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Molecular and Biochemical Parasitology Nov 2022Caenorhabditis elegans is a uniquely powerful tool to aid understanding of fundamental nematode biology. While C. elegans boasts an unrivalled array of functional... (Review)
Review
Caenorhabditis elegans is a uniquely powerful tool to aid understanding of fundamental nematode biology. While C. elegans boasts an unrivalled array of functional genomics tools and phenotype bioassays the inherent differences between free-living and parasitic nematodes underscores the need to develop these approaches in tractable parasite models. Advances in functional genomics approaches, including RNA interference and CRISPR/Cas9 gene editing, in the parasitic nematodes Strongyloides ratti and Strongyloides stercoralis provide a unique and timely opportunity to probe basic parasite biology and reveal novel anthelmintic targets in species that are both experimentally and therapeutically relevant pathogens. While Strongyloides functional genomics tools have progressed rapidly, the complementary range of bioassays required to elucidate phenotypic outcomes post-functional genomics remain more limited in scope. To adequately support the exploitation of functional genomic pipelines for studies of gene function in Strongyloides a comprehensive set of species- and parasite-specific quantitative bioassays are required to assess nematode behaviours post-genetic manipulation. Here we review the scope of the current Strongyloides bioassay toolbox, how established Strongyloides bioassays have advanced knowledge of parasite biology, opportunities for Strongyloides bioassay development and, the need for investment in tractable model parasite platforms such as Strongyloides to drive the discovery of novel targets for parasite control.
Topics: Animals; Parasites; Caenorhabditis elegans; Nematoda; Genomics; Strongyloides stercoralis; Biological Assay
PubMed: 36240960
DOI: 10.1016/j.molbiopara.2022.111526 -
Scientific Reports Jun 2022Strongyloidiasis is a neglected tropical disease caused by the soil-transmitted nematode by Strongyloides stercoralis, that affects approximately 600 million people...
Strongyloidiasis is a neglected tropical disease caused by the soil-transmitted nematode by Strongyloides stercoralis, that affects approximately 600 million people worldwide. In immunosuppressed individuals disseminated strongyloidiasis can rapidly lead to fatal outcomes. There is no gold standard for diagnosing strongyloidiasis, and infections are frequently misdiagnosed. A better understanding of the molecular biology of this parasite can be useful for example for the discovery of potential new biomarkers. Interestingly, recent evidence showed the presence of small RNAs in Strongyloididae, but no data was provided for S. stercoralis. In this study, we present the first identification of miRNAs of both L1 and iL3 larval stages of S. stercoralis. For our purpose, the aims were: (i) to analyse the miRNome of L1 and iL3 S. stercoralis and to identify potential miRNAs of this nematode, (ii) to obtain the mRNAs profiles in these two larval stages and (iii) to predict potential miRNA target sites in mRNA sequences. Total RNA was isolated from L1 and iL3 collected from the stool of 5 infected individuals. For the miRNAs analysis, we used miRDeep2 software and a pipeline of bio-informatic tools to construct a catalog of a total of 385 sequences. Among these, 53% were common to S. ratti, 19% to S. papillosus, 1% to Caenorhabditis elegans and 44% were novel. Using a differential analysis between the larval stages, we observed 6 suggestive modulated miRNAs (STR-MIR-34A-3P, STR-MIR-8397-3P, STR-MIR-34B-3P and STR-MIR-34C-3P expressed more in iL3, and STR-MIR-7880H-5P and STR-MIR-7880M-5P expressed more in L1). Along with this analysis, we obtained also the mRNAs profiles in the same samples of larvae. Multiple testing found 81 statistically significant mRNAs of the total 1553 obtained (FDR < 0.05; 32 genes expressed more in L1 than iL3; 49 genes expressed more in L3 than iL1). Finally, we found 33 predicted mRNA targets of the modulated miRNAs, providing relevant data for a further validation to better understand the role of these small molecules in the larval stages and their valuein clinical diagnostics.
Topics: Animals; Feces; Humans; Larva; MicroRNAs; RNA, Messenger; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35705621
DOI: 10.1038/s41598-022-14185-y -
Parasites & Vectors Jun 2022The WHO has established a control strategy for Strongyloides stercoralis in school-aged children as well as targets and to maintain control programs for Ascaris...
