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Biotherapy targets molecules that alter the immune response. It involves a plethora of organisms known to alter the course of myriad diseases and ailments. Many of these diseases can be life-threatening to the humans and animals, and exhibit resistance to available antimicrobial medications. To address such ailments, traditional and modernized therapies that target specific molecules responsible for altering the immune response are currently being explored. Such therapies utilize various organisms that are known to impact the progression of numerous diseases and disorders. Diseases caused by certain organisms can also alter the courses or outcomes of other diseases. Biotherapies such as helminth therapy, maggot debridement therapy, and hirudotherapy use parasites (roundworms and flatworms), arthropods (maggots), and leeches (annelids), respectively, as potential biological therapeutic sources to treat autoimmune and other chronic diseases. Where conventional medicine fails, these traditional-turned-modern alternative therapies can serve to boost the health prospects of patients who are vulnerable to the misery and pain inflicted by their ailments. Patients dealing with these circumstances are prevalent in developed countries, where there is enormous market potential for any novel alternative treatments discovered. In this review, we provide a brief outlook on the mechanisms of action of these biotherapies, and summarize their roles in human and veterinary medicine. [ABSTRACT FROM AUTHOR]

Background: Estimation of prevalence of Strongyloides stercoralis infection is required in endemic areas, in order to identify areas in need of control programmes. Data on prevalence of strongyloidiasis in Madagascar are scant. Aim of this work was to estimate prevalence of S. stercoralis in four districts of Madagascar. Methods: Fecal and serum samples collected in the context of a previous study on schistosomiasis were tested with S. stercoralis real-time PCR and serology, respectively. A multiplex real-time PCR for Ascaris lumbricoides, Ancylostoma duodenalis, Necator americanus, and Trichuris trichiura was done on fecal samples collected in the areas demonstrating higher prevalence of strongyloidiasis. Comparisons between proportions were made using Fisher exact test, with false discovery rate correction used for post-hoc comparisons. A multivariable Firth logistic regression model was used to assess potential risk factors for S. stercoralis infection. Results: Overall, 1775 serum samples were tested, of which 102 of 487 (20.9%) and 104 of 296 (35.2%) were serological-positive in Marovoay and in Vatomandry districts (both coastal areas), respectively, compared to 28 of 496 (5.6%) and 30 of 496 (6.1%) in Tsiroanomandidy and in Ambositra districts (both highlands), respectively (adj. p < 0.001). PCR for S. stercoralis was positive in 15 of 210 (7.1%) and in 11 of 296 (3.7%) samples from Marovoay from Vatomandry, respectively, while was negative for all samples tested in the other two districts. High prevalence of A. lumbricoides (45.9%), hookworm (44.6%) and T. trichiura (32.1%) was found in Vatomandry. In the multivariable analysis, strongyloidiasis was associated with hookworm infection. Hookworm infection was also associated with male sex and lower education level. Conclusions: S. stercoralis prevalence proved higher in coastal areas compared to highlands. Different climatic conditions may explain this distribution, along with previous rounds of anthelminthics distributed in the country, which may have reduced the parasite load in the population. The high prevalence of the other soil-transmitted helminths (STH) in Vatomandry was unexpected, given the good coverage with benzimidazole in control campaigns. Further studies are needed to explore the risk factors for STH and S. stercoralis infections in Madagascar, in order to align with the WHO recommendations. [ABSTRACT FROM AUTHOR]

Background: Helminth infections are a public health issue in countries with poor sanitation facilities. However, there little information on the epidemiological association between helminths in wastewater and soil samples and rates of helminth infection among farming households along the Akaki River in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted between November 2021 and February 2022. A stratified random sampling technique was used to select farming households. The sample size for each district was determined by a proportionate allocation to the number of households. From wastewater-irrigated farms, 70 wastewater samples, 28 soil samples, and 86 farmers' stool samples were collected and analyzed for helminths. A questionnaire was used to gather ethnographic data, about farming households, whereas wastewater and soil sample analysis was used to generate quantitative data on helminth loads. The data were systematically analysed by developing themes, and bias evaluated using triangulation validation methodologies. Potential pathways to helminth infection were evaluated by measuring. Total number of helminth eggs in wastewater, soil samples and farmer's stools was investigated using Poisson regression. Results: In this study, 82.9% of wastewater samples, 57.1% of soil samples, and 18.6% of farmers' stool samples contained helminth eggs. The most prevalent helminth was Ascaris lumbricoides in all samples (wastewater 67%, soil 25%, and stool 10.5%), followed by hookworm (wastewater 10%, soil 21.4%, and stool 6.9%) and Trichuris trichiura eggs (wastewater 5.7%, soil 10.7%, and stool 1.2%). There was a positive association between the total number of helminth eggs in wastewater and soil samples with counts in farmers' stool. The Poisson regression coefficients for wastewater and soil were, 1.63 (95% CI = 1.34–1.92) and 1.70 (95% CI = 1.39–2.01), (p < 0.05). Conclusions: This research has shown a clear association between the total helminth eggs in wastewater and soil samples and farmer stools along the Akaki River. Therefore, an integrated approach is essential to address the issue in this area and prevent the spread of further helminth infections. [ABSTRACT FROM AUTHOR]

Different human and animal pathogens trigger distinct immune responses in their hosts. The infection of bacteria or viruses can trigger type I pro-inflammatory immune responses (e.g., IFN-γ, TNF-α, TH1 cells), whereas infection by helminths typically elicits a type II host resistance and tolerizing immune response (e.g., IL-4, IL-5, IL-13, TH2 cells). In some respects, the type I and II immune responses induced by these different classes of pathogens are antagonistic. Indeed, recent studies indicate that infection by helminths differentially shapes the response and outcome of subsequent infection by viruses and bacteria. In this review, we summarize the current knowledge on how helminth infections influence concurrent or subsequent microbial infections and also discuss the implications for helminth-mediated immunity on the outcome of SARS-CoV-2 disease. [ABSTRACT FROM AUTHOR]

Background: The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory (Cichorium intybus) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Results: Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more diverse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus. Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris, concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Conclusions: Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is a major neglected tropical disease that affects up to 250 million individuals worldwide. The diagnosis of human schistosomiasis is mainly based on the microscopic detection of the parasite's eggs in the feces (i.e., for Schistosoma mansoni or Schistosoma japonicum) or urine (i.e., for Schistosoma haematobium) samples. However, these techniques have limited sensitivity, and microscopic expertise is waning outside endemic areas. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) has become the gold standard diagnostic method for the identification of bacteria and fungi in many microbiological laboratories. Preliminary studies have recently shown promising results for parasite identification using this method. The aims of this study were to develop and validate a species-specific database for adult Schistosoma identification, and to evaluate the effects of different storage solutions (ethanol and RNAlater) on spectra profiles. Methods: Adult worms (males and females) of S. mansoni and S. japonicum were obtained from experimentally infected mice. Species identification was carried out morphologically and by cytochrome oxidase 1 gene sequencing. Reference protein spectra for the creation of an in-house MALDI-TOF MS database were generated, and the database evaluated using new samples. We employed unsupervised (principal component analysis) and supervised (support vector machine, k-nearest neighbor, Random Forest, and partial least squares discriminant analysis) machine learning algorithms for the identification and differentiation of the Schistosoma species. Results: All the spectra were correctly identified by internal validation. For external validation, 58 new Schistosoma samples were analyzed, of which 100% (58/58) were correctly identified to genus level (log score values ≥ 1.7) and 81% (47/58) were reliably identified to species level (log score values ≥ 2). The spectra profiles showed some differences depending on the storage solution used. All the machine learning algorithms classified the samples correctly. Conclusions: MALDI-TOF MS can reliably distinguish adult S. mansoni from S. japonicum. [ABSTRACT FROM AUTHOR]

