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Nature Reviews. Disease Primers Dec 2016Hookworms are soil-transmitted nematode parasites that can reside for many years in the small intestine of their human hosts; Necator americanus is the predominant... (Review)
Review
Hookworms are soil-transmitted nematode parasites that can reside for many years in the small intestine of their human hosts; Necator americanus is the predominant infecting species. Adult worms feed on the blood of a host and can cause iron deficiency anaemia, especially in high-risk populations (children and women of childbearing age). Almost 500 million people in developing tropical countries are infected, and simulation models estimate that hookworm infection is responsible for >4 million disability-adjusted life years lost annually. Humans mount an immune response to hookworms, but it is mostly unsuccessful at removing adult worms from the bowel. Accordingly, the host switches to an immune-tolerant state that enables hookworms to reside in the gut for many years. Although anthelmintic drugs are available and widely used, their efficacy varies and the drugs do not prevent reinfection. Thus, other control strategies aimed at improving water quality, sanitation and hygiene are needed. In addition, efforts are underway to develop a human hookworm vaccine through public-private partnerships. However, hookworms could also be a resource; as hookworms have the capability to regulate the host's inflammation, researchers are experimentally infecting patients to treat some inflammatory diseases as an approach to discover new anti-inflammatory molecules. This area of endeavour might well yield new biotherapeutics for autoimmune and allergic diseases.
Topics: Albendazole; Ancylostomatoidea; Anemia; Animals; Anthelmintics; Factor VIIa; Factor XIa; Factor Xa; Feces; Hemorrhage; Hookworm Infections; Humans; Intestine, Small; Larva Migrans; Mebendazole; Necator americanus; Prevalence; Risk Factors; Soil
PubMed: 27929101
DOI: 10.1038/nrdp.2016.88 -
The New England Journal of Medicine May 2023Current treatments for soil-transmitted helminth infections in humans have low efficacy against . Emodepside - a drug in veterinary use and under development for the... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Current treatments for soil-transmitted helminth infections in humans have low efficacy against . Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection.
METHODS
We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo.
RESULTS
A total of 266 persons were enrolled in the trial and 176 in the hookworm trial. The predicted cure rate against in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events.
CONCLUSIONS
Emodepside showed activity against and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).
Topics: Adult; Animals; Humans; Albendazole; Feces; Hookworm Infections; Soil; Trichuriasis; Trichuris; Depsipeptides; Antinematodal Agents; Young Adult; Middle Aged; Administration, Oral; Dose-Response Relationship, Drug
PubMed: 37195942
DOI: 10.1056/NEJMoa2212825 -
Pediatric Clinics of North America Feb 2022Intestinal nematode infections caused by soil-transmitted helminths (STH), such as the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura, and the... (Review)
Review
Intestinal nematode infections caused by soil-transmitted helminths (STH), such as the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura, and the hookworms Ancylostoma duodenale, and Necator americanus, infect more than 1 billion people throughout the world. School-aged children tend to harbor the greatest numbers of intestinal worms, and as a result, experience more adverse health consequences, such as poor growth, anemia, and cognitive decline. Clinicians should maintain a high degree of suspicion in endemic areas when patients present with surgical abdomens, particularly children. Current antihelminthic drugs are moderately effective, but reinfection is possible. Global efforts are needed to eradicate STH infections.
Topics: Adolescent; Albendazole; Ancylostoma; Anemia; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Child, Preschool; Female; Helminthiasis; Hookworm Infections; Humans; Hygiene; Infant; Intestinal Diseases, Parasitic; Male; Necator americanus; Nematode Infections; Soil; Trichuriasis; Trichuris
PubMed: 34794670
DOI: 10.1016/j.pcl.2021.08.005 -
Parasite Immunology Feb 2018Hookworm is a major public health concern, yet still relatively little is known about the immunological responses involved in human infection. Animal studies are mainly... (Review)
Review
Hookworm is a major public health concern, yet still relatively little is known about the immunological responses involved in human infection. Animal studies are mainly confined to using the natural rodent helminth Nippostrongylus brasiliensis as this has been proposed as the most accurate model of hookworm infection in the mouse, with both its life cycle and the immune responses it invokes having been extremely well characterized. In this review, we examine the roles that type 2 innate lymphoid cells (ILC2s) play in immunity and host tolerance to hookworm infection, particularly N. brasiliensis. This includes their role in the initiation and regulation of immune responses, as well as in the resolution and limitation of tissue damage required after an infection with a large organism, such as a helminth.
Topics: Ancylostomatoidea; Animals; Cytokines; Disease Models, Animal; Female; Hookworm Infections; Humans; Immunity, Innate; Male; Mice; Neglected Diseases; Nippostrongylus; Th2 Cells
PubMed: 28369954
DOI: 10.1111/pim.12429 -
The Journal of Allergy and Clinical... Dec 2021Hookworms are hematophagous nematode parasites that have infected a billion people worldwide. Anthelmintic drugs have limited efficacy and do not prevent reinfection.... (Review)
Review
Hookworms are hematophagous nematode parasites that have infected a billion people worldwide. Anthelmintic drugs have limited efficacy and do not prevent reinfection. Therefore, prophylactic vaccines are in high demand. Whole parasite vaccines are allergic and unsafe; thus, research into subunit vaccines has been warranted. A comprehensive overview of protein or peptide subunit vaccines' safety, protective efficacy, and associated immune responses is provided herein. The differences between the immune responses against hookworm infection by patients from epidemic versus nonepidemic areas are discussed in detail. Moreover, the different immunologic mechanisms of protection are discussed, including those that rely on allergic and nonallergic humoral and antibody-dependent cellular responses. The allergic and autoimmune potential of hookworm antigens is also explored, as are the immunoregulatory responses induced by the hookworm secretome. The potential of oral mucosal immunizations has been overlooked. Oral immunity against hookworms is a long-lived and safer immune response that is associated with elimination of infection and protective against reinfections. However, the harsh conditions of the gastrointestinal environment necessitates special oral delivery systems to unlock vaccines' protective potential. The potential for development of safer and more effective peptide- and protein-based anthelmintic vaccines is explored herein.
Topics: Ancylostomatoidea; Animals; Antigens, Helminth; Hookworm Infections; Humans; Immunity, Mucosal; Intestines; Necatoriasis; Vaccines; Vaccines, Subunit
PubMed: 34872650
DOI: 10.1016/j.jaci.2021.10.013 -
Parasitology International Apr 2020Helminth diseases are the ancient scourges of humans and their damages are 'silent and insidious'. Of the helminth infections, schistosomiasis and hookworm infection... (Review)
Review
Helminth diseases are the ancient scourges of humans and their damages are 'silent and insidious'. Of the helminth infections, schistosomiasis and hookworm infection have a great impact. This review covers information regarding vaccine candidates against schistosomiasis and hookworms that reached at least up to the phase-1 trial and literatures regarding other vaccine candidates have been excluded. For clinical manifestations, all available literatures were included, and for epidemiology and global burden of the diseases (GBD), literatures only within 2000-2019 were included. Literatures were searched surfing various databases including PubMED, Google Scholar, and Science Direct and overall over 150 literatures were identified. Globally ~250 million people are suffering from schistosomiasis, resulting 1430 thousand DALY (disability adjusted life year) per year. On the other hand, about 1.3 billion people are infected with hookworm (HW), and according to WHO, ~878 million school-age children (SAC) are at risk. HW is estimated to cause 65,000 deaths annually, accounts for 845 thousand DALYs as well as to cause 6-35.3% loss in productivity. Despite tremendous efforts, very few anthelmintic vaccine candidates such as Na-GST-1, Na-APR-1 and Na-ASP-2 against HW, and Sm28GST/Sh28GST, Sm-p80, Sm14 and Sm-TSP-1/SmTSP-2 against schistosomiasis reached up to the clinical trials. More efforts are needed to achieve the WHO targets taken against the maladies.
Topics: Cost of Illness; Hookworm Infections; Humans; Schistosomiasis; Vaccines
PubMed: 31911156
DOI: 10.1016/j.parint.2020.102051 -
Parasites & Vectors Mar 2020Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many... (Review)
Review
Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.
Topics: Ancylostoma; Ancylostomatoidea; Animals; Antioxidants; Body Fluids; Cloning, Molecular; Female; Helminth Proteins; Hookworm Infections; Host-Parasite Interactions; Humans; Immunologic Factors; Male; Peptide Hydrolases; Protease Inhibitors; Vaccines
PubMed: 32171305
DOI: 10.1186/s13071-020-04010-8 -
Parasite Immunology Aug 2014Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a... (Review)
Review
Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a human infection, is not available for the study of human hookworm infection. Much of our current understanding of the human immune response during hookworm infection relies on the studies from experimental infection of hookworm-naïve individuals or the natural infections from individuals residing in hookworm-endemic areas. The experimental human infections tend to be acute, dose-controlled infections, often with a low larval inoculum so that they are well tolerated by human volunteers. Natural hookworm infections usually occur in areas where hookworm transmission is constant and infection is chronic. In cases where there has been drug administration in an endemic area, re-infection often occurs quickly even amongst those who were treated. Hence, although many of the characteristics of experimental and natural hookworm infection differ, both models have elements in common: mainly an intense Th2 response with the production of total and specific IgE as well as elevated levels of eosinophilia, IL-5, IL-10 and TNF. While hookworm infection affects millions of individuals worldwide, much of the human immunology of this infection still needs to be studied and understood.
Topics: Ancylostomatoidea; Animals; Cytokines; Gene Expression Regulation; Hookworm Infections; Humans
PubMed: 25337625
DOI: 10.1111/pim.12088 -
Trends in Parasitology Jun 2024Hookworms are parasites, closely related to the model nematode Caenorhabditis elegans, that are a major economic and health burden worldwide. Primarily three hookworm... (Review)
Review
Hookworms are parasites, closely related to the model nematode Caenorhabditis elegans, that are a major economic and health burden worldwide. Primarily three hookworm species (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) infect humans. Another 100 hookworm species from 19 genera infect primates, ruminants, and carnivores. Genetic data exist for only seven of these species. Genome sequences are available from only four of these species in two genera, leaving 96 others (particularly those parasitizing wildlife) without any genomic data. The most recent hookworm genomes were published 5 years ago, leaving the field in a dusk. However, assembling genomes from single hookworms may bring a new dawn. Here we summarize advances, challenges, and opportunities for studying these neglected but important parasitic nematodes.
Topics: Animals; Genomics; Genome, Helminth; Hookworm Infections; Ancylostomatoidea; Humans
PubMed: 38677925
DOI: 10.1016/j.pt.2024.04.003 -
Parasite Immunology Feb 2021Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million... (Review)
Review
Hookworm infection is considered the most prevalent human soil-transmitted helminth infection affecting approximately 500 million people and accounting for 3.2 million disability-adjusted life years lost annually. As with many other neglected tropical diseases, no international surveillance mechanisms that show accurate data on the prevalence of hookworm infection are in place, thus hindering strategies to control parasite transmission. In this review, we unravel the current knowledge in immunopathology and immunoregulation of hookworm infection and present discoveries in drug therapies based on the capability of hookworms to regulate inflammation to treat allergic, inflammatory and metabolic diseases. Additionally, we highlight potential vaccine development and treatments and propose avenues for further inquiry.
Topics: Ancylostomatoidea; Animals; Antibodies, Helminth; Hookworm Infections; Host-Parasite Interactions; Humans; Immunity, Cellular; Immunomodulation; Male; Prevalence; Soil; Vaccines
PubMed: 33012113
DOI: 10.1111/pim.12798