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Identifying correlates of immunity or susceptibility to disease promotes understanding of pathogenesis and development of diagnostic tools, treatments, and vaccines. There is evidence that type 1 cytokine responses are associated with protection against tuberculosis, and suppression of type 1, or switching to type 2 responses, with susceptibility, but this has not been studied prospectively. We studied a cohort of 631 HIV-1-infected Ugandan adults. At enrollment we performed whole blood cultures for type 1 (interferon [IFN]-gamma, interleukin [IL]-2) and type 2/immunosuppressive (IL-5, IL-10) responses to mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). The incidence of tuberculosis was not associated with IFN-gamma responses, but was higher among participants with IL-2 responses (adjusted rate ratios [RR]: PPD 3.48; CFP 3.99; P < 0.001). For tuberculin skin test-positive participants, high incidence was also associated with an IL-10 response to PPD (adjusted RR 6.24, P = 0.03); for those with a BCG scar, high incidence was associated with positive IL-5 responses (adjusted RRs: PPD 3.64, P = 0.006; CFP 3.44, P = 0.04). The association with IL-2 production may reflect a response to tuberculous infection or to activating disease; the associations with IL-10 and IL-5 are in keeping with the expected role of immunosuppressive or type 2 cytokines.

It has been suggested that type 1 immune responses protect against tuberculosis (TB), while type 2 responses, such as those induced by helminths, may suppress protective responses and increase susceptibility to TB. Factors associated with progression to active TB were investigated in a cohort of HIV-1-infected Ugandan adults, a group at high risk of TB. High rates of subsequent