Trichuris Infection Research Articles

Nematode infections in Slovak children hospitalised during 2008–2009

Abstract A study involved 1800 hospitalised children (age: 9 months to 16 years) examined by ovoscopic analyses and confirmed the occurrence of Ascaris lumbricoides and Trichuris trichiura in 46 patients (2.55 %). Of these, 30 patients had Ascaris infection, 13 were positive for both nematodes and 3 patients had Trichuris infection. The mean count of A. lumbricoides eggs in positive cases was 1050 eggs per gramme (EPG) in range 150–4450 EPG. The mean count of T. trichiura eggs was 150 EPG (50–250 EPG). The highest intensities of A. lumbricoides and T. trichiura infections occurred in children 3–5 years of age living in poor hygienic conditions. Most common clinical conditions in all the patients included anaemia combined with complicated bronchopneumonia, colitis and gastritis. The strongest correlation between the parasite burden and selected laboratory test data (eosinophil count, haemoglobin, total serum iron) was found in children of 2 years of age (P < 0.05) and decreased with age.

Intenstinal Parasitic Infections in Primary School in Pulau Panggang and Pulau Pramuka, Kepulauan Seribu

Stool samples were collected and examined for soil-transmitted helminthic and protozoal infection in the first grade of three primary schools, located on Pulau Panggang and Pulau Pramuka, which are parts of a group of islands not far from the north coast of Jakarta. The stool examinations were part of activities during a control program on soil-transmitted helminthic infections. The schools have never participated with control programs on soil-transmitted helminthiases. For the examination of the samples a semi-quantitative Kato thick smear method was used and the direct smear with a 2% iodine solution. Four intestinal helminth species and five protozoa species were found in a total of 101 stool samples. Ascaris and Trichuris infections were found in 68.8% or more. Hookworm infection was only found in one school (2.9%). Eggs of Hymenolepis nana were detected in one sample. Cysts of Entamoeba histolytica and Entamoeba coli were both found in 5.0% of the samples, whereas Endolimax nana was recovered from 2.0% of the samples. High prevalence rates were detected for Blastocystis hominis (36.0%) and for Giardia lamblia it was 30.0%. Most of the Ascaris infections were categorized as light infections at School I (69.0%) and not a single heavy infection were found in this school. In School II and III most of the infections were moderate i.e. respectively 51.4 and 81.8%. Also in Schools II and III heavy infections were detected, respectively 11.4 and 5.8%. Fertilized Ascaris eggs were detected in 93.1%, 100% and 95.5% at School I, II and III respectively. As a whole among 86 positive samples 96.5% were recorded as samples with fertilized eggs, whereas 3.5% contained unfertilized eggs. The high prevalences of Ascaris and Trichuris infections in this area could be expected due to the low level of environmental hygiene and sanitation. Among the protozoal infections B. hominis and G. lamblia were the dominant species.

Early Helminth Infections Are Inversely Related to Anemia, Malnutrition, and Malaria and Are Not Associated with Inflammation in 6- to 23-Month-Old Zanzibari Children

Helminths aggravate anemia and malnutrition among school children. We studied this association in a cross-sectional study of 6- to 23-month-old Zanzibari children (N = 2322) and a sub-sample of 690 children matched on age and helminth infection status. Ascaris, hookworm, and Trichuris infections were diagnosed along with recent fever, malaria infection, mid-upper arm circumference (MUAC) and hemoglobin concentration (Hb). Alpha-1-acid glycoprotein (AGP), C-reactive protein (CRP), height, and weight were measured in the sub-sample. Infected children had higher Hb (beta = 5.44 g/L, P < 0.001) and MUAC-for-age Z score (beta = 0.30 Z, P < 0.001) compared with uninfected children after adjusting for covariates. Although helminths were not associated with inflammation, their association with Hb or MUAC-for-age Z score was modified by inflammation. Malaria-infected children were less likely to be infected with helminths (adjusted odds ratios 0.63 [95% confidence interval: 0.49, 0.81]). Non-anemic, better nourished, or non-malaria-infected children may be more exploratory of their environments and therefore increase their exposure to soil-transmitted helminths.

