Helminths and HIV infection: epidemiological observations on immunological hypotheses

M Brown, P A Mawa, P Kaleebu, A M Elliott, M Brown, P A Mawa, P Kaleebu, A M Elliott

Abstract

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection.

References

    1. Bundy D, Sher A, Michael E. Good worms or bad worms: do worm infections affect the epidemiological patterns of other diseases? Parasitol Today. 2000;16:273–274.
    1. Maizels RM. Infections and allergy – helminths, hygiene and host immune regulation. Curr Opin Immunol. 2005;17:656–661.
    1. Elliott AM, Mpairwe H, Quigley M, et al. Helminth infection during pregnancy and development of infantile eczema. JAMA. 2005;294:2032–2034.
    1. Cooke A, Tonks P, Jones FM, et al. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice. Parasite Immunol. 1999;21:169–176.
    1. Summers RW, Elliott DE, Urban JF, Jr, Thompson RA, Weinstock JV. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology. 2005;128:825–832.
    1. Summers RW, Elliott DE, Urban JF, Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005;54:87–90.
    1. Nacher M. Interactions between worm infections and malaria. Clin Rev Allergy Immunol. 2004;26:85–92.
    1. Druilhe P, Adama J, Sokhna C. Worms can worsen malaria: towards a new means to roll back malaria. Trends Parasitol. 2005;21:359–362.
    1. Actor J, Shirai M, Kullberg M, Buller R, Sher A, Berzofsky J. Helminth infection results in decreased virus-specific CD8+ cytotoxic T-cell and Th1 cytokine responses as well as delayed virus clearance. Proc Natl Acad Sci USA. 1993;90:948–952.
    1. Brady MT, O-Neill SM, Dalton JP, Mills KH. Fasciola hepatica suppresses a protective Th1 response against Bordetella pertussis. Infect Immun. 1999;67:5372–5378.
    1. Elias D, Akuffo H, Thors C, Pawlowski A, Britton S. Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice. Clin Exp Immunol. 2005;139:398–404.
    1. Chenine A-L, Buckley KA, Li P-L, et al. Schistosoma mansoni promotes SVIV clade C replication in rhesus macaques. AIDS. 2005;19:1793–1797.
    1. Gordin F, Simon G, Wofsy C, Mills J. Adverse reactions to trimethoprim-sulphamethoxazole in patients with the acquired immunodeficiency syndrome. Ann Intern Med. 1984;100:495–499.
    1. Nunn P, Kibuga D, Gthua S, et al. Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis. Lancet. 1991;377:627–630.
    1. Bentwich Z, Kalinkovich A, Weisman Z. Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol Today. 1995;16:187–191.
    1. Bentwich Z, Kalinkovich A, Weisman Z, Borkow G, Beyers N, Beyers AD. Can eradication of helminthic infections change the face of AIDS and tuberculosis. Immunol Today. 1999;20:485–487.
    1. Kalinkovich A, Borkow G, Weisman Z, Tsimanis A, Stein M, Bentwich Z. Increased CCR5 and CXCR4 expression in Ethiopians living in Israel: environmental and constitutive factors. Clin Immunol. 2001;100:107–117.
    1. Secor WE, Shah A, Mwinzi PM, Ndenga BA, Watta CO, Karanja DM. Increased density of human immunodeficiency virus type 1 coreceptors CCR5 and CXCR4 on the surface of CD4(+) T cells and monocytes of patients with Schistosoma mansoni infection. J Infect Dis. 2001;184:488–496.
    1. Hoerauf A, Satoguina J, Saeftel M, Specht S. Immunomodulation by filarial nematodes. Parasite Immunol. 2005;27:417–429.
    1. Elson LH, Days A, Calvopina MH, et al. In utero exposure to Onchocerca volvulus: relationship to subsequent infection intensity and cellular immune responsiveness. Infect Immun. 1996;64:5061–5065.
