The interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is... Show moreThe interaction of malaria parasites with their human host is extensively studied, yet only few studies reported how P. falciparum infection affects urinary metabolite profiles and how this is associated with immunity. We present a longitudinal study of the urinary metabolic profiles of twenty healthy Africans with lifelong exposure to malaria and five malaria-naive Europeans, who were all challenged with direct venous inoculation of live P. falciparum sporozoites (PfSPZ) and followed up until they developed symptoms or became thick blood smear positive (TBS). Urine samples were collected before and at 2, 5, 9 and 11 days post challenge and were analysed. Upon infection, all Europeans became TBS positive, while Africans showed either a delay in time to parasitaemia or controlled infection. Our metabolic data showed that Europeans and Africans had distinct alterations in metabolite patterns, with changes mostly seen on days 5 and 9 post PfSPZ infection, and more prominently in Europeans. Within the African group, the levels of formate, urea, trimethylamine, threonine, choline, myo-inositol and acetate were significantly higher in TBS positive whereas the levels of pyruvate, 3-methylhistidine and dimethylglycine were significantly lower in individuals who remained TBS negative. Notably, before inoculation with PfSPZ, a group of metabolites including phenylacetylglutamine can potentially be used to predict parasitaemia control among Africans. Taken together, this study highlights the difference in urinary metabolic changes in response to malaria infection as a consequence of lifelong exposure to malaria and that change detectable before challenge might predict the control of parasitaemia in malaria-endemic areas. Show less
The substantial increase in the prevalence of non-communicable diseases in Indonesia might be driven by rapid socio-economic development through urbanization. Here, we carried out a longitudinal 1... Show moreThe substantial increase in the prevalence of non-communicable diseases in Indonesia might be driven by rapid socio-economic development through urbanization. Here, we carried out a longitudinal 1-year follow-up study to evaluate the effect of urbanization, an important determinant of health, on metabolic profiles of young Indonesian adults. University freshmen/women in Jakarta, aged 16-25 years, who either had recently migrated from rural areas or originated from urban settings were studied. Anthropometry, dietary intake, and physical activity, as well as fasting blood glucose and insulin, leptin, and adiponectin were measured at baseline and repeated at one year follow-up. At baseline, 106 urban and 83 rural subjects were recruited, of which 81 urban and 66 rural were followed up. At baseline, rural subjects had better adiposity profiles, whole-body insulin resistance, and adipokine levels compared to their urban counterparts. After 1-year, rural subjects experienced an almost twice higher increase in BMI than urban subjects (estimate (95%CI): 1.23 (0.94; 1.52) and 0.69 (0.43; 0.95) for rural and urban subjects, respectively, P-int < 0.01). Fat intake served as the major dietary component, which partially mediates the differences in BMI between urban and rural group at baseline. It also contributed to the changes in BMI over time for both groups, although it does not explain the enhanced gain of BMI in rural subjects. A significantly higher increase of leptin/adiponectin ratio was also seen in rural subjects after 1-year of living in an urban area. In conclusion, urbanization was associated with less favorable changes in adiposity and adipokine profiles in a population of young Indonesian adults. Show less
Background: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between... Show moreBackground: Adjuvants are essential in the induction of immunity by vaccines and interact with receptors, including the Toll-like receptors (TLRs). Responsiveness of these receptors differs between and within populations, which impacts vaccine effectiveness. Objective: Here we examine how the innate cytokine response towards TLR ligands differs between high and low socioeconomic status (SES) school-aged children from Makassar, Indonesia. Methods: We stimulated whole blood from children, of which 27 attended a high SES school and 27 children a low SES school, with ligands for TLR-2/1, -2/6, -3, -4, -5, -7, -9 and measured pro- (TNF) and anti-inflammatory (IL-10) cytokines released. Results: In the low SES there is an increased pro-inflammatory response after 24 h stimulation with TLR-2/1 ligand Pam3 and TLR-4 ligand LPS compared to the high SES. Comparison of the response to LPS after 24 h versus 72 h stimulation revealed that the pro-inflammatory response in the low SES after 24 h shifts to an antiinflammatory response, whereas in the high SES the initial anti-inflammatory response shifts to a strong proinflammatory response after 72 h stimulation. Conclusion: We observed differences in the TLR-mediated innate immune response between children attending low and high SES schools, which can have important implications for vaccine development Show less
