Haemostatic changes in urogenital schistosomiasis haematobium: a case-control study in Gabonese schoolchildren.

In many tropical areas schistosomiasis is a major health problem causing hepatosplenic, intestinal or urogenital complaints. Hepatosplenic schistosomiasis mansoni is also characterized by blood coagulation abnormalities. Liver pathology plays a role in the development of haemostatic changes and the parasitic infection may directly affect coagulation. However, these contributing factors cannot be studied separately in hepatosplenic schistosomiasis infections. This pilot study provides insight in haemostatic changes in urinary schistosomiasis by studying coagulation parameters in schistosomiasis haematobium-infected Gabonese schoolchildren. Selection on urinary schistosomiasis patients without hepatosplenic complaints allows for the investigation of the direct effects of the parasite on haemostasis. Levels of von Willebrand Factor (VWF) antigen, active VWF and osteoprotegerin were elevated, indicating inflammation-mediated endothelial activation. In contrast to hepatosplenic schistosomiasis, thrombin-antithrombin complex and D-dimer levels were not affected. Despite its small sample size, this study clearly indicates that Schistosoma haematobium directly alters the activation status of the endothelium, without initiation of coagulation.

Opisthorchis felineus negatively associates with skin test reactivity in Russia-EuroPrevall-International Cooperation study.

BACKGROUND: Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country. METHODS: Schoolchildren aged 7-11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples. RESULTS: Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms. CONCLUSIONS: There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country.

Helminths, hygiene hypothesis and type 2 diabetes.

Worldwide, there is little overlap between the prevalence of soil-transmitted helminths and type 2 diabetes (T2D). Helminth-induced type 2 immune responses and immune regulatory network might modulate the obesity-induced activation of inflammatory pathways that are associated with the development of insulin resistance, a strong predictor of the development of T2D. However, other factors such as helminth-associated changes in adiposity and gut microbiome might also contribute to improved metabolic outcomes. In this review, we summarize epidemiological evidence for the link between helminths and T2D and discuss the potential mechanisms, based on findings from experimental studies as well as the limited number of studies in humans.

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases.

Maternal and child cytokine relationship in early life is not altered by cytokine gene polymorphisms.

The development of immune responses is influenced by the interaction between environmental and genetic factors. Our previous study showed a close association between maternal and young infant's cytokine responses. The question is how this association evolves over time and the contribution of genetic polymorphisms to this association. Five cytokines in mitogen-stimulated whole blood culture were measured from pregnant mothers and their children aged 2, 5, 12, 24 and 48 months. Cytokine gene polymorphisms were determined in both mothers and children. High production of maternal interleukin (IL)-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly associated with higher levels of the corresponding cytokines in their children at 2 months (T2), but the association decreased over time. Maternal single-nucleotide polymorphism (SNP) in IFN-γ gene, rs3181032, was found to be associated with child's IFN-γ levels at T2 only, whereas maternal IL-10 rs4579758 and child's TNF-α rs13215091 were associated with child's corresponding cytokines at later ages but not at T2. In the final models including the gene polymorphisms, maternal cytokines were still the strongest determinant of child cytokines. Maternal cytokine during pregnancy, which could be a proxy for child's environmental factors, showed its highest impact at early age, with no or little influence from genetic factors.

Prevalence of food sensitization and probable food allergy among adults in India: the EuroPrevall INCO study.

BACKGROUND: Data are lacking regarding the prevalence of food sensitization and probable food allergy among general population in India. We report the prevalence of sensitization and probable food allergy to 24 common foods among adults from general population in Karnataka, South India. METHODOLOGY: The study was conducted in two stages: a screening study and a case-control study. A total of 11 791 adults in age group 20-54 were randomly sampled from general population in South India and answered a screening questionnaire. A total of 588 subjects (236 cases and 352 controls) participated in the case-control study involving a detailed questionnaire and specific IgE estimation for 24 common foods. RESULTS: A high level of sensitization (26.5%) was observed for most of the foods in the general population, higher than that observed among adults in Europe, except for those foods that cross-react with birch pollen. Most of the sensitization was observed in subjects who had total IgE above the median IgE level. A high level of cross-reactivity was observed among different pollens and foods and among foods. The prevalence of probable food allergy (self-reports of adverse symptoms after the consumption of food and specific IgE to the same food) was 1.2%, which was mainly accounted for cow's milk (0.5%) and apple (0.5%). CONCLUSION: Very high levels of sensitization were observed for most foods, including those not commonly consumed in the general population. For the levels of sensitization, the prevalence of probable food allergy was low. This disassociation needs to be further explored in future studies.

