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Abena S Amoah,
Benedicta B Obeng,
Irene A Larbi,
Serge A Versteeg,
Yvonne Aryeetey,
Jaap H Akkerdaas,
Laurian Zuidmeer,
Jonas Lidholm,
Montserrat Fernández-Rivas,
Franca C Hartgers,
Daniel A Boakye,
Ronald van Ree, Maria Yazdanbakhsh
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ABSTRACT: 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.
The Journal of allergy and clinical immunology 06/2013; · 9.17 Impact Factor
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Maria Mm Kaisar,
Taniawati Supali,
Aprilianto E Wiria,
Firdaus Hamid,
Linda J Wammes,
Erliyani Sartono,
Adrian Jf Luty,
Eric At Brienen, Maria Yazdanbakhsh,
Lisette van Lieshout,
Jaco J Verweij
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ABSTRACT: BACKGROUND: DNA-based diagnostic methods have been shown to be highly sensitive and specific for the detection of malaria. An 18S-rRNA-based, real-time polymerase chain reaction (PCR) was used to determine the prevalence and intensity of Plasmodium infections on Flores Island, Indonesia. METHODS: Microscopy and real-time multiplex PCR for the detection of Plasmodium species was performed on blood samples collected in a population-based study in Nangapanda Flores Island, Indonesia. RESULTS: A total 1,509 blood samples were analysed. Real-time PCR revealed prevalence for Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae to be 14.5%, 13.2%, and 1.9% respectively. Sub-microscopic parasitaemia were found in more than 80% of all positive cases. The prevalence of P. falciparum and P. vivax was significantly higher in subjects younger than 20 years (p <= 0.01). In the present study, among non-symptomatic healthy individuals, anaemia was strongly correlated with the prevalence and load of P. falciparum infections (p <= 0.01; p = 0.02) and with the load of P. vivax infections (p = 0.01) as detected with real-time PCR. Subjects with AB blood group tend to have a higher risk of being infected with P. falciparum and P. vivax when compared to other blood groups. CONCLUSION: The present study has shown that real-time PCR provides more insight in the epidemiology of Plasmodium infections and can be used as a monitoring tool in the battle against malaria. The unsurpassed sensitivity of real-time PCR reveals that sub microscopic infections are common in this area, which are likely to play an important role in transmission and control.Trial registration: Trials number ISRCTN83830814.
Malaria Journal 05/2013; 12(1):169. · 3.19 Impact Factor
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ABSTRACT: BACKGROUND: Helminth infections and allergies are associated with TH2 responses. Whereas the development of TH2 responses and allergic disorders in pediatric populations has been examined in affluent countries, no or little data exist from low income regions of the world.The aim of this study is to examine factors influencing the development of TH2 responses of children born in areas endemic for helminth infections and to relate these factors to atopic sensitization at 4 years of age. METHODS: Data were collected from pregnant mothers on helminth infections, education and socioeconomic status (SES). Total IgE, IL-5 in response to mitogen, and helminth antigens were measured in children at 2, 5, 12, 24 and 48 months of age. Skin prick testing (SPT) and allergen-specific IgE were determined at 4 years of age. RESULTS: Strong TH2 responses were seen at 5 months of age and increased with time. Although maternal filarial infection was associated with helminth-antigen specific TH2 responses, it was low maternal education or SES but not helminth infection, which was associated with the development of high total IgE and PHA-induced IL-5. At 4 years of age when allergen reactivity was assessed by SPT, the high general TH2 responses did not translate into higher SPT. The risk factor for SPT reactivity was low maternal education which decreased the risk of SPT positivity to allergens (adjusted OR, 0.32; 95% CI, 0.12 -- 0.87) independently of maternal filarial infection which tended to reduce the child's risk for being SPT positive (adjusted OR, 0.35; 95% CI, 0.07 -- 1.70). CONCLUSIONS: In areas endemic for helminths, potent TH2 responses were seen early in life, but did not translate to a higher SPT reactivity to allergens. Therefore, in many parts of the world TH2 responses in general and IgE in particular cannot be used for diagnosis of allergic diseases.
Allergy Asthma and Clinical Immunology 04/2013; 9(1):13.
