana.

BACKGROUND: Factors which determine the development of atopy and the observed rural-urban gradient in its prevalence are not fully understood. High body mass index (BMI) has been associated with asthma and potentially atopy in industrialized countries. In developing countries, the transition from rural to urban areas has been associated with lifestyle changes and an increased prevalence of high BMI; however, the effect of high BMI on atopy remains unknown in this population. We therefore investigated the association between high BMI and atopy among schoolchildren living in rural and urban areas of Ghana. METHODS: Data on skin prick testing, anthropometric, parasitological, demographic and lifestyle information for 1,482 schoolchildren aged 6-15 years was collected. Atopy was defined as sensitization to at least one tested allergen whilst the Centres for Disease Control and Prevention (CDC, Atlanta) growth reference charts were used in defining high BMI as BMI ≥ the 85th percentile. Logistic regression was performed to investigate the association between high BMI and atopy whilst adjusting for potential confounding factors. RESULTS: The following prevalences were observed for high BMI [Rural: 16%, Urban: 10.8%, p < 0.001] and atopy [Rural: 25.1%, Urban: 17.8%, p < 0.001]. High BMI was not associated with atopy; but an inverse association was observed between underweight and atopy [OR: 0.57, 95% CI: 0.33-0.99]. Significant associations were also observed with male sex [Rural: OR: 1.49, 95% CI: 1.06-2.08; Urban: OR: 1.90, 95% CI: 1.30-2.79], and in the urban site with older age [OR: 1.76, 95% CI: 1.00-3.07], family history of asthma [OR: 1.58, 95% CI: 1.01-2.47] and occupational status of parent [OR: 0.33, 95% CI: 0.12-0.93]; whilst co-infection with intestinal parasites [OR: 2.47, 95% CI: 1.01-6.04] was associated with atopy in the rural site. After multivariate adjustment, male sex, older age and family history of asthma remained significant. CONCLUSIONS: In Ghanaian schoolchildren, high BMI was not associated with atopy. Further studies are warranted to clarify the relationship between body weight and atopy in children subjected to rapid life-style changes associated with urbanization of their environments.

Enhanced Toll-like receptor responsiveness associated with mitogen-activated protein kinase activation in Plasmodium falciparum-infected children.

Acute Plasmodium falciparum infection is associated with strongly upregulated cytokine responses that are at least partly the result of activation of Toll-like receptors (TLRs). Whether and how TLR expression/responsiveness changes upon malarial infection is, however, currently not well understood. To assess this, we examined expression of TLRs and used the TLR ligand lipopolysaccharide (LPS) and Pam(3)Cys to stimulate peripheral blood mononuclear cells (PBMCs) from Ghanaian schoolchildren who live in a rural area where P. falciparum is endemic. Expression of TLR2 was higher, and responses to its ligand, Pam(3)Cys, were enhanced in P. falciparum-infected children compared to their uninfected counterparts. In cells from the same children, stimulation by Pam(3)Cys resulted in higher p38 mitogen-activated protein kinase activation and higher cytokine production. In vitro experiments confirmed that preincubation of PBMCs with P. falciparum-infected red blood cells enhanced responsiveness to TLR ligands. Taken together, the data indicate that P. falciparum-infected children in areas where malaria is endemic have an altered innate immune system, which might be important for the balance between immunity and pathology when new infections are encountered or when novel vaccines are introduced.

Immune responses during helminth-malaria co-infection: a pilot study in Ghanaian school children.

Malaria and helminth infections have a shared geographical distribution and therefore co-infections are frequent in tropical areas of the world. Human populations of helminth and malaria co-infection have shown contradictory results for the course of malarial infection and disease, possibly depending on the type of helminth studied, the intensity of helminth infection and the age of the study population. Although immunological studies might clarify the underlying mechanisms of protection or increased susceptibility, there are very few studies that have looked at immunological parameters in helminth and malaria co-infection. After discussing the available immunological data on co-infection, we describe a pilot study performed in Ghanaian school children where we compare anti-malarial responses in children living in an urban area, where the prevalence of helminth and Plasmodium falciparum infections was low, with that of children living in a rural area with high prevalence of helminth and Plasmodium falciparum infections.

Molecular diagnosis of Schistosoma infections in urine samples of school children in Ghana.

Recent studies using an internal transcribed spacer (ITS)-based real-time polymerase chain reaction (PCR) for the detection of Schistosoma DNA in urine samples has shown high sensitivity and specificity when performed on controls and known microscopy-positive samples. In this study, using 730 urine samples collected from children in five primary schools from different communities in the Greater Accra region of Ghana, specific detection of Schistosoma DNA showed excellent sensitivity of 100% and 85.2% in urines with > 50 eggs/10 mL urine and ≤ 50 eggs/10 mL of urine, respectively. Additionally, Schistosoma-specific DNA was amplified in 102 of 673 samples in which Schistosoma eggs could not be detected with microscopy. Taking microscopy and/or PCR-positive samples as true positives, the negative predictive value calculated was 94.6-100% for each school sampled as compared with 54.3-95.7% using microscopy. This ITS-based real-time PCR proves to be a powerful tool in epidemiological surveys of schistosomiasis providing more precise and sensitive results than microscopy.

Responses to malarial antigens are altered in helminth-infected children.

Malaria and helminth infections often coincide in the same tropical regions. Studies of the consequences of helminth and malaria coinfection in humans have been few and are mainly epidemiological, with little information on cellular immune responses. In this study, we investigated the antimalarial immune responses of Ghanaian children living in a rural area with a high prevalence of both helminth infection and Plasmodium falciparum infection. Whole blood specimens were cultured with P. falciparum-infected red blood cells (iRBCs), and pro- and anti-inflammatory cytokines and immune regulatory molecules were measured. In response to iRBCs, levels of interleukin (IL)-10, but not tumor necrosis factor-alpha,were higher in samples from helminth-infected children than in those from uninfected children, as was expression of the regulatory molecules suppressor of cytokine signaling (SOCS)-3, Foxp3, and programmed death (PD)-1. Furthermore, a significant correlation was found between SOCS-3 gene expression and IL-10 production. These results indicate that the presence of helminth infection modulates the immune response to malarial parasites, making it more anti-inflammatory.

Lower expression of TLR2 and SOCS-3 is associated with Schistosoma haematobium infection and with lower risk for allergic reactivity in children living in a rural area in Ghana.

BACKGROUND: Helminth infections are prevalent in rural areas of developing countries and have in some studies been negatively associated with allergic disorders and atopy. In this context little is known of the molecular mechanisms of modulation involved. We have characterized the innate immune responses, at the molecular level, in children according to their helminth infection status and their atopic reactivity to allergens. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana. Helminth infections were common and atopy rare in the study area. The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins. Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection. CONCLUSIONS: S. haematobium infections modulate the expression of genes of the innate immune system (TLR2 and SOCS-3); these are genes that are associated with increased allergic inflammatory processes, providing a molecular link between the negative association of this infection and atopy in rural children in Ghana.