Geophagy As A Risk Factor For Helminth Infections In Pregnant Women In Lusaka, Zambia

It has been reported that geophagy is closely associated with helminthic diseases (1, 2, 3) and it has been especially linked to Ascaris and Trichuris infections among pregnant women (4). Hitherto proof of existence of viable infective ova in geophageal material has been anecdotal. This study was undertaken to determine the possible direct role of geophagy in helminthiases of pregnant women. Eighty-five pregnant women between the ages of 15 and 44 years of age were recruited into the study in order to determined the prevalence of geophagy among pregnant women resident in high a density and low income areas of Lusaka. The study showed that 31,8% of the pregnant women interviewed practised geophagy at the time of the study, and that 71% had a history of deliberate ingestion of soil. The preferences for the soil types were ranked as clay, termite mounds from tree trunks, and soft stone. Some respondents reported a preference for smoked, roasted or baked clay soils. Perceived benefits of geophagy included diminished craving when they ate soil ( 35.2% ), prevention of vomiting and nausea ( 32.4% ), and others ingested soil for the taste (32.4% ). Most women who were interviewed (91.8%) were aware of possible health risks involved in geophagy such as constipation, heartburn, anemia, coughing, infections with worms, and abdominal discomfort. This study sought to recover and identify helminth ova from a total 3.15Kg. Submitted or collected soil types ingested by the women in the study. No ova was recovered from the soil samples by both the sedimentation and Zinc Sulphate, as well as saturated sodium chloride floatation techniques. These techniques reliably yielded Ascaris, Schistosome, and hookworm ova and Strongyloides larvae in spiked control specimens. Notably, Ascaris lumbricoides, and Trichuris trichiura ova require moisture to survive and embryonate. The soils ingested by the respondents were dried, some of which are roasted, backed or smoked before ingestion and thus rendering them unsuitable for the survival of ova, let alone the support of embryonated ova which are the infectious stages. This study has demonstrated that no ova were recovered from any of the soil types preferred by the pregnant women, and as such geophagy was an unlikely risk factor for geohelminth infections. Other explanations for the high helminth infection rates among pregnant women recorded in the literature must be sought, such as pica, poor hygiene, and unsanitary environments.

IL-31-IL-31R Interactions Limit the Magnitude of Th2 Cytokine-Dependent Immunity and Inflammation following Intestinal Helminth Infection

IL-31 is a recently identified cytokine made predominantly by CD4(+) Th2 cells and its receptor, IL-31R, is expressed by a number of cell types including monocytes, epithelial cells, and T cells. Originally identified as a potential mediator of inflammation in the skin, we recently reported a novel function for endogenous IL-31R interactions in limiting type 2 inflammation in the lung. However, whether IL-31-IL-31R interactions regulate immunity or inflammation at other mucosal sites, such as the gut, is unknown. In this study, we report a regulatory role for IL-31-IL-31R interactions in the intestine following infection with the gastrointestinal helminth Trichuris muris, immunity to which is critically dependent on CD4(+) Th2 cells that produce IL-4 and IL-13. IL-31Ralpha was constitutively expressed in the colon and exposure to Trichuris induced the expression of IL-31 in CD4(+) T cells. In response to Trichuris infection, IL-31Ralpha(-/-) mice exhibited increased Th2 cytokine responses in the mesenteric lymph nodes and elevated serum IgE and IgG1 levels compared with wild type mice. IL-31Ralpha(-/-) mice also displayed enhanced goblet cell hyperplasia and a marked increase in secretion of goblet cell-derived resistin-like molecule beta into the intestinal lumen. Consistent with their exacerbated type 2 inflammatory responses, IL-31Ralpha(-/-) mice exhibited accelerated expulsion of Trichuris with significantly decreased worm burdens compared with their wild type counterparts early following infection. Collectively, these data provide the first evidence of a function for IL-31-IL-31R interactions in limiting the magnitude of type 2 inflammatory responses within the intestine.

