Volume 74, Issue 5
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Rates of tuberculosis (TB) in Africa are highest among people infected with HIV. Searching for additional risk factors in a cohort of HIV-infected Ugandan adults, we previously found that a type 2 cytokine bias and eosinophilia were associated with progression to active TB. A possible role for helminth infection was assessed in this study. We analyzed TB incidence in 462 members of this cohort who were screened for filarial infections, gastrointestinal nematodes, and schistosomiasis. Progression to TB was not associated with gastrointestinal nematodes (rate ratio [RR], 1.18; confidence intervals [CIs], 0.66–2.10) or (RR, 0.42; CI, 0.13–1.34). A weak association between infection and TB was found (RR, 1.42; CI, 0.86–2.34); after adjusting for potential explanatory variables and using more stringent diagnostic criteria, the association was strengthened (RR, 2.31; 1.00–5.33). This analysis suggests an effect of infection on progression to active TB among HIV-1–infected Ugandans.


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  1. Corbett EL, Steketee RW, ter Kuile FO, Latif AS, Kamali A, Hayes RJ, 2002. HIV-1/AIDS and the control of other infectious diseases in Africa. Lancet 359 : 2177–2187.
  2. Lucas SB, Hounnou A, Peacock C, Beaumel A, Djomand G, N’Gbichi JM, Yeboue K, Honde M, Diomande M, Giordano C, 1993. The mortality and pathology of HIV infection in a west African city. AIDS 7 : 1569–1579.
  3. Whalen C, Horsburgh CR, Hom D, Lahart C, Simberkoff M, Ellner J, 1995. Accelerated course of human immunodeficiency virus infection after tuberculosis. Am J Respir Crit Care Med 151 : 129–135.
  4. Lawn SD, Shattock RJ, Acheampong JW, Lal RB, Folks TM, Griffin GE, Butera ST, 1999. Sustained plasma TNF-α and HIV-1 load despite resolution of other immune activation parameters during treatment of tuberculosis in Africans. AIDS 13 : 2231–2237.
  5. World Health Organisation Global Tuberculosis Programme and UNAIDS, 1998. Policy Statement on Preventive Therapy Against Tuberculosis in People Living With HIV. Geneva, World Health Organization.
  6. Lugada ES, Watera C, Nakiyingi J, Elliott A, Brink A, Nanyunja M, French N, Antivelink L, Gilks C, Whitworth J, 2002. Operational assessment of isoniazid prophylaxis in a community AIDS service organisation in Uganda. Int J Tuberc Lung Dis 6 : 326–331.
  7. Creese A, Floyd K, Alban A, Guinness L, 2002. Cost-effectiveness of HIV/AIDS interventions in Africa: a systematic review of the evidence. Lancet 359 : 1635–1643.
  8. Elliott AM, Kyosiimire J, Quigley MA, Nakiyingi J, Watera C, Brown M, Joseph S, French N, Gilks CF, Whitworth JAG, 2003. Eosinophilia and progression to active tuberculosis in HIV-1-infected Ugandans. Trans R Soc Trop Med Hyg 97 : 477–480.
  9. Brown M, Kizza M, Watera C, Quigley MA, Rowland S, Hughes P, Whitworth JAG, Elliott AM, 2004. Helminth infection is not associated with more advanced HIV disease in co-infected adults in Uganda. J Infect Dis 190 : 1869–1879.
  10. Brown M, Mawa P, Joseph S, Bukusuba J, Watera C, Whitworth JAG, Dunne DW, Elliott AM, 2005. Treatment of Schistosoma mansoni increases helminth-specific type 2 cytokines and HIV-1 RNA concentrations in co-infected Ugandan adults. J Infect Dis 191 : 1648–1657.
  11. French N, Nakiyingi J, Carpenter LM, Lugada E, Watera C, Moi K, Moore M, Antvelink D, Mulder D, Janoff EN, Whitworth J, Gilks CF, 2000. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet 355 : 2106–2111.
  12. Katz N, Chaves A, Pellegrino N, 1972. A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev Inst Med Trop Sao Paulo 14 : 397–400.
  13. Deelder AM, De Jonge N, Boerman OC, Fillie YE, Hilberath GW, Rotmans JP, Gerritse MJ, Schut DW, 1989. Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies. Am J Trop Med Hyg 40 : 268–272.
  14. Karanja DM, Colley DG, Nahlen BL, Ouma JH, Secor WE, 1989. Studies on schistosomiasis in western Kenya: I. Evidence for immune- facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections. Am J Trop Med Hyg 56 : 515–521.
  15. Melrose WD, Turner PF, Pisters P, Turner B, 2000. An improved Knott’s concentration test for the detection of microfilariae. Trans R Soc Trop Med Hyg 94 : 176.
  16. Brown M, Bukusuba J, Hughes P, Nakiyingi J, Watera C, Elliott A, Whitworth J, 2003. Screening for intestinal helminth infestation in a semi-urban cohort of HIV-infected people in Uganda: a combination of techniques may enhance diagnostic yield in the absence of multiple stool samples. Trop Doct 33 : 72–76.
  17. Pearlman E, Kazura JW, Hazlett FE Jr, Boom WH, 1993. Modulation of murine cytokine responses to mycobacterial antigens by helminth-induced T helper 2 cell responses. J Immunol 151 : 4857–4864.
