Soil-transmitted helminth infections in school children of three districts of Malakand region, Khyber Pakhtunkhwa, Pakistan.

Information on prevalence of soil-transmitted helminth (STH) infections among school children is scarce in Pakistan. This study was aimed to investigate the prevalence of soil-transmitted helminth in school children of three districts in, Khyber Pakhtunkhwa, Pakistan. A total of 300 stool samples were examined from August 2015 to August 2016 using direct smear (Normal saline and Lugol's Iodine solution) and the concentration methods. One hundred and eighty seven (62.3%) pupils were found infected with soil-transmitted helminths. One hundred and forty five (77.5%) were infected with single parasite and forty two (22.4%) with multiple infections. Ascaris lumbricoides 125 (66.4%), Trichuris trichura 50 (26.5%) and Ancylostoma duedenale 13 (6.91%) were detected. The children above 8 years in age were more parasitized than below 8 years (p=0.7832; P>0.05). Males were found more parasitized than females (p=0.9315; P>0.05). Children in lower Dir district were found more infected followed by Swat and upper Dir (P< 0.0001; p<0.05). No significant relationship was found among the examined and that of infected children for ages and sex in all the districts. Malakand division is an area with poor hygiene located in temperate zone near the border of Afghanistan and China. The prevalence of reported nematode parasites here compared with the same studies is unexpectedly high. These types of studies should continue time to time to know the hazardous nature of such parasitic infections for the betterment of the human health.

Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

Effect of anthelminthic treatment on helminth infection and related anaemia among school-age children in northwestern Ethiopia.

BACKGROUND: Information about improvements in the health status of population at-risk of helminth infection after anthelminthic treatment helps to evaluate the effectiveness of the large scale deworming program. The objectives of this study were to assess the impact of anthelminthic treatment on the prevalence and intensity of intestinal helminth infection, haemoglobin level and prevalence of anaemia among school-age children. METHODS: A total of 403 children attending Tikur Wuha Elementary School in Jiga, northwestern Ethiopia were enrolled in this study between February and March 2011. Formol-ether concentration and Kato-Katz methods were used to examine stool for intestinal helminth infections at baseline and one month after anthelminthic treatment. Haemoglobin level was measured using Hemocue machine at baseline and one month after anthelminthic treatment. RESULTS: Out of 403 school children examined, 15.4 % were anaemic and 58.3 % were infected with intestinal helminths at baseline. Hookworms (46.9 %), Schistosoma mansoni (24.6 %), Ascaris lumbricoides (4.2 %) and Trichuris trichiura (1.7 %) infections were common. The odds of anaemia was higher among children infected with helminths (adjusted odds ratio (aOR) = 3.83, 95 % CI = 1.92, 7.62) especially in those infected with hookworm (aOR = 2.42, 95 % CI = 1.34, 4.39) or S. mansoni (aOR = 2.67, 95 % CI = 1.46, 4.88) and two or more helminth species (aOR = 7.31, 95 % CI = 3.27, 16.35) than those uninfected with intestinal helminths at baseline. Significant reduction in prevalence of helminth infection (77.0 %) and increment in mean haemoglobin level (+3.65 g/l) of children infected with helminths was observed one month after anthelminthic treatment. The increase in haemoglobin level after anthelminthic treatment was significantly positively associated with the age, but negatively associated with the haemoglobin level at baseline. The change in mean haemoglobin level was significantly higher among undernourished than normal children. Percent reduction in the prevalence of anaemia among children infected with helminths was 25.4 % after anthelminthic treatment. CONCLUSIONS: The present study provides evidence that anthelminthic treatment of school-age children infected with intestinal helminth can improve haemoglobin level in addition to reducing the prevalence and intensity of helminth infections one month after treatment. This suggests that deworming of children may benefit the health of children in sub-Sharan Africa where hookworm and S. mansoni infections are prevalent.

Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

Genetic analysis of the Trichuris muris-induced model of colitis reveals QTL overlap and a novel gene cluster for establishing colonic inflammation.