Geohelminth infection and re-infection after chemotherapy among slum-dwelling children in Durban, South Africa

The prevalences and intensities of Ascaris lumbricoides, Trichuris trichiura and hookworm (probably Necator americanus) infection were measured in the young children (aged 2-10 years) living in 10 urban slums in Durban, South Africa. Re-infection was assessed at 4-6 and 12 months post-treatment. The baseline prevalences of A. lumbricoides and T. trichiura were 81.7%-96.3% and 54.5%-86.2%, respectively, and the corresponding geometric mean intensities were 960 and 91 eggs/g faeces. Most (85%) of the children found infected with A. lumbricoides and 23% of those found infected with T. trichiura had moderate-heavy infections. A few of the children investigated had intensities of Ascaris and Trichuris infection that were considerably higher than those previously recorded in South Africa. The baseline prevalences of hookworm infection (0%-20% in individual slums, with a mean of 4.7%) and intensities of such infection (geometric mean=17 eggs/g) were relatively low. Albendazole proved very effective against A. lumbricoides and hookworm but less so against T. trichiura. Re-infection by A. lumbricoides and T. trichiura reached pre-treatment prevalences by 4-6 months post-treatment in some of the slums and by 12 months in all the other slums. By 12 months post-treatment, the intensities of A. lumbricoides infection had reached their pre-treatment levels while those of T. trichiura infection were higher than at baseline. Approximately 50% of children had moderate-heavy T. trichiura infections at 12 months post-treatment compared with approximately 23% at baseline. Hookworm infections did not re-appear after treatment. The results show clearly that urban slums should be included in any future helminth-control programmes in South Africa.

IL-25 promotes TH2 responses through the induction of IL-2 (47.34)

Abstract Dysregulated CD4+ T helper type 2 (TH2) responses are a predominant feature of allergic inflammation, asthma and ulcerative colitis. Unlike TH1 and TH17 cells that employ distinct innate cell-derived cytokines to initiate their differentiation programs (IL-12 for TH1 cells and IL-6 and TGF-β for TH17 cells), TH2 cell development appears to be regulated primarily by autocrine IL-2 and IL-4. However, the factors that regulate expression of IL-2 in developing TH2 cells remain unclear. Here, we demonstrate that the cytokine IL-25 (IL-17E) induces early expression of IL-2 in developing TH2 cells, enhances TH2 cell proliferation and can promote TH2 cell development in the absence of IL-4Rα signaling. Surprisingly, IL-2 was not required for the IL-25-induced increase in CD4+ T cell proliferation, but the ability of IL-25 to promote TH2 responses was lost in the absence of IL-2. In vivo, treatment of resistant mice with an antibody against IL-2 results in impaired TH2 cell-mediated immunity to Trichuris infection. Together, these results identify IL-25 as an upstream differentiation factor for TH2 cells and suggest that manipulation of IL-25 may provide therapeutic benefits for diseases associated with dysregulated TH2 responses.

High heritability for Ascaris and Trichuris infection levels in pigs

Aggregated distributions of macroparasites within their host populations are characteristic of most natural and experimental infections. We designed this study to measure the amount of variation that is attributable to host genetic factors in a pig-helminth system. In total, 195 piglets were produced after artificial insemination of 19 sows (Danish Landrace-Yorkshire crossbreds) with semen selected from 13 individual Duroc boars (1 or 2 sows per boar; mean litter size: 10.3; 5-14 piglets per litter). Starting at 10 weeks of age, piglets were repeatedly infected with the gastrointestinal helminths Trichuris suis and Ascaris suum by administering eggs in the feed for 14 weeks until necropsy. Faecal egg counts (FECs) were estimated regularly and A. suum worm burden was obtained at necropsy. Heritability calculations for log (FEC+1) at weeks 7-10 post-infection (p.i.) showed that 0.32-0.73 of the phenotypic variation for T. suis could be attributed to genetic factors. For A. suum, heritabilities of 0.29-0.31 were estimated for log (FEC+1) at weeks 7-14 p.i., whereas the heritability of log worm counts was 0.45. Strong positive genetic correlations (0.75-0.89) between T. suis and A. suum FECs suggest that resistance to both infections involves regulation by overlapping genes. Our data demonstrate that there is a strong genetic component in resistance to A. suum and T. suis infections in pigs. Identification of responsible genes would enhance our understanding of the host immune response to these common nematodes and for the closely related species (T. trichiura and A. lumbricoides) in man infecting more than a billion people.

The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden.