BACKGROUND
The WHO has established a control strategy for Strongyloides stercoralis in school-aged children as well as targets and to maintain control programs for Ascaris lumbricoides, Trichuris trichiura and hookworms. For an efficient development of control programs, it is necessary to know the target countries around the world, as well as the areas within each country where efforts should be focused. Therefore, maps that provide information on the areas at risk for soil-transmitted helminth (STH) infections on a national and sub-national scale would allow for a better allocation of resources.
METHODS
We used the ecological niche models MaxEnt and Kuenm R library to estimate the global distribution of S. stercoralis and hookworms. We used occurrence points of both species extracted from surveys of two literature reviews and from the Global Atlas of Helminth Infection database, together with 14 raster maps of environmental variables.
RESULTS
We obtained two raster maps with the presence probability of S. stercoralis and hookworm infections at a global level and then estimated the global population at risk to be 2.6 and 3.4 billion, respectively. The population at risk was also estimated at the country level using estimations for areas as small as 25 km. A relationship was found between the probability of the presence of S. stercoralis and its prevalence, and a raster map was generated. Annual precipitation, annual temperature, soil carbon content and land cover were the main associated environmental variables. The ecological niches of Strongyloides stercoralis and hookworms had an overlap of 68%.
CONCLUSIONS
Here we provide information that can be used for developing more efficient and integrated control strategies for S. stercoralis and hookworm infections. This information can be annexed to the study of other risk factors or even other diseases to assess the health status of a community. GRAPHICAL ABSTARCT.
Topics: Ancylostomatoidea; Animals; Ascaris lumbricoides; Child; Ecosystem; Feces; Helminthiasis; Hookworm Infections; Humans; Prevalence; Soil; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35676740
DOI: 10.1186/s13071-022-05284-w -
Parasites & Vectors May 2020Strongyloidiasis is a soil borne helminthiasis, which in most cases is caused by Strongyloides stercoralis. Human infections with S. fuelleborni fuelleborni and S....
BACKGROUND
Strongyloidiasis is a soil borne helminthiasis, which in most cases is caused by Strongyloides stercoralis. Human infections with S. fuelleborni fuelleborni and S. fuelleborni kellyi also occur. Although up to 370 million people are currently estimated to be infected with S. stercoralis, this parasite is frequently overlooked. Strongyloides stercoralis is prevalent among humans in Thailand; however, S. fuelleborni fuelleborni has also been reported. Three recent genomic studies of individual S. stercoralis worms found genetically diverse populations of S. stercoralis, with comparably low heterozygosity in Cambodia and Myanmar, and less diverse populations with high heterozygosity in Japan and southern China that presumably reproduce asexually.
METHODS
We isolated individual Strongyloides spp. from different localities in northern and western Thailand and determined their nuclear small ribosomal subunit rDNA (18S rDNA, SSU), in particular the hypervariable regions I and IV (HVR-I and HVR-IV), mitochondrial cytochrome c oxidase subunit 1 (cox1) and for a subset whole genome sequences. These sequences were then compared with each other and with published sequences from different geographical locations.
RESULTS
All 237 worms isolated from 16 different human hosts were S. stercoralis, no S. fuelleborni was found. All worms had the common S. stercoralis SSU HVR IV haplotype A. Two different SSU HVR I haplotypes (I and II), both previously described in S. stercoralis, were found. No animal heterozygous for the two haplotypes was identified. Among the twelve cox1 haplotypes found, five had not been previously described. Based upon the mitochondrial cox1 and the nuclear whole genome sequences, S. stercoralis in Thailand was phylogenetically intermixed with the samples from other Southeast Asian countries and did not form its own branch. The genomic heterozygosity was even slightly lower than in the samples from the neighboring countries.
CONCLUSIONS
In our sample from humans, all Strongyloides spp. were S. stercoralis. The S. stercoralis from northern and western Thailand appear to be part of a diverse, intermixing continental Southeast Asian population. No obvious indication for genetic sub-structuring of S. stercoralis within Thailand or within the Southeast Asian peninsula was detected.