Background: Although wild ungulate populations are heavily monitored throughout Europe, we understand little of how parasites affect population dynamics, and there is no systematic, long-term monitoring of parasite diversity and parasite loads. Such monitoring is in part hampered by a lack of time- and cost-effective assay methodologies with high sensitivity and good taxonomic resolution. DNA metabarcoding has been successfully used to characterize the parasitic nemabiome with high taxonomic resolution in a variety of wild and domestic hosts. However, in order to implement this technique in large-scale, potentially non-invasive monitoring of gastrointestinal parasitic nematodes (GIN), protocol optimization is required to maximize biodiversity detection, whilst maintaining time- and cost-effectiveness. Methods: Faecal samples were collected from a wild moose population and GIN communities were characterized and quantified using both parasitological techniques (egg and larva counting) and DNA metabarcoding of the ITS2 region of rDNA. Three different isolation methods were compared that differed in the volume of starting material and cell lysis method. Results: Similar nematode faunas were recovered from all samples using both parasitological and metabarcoding methods, and the approaches were largely congruent. However, metabarcoding assays showed better taxonomic resolution and slightly higher sensitivity than egg and larvae counts. The metabarcoding was not strictly quantitative, but the proportion of target nematode sequences recovered was correlated with the parasitologically determined parasite load. Species detection rates in the metabarcoding assays were maximized using a DNA isolation method that included mechanical cell disruption and maximized the starting material volume. Conclusions: DNA metabarcoding is a promising technique for the non-invasive, large-scale monitoring of parasitic GINs in wild ungulate populations, owing to its high taxonomic resolution, increased assay sensitivity, and time- and cost-effectiveness. Although metabarcoding is not a strictly quantitative method, it may nonetheless be possible to create a management- and conservation-relevant index for the host parasite load from this data. To optimize the detection rates and time- and cost-effectiveness of metabarcoding assays, we recommend choosing a DNA isolation method that involves mechanical cell disruption and maximizes the starting material volume. [ABSTRACT FROM AUTHOR]

Background: While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce, and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from five villages with different prevalence of helminth infections. Results: Individuals from villages with higher prevalences of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment were observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection. Conclusions: Our results indicate that helminth effects on the microbiota were highly dependent on context, and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains unannotated, and this large dataset from an indigenous population associated with helminth infections is a valuable resource for future studies. AEGeXaED_X6wKACk1ZMX_F Video Abstract [ABSTRACT FROM AUTHOR]

Background: Wildlife hosts may serve as reservoirs for strongyles, which can be transmitted to domestic livestock. Therefore, studies evaluating nemabiome compositions in wildlife ruminants are of great use in assessing the possibility of transmission of important nematode pathogens to domestic sheep in Sweden. Methods: First, fecal samples were collected from roe deer (n = 125), fallow deer (n = 106), red deer (n = 18) and mouflon (n = 13) in south central Sweden during the hunting season in 2019. Second, after fecal examination samples were cultured and the larvae were harvested, followed by DNA extractions. Third, all samples were barcoded and processed for sequence analysis on the PacBio platform. Finally, bioinformatic sequence analysis was conducted with DADA2, while species diversity and richness, as well as interactions between the different hosts, were calculated and analyzed in R. Results: Nematode ITS2 sequences were found in 225 of 262 (86%) samples. In total, 31 taxa were identified, among which 26 (86%) to the species level. These were found in different combinations, among which 24 (77%) occurred in roe deer, 19 (61%) in fallow deer, 20 (65%) in red deer and 10 (32%) in mouflon. Five of the species found are known to be associated with livestock (Chabertia ovina, Haemonchus contortus, Oesophagostomum venulosum, Teladorsagia circumcincta and Trichostrongylus axei). However, in the present study the relative abundance and prevalence of most of these species were low. The most striking exception was T. axei, which was relatively abundant in all wildlife hosts. Mostly a wide range of wildlife specific nematodes such as Ostertagia leptospicularis and Spiculopteragia spp. were identified including the invasive nematode Spiculopteragia houdemeri, which was found for the first time in red deer, fallow deer, and mouflon in Sweden. The difference in the number of shared species between mouflon and all cervids (n = 6) was less than among all three cervids (n = 8). Conclusion: In this study, we investigated the community structure of parasitic intestinal nematodes in four wildlife hosts, and we found that the majority of the parasite species identified were wildlife specific. We also found a new, potentially invasive species not reported before. After comparing the nemabiome of the wildlife hosts in this study with a previous study in sheep from the same geographical region, we conclude that the horizontal transmission potential appears to be relatively low. Still, cross-infections of nematodes between game and sheep cannot be completely ignored. [ABSTRACT FROM AUTHOR]

Background: MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression in organisms ranging from viruses to mammals. There is great relevance in understanding how miRNAs regulate genes involved in the growth, development, and maturation of the many parasitic worms (helminths) that together afflict more than 2 billion people. Results: Here, we describe the miRNAs expressed by each of the predominant intra-mammalian development stages of Fasciola hepatica, a foodborne flatworm that infects a wide range of mammals worldwide, most importantly humans and their livestock. A total of 124 miRNAs were profiled, 72 of which had been previously reported and three of which were conserved miRNA sequences described here for the first time. The remaining 49 miRNAs were novel sequences of which, 31 were conserved with F. gigantica and the remaining 18 were specific to F. hepatica. The newly excysted juveniles express 22 unique miRNAs while the immature liver and mature bile duct stages each express 16 unique miRNAs. We discovered several sequence variant miRNAs (IsomiRs) as well as miRNA clusters that exhibit strict temporal expression paralleling parasite development. Target analysis revealed the close association between miRNA expression and stage-specific changes in the transcriptome; for example, we identified specific miRNAs that target parasite proteases known to be essential for intestinal wall penetration (cathepsin L3). Moreover, we demonstrate that miRNAs fine-tune the expression of genes involved in the metabolic pathways that allow the parasites to move from an aerobic external environment to the anerobic environment of the host. Conclusions: These results provide novel insight into the regulation of helminth parasite development and identifies new genes and miRNAs for therapeutic development to limit the virulence and pathogenesis caused by F. hepatica. [ABSTRACT FROM AUTHOR]

Background: Parasitic conjunctivitis caused by Philophthalmus spp. is a common ophthalmic disease in birds, with localized outbreaks occurring worldwide. There is no consensus on treating this disease; mechanical removal is considered a standard recommendation, but is associated with disease relapses within days or weeks. Methods: From 2015 to 2020, we examined 4295 Larus michahellis and Larus fuscus gulls in southern Portugal for the presence of Philophthalmus spp. Due to the need to treat dozens of infected gulls in the rescue station, we tested three treatment regimens aimed at targeting Philophthalmus lucipetus in the infected gulls: (I) the ophthalmic application of levamisole; (II) the oral application of milbemycin in combination with praziquantel; and (III) the subcutaneous application of ivermectin. Results: The outbreak of philophthalmosis in gulls in southern Portugal has been ongoing since the first cases were reported in 2015–2016. The prevalence of philophthalmosis has fluctuated annually, peaking a maximum of 10.3% in L. fuscus in 2017 and at 2.1% in L. michahellis in 2016. The infection intensity peaked at a median of 11.5 eye-flukes per host bird in L. fuscus in 2016 and a median of six eye-flukes per host bird in L. michahellis in 2017. Nine gulls were infected with >50 eye-flukes. None of the treatment options were effective at treating P. lucipetus infections: the numbers of eye-flukes in the infected birds did not decrease, and the clinical signs of the disease did not change. Conclusions: An outbreak of philophthalmosis in southern Portugal has massively affected two species of gulls in the region. Two previously suggested philophthalmosis treatments (ocular levamisole and praziquantel given orally), as well as a third mode of treatment with a previously failed compound (ivermectin administered subcutaneously) were used. However, the treatments did not affect the numbers of P. lucipetus in the eyes of the treated gulls. Further research should address ophthalmic gel formulations or sub-conjunctival delivery mode for antihelminthic drugs that are effective against Philophthalmus spp. in vitro. [ABSTRACT FROM AUTHOR]

Parasites, including viruses, bacteria, fungi, protists, helminths, and arthropods, are ubiquitous in the animal kingdom. Consequently, hosts are frequently infected with more than one parasite species simultaneously. The assessment of such co-infections is of fundamental importance for disease ecology, but relevant studies involving non-domesticated animals have remained scarce. Many amphibians are in decline, and they generally have a highly diverse parasitic fauna. Here we review the literature reporting on field surveys, veterinary case studies, and laboratory experiments on co-infections in amphibians, and we summarize what is known about within-host interactions among parasites, which environmental and intrinsic factors influence the outcomes of these interactions, and what effects co-infections have on hosts. The available literature is piecemeal, and patterns are highly diverse, so that identifying general trends that would fit most host–multiparasite systems in amphibians is difficult. Several examples of additive, antagonistic, neutral, and synergistic effects among different parasites are known, but whether members of some higher taxa usually outcompete and override the effects of others remains unclear. The arrival order of different parasites and the time lag between exposures appear in many cases to fundamentally shape competition and disease progression. The first parasite to arrive can gain a marked reproductive advantage or induce cross-reaction immunity, but by disrupting the skin and associated defences (i.e., skin secretions, skin microbiome) and by immunosuppression, it can also pave the way for subsequent infections. Although there are exceptions, detrimental effects to the host are generally aggravated with increasing numbers of co-infecting parasite species. Finally, because amphibians are ectothermic animals, temperature appears to be the most critical environmental factor that affects co-infections, partly via its influence on amphibian immune function, partly due to its direct effect on the survival and growth of parasites. Besides their importance for our understanding of ecological patterns and processes, detailed knowledge about co-infections is also crucial for the design and implementation of effective wildlife disease management, so that studies concentrating on the identified gaps in our understanding represent rewarding research avenues. [ABSTRACT FROM AUTHOR]