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ABSTRACT: OBJECTIVES: Skin diseases, especially skin infections, among schoolchildren in Africa can be a major health problem. The objective of this study was to determine the prevalences of skin diseases among children in rural and urban schools in three different African countries and to study the influence of socioeconomic level. METHODS: Cross-sectional, population-based studies were performed in Ghana, Gabon, and Rwanda. Point prevalences of skin diseases were estimated on the basis of physical examination by at least one dermatologist. RESULTS: A total of 4839 schoolchildren were seen. The overall prevalence of schoolchildren with any skin disease was high and amounted to 34.6% and 42.0% in two Ghanaian studies, 45.8% in Gabon, and 26.7% in Rwanda. In children with skin diseases, skin infections represented the greatest proportion of disease, accounting for 14.7% and 17.6% of skin disease in the Ghanaian studies, and 27.7% and 22.7% in Gabon and Rwanda, respectively. Diseases with the highest prevalence were tinea capitis and bacterial skin infections, especially in rural areas and in schools serving children living at lower socioeconomic levels. CONCLUSIONS: The prevalences of skin diseases among African schoolchildren were high. Skin infections such as tinea capitis and pyoderma predominated.
International journal of dermatology 04/2013; · 1.18 Impact Factor
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The Lancet Infectious Diseases 04/2013; · 17.39 Impact Factor
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ABSTRACT: 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.
The American journal of tropical medicine and hygiene 03/2013; · 2.59 Impact Factor
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ABSTRACT: BACKGROUND: Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. METHODS: Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. RESULTS: Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR)=4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR=1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR=1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p=0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p=0.006), and increased IL-10 in the late sample group (p=0.03). CONCLUSION: BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination.
Vaccine 03/2013; · 3.77 Impact Factor
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Lucja A Labuda,
Ulysse Ateba-Ngoa,
Eliane Ngoune Feugap,
Jorn J Heeringa,
Luciën E P M van der Vlugt,
Regina B A Pires,
Ludovic Mewono,
Peter G Kremsner,
Menno C van Zelm,
Ayola A Adegnika, Maria Yazdanbakhsh,
Hermelijn H Smits
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ABSTRACT: Antibody responses are thought to play an important role in control of Schistosoma infections, yet little is known about the phenotype and function of B cells in human schistosomiasis. We set out to characterize B cell subsets and B cell responses to B cell receptor and Toll-like receptor 9 stimulation in Gabonese schoolchildren with Schistosoma haematobium infection. Frequencies of memory B cell (MBC) subsets were increased, whereas naive B cell frequencies were reduced in the schistosome-infected group. At the functional level, isolated B cells from schistosome-infected children showed higher expression of the activation marker CD23 upon stimulation, but lower proliferation and TNF-α production. Importantly, 6-months after 3 rounds of praziquantel treatment, frequencies of naive B cells were increased, MBC frequencies were decreased and with the exception of TNF-α production, B cell responsiveness was restored to what was seen in uninfected children. These data show that S. haematobium infection leads to significant changes in the B cell compartment, both at the phenotypic and functional level.
PLoS Neglected Tropical Diseases 03/2013; 7(3):e2094. · 4.69 Impact Factor
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ABSTRACT: BACKGROUND: The classic technique used to detect hookworm infections in population-based surveys is microscopic examination of Kato thick smears of multiple faecal samples per person as variation in soil-transmitted helminth egg output is common. METHODS: As an alternative to this time-consuming and logistically difficult procedure, a PCR-based method to detect hookworm infections was evaluated. Faecal samples collected from 65 Ghanaian school children during February-June 2006 were examined using both techniques. RESULTS: Thirty-one children with a hookworm infection were detected by Kato examination of three faecal samples compared with 30 children detected by PCR of a single faecal sample and 39 detected by PCR of three faecal samples. CONCLUSION: PCR provides a sensitive alternative to the conventional microscopic detection of hookworm infections.
Transactions of the Royal Society of Tropical Medicine and Hygiene 02/2013; · 2.16 Impact Factor
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Linda J Wammes,
Aprilianto E Wiria,
Christa Toenhake,
Firdaus Hamid,
Kit Yeng Liu,
Heni Suryani,
Maria M M Kaisar,
Jaco J Verweij,
Erliyani Sartono,
Taniawati Supali,
Hermelijn H Smits,
Adrian J F Luty, Maria Yazdanbakhsh
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ABSTRACT: Background. In malaria-endemic areas, a proportion of the population becomes chronic carriers of parasites with few or no clinical signs. There is little information on cellular immune responses in asymptomatic parasite carriers.Methods. In 80 schoolchildren residing in a malaria-endemic area of Flores Island, Indonesia, T-helper subsets, regulatory T-cell (Treg) frequencies, TNFRII expression on Treg and P. falciparum-infected red blood cell (PfRBC)-induced cytokine responses were measured and asymptomatic infected subjects were compared to uninfected controls. To ascertain that alterations found was due to the presence of malaria parasites, the immune responses were analyzed in 16 children before and one month after anti-malarial treatment.Results. TNFRII expression, a marker of activation on Treg, was higher during infection, but decreased upon treatment. GATA3-positive cells as well as level of IL-13 secretion in response to PfRBC appeared to be suppressed by plasmodial infection as both increased after anti-malarial treatment. TNFRII expression on Treg correlated positively with TNF in response to PfRBC, but this association disappeared following treatment.Conclusions. Malaria parasites associated with asymptomatic infections seem to result in increased TNFRII expression on Tregs as well as suppressed Th2 cytokine responses, features that might be important for survival of the parasites in asymptomatic carriers.
The Journal of Infectious Diseases 02/2013; · 6.41 Impact Factor
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Aprilianto Eddy Wiria,
Linda J Wammes,
Firdaus Hamid,
Olaf M Dekkers,
Margaretta A Prasetyani,
Linda May,
Maria M M Kaisar,
Jaco J Verweij,
Jouke T Tamsma,
Felix Partono,
Erliyani Sartono,
Taniawati Supali, Maria Yazdanbakhsh,
Johannes W A Smit
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ABSTRACT: Objective: To examine the association between helminth infections and atherosclerosis. Background: Chronic helminth infection, which can lead to poor nutritional status and anti-inflammatory response, might protect against the development of atherosclerosis.
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Aprilianto E Wiria,
Firdaus Hamid,
Linda J Wammes,
Maria M M Kaisar,
Linda May,
Margaretta A Prasetyani,
Sitti Wahyuni,
Yenny Djuardi,
Iwan Ariawan,
Heri Wibowo, [......],
Lisette van Lieshout,
Anton J M de Craen,
Ronald van Ree,
Jaco J Verweij,
Roula Tsonaka,
Jeanine J Houwing-Duistermaat,
Adrian J F Luty,
Erliyani Sartono,
Taniawati Supali, Maria Yazdanbakhsh
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ABSTRACT: Helminth infections are proposed to have immunomodulatory activities affecting health outcomes either detrimentally or beneficially. We evaluated the effects of albendazole treatment, every three months for 21 months, on STH, malarial parasitemia and allergy.
A household-based cluster-randomized, double-blind, placebo-controlled trial was conducted in an area in Indonesia endemic for STH. Using computer-aided block randomization, 481 households (2022 subjects) and 473 households (1982 subjects) were assigned to receive placebo and albendazole, respectively, every three months. The treatment code was concealed from trial investigators and participants. Malarial parasitemia and malaria-like symptoms were assessed in participants older than four years of age while skin prick test (SPT) to allergens as well as reported symptoms of allergy in children aged 5-15 years. The general impact of treatment on STH prevalence and body mass index (BMI) was evaluated. Primary outcomes were prevalence of malarial parasitemia and SPT to any allergen. Analysis was by intention to treat. At 9 and 21 months post-treatment 80.8% and 80.1% of the study subjects were retained, respectively. The intensive treatment regiment resulted in a reduction in the prevalence of STH by 48% in albendazole and 9% in placebo group. Albendazole treatment led to a transient increase in malarial parasitemia at 6 months post treatment (OR 4.16(1.35-12.80)) and no statistically significant increase in SPT reactivity (OR 1.18(0.74-1.86) at 9 months or 1.37 (0.93-2.01) 21 months). No effect of anthelminthic treatment was found on BMI, reported malaria-like- and allergy symptoms. No adverse effects were reported.
The study indicates that intensive community treatment of 3 monthly albendazole administration for 21 months over two years leads to a reduction in STH. This degree of reduction appears safe without any increased risk of malaria or allergies.
Controlled-Trials.com ISRCTN83830814.
PLoS ONE 01/2013; 8(3):e57899. · 4.09 Impact Factor
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Anouk K Gloudemans,
Maud Plantinga,
Martin Guilliams,
Monique A Willart,
Arifa Ozir-Fazalalikhan,
Alwin van der Ham,
Louis Boon,
Nicola L Harris,
Hamida Hammad,
Henk C Hoogsteden, Maria Yazdanbakhsh,
Rudi W Hendriks,
Bart N Lambrecht,
Hermelijn H Smits
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ABSTRACT: It is currently unknown how mucosal adjuvants cause induction of secretory immunoglobulin A (IgA), and how T cell-dependent (TD) or -independent (TI) pathways might be involved. Mucosal dendritic cells (DCs) are the primary antigen presenting cells driving TI IgA synthesis, by producing a proliferation-inducing ligand (APRIL), B cell activating factor (BAFF), Retinoic Acid (RA), TGF-β or nitric oxide (NO). We hypothesized that the mucosal adjuvant Cholera Toxin subunit B (CTB) could imprint non-mucosal DCs to induce IgA synthesis, and studied the mechanism of its induction. In vitro, CTB-treated bone marrow derived DCs primed for IgA production by B cells without the help of T cells, yet required co-signaling by different Toll-like receptor (TLR) ligands acting via the MyD88 pathway. CTB-DC induced IgA production was blocked in vitro or in vivo when RA receptor antagonist, TGF-β signaling inhibitor or neutralizing anti-TGF-β was added, demonstrating the involvement of RA and TGF-β in promoting IgA responses. There was no major involvement for BAFF, APRIL or NO. This study highlights that synergism between CTB and MyD88-dependent TLR signals selectively imprints a TI IgA-inducing capacity in non-mucosal DCs, explaining how CTB acts as an IgA promoting adjuvant.
PLoS ONE 01/2013; 8(3):e59822. · 4.09 Impact Factor
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Aprilianto Eddy Wiria,
Linda J Wammes,
Firdaus Hamid,
Olaf M Dekkers,
Margaretta A Prasetyani,
Linda May,
Maria M M Kaisar,
Jaco J Verweij,
Jouke T Tamsma,
Felix Partono,
Erliyani Sartono,
Taniawati Supali, Maria Yazdanbakhsh,
Johannes W A Smit
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ABSTRACT: To examine the association between helminth infections and atherosclerosis.
Chronic helminth infection, which can lead to poor nutritional status and anti-inflammatory response, might protect against the development of atherosclerosis.
A cross-sectional study was performed in Flores, Indonesia, an area highly endemic for soil-transmitted helminths (STH). Stool samples from 675 participants aged 18-80 years were collected and screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. We collected data on body mass index (BMI), waist to hip ratio (WHR), blood pressure, fasting blood glucose (FBG), lipid, high sensitive C-reactive protein (hs-CRP), total immunoglobulin-E (TIgE) and Escherichia coli lipopolysaccharide stimulated cytokines (tumor necrosis factor and interleukin-10). In a subset of 301 elderly adults (≥40 years of age) carotid intima media thickness (cIMT) was measured.
Participants with any STH infection had lower BMI (kg/m2) (mean difference -0.66, 95%CI [-1.26, -0.06]), WHR (-0.01, [-0.02, -0.00]), total cholesterol (mmol/L) (-0.22, [-0.43, -0.01]) and LDL-cholesterol (mmol/L) (-0.20, [-0.39, -0.00]) than uninfected participants. After additional adjustment for BMI the association between helminth infection and total cholesterol (mean difference -0.17, 95%CI [-0.37, 0.03]) as well as LDL-cholesterol (-0.15, [-0.33, 0.04]) was less pronounced. BMI, WHR, and total cholesterol were negatively associated with number species of helminth co-infections. Participants with high TIgE, an indicator of exposure to helminths, had lower FBG, TC, and HDL. The association between TIgE and TC and HDL remained significant after adjustment with BMI. No clear association was found between STH infection or TIgE and mean cIMT.
This cross-sectional study presents evidence that helminth infections were negatively associated with risk factors for cardiovascular disease, an association at least partially mediated by an effect on BMI. The significance of this finding needs to be determined.