Topics: Animals; DNA, Helminth; Feces; Female; Genetic Variation; Genome, Helminth; Genomics; Genotype; Humans; Male; Neglected Diseases; Phylogeny; RNA, Ribosomal, 18S; Strongyloides stercoralis; Strongyloidiasis; Thailand; Whole Genome Sequencing
PubMed: 32404172
DOI: 10.1186/s13071-020-04115-0 -
Molecular and Biochemical Parasitology Jul 2022The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and... (Review)
Review
The oft-neglected human-parasitic threadworm, Strongyloides stercoralis, infects roughly eight percent of the global population, placing disproportionate medical and economic burden upon marginalized communities. While current chemotherapies treat strongyloidiasis, disease recrudescence and the looming threat of anthelminthic resistance necessitate novel strategies for nematode control. Throughout its life cycle, S. stercoralis relies upon sensory cues to aid in environmental navigation and coordinate developmental progression. Odorants, tastants, gases, and temperature have been shown to shape parasite behaviors that drive host seeking and infectivity; however, many of these sensory behaviors remain poorly understood, and their underlying molecular and neural mechanisms are largely uncharacterized. Disruption of sensory circuits essential to parasitism presents a promising strategy for future interventions. In this review, we describe our current understanding of sensory behaviors - namely olfactory, gustatory, gas sensing, and thermosensory behaviors - in Strongyloides spp. We also highlight the ever-growing cache of genetic tools optimized for use in Strongyloides that have facilitated these findings, including transgenesis, CRISPR/Cas9-mediated mutagenesis, RNAi, chemogenetic neuronal silencing, and the use of fluorescent biosensors to measure neuronal activity. Bolstered by these tools, we are poised to enter an era of rapid discovery in Strongyloides sensory neurobiology, which has the potential to shape pioneering advances in the prevention and treatment of strongyloidiasis.
Topics: Animals; Humans; Life Cycle Stages; Nematoda; Strongyloides stercoralis; Strongyloidiasis; Symbiosis
PubMed: 35697205
DOI: 10.1016/j.molbiopara.2022.111491 -
Biomedica : Revista Del Instituto... Mar 2022Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low...
INTRODUCTION
Individuals infected with the human T-lymphotropic virus type 1 (HTLV-1) may present severe and disseminated forms of Strongyloides stercoralis infection with low therapeutic response.
OBJECTIVE
To investigate the S. stercoralis infection and the seroprevalence of IgG anti-S. stercoralis antibodies in individuals infected with HTLV-1 attending the Reference Center for HTLV-1 (CHTLV) in Salvador, Bahia, Brazil.
MATERIALS AND METHODS
We conducted a cross-sectional study in 178 HTLV-1-infected individuals treated at the HTLV specialized center between January, 2014, and December, 2018. The parasitological diagnosis of S. stercoralis was performed using the Hoffman, Pons and Janer, agar plate culture, and Baermann-Morais methods. The IgG anti-S. stercoralis detection was performed using an in house enzyme-linked immunosorbent assay (ELISA). The HTLV-1 infection was diagnosed using a commercial ELISA and confirmed by Western blot.
RESULTS
The frequency of S. stercoralis infection was 3.4% (6/178). Individuals infected with S. stercoralis from rural areas (50.0%; 3/6) also showed S. stercoralis hyperinfection (>3,000 larvae/gram of feces). The frequency of circulating anti-S. stercoralis IgG antibodies was 20.8% (37/178).
CONCLUSIONS
HTLV-1-infected people living in precarious sanitary conditions are more prone to develop severe forms of S. stercoralis infection. Considering the high susceptibility and unfavorable outcome of the infection in these individuals, the serological diagnosis for S. stercoralis should be considered when providing treatment.
Topics: Animals; Cross-Sectional Studies; Human T-lymphotropic virus 1; Humans; Immunoglobulin G; Seroepidemiologic Studies; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35471168
DOI: 10.7705/biomedica.5888 -
World Journal of Gastroenterology Sep 2017Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential...