  18. Del Prete GF, De Carli M, Mastromauro C, Biagiotti R, Macchia D, Falagiani P, Ricci M, Romagnani S, 1991. Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production. J Clin Invest 88 : 346–350.
  19. Stewart GR, Boussinesq M, Coulson T, Elson T, Nutman T, Bradley JE, 1999. Onchocerciasis modulates the immune response to mycobacterial antigens. Clin Exp Immunol 117 : 517–523.
  20. Sacco R, Hagen M, Sandor M, Weinstock J, Lynch R, 2002. Established T(H1) Granulomatous Responses Induced by Active Mycobacterium avium Infection Switch to T(H2) Following Challenge with Schistosoma mansoni. Clin Immunol 104 : 274.
  21. Borkow G, Leng Q, Weisman Z, Stein M, Galai N, Kalinkovich A, Bentwich Z, 2000. Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy. J Clin Invest 106 : 1053–1060.
  22. Malhotra I, Mungai P, Wamachi A, Wamachi A, Kioko J, Ouma JH, Kazura JW, King CL, 1999. Helminth- and Bacillus Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J Immunol 162 : 6843–6848.
  23. Elias D, Akuffo H, Pawlowski A, Haile M, Schön T, Britton S, 2005. Schistosoma mansoni infection reduces the protective efficacy of BCG vaccination against virulent Mycobacterium tuberculosis. Vaccine 23 : 1326–1334.
  24. Elias D, Wolday D, Akuffo H, Petros B, Bronner U, Britton S, 2001. Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination. Clin Exp Immunol 123 : 219–225.
  25. Tristão-Sá R, Ribeiro-Rodrigues R, Johnson LT, Pereira FEL, Dietze R, 2002. Intestinal nematodes and pulmonary tuberculosis. Rev Soc Bras Med Trop 35 : 533–535.
  26. Elliott AM, Hodsdon WS, Kyosiimire J, Quigley MA, Nakiyingi JS, Namujju PB, Watera C, French N, Gilks CF, Dockrell HM, Whitworth JAG, 2004. Cytokine responses and progression to active tuberculosis in HIV-1-infected Ugandans: a prospective study. Trans R Soc Trop Med Hyg 98 : 660–670.
  27. Brown M, 2004. Is helminth infection associated with an increased rate of progression of HIV disease in Uganda? PhD thesis, University of London, London.
  28. Brown M, Nkurunziza P, Pickering J, Khaukha P, Kizza M, Mawa PA, Watera C, Whitworth JAG, Elliott AM, 2003. Mansonella perstans infection in a cohort of HIV-infected adults in Uganda. Clin Microbiol Infect 9 : 64.
  29. Diallo TO, Remoué F, Schacht AM, Charrier N, Dompnier J-P, Pillet S, Garraud O, N’Diaye AA, Capron A, Capron M, Riveau G, 2004. Schistosomiasis co-infection in humans influences inflammatory markers in uncomplicated Plasmodium falciparum malaria. Parasite Immunol 26 : 365–369.
  30. Van Den Biggelaar AH, van Ree R, 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.
  31. Othieno C, Hirsch CS, Hamilton BD, Wilkinson K, Ellner JJ, Toossi Z, 1999. Interaction of Mycobacterium tuberculosis-induced transforming growth factor β1 and interleukin-10. Infect Immun 67 : 5730–5735.
  32. Hirsch CS, Toossi Z, Othieno C, Johnson JL, Schwander SK, Robertson S, Wallis RS, Edmonds K, Okwera A, Mugerwa R, Peters P, Ellner JJ, 1999. Depressed T-cell interferon-γ responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. J Infect Dis 180 : 2069–2073.
  33. 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.
  34. Bentwich Z, Kalinkovich A, Weisman Z, 1995. Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol Today 16 : 187–191.
  35. Clerici M, Butto S, Lukwiya M, Saresella M, Declich S, Trabattoni D, Pastori C, Piconi S, Fracasso C, Fabiani M, Ferrante P, Rizzardini G, Lopalco L, 2000. Immune activation in Africa is environmentally-driven and is associated with upregulation of CCR5. Italian-Ugandan AIDS Project. AIDS 14 : 2083–2092.
  36. Rizzardini G, Trabattoni D, Saresella M, Piconi S, Lukwiya M, Declich S, Fabiani M, Ferrante P, Clerici M, 1998. Immune activation in HIV-infected African individuals. Italian-Ugandan AIDS cooperation program. AIDS 12 : 2387–2396.
  37. Lawn SD, Butera ST, Folks TM, 2001. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev 14 : 753–777.
  38. Eggena MP, Barugahare B, Okello M, Mutyala S, Jones N, Ma Y, Kityo C, Mugyenyi P, Cao H, 2005. T cell activation in HIV-seropositive Ugandans: differential associations with viral load, CD4+ T cell depletion, and coinfection. J Infect Dis 191 : 694–701.
  39. Kassu A, Tsegaye A, Wolday D, Petros B, Aklilu M, Sanders EJ, Fontanet AL, Van Baarle D, Hamann D, De Wit TF, 2003. Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians. Clin Exp Immunol 132 : 113–119.
  40. Rhodes SG, Graham SP, 2002. Is ’timing’ important for cytokine polarization? Trends Immunol 23 : 246–249.
  41. Yazdanbakhsh M, Kremsner PG, van Ree R, 2002. Allergy, parasites, and the hygiene hypothesis. Science 296 : 490–494.

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  • Received : 18 Sep 2005
  • Accepted : 21 Dec 2005

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