Allergic disorders and socio-economic status: a study of schoolchildren in an urban area of Makassar, Indonesia.

BACKGROUND: In urban centres of developing countries, there is great variation in socio-economic status (SES) and lifestyle; however, little information is available on allergic disorders in groups with high- or low-SES within the same urban area. OBJECTIVE: To determine the prevalence of allergic disorders and investigate risk factors related to them among high- and low-SES schoolchildren in Makassar, the capital city of South Sulawesi, Indonesia. METHOD: This cross-sectional study was performed in 623 children originating from high- (N = 349) and low-SES (N = 274) schools. Information on reported allergic symptoms and potential factors associated with allergic disorders was obtained by questionnaire. Specific IgE and skin prick test (SPT) reactivity were determined against aeroallergens [Dermatophagoides pteronyssinus (HDM) and cockroach]. Total IgE and helminth infections were also assessed. RESULT: The prevalence of SPT to any aeroallergens was significantly higher in high-SES than in low-SES school (25% vs. 8%, P < 0.001, respectively). However, specific IgE against cockroach and total IgE were significantly lower in high- than in low-SES children. Allergic symptoms were reported more often in low- compared to high-SES children. Specific IgE to aeroallergens significantly increased the risk of SPT positivity to the same aeroallergen in the high-, but not in the low-SES children. In the high- but not in low-SES, there was a significant positive association between SPT to HDM and wheeze. Similarly, cockroach skin reactivity and elevated BMI increased the risk of eczema in the high-SES children only. CONCLUSION AND CLINICAL RELEVANCE: Skin prick test is higher in high-SES, whereas IgE and allergic symptoms are higher in low-SES children. Specific IgE is a risk factor for being SPT-positive, and SPT positivity is a risk factor for allergic symptoms but only in children of high- and not low-SES school. Therefore, the socio-economic status of a child might affect the diagnosis of allergic disease in a developing country.

Urban-rural differences in the gene expression profiles of Ghanaian children.

Recent studies indicate that urbanization is having a pronounced effect on disease patterns in developing countries. To understand the immunological basis of this, we examined mRNA expression in whole blood of genes involved in immune activation and regulation in 151 children aged 5-13 years attending rural, urban low socioeconomic status (SES) and urban high-SES schools in Ghana. Samples were also collected to detect helminth and malaria infections. Marked differences in gene expression were observed between the rural and urban areas as well as within the urban area. The expression of both interleukin (IL)-10 and programmed cell death protein 1 increased significantly across the schools from urban high SES to urban low SES to rural (P-trend <0.001). Although IL-10 gene expression was significantly elevated in the rural compared with the urban schools (P<0.001), this was not associated with parasitic infection. Significant differences in the expression of toll-like receptors (TLRs) and their signaling genes were seen between the two urban schools. Genetic differences could not fully account for the gene expression profiles in the different groups as shown by analysis of IL-10, TLR-2 and TLR-4 gene polymorphisms. Immune gene expression patterns are strongly influenced by environmental determinants and may underlie the effects of urbanization seen on health outcomes.

Schistosome infection is negatively associated with mite atopy, but not wheeze and asthma in Ghanaian schoolchildren.