Animal models and clinical studies have shown that helminth infections exert immunomodulatory activity, altering intestinal permeability and providing a potential beneficial action on autoimmune and inflammatory disorders in human beings, such as inflammatory bowel disease (IBD) and celiac disease. This is consistent with the theory that intestinal microbiota is responsible for shaping human immunological responses. With the arrival of the immunobiologic era and the use of antibodies, we propose a distinctive pathway for treating patients with IBD and celiac disease. We have some evidence about the safety and tolerability of helminth use, but evidence about their impact on disease activity is lacking. Using worms to treat diseases could be a possible way to lower treatment costs, since the era of immunobiologic agents is responsible for a significant rise in expenses. Some questions remain to be investigated regarding the use of helminths in intestinal disease, such as the importance of the specific species of helminths used, appropriate dosing regimens, optimal timing of treatment, the role of host genetics, diet, environment, and the elucidation of the exact mechanisms of action. One promising approach is the use of helminth-derived anti-inflammatory molecules as drugs. Yet there are still many challenges with this method, especially with regard to safety. Studies on intestinal permeability point to as a useful nematode for these purposes.
Topics: Animals; Biological Products; Biological Therapy; Celiac Disease; Clinical Trials as Topic; Complementary Therapies; Humans; Hygiene Hypothesis; Immunotherapy; Inflammatory Bowel Diseases; Intestinal Mucosa; Permeability; Strongyloides stercoralis; Treatment Outcome
PubMed: 28970717
DOI: 10.3748/wjg.v23.i33.6009 -
Strongyloides stercoralis prevalence and diagnostics in Vientiane, Lao People's Democratic Republic.Infectious Diseases of Poverty Sep 2020Despite the high prevalence of strongyloidiasis in the Laotian population, Laotian hospitals still lack diagnostic capacity to appropriately diagnose Strongyloides...
BACKGROUND
Despite the high prevalence of strongyloidiasis in the Laotian population, Laotian hospitals still lack diagnostic capacity to appropriately diagnose Strongyloides stercoralis infections. This cross-sectional hospital-based study was conducted to assess the prevalence of Strongyloides stercoralis infection among hospitalized patients treated at Mahosot Hospital, the primary reference hospital of Lao People's Democratic Republic (Lao PDR), and to validate feasible methods for diagnosing S. stercoralis infection at hospital's laboratory.
METHODS
Between September and December 2018, stool samples of 104 inpatients were investigated for S. stercoralis infection by wet smear, Baermann technique, Koga Agar plate culture (KAPC), and real-time detection polymerase chain reaction (RTD-PCR) at the Infectious Diseases Ward of the Mahosot Hospital in Vientiane. The sensitivity, the specificity, the negative predictive value (NPV) of each diagnostic test, as well as their combination(s) was calculated using a composite reference standard (CRS). The correlation of the different test methods was assessed by chi-square or Fisher's exact test. Cohen's kappa coefficient was used to assess the diagnostic agreement of the different test methods.
RESULTS
The overall prevalence of S. stercoralis infections among the study population was 33.4%. The cumulative infection prevalence statistically significantly increased from the lowest age group of 40 years and below (22.4%), to the medium (40.0%) and to the oldest age group of 61 year and above (72.7%)(P = 0.003). The cumulative infection prevalence of CRS was considerably higher in male (40.4%) compared to female patients (28.1%), but not statistically different (P = 0.184). The diagnostic sensitivity of Baermann technique, KAPC, RTD-PCR, and the combination of Baermann technique and KAPC were 60.0, 60.0, 74.3, and 77.1%, respectively. Only 13 patients (37.1%) of the total 35 S. stercoralis patients diagnosed with any technique had a simultaneously positive diagnostic test with Baermann, KAPC and RTD-PCR.
CONCLUSIONS
We identified Baermann technique and KAPC to be currently the most feasible and implementable standard methods for diagnosing S. stercoralis at a hospital setting such as Mahosot Hospital and provincial and district hospitals in Lao PDR and other low- and middle income countries in Southeast Asia.
TRIAL REGISTRATION
This study was approved by the National Ethics Committee for Health Research in Lao PDR (reference no. 083/NECHR) and by the Ethics Committee Northwest and Central Switzerland (reference no. 2018-00594).