ObjectiveTo estimate the degree of synergism between helminth species in their combined effects on anemia.MethodsQuantitative egg counts using the Kato–Katz method were determined for Ascaris lumbricoides, hookworm, Trichuris trichiura, and Schistosoma japonicum in 507 school-age children from helminth-endemic villages in The Philippines. Infection intensity was defined in three categories: uninfected, low, or moderate/high (M+). Anemia was defined as hemoglobin <11 g/dL. Logistic regression models were used to estimate odds ratios (OR), 95% confidence intervals (CI), and synergy index for pairs of concurrent infections.ResultsM+ co-infection of hookworm and S. japonicum (OR = 13.2, 95% CI: 3.82–45.5) and of hookworm and T. trichiura (OR = 5.34, 95% CI: 1.76–16.2) were associated with higher odds of anemia relative to children without respective M+ co-infections. For co-infections of hookworm and S. japonicum and of T. trichiura and hookworm, the estimated indices of synergy were 2.9 (95% CI: 1.1–4.6) and 1.4 (95% CI: 0.9–2.0), respectively.ConclusionCo-infections of hookworm and either S. japonicum or T. trichiura were associated with higher levels of anemia than would be expected if the effects of these species had only independent effects on anemia. This suggests that integrated anti-helminthic treatment programs with simultaneous deworming for S. japonicum and some geohelminths could yield a greater than additive benefit for reducing anemia in helminth-endemic regions.

A randomized, double-blind, multicenter clinical trial on the efficacy of ivermectin against intestinal nematode infections in China

To assess the efficacy of ivermectin against intestinal nematode infections, a randomized, double-blind, multicenter clinical trial was carried out in a total of 816 human individuals infected with different nematodes from three counties in China. The subjects were randomly assigned into experimental and control groups and orally given a single dose of 0.1, 0.2, 0.2 and 0.2 mg/kg ivermectin against Ascaris lumbricoides, hookworm, Trichuris trichiura and Enterobius vermicularis, respectively. Parallel control groups to each of the ivermectin groups were given a single oral dose of 6.7 mg/kg albendazole. The cure rates with ivermectin and albendazole were 100% (102/102) and 99.0% (101/102) for Ascaris, and 66.7% (68/102) and 67.7% (69/102) for Trichuris, respectively, with no significant difference ( P > 0.05) between the two treatments. The parasitological cure rates of albendazole were 69.6% (71/102) for hookworm and 94.1% (96/102) for Enterobius, which were significantly higher than ivermectin (33.3% and 52.9%, respectively, P < 0.0001). The expulsion of worm in the feces reached its peak 1–2 days after ivermectin treatment. The study showed that ivermectin, with few side effects, could be used as an additional treatment tool for intestinal nematodes, especially for the treatment of Ascaris and Trichuris infections in China.

TSLP‐TSLPR interactions license dendritic cell responses and CD4+ T cell dependent immunity and inflammation in the intestine

Thymic stromal lymphopoeitin (TSLP) is an epithelial cell derived cytokine that has been shown to promote Th2 cytokine‐dependent inflammation in the skin and lung. However, the role of TSLP in regulating Th2 cytokine‐dependent immunity and inflammation in the intestine has not been tested. Utilizing TSLPR−/− mice we showed that TSLP‐TSLPR interactions are critical for immunity to the intestinal pathogen Trichuris. While littermate controls exhibited expression of Th2 cytokines and cleared infection, TSLPR−/− mice produced increased levels of Trichuris‐specific IFNγ and remained persistently infected. In vitro, pre‐exposure of DCs to rTSLP selectively inhibited LPS‐induced IL‐12/23p40 expression suggesting that TSLP functions to inhibit proinflammatory cytokines. To address whether TSLP‐TSLPR interactions were necessary for the induction of the protective Th2 cytokine response following Trichuris infection, TSLPR−/− mice were infected and treated with neutralizing anti‐IFNγ antibodies. Following anti‐IFNγ treatment, TSLPR−/− mice exhibited a protective Th2 immune response and cleared infection. Taken together, these data suggest that within the intestine TSLP‐TSLPR interactions are not required to directly promote pathogen‐specific Th2 cytokine responses, but instead create a Th2 permissive environment through inhibition of DC‐derived proinflammatory cytokines.

A dual function for RELMβ in promoting TH1 immune responses and infection‐induced intestinal inflammation

The secreted goblet cell‐derived protein Resistin‐like moleculeβ (RELMβ) has been implicated in divergent functions including immunity to intestinal infection and promotion of chemical‐induced colitis. However, the mechanisms through which RELMβ influences proinflammatory responses and adaptive immunity are undefined. To investigate the function of RELMβ in this context, we employed a model of chronic Trichuris infection characterized by RELMβ expression, IFNγ production and severe intestinal inflammation. In contrast to WT mice, RELMβ −/− mice failed to establish chronic infection, and parasite clearance was associated with decreased production of IFNγ and TNFα and reduced intestinal inflammation. Based on these findings, we hypothesized a role for RELMβ in promoting proinflammatory responses by influencing accessory cell function and/or through direct effects on CD4 T cells. While recombinant RELMβ did not directly affect CD4 T cells, rRELMβ treatment of macrophages induced MHC Class II expression, secretion of IL‐12 and TNFα , and augmented their ability to promote antigen‐specific TH1 cell differentiation. Taken together, these data demonstrate a previously unidentified role for an intestinal goblet cell‐derived factor in the modulation of proinflammatory responses and adaptive immunity through direct effects on macrophages.

High titre of anti‐Ascaris immunoglobulin E associated with bronchial asthma symptoms in 5‐year‐old rural Bangladeshi children

Increasing interest has arisen whether helminthic infections protect against asthma and allergy. The prevalence of wheezing among Bangladeshi children is higher in rural areas where helminthic infectious burden is greater, which is contrary to the general assumption. We therefore examined the association between Ascaris infection, serum level of anti-Ascaris IgE, which should be investigated differently from the infection, and wheezing in 5-year-old children from rural Bangladesh. A total of 219 children who reported wheezing during the previous 12 months and 122 randomly selected age-matched individuals who had never experienced wheezing were tested for serum levels of total and specific Ascaris, Dermatophagoides pteronyssinus, alternaria and cockroach IgEs, and for intestinal helminth infection as well. Anti-Ascaris IgE levels were significantly and independently associated with current wheezing during the previous 12 months [odds ratio (OR) per log(e) increment is 1.31 (95% confidence interval (CI) 1.08-1.60), P=0.007], a history of at least four episodes of wheezing [OR per log(e) increment is 1.52 (95% CI 1.18-1.96), P=0.001], wheezing with sleep disturbances [OR per log(e) increment is 1.35 (95% CI 1.10-1.64), P=0.011] and wheezing with speech disturbances [OR per log(e) increment is 1.57 (95% CI 1.19-2.08), P=0.001]. These were adjusted for gender, pneumonia history, parental asthma, Trichuris infection, use of dry leaves as fuel and other specific IgE levels. The prevalence of Ascaris infection by the presence of wheezing was not significantly different (76% vs. 72%, respectively). We conclude that a high titre of anti-Ascaris IgE is associated with an increased risk of asthma symptoms among 5-year-old rural Bangladeshi children with a high helminthic infectious load.

Anemia and intestinal parasite infection in school children in rural Vietnam.

This study hypothesized that besides iron deficiency, intestinal parasites infection is also a determinant of anemia in schoolchildren in rural Vietnam. 400 primary schoolchildren from 20 primary schools in Tam Nong district, a poor rural area in Vietnam, were randomly selected from enrollment lists. Venous blood (5ml) was collected in a cross sectional study and analyzed for hemoglobin (Hb), serum ferritin (SF), serum transferrin receptor (TfR), serum C-reactive protein (CRP) and total immunoglobulin E (IgE). Stools samples were examined for hookworm, Trichuris, and Ascaris infection. Logistic regression was used to assess the effect of intestinal parasites on anemia. The prevalence of anemia (Hb < 115g/l) was 25%. Iron deficiency (TfR > 8.5mg/L) occurred in 2% of the children. The prevalence of intestinal parasites was 92% with the highest prevalence for Trichuris (76%) and Ascaris (71%). More than 30% and 80% of the children showed an elevated CRP (> or = 8 mg/L) and IgE (> 90 IU/ml) concentration. Anemia status was borderline significantly associated with SF and not associated with TfR and CRP. The prevalence odds ratio for Trichuris infection was 1.96 (95% CI 1.07-3.59) and 2.00 (95% CI 1.08-3.65) with iron deficiency reflected by TfR and SF, respectively. Anemia is highly prevalent among schoolchildren in Vietnam but may not be associated with iron deficiency. Trichuris infection is associated with a doubled risk of anemia, not mediated through iron deficiency. Chronic infection may play a role in anemia, but needs further investigation.

