Volume 79, Issue 3
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


We previously reported that treatment for schistosomiasis in persons infected with human immunodeficiency virus 1 (HIV-1) attenuated HIV replication as measured by plasma HIV RNA. We investigated systemic inflammation as measured by plasma levels of soluble tumor necrosis factor-α receptor II (sTNF-rII), interleukin-8, (IL-8), and IL-10 during schistosomiasis and HIV co-infection and after schistosomiasis treatment. The cohort was composed of 378 persons who were or were not infected with HIV-1, , or . Schistosomiasis-infected persons were randomized to receive praziquantel (40 mg/kg) at baseline or at the three-month follow-up. sTNF-rII and IL-8 were positively associated with schistosomiasis intensity as measured by circulating anodic antigen (CAA), regardless of HIV status. Interleukin-10 was positively associated with CAA in HIV-negative participants. IL-8 levels were higher in -infected individuals. Treatment for schistosomiasis caused a decrease in levels of sTNF-rII ( < 0.05) and IL-10 ( < 0.001). Our results indicate that schistosomiasis treatment may attenuate HIV replication by decreasing systemic inflammation.


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  1. UNAIDS. UNAIDS: 2007 Epidemic Update. 2007; Available at: http://www.unaids.org/en/KnowledgeCentre/HIVData/EpiUpdate/EpiUpdArchive/2007/. Accessed July 16, 2008.
  2. Chitsulo L, Loverde P, Engels D, 2004. Schistosomiasis. Nat Rev Microbiol 2 : 12–13. [Google Scholar]
  3. Kallestrup P, Zinyama R, Gomo E, Butterworth AE, van Dam GJ, Erikstrup C, Ullum H, 2005. Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs. J Infect Dis 191 : 1311–1320. [Google Scholar]
  4. Brown M, Kizza M, Watera C, Quigley MA, Rowland S, Hughes P, Whitworth JAG, Elliott AM, 2004. Helminth infection is not associated with faster progression of HIV disease in coinfected adults in Uganda. J Infect Dis 190 : 1869–1879. [Google Scholar]
  5. Brown M, Mawa PA, Joseph S, Bukusuba J, Watera C, Whitworth JA, Dunne DW, Elliott AM, 2005. Treatment of Schistosoma mansoni infection increases helminth-specific type 2 cytokine responses and HIV-1 loads in coinfected Ugandan adults. J Infect Dis 191 : 1648–1657. [Google Scholar]
  6. Lawn SD, Karanja DM, Mwinzia P, Andove J, Colley DG, Folks TM, Secor WE, 2000. The effect of treatment of schistosomiasis on blood plasma HIV-1 RNA concentration in coinfected individuals. AIDS 14 : 2437–2443. [Google Scholar]
  7. Kallestrup P, Zinyama R, Gomo E, Butterworth AE, Mudenge B, van Dam GJ, Gerstoft J, Erikstrup C, Ullum H, 2005. Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load. J Infect Dis 192 : 1956–1961. [Google Scholar]
  8. Lähdevirta J, Maury CP, Teppo AM, Repo H, 1988. Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. Am J Med 85 : 289–291. [Google Scholar]
  9. Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, Hirano T, Kishimoto T, Martinez-Maza O, 1990. Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 144 : 480–484. [Google Scholar]
  10. Stylianou E, Aukrust P, Kvale D, Müller F, Frøland SS, 1999. IL-10 in HIV infection: increasing serum IL-10 levels with disease progression–down-regulatory effect of potent anti-retroviral therapy. Clin Exp Immunol 116 : 115–120. [Google Scholar]
  11. Kalinkovich A, Weisman Z, Leng Q, Borkow G, Stein M, Greenberg Z, Zlotnikov S, Eitan S, Bentwich Z, 1999. Increased CCR5 expression with decreased beta chemokine secretion in Ethiopians: relevance to AIDS in Africa. J Hum Virol 2 : 283–289. [Google Scholar]
  12. Kalinkovich A, Borkow G, Weisman Z, Tsimanis A, Stein M, Bentwich Z, 2001. Increased CCR5 and CXCR4 expression in Ethiopians living in Israel: environmental and constitutive factors. Clin Immunol 100 : 107–117. [Google Scholar]