    1. Malhotra I, Mungai PL, Wamachi AN, et al. Prenatal T cell immunity to Wuchereria bancrofti and its effect on filarial immunity and infection susceptibility during childhood. J Infect Dis. 2006;193:1005–1013.
    1. Thornton AM, Shevach EM. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol. 2000;164:183–190.
    1. Nixon DF, Aandahl EM, Michaëlsson J. CD4+CD25+ regulatory T cells in HIV infection. Microbes Infect. 2005;7:1063–1065.
    1. Eggena MP, Barugahare B, Jones N, et al. Depletion of regulatory T cells in HIV infection is associated with immune activation. J Immunol. 2005;174:4407–4414.
    1. Andersson J, Boasso A, Nilsson J, et al. The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. J Immunol. 2005;174:3143–3147.
    1. Aandahl EM, Michaëlsson J, Moretto WJ, Hecht FM, Nixon DF. Human CD4+CD25+ regulatory T cells control T-cell responses to human immunodeficiency virus and cytomegalovirus antigens. J Virol. 2004;78:2454–2459.
    1. Weiss L, Donkova-Petrini V, Caccavelli L, Balbo M, Carbonneil C, Levy Y. Human immunodeficiency virus-driven expansion of CD4+CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood. 2004;104:3249–3256.
    1. Kinter AL, Hennessey M, Bell A, et al. CD25+CD4+ regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4+ and CD8+ HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J Exp Med. 2004;200:331–343.
    1. Duh EJ, Maury WJ, Folks TM, Fauci AS, Rabson AB. Tumor necrosis factor α activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-κB sites in the long terminal repeat. Proc Nat Acad Sci USA. 1989;86:5974–5978.
    1. Schottelius AJ, Mayo MW, Sartor RB, Baldwin AS., Jr Interleukin-10 signaling blocks inhibitor of κB kinase activity and nuclear factor κB DNA binding. J Biol Chem. 1999;274:31868–31874.
    1. Oswald-Richter K, Grill SM, Shariat N, et al. HIV infection of naturally occurring and genetically reprogrammed human regulatory T-cells. PLoS Biol. 2004;2:955–966.
    1. Tsunemi S, Iwasaki T, Imado T, et al. Relationship of CD4+CD25+ regulatory T cells to immune status in HIV-infected patients. AIDS. 2005;19:879–886.
    1. Morgan D, Whitworth J. The natural history of HIV-1 infection in Africa. Nature Med. 2001;7:143–145.
    1. Kallestrup P, Zinyama R, Gomo E, et al. 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. 2005;192:1956–1961.
    1. Kjetland EF, Ndhlovu PD, Gomo E, et al. Association between genital schistosomiasis and HIV in rural Zimbabwean women. AIDS. 2006;20:593–600.
    1. Gallagher M, Malhotra I, Mungai PL, et al. The effects of maternal malaria and helminth infections on mother-to-child HIV transmission. AIDS. 2005;19:1849–1855.
    1. Da Silva CV, Ferreira MS, Borges AS, Costa-Cruz JM. Intestinal parasitic infections in HIV/AIDS patients: experience at a teaching hospital in central Brazil. Scand J Infect Dis. 2005;37:211–215.
    1. Kallestrup P, Zinyama R, Gomo E, et al. Schistosomiasis and HIV-1 infection in rural Zimbabwe: implications of coinfection for excretion of eggs. J Infect Dis. 2005;191:1311–1320.
    1. Pinlaor S, Mootsikapun P, Pinlaor P, Pipitgool V, Tuangnadee R. Detection of opportunistic and non-opportunistic intestinal parasites and liver flukes in HIV-positive and HIV-negative subjects. Southeast Asian J Trop Med Public Health. 2005;36:841–845.
    1. Hailemariam G, Kassu A, Abebe G, et al. Intestinal parasitic infections in HIV/AIDS and HIV seronegative individuals in a teaching hospital, Ethiopia. Jpn J Infect Dis. 2004;57:41–43.