BACKGROUND: Epidemiological evidence suggests that helminth infection and rural living are inversely associated with allergic disorders. OBJECTIVE: The aim of the study was to investigate the effect of helminth infections and urban versus rural residence on allergy in schoolchildren from Ghana. METHODS: In a cross-sectional study of 1385 children from urban-high socio-economic status (SES), urban-low SES and rural schools, associations between body mass index (BMI), allergen-specific IgE (sIgE), parasitic infections and allergy outcomes were analysed. Allergy outcomes were skin prick test (SPT) reactivity, reported current wheeze and asthma. RESULTS: Helminth infections were found predominantly among rural subjects, and the most common were hookworm (9.9%) and Schistosoma spp (9.5%). Being overweight was highest among urban-high SES (14.6%) compared to urban-low SES (5.5%) and rural children (8.6%). The prevalence of SPT reactivity to any allergen was 18.3%, and this was highest among rural children (21.4%) followed by urban-high SES (20.2%) and urban-low SES (10.5%) children. Overall, SPT reactivity to mite (12%) was most common. Wheeze and asthma were reported by 7.9% and 8.3%, respectively. In multivariate analyses, factors associated with mite SPT were BMI (aOR 2.43, 95% CI 1.28-4.60, P = 0.007), schistosome infection (aOR 0.15, 95% CI 0.05-0.41) and mite sIgE (aOR 7.40, 95% CI 5.62-9.73, P < 0.001) but not area. However, the association between mite IgE and SPT differed by area and was strongest among urban-high SES children (aOR = 15.58, 95% CI 7.05-34.43, P < 0.001). Compared to rural, urban-low SES area was negatively associated with current wheeze (aOR 0.41, 95% CI 0.20-0.83, P = 0.013). Both mite sIgE and mite SPT were significantly associated with current wheeze and asthma. CONCLUSION AND CLINICAL RELEVANCE: Infection with schistosomes appeared to protect against mite SPT reactivity. This needs to be confirmed in future studies, preferably in a longitudinal design where schistosome infections are treated and allergic reactions reassessed.

CD24(hi)CD27(+) B cells from patients with allergic asthma have impaired regulatory activity in response to lipopolysaccharide.

BACKGROUND: Regulatory B cells have been identified that strongly reduce allergic and auto-immune inflammation in experimental models by producing IL-10. Recently, several human regulatory B-cell subsets with an impaired function in auto-immunity have been described, but there is no information on regulatory B cells in allergic asthma. OBJECTIVE: In this study, the frequency and function of IL-10 producing B-cell subsets in allergic asthma were investigated. METHODS: Isolated peripheral blood B cells from 13 patients with allergic asthma and matched healthy controls were analyzed for the expression of different regulatory B-cell markers. Next, the B cells were activated by lipopolysaccharide (LPS), CpG or through the B-cell receptor, followed by co-culture with endogenous memory CD4(+) T cells and house dust mite allergen DerP1. RESULTS: Lower number of IL-10 producing B cells were found in patients in response to LPS, however, this was not the case when B cells were activated through the B-cell receptor or by CpG. Further dissection showed that only the CD24(hi)CD27(+) B-cell subset was reduced in number and IL-10 production to LPS. In response to DerP1, CD4(+) T cells from patients co-cultured with LPS-primed total B cells produced less IL-10 compared to similar cultures from controls. These results are in line with the finding that sorted CD24(hi)CD27(+) B cells are responsible for the induction of IL-10(+) CD4(+) T cells. CONCLUSIONS: Taken together, these data indicate that CD24(hi)CD27(+) B cells from allergic asthma patients produce less IL-10 in response to LPS leading to a weaker IL-10 induction in T cells in response to DerP1, which may play a role in allergic asthma.

Serum and CSF PDGF-AA and FGF-2 in relapsing-remitting multiple sclerosis: a case-control study.

BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-A (PDGF-AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF-2 and PDGF-AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RR-MS) and compared these values with control subjects. METHODS: Twenty-three patients with RR-MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann-Whitney U-test and Spearman's rank correlation were used for analysis. P values of <0.05 were considered significant. RESULTS: Age and sex distribution were similar in both groups. Serum values of FGF-2 were higher in relapse phase compared with remission phase, with a trend toward significance (P=0.052). CSF PDGF-AA showed significant negative correlation with disease duration (correlation coefficient=-0.58, P=0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF-AA was observed (mean±SEM 2.78±0.8 in controls vs. 0.55±0.29 in patients with MS≥2 years, P<0.05). CONCLUSION: Our study was the first to show that CSF PDGF-AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.

Point and period prevalences of eczema in rural and urban schoolchildren in Ghana, Gabon and Rwanda.