  13. Griffin GE, Leung K, Folks TM, Kunkel S, Nabel GJ, 1991. Induction of NF-kappa B during monocyte differentiation is associated with activation of HIV-gene expression. Res Virol 142 : 233–238. [Google Scholar]
  14. Herbein G, Gordon S, 1997. 55- and 75-kilodalton tumor necrosis factor receptors mediate distinct actions in regard to human immunodeficiency virus type 1 replication in primary human macrophages. J Virol 71 : 4150–4156. [Google Scholar]
  15. Lane BR, Lore K, Bock PJ, Andersson J, Coffey MJ, Strieter RM, Markovitz DM, 2001. Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy. J Virol 75 : 8195–8202. [Google Scholar]
  16. Poli G, Kinter A, Justement JS, Kehrl JH, Bressler P, Stanley S, Fauci AS, 1990. Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression. Proc Natl Acad Sci USA 87 : 782–785. [Google Scholar]
  17. Weissman D, Poli G, Fauci AS, 1994. Interleukin 10 blocks HIV replication in macrophages by inhibiting the autocrine loop of tumor necrosis factor alpha and interleukin 6 induction of virus. AIDS Res Hum Retroviruses 10 : 1199–1206. [Google Scholar]
  18. Tesselaar K, Arens R, van Schijndel GM, Baars PA, van der Valk MA, Borst J, van Oers MH, van Lier RA, 2003. Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 4 : 49–54. [Google Scholar]
  19. Bentwich Z, Weisman Z, Moroz C, Bar-Yehuda S, Kalinkovich A, 1996. Immune dysregulation in Ethiopian immigrants in Israel: relevance to helminth infections? Clin Exp Immunol 103 : 239–243. [Google Scholar]
  20. Kalinkovich A, Weisman Z, Greenberg Z, Nahmias J, Eitan S, Stein M, Bentwich Z, 1998. Decreased CD4 and increased CD8 counts with T cell activation is associated with chronic helminth infection. Clin Exp Immunol 114 : 414–421. [Google Scholar]
  21. Montenegro SM, Miranda P, Mahanty S, Abath FG, Teixeira KM, Coutinho EM, Brinkman J, Gonçalves I, Domingues LA, Domingues AL, Sher A, Wynn TA, 1999. Cytokine production in acute versus chronic human Schistosomiasis mansoni: the cross-regulatory role of interferon-gamma and interleukin-10 in the responses of peripheral blood mononuclear cells and splenocytes to parasite antigens. J Infect Dis 179 : 1502–1514. [Google Scholar]
  22. Hoffmann KF, Wynn TA, Dunne DW, 2002. Cytokine-mediated host responses during schistosome infections; walking the fine line between immunological control and immunopathology. Adv Parasitol 52 : 265–307. [Google Scholar]
  23. Maizels RM, Yazdanbakhsh M, 2003. Immune regulation by helminth parasites: cellular and molecular mechanisms. Nat Rev Immunol 3 : 733–744. [Google Scholar]
  24. Pearce EJ, MacDonald AS, 2002. The immunobiology of schistosomiasis. Nat Rev Immunol 2 : 499–511. [Google Scholar]
  25. McElroy MD, Elrefaei M, Jones N, Ssali F, Mugyenyi P, Barugahare B, Cao H, 2005. Coinfection with Schistosoma mansoni is associated with decreased HIV-specific cytolysis and increased IL-10 production. J Immunol 174 : 5119–5123. [Google Scholar]
  26. Mwinzi PN, Karanja DM, Colley DG, Orago AS, Secor WE, 2001. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J Infect Dis 184 : 488–496. [Google Scholar]
  27. Aderka D, 1996. The potential biological and clinical significance of the soluble tumor necrosis factor receptors. Cytokine Growth Factor Rev 7 : 231–240. [Google Scholar]
  28. van Deuren M, 1994. Kinetics of tumour necrosis factor-alpha, soluble tumour necrosis factor receptors, interleukin 1-beta and its receptor antagonist during serious infections. Eur J Clin Microbiol Infect Dis 13 (Suppl 1): S12–S16. [Google Scholar]
  29. Mott KE, Baltes R, Bambagha J, Baldassini B, 1982. Field studies of a reusable polyamide filter for detection of Schistosoma haematobium eggs by urine filtration. Tropenmed Parasitol 33 : 227–228. [Google Scholar]