    1. Marchi Blatt J, Cantos GA. Evaluation of techniques for the diagnosis of Strongyloides stercoralis in human immunodeficiency virus (HIV) positive and HIV negative individuals in the city of Itajai, Brazil. Braz J Infect Dis. 2003;7:402–408.
    1. Feitosa G, Bandeira AC, Sampaio DP, Badaró R, Brites C. High prevalence of giardiasis and strongyloidiasis among HIV-infected patients in Bahia, Brazil. Braz J Infect Dis. 2001;5:339–344.
    1. Fontanet AL, Woldemichael T, Sahlu T, et al. Epidemiology of HIV and Schistosoma mansoni infections among sugar-estate residents in Ethiopia. Ann Trop Med Parasitol. 2000;94:145–155.
    1. Lindo JF, Dubon JM, Ager AL, et al. Intestinal parasitic infections in human immunodeficiency virus (HIV)-positive and HIV-negative individuals in San Pedro Sula, Honduras. Am J Trop Med Hyg. 1998;58:431–435.
    1. Fischer P, Kipp W, Kabwa P, Buttner DW. Onchocerciasis and human immunodeficiency virus in western Uganda: prevalences and treatment with ivermectin. Am J Trop Med Hyg. 1995;53:171–178.
    1. Gomez Morales MA, Atzori C, Ludovisi A, Rossi P, Scaglia M, Pozio E. Opportunistic and non-opportunistic parasites in HIV-positive and negative patients with diarrhoea in Tanzania. Trop Med Parasitol. 1995;46:109–114.
    1. N’Zoukoudi-N'Doundou MY, Dirat I, Akouala JJ, Penchenier L, Makuwa M, Rey JL. Bilharziasis and human immunodeficiency virus infection in Congo. Med Trop (Mars) 1995;55:249–251.
    1. Leutscher PD, Pedersen M, Raharisolo C, et al. Increased prevalence of leukocytes and elevated cytokine levels in semen from Schistosoma haematobium infected individuals. J Infect Dis. 2005;191:1639–1647.
    1. Feldmeier H, Krantz I, Poggensee G. Female genital schistosomiasis as a risk factor for the transmission of HIV. Int J STD AIDS. 1994;5:368–372.
    1. Allen HE, Crompton DWT, de Silva N, LoVerde PT, Olds GR. New policies for using anthelminthics in high risk groups. Trends Parasitol. 2002;18:381–382.
    1. Modjarrad K, Zulu I, Redden DT, et al. Treatment of intestinal helminths does not reduce plasma concentrations of HIV-1 RNA in co-infected Zambian adults. J Infect Dis. 2005;192:1277–1283.
    1. Brown M, Kizza M, Watera C, et al. Helminth infection is not associated with faster HIV disease progression in co-infected adults in Uganda. J Infect Dis. 2004;190:1869–1879.
    1. Elliott AM, Mawa PA, Joseph S, et al. Associations between helminth infection and CD4+ T cell count, viral load and cytokine responses in HIV-1-infected Ugandan adults. Trans Roy Soc Trop Med Hyg. 2003;97:103–108.
    1. Wolday D, Mayaan S, Mariam ZG, et al. Treatment of intestinal worms is associated with decreased HIV plasma viral load. J Acquired Immune Defic Syndr. 2002;31:56–62.
    1. Brown M, Mawa P, Joseph S, et al. Treatment of Schistosoma mansoni increases helminth-specific type 2 cytokines and HIV-1 RNA concentrations in co-infected Ugandan adults. J Infect Dis. 2005;191:1648–1657.
    1. Lawn SD, Karanja DMS, Mwinzi P, et al. The effect of treatment of schistosomiasis on blood plasma HIV-1 RNA concentration in coinfected individuals. AIDS. 2000;14:2437–2443.
    1. Brown M, Miiro G, Nkurunziza P, et al. Schistosoma mansoni, nematode infections and progression to active tuberculosis among HIV-1-infected Ugandans. Am J Trop Med Hyg. 2006;74:819–825.
    1. Goletti D, Weissman D, Jackson RW, et al. Effect of Mycobacterium tuberculosis on HIV replication: role of immune activation. J Immunol. 1996;157:1271–1278.
