ABSTRACT
Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies.
Subject(s)
Larva/physiology , Models, Biological , Necator americanus/cytology , Necator americanus/physiology , Necatoriasis/physiopathology , Animals , Bayes Theorem , Blood Cell Count , Eosinophils , Feces/parasitology , Female , Follow-Up Studies , Healthy Volunteers , Humans , Kinetics , Male , Necatoriasis/parasitology , Young AdultABSTRACT
In the present study, we demonstrate that Jurkat T cells undergo apoptosis when cocultured with the human hook-worm Necator americanus. Pro-apoptotic activity was dose-dependent and readily detectable in hookworm secretions. This pro-apoptotic effect appears to be specific to cells of T lineage since the monocytic cell line, THP-1, the erythroleukaemic cell line, K562, and the basophil cell line, KU812, were unaffected. The induction of apoptosis in Jurkat T cells by the hookworm secretions did not involve cell activation or the Fas/Fas ligand interaction. In addition, the pro-apoptotic effect of the hookworm, or its secretions, was observed with activated human T cells but not with resting peripheral blood lymphocytes. These findings support the hypothesis that the hookworms' ability to recurrently infect humans is due to the parasite creating a site of 'immune privilege' around itself. This strategy promptly induces any reactive host leucocytes infiltrating the site of parasite colonization to undergo apoptosis, which reduces inflammation and renders the infection relatively asymptomatic.
Subject(s)
Antigens, Helminth/immunology , Apoptosis , Necator americanus/immunology , T-Lymphocytes/immunology , Animals , Cell Lineage , Cells, Cultured , Coculture Techniques , Erythrocytes/immunology , Fas Ligand Protein , Humans , Jurkat Cells , Membrane Glycoproteins/metabolism , Monocytes/immunology , Necator americanus/cytology , T-Lymphocytes/cytology , fas Receptor/metabolismABSTRACT
Intestinal parasites cause significant morbidity and mortality. Diseases caused by Enterobius vermicularis, Giardia lamblia, Ancylostoma duodenale, Necator americanus, and Entamoeba histolytica occur in the United States. E. vermicularis, or pinworm, causes irritation and sleep disturbances. Diagnosis can be made using the "cellophane tape test." Treatment includes mebendazole and household sanitation. Giardia causes nausea, vomiting, malabsorption, diarrhea, and weight loss. Stool ova and parasite studies are diagnostic. Treatment includes metronidazole. Sewage treatment, proper handwashing, and consumption of bottled water can be preventive. A. duodenale and N. americanus are hookworms that cause blood loss, anemia, pica, and wasting. Finding eggs in the feces is diagnostic. Treatments include albendazole, mebendazole, pyrantel pamoate, iron supplementation, and blood transfusion. Preventive measures include wearing shoes and treating sewage. E. histolytica can cause intestinal ulcerations, bloody diarrhea, weight loss, fever, gastrointestinal obstruction, and peritonitis. Amebas can cause abscesses in the liver that may rupture into the pleural space, peritoneum, or pericardium. Stool and serologic assays, biopsy, barium studies, and liver imaging have diagnostic merit. Therapy includes luminal and tissue amebicides to attack both life-cycle stages. Metronidazole, chloroquine, and aspiration are treatments for liver abscess. Careful sanitation and use of peeled foods and bottled water are preventive.