Parasite and maternal risk factors for malnutrition in preschool-age children in Belen, Peru using the new WHO Child Growth Standards

Child malnutrition, including wasting, underweight and stunting, is associated with infections, poor nutrient intake, and environmental and socio-demographic factors. Preschool-age children are especially vulnerable due to their high growth requirements. To target interventions for preschool-age children in a community of extreme poverty in Peru, we conducted a household survey between October 2005 and January 2006 to determine the prevalence of malnutrition and its risk factors. Of 252 children < 5 years old, the prevalence of wasting, underweight and stunting was 26.6, 28.6 and 32.1 %, respectively, based on the new WHO Child Growth Standards. Risk factors for wasting were: (1) moderate-high intensity Trichuris infection (OR 2.50; 95 % CI 1.06, 5.93); (2) hookworm infection (OR 6.67; 95 % CI 1.08, 41.05); (3) age (OR6-month 1.27; 95 % CI 1.11, 1.46); (4) maternal education (secondary incomplete) (OR 5.77; 95 % CI 2.38, 13.99); and (5) decreasing maternal BMI (OR1 kg/m2 1.12; 95 % CI 1.02, 1.23). Risk factors for underweight were: (1) moderate-high intensity Trichuris infection (OR 4.74; 95 % CI 1.99, 11.32); (2) age (OR6-month 1.22; 95 % CI 1.07, 1.38); (3) maternal education (secondary incomplete) (OR 2.92; 95 % CI 1.40, 6.12); and (4) decreasing maternal BMI (OR1 kg/m2 1.11; 95 % CI 1.02, 1.21). Risk factors for stunting were: (1) age (OR6-month 1.14; 95 % CI 1.02, 1.27) and (2) decreasing maternal height (OR1 cm 1.12; 95 % CI 1.06, 1.20). Overall, risk factors for malnutrition included both child and maternal determinants. Based on these data, locally appropriate and cost-effective dietary, de-worming and educational programmes should be targeted to mothers and preschool-age children.

Helminth infections among people using wastewater and human excreta in peri‐urban agriculture and aquaculture in Hanoi, Vietnam

To assess the prevalence of helminth infections and their associated risks in a community using both wastewater and human excreta in agriculture and aquaculture. A cross-sectional study was conducted in a peri-urban area in Hanoi, Vietnam. Data on the demography, socioeconomics and sanitation were collected from a survey of 400 agricultural households. Parasitological examination for the eggs of Ascaris sp., Trichuris sp. and hookworm was performed on single stool specimens obtained from study household members' 15-70 years and 0-72 months of age. Of 807 stool samples collected from 620 adults and 187 children, 39% were infected with helminths. The prevalence of infections with Ascaris sp., Trichuris sp. and hookworm was 21.6%, 9.8% and 21.8%, respectively. Univariate and multivariate analyses showed that being an adult, female gender, living in a household without a latrine, excreta composted for less than 1 month and use of fresh human excreta were significantly associated with co-infection with all three helminths. Being an adult was an independent determinant for infections with individual helminths. The absence of a latrine and use of stored urine for irrigation were associated with an increased risk of Ascaris infection. Risk factors for Trichuris infection were inadequately composted excreta and year-round wastewater contact; risk factors for hookworm infection were female gender, household without a latrine and use of fresh human excreta. Wastewater exposure did not pose a major risk for helminth infection in this community. Instead, lack of sanitation facilities and use of fresh or inadequately composted human excreta in agriculture were important risk factors.