BACKGROUND: Eczema is a growing problem in Africa, particularly amongst children. OBJECTIVES: To investigate the point-prevalences of eczema by physical examination in schoolchildren living in rural and urban areas and with different socioeconomic backgrounds in Ghana, Gabon and Rwanda. In Ghana period-prevalences were also estimated by questionnaire and compared with the point-prevalences. METHODS: In total, 4839 schoolchildren in Ghana, Gabon and Rwanda were seen by at least one dermatologist. The point-prevalences of eczema were estimated on the basis of physical examination. Period-prevalences were measured in Ghana with questionnaire based-interviews adapted from the International Study of Asthma and Allergies in Childhood (ISAAC). RESULTS: The point-prevalences were 1.5% and 1.6% in the two Ghanaian studies; 4% in Gabon and 0.8% in Rwanda. The period-prevalences were 2.6% and 4.4% in the two Ghanaian studies. The prevalences of eczema were not significantly different when comparing the urban and rural groups as well as the different socioeconomic levels. The sensitivity and positive predictive value to identify eczema cases based on the questionnaires compared to the diagnoses by physical examination were only 33% and 22% in the first Ghanaian study and 10% and 4% in the second Ghanaian study respectively. CONCLUSIONS: The point-prevalences of eczema in the three African countries studied were low compared with industrialized countries. Physical examination by a dermatologist is still the gold standard to identify eczema cases because the sensitivity and the positive predictive value to identify eczema cases with questionnaires were low in the two Ghanaian studies.

Prevalence and causative fungal species of tinea capitis among schoolchildren in Gabon.

Tinea capitis is endemic among schoolchildren in tropical Africa. The objective was to determine the prevalence of symptomatic tinea capitis in schoolchildren in Gabon. A cross-sectional study was conducted with 454 children aged 4-17 years, attending a rural school and an urban school. The diagnosis of tinea capitis was based on clinically manifest infection, direct microscopic examination using 20% potassium hydroxide (KOH) solution and fungal culture. Based on clinical examination, 105 (23.1%) of 454 children had tinea capitis. Seventy-four (16.3%) children were positive by direct examination (KOH) and/or fungal culture. The prevalence of tinea capitis depended on the school studied and ranged from 20.4% in the urban school with a higher socioeconomic status to 26.3% in the rural school with a lower socioeconomic status. Similarly, the spectrum of causative species varied between the different schools. Taken the schools together, Trichophyton soudanense (29.4%) was the most prominent species, followed by Trichophyton tonsurans (27.9%) and Microsporum audouinii (25.0%). Clinically manifest tinea capitis is endemic among schoolchildren in the Lambaréné region in Gabon. The prevalence of tinea capitis and the causative species depended on the type of school that was investigated.

The EuroPrevall-INCO surveys on the prevalence of food allergies in children from China, India and Russia: the study methodology.

BACKGROUND: Very little is known regarding the global variations in the prevalence of food allergies. The EuroPrevall-INCO project has been developed to evaluate the prevalence of food allergies in China, India and Russia using the standardized methodology of the EuroPrevall protocol used for studies in the European Union. The epidemiological surveys of the project were designed to estimate variations in the prevalence of food allergy and exposure to known or suspected risk factors for food allergy and to compare the data with different European countries. METHODS: Random samples of primary schoolchildren were recruited from urban and rural regions of China, Russia and India for screening to ascertain possible adverse reactions to foods. Cases and controls were then selected to answer a detailed questionnaire designed to evaluate the possible risk factors of food allergies. Objective evidence of sensitisation including skin-prick test and serum specific IgE measurement was also collected. RESULTS: More than 37 000 children from the three participating countries have been screened. The response rates for the screening phase ranged from 83% to 95%. More than 3000 cases and controls were studied in the second phase of the study. Further confirmation of food allergies by double blind food challenge was conducted. CONCLUSIONS: This will be the first comparative study of the epidemiology of food allergies in China, India, and Russia using the same standardized methodology. The findings of these surveys will complement the data obtained from Europe and provide insights into the development of food allergy.

The multinational birth cohort of EuroPrevall: background, aims and methods.