Topics: Adult; Aged; Aged, 80 and over; Animals; Cross-Sectional Studies; DNA, Helminth; Feasibility Studies; Feces; Female; Humans; Inpatients; Laos; Male; Middle Aged; Prevalence; Reagent Kits, Diagnostic; Real-Time Polymerase Chain Reaction; Strongyloides stercoralis; Strongyloidiasis; Young Adult
PubMed: 32958071
DOI: 10.1186/s40249-020-00750-y -
Open Forum Infectious Diseases Mar 2023is an intestinal nematode most commonly found in subtropical and tropical locations. Military service members are believed to be at increased risk of exposure due to...
BACKGROUND
is an intestinal nematode most commonly found in subtropical and tropical locations. Military service members are believed to be at increased risk of exposure due to their unique occupational exposures in endemic regions.
METHODS
Burden, clinical course, and risk factors associated with all infections within the US Military Health System from fiscal years 2012 to 2019 were assessed by manual chart review of records with / codes for s infection. Infection risk in demographic subgroups based on region of birth, military occupation, and age was quantified with univariate analysis and multivariate logistic regression.
RESULTS
We reviewed 243 charts based on diagnosis coding, yielding 210 confirmed diagnoses (86.4%). Immigrant patients born in Latin America/Caribbean, sub-Saharan Africa, and East Asia/Pacific regions had statistically significant increased risk ratios of infection at 34.4, 32.0, and 22.4, respectively, when compared to patients born in Europe and North America. In univariate analysis, active duty members in the healthcare occupational category had a statistically significant increased risk ratio of infection at 2.31 compared to those outside this occupation. Multivariate logistic regression analysis demonstrated that occupational categories of healthcare, admininstrative/support, warfighter/combat specialist, and engineering/repair/maintenance occupations, being an immigrant patient, and age ≥65 were all associated with statistically significant increased odds ratios for infection.
CONCLUSIONS
In the Military Health System, occupational exposures, region of birth, and age serve as risk factors for infection. Because infections may be chronic, the impact of targeted screening programs to complement routine medical care should be considered.
PubMed: 37008572
DOI: 10.1093/ofid/ofad127 -
PLoS Neglected Tropical Diseases Jul 2023Strongyloides stercoralis is a neglected soil-transmitted helminth (STH) that leads to significant morbidity in endemic populations. Infection with this helminth has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Strongyloides stercoralis is a neglected soil-transmitted helminth (STH) that leads to significant morbidity in endemic populations. Infection with this helminth has recently been recognised by the World Health Organization (WHO) as a major global health problem to be addressed with ivermectin preventive chemotherapy, and therefore, there is now, the need to develop guidelines for strongyloidiasis control that can be implemented by endemic countries. This study aimed to evaluate the impact of ivermectin preventive chemotherapy (PC) on S. stercoralis prevalence in endemic areas to generate evidence that can inform global health policy.
METHODOLOGY/PRINCIPAL FINDINGS
This study was a systematic review and meta-analysis. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and LILACS for literature published between 1990 and 2022 and reporting prevalence of S. stercoralis before and after PC with ivermectin, administered either at school or at community level. The search strategy identified 933 records, eight of which were included in the meta-analysis. Data extraction and quality assessment were carried out by two authors. Meta-analysis of studies based on fecal testing demonstrated a significant reduction of S. stercoralis prevalence after PC: prevalence Risk Ratio (RR) 0.18 (95% CI 0.14-0.23), I2 = 0. A similar trend was observed in studies that used serology for diagnosis: RR 0.35 (95% CI 0.26-0.48), I2 = 4.25%. A sensitivity analysis was carried out for fecal tests where low quality studies were removed, confirming a post-intervention reduction in prevalence. The impact of PC could not be evaluated at different time points or comparing annual vs biannual administration due to insufficient data.
CONCLUSIONS/SIGNIFICANCE
Our findings demonstrate a significant decrease of S. stercoralis prevalence in areas where ivermectin PC has taken place, supporting the use of ivermectin PC in endemic areas.
Topics: Animals; Humans; Strongyloides stercoralis; Ivermectin; Strongyloidiasis; Chemoprevention; Prevalence
PubMed: 37428815
DOI: 10.1371/journal.pntd.0011473