View More View Less
  • 1 Department of International and Environmental Parasitology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
  • | 2 Institute of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 27, 12203, Berlin, Germany
  • | 3 Foundation for Tropical Medicine in Amazonia (FMT-AM), Av. Pedro Teixeira 25, Manaus, 69040000, Amazonas, Brazil
  • | 4 Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, Spandauer Damm 130, 14050, Berlin, Germany
Restricted access

Abstract

Hookworm-related cutaneous larva migrans (Hr-CLM) is caused by animal hookworm larvae migrating in the human epidermis where they elicit an inflammatory response. This study describes the immunological profile in Hr-CLM patients.

In 77 Hr-CLM patients from Manaus, Brazil, peripheral eosinophils were counted, and serum concentrations of total immunoglobulin E (IgE) and selected cytokines were determined by ELISA before and after treatment with ivermectin. Controls included patients’ household members (endemic controls), non-endemic Brazilian and Japanese individuals.

Eosinophil counts and total IgE in Hr-CLM patients were higher than in controls and correlated with disease severity. Concentrations of interleukin (IL)-4, IL-5, IL-6, and IL-10 were higher in Hr-CLM patients than in endemic controls (p < 0.001) while no differences were detected for interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-1β, IL-2, or transforming growth factor (TGF)-β. Following ivermectin treatment, numbers of eosinophils and concentrations of IL-4, IL-5, and IL-10 decreased whereas IgE, IFN-γ, and TGF-β concentrations increased. The IL-5/IFN-γ ratio declined from 5.9 (interquartile range [IQR] 0.8–31.6) before to 0.1 (IQR 0.05–0.2; p = 0.001) after treatment.

Thus, although an impact of other infections on the immune parameters determined cannot be excluded, Hr-CLM in endemic areas is associated with eosinophilia and elevated cytokine levels, particularly of IL-5 and IL-10, which decrease following ivermectin treatment.

  • 1. P Hochedez E Caumes 2007 Hookworm-related cutaneous larva migrans J Travel Med 14 326 333.

  • 2. H Feldmeier A Schuster 2012 Mini review: Hookworm-related cutaneous larva migrans Eur J Clin Microbiol Infect Dis 31 915 918.

  • 3. A Jackson J Heukelbach CM Calheiros L Vde Soares G Harms 2006 A study in a community in Brazil in which cutaneous larva migrans is endemic Clin Infect Dis 43 e13 e18.

    • Search Google Scholar
    • Export Citation
  • 4. J Heukelbach H Feldmeier 2008 Epidemiological and clinical characteristics of hookworm-related cutaneous larva migrans Lancet Infect Dis 8 302 309.

    • Search Google Scholar
    • Export Citation
  • 5. S Kannathasan A Murugananthan N Rajeshkannan NR de Silva 2012 Cutaneous larva migrans among devotees of the Nallur temple in Jaffna, Sri Lanka PLoS One 7 e30516.

    • Search Google Scholar
    • Export Citation
  • 6. A Schuster H Lesshafft S Talhari S Guedes de Oliveira R Ignatius 2011 Life quality impairment caused by hookworm-related cutaneous larva migrans in resource-poor communities in Manaus, Brazil PLoS Negl Trop Dis 5 e1355.

    • Search Google Scholar
    • Export Citation
  • 7. H Lesshafft A Schuster F Reichert S Talhari R Ignatius 2012 Knowledge, attitudes, perceptions, and practices regarding cutaneous larva migrans in deprived communities in Manaus, Brazil J Infect Dev Ctries 6 422 429.

    • Search Google Scholar
    • Export Citation
  • 8. RM Anthony LI Rutitzky JF Urban Jr. MJ Stadecker WC Gause 2007 Protective immune mechanisms in helminth infection Nat Rev Immunol 7 975 987.

    • Search Google Scholar
    • Export Citation
  • 9. JE Allen RM Maizels 2011 Diversity and dialogue in immunity to helminths Nat Rev Immunol 11 375 388.