BACKGROUND/AIM: The true prevalence and risk factors of food allergies in children are not known because estimates were based predominantly on subjective assessments and skin or serum tests of allergic sensitization to food. The diagnostic gold standard, a double-blind placebo-controlled food provocation test, was not performed consistently to confirm suspected allergic reactions in previous population studies in children. This protocol describes the specific aims and diagnostic protocol of a birth cohort study examining prevalence patterns and influential factors of confirmed food allergies in European children from different regions. METHODS: Within the collaborative translational research project EuroPrevall, we started a multi-center birth cohort study, recruiting a total of over 12 000 newborns in nine countries across Europe in 2005-2009. In addition to three telephone interviews during the first 30 months, parents were asked to immediately inform the centers about possible allergic reactions to food at any time during the follow-up period. RESULTS: All children with suspected food allergy symptoms were clinically evaluated including double-blind placebo-controlled food challenge tests. We assessed sensitization to different food allergens by measurements of specific serum immunoglobulin E and skin prick tests, collect blood, saliva or buccal swabs for genetic tests, breast milk for measurement of food proteins/cytokines, and evaluate quality-of-life and economic burden of families with food allergic children. CONCLUSIONS: This birth cohort provides unique data on prevalence, risk factors, quality-of-life, and costs of food allergies in Europe, leading to the development of more informed and integrated preventative and treatment strategies for children with food allergies.

Allergic characteristics of urban schoolchildren with atopic eczema in Ghana.

BACKGROUND: Atopic eczema is an increasing clinical problem in Africa. OBJECTIVE: To determine allergic characteristics and to identify possible risk factors for eczema among schoolchildren in an urbanized area in Ghana. PATIENTS AND METHODS: Schoolchildren aged 3-16 years with eczema were recruited. For each patient, one to three age- and sex-matched controls were selected. All children completed a questionnaire and were skin prick tested with a panel of allergens. Blood was drawn to determine the total and allergen-specific IgE. Conditional logistic regression models with the matching factors included in the model were used to calculate the odds ratios and to adjust for possible confounders. RESULTS: A total of 52 children with eczema (27 boys and 25 girls) and 99 controls were included. Levels of total IgE were found to be 9.1 (1.1; 78.4) times more often elevated in children with eczema. This association was mainly driven by elevated IgE levels against cockroach antigen. Children with eczema were found to have 2.0 (0.87; 4.7) times more often positive skin prick tests (SPT), but this association diminished to 1.2 (0.40; 3.6) after adjustment for total IgE levels. Frequent washing with soap was identified as a risk factor for the development of eczema among these children. CONCLUSION: Schoolchildren with eczema in Ghana were characterized by elevated IgE levels especially against cockroach antigen. The association between eczema and positive SPT was much weaker suggesting immune hyporesponsiveness of the skin. After adjustment for IgE level, SPT were less suitable to distinguish children with and without eczema.

Doxycycline treatment of Brugia malayi-infected persons reduces microfilaremia and adverse reactions after diethylcarbamazine and albendazole treatment.

BACKGROUND: The efficacy of doxycycline for treating the causal agent of human lymphatic filariasis, Brugia malayi, is unknown. Standard treatment with diethylcarbamazine-albendazole is associated with adverse reactions. We assessed whether doxycycline alone or in combination with diethylcarbamazine-albendazole would lead to sustained amicrofilaremia and reduced incidence of adverse reactions. METHODS: A double-blind, randomized, placebo-controlled 6-week field trial of doxycycline treatment (100 mg/day) of 161 persons infected with B. malayi was conducted. Four months after receiving doxycycline (n=119) or placebo (n=42), participants received diethylcarbamazine (6 mg/kg) plus albendazole (400 mg) or a matching placebo. Adverse reactions were assessed 48 and 60 h after administration of diethylcarbamazine-albendazole. Treatment efficacy was evaluated at 2, 4, and 12 months after the initial doxycycline treatment. RESULTS: Four months after beginning doxycycline treatment, Wolbachia loads were reduced by 98%. Doxycycline treatment reduced the prevalence of microfilaremia at 2, 4, and 12 months of follow-up (P<.001 for all time points). At the 1-year follow-up, prevalence was reduced by 77% and 87.5% in patients receiving doxycycline alone or doxycycline plus diethylcarbamazine-albendazole, respectively. In contrast, the reduction of microfilaremia in the group receiving placebo doxycycline plus diethylcarbamazine-albendazole was merely 26.7%. Adverse reactions were lowest in the group receiving doxycycline plus placebo diethylcarbamazine-albendazole and highest in the group receiving placebo doxycycline plus diethylcarbamazine-albendazole. The proportion of persons with high fever and severe adverse reactions was significantly reduced in the group treated with doxycycline plus diethylcarbamazine-albendazole. CONCLUSIONS: A 6-week course of doxycycline, either alone or in combination with diethylcarbamazine-albendazole, leads to a decrease in microfilaremia and reduces adverse reactions to antifilarial treatment in B. malayi-infected persons.