Background: Genetic markers are employed widely in molecular studies, and their utility depends on the degree of sequence variation, which dictates the type of application for which they are suited. Consequently, the suitability of a genetic marker for any specific application is complicated by its properties and usage across studies. To provide a yardstick for future users, in this study we assess the suitability of genetic markers for molecular systematics and species identification in helminths and provide an estimate of the cut-off genetic distances per taxonomic level. Methods: We assessed four classes of genetic markers, namely nuclear ribosomal internal transcribed spacers, nuclear rRNA, mitochondrial rRNA and mitochondrial protein-coding genes, based on certain properties that are important for species identification and molecular systematics. For molecular identification, these properties are inter-species sequence variation; length of reference sequences; easy alignment of sequences; and easy to design universal primers. For molecular systematics, the properties are: average genetic distance from order/suborder to species level; the number of monophyletic clades at the order/suborder level; length of reference sequences; easy alignment of sequences; easy to design universal primers; and absence of nucleotide substitution saturation. Estimation of the cut-off genetic distances was performed using the 'K-means' clustering algorithm. Results: The nuclear rRNA genes exhibited the lowest sequence variation, whereas the mitochondrial genes exhibited relatively higher variation across the three groups of helminths. Also, the nuclear and mitochondrial rRNA genes were the best possible genetic markers for helminth molecular systematics, whereas the mitochondrial protein-coding and rRNA genes were suitable for molecular identification. We also revealed that a general gauge of genetic distances might not be adequate, using evidence from the wide range of genetic distances among nematodes. Conclusion: This study assessed the suitability of DNA genetic markers for application in molecular systematics and molecular identification of helminths. We provide a novel way of analyzing genetic distances to generate suitable cut-off values for each taxonomic level using the 'K-means' clustering algorithm. The estimated cut-off genetic distance values, together with the summary of the utility and limitations of each class of genetic markers, are useful information that can benefit researchers conducting molecular studies on helminths. [ABSTRACT FROM AUTHOR]

Background: Microbial eukaryotes are found alongside bacteria and archaea in natural microbial systems, including host-associated microbiomes. While microbial eukaryotes are critical to these communities, they are challenging to study with shotgun sequencing techniques and are therefore often excluded. Results: Here, we present EukDetect, a bioinformatics method to identify eukaryotes in shotgun metagenomic sequencing data. Our approach uses a database of 521,824 universal marker genes from 241 conserved gene families, which we curated from 3713 fungal, protist, non-vertebrate metazoan, and non-streptophyte archaeplastida genomes and transcriptomes. EukDetect has a broad taxonomic coverage of microbial eukaryotes, performs well on low-abundance and closely related species, and is resilient against bacterial contamination in eukaryotic genomes. Using EukDetect, we describe the spatial distribution of eukaryotes along the human gastrointestinal tract, showing that fungi and protists are present in the lumen and mucosa throughout the large intestine. We discover that there is a succession of eukaryotes that colonize the human gut during the first years of life, mirroring patterns of developmental succession observed in gut bacteria. By comparing DNA and RNA sequencing of paired samples from human stool, we find that many eukaryotes continue active transcription after passage through the gut, though some do not, suggesting they are dormant or nonviable. We analyze metagenomic data from the Baltic Sea and find that eukaryotes differ across locations and salinity gradients. Finally, we observe eukaryotes in Arabidopsis leaf samples, many of which are not identifiable from public protein databases. Conclusions: EukDetect provides an automated and reliable way to characterize eukaryotes in shotgun sequencing datasets from diverse microbiomes. We demonstrate that it enables discoveries that would be missed or clouded by false positives with standard shotgun sequence analysis. EukDetect will greatly advance our understanding of how microbial eukaryotes contribute to microbiomes. EDH-t7L4v5WEFMvCw3ubMS Video abstract [ABSTRACT FROM AUTHOR]

Background: The rapid growth of Qatar in the last two decades has been associated with an enormous expansion of building programs in its cities and in the provision of new service industries. This in turn has attracted a large influx of immigrant workers seeking employment in jobs associated with food handling, domestic service, and the building industry. Many of these immigrants come from countries in the tropics and subtropics where intestinal parasitic infections are common. In this study, we explored the environmental and socio-demographic characteristics of immigrant workers in Doha Qatar, which might explain the persistence of the parasites that they harbor. Methodology: This cross-sectional survey was conducted among 2486 newly arrived immigrant workers and those who visited Qatar previously during the period 2012–2014. Through questionnaires and census data, we characterized the socio-demographic conditions at an individual, family, and neighborhood levels. Results: Overall, the prevalence of combined protozoan infection was 11.7% and that of helminth was 7.0%. Combined protozoan infections were significantly associated with immigrant workers arriving in Doha for the first time. In univariate log-linear statistical models fitted in phase 1 of the analysis, significant associations were observed between the prevalence of combined protozoan infections and personal and familial factors that included religion, the level of education of subjects, both parents' educational levels and their jobs, and the number of siblings. Furthermore, environmental effects on the prevalence of protozoan infections including the country of origin, the floor of the house, toilet type, household content index, provision of household water, farming background showed strong associations with protozoan infections. However, in phase 2, multifactorial binary logistic generalized linear models focusing only on the significant effects identified in phase 1, showed that only five factors retained significance (age class, floor of the house, household contents index, father's education, and the number of siblings). The only factors that had a significant effect on the prevalence of helminth infections were the subjects' age class and the mother's educational level. Conclusions: The prevalence of intestinal protozoan parasites among immigrant workers in Qatar is clearly multifactorial in origin determined by key familial relationships of subjects and also the environment, in which the subjects lived prior to their arrival in Qatar. Moreover, our results suggest that screening protocols for applicants for visas/work permits need to be revised giving more careful attention to the intestinal protozoan infections that potential immigrant workers may harbor. [ABSTRACT FROM AUTHOR]

Background: Dirofilaria immitis is responsible for heartworm disease in dogs in endemic areas worldwide. Screening for this infection is done by blood tests. Antigen testing is the most sensitive method to detect an infection with adult (female) worms. Microscopic examination of a blood smear or Knott's test can be used to detect circulating microfilariae, the infective larvae. To increase the sensitivity of the antigen test by decreasing the false negative test results, heating of the blood sample has been recommended in recent guidelines. Heating is believed to remove blocking immune-complexes. Circulating microfilariae are not specific findings for heartworm infection, as other nematodes (among others, Acanthocheilonema dracunculoides) can also result in microfilaremia. Although the type of microfilariae cannot be determined by microscopy alone, real-time PCR can reliably identify the infecting nematode species. Correct identification of the parasite is of major importance, as an infection with D. immitis requires antiparasitic therapy, whereas A. dracunculoides is thought to be a clinically irrelevant coincidental finding. The present case report describes a microfilaremic dog where the initial antigen test for D. immitis turned positive after heat treatment, whereas real-time PCR revealed that the microfilariae were A. dracunculoides (syn. Dipetalonema dracunculoides). Results: A circa 5-year old, asymptomatic Spanish mastiff dog was referred for heartworm therapy because microfilariae were found via a screening blood test. The dog was recently imported to the Netherlands from Spain, where it had been a stray dog. Antigen tests on a plasma sample for D. immitis were performed with three different test kits, which all turned out to be negative. However, heat treatment of two of these samples were carried out and both of them led to a positive antigen test result. Real-time PCR showed that the circulating microfilariae belonged to A. dracunculoides species. Three administrations of moxidectin spot-on at monthly intervals resulted in a negative antigen and a negative Knott's tests one month after the last treatment. Conclusions: We conclude that heat treatment of initially negative blood samples for D. immitis could lead to false positive antigen test results if the dog is infected with A. dracunculoides. [ABSTRACT FROM AUTHOR]

Background: Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. Main text: Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. Conclusions: This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country. [ABSTRACT FROM AUTHOR]