  • 10. J Scheller A Chalaris D Schmidt-Arras S Rose-John 2011 The pro- and anti-inflammatory properties of the cytokine interleukin-6 Biochim Biophys Acta 1813 878 888.

    • Search Google Scholar
    • Export Citation
  • 11. MK Fallahzadeh J Roozbeh B Geramizadeh MR Namazi 2011 Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications Nephrol Dial Transplant 26 3338 3344.

    • Search Google Scholar
    • Export Citation
  • 12. R Sharma SS Sung F Gaskin SM Fu ST Ju 2012 A novel function of IL-2: chemokine/chemoattractant/retention receptor genes induction in Th subsets for skin and lung inflammation J Autoimmun 38 322 331.

    • Search Google Scholar
    • Export Citation
  • 13. KJ Erb 2007 Helminths, allergic disorders and IgE-mediated immune responses: where do we stand? Eur J Immunol 37 1170 1173.

  • 14. AD Klion TB Nutman 2004 The role of eosinophils in host defense against helminth parasites J Allergy Clin Immunol 113 30 37.

  • 15. T Jelinek H Maiwald HD Nothdurft T Loscher 1994 Cutaneous larva migrans in travelers: synopsis of histories, symptoms, and treatment of 98 patients Clin Infect Dis 19 1062 1066.

    • Search Google Scholar
    • Export Citation
  • 16. ET Cadman RA Lawrence 2010 Granulocytes: effector cells or immunomodulators in the immune response to helminth infection? Parasite Immunol 32 1 19.

    • Search Google Scholar
    • Export Citation
  • 17. CA Behm KS Ovington 2000 The role of eosinophils in parasitic helminth infections: insights from genetically modified mice Parasitol Today 16 202 209.

    • Search Google Scholar
    • Export Citation
  • 18. DJ McLaren JR McKean I Olsson P Venges AB Kay 1981 Morphological studies on the killing of schistosomula of Schistosoma mansoni by human eosinophil and neutrophil cationic proteins in vitro Parasite Immunol 3 359 373.

    • Search Google Scholar
    • Export Citation
  • 19. KJ Hamann RL Barker DA Loegering GJ Gleich 1987 Comparative toxicity of purified human eosinophil granule proteins for newborn larvae of Trichinella spiralis J Parasitol 73 523 529.

    • Search Google Scholar
    • Export Citation
  • 20. KJ Hamann GJ Gleich JL Checkel DA Loegering JW McCall 1990 In vitro killing of microfilariae of Brugia pahangi and Brugia malayi by eosinophil granule proteins J Immunol 144 3166 3173.

    • Search Google Scholar
    • Export Citation
  • 21. LA Dent CM Daly G Mayrhofer T Zimmerman A Hallett 1999 Interleukin-5 transgenic mice show enhanced resistance to primary infections with Nippostrongylus brasiliensis but not primary infections with Toxocara canis Infect Immun 67 989 993.

    • Search Google Scholar
    • Export Citation
  • 22. CM Daly G Mayrhofer LA Dent 1999 Trapping and immobilization of Nippostrongylus brasiliensis larvae at the site of inoculation in primary infections of interleukin-5 transgenic mice Infect Immun 67 5315 5323.

    • Search Google Scholar
    • Export Citation
  • 23. RL Coffman BW Seymour S Hudak J Jackson D Rennick 1989 Antibody to interleukin-5 inhibits helminth-induced eosinophilia in mice Science 245 308 310.

    • Search Google Scholar
    • Export Citation
  • 24. ML Knott KI Matthaei PR Giacomin H Wang PS Foster 2007 Impaired resistance in early secondary Nippostrongylus brasiliensis infections in mice with defective eosinophilopoeisis Int J Parasitol 37 1367 1378.

    • Search Google Scholar
    • Export Citation
  • 25. BA Vallance KI Matthaei S Sanovic IG Young SM Collins 2000 Interleukin-5 deficient mice exhibit impaired host defence against challenge Trichinella spiralis infections Parasite Immunol 22 487 492.