Objective To report the prevalence of polyparasitism during pregnancy in the Lambarene region of Gabon and its association with newborn birth weight.Method Pregnant women in their third trimester... Show moreObjective To report the prevalence of polyparasitism during pregnancy in the Lambarene region of Gabon and its association with newborn birth weight.Method Pregnant women in their third trimester were recruited in a prospective study between November 2011 and March 2015. Parasite infection status was assessed microscopically in stool, urine and blood samples. Maternal demographic and obstetrical characteristics and newborns anthropometric data were collected. Multivariable logistic regression was used to assess the association between low birth weight and polyparasitism.Results 678 of 927 pregnant women were included for analysis with mean age (SD) of 25 (6.8) years. The analysis showed that 69% (468/678) were infected with at least one parasite (Plasmodium spp., Schistosoma spp., soil-transmitted helminths, filarial infections). This comprised of 38% with monoparasitism and 31% polyparasitism. The proportion of newborn babies with a weight below 2500 g (LBW) in our study was 21% (142/678). Compared to pregnant women without infection, women with monoparasitic infection had adjusted Odds Ratio confidence interval 95% CI (aOR [95%CI]) of 1.6 [0.95-2.73], those with two parasites had aOR 95%CI of 2.63 [1.51-4.62], and those with more than two parasites had aOR of 5.08 [2.5-10.38] for delivering a newborn with low birth weight.Conclusion In Lambarene, an endemic area for multiple parasite infections, there is a high prevalence of polyparasitism in pregnant women. Polyparasitism is associated with low birth weight. Therefore, there is an urgent need for active screening and treatment of parasite infections in pregnant women to assess the potential public health benefit of such interventions. Show less
Hoogerwerf, M.A.; Koopman, J.P.R.; Janse, J.J.; Langenberg, M.C.C.; Schuijlenburg, R. van; Kruize, Y.C.M.; ... ; Roestenberg, M. 2021
Background. Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output,... Show moreBackground. Controlled human hookworm infections could significantly contribute to the development of a hookworm vaccine. However, current models are hampered by low and unstable egg output, reducing generalizability and increasing sample sizes. This study aims to investigate the safety, tolerability, and egg output of repeated exposure to hookworm larvae.Methods. Twenty-four healthy volunteers were randomized, double-blindly, to 1, 2, or 3 doses of 50 Necator americanus L3 larvae at 2-week intervals. Volunteers were monitored weekly and were treated with albendazole at week 20.Results. There was no association between larval dose and number or severity of adverse events. Geometric mean egg loads stabilized at 697, 1668, and 1914 eggs per gram feces for the 1 x 50L3, 2 x 501.3, and 3 x 50L3 group, respectively. Bayesian statistical modeling showed that egg count variability relative to the mean was reduced with a second infectious dose; however, the third dose did not increase egg load or decrease variability. We therefore suggest 2 x 50L3 as an improved challenge dose. Model-based simulations indicates increased frequency of stool sampling optimizes the power of hypothetical vaccine trials.Conclusions. Repeated infection with hookworm larvae increased egg counts to levels comparable to the field and reduced relative variability in egg output without aggravating adverse events. Show less
Background Hookworms cause substantial morbidity in children and women of reproductive age. The control strategy of mass drug administration is suboptimal, hence the need for a vaccine. Necator... Show moreBackground Hookworms cause substantial morbidity in children and women of reproductive age. The control strategy of mass drug administration is suboptimal, hence the need for a vaccine. Necator americanus aspartic protease-1 (Na-APR-1) and N americanus glutathione S-transferase-1 (Na-GST-1) are involved in the digestion and detoxification of haemoglobin in the hookworm digestive tract. In animal models, vaccination against these antigens resulted in protection from challenge infection. Both vaccine candidates were shown to be safe and well tolerated when administered separately to healthy adults. We assessed the safety and immunogenicity of co-administered Na-GST-1 and Na-APR-1 (M74) vaccines in healthy Gabonese adults.Methods This randomised, controlled, double-blind, phase 1, dose-escalation trial was done at the Centre de Recherches Medicales de Lambarene, in a region of Gabon where N americanus and other helminths are prevalent. Healthy adults aged 18-50 years and living in Lambarene or the surrounding areas were recruited to the study. Participants were enrolled consecutively into two dose cohorts (30 mu g or 100 mu g of the experimental