BACKGROUND: Genetic susceptibility to colonic inflammation is poorly defined at the gene level. Although Genome Wide Association studies (GWAS) have identified loci in the human genome which confer susceptibility to Inflammatory Bowel Disease (Crohn's and Ulcerative Colitis), it is not clear if precise loci exist which confer susceptibility to inflammation at specific locations within the gut e.g. small versus large intestine. Susceptibility loci for colitis in particular have been defined in the mouse, although specific candidate genes have not been identified to date. We have previously shown that infection with Trichuris muris (T. muris) induces chronic colitis in susceptible mouse strains with clinical, histological, and immunological homology to human colonic Crohn's disease. We performed an integrative analysis of colitis susceptibility, using an F2 inter-cross of resistant (BALB/c) and susceptible (AKR) mice following T. muris infection. Quantitative Trait Loci (QTL), polymorphic and expression data were analysed alongside in silico workflow analyses to discover novel candidate genes central to the development and biology of chronic colitis. RESULTS: 7 autosomal QTL regions were associated with the establishment of chronic colitis following infection. 144 QTL genes had parental strain SNPs and significant gene expression changes in chronic colitis (expression fold-change ≥ +/-1.4). The T. muris QTL on chromosome 3 (Tm3) mapped to published QTL in 3 unrelated experimental models of colitis and contained 33 significantly transcribed polymorphic genes. Phenotypic pathway analysis, text mining and time-course qPCR replication highlighted several potential cis-QTL candidate genes in colitis susceptibility, including FcgR1, Ptpn22, RORc, and Vav3. CONCLUSION: Genetic susceptibility to induced colonic mucosal inflammation in the mouse is conserved at Tm3 and overlays Cdcs1.1. Genes central to the maintenance of intestinal homeostasis reside within this locus, implicating several candidates in susceptibility to colonic inflammation. Combined methodology incorporating genetic, transcriptional and pathway data allowed identification of biologically relevant candidate genes, with Vav3 newly implicated as a colitis susceptibility gene of functional relevance.

Anemia and undernutrition in intestinally parasitized schoolchildren from Gakenke district, Northern Province of Rwanda.

BACKGROUND: Rwanda is a sub-Saharan country, where intestinal parasite infections, anemia and undernutrition coexist. The purpose of this research is to study the relationship between intestinal parasite infections and undernutrition/anemia to clarify the priorities of intervention in the rural area of Gakenke district in the Northern Province of Rwanda. MATERIALS AND METHODS: A total of 674 students from Nemba I School, participated in a cross-sectional study, in which their parasitological and nutritional status were analysed. Statistical analysis was performed by χ2 test, univariate analysis and Odds ratios (OR). RESULTS: A total of 95.3% of children presented intestinal parasitism, most of whom (94.5%) infected by protozoa and 36.1% infected by soil-transmitted helminths (STH), with Trichuris trichiura (27.3%) being the most prevalent. Multiple infections were found to be high (83.8%), with protozoa and STH co-infections in 30.6%. STH infections were mainly of low/moderate intensity. Neither infection nor STH infection of any intensity profile, was significantly related to anemia. In addition, STH infection, regardless of the intensity profile, was not associated with stunting, underweight or thinness. There was no difference between genders nor among ages in odds of anemia and nutritional status in STH-infected schoolchildren. CONCLUSION: Multiparasitism remains high among Rwandan schoolchildren and is likely to cause nutritional problems. This work emphasizes the importance of keeping up health programs to reduce the prevalence of infection.

Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection.

BACKGROUND & AIMS: Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric infections, including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of nematode infection. METHODS: Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the nematode, Trichuris muris, and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after infection. RESULTS: The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)-stained intestinal goblet cells was observed in Muc2-deficient mice, as infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status. CONCLUSIONS: Mucins are an important component of innate defense in enteric infection; this is the first demonstration of the important functional contribution of mucins to host protection from nematode infection.

Regulation of colonic epithelial cell turnover by IDO contributes to the innate susceptibility of SCID mice to Trichuris muris infection.

Tryptophan catabolism via the kynurenine pathway is dependent on the enzyme Indoleamine 2,3-dioxygenase (IDO). Expression of IDO is upregulated in a number of inflammatory settings such as wounding and infection, and the resulting local tryptophan depletion may inhibit the replication of intracellular pathogens. Indo gene expression is upregulated in the gut during chronic infection with the mouse whipworm Trichuris muris. We demonstrate an increase in the rate of colonic epithelial cell turnover after inhibition of IDO in T. muris-infected SCID mice, leading to a significant expulsion of parasite burden. We identify the goblet cell as a novel source of IDO and present data revealing a new role for IDO in the regulation of epithelial cell turnover post-infectious challenge.

Social contact behaviors are associated with infection status for Trichuris sp. in wild vervet monkeys (Chlorocebus pygerythrus).