    1. Whalen C, Horsburgh CR, Hom D, Lahart C, Simberkoff M, Ellner JJ. Accelerated course of human immunodeficiency virus infection after tuberculosis. Am J Respir Crit Care Med. 1995;151:129–135.
    1. Gallo RC. The end or the beginning of the drive to an HIV-preventive vaccine: a view from over 20 years. Lancet. 2005;366:1894–1898.
    1. Kilian HD, Nielsen G. Cell mediated and humoral immune response to tetanus vaccinations in onchocerciasis patients. Trop Med Parasitol. 1989;40:285–291.
    1. Kilian HD, Nielsen G. Cell mediated and humoral immune responses to BCG and rubella vaccinations and to recall antigens in onchocerciasis patients. Trop Med Parasitol. 1989;40:445–453.
    1. Sabin EA, Ilma Araujo M, Carvalho EM, Pearce EJ. Impairment of tetanus toxoid-specific Th1-like immune responses in humans infected with Schistosoma mansoni. J Infect Dis. 1996;173:269–272.
    1. Cooper PJ, Espinel I, Paredes W, Guderian RH, Nutman TB. Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis. J Infect Dis. 1998;178:1133–1138.
    1. Malhotra I, Mungai P, Wamachi A, et al. Helminth- and Bacillus-Calmette-Guerin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. J Immunol. 1999;162:6843–6848.
    1. Cooper PJ, Chico ME, Losonsky G, et al. Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR. J Infect Dis. 2000;182:1199–1206.
    1. Cooper PJ, Chico M, Sandoval C, et al. Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Infect Immun. 2001;69:1574–1580.
    1. Elias D, Wolday D, Akuffo H, Petros B, Bronner U, Britton S. 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. 2001;123:219–225.
    1. Elliott AM, Namujju PB, Mawa PA, et al. A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guerin (BCG) immunisation [ISRCTN32849447] BMC Infectious Dis. 2005;5:115.
    1. Guimaraes-Walker A, Mackie N, McMichael A, et al. Lausanne, Switzerland: AIDS Vaccine 04; 2004. Priming with a candidate HIV-1 clade A DNA vaccine followed by booster with HIV-1 clade A MVA vaccine in volunteers at low risk of HIV infection. 55 (Abstract)
    1. Jaoko W, Omosa G, Bhatt K, et al. Lausanne, Switzerland: AIDS Vaccine 04; 2004. Safety and immunogenicity of DNA and MVA HIVA vaccines in phas1 HIV-1 vaccine trials in Nairobi, Kenya. 56 (Abstract)
    1. Nakwagala F, Birungi J, Schmidt C, et al. Lausanne, Switzerland: AIDS Vaccine 04; 2004. Safety and immunogenicity of HIV-1 clade A vaccines in HIV-uninfected adult Ugandan volunteers. Abstract P244.
    1. Doenhoff MJ, Hassounah O, Murare H, Bain J, Lucas S. The schistosome egg granuloma: immunopathology in the cause of host protection or parasite survival? Trans R Soc Trop Med Hyg. 1986;80:503–514.
    1. Karanja DM, Colley DG, Nahlen BL, Ouma JH, Secor WE. 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. 1997;56:515–521.
    1. Mwanakasale V, Vounatsou P, Sukwa T, Ziba M, Ernest A, Tanner M. Interaction between Schistosoma haematobium and human immunodeficiency virus type 1: the effects of coinfection on treatment outcomes in rural Zambia. Am J Trop Med Hyg. 2003;69:420–428.
    1. Fernando R, Miller R. Immune reconstitution eosinophilia due to schistosomiasis. Sex Transm Infect. 2002;78:76.
    1. de Silva S, Walsh J, Brown M. Symptomatic Schistosoma mansoni infection as an immune restoration phenomenon in a patient receiving antiretroviral therapy. Clin Infect Dis. 2006;42:303–304.