Geophagia is not associated with Trichuris or hookworm transmission in Zanzibar, Tanzania

Geophagia may be harmful as a method for the transmission of geohelminths. In this study, we pose two questions in a representative sample of 970 pregnant women from Pemba Island, Zanzibar, Tanzania. Can consumed earth be a vector for geohelminth infection? And do geophagists have differential parasitic infection? The parasitological content of 59 non-food substance samples was analysed. Cross-sectional data regarding pica behaviour were collected through interviews conducted by local researchers. Ascaris, Trichuris and hookworm status was ascertained through Kato-Katz smears. The prevalence of geophagia at baseline was 5.6% and the overall prevalence of Ascaris, Trichuris and hookworm infection was 5.6%, 33.2% and 32.9%, respectively. No consumed soil samples contained infectious parasitic stages, and only one of the consumed pica substances (charcoal) contained parasites of potential risk to human health. In bivariate analyses, neither the prevalence nor the intensity of infection with Ascaris, Trichuris or hookworm differed significantly by geophagia status. Furthermore, in multivariate models, geophagia was not a significant predictor of helminth infection status. We conclude that geophagia is not a source of Trichuris or hookworm infection among pregnant women in Pemba (insufficient power to evaluate the effect of Ascaris), which is in contrast to existing findings of helminth infection and geophagia.

Trichuris suis excretory/secretory antigen‐specific antibodies in serum from single‐inoculated pigs

The humoral immune response induced by Trichuris infections has mostly been described in mouse models and in infected humans, but as the immunomodulatory effect of Trichuris suis, the swine whipworm, becomes increasingly documented, the need for understanding the response induced by this specific parasite species grows. In the present study we describe changes in serum IgG1, IgG2, IgA and IgM antibodies specific to adult T. suis excretory/secretory (E/S) antigens in the time course of a primary infection in swine. The average levels of specific IgG1, IgG2 and IgM peaked at 9 weeks post-inoculation and then declined within a few weeks of worm expulsion. The IgA level rose earlier and remained elevated after worm expulsion. The protective role of Trichuris-specific antibodies is uncertain, but some of them presumably reflect the presence of worms in the intestine. Further development of this analysis could have diagnostic value in swine and humans infected with T. suis for experimental or therapeutic purposes.

Epithelial cell-intrinsic IKKβ expression regulates innate and adaptive immunity in the gut (42.4)

Abstract Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the regulation of immunity is unknown. Here we show that IEC-intrinsic IKKβ-dependent gene expression is a critical regulator of dendritic cell (DC) and CD4+ T cell responses in the gut. Following infection with the parasite Trichuris, littermate control mice develop pathogen-specific TH2 cytokine responses and eradicate infection while mice with an IEC-specific deletion of IKKβ (IkkbΔIEC mice) fail to do so. Further, IkkbΔIEC mice exhibit exacerbated production of DC-derived IL-12/23p40 and TNF-α, heightened levels of CD4+ T cell-derived IFN-γ and IL-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKKβ in IECs to promote CD4+ TH2 cell-dependent immunity, identifying a critical role for IECs in limiting type 1 cytokine production in the GI tract. These results suggest that the balance of IKKβ-dependent gene expression is critical for intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation. This work is funded by the NIH, CCFA and the Irvington Institute.

Epithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis

Intestinal epithelial cells (IECs) provide a primary physical barrier against commensal and pathogenic microorganisms in the gastrointestinal (GI) tract, but the influence of IECs on the development and regulation of immunity to infection is unknown. Here we show that IEC-intrinsic IkappaB kinase (IKK)-beta-dependent gene expression is a critical regulator of responses of dendritic cells and CD4+ T cells in the GI tract. Mice with an IEC-specific deletion of IKK-beta show a reduced expression of the epithelial-cell-restricted cytokine thymic stromal lymphopoietin in the intestine and, after infection with the gut-dwelling parasite Trichuris, fail to develop a pathogen-specific CD4+ T helper type 2 (T(H)2) response and are unable to eradicate infection. Further, these animals show exacerbated production of dendritic-cell-derived interleukin-12/23p40 and tumour necrosis factor-alpha, increased levels of CD4+ T-cell-derived interferon-gamma and interleukin-17, and develop severe intestinal inflammation. Blockade of proinflammatory cytokines during Trichuris infection ablates the requirement for IKK-beta in IECs to promote CD4+ T(H)2 cell-dependent immunity, identifying an essential function for IECs in tissue-specific conditioning of dendritic cells and limiting type 1 cytokine production in the GI tract. These results indicate that the balance of IKK-beta-dependent gene expression in the intestinal epithelium is crucial in intestinal immune homeostasis by promoting mucosal immunity and limiting chronic inflammation.