vaccines) and randomly assigned in blocks (block size four) to receive three doses of either co-administered Na-GST-1 plus Na-APR-1 (M74; 30 mu g or 100 mu g of each), adjuvanted with Alhydrogel (aluminium hydroxide gel suspension) together with an aqueous formulation of glucopyranosyl lipid A, or hepatitis B vaccine plus saline (control group). Vaccines were administered intramuscularly on days 0, 28, and 180. The primary endpoint was safety, with immunogenicity a secondary endpoint. The intention-to-treat population was used for safety analyses, whereas for immunogenicity analyses, the per-protocol population was used (participants who received all scheduled vaccinations). Control vaccine recipients for both dose cohorts were combined for the analyses. The trial is registered with ClinicalTrials.gov, NCT02126462.Findings Between Oct 27, 2014, and Jan 31, 2015, 56 individuals were screened for eligibility, of whom 32 were enrolled and randomly assigned to one of the three study groups (12 each in the 30 mu g and 100 mu g experimental vaccine groups and eight in the control group). Both study vaccines were well tolerated in both dose groups. The most common adverse events were mild-to-moderate injection-site pain, headache, myalgia, and nausea. No severe or serious adverse events related to the vaccines were recorded. 52 unsolicited vaccine-related adverse events occurred during the study, but there was no difference in frequency between vaccine groups. IgG antibodies were induced to each of the vaccine antigens, with mean IgG levels increasing after each vaccination. Vaccination with 100 mu g of each vaccine antigen consistently induced IgG seroconversion (IgG levels above the reactivity threshold). Peak IgG responses were observed 2 weeks after the third vaccine dose for both antigens, with all participants who received the 100 mu g doses seroconverting at that timepoint. IgG levels steadily declined until the final study visit 6 months after the third vaccination, although they remained significantly higher than baseline in the 100 mu g dose group.Interpretation Vaccination with recombinant Na-GST-1 and Na-APR-1 (M74) in healthy adults living in N americanusendemic areas of Gabon was safe and induced IgG to each antigen. To our knowledge, this study is the first to report results of Na-APR-1 (M74) co-administered with Alhydrogel in participants from an N americanus-endemic area. Further clinical development of these vaccines should involve efficacy studies. Funding European Union Seventh Framework Programme. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
Mbow, M.; Lell, B.; Jochems, S.P.; Cisse, B.; Mboup, S.; Dewals, B.G.; ... ; Yazdanbakhsh, M. 2020
BACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food... Show moreBACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food allergy in the developed world.OBJECTIVE: We used a standardized methodology to determine the prevalence and types of food-specific allergic sensitization and food allergies in schoolchildren from urban and rural regions of China, Russia, and India.METHODS: The current study is a multicenter epidemiological survey of children recruited from 5 cities in China (Hong Kong and Guangzhou), Russia (Tomsk), and India (Bengaluru and Mysore) and 1 rural county in Southern China (Shaoguan). A total of 35,549 children aged 6 to 11 years from 3 countries participated in this survey. Random samples of children from 3 countries were first screened by the EuroPrevall screening questionnaire. Children with and without a history of adverse reactions to foods were then recruited for the subsequent case-control comparative studies. We determined the prevalence rates of food-specific IgE sensitization and food allergies using the predefined criteria.RESULTS: The prevalence rates of food-specific IgE sensitization (>= 0.7 kU/L) to at least 1 food were 16.6% in Hong Kong, 7.0% in Guangzhou, 16.8% in rural Shaoguan, 8.0% in Tomsk, and 19.1% in India. Using a definition of probable food allergy as reporting allergic symptoms within 2 hours of ingestion of a specific food plus the presence of allergic sensitization to the specific food (positive IgE and/or positive skin prick test result), the prevalence of food allergy was highest in Hong Kong (1.50%), intermediate in Russia (0.87%), and lowest in Guangzhou (0.21%), Shaoguan (0.69%), and India (0.14%). For children recruited from Hong Kong, both sensitization and food allergy were significantly higher in children who were born and raised in Hong Kong when compared with those who were born in mainland China and migrated to Hong Kong, highlighting the importance of early-life exposures in affecting the subsequent development of food sensitization and food allergy.CONCLUSIONS: There are wide variations in the prevalence of food-specific IgE sensitization and food allergy in the 3 participating countries. Food allergy appears to be less common when compared with developed countries. The variations in the prevalence of food allergen sensitization cannot be explained by the differences in the degree of urbanization. Despite the high prevalence of food-specific IgE sensitization in India and rural China, food allergy is still extremely uncommon. In addition to IgE sensitization, other factors must play important roles resulting in the clinical manifestations of food allergies. (C) 2019 American Academy of Allergy, Asthma & Immunology Show less