Social grooming in the animal kingdom is common and serves several functions, from removing ectoparasites to maintaining social bonds between conspecifics. We examined whether time spent grooming with others in a highly social mammal species was associated with infection status for gastrointestinal parasites. Of six parasites detected, one (Trichuris sp.) was associated with social grooming behaviors, but more specifically with direct physical contact with others. Individuals infected with Trichuris sp. spent significantly less time grooming conspecifics than those not infected, and time in direct contact with others was the major predictor of infection status. One model correctly predicted infection status for Trichuris sp. with a reliability of 95.17% overall when the variables used were time spent in direct contact and time spent grooming others. This decrease in time spent grooming and interacting with others is likely a sickness behavior displayed by individuals with less energy or motivation for non-essential behaviors. This study emphasizes the possible links between host behavior and parasitic infections and highlights the need for an understanding of a study population's parasitic infections when attempting to interpret animal behavior.

Protective Effect of Intestinal Helminthiasis Against Tuberculosis Progression Is Abrogated by Intermittent Food Deprivation.

Background: Tuberculosis (TB) is still a major challenge for humankind. Because regions with the highest incidence also have a high prevalence of helminthiasis and nutritional scarcity, we wanted to understand the impact of these on TB progression. Methods: We have developed an experimental murine model for active TB in C3HeB/FeJ, coinfected with Trichuris muris and Heligmosomoides polygyrus nematodes, and exposed to an environmental mycobacterium (M. manresensis) and intermittent fasting. Cause-effect relationships among these factors were explored with Partial Least Squares Path modelling (PLSPM). Results: Previous parasitization had a major anti-inflammatory effect and reduced systemic levels of ADA, haptoglobin, local pulmonary levels of IL-1ß, IL-6, TNF-α, CXCL-1, CXCL-5 and IL-10. Oral administration of heat-killed M. manresensis resulted in a similar outcome. Both interventions diminished pulmonary pathology and bacillary load, but intermittent food deprivation reduced this protective effect increasing stress and inflammation. The PLSPM revealed nematodes might have protective effects against TB progression. Conclusions: Significantly higher cortisol levels in food-deprivation groups showed it is a stressful condition, which might explain its deleterious effect. This highlights the impact of food security on TB eradication policies and the need to prioritize food supply over deworming activities.

CD4+ T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by G alpha i-coupled receptors but is CCR6- and CXCR3-independent.

Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4(+) T cells play a critical role in protective immunity, and that CD4(+) T cells localize to the infected large intestinal mucosa to confer protection. Further, transfer of CD4(+) T cells from immune mice to immunodeficient SCID mice can prevent the development of a chronic infection. In the current study, we characterize the protective CD4(+) T cells, describe their chemokine receptor expression and explore the functional significance of these receptors in recruitment to the large intestinal mucosa post-T. muris infection. We show that the ability to mediate expulsion resides within a subpopulation of CD4(+) T cells marked by down-regulation of CD62L. These cells can be isolated from intestine-draining mesenteric lymph nodes (MLN) from day 14 post-infection, but are rare or absent in MLN before this and in spleen at all times post-infection. Among CD4(+) CD62L(low) MLN cells, the two most abundantly expressed chemokine receptors were CCR6 and CXCR3. We demonstrate for the first time that CD4(+) CD62L(low) T-cell migration to the large intestinal mucosa is dependent on the family of G alpha(i)-coupled receptors, to which chemokine receptors belong. CCR6 and CXCR3 were however dispensable for this process because neutralization of CCR6 and CXCR3 did not prevent CD4(+) CD62L(low) cell migration to the large intestinal mucosa during T. muris infection.

Development of improved methods for delivery of Trichuris muris to the laboratory mouse.

Murine immunological responses to experimental infection with Trichuris muris and the effects of the resident microbiota on these responses are of increasing interest. For these studies, accurate dose delivery and improved sterilization of inocula are essential to prevent co-infection with unknown contaminants. We found that washing T. muris eggs with antibiotics may not be sufficient for sterilization of inocula. However, washing eggs in 6.25% hypochlorite/bleach eliminated bacteria and fungi, as determined by culture and PCR, did not harm viable T. muris eggs and reduced the number of non-viable eggs in the inocula. A hatching assay and propidium iodide staining method were developed and found to increase the accuracy for assessing T. muris egg viability prior to infection for rapid dose evaluation. In addition, metal gavage feeding needles increased the accuracy and precision of the dose delivered to the mice compared to flexible rubber tubes. These methods will improve experimental Trichuris studies by decreasing the variability in outcome due to unintended carryover of adherent microorganisms and unrecognized variation in inocula.