Background: Human infections by the gastrointestinal helminth Strongyloides stercoralis and the enteric protozoans Giardia duodenalis, Cryptosporidium spp. and Blastocystis spp. are not formally included in the list of 20 neglected tropical diseases prioritised by the World Health Organization. Although largely underdiagnosed and considered of lower public health relevance, these infections have been increasingly demonstrated to cause significant morbidity and even mortality globally, particularly among children living in resource-poor settings. Methods: In this cross-sectional survey the prevalence, frequency and molecular diversity of S. stercoralis, G. duodenalis, Cryptosporidium spp. and Blastocystis spp. were investigated in a school children population in the province of Benguela (Angola). A total of 351 stool samples were collected during January to June 2015. The presence of S. stercoralis and G. duodenalis was confirmed by qPCR methods. Giardia duodenalis assemblages and sub-assemblages were determined by multilocus sequence-based genotyping of the glutamate dehydrogenase and β-giardin genes of the parasite. Detection and identification of Cryptosporidium and Blastocystis species and subtypes was carried out by amplification and sequencing of a partial fragment of the small-subunit ribosomal RNA gene of both protozoan. Analyses of risk factors potentially associated with the transmission of these pathogens were also conducted. Results: Prevalences of S. stercoralis, G. duodenalis, Cryptosporidium spp., and Blastocystis spp. were estimated at 21.4% (95% CI: 17.1-25.7%), 37.9% (95% CI: 32.8-43.0%), 2.9% (95% CI: 1.1-4.5%) and 25.6% (95% CI: 21.18-30. 2%), respectively. Overall, 64.1% (225/351) of the children were infected by at least one of the pathogens investigated. Sequence analyses of the 28 G. duodenalis isolates that were successfully genotyped allowed the identification of sub-assemblages AI (14.3%), AII (14.3%), BIII (7.1%) and BIV (25.0%). Discordant typing results AII/AIII and BIII/BIV were identified in 7.1% and 14.3% of the isolates, respectively. A total of five additional isolates (17.9%) were identified as assemblage B. Three Cryptosporidium species including C. hominis (70%), C. parvum (20%) and C. canis (10%) were found circulating in the children population under study. A total of 75 Blastocystis isolates were assigned to the subtypes ST1 (30.7%), ST2 (30.7%), ST3 (36.0%), ST5 (1.3%) and ST7 (1.3%), respectively. Children younger than seven years of age had significantly higher risk of infections by protozoan enteropathogens (PRR: 1.35, P< 0.01), whereas being underweight seemed to have a protective effect against these infections (PRR: 0.74, P = 0.005). Conclusions: The burden of disease attributable to human strongyloidiasis, giardiosis, cryptosporidiosis and blastocystosis in Angola is considerably higher than initially estimated in previous surveys. Surveillance and control of these infections should be jointly tackled with formally considered neglected tropical diseases in order to maximize effort and available resources. Our data also demonstrate the added value of using molecular diagnostic methods in high transmission areas. [ABSTRACT FROM AUTHOR]

Objective: Intestinal parasitic infection is one of the major childhood health problems in developing countries. In Ethiopia, epidemiological data for several localities is limited. Hence, the aim of this study is to assess intestinal parasitic infections among under-five children attending in Debre Birhan referral hospital, which could help to decrease morbidity and mortality in children. A cross-sectional study was conducted in February, 2014. Stool specimens were collected and examined using concentration method. Results: Out of the 247 under-five children participated, 17.4% (95% CI 12.7–22.1%) of the children were infected with at least one or more protozoa parasites (14.2% [95% CI 9.9–18.5%]) and helminthes (3.2% [95% CI 1.0–5.4%]). Giardia lamblia (8.5%), Entamoeba histolytica/dispar (5.7%), Trichuris trichiura (1.6%) and Ascaris lumbricoides (1.2%) were the most identified parasites. Parasitic infection was higher in children who had source of drinking water from the river (36.8%), among children from mothers with poor hand washing practice (31.7%), and among children born from illiterate mothers (27.5%). This revealed that intestinal parasites affect the health of under-five children in the setting. Hence, improving environmental hygiene and inadequate water sanitation, and health education for behavioral changes to personal hygiene would be crucial for effective control of the parasite infections. [ABSTRACT FROM AUTHOR]

Background: Helminth infections have a terrible impact on child growth and development, and harm pregnant women. Regular treatment and long term preventive interventions are important measures to break the transmission routes. Hence, identifying the status of helminth infection and practices of prevention and control measures among pregnant women is important in different geographical areas of Ethiopia including our setting. Methods: A cross-sectional study was conducted on 180 pregnant women from March to June, 2015. About 2 g of stool was collected and examined to identify helminth infections. Proportions and risk factors of helminth infections were calculated using SPSS version 20. Results: Among the total 180 study participants, 38 (21.1% [95% CI 15.2-27.0%]) pregnant women had helminth infections. Hookworm and Schistosoma mansoni were the only identified helminth species. Thirty-six (20.0% [95% CI 14.3-25.7%]) and 4 (2.2% [95% CI 0.2-4.2%]) pregnant women had hookworm and S. mansoni infections, respectively. Of which, double infection (hookworm and S. mansoni) was found in two pregnant women. Only 32 (17.8%) pregnant women had proper hand wash practice after toilet, 48 (26.7%) drank treated water, and 40 (22.2%) wore shoes regularly. Those pregnant women who did not take albendazole or mebendazole dewormers (AOR 3.57; 95% CI 1.19-10.69; P 0.023) were more infected from helminth infections. Conclusions: This study showed that there was a high intestinal helminth infection among pregnant women, and low practice of prevention and control measures. Thus, prevention and control measures should be strengthened in the setting. [ABSTRACT FROM AUTHOR]

The involvement of CD8+T cells in schistosomiasis is being increasingly appreciated, but the underlying mechanism is not well defined. Results: In this study, we showed that the absence of Batf3 alleviated liver damage in Batf3-/- mice infected with S. japonicum. We found alleviated liver granulomatous inflammation in Batf3-/- mice with schistosomiasis japonica could not be attributed to the difference in schistosome egg or worm burden. The stronger Tc1 cell responses observed in Batf3-/- mice suggested that the deletion of Batf3 resulted in more activation of CD8+T cells unexpectedly during the natural infection of schistosomes. We detected a small amount of CD8α+ DCs in the spleen of Batf3+ mice at 9w post-infection. This small amount of newly generated CD8α+ DCs might contribute to enhanced activation of CD8+T cells via cross-presentation and activation which then attenuate hepatic pathological damage found in Batf3-/- mice. Conclusions: Our study provides evidence that Batf3 is associated with the immunoregulation of the liver granuloma formation, which may confer a new options for schistosomiasis treatment. [ABSTRACT FROM AUTHOR]

Background: Classical faecal egg counts (FEC) provide less reliable diagnostic information for nematode infections in chickens. We developed an ELISA based on Ascaridia galli antigens and tested two hypotheses, as follows: (i) IgY antibodies developed against A. galli will also be useful to identify Heterakis gallinarum infections, and (ii) circulating antibodies stored in egg yolks are as good as plasma samples, so a non-invasive diagnosis is possible. The aim of this study, therefore, was to compare the diagnostic accuracy of the ELISA system with FEC, using both plasma and egg yolks from experimentally infected hens. In addition, naturally infected animals were evaluated to validate the assay. Results: The assay quantified large differences (P < 0.001) in plasma or in egg-yolk IgY concentrations between infected and uninfected animals in two experiments, each performed with either of the nematode species. The assay performed with high accuracy as quantified with the area under the ROC curve (AUC) values of > 0.90 for both nematodes using either plasma or egg yolks. Sensitivity of the assay was 94 and 93% with plasma and egg yolk samples, respectively, whereas FEC yielded in a sensitivity of 84% in A. galli experiment. Total test accuracy of the assay with plasma samples (AUC = 0.99) tended to be higher (P = 0.0630) than FEC (AUC = 0.92) for A. galli, while the assay with either sample matrix performed similar to FEC (AUC ⩾ 0.91) for H. gallinarum. Among the three tests, the FECs correlated better with A. galli burden than the ELISA. Although 90% of naturally infected hens were correctly identified by the ELISA, 45% of the infected hens tested negative with FEC, indicating the validity of the higher test accuracy of the ELISA. Conclusions: Antigens of A. galli can be used successfully to identify H. gallinarum-infected animals, indicating that chickens develop cross-reactive antibodies against the two closely related species. Egg yolks are as informative as plasma samples, so that animal welfare-friendly sampling is possible. Although the assay with plasma samples reveals qualitative information of higher quality than FECs on the infection status of naturally infected birds, the latter is still a better tool to assess the intensity of A. galli but not of H. gallinarum infections. [ABSTRACT FROM AUTHOR]