PLoS ONE 01/2013; 8(1):e54855. · 4.09 Impact Factor
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ABSTRACT: Helminth infections are highly prevalent in developing countries, especially in rural areas. With gradual development, there is a transition from living conditions that are dominated by infection, poor sanitation, manual labor, and traditional diet to a situation where burden of infections is reduced, infrastructure is improved, sedentary lifestyle dominates, and processed food forms a large proportion of the calorie intake. The combinations of some of the changes in lifestyle and environment are expected to result in alteration of the landscape of diseases, which will become dominated by non-communicable disorders. Here we review how the major helminth infections affect a large proportion of the population in the developing world and discuss their impact on the immune system and the consequences of this for other infections which are co-endemic in the same areas. Furthermore, we address the issue of decreasing helminth infections in many parts of the world within the context of increasing inflammatory, metabolic, and cardiovascular diseases.
Seminars in Immunopathology 11/2012; · 6.27 Impact Factor
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Moustapha Mbow,
Bridget M Larkin,
Lynn Meurs,
Linda J Wammes,
Sanne E de Jong,
Lucja A Labuda,
Makhtar Camara,
Hermelijn H Smits,
Katja Polman,
Tandakha N Dieye,
Souleymane Mboup,
Miguel J Stadecker, Maria Yazdanbakhsh
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ABSTRACT: Background. Schistosome infections are often clinically silent, but some individuals develop severe pathological reactions. In several disease processes Th17 cells have been linked to tissue injuries, while regulatory T (Treg) cells are thought to down-modulate inflammatory reactions. We assessed whether bladder pathology in human Schistosoma haematobium infection is related to the balance of Th17 and Treg cells. Using a murine model of Schistosoma mansoni infection we further investigated whether the peripheral profiles reflected ongoing events in tissues.Methods. We characterized T helper subsets in the peripheral blood of children residing in a S. haematobium-endemic area and in peripheral blood as well as in spleen and hepatic granulomas of S. mansoni-infected high-pathology CBA and low-pathology C57BL/6 mice. S. haematobium-infected children with bladder pathology had a significantly higher percentage of Th17 cells than those without pathology. Moreover, the Th17/Treg ratios were significantly higher in children with pathology compared to infected children without pathology.Results. Percentages of IL-17-producing cells were significantly more abundant in the spleen and granulomas of CBA compared to C57BL/6 mice. This difference was also reflected in the peripheral blood.Conclusions. Our results indicate for the first time that Th17 cells may be involved in the pathogenesis of human schistosomiasis.
The Journal of Infectious Diseases 10/2012; · 6.41 Impact Factor
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Meral Esen,
Benjamin Mordmüller,
Pablo Martinez de Salazar,
Ayola Akim Adegnika,
Selidji Todagbe Agnandji,
Frieder Schaumburg,
Aurore Bouyoukou Hounkpatin,
Sina Brückner,
Michael Theisen,
Sabine Bélard,
Ulysse Ateba Ngoa,
Saadou Issifou, Maria Yazdanbakhsh,
Peter G Kremsner
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ABSTRACT: BACKGROUND: Helminth infections are highly prevalent in the tropics and may have an effect on immune responses to vaccines due to their immunomodulatory effect. The prevalence of helminth infections in young children, the target group for malaria and most other vaccines, is high. Therefore we assessed the influence of helminth infection on vaccine-induced immune responses in a phase I clinical trial of the malaria vaccine candidate GMZ2. METHODS: Twenty Gabonese preschool-age children were vaccinated with GMZ2, a blood stage malaria vaccine candidate. Humoral immune response against the vaccine antigens and parasitological status were assessed. Vaccine-specific antibody concentrations and memory B-cell numbers were compared in worm infected and non-infected participants. RESULTS: Antibody response to GMZ2 was 3.4-fold (95% confidence interval: 1.6, 7.4) higher in Trichuris trichiura negative subjects compared to positive participants, whereas immunoglobulin subclass distribution was similar. Memory B-cell response was moderately increased in T. trichiura negative individuals, although the difference was not significant. CONCLUSIONS: Future malaria vaccine development programs need to account for worm-mediated hyporesponsiveness of immune reactions.