Welch, V.A.; Hossain, A.; Ghogomu, E.; Riddle, A.; Cousens, S.; Gaffey, M.; ... ; Wells, G.A. 2019
Intestinal parasites affect millions of children globally. We aimed to assess effects of deworming children on nutritional and cognitive outcomes across potential effect modifiers using individual... Show moreIntestinal parasites affect millions of children globally. We aimed to assess effects of deworming children on nutritional and cognitive outcomes across potential effect modifiers using individual participant data (IPD). We searched multiple databases to 27 March 2018, grey literature, and other sources. We included randomised and quasi randomised trials of deworming compared to placebo or other nutritional interventions with data on baseline infection. We used a random-effects network meta-analysis with IPD and assessed overall quality, following a pre-specified protocol. We received IPD from 19 trials of STH deworming. Overall risk of bias was low. There were no statistically significant subgroup effects across age, sex, nutritional status or infection intensity for each type of STH. These analyses showed that children with moderate or heavy intensity infections, deworming for STH may increase weight gain (very low certainty). The added value of this review is an exploration of effects on growth and cognition in children with moderate to heavy infections as well as replicating prior systematic review results of small effects at the population level. Policy implications are that complementary public health strategies need to be assessed and considered to achieve growth and cognition benefits for children in helminth endemic areas. Show less
Background: Soil-transmitted helminths have been shown to have the immune regulatory capacity, which they use to enhance their long term survival within their host. As these parasites reside in the... Show moreBackground: Soil-transmitted helminths have been shown to have the immune regulatory capacity, which they use to enhance their long term survival within their host. As these parasites reside in the gastrointestinal tract, they might modulate the immune system through altering the gut bacterial composition. Although the relationships between helminth infections or the microbiome with the immune system have been studied separately, their combined interactions are largely unknown. In this study we aim to analyze the relationship between bacterial communities with cytokine response in the presence or absence of helminth infections. Results: For 66 subjects from a randomized placebo-controlled trial, stool and blood samples were available at both baseline and 21 months after starting three-monthly albendazole treatment. The stool samples were used to identify the helminth infection status and fecal microbiota composition, while whole blood samples were cultured to obtain cytokine responses to innate and adaptive stimuli. When subjects were free of helminth infection (helminth-negative), increasing proportions of Bacteroidetes was associated with lower levels of IL-10 response to LPS {estimate [95% confidence interval (CI)] -1.96 (-3.05, -0.87)}. This association was significantly diminished when subjects were helminth-infected (helminth positive) (p-value for the difference between helminth-negative versus helminth-positive was 0.002). Higher diversity was associated with greater IFN-gamma responses to PHA in helminth-negative (0.95 (0.15, 1.75); versus helminth-positive [-0.07 (-0.88, 0.73), p-value = 0.056] subjects. Albendazole treatment showed no direct effect in the association between bacterial proportion and cytokine responses, although the Bacteroidetes' effect on IL-10 responses to LPS tended downward in the albendazole-treated group [-1.74 (-4.08, 0.59)] versus placebo [-0.11 (-0.84, 0.62); p-value = 0.193]. Conclusion: We observed differences in the relationship between gut microbiome composition and immune responses, when comparing individuals infected or uninfected with geohelminths. Although these findings are part of a preliminary exploration, the data support the hypothesis that intestinal helminths may modulate immune responses, in unison with the gut microbiota. Show less
Parasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we... Show moreParasitic helminths evade, skew and dampen human immune responses through numerous mechanisms. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effects that soluble egg antigen (SEA) from Schistosoma mansoni had on modulating HIV-1 infection and cytokine/chemokine production in vitro. We determined that SEA, specifically through kappa-5, can potently bind to DC-SIGN and thereby blocks DC-SIGN mediated HIV-1 trans-infection (p<0.05) whilst not interfering with cis-infection. DCs exposed to SEA whilst maturing under Th2 promoting conditions, will upon co-culture with naive T-cells induce a T-cell population that was less susceptible to HIV-1 R5 infection (p<0.05) compared to DCs unexposed to SEA, whereas HIV-1 X4 virus infection was unaffected. This was not observed for DCs exposed to SEA while maturing under Th1 or Th1/Th2 (T-mix) promoting conditions. All T-cell populations induced by SEA exposed DCs demonstrate a reduced capacity to produce IFN-gamma and MIP-1 beta. The infection profile of T-cells infected with HIV-1 R5 was not associated with down-modulation of CCR5 cell surface expression. We further show that DCs maturing under T-mix conditions exposed to plant recombinant omega-1 protein (r omega-1), which demonstrates similar functions to natural omega-1, induced T-cell populations that were less sensitive for HIV-1 R5 infection (p<0.05), but not for X4 virus infection. This inhibition associated again with a reduction in IFN-gamma and MIP-1 beta expression, but additionally correlated with reduced CCR5 expression. We have shown that SEA parasite antigens and more specifically r omega-1 can modulate HIV-1 infectivity with the potential to influence disease course in co-infected individuals.Author summary Parasitic helminths have developed a number of strategies to evade, skew and dampen human immune responses. Such effects will likely have consequences for HIV-1 transmission and disease progression. Here we analyzed the effect that soluble egg antigen (SEA) from Schistosoma mansoni had on HIV-1 infection in vitro. We determined that SEA, through kappa-5, can potently block DC-SIGN mediated HIV-1 trans-infection of CD4(+) T-lymphocytes, but not block cis-infection. Dendritic cells (DC) exposed to SEA during maturation under Th2 skewing conditions, induce T-cell populations that are less susceptible to HIV-1 R5 infection compared to cells induced by unexposed DCs. HIV-1 X4 infection was unaffected. This restricted infection profile was not associated with down-modulation of CCR5 surface expression or observed differences in cytokine/chemokine production. Using recombinant omega-1, an abundant component of SEA, HIV-1 R5 infection was similarly inhibited with no effect on HIV-1 X4 infection levels. Hence SEA possesses antigens, namely omega-1, that can modulate HIV-1 infection and potentially influence disease course in co-infected individuals. Show less
Monino-Romero, S.; Lexmond, W.S.; Singer, J.; Bannert, C.; Amoah, A.S.; Yazdanbakhsh, M.; ... ; Szepfalusi, Z. 2019
Background: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.Objective:... Show moreBackground: It is proposed that helminth exposure protects against allergy-related disease, by mechanisms that include disconnecting risk factors (such as atopy) from effector responses.Objective: We aimed to assess how helminth exposure influences rural-urban differences in risk factors for allergy-related outcomes in tropical low- and middle-income countries.Methods: In cross-sectional surveys in Ugandan rural Schistosoma mansoni (Sm)-endemic islands, and in nearby mainland urban communities with lower helminth exposure, we assessed risk factors for atopy (allergen-specific skin prick test [SPT] reactivity and IgE [asIgE] sensitization) and clinical allergy-related outcomes (wheeze, urticaria, rhinitis and visible flexural dermatitis), and effect modification by Sm exposure.Results: Dermatitis and SPT reactivity were more prevalent among urban participants, urticaria and asIgE sensitization among rural participants. Pairwise associations between clinical outcomes, and between atopy and clinical outcomes, were stronger in the urban survey. In the rural survey, SPT positivity was inversely associated with bathing in lakewater, Schistosoma-specific IgG4 and Sm infection. In the urban survey, SPT positivity was positively associated with age, non-Ugandan maternal tribe, being born in a city/town, BCG scar and light Sm infection. Setting (rural vs urban) was an effect modifier for risk factors including Sm- and Schistosoma-specific IgG4. In both surveys, the dominant risk factors for asIgE sensitization were Schistosoma-specific antibody levels and helminth infections. Handwashing and recent malaria treatment reduced odds of asIgE sensitization among rural but not urban participants. Risk factors for clinical outcomes also differed by setting. Despite suggestive trends, we did not find sufficient evidence to conclude that helminth (Sm) exposure explained rural-urban differences in risk factors.Conclusions and clinical relevance: Risk factors for allergy-related outcomes differ between rural and urban communities in Uganda but helminth exposure is unlikely to be the sole mechanism of the observed effect modification between the two settings. Other environmental exposures may contribute significantly. Show less
Ruiter, K. de; Tahapary, D.L.; Sartono, E.; Nutman, T.B.; Smit, J.W.A.; Koenderman, L.; ... ; Yazdanbakhsh, M. 2019