    1. Mwinzi PNM, Karanja DMS, Kareko I, et al. Evaluation of hepatic fibrosis in persons co-infected with Schistosoma mansoni and human immunodeficiency virus 1. Am J Trop Med Hyg. 2004;71:783–786.
    1. Sabah AA, Fletcher C, Webbe G, Doenhoff MJ. Schistosoma mansoni: reduced efficacy of chemotherapy in infected T-cell-deprived mice. Exp Parasitol. 1985;60:348–354.
    1. Karanja DM, Boyer AE, Strand M, et al. Studies on schistosomiasis in western Kenya: II. Efficacy of praziquantel for treatment of schistosomiasis in persons coinfected with human immunodeficiency virus-1. Am J Trop Med Hyg. 1998;59:307–311.
    1. Karanja DM, Hightower AW, Colley DG, et al. Resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and effect of HIV-1 co-infection on susceptibility to schistosomiasis: a longitudinal study. Lancet. 2002;360:592–596.
    1. Mwinzi PN, Karanja DM, Colley DG, Orago AS, Secor WE. Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection. J Infect Dis. 2001;184:488–496.
    1. Joseph S, Jones FM, Laidlaw ME, et al. Impairment of the Schistosoma mansoni-specific immune responses elicited by treatment with Praziquantel in Ugandans with HIV-1 co-infection. J Infect Dis. 2004;190:613–618.
    1. Sentongo E, Rubaale T, Buttner DW, Brattig NW. T cell responses in coinfection with Onchocerca volvulus and the human immunodeficiency virus type 1. Parasite Immunol. 1998;20:431–439.
    1. Fischer P, Kipp W, Kabwa P, Buttner DW. Onchocerciasis and human immunodeficiency virus in western Uganda: prevalence and treatment. Am J Trop Med Hyg. 1995;53:171–178.
    1. Tawill SA, Gallin M, Erttmann KD, Kipp W, Bamuhiiga J, Buttner DW. Impaired antibody responses and loss of reactivity to Onchocerca volvulus antigens by HIV-seropositive onchocerciasis patients. Trans R Soc Trop Med Hyg. 1996;90:85–89.
    1. Kipp W, Bamuhiiga J, Rubaale T. Simulium neavei-transmitted onchocerciasis: HIV infection increases severity of onchocercal skin disease in a small sample of patients. Trans R Soc Trop Med Hyg. 2003;97:310–311.
    1. Lucas SB, Hounnou A, Peacock C, et al. The mortality and pathology of HIV infection in a west African city. AIDS. 1993;7:1569–1579.
    1. Harvey SC, Gemmill AW, Read AF, Viney ME. The control of morph development in the parasitic nematode Strongyloides ratti. Proc R Soc Lond B Biol Sci. 2000;267:2057–2063.
    1. Viney ME, Brown M, Omoding NE, et al. Why does HIV infection not lead to disseminated strongyloidiasis? J Infect Dis. 2004;190:2175–2180.
    1. Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci. 1998;94:557–572.
    1. Neva FA, Filho JO, Gam AA, et al. Interferon-gamma and interleukin-4 responses in relation to serum IgE levels in persons infected with human T lymphotropic virus type I and Strongyloides stercoralis. J Infect Dis. 1998;178:1856–1859.
    1. Clerici M, Hakim FT, Venzon DJ, et al. Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. J Clin Invest. 1993;91:759–765.
    1. Kim A, Lupatkin HC. Strongyloides stercoralis infection as a manifestation of immune restoration syndrome. Clin Infect Dis. 2004;39:439–440.
    1. Lanzafame M, Faggian F, Lattuada E, Antolini D, Vento S. Strongyloidiasis in an HIV-1-infected patient after highly active antiretroviral therapy-induced immune restoration. J Infect Dis. 2005;191:1027.
    1. Brown M, Cartledge JD, Miller RF. Dissemination of Strongyloides stercoralis as an immune restoration phenomenon in an HIV-1-infected man on antiretroviral therapy. Int J STD AIDS. 2006;17:000–000. in press.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe