1921
Volume 75, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Epidemiological studies suggest that a hookworm infection producing 50 eggs/gram of feces may protect against asthma. We conducted a dose-ranging study to identify the dose of hookworm larvae necessary to achieve 50 eggs/gram of feces for therapeutic trials of asthma. Ten healthy subjects without asthma or airway hyperresponsiveness to inhaled methacholine received 10, 25, 50, or 100 larvae administered double blind to an area of skin on the arm. Subjects were seen weekly for 12 weeks and were then treated with mebendazole. Skin itching at the entry site and gastrointestinal symptoms were common at higher doses. Lung function did not change. Levels of blood eosinophils and IgE increased transiently, and levels of IgG increased progressively. All doses resulted in at least 50 eggs/gram of feces in the eight subjects who completed the study. Infection with 10 larvae is well tolerated, elicits a modest host eosinophil response, and is potentially suitable for use in preliminary clinical therapeutic trials.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.2006.75.914
2006-11-01
2017-09-26
Loading full text...

Full text loading...

/deliver/fulltext/14761645/75/5/0750914.html?itemId=/content/journals/10.4269/ajtmh.2006.75.914&mimeType=html&fmt=ahah

References

  1. de Silva NR, Brooker S, Hotez PJ, Montresor A, Engels D, Savioli L, 2003. Soil-transmitted helminth infections: updating the global picture. Trends Parasitol 19 : 547–551.
  2. Hotez PJ, Pritchard DI, 1995. Hookworm infection. Sci Am 272 : 68–74.
  3. Editorial, 1976. IgE, parasites, and allergy. Lancet 1 : 894–895.
  4. Masters S, Barrett-Connor E, 1985. Parasites and asthma: predictive or protective? Epidemiol Rev 7 : 49–58.
  5. Yazdanbakhsh M, Matricardi PM, 2004. Parasites and the hygiene hypothesis: regulating the immune system? Clin Rev Allergy Immunol 26 : 15–24.
  6. Pritchard DI, Quinnell RJ, Walsh EA, 1995. Immunity in humans to Necator americanus: IgE, parasite weight and fecundity. Parasite Immunol 17 : 71–75.
  7. Moqbel R, Pritchard D, 1997. Allergy and helminthic parasites: are atopics protected against infection? Kay AB, ed. Allergy and Allergic Diseases. Boston: Blackwell Science, 1163–1176.
  8. Quinnell RJ, Pritchard DI, Raiko A, Brown AP, Shaw MA, 2004. Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection. J Infect Dis 190 : 430–438.
  9. Yazdanbakhsh M, Kremsner PG, van RR, 2002. Allergy, parasites, and the hygiene hypothesis. Science 296 : 490–494.
  10. Loukas A, Prociv P, 2001. Immune responses in hookworm infections. Clin Microbiol Rev 14 : 689–703.
  11. Wilson MS, Maizels RM, 2004. Regulation of allergy and autoimmunity in helminth infection. Clin Rev Allergy Immunol 26 : 35–50.
  12. van den Biggelaar AH, van RR, Rodrigues LC, Lell B, Deelder AM, Kremsner PG, Yazdanbakhsh M, 2000. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356 : 1723–1727.
  13. Nyan OA, Walraven GE, Banya WA, Milligan P, van der SM, Ceesay SM, del Prete G, McAdam KP, 2001. Atopy, intestinal helminth infection and total serum IgE in rural and urban adult Gambian communities. Clin Exp Allergy 31 : 1672–1678.
  14. Scrivener S, Yemaneberhan H, Zebenigus M, Tilahun D, Girma S, Ali S, McElroy P, Custovic A, Woodcock A, Pritchard D, Venn A, Britton J, 2001. Independent effects of intestinal parasite infection and domestic allergen exposure on risk of wheeze in Ethiopia: a nested case-control study. Lancet 358 : 1493–1499.
  15. Dagoye D, Bekele Z, Woldemichael K, Nida H, Yimam M, Hall A, Venn AJ, Britton JR, Hubbard R, Lewis SA, 2003. Wheezing, allergy, and parasite infection in children in urban and rural Ethiopia. Am J Respir Crit Care Med 167 : 1369–1373.
  16. Cooper PJ, Chico ME, Rodrigues LC, Strachan DP, Anderson HR, Rodriguez EA, Gaus DP, Griffin GE, 2004. Risk factors for atopy among school children in a rural area of Latin America. Clin Exp Allergy 34 : 845–852.
  17. Cooper PJ, Chico ME, Bland M, Griffin GE, Nutman TB, 2003. Allergic symptoms, atopy, and geohelminth infections in a rural area of Ecuador. Am J Respir Crit Care Med 168 : 313–317.
  18. Cooper PJ, Chico ME, Rodrigues LC, Ordonez M, Strachan D, Griffin GE, Nutman TB, 2003. Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics. J Allergy Clin Immunol 111 : 995–1000.
  19. van den Biggelaar AH, Lopuhaa C, van Ree R, van der Zee JS, Jans J, Hoek A, Migombet B, Borrmann S, Luckner D, Kremsner PG, Yazdanbakhsh M, 2001. The prevalence of parasite infestation and house dust mite sensitization in Gabonese schoolchildren. Int Arch Allergy Immunol 126 : 231– 238.
  20. Bashir ME, Andersen P, Fuss IJ, Shi HN, Nagler-Anderson C, 2002. An enteric helminth infection protects against an allergic response to dietary antigen. J Immunol 169 : 3284–3292.
  21. Wang CC, Nolan TJ, Schad GA, Abraham D, 2001. Infection of mice with the helminth Strongyloides stercoralis suppresses pulmonary allergic responses to ovalbumin. Clin Exp Allergy 31 : 495–503.
  22. Silveira MR, Nunes KP, Cara DC, Souza DG, Correa A Jr, Teixeira MM, Negrao-Correa D, 2002. Infection with Strongyloides venezuelensis induces transient airway eosinophilic inflammation, an increase in immunoglobulin E, and hyperresponsiveness in rats. Infect Immun 70 : 6263–6272.
  23. Negrao-Correa D, Silveira MR, Borges CM, Souza DG, Teixeira MM, 2003. Changes in pulmonary function and parasite burden in rats infected with Strongyloides venezuelensis concomitant with induction of allergic airway inflammation. Infect Immun 71 : 2607–2614.
  24. Yan K, Salome C, Woolcock AJ, 1983. Rapid method for measurement of bronchial responsiveness. Thorax 38 : 760–765.
  25. Kumar S, Pritchard DI, 1992. The partial characterization of proteases present in the excretory/secretory products and ex-sheathing fluid of the infective (L3) larva of Necator americanus. Int J Parasitol 22 : 563–572.
  26. Pritchard DI, Walsh EA, 1995. The specificity of the human IgE response to Necator americanus. Parasite Immunol 17 : 605– 607.
  27. Pritchard DI, Quinnell RJ, Slater AF, McKean PG, Dale DD, Raiko A, Keymer AE, 1990. Epidemiology and immunology of Necator americanus infection in a community in Papua New Guinea: humoral responses to excretory-secretory and cuticular collagen antigens. Parasitology 100 : 317–326.
  28. Carr A, Pritchard DI, 1987. Antigen expression during development of the human hookworm, Necator americanus (Nematoda). Parasite Immunol 9 : 219–234.
  29. Schad GA, 1990. Hypobiosis and related phenomena in hookworm infection. Schad GA, Warren KS, eds. Hookworm Disease: Current Status and New Directions. London: Taylor and Francis, 71–88.
  30. Turton JA, 1976. IgE, parasites, and allergy. Lancet 2 : 686.
  31. Ogilvie BM, Bartlett A, Godfrey RC, Turton JA, Worms MJ, Yeates RA, 1978. Antibody responses in self-infections with Necator americanus. Trans R Soc Trop Med Hyg 72 : 66–71.
  32. Cline BL, Little MD, Bartholomew RK, Halsey NA, 1984. Larvicidal activity of albendazole against Necator americanus in human volunteers. Am J Trop Med Hyg 33 : 387–394.
  33. Maxwell C, Hussain R, Nutman TB, Poindexter RW, Little MD, Schad GA, Ottesen EA, 1987. The clinical and immunologic responses of normal human volunteers to low dose hookworm (Necator americanus) infection. Am J Trop Med Hyg 37 : 126– 134.
  34. Beaver PC, 1988. Light, long-lasting Necator infection in a volunteer. Am J Trop Med Hyg 39 : 369–372.
  35. Palmer ED, 1955. Course of egg output over a 15 year period in a case of experimentally induced necatoriasis americanus, in the absence of hyperinfection. Am J Trop Med Hyg 4 : 756–757.
  36. Summers RW, Elliott DE, Urban JF Jr, Thompson RA, Weinstock JV, 2005. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128 : 825–832.
  37. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV, 2005. Trichuris suis therapy in Crohn’s disease. Gut 54 : 87–90.
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2006.75.914
Loading
/content/journals/10.4269/ajtmh.2006.75.914
Loading

Data & Media loading...

  • Received : 15 Aug 2005
  • Accepted : 23 Jun 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error