Background. Eosinophils are a prominent cell type in the host response to helminths, and some evidence suggests that neutrophils might also play a role. However, little is known about the... Show moreBackground. Eosinophils are a prominent cell type in the host response to helminths, and some evidence suggests that neutrophils might also play a role. However, little is known about the activation status of these granulocytes during helminth infection.Methods. We analyzed the expression of eosinophil and neutrophil activation markers in peripheral blood by flow cytometry and measured serum levels of eosinophil granule proteins in 300 subjects residing in an area endemic for soil-transmitted helminths (STH). The data generated are on samples before and after 1 year of 3-monthly albendazole treatment.Results. Anthelmintic treatment significantly reduced the prevalence of STH. While eosinophil numbers were significantly higher in STH-infected compared to uninfected subjects and significantly decreased following albendazole treatment, there was no effect exerted by the helminths on either eosinophil nor neutrophil activation. Although at baseline eosinophil granule protein levels were not different between STH-infected and uninfected subjects, treatment significantly reduced the levels of eosinophil-derived neurotoxin (EDN) in those infected at baseline.Conclusions. These results show that besides decreasing eosinophil numbers, anthelmintic treatment does not significantly change the activation status of eosinophils, nor of neutrophils, and the only effect seen was a reduction in circulating levels of EDN. Show less
Amaruddin, A.I.; Wahyuni, S.; Hamid, F.; Chalid, M.T.; Yazdanbakhsh, M.; Sartono, E. 2019
ObjectiveTo investigate factors that determine the response to Bacille Calmette–Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to... Show moreObjectiveTo investigate factors that determine the response to Bacille Calmette–Guérin (BCG) vaccination in urban environments with respect to socioeconomic status (SES), prenatal exposure to infections or newborn's nutritional status.MethodsThe study was conducted in an urban area, in Makassar, Indonesia. At baseline, 100 mother and newborns pair from high and low SES communities were included. Intestinal protozoa, soil-transmitted helminths, total IgE, anti‐Hepatitis A Virus IgG and anti‐Toxoplasma IgG were measured to determine exposure to infections. Information on gestational age, birth weight/height and delivery status were collected. Weight‐for‐length z‐score, a proxy for newborns adiposity, was calculated. Leptin and adiponectin from cord sera were also measured. At 10 months of age, BCG scar size was measured from 59 infants. Statistical modelling was performed using multiple linear regression.ResultsBoth SES and birth nutritional status shape the response towards BCG vaccination at 10 months of age. Infants born to low SES families have smaller BCG scar size compared to infants born from high SES families and total IgE contributed to the reduced scar size. On the other hand, infants born with better nutritional status were found to have bigger BCG scar size but this association was abolished by leptin levels at birth.ConclusionThis study provides new insights into the importance of SES and leptin levels at birth on the development of BCG scar in 10 months old infants. Show less
Nkurunungi, G.; Diepen, A. van; Nassuuna, J.; Sanya, R.E.; Nampijja, M.; Nambuya, I.; ... ; Hokke, C.H. 2019
Core beta-1,2-xylose and alpha-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of... Show moreCore beta-1,2-xylose and alpha-1,3-fucose are antigenic motifs on schistosome N-glycans, as well as prominent IgE targets on some plant and insect glycoproteins. To map the association of schistosome infection with responses to these motifs, we assessed plasma IgE and IgG reactivity using microarray technology among Ugandans from rural Schistosoma mansoni (Sm)-endemic islands (n = 209), and from proximate urban communities with lower Sm exposure (n = 62). IgE and IgG responses to core beta-1,2-xylose and alpha-1,3-fucose modified N-glycans were higher in rural versus urban participants. Among rural participants, IgE and IgG to core beta-1,2-xylose were positively associated with Sm infection and concentration peaks coincided with the infection intensity peak in early adolescence. Responses to core alpha-1,3-fucose were elevated regardless of Sm infection status and peaked before the infection peak. Among urban participants, Sm infection intensity was predominantly light and positively associated with responses to both motifs. Principal component and hierarchical cluster analysis reduced the data to a set of variables that captured core beta-1,2-xylose- and alpha-1,3-fucose-specific responses, and confirmed associations with Sm and the rural environment. Responses to core beta-1,2-xylose and alpha-1,3-fucose have distinctive relationships with Sm infection and intensity that should further be explored for associations with protective immunity, and cross-reactivity with other exposures. Show less