Whipworm and roundworm infections.

Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field.

Soil-transmitted helminth infections among pre-school aged children in Gamo Gofa zone, Southern Ethiopia: Prevalence, intensity and intervention status.

BACKGROUND: Soil-transmitted helminths (STH), i.e., Ascaris lumbricoides, Trichuris trichiura and hookworms are among the most prevalent Neglected Tropical Diseases (NTDs) in Ethiopia. Although pre-school aged children pay a high morbidity toll associated with STH infections, evidence on prevalence, intensity and intervention status is lacking in Ethiopia. This study, therefore, aimed to address these gaps to inform decision made on STH. METHODS: We did a community-based cross-sectional study in five districts of Gamo Gofa zone, Southern Ethiopia; in January 2019. Data were collected using pre-tested questionnaire, and the Kato-Katz technique was used to diagnose parasites eggs in stool. Then, collected data were edited and entered into EpiData 4.4.2, and exported to SPSS software (IBM, version 25) for analysis. RESULTS: A total of 2462 PSAC participated in this study. Overall, the prevalence of STH was 23.5% (578/2462) (95% confidence interval (CI) = 21.8%-25.2%). As caris lumbricoides was the most prevalent (18.6%), followed by Trichuris trichiura (9.2%), and hookworms (3.1%). Of the total, 7.4% PSAC were infected with two STH species. Most of the positive cases with STH showed low infection intensities, while 15.1% ascariasis cases showed moderate infection intensities. The study found that 68.7% of PSAC were treated with albendazole. Also, household's level data showed that 39.4% used water from hand-dug well; 52.5% need to travel ≥30 minutes to collect water; 77.5% did not treat water, and 48.9% had no hand washing facility. In addition, almost 93% care givers achieved less than the mean knowledge and practice score (≤5) on STH prevention. CONCLUSIONS: This study showed that significant proportions of pre-school aged children are suffering from STH infections despite preventive chemotherapy exist at the study area. Also, gaps in the interventions against STH were highlighted. Thus, a call for action is demanding to eliminate STH among PSAC in Ethiopia by 2030.

New and emerging therapies for inflammatory bowel diseases.

The inflammatory bowel diseases have undergone an explosion of discovery in the last 10 years. The overwhelming focus of this has been in genetics and immune mechanisms of disease. While the former has provided critical information on predisposing factors, the latter has resulted in a panoply of novel immune-based therapies and technologies. These range from an improved approach to the use of conventional immunomodulators, such as azathioprine and 6-mercaptopurine, to commonplace availability of anti-tumor necrosis factor agents such as infliximab and adalimumab, through to small molecule inhibition of immune mediators. Unusual treatments, such as helminth infestation, stem cell transplantation, and leucocytapheresis, all derive from the burgeoning understanding of pathogenesis. Most important to our successful use of these therapies will be a fundamental understanding of the patient phenotypes and genotypes that will dictate particular treatment approaches in the future.

Altitude and human disturbance are associated with helminth diversity in an endangered primate, Procolobus gordonorum.

Gastrointestinal parasites colonizing the mammalian gut influence the host immune system and health. Parasite infections, mainly helminths, have been studied intensively in both humans and non-human animals, but relatively rarely within a conservation framework. The Udzungwa red colobus monkey (Procolobus gordonorum) is an endangered endemic primate species living in the Udzungwa Mountains of Tanzania, a global biodiversity hotspot. Since this endemic primate species is highly sensitive to human disturbance, here we investigate whether habitat type (driven by natural and human-induced factors) is associated with helminth diversity. Using standard flotation and sedimentation techniques, we analyzed 251 fecal samples belonging to 25 social groups from four different forest blocks within the Udzungwa Mountains. Five parasitic helminth taxa were recovered from Udzungwa red colobus, including Trichuris sp., Strongyloides fulleborni, S. stercoralis, a strongylid nematode and Colobenterobius sp. We used Generalized Linear Mixed Models to explore the contribution of habitat type, altitude and fecal glucocorticoid levels (as biomarkers of stress) in predicting gut parasite variation. Although some parasites (e.g., Trichuris sp.) infected more than 50% of individuals, compared to others (e.g., Colobenterobius sp.) that infected less than 3%, both parasite richness and prevalence did not differ significantly across forests, even when controlling for seasonality. Stress hormone levels also did not predict variation in parasite richness, while altitude could explain it resulting in lower richness at lower altitudes. Because human activities causing disturbance are concentrated mainly at lower altitudes, we suggest that protection of primate forest habitat preserves natural diversity at both macro- and microscales, and that the importance of the latter should not be underestimated.

Characterization of the Complete Mitochondrial Genome of a Whipworm Trichuris skrjabini (Nematoda: Trichuridae).

The complete mitochondrial (mt) genome of Trichuris skrjabini has been determined in the current study and subsequently compared with closely related species by phylogenetic analysis based on concatenated datasets of mt amino acid sequences. The whole mt genome of T. skrjabini is circular and 14,011 bp in length. It consists of a total of 37 genes including 13 protein coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNAs) genes, and two non-coding regions. The gene arrangement and contents were consistent with other members of the Trichuridae family including Trichuris suis, Trichuris trichiura, Trichuris ovis, and Trichuris discolor. Phylogenetic analysis based on concatenated datasets of amino acids of the 12 PCGs predicted the distinctiveness of Trichuris skrjabini as compared to other members of the Trichuridae family. Overall, our study supports the hypothesis that T. skrjabini is a distinct species. The provision of molecular data of whole mt genome of T. skrjabini delivers novel genetic markers for future studies of diagnostics, systematics, population genetics, and molecular epidemiology of T. skrjabini.

Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway.

Expulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein; Myc Induced Nuclear Antigen (Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Mina may negatively regulate nematode expulsion. Here we report that expulsion of the parasitic nematode Trichuris muris was indeed accelerated in Mina deficient mice. Unexpectedly, this was associated not with an elevated Th2- but rather an impaired Th1-type response. Further reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Mina in intestinal epithelial cells (IECs). Transcriptional profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Mina-dependent retention of worms in infected mice. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Mina and point to α-defensins as important effectors that together with Mina may be attractive therapeutic targets for the control of nematode infection.

Parasitic infections and resource economy of Danish Iron Age settlement through ancient DNA sequencing.

In this study, we screen archaeological soil samples by microscopy and analyse the samples by next generation sequencing to obtain results with parasites at species level and untargeted findings of plant and animal DNA. Three separate sediment layers of an ancient man-made pond in Hoby, Denmark, ranging from 100 BC to 200 AD, were analysed by microscopy for presence of intestinal worm eggs and DNA analysis were performed to identify intestinal worms and dietary components. Ancient DNA of parasites, domestic animals and edible plants revealed a change in use of the pond over time reflecting the household practice in the adjacent Iron Age settlement. The most abundant parasite found belonged to the Ascaris genus, which was not possible to type at species level. For all sediment layers the presence of eggs of the human whipworm Trichuris trichiura and the beef tapeworm Taenia saginata suggests continuous disposal of human faeces in the pond. Moreover, the continuous findings of T. saginata further imply beef consumption and may suggest that cattle were living in the immediate surrounding of the site throughout the period. Findings of additional host-specific parasites suggest fluctuating presence of other domestic animals over time: Trichuris suis (pig), Parascaris univalens (horse), Taenia hydatigena (dog and sheep). Likewise, alternating occurrence of aDNA of edible plants may suggest changes in agricultural practices. Moreover, the composition of aDNA of parasites, plants and vertebrates suggests a significant change in the use of the ancient pond over a period of three centuries.

The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock.

Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up to 4 weeks in mice. Here, we show that the time-of-day of the initial infection affects efficiency of worm expulsion, with strong TH2 bias and early expulsion in morning-infected mice. Conversely, mice infected at the start of the night show delayed resistance to infection, and this is associated with feeding-driven metabolic cues, such that feeding restriction to the day-time in normally nocturnal-feeding mice disrupts parasitic expulsion kinetics. We deleted the circadian regulator BMAL1 in antigen-presenting dendritic cells (DCs) in vivo and found a loss of time-of-day dependency of helminth expulsion. RNAseq analyses revealed that IL-12 responses to worm antigen by circadian-synchronised DCs were dependent on BMAL1. Therefore, we find that circadian machinery in DCs contributes to the TH1/TH2 balance, and that environmental, or genetic perturbation of the DC clock results in altered parasite expulsion kinetics.