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Expert Opinion on Investigational Drugs May 2000Two hookworm parasites, Necator americanus and Ancylostoma duodenale, infect approximately one billion people worldwide. These hookworms are one of the leading causes of... (Review)
Review
Two hookworm parasites, Necator americanus and Ancylostoma duodenale, infect approximately one billion people worldwide. These hookworms are one of the leading causes of iron-deficiency anaemia especially in children, resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L(4)) larva and adult worms. If ignored, human hookworm infections can retard growth and the intellectual development of children. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognised, usually self-limiting condition caused by the infectious larvae of nematodes, especially Ancylostoma spp. CLM is characterised by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm A. braziliense and A. caninum are the most common nematodes causing CLM, although many other species have also been implicated. The major subject of this review article will be discussion of the evolution of therapies and treatment of human necatoriasis and the development of experimental infections with N. americanus. Difference in the clinical efficacy of mebendazole and albendazole will be discussed along with drug resistance of N. americanus.
Topics: Ancylostomiasis; Anemia, Iron-Deficiency; Animals; Antinematodal Agents; Humans; Larva Migrans; Necatoriasis
PubMed: 11060728
DOI: 10.1517/13543784.9.5.1065 -
Current Pharmaceutical Design Jul 1999Necator americanus is a nematode hookworm of the family Ancylostomatidae, subfamily Necatorinae. This nematode parasite, which is distinguished by two chitinous cutting... (Review)
Review
Necator americanus is a nematode hookworm of the family Ancylostomatidae, subfamily Necatorinae. This nematode parasite, which is distinguished by two chitinous cutting plates in the buccal cavity and fused male copulatory spicules, is the causative agent of necatoriasis, a hookworm disease prevalent in the Americas as well as in the tropical regions of Africa, southern Asia, and Polynesia. The adult parasites attached to the villi of the small intestines will suck blood causing abdominal discomfort, diarrhea and cramps, anorexia, wight loss, and in advanced disease, hypochromic microcytic anemia. Hookworm infections in man, especially in children, are one of the leading causes of iron-deficiency anemia resulting directly from intestinal capillary blood loss following the feeding activities of fourth-stage (L4) larva and adult worms. Another clinical manifestation often associated with hookworm infections is cutaneous larva migrans (CLM). It is a well recognized, usually self-limiting condition caused by the infectious larvae of nematodes. CLM is characterized by skin eruption and represents a clinical description rather than a definitive diagnosis. Of the hookworm parasites, the dog and cat worm Ancylostoma braziliense is the most common causing CLM, although many other species have been implicated. The major subject of this review article will be discussion of the evolution of therapies and treatment of human necatoriasis and the development of experimental infections with N. americanus. Difference in the clinical efficacies of mebendazole and albendazole will be discussed along with drug resistance of N. americanus.
Topics: Albendazole; Anemia, Iron-Deficiency; Animals; Drug Resistance; Humans; Mebendazole; Necatoriasis
PubMed: 10438896
DOI: No ID Found -
Clinical Infectious Diseases : An... Jan 2008Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide.... (Review)
Review
Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.
Topics: Ancylostoma; Animals; Antigens, Helminth; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Necator americanus; Necatoriasis; Vaccines; Vaccines, Synthetic
PubMed: 18171264
DOI: 10.1086/524070 -
Scientific American Jun 1995It retards growth and intellectual development in millions of children yet is largely ignored by researchers. New findings suggest excellent possibilities for a vaccine. (Review)
Review
It retards growth and intellectual development in millions of children yet is largely ignored by researchers. New findings suggest excellent possibilities for a vaccine.
Topics: Adolescent; Ancylostoma; Ancylostomiasis; Animals; Child; Female; Humans; Male; Necator americanus; Necatoriasis; Protozoan Vaccines
PubMed: 7761817
DOI: 10.1038/scientificamerican0695-68 -
Arthritis & Rheumatology (Hoboken, N.J.) Mar 2014
Topics: Arthritis, Reactive; Humans; Male; Necatoriasis; Young Adult
PubMed: 24574217
DOI: 10.1002/art.38289 -
The Journal of Infectious Diseases Aug 2004Cytokine and proliferative responses to Necator americanus infection were measured in a treatment-reinfection study of infected subjects from an area of Papua New Guinea...
Cytokine and proliferative responses to Necator americanus infection were measured in a treatment-reinfection study of infected subjects from an area of Papua New Guinea where N. americanus is highly endemic. Before treatment, most subjects produced detectable interleukin (IL)-4 (97%), IL-5 (86%), and interferon (IFN)- gamma (64%) in response to adult N. americanus antigen. Pretreatment IFN- gamma responses were negatively associated with hookworm burden, decreasing by 18 pg/mL for each increase of 1000 eggs/gram (epg) (n=75; P<.01). Mean IFN- gamma responses increased significantly after anthelmintic treatment, from 166 to 322 pg/mL (n=42; P<.01). The intensity of reinfection was significantly negatively correlated with pretreatment IL-5 responses, decreasing by 551 epg for each 100 pg/mL increase in production of IL-5 (n=51; P<.01). These data indicate that there is a mixed cytokine response in necatoriasis, with worm burden-associated suppression of IFN- gamma responses to adult N. americanus antigen. Resistance to reinfection is associated with the parasite-specific IL-5 response.
Topics: Adolescent; Adult; Aged; Animals; Antigens, Helminth; Child; Cytokines; Female; Humans; Interleukin-5; Lymphocyte Activation; Male; Middle Aged; Necator americanus; Necatoriasis; Papua New Guinea; Parasite Egg Count; Recurrence
PubMed: 15243914
DOI: 10.1086/422256 -
Parasite Immunology Jun 1995In this paper we describe the relationship between antibodies to Necator americanus stage-specific antigens and parasite burden in an endemically-infected population in...
In this paper we describe the relationship between antibodies to Necator americanus stage-specific antigens and parasite burden in an endemically-infected population in Papua New Guinea. Using an age-structured analysis, we show that the correlation coefficient between levels of IgG against adult worm excretory-secretory (ES) antigen and parasite burden declined significantly with host age from positive in younger hosts to significantly negative in older hosts. A trend towards similar patterns was present for anti-larval IgG both pretreatment and after reinfection, and for anti-ES IgM and anti-ES IgE pretreatment. These patterns are consistent with a role for these isotypes in a protective immune response, although parasite-induced immunosuppression may provide an alternate explanation. This is another demonstration of possibly protective responses to N. americanus infection.
Topics: Adolescent; Adult; Aging; Animals; Antibodies, Helminth; Antigens, Helminth; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin Isotypes; Male; Middle Aged; Necator americanus; Necatoriasis; Papua New Guinea; Recurrence; Seroepidemiologic Studies
PubMed: 7494644
DOI: 10.1111/j.1365-3024.1995.tb00897.x -
The Lancet. Infectious Diseases May 2018
Topics: Animals; Eye Infections, Parasitic; Female; Humans; Male; Middle Aged; Necator americanus; Necatoriasis
PubMed: 29695368
DOI: 10.1016/S1473-3099(18)30097-5 -
Seminars in Respiratory Infections Jun 1997Ascariasis and hookworm (ancylostomiasis) remain the most common intestinal nematodes in the world with significant economic, social, and medical impact. An... (Review)
Review
Ascariasis and hookworm (ancylostomiasis) remain the most common intestinal nematodes in the world with significant economic, social, and medical impact. An understanding of the transmission and pathogenesis of ascariasis and hookworm are necessary to recognize their clinical manifestations and to manage the pulmonary sequelae of infection. Transmission occurs predominantly in the tropics and rural areas where there is suboptimal sanitation, personal hygiene, and education regarding these parasites. Ascariasis generally occurs through hand-to-mouth ingestion of agricultural products or food contaminated with parasite eggs. Hookworm is transmitted through larval penetration of the skin. Larval pulmonary migration generally is asymptomatic. However, symptomatic pulmonary disease may occur with fever, cough, chest pain, hemoptysis, dyspnea, and wheezing due to (1) Loffler's syndrome, (2) the effects of larval tissue migration, (3) airway reactivity or bronchospasm, (4) infectious bacterial complications from parasitic migration and associated aspiration, and rarely (5) chronic eosinophilic pneumonia, transdiaphragmatic penetration, or symptoms of upper airway obstruction. Clinical evaluation shows pulmonary opacities on chest radiograph, peripheral blood eosinophilia, and larvae in respiratory or gastric secretions. Symptomatic treatment may be necessary with bronchodilators and systemic steroids or antibiotics for bacterial complications. The drug of choice is mebendazole (Vermox) 100 mg twice a day for 3 days. Alternatives include a single dose of pyrantel pamoate (Antiminth) 11 mg/kg (maximum dose, 1 g) or albendazole (Zentel) 400 mg orally once. Invermectin (Mectizan) is available through the World Health Organization, and, in the United States, through the manufacturer on a compassionate-use basis. Ivermectin is as effective as currently available drugs against Ascaris but shows only partial efficacy against hookworms, which infest humans. Preventive measures, improvement of sanitary facilities, education, and school screening may be important in the endemic areas to control these parasitic infections.
Topics: Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Humans; Ivermectin; Lung Diseases, Parasitic; Necator americanus; Necatoriasis
PubMed: 9195678
DOI: No ID Found -
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