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Parasites & Vectors Jan 2018We present evidence that the dog hookworm (Ancylostoma caninum) is underutilised in the study of host-parasite interactions, particularly as a proxy for the... (Review)
Review
We present evidence that the dog hookworm (Ancylostoma caninum) is underutilised in the study of host-parasite interactions, particularly as a proxy for the human-hookworm relationship. The inability to passage hookworms through all life stages in vitro means that adult stage hookworms have to be harvested from the gut of their definitive hosts for ex vivo research. This makes study of the human-hookworm interface difficult for technical and ethical reasons. The historical association of humans, dogs and hookworms presents a unique triad of positive evolutionary pressure to drive the A. caninum-canine interaction to reflect that of the human-hookworm relationship. Here we discuss A. caninum as a proxy for human hookworm infection and situate this hookworm model within the current research agenda, including the various 'omics' applications and the search for next generation biologics to treat a plethora of human diseases. Historically, the dog hookworm has been well described on a physiological and biochemical level, with an increasing understanding of its role as a human zoonosis. With its similarity to human hookworm, the recent publications of hookworm genomes and other omics databases, as well as the ready availability of these parasites for ex vivo culture, the dog hookworm presents itself as a valuable tool for discovery and translational research.
Topics: Ancylostoma; Ancylostomiasis; Animals; Disease Models, Animal; Dog Diseases; Dogs; Host-Parasite Interactions; Humans; Translational Research, Biomedical
PubMed: 29370855
DOI: 10.1186/s13071-018-2621-2 -
Cytokine May 2024Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in...
Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in laboratories and living organisms, there are still unanswered questions due to the complex nature of these fields. In this study we investigated the effects of hookworm infection on iron metabolism and how the hosts response to anemia is affected using hamsters infected with Ancylostoma ceylanicum as a model. Our data revealed interesting relationships between infection-induced anemia, erythropoiesis, iron metabolism, and immune modulation, such that the elevated production of erythropoietin (EPO) in renal tissue indicated intensified erythropoiesis in response to anemia. Additionally, the increased expression of the erythroferrone (ERFE) gene in the spleen suggested its involvement in iron regulation and erythropoiesis. Gene expression patterns of genes related to iron metabolism varied in different tissues, indicating tissue-specific adaptations to hypoxia. The modulation of pro-inflammatory and anti-inflammatory cytokines highlighted the delicate balance between immune response and erythropoiesis. Data derived from the investigation of changes induced in iron metabolism and stress erythropoiesis following anemia aid in our understanding of mechanisms related to blood spoliation and anemia, which could potentially be extrapolated or compared to other types or causes of anemia. These findings also contribute to our understanding of the pathophysiology of erythropoiesis in the context of blood loss.
Topics: Humans; Erythropoiesis; Hepcidins; Anemia; Iron; Erythropoietin; Hookworm Infections
PubMed: 38412767
DOI: 10.1016/j.cyto.2024.156559 -
MMW Fortschritte Der Medizin Jun 2021
Review
Topics: Ancylostomatoidea; Animals; Coronavirus; Coronavirus Infections; Hookworm Infections; Humans; Ivermectin
PubMed: 34086220
DOI: 10.1007/s15006-021-0066-6 -
International Journal For Parasitology Dec 2021The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important... (Review)
Review
The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products.
Topics: Ancylostomatoidea; Animals; Ascariasis; Helminthiasis; Helminths; Hookworm Infections; Humans; Nematoda; Prevalence; Soil; Trichuriasis; Trichuris; Vaccines
PubMed: 34774540
DOI: 10.1016/j.ijpara.2021.11.001 -
Parasite Immunology Jun 2022In Hookworm infection, neutrophils have long had the image of the villain, being recruited to the site of larval migration because of damage but participating themselves... (Review)
Review
In Hookworm infection, neutrophils have long had the image of the villain, being recruited to the site of larval migration because of damage but participating themselves in tissue injury. With recent developments in neutrophil biology, there is an increasing body of evidence for the role of neutrophils as effector cells in hookworm immunity. In particular, their ability to release extracellular traps, or neutrophil extracellular traps (NETs), confer neutrophils a larvicidal activity. Here, we review recent evidence in this nascent field and discuss the avenue for future research on NETs/hookworm interactions.
Topics: Ancylostomatoidea; Animals; Extracellular Traps; Hookworm Infections; Neutrophils
PubMed: 35124825
DOI: 10.1111/pim.12911 -
Antimicrobial Agents and Chemotherapy Jan 2021Tribendimidine has been successful in treating hookworm infections and may serve as an alternative to albendazole should resistance arise. Our aims were to (i)...
Tribendimidine has been successful in treating hookworm infections and may serve as an alternative to albendazole should resistance arise. Our aims were to (i) characterize the pharmacokinetics (PK) of tribendimidine's primary metabolite, deacetylated amidantel (dADT), and secondary metabolite, acetylated derivative of amidantel (adADT), in school-aged children and adolescents, (ii) link exposure to efficacy against hookworm, and (iii) evaluate whether tribendimidine pharmacotherapy in children could be further improved. First, a population PK model was developed based on dried-blood-spot samples collected from 155 school-aged children and adolescents with hookworm infections, following tribendimidine doses ranging from 100 to 400 mg. Second, an exposure-response analysis was conducted to link the active metabolite dADT to cure rates (CRs) and egg reduction rates (ERRs). Third, simulations were performed to identify a treatment strategy associated with >90% CRs. A two-compartmental model with transit compartments describing observed delay in absorption adequately described PK data of dADT and adADT. Allometric scaling was included to account for growth and development. The absorption rate was 56% lower with 200-mg tablets than with 50-mg tablets, while the extent of absorption remained unaffected. The identified models linking dADT exposure to ERRs and CRs showed shallow curves, as increasing exposure led to marginal efficacy increase. Combination therapy should be considered, as a 12-fold-higher dose would be needed to achieve 95% ERRs and CRs >90% with tribendimidine alone. Further studies are warranted to evaluate safety of higher tribendimidine doses and combination therapies with other anthelmintic agents to improve treatment strategy for children with hookworm infection.
Topics: Adolescent; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Child; Hookworm Infections; Humans; Phenylenediamines; Treatment Outcome
PubMed: 33139293
DOI: 10.1128/AAC.01778-20 -
Molecular and Biochemical Parasitology Sep 2019Obesity and ancylostomiasis are considered public health problems. Recent studies have shown that infection by intestinal helminths in obese individuals can ameliorate...
Obesity and ancylostomiasis are considered public health problems. Recent studies have shown that infection by intestinal helminths in obese individuals can ameliorate metabolic disorder and improve glucose tolerance by decreasing both insulin resistance and low-intensity inflammation. However, few helminth species have been studied in this context, and some modulation mechanisms still require deeper investigation. Therefore, the present work aimed to investigate the role of experimental infection with Ancylostoma ceylanicum in the modulation of the immune response in an obese experimental model. Four groups of hamsters were used as follows: two groups were submitted to a hyperlipidic and hypercaloric diet capable of inducing obesity, one infected and the other uninfected; and two normonourished control groups, one infected and one uninfected by A. ceylanicum. Biochemical, haematological, parasitological and immunological parameters were evaluated. The results demonstrated that A. ceylanicum infection accentuated weight loss in obese animals compared to normonourished animals. However, obesity reduced the recovery of worms and oviposition of the females, and both infected groups showed decreased levels of haemoglobin, albumin, iron and erythrocytes. Significant relations were observed for pathogenesis in the following cases: infection interfered in lipid metabolism, which increased levels of total cholesterol and triglycerides in the obese group, and caused a decrease in HDL levels in both groups. Obesity led to an increase in glucose levels, and the infection exacerbated this parameter in both the normonourished and obese groups. Inflammation was intensified in obese animals that showed elevated macrophage and neutrophil activation in adipose tissue, enlargement of the spleen and accumulation of lipids in the liver and faeces. Despite the decrease in IFN-γ levels, the infection did not potentiated the expression of the Foxp3, IL-10 and IL-2 transcription factor for any of the infected groups, markers that could positively compensate the host from the damage caused by obesity.
Topics: Ancylostoma; Ancylostomiasis; Animals; Cholesterol; Cricetinae; Female; Glucose; Humans; Interleukin-10; Interleukin-12; Liver; Male; Obesity; Oviposition; Triglycerides
PubMed: 31306675
DOI: 10.1016/j.molbiopara.2019.111200 -
Parasites & Vectors Jan 2016Soil-transmitted helminth (STH) infections of humans fall within the World Health Organization's (WHO) grouping termed the neglected tropical diseases (NTDs). It is... (Review)
Review
Soil-transmitted helminth (STH) infections of humans fall within the World Health Organization's (WHO) grouping termed the neglected tropical diseases (NTDs). It is estimated that they affect approximately 1.4 billion people worldwide. A significant proportion of these infections are in the population of Southeast Asia. This review analyses published data on STH prevalence and intensity in Southeast Asia over the time period of 1900 to the present to describe age related patterns in these epidemiological measures. This is with a focus on the four major parasite species affecting humans; namely Ascaris lumbricoides, Trichuris trichiura and the hookworms; Necator americanus and Ancylostoma duodenale. Data were also collected on the diagnostic methods used in the published surveys and how the studies were designed to facilitate comparative analyses of recorded patterns and changes therein over time. PubMed, Google Scholar, EMBASE, ISI Web of Science, Cochrane Database of Systematic Reviews and the Global Atlas of Helminth Infections search engines were used to identify studies on STH in Southeast Asia with the search based on the major key words, and variants on, "soil-transmitted helminth" "Ascaris" "Trichuris" "hookworm" and the country name. A total of 280 studies satisfied the inclusion criteria from 11 Southeast Asian countries; Brunei, Cambodia, Indonesia, Lao People's Democratic Republic (Lao PDR), Malaysia, Myanmar, Philippines, Singapore, Thailand, Timor-Leste and Vietnam. It was concluded that the epidemiological patterns of STH infection by age and species mix in Southeast Asia are similar to those reported in other parts of the world. In the published studies there were a large number of different diagnostic methods used with differing sensitivities and specificities, which makes comparison of the results both within and between countries difficult. There is a clear requirement to standardise the methods of both STH diagnosis in faecal material and how the intensity of infection is recorded and reported in future STH research and in monitoring and evaluation (M&E) of the impact of continuing and expanding mass drug administration (MDA) programmes.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Ascariasis; Ascaris lumbricoides; Asia, Southeastern; Feces; Helminthiasis; Helminths; Hookworm Infections; Humans; Prevalence; Research; Soil; Surveys and Questionnaires; Trichuriasis; Trichuris
PubMed: 26813007
DOI: 10.1186/s13071-016-1310-2 -
The Kaohsiung Journal of Medical... Nov 2023
Topics: Humans; Hookworm Infections; Colonoscopy
PubMed: 37650581
DOI: 10.1002/kjm2.12748 -
PLoS Neglected Tropical Diseases Jun 2021Soil-Transmitted Helminths (STH) are highly prevalent Neglected Tropical Disease in Ethiopia, an estimated 26 million are infected. Geographic Information Systems and...
Soil-Transmitted Helminths (STH) are highly prevalent Neglected Tropical Disease in Ethiopia, an estimated 26 million are infected. Geographic Information Systems and Remote Sensing (RS) technologies assist data mapping and analysis, and the prediction of the spatial distribution of infection in relation to environmental variables. The influence of socioeconomic, environmental and soil characteristics on hookworm infection at the individual and household level is explored in order to identify spatial patterns of infection in rural villages from Zenzelema (Amhara region). Inhabitants greater than 5 years old were recruited in order to assess the presence of STH. Socioeconomic and hookworm infection variables at the household level and environmental variables and soil characteristics using RS were obtained. The dominant STH found was hookworm. Individuals which practiced open defecation and those without electricity had a significant higher number of hookworm eggs in their stool. Additionally, adults showed statistically higher hookworm egg counts than children. Nonetheless, the probability of hookworm infection was not determined by socioeconomic conditions but by environmental characteristics surrounding the households, including a combination of vigorous vegetation and bare soil, high temperatures, and compacted soils (high bulk density) with more acidic pH, given a pH of 6.0 is optimal for hatching of hookworm eggs. The identification of high-risk environmental areas provides a useful tool for planning, targeting and monitoring of control measures, including not only children but also adults when hookworm is concerned.
Topics: Ancylostomatoidea; Animals; Environment; Ethiopia; Hookworm Infections; Housing; Humans; Hydrogen-Ion Concentration; Rural Population; Socioeconomic Factors; Soil; Temperature
PubMed: 34157019
DOI: 10.1371/journal.pntd.0009466