Vaccine 10/2012; · 3.77 Impact Factor
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Bart Everts,
Leonie Hussaarts,
Nicole N Driessen,
Moniek H J Meevissen,
Gabriele Schramm,
Alwin J van der Ham,
Barbara van der Hoeven,
Thomas Scholzen,
Sven Burgdorf,
Markus Mohrs,
Edward J Pearce,
Cornelis H Hokke,
Helmut Haas,
Hermelijn H Smits, Maria Yazdanbakhsh
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ABSTRACT: Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni eggs and abundantly present in soluble egg antigen, has recently been shown to condition dendritic cells (DCs) to prime Th2 responses. However, the molecular mechanisms underlying this effect remain unknown. We show in this study by site-directed mutagenesis of omega-1 that both the glycosylation and the RNase activity are essential to condition DCs for Th2 polarization. Mechanistically, we demonstrate that omega-1 is bound and internalized via its glycans by the mannose receptor (MR) and subsequently impairs protein synthesis by degrading both ribosomal and messenger RNA. These experiments reveal an unrecognized pathway involving MR and interference with protein synthesis that conditions DCs for Th2 priming.
Journal of Experimental Medicine 09/2012; 209(10):1753-67. · 13.85 Impact Factor
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ABSTRACT: Vitamin A supplementation (VAS) at birth was not associated with improved survival in a randomised, placebo-controlled trial in Guinea-Bissau. However, a negative sex-differential effect, which became evident after diphtheria-tetanus-pertussis (DTP) vaccination, was noted; among girls who had received DTP, VAS at birth was associated with two-fold higher mortality than placebo. The objective of the present study was to investigate the immunological effects of VAS at birth within a subgroup of participants in the randomised trial. Guided by the mortality results, we further explored whether VAS had a differential effect according to sex and DTP status. At 6 weeks after randomisation and supplementation, we measured differential leucocyte counts and TNF-α, interferon-γ, IL-10, IL-13 and IL-5 production in a whole-blood culture assay. A total of 471 children were included. VAS compared with placebo at birth was associated with a higher proportion of monocytes (relative risk ratio 1·26, 95 % CI 1·07, 1·49, P = 0·04), while spontaneous TNF-α production was lower in the VAS group (geometric mean ratio 0·54, 95 % CI, 0·37, 0·78, P = 0·001). Stratified analysis showed that VAS was associated with lower TNF-α and IL-10 production for girls without DTP and boys with DTP, resulting in significant three-way interactions between VAS, sex and DTP vaccination status (P = 0·03 and P = 0·04, respectively) for spontaneous TNF-α and IL-10 production. The results substantiate the potential role of VAS as an immunomodulatory intervention, which has different effects depending on concomitant health interventions and the sex of the recipient.
The British journal of nutrition 07/2012; · 3.45 Impact Factor
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ABSTRACT: Infection with filarial parasites is associated with T cell hyporesponsiveness, which is thought to be partly mediated by their ability to induce regulatory T cells (Tregs) during human infections. This study investigates the functional capacity of Tregs from different groups of filarial patients to suppress filaria-specific immune responses during human filariasis. Microfilaremic (MF), chronic pathology (CP) and uninfected endemic normal (EN) individuals were selected in an area endemic for Brugia timori in Flores island, Indonesia. PBMC were isolated, CD4CD25(hi) cells were magnetically depleted and in vitro cytokine production and proliferation in response to B. malayi adult worm antigen (BmA) were determined in total and Treg-depleted PBMC. In MF subjects BmA-specific T and B lymphocyte proliferation as well as IFN-gamma, IL-13 and IL-17 responses were lower compared to EN and CP groups. Depletion of Tregs restored T cell as well as B cell proliferation in MF-positives, while proliferative responses in the other groups were not enhanced. BmA-induced IL-13 production was increased after Treg removal in MF-positives only. Thus, filaria-associated Tregs were demonstrated to be functional in suppressing proliferation and possibly Th2 cytokine responses to BmA. These suppressive effects were only observed in the MF group and not in EN or CP. These findings may be important when considering strategies for filarial treatment and the targeted prevention of filaria-induced lymphedema.
PLoS Neglected Tropical Diseases 05/2012; 6(5):e1655. · 4.69 Impact Factor