    • Search Google Scholar
    • Export Citation
  • 26. UM Padigel JJ Lee TJ Nolan GA Schad D Abraham 2006 Eosinophils can function as antigen-presenting cells to induce primary and secondary immune responses to Strongyloides stercoralis Infect Immun 74 3232 3238.

    • Search Google Scholar
    • Export Citation
  • 27. UM Padigel JA Hess JJ Lee JB Lok TJ Nolan 2007 Eosinophils act as antigen-presenting cells to induce immunity to Strongyloides stercoralis in mice J Infect Dis 196 1844 1851.

    • Search Google Scholar
    • Export Citation
  • 28. EA Sabin MA Kopf EJ Pearce 1996 Schistosoma mansoni egg-induced early IL-4 production is dependent upon IL-5 and eosinophils J Exp Med 184 1871 1878.

    • Search Google Scholar
    • Export Citation
  • 29. RM Reiman RW Thompson CG Feng D Hari R Knight 2006 Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity Infect Immun 74 1471 1479.

    • Search Google Scholar
    • Export Citation
  • 30. LY Liu ME Bates NN Jarjour WW Busse PJ Bertics 2007 Generation of Th1 and Th2 chemokines by human eosinophils: evidence for a critical role of TNF-alpha J Immunol 179 4840 4848.

    • Search Google Scholar
    • Export Citation
  • 31. CA Figueiredo ML Barreto LC Rodrigues PJ Cooper NB Silva 2010 Chronic intestinal helminth infections are associated with immune hyporesponsiveness and induction of a regulatory network Infect Immun 78 3160 3167.

    • Search Google Scholar
    • Export Citation
  • 32. S Gaze HJ McSorley J Daveson D Jones JM Bethony 2012 Characterising the mucosal and systemic immune responses to experimental human hookworm infection PLoS Pathog 8 e1002520.

    • Search Google Scholar
    • Export Citation
  • 33. P Kourilova KG Hogg L Kolarova AP Mountford 2004 Cercarial dermatitis caused by bird schistosomes comprises both immediate and late phase cutaneous hypersensitivity reactions J Immunol 172 3766 3774.

    • Search Google Scholar
    • Export Citation
  • 34. FD Finkelman T Shea-Donohue SC Morris L Gildea R e Strait 2004 Interleukin-4- and interleukin-13-mediated host protection against intestinal nematode parasites Immunol Rev 201 139 155.

    • Search Google Scholar
    • Export Citation
  • 35. JF Urban Jr. IM Katona WE Paul FD Finkelman 1991 Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice Proc Natl Acad Sci U S A 88 5513 5517.

    • Search Google Scholar
    • Export Citation
  • 36. PC Cook SA Aynsley JD Turner GR Jenkins N Van Rooijen 2011 Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells PLoS Pathog 7 e1001323.

    • Search Google Scholar
    • Export Citation
  • 37. D Nagy O Bede J Danka Z Szenasi S Sipka 2012 Analysis of serum cytokine levels in children with chronic cough associated with Toxocara canis infection Parasite Immunol 34 581 588.

    • Search Google Scholar
    • Export Citation
  • 38. NW Brattig P Racz A Hoerauf DW Buttner 2011 Strong expression of TGF-beta in human host tissues around subcutaneous Dirofilaria repens Parasitol Res 108 1347 1354.

    • Search Google Scholar
    • Export Citation
  • 39. JP Hewitson JR Grainger RM Maizels 2009 Helminth immunoregulation: the role of parasite secreted proteins in modulating host immunity Mol Biochem Parasitol 167 1 11.

    • Search Google Scholar
    • Export Citation
  • 40. E Danilowicz-Luebert NL O'Regan S Steinfelder S Hartmann 2011 Modulation of specific and allergy-related immune responses by helminths J Biomed Biotechnol 2011 821578.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 55 55 5
Full Text Views 11 8 0
PDF Downloads 3 3 0