  30. Knight WB, Hiatt RA, Cline BL, Ritchie LS, 1976. A modification of the formol-ether concentration technique for increased sensitivity in detecting Schistosoma mansoni eggs. Am J Trop Med Hyg 25 : 818–823. [Google Scholar]
  31. Leutscher PD, Pedersen M, Raharisolo C, Jensen JS, Hoffmann S, Lisse I, Ostrowski SR, Reimert CM, Mauclere P, Ullum H, 2005. Increased prevalence of leukocytes and elevated cytokine levels in semen from Schistosoma haematobium-infected individuals. J Infect Dis 191 : 1639–1647. [Google Scholar]
  32. Polman K, Diakhate MM, Engels D, Nahimana S, Van Dam GJ, Falcão Ferreira ST, Deelder AM, Gryseels B, 2000. Specificity of circulating antigen detection for Schistosomiasis mansoni in Senegal and Burundi. Trop Med Int Health 5 : 534–537. [Google Scholar]
  33. Kallestrup P, Zinyama R, Gomo E, Butterworth AE, van Dam GJ, Gerstoft J, Erikstrup C, Ullum H, 2006. Schistosomiasis and HIV in rural Zimbabwe: efficacy of treatment of schistosomiasis in individuals with HIV coinfection. Clin Infect Dis 42 : 1781–1789. [Google Scholar]
  34. Erikstrup C, Kallestrup P, Zinyama-Gutsire RB, Gomo E, Butterworth AE, Pedersen BK, Ostrowski SR, Gerstoft J, Ullum H, 2007. Reduced mortality and CD4 cell loss among carriers of the interleukin-10-1082G allele in a Zimbabwean cohort of HIV-1-infected adults. AIDS 21 : 2283–2291. [Google Scholar]
  35. Aukrust P, Müller F, Lien E, Nordoy I, Liabakk NB, Kvale D, Espevik T, Froland SS, 1999. Tumor necrosis factor (TNF) system levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy: persistent TNF activation is associated with virologic and immunologic treatment failure. J Infect Dis 179 : 74–82. [Google Scholar]
  36. Ostrowski SR, Katzenstein TL, Piironen T, Gerstoft J, Pedersen BK, Ullum H, 2004. Soluble urokinase receptor levels in plasma during 5 years of highly active antiretroviral therapy in HIV-1-infected patients. J Acquir Immune Defic Syndr 35 : 337–342. [Google Scholar]
  37. King CL, Malhotra I, Mungai P, Wamachi A, Kioko J, Muchiri E, Ouma JH, 2001. Schistosoma haematobium-induced urinary tract morbidity correlates with increased tumor necrosis factor-alpha and diminished interleukin-10 production. J Infect Dis 184 : 1176–1182. [Google Scholar]
  38. Wynn TA, Morawetz R, Scharton-Kersten T, Hieny S, Morse HC, Kühn R, Müller W, Cheever AW, Sher A, 1997. Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1-and T helper cell 2-type cytokine responses in vivo. J Immunol 159 : 5014–5023. [Google Scholar]
  39. Hoffmann KF, Cheever AW, Wynn TA, 2000. IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol 164 : 6406–6416. [Google Scholar]
  40. Ostrowski SR, Katzenstein TL, Pedersen M, Høyer-Hansen G, Gerstoft J, Pedersen BK, Ullum H, 2006. Plasma levels of intact and cleaved urokinase receptor decrease in HIV-1-infected patients initiating highly active antiretroviral therapy. Scand J Immunol 63 : 478–486. [Google Scholar]
  41. Brown M, Mawa PA, Kaleebu P, Elliott AM, 2006. Helminths and HIV infection: epidemiological observations on immunological hypotheses. Parasite Immunol 28 : 613–623. [Google Scholar]
  42. Maizels RM, 2005. Infections and allergy: helminths, hygiene and host immune regulation. Curr Opin Immunol 17 : 656–661. [Google Scholar]
  43. Ostrowski SR, Gerstoft J, Pedersen BK, Ullum H, 2003. Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients. AIDS 17 : 521–530. [Google Scholar]
  44. Agnew A, Fulford AJ, De Jonge N, Krijger FW, Rodriguez-Chacon M, Gutsmann V, Deelder AM, 1995. The relationship between worm burden and levels of a circulating antigen (CAA) of five species of Schistosoma in mice. Parasitology 111 : 67–76. [Google Scholar]

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  • Received : 14 Jan 2008
  • Accepted : 05 Jun 2008

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