T-cell regulation in helminth parasite infections: implications for inflammatory diseases.

The field of infectious disease immunology is at an exciting intersection with new concepts in immune regulation meeting with the dynamics of infectious diseases. We discuss how the identification of regulatory mechanisms has already helped develop new models to understand helminth infections, which remain among the most prevalent chronic diseases in the world today. The epidemiological imbalance between helminth infections in developing countries, and intensifying allergies and autoimmune pathologies in the industrialised nations, seems to reflect a fundamental shift in regulation of immune responsiveness. Experimental studies have verified that helminths can downmodulate a range of immunopathological conditions, with the regulatory T cell being one of the most common mechanisms in play. We discuss further the context of host genetic predisposition, together with the impact of infection on the evolution of the human immune system, and suggest future strategies to harness our new understanding of helminth organisms in order to control both infectious and non-infectious immunological disorders.

A comparison of ex vivo cytokine production in venous and capillary blood.

We performed a randomized study of the immunological effects of an early measles vaccine given at 4.5 months of age and aimed to obtain venous samples from the infants at baseline and 6 weeks later. If this was not feasible, a capillary sample was obtained. We analysed baseline samples from the first 50 children enrolled in the study to investigate the potential differences in ex vivo cytokine production between venous blood and capillary blood. We also obtained paired venous and capillary blood samples from 11 adult volunteers. Whole blood was stimulated with lipopolysaccharide (LPS) [a Toll-like receptor (TLR)-4 ligand], (S)-(2, 3-bis (palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH, trihydrochloride (PAM3Cys) (a TLR-2 ligand), phytohaemagglutinin (PHA) or purified protein derivative (PPD). Cytokine concentrations in the supernatants were assessed by a multiplexed assay and were compared between venous and capillary samples in both infants and adults. The production of both the pro- and the anti-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-10, was higher in cultures of capillary blood compared with venous blood. This was found in non-stimulated control samples as well as in blood stimulated with PAM3Cys and PPD. Adults produced more IL-5 in venous blood than in capillary blood upon PHA stimulation. We found no other difference in the levels of IL-5 or IFN-gamma between venous and capillary blood. In capillary blood we found sex differences in response to PHA but this was not the case in venous blood. We found significant differences in the production of cytokines between venous and capillary blood. Such differences should be taken into account when setting up immuno-epidemiological studies.

Effect of anthelmintic treatment on leptin, adiponectin and leptin to adiponectin ratio: a randomized-controlled trial.

Emerging evidence suggests that helminths might confer protection against the development of type 2 diabetes. We aimed to assess the role of adipokines in mediating the effect of helminths on insulin resistance. Serum samples were obtained from a randomized-controlled trial of anthelmintic treatment in an area endemic for soil-transmitted helminths (STH), Flores Island, Indonesia. In STH-infected subjects, anthelmintic treatment significantly increased the ratio of leptin to adiponectin (treatment effect factor (95% confidence interval (CI)), P-value for interaction: 1.20 (1.06-1.35), P=0.010), which largely stemmed from a significant reduction in adiponectin (0.91 (0.85-0.98), P=0.020) and a trend for an increase in leptin level (1.10 (1.00-1.21), P=0.119). No significant effect on resistin level was observed. This increase in leptin to adiponectin ratio seemed to contribute to the observed effect of deworming on increased insulin resistance (IR) as adjustment for leptin to adiponectin ratio attenuated the effect on IR from 1.07 (1.01-1.14, P=0.023) to 1.05 (0.99-1.11, P=0.075). Anthelmintic treatment in STH-infected subjects increases leptin to adiponectin ratio which may in small part contribute to the modest increase in IR. Further studies will be needed to assess the effect of the changes in adipokine levels on the host immune response and metabolism.