Background: Helminths affect the outcome of tuberculosis by shifting cell mediated immune response to humoral and by total suppression of the host immune system. On the reverse, Mycobacterium infection favors immune escape of helminths. Therefore assessing helminth co-infection rate and predisposing factors in tuberculosis patients is mandatory to set strategies for better case management.Methods: Facility based cross-sectional study was conducted in Arba Minch to assess the prevalence and associated factors of intestinal helminths among pulmonary tuberculosis patients from January to August, 2016. A structured questionnaire was used to capture data about socio-demographic characteristics, clinical history and possible risk factors for intestinal helminth infections. Height and weight were measured to calculate body-mass index. Appropriate amount of stool was collected and processed by direct saline and formol-ether concentration techniques following standard protocols. All the data were analyzed using SPSS version 20.0.Results: A total of 213 (57.3% male and 42.7% female) pulmonary tuberculosis patients were participated in the study. The overall co-infection rate of intestinal parasites was 26.3%. The infection rate of intestinal helminths account 24.4% and that of intestinal protozoa was 6.1%. Ascaris lumbricoides accounted the highest frequency of 11.3%. Living in rural residence (AOR = 3.175, 95% CI: 1.102-9.153, p = 0.032), Eating vegetables/ fruits without washing or peeling off (AOR = 2.208, 95% CI: 1.030-4.733, p = 0.042) and having body-mass index <18.5 (AOR = 3.511, 95% CI: 1.646-7.489, p = 0.001) were associated with intestinal helminth infection.Conclusion: The infection rate by intestinal helminths was 24.4%. Ascaris lumbricoides was the most prevalent helminth. Residence, habit of washing vegetables/fruits before use and body-mass index were associated factors with intestinal helminthiasis. Therefore health care providers should screen and treat TB patients for intestinal helminthiasis in order to ensure good prognosis. [ABSTRACT FROM AUTHOR]

Background: In the last decades, the enormous influx of immigrants to industrialized countries has led to outbreaks of parasitic diseases, with enteric infections being amongst the most frequently encountered. In its strategy to control such infection, Qatar has established the Pre-Employment Certificate (PEC) program which requires medical inspection before arrival in Qatar and which is mandatory for immigrant workers travelling to the country. To assess the reliability of the PEC, we conducted a survey of intestinal parasites, based on examination of stool samples provided by immigrant workers (n = 2,486) recently arrived in Qatar. Results: Overall prevalence of helminths was 7.0% and that of protozoa was 11.7%. Prevalence of combined helminths was highest among the western Asians and the highest prevalence of combined protozoan parasites was among workers from North to Saharan Africa. Analysis of temporal changes showed an increasing trend of protozoan infections over the investigated 3 years. A major contribution to this temporal change in prevalence came from Blastocystis hominis as well as from other protozoan species: Giardia duodenalis and Endolimax nana. Analysis of the temporal trend in species richness of the protozoan species showed a significant increase in the mean number of species harboured per subject across this period. Conclusion: The increase of protozoan infections over recent years raises some concerns. It suggests that screening protocols for applicants for visas/work permits needs to be revised giving more careful attention to the intestinal protozoan infections that potential immigrants may harbor. [ABSTRACT FROM AUTHOR]

Background: The frequency of Taenia solium, a zoonotic helminth, is increasing in many countries of sub-Saharan Africa, where the prevalence of the human immunodeficiency virus (HIV) is also high. However, little is known about how these two infections interact. The aim of this study was to compare the proportion of HIV positive (+) and negative (-) individuals who are infected with Taenia solium (TSOL) and who present with clinical and neurological manifestations of cysticercosis (CC). Methods: In northern Tanzania, 170 HIV+ individuals and 170 HIV- controls matched for gender, age and village of origin were recruited. HIV staging and serological tests for TSOL antibodies (Ab) and antigen (Ag) were performed. Neurocysticercosis (NCC) was determined by computed tomography (CT) using standard diagnostic criteria. Neurological manifestations were confirmed by a standard neurological examination. In addition, demographic, clinical and neuroimaging data were collected. Further, CD4+ cell counts as well as information on highly active antiretroviral treatment (HAART) were noted. Results: No significant differences between HIV+ and HIV- individuals regarding the sero-prevalence of taeniosis-Ab (0.6% vs 1.2%), CC-Ab (2.4% vs 2.4%) and CC-Ag (0.6% vs 0.0%) were detected. A total of six NCC cases (3 HIV+ and 3 HIV-) were detected in the group of matched participants. Two individuals (1 HIV+ and 1 HIV-) presented with headaches as the main symptom for NCC, and four with asymptomatic NCC. Among the HIV+ group, TSOL was not associated with CD4+ cell counts, HAART duration or HIV stage. Conclusions: This study found lower prevalence of taeniosis, CC and NCC than had been reported in the region to date. This low level of infection may have resulted in an inability to find cross-sectional associations between HIV status and TSOL infection or NCC. Larger sample sizes will be required in future studies conducted in that area to conclude if HIV influences the way NCC manifests itself. [ABSTRACT FROM AUTHOR]

Background: Infections with intestinal parasites (helminths and intestinal protozoa) are endemic in Southeast Asia and inappropriate management and reuse of wastewater might exacerbate the risk of human infections. In rapidly growing urban settings, little is known about the extent of intestinal parasite infections. We assessed the pointprevalence and risk factors of intestinal parasite infections in population groups differently exposed to wastewater in urban and peri-urban transition zones in Hanoi, the capital of Vietnam. Methods: A cross-sectional survey was carried out between April and June 2014 in people aged ≥ 18 years at risk of wastewater exposure from To Lich River: workers maintaining wastewater treatment facilities; urban farmers reusing wastewater; and urban dwellers at risk of flooding events. For comparison, two peri-urban population groups living in close proximity to the Red River were chosen: farmers using river water for irrigation purposes; and people living in the same communities. A single stool sample was subjected to Kato-Katz and formalin-ether concentration methods for the diagnosis of helminth and intestinal protozoa infections. A questionnaire was administered to determine risk factors and self-reported signs and symptoms. Results: A total of 681 individuals had complete data records. Highest point-prevalence rates of intestinal parasite infections were observed for peri-urban farmers (30 %). Hookworm and Trichuris trichiura were the predominant helminth species (25 % and 5 %, respectively). Peri-urban farmers were at higher odds of infection with intestinal parasites than any other groups (adjusted odds ratio 5.8, 95 % confidence interval 2.5 to 13.7). Lack of access to improved sanitation and not receiving deworming within the past 12 months were associated with higher infection risk, while higher educational attainment and socioeconomic status were negatively associated with intestinal parasite infections. Conclusions: Our results suggest that exposure to wastewater was not directly associated with infection with helminths and intestinal protozoa in different population groups in Hanoi. These findings might be explained by a high level of awareness of health risks and access to safe sanitary infrastructure in urban areas. The high prevalence rates observed in peri-urban farmers call for specific interventions targeting this population group. [ABSTRACT FROM AUTHOR]

Background: The impact of drug selection pressure on the overall genetic diversity of parasitic nematode populations in the field is poorly understood. In this study, we address this issue for the small ruminant parasite Haemonchus contortus in the Punjab, Pakistan. This region provides an opportunity to compare H. contortus populations that have been subjected to a prolonged period of frequent benzimidazole drug treatments on government farms with parasite populations that have been exposed to little or no drug treatment in neighbouring pastoral herds. Methods: Adult H. contortus worms were collected from the abomasa of small ruminants from three government farms frequently using benzimidazole drugs, and closed to animal movement, for over 30 years and also from from eighteen pastoral herds subject to minimal drug selection. The frequency of three known benzimidazole resistance associated mutations was determined in each parasite population. For the seven parasite populations in which resistance mutations were found, the diversity, geographical distribution and phylogenetic relationships of isotype-1 β-tubulin benzimidazole resistance haplotypes were determined. In addition, the genetic diversity of the parasite populations on the three government farms were compared with those from four pastoral herds. Results: The F200Y (TAC) resistance mutation was present at a very high frequency in H. contortus populations from government herds, but not from pastoral herds, consistent with their respective drug selection histories. Population genetic analysis, using a panel of microsatellite markers, revealed that there was little genetic differentiation among the parasite populations with no significant difference in the overall genetic diversity between government and pastoral herds. In addition, sequence analysis of the isotype-1 β-tubulin locus revealed multiple F200Y (TAC) haplotypes demonstrating soft selective sweeps even in government herds with little or no contemporary parasite migration. Conclusions: The results suggest that, although the frequent drug treatment used on government farms has selected for a high frequency of benzimidazole resistance mutations, there has been little or no reduction in the overall genetic diversity of the selected parasite populations. [ABSTRACT FROM AUTHOR]

Background: Echinostoma caproni is an intestinal trematode extensively used as experimental model for the study of factors that determine the course of intestinal helminth infections, since this markedly depends on the host species. Although the host-dependent mechanisms for either chronic establishment or early parasite rejection have been broadly studied, little is known regarding the parasite response against different host environments. Methods: To identify host-dependent differentially expressed proteins, a comparative proteomic analysis of the excretory/secretory products released from E. caproni adults, isolated from hosts displaying different compatibility with this trematode, was performed. Results: A total of 19 differential protein spots were identified (14 overexpressed in mice and 5 overexpressed in rats). The establishment of chronic infections in mice is mainly associated with the overexpression by adult worms of antioxidant and detoxifying enzymes (e.g. glutathione S-transferase, hydroxyacylglutathione hydrolase, thiopurine S-transferase, etc.) and metabolic enzymes like enolase, leucine aminopeptidase or malate dehydrogenase. However, the overexpression of cathepsin L and the structural protein actin observed in worms isolated from rats seems not to be effective for the colonization of the intestinal mucosa of this host. Conclusions: The observed differences suggest that protein expression and/or release is modulated by the local environment generated inside the host and provide useful insights in regards to the resistance mechanisms developed by parasites to ensure their long-term survival. [ABSTRACT FROM AUTHOR]

Background: Malayan filariasis is a lymphatic filariasis caused by Brugia malayi. It is easily misdiagnosed in non-endemic areas for atypical symptoms and rare diagnostic experience. A 34-year-old Chinese woman in New York presented with diffuse erythema on her body, swelling of her body, and watery, itchy, red, sore, swollen and stinging of the eyes, and severe night-time itching. No hospital that the patient visited could make a definite diagnosis by conventional diagnostic methods. It is therefore necessary to explore a new effective method to detect the pathogen that infected the patient. Findings: An unbiased metagenomic approach was used in this study. After DNA was extracted from the patient's eye discharge sample and subcutaneous tissue sample, extended parallel sequencing was performed. The obtained raw reads were aligned to human genome to filter out the reads of the host, and the remaining reads were aligned to a candidate pathogenic protein database and four filarial genomes. The result showed that the reads of B. malayi accounted for an overwhelming ratio in the two samples, which indicated that the patient suffered from malayan filariasis. The subsequent therapeutic efficacy of anti-filariasis treatment validated the result of metagenomics assay. Conclusions: The present study proved that metagenomic assay can be an effective approach in the diagnosis of parasitic infection. We report a rare case of malayan filariasis from the United States. [ABSTRACT FROM AUTHOR]

Introduction: Immunosenescence (deteriorating immune function at old age) affects humans and laboratory animals, but little is known about immunosenescence in natural populations despite its potential importance for population and disease dynamics and individual fitness. Although life histories and immune system profiles often differ between the sexes, sex-specific effects of aging on health are rarely studied in the wild. Life history theory predicts that due to their shorter lifespan and higher investment into reproduction at the expense of immune defences, males might experience accelerated immunosenescence. We tested this hypothesis by examining sex-specific age trajectories of endoparasite burden (helminth prevalence and morphotype richness measured via fecal egg counts), an indicator of overall health, in wild gray mouse lemurs (Microcebus murinus). To account for potential interactions between seasonality and host sex or age we examined the predictors of parasite burdens separately for the dry and rainy season. Results: Contrary to the prediction of immunosenescence, parasite prevalence and morphotype richness decreased at old age in the dry season, indicating acquired immunity by older animals. This pattern was primarily caused by within-individual decline in parasite loads rather than the earlier mortality of highly parasitized individuals. With the exception of an increasing cestode prevalence in males from yearlings to prime age in the rainy season, no evidence was found of male-biased ageing in parasite resistance. Besides this sex*age interaction, host age was uncorrelated with rainy season parasite loads. Seasonality did not affect the overall parasite loads but seasonal patterns were found in the predictors of parasite prevalence and morphotype richness. Conclusions: These results provide rare information about the age-related patterns of health in a wild vertebrate population and suggest improvement rather than senescence in the ability to resist helminth infections at old age. Overall, males appear not to suffer from earlier immunosenescence relative to females. This may partially reflect the earlier mortality of males, which can render senescence difficult to detect. While helminth infections are not strongly associated with survival in wild gray mouse lemurs, parasite load may, however, reflect overall good phenotypic quality of long-lived individuals, and is a potential correlate of fitness. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus. Chronic helminth infections might protect against insulin resistance via a caloric restriction state and indirectly via T-helper-2 polarization of the immune system. Therefore the elimination of helminths might remove this beneficial effect on insulin resistance. Methods/Design: To determine whether soil-transmitted helminth infections are associated with a better whole-body insulin sensitivity and whether this protection is reversible by anthelmintic treatment, a household-based cluster-randomized, double blind, placebo-controlled trial was conducted in the area of Nangapanda on Flores Island, Indonesia, an area endemic for soil-transmitted helminth infections. The trial incorporates three monthly treatment with albendazole or matching placebo for one year, whereby each treatment round consists of three consecutive days of supervised drug intake. The presence of soil-transmitted helminths will be evaluated in faeces using microscopy and/or PCR. The primary outcome of the study will be changes in insulin resistance as assessed by HOMA-IR, while the secondary outcomes will be changes in body mass index, waist circumference, fasting blood glucose, 2 h-glucose levels after oral glucose tolerance test, HbA1c, serum lipid levels, immunological parameters, and efficacy of anthelmintic treatment. Discussion: The study will provide data on the effect of helminth infections on insulin resistance. It will assess the relationship between helminth infection status and immune responses as well as metabolic parameters, allowing the establishment of a link between inflammation and whole-body metabolic homeostasis. In addition, it will give information on anthelmintic treatment efficacy and effectiveness. Trial registration: This study has been approved by the ethical committee of Faculty of Medicine Universitas Indonesia (ref: 549/H2.F1/ETIK/2013), and has been filed by the ethics committee of Leiden University Medical Center, clinical trial number: ISRCTN75636394. The study is reported in accordance with the CONSORT guidelines for cluster-randomised trials. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is an immunologically mediated disease. Notably, it is less common in countries where there is a greater risk of exposure to helminths. In our study, we examined the modulatory effect of the laminated layer extracted from the cyst wall of a helminth parasite, Echinococcus granulosus, on dextran sulfate sodium (DSS)-induced colitis in mice. Methods: An acute colitis was induced in BALB/c mice using 2.5% w/v DSS in drinking water. The crude extract of E. granulosus laminated layer was injected intraperitoneally daily, starting 3 days before colitis induction. The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Nitric oxide (NO) and cytokine levels (interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10)) were assessed by enzyme-linked immunosorbent assay. In addition, the colonic expression of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) was examined. Statistical analyses were performed by one-way analysis of variance and the survival rate was analyzed by the long rank test. Results: Hydatid laminated layer pretreatment significantly improved the clinical symptoms and histological scores (*** p < 0.01) observed during DSS-induced colitis and maintained mucus production by goblet cells. Furthermore, treatment with hydatid laminated layer caused a significant decrease in NO, IFN-γ (** p < 0.01) and TNF-α production (* p < 0.05) and an increase in IL-10 production. These results were associated with localized downregulation of iNOS and NF-κB expression. Conclusions: Our results demonstrate the potent anti-inflammatory effects of hydatid laminated layer. Furthermore, preventive treatment with the laminated layer played a beneficial role in maintaining the integrity of the intestinal mucosal barrier against DSS-induced injury. [ABSTRACT FROM AUTHOR]

Background Neurocysticercosis (NCC) is a disease of the central nervous system (CNS) caused by the cestode Taenia solium. The infection exhibits a long asymptomatic phase, typically lasting 3 to 5 years, before the onset of the symptomatic phase. The severity of the symptoms is thought to be associated with the intensity of the inflammatory response elicited by the degenerating parasite. In contrast, the asymptomatic phase shows an absence of brain inflammation, which is presumably due to immunosuppressive effects of the live parasites. However, the host factors and/or pathways involved in inhibiting inflammation remain largely unknown. Recently, using an animal model of NCC in which mice were intracranially inoculated with a related helminth parasite, Mesocestoides corti, we reported that Toll-like receptor (TLR)-associated signaling contributes to the development of the inflammatory response. As microglia shape the initial innate immune response in the CNS, we hypothesized that the negative regulation of a TLR-induced inflammatory pathway in microglia may be a novel helminth-associated immunosuppressive mechanism in NCC. Methods and results Here we report that helminth soluble factors (HSFs) from Mesocestoides corti inhibited TLR ligation-induced production of inflammatory cytokines in primary microglia. This was correlated with an inhibition of TLR-initiated upregulation of both phosphorylation and acetylation of the nuclear factor κB (NF-κB) p65 subunit, as well as phosphorylation of JNK and ERK1/2. As Ca2+ influx due to store-operated Ca2+ entry (SOCE) has been implicated in induction of downstream signaling, we tested the inhibitory effect of HSFs on agonistinduced Ca2+ influx and specific Ca2+ channel activation. We discovered that HSFs abolished the lipopolysaccharide (LPS)- or thapsigargin (Tg)-induced increase in intracellular Ca2+ accumulation by blocking the ER store release and SOCE. Moreover, electrophysiological recordings demonstrated HSF-mediated inhibition of LPS- or Tg-induced SOCE currents through both TRPC1 and ORAI1 Ca2+ channels on plasma membrane. This was correlated with a decrease in the TRPC1-STIM1 and ORAI1-STIM1 clustering at the plasma membrane that is essential for sustained Ca2+ entry through these channels. Conclusion Inhibition of TRPC1 and ORAI1 Ca2+ channel-mediated activation of NF-κB and MAPK pathways in microglia is likely a novel helminth-induced immunosuppressive mechanism that controls initiation of inflammatory response in the CNS. [ABSTRACT FROM AUTHOR]

Background: Anthropogenic habitat change often results in altered landscapes that can provide new environments where hosts, parasites and pathogens can interact. The latter can have implications for human and animal health when in close proximity to developed areas. We recorded the helminth species richness and level of infestation in the peri-domestic rodent, Rhabdomys pumilio, in three different human linked landscapes. The aim was, to investigate the potential of R. pumilio to act as a reservoir host for zoonotic helminths and to compare the effect of anthropogenic habitat change on its parasite infestation patterns. Methods: Rodents (n = 518) were trapped in natural areas (nature reserves) and in three human linked landscapes (crop, livestock and urban fragments). Gastrointestinal parasite burdens were recovered and helminths identified from each animal. Generalized linear models were applied to investigate the effect of different landscape types on helminth infestation. Results: Rhabdomys pumilio was the most abundant rodent species within each landscape type. Eight helminths species were recovered and overall helminth prevalence was 86.68%. Mean helminth species richness, prevalence and abundance were significantly higher in crop fragments compared to natural landscapes and overall lower for nematodes in livestock and urban areas. Cestode prevalence showed a tendency to be elevated at anthropogenic linked landscape types. Conclusions: Host parameters and parasite infestations were strongly influenced by landscape characteristics. Resource-rich landscapes (crop fragments) provide favorable conditions for helminth infestations, while landscapes that are more closely associated with humans (livestock and urban landscapes) pose a larger risk by zoonotic species. [ABSTRACT FROM AUTHOR]

Background While in developed countries the prevalence of allergic diseases is rising, inflammatory diseases are relatively uncommon in rural developing areas. High prevalence rates of helminth and protozoan infections are commonly found in children living in rural settings and several studies suggest an inverse association between helminth infections and allergies. No studies investigating the relationship between parasitic infections and atopic diseases in rural children of developing countries under the age of 2 years have been published so far. We performed a cross-sectional survey to investigate the association of helminth and protozoan infections and malnutrition with recurrent wheezing and atopic eczema in Warao Amerindian children in Venezuela. Methods From August to November 2012, 229 children aged 0 to 2 years residing in the Orinoco Delta in Venezuela were enrolled. Data were collected through standardized questionnaires and physical examination, including inspection of the skin and anthropometric measurements. A stool sample was requested from all participants and detection of different parasites was performed using microscopy and real time polymerase chain reaction (PCR). Results We observed high prevalence rates of atopic eczema and recurrent wheezing, respectively 19% and 23%. The prevalence of helminth infections was 26% and the prevalence of protozoan infections was 59%. Atopic eczema and recurrent wheezing were more frequently observed in stunted compared with non-stunted children in multivariable analysis (OR 4.3, 95% CI 1.3 – 13.6, p = 0.015 and OR 4.5, 95% CI 0.97 – 21.2, p = 0.055). Furthermore, recurrent wheezing was significantly more often observed in children with protozoan infections than in children without protozoan infections (OR 6.7, 95% CI 1.5 – 30.5). Conclusions High prevalence rates of atopic eczema and recurrent wheezing in Warao Amerindian children under 2 years of age were related to stunting and intestinal protozoan infections respectively. Helminth infections were not significantly associated with either atopic eczema or recurrent wheezing. [ABSTRACT FROM AUTHOR]

Background Polyparasitism is still widespread in rural communities of the developing world. However, the epidemiology of polyparasitism and implications for morbidity are poorly understood. We studied patterns of multiple species parasite infection in two rural communities of Côte d'Ivoire, including associations and interactions between infection, clinical indicators and self-reported morbidity. Methods Between August and September 2011, two purposely selected rural communities in southern Côte d'Ivoire were screened for helminth, intestinal protozoa and Plasmodium infection, using a suite of quality-controlled diagnostic methods. Additionally, participants were examined clinically and we measured haemoglobin level, height, weight and mid-upper arm circumference to determine nutritional status. An anamnestic questionnaire was administered to assess people's recent history of diseases and symptoms, while a household questionnaire was administered to heads of household to collect socioeconomic data. Multivariate logistic regression models were applied for assessment of possible associations between parasitic (co- ) infections and morbidity outcomes. Results 912/1,095 (83.3%) study participants had complete parasitological data and 852 individuals were considered for in-depth analysis. The rate of polyparasitism was high, with Plasmodium falciparum diagnosed as the predominant species, followed by Schistosoma haematobium, Schistosoma mansoni and hookworm. There were considerable differences in polyparasitic infection profiles among the two settings. Clinical morbidity such as anaemia, splenomegaly and malnutrition was mainly found in young age groups, while in adults, self-reported morbidity dominated. High parasitaemia of P. falciparum was significantly associated with several clinical manifestations such as anaemia, splenomegaly and fever, while light-intensity helminth infections seemed to have beneficial effects, particularly for co-infected individuals. Conclusions Clinical morbidity is disturbingly high in young age groups in rural communities of Côte d'Ivoire and mainly related to very high P. falciparum endemicity. Interactions between helminth infections and P. falciparum burden (parasitaemia and clinical morbidity) are evident and must be taken into account to design future interventions. [ABSTRACT FROM AUTHOR]

Background The global epidemiology of parasitic helminths and mycobacterial infections display extensive geographical overlap, especially in the rural and urban communities of developing countries. We investigated whether co-infection with the gastrointestinal tract-restricted helminth, Trichuris muris, and the intracellular bacterium, Mycobacterium bovis (M. bovis) BCG, would alter host immune responses to, or the pathological effect of, either infection. Results We demonstrate that both pathogens are capable of negatively affecting local and systemic immune responses towards each other by modifying cytokine phenotypes and by inducing general immune suppression. T. muris infection influenced non-specific and pathogenspecific immunity to M. bovis BCG by down-regulating pulmonary TH1 and Treg responses and inducing systemic TH2 responses. However, co-infection did not alter mycobacterial multiplication or dissemination and host pulmonary histopathology remained unaffected compared to BCG-only infected mice. Interestingly, prior M. bovis BCG infection significantly delayed helminth clearance and increased intestinal crypt cell proliferation in BALB/c mice. This was accompanied by a significant reduction in systemic helminthspecific TH1 and TH2 cytokine responses and significantly reduced local TH1 and TH2 responses in comparison to T. muris-only infected mice. Conclusion Our data demonstrate that co-infection with pathogens inducing opposing immune phenotypes, can have differential effects on compartmentalized host immune protection to either pathogen. In spite of local and systemic decreases in TH1 and increases in TH2 responses co-infected mice clear M. bovis BCG at the same rate as BCG only infected animals, whereas prior mycobacterial infection initiates prolonged worm infestation in parallel to decreased pathogen-specific TH2 cytokine production. [ABSTRACT FROM AUTHOR]

Background: Malaria and helminth infections are thought to negatively affect children’s nutritional status and to impair their physical and cognitive development. Yet, the current evidence-base is weak. The purpose of this study was to determine the effect of deworming against soil-transmitted helminthiasis and schistosomiasis on children’s physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic setting of Côte d’Ivoire. Methods: We designed an intervention study with a 5-month follow-up among schoolchildren aged 5–14 years from Niablé, eastern Côte d’Ivoire. In late 2012, a baseline cross-sectional survey was conducted. Finger-prick blood, stool and urine samples were subjected to standardised, quality-controlled techniques for the diagnosis of Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal protozoa infections. Haemoglobin level was determined and anthropometric measurements were taken for appraisal of anaemia and nutritional status. Children underwent memory (digit span) and attention (code transmission) cognitive testing, and their physical fitness and strength were determined (20 m shuttle run, standing broad jump and grip strength test). All children were treated with albendazole (against soil-transmitted helminthiasis) and praziquantel (against schistosomiasis) after the baseline cross-sectional survey and again 2 months later. Five months after the initial deworming, the same battery of clinical, cognitive and physical fitness tests was performed on the same children. Results: Lower scores in strength tests were significantly associated with children with harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma mansoni achieved longer jumping distances than their non-infected counterparts. Light-intensity infection with S. mansoni was associated with slightly better aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia, but children with moderate- to heavy-intensity Schistosoma infection at baseline gained weight more pronouncedly than non-infected children. Interestingly, children with soil-transmitted helminth or Schistosoma infection at baseline performed significantly better in the sustained attention test than their non-infected counterparts at the 5-month follow-up. Conclusions: This study revealed conflicting results regarding clinical parameters and cognitive behaviour of children after two rounds of deworming. We speculate that potential beneficial effects of deworming are likely to be undermined in areas where malaria is co-endemic and nutritional deficiencies are widespread. [ABSTRACT FROM AUTHOR]

This review presents a comprehensive picture of the zoonotic parasitic diseases in Egypt, with particular reference to their relative prevalence among humans, animal reservoirs of infection, and sources of human infection. A review of the available literature indicates that many parasitic zoonoses are endemic in Egypt. Intestinal infections of parasitic zoonoses are widespread and are the leading cause of diarrhea, particularly among children and residents of rural areas. Some parasitic zoonoses are confined to specific geographic areas in Egypt, such as cutaneous leishmaniasis and zoonotic babesiosis in the Sinai. Other areas have a past history of a certain parasitic zoonoses, such as visceral leishmaniasis in the El-Agamy area in Alexandria. As a result of the implementation of control programs, a marked decrease in the prevalence of other zoonoses, such as schistosomiasis and fascioliasis has been observed. Animal reservoirs of parasitic zoonoses have been identified in Egypt, especially in rodents, stray dogs and cats, as well as vectors, typically mosquitoes and ticks, which constitute potential risks for disease transmission. Prevention and control programs against sources and reservoirs of zoonoses should be planned by public health and veterinary officers based on reliable information from systematic surveillance. [ABSTRACT FROM AUTHOR]

Background: Vaccine failure is an important concern in the tropics with many contributing elements. Among them, it has been suggested that exposure to natural infections might contribute to vaccine failure and recurrent disease outbreaks. We tested this hypothesis by examining the influence of co-infections on maternal and infant measles-specific IgG levels. Methods: We conducted an observational analysis using samples and data that had been collected during a larger randomised controlled trial, the Entebbe Mother and Baby Study (ISRCTN32849447). For the present study, 711 pregnant women and their offspring were considered. Helminth infections including hookworm, Schistosoma mansoni and Mansonella perstans, along with HIV, malaria, and other potential confounding factors were determined in mothers during pregnancy and in their infants at age one year. Infants received their measles immunisation at age nine months. Levels of total IgG against measles were measured in mothers during pregnancy and at delivery, as well as in cord blood and from infants at age one year. Results: Among the 711 pregnant women studied, 66% had at least one helminth infection at enrolment, 41% had hookworm, 20% M. perstans and 19% S. mansoni. Asymptomatic malaria and HIV prevalence was 8% and 10% respectively. At enrolment, 96% of the women had measles-specific IgG levels considered protective (median 4274 mIU/ml (IQR 1784, 7767)). IgG levels in cord blood were positively correlated to maternal measles-specific IgG levels at delivery (r = 0.81, p < 0.0001). Among the infants at one year of age, median measles-specific IgG levels were markedly lower than in maternal and cord blood (median 370 mIU/ml (IQR 198, 656) p < 0.0001). In addition, only 75% of the infants had measles-specific IgG levels considered to be protective. In a multivariate regression analysis, factors associated with reduced measles-specific antibody levels in infancy were maternal malaria infection, infant malaria parasitaemia, infant HIV and infant wasting. There was no association with maternal helminth infection. Conclusion: Malaria and HIV infection in mothers during pregnancy, and in their infants, along with infant malnutrition, may result in reduction of the antibody response to measles immunisation in infancy. This re-emphasises the importance of malaria and HIV control, and support for infant nutrition, as these interventions may have benefits for vaccine efficacy in tropical settings. [ABSTRACT FROM AUTHOR]

Background: In rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. A specific, balanced and, to an extent, protective immunity will develop over time in response to repeated parasite encounters, with immune responses initially being poorly adapted and non-protective. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly. Results: In children schistosomiasis prevailed (33%) while hookworm and Entamoeba histolytica/E. dispar was found in up to half of adults and the elderly. Mansonella perstans filariasis was only present in adults (24%) and the elderly (25%). Two or more parasite infections were diagnosed in 41% of children, while such polyparasitism was present in 34% and 38% of adults and the elderly. Cytokine and chemokine production was distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine IL-19 was activated by Entamoeba and Ascaris antigens, being low in neonates and children while IL-19 production enhanced "stepwise" in adults and elderly. In contrast, highest production of MIP-1delta/CCL15 was present in neonates and children and inducible by Entamoeba-specific antigens only. Adults and the elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably inducible by helminth- and Entamoeba-specific antigens and fungus-derived allergens. The lower cellular responsiveness in neonates and children highlighted the development of a parasite-specific cellular response profile in response to repeated episodes of exposure and re-infection. Conclusions: Following repeated exposure to parasites, and as a consequence of host inability to prevent or eliminate intestinal helminth or protozoa infections, a repertoire of immune responses will evolve with lessened pro-inflammatory and pronounced regulatory cytokines and chemokines; this is required for partial parasite control as well as for preventing inadequate and excessive host tissue and organ damage. [ABSTRACT FROM AUTHOR]

Background: Helminth infections and allergies are associated with TH2 responses. Whereas the development of TH2 responses and allergic disorders in pediatric populations has been examined in affluent countries, no or little data exist from low income regions of the world. The aim of this study is to examine factors influencing the development of TH2 responses of children born in areas endemic for helminth infections and to relate these factors to atopic sensitization at 4 years of age. Methods: Data were collected from pregnant mothers on helminth infections, education and socioeconomic status (SES). Total IgE, IL-5 in response to mitogen, and helminth antigens were measured in children at 2, 5, 12, 24 and 48 months of age. Skin prick testing (SPT) and allergen-specific IgE were determined at 4 years of age. Results: Strong TH2 responses were seen at 5 months of age and increased with time. Although maternal filarial infection was associated with helminth-antigen specific TH2 responses, it was low maternal education or SES but not helminth infection, which was associated with the development of high total IgE and PHA-induced IL-5. At 4 years of age when allergen reactivity was assessed by SPT, the high general TH2 responses did not translate into higher prevalence of SPT. The risk factor for SPT reactivity was low maternal education which decreased the risk of SPT positivity to allergens (adjusted OR, 0.32; 95% CI, 0.12 - 0.87) independently of maternal filarial infection which tended to reduce the child's risk for being SPT positive (adjusted OR, 0.35; 95% CI, 0.07 - 1.70). Conclusions: In areas endemic for helminths, potent TH2 responses were seen early in life, but did not translate into a higher SPT reactivity to allergens. Therefore, in many parts of the world TH2 responses in general and IgE in particular cannot be used for diagnosis of allergic diseases. [ABSTRACT FROM AUTHOR]

A pen study was conducted to assess the effect of providing daily copper mineral supplement, or copper wire particle (COWP) capsules, on established or incoming mixed nematode infections in young sheep. For lambs with established (6 week old) infections, COWP resulted in 97% and 56% reduction of the adult and early L4 stages of H. contortus, respectively, compared with controls (p<0.001). Additionally there was a 74% reduction in Teladorsagia circumcincta infections in the COWP lambs compared with controls (p<0.01). However, no effect was observed when COWP were given at the commencement of a larval dosing period of 6 weeks. There was no significant effect of copper mineral supplement (given at the recommended rate to prevent Cu deficiency) on either established, or developing parasite infections. In addition, a field trial was conducted on a commercial farm to assess the effects of COWP in the management of recurrent H. contortus infections, but lack of parasites during the grazing season prevented an adequate assessment from being made. These results indicate that there is little, if any, benefit from a parasite control standpoint in recommending copper therapy, specifically to control parasites in Swedish sheep flocks. [ABSTRACT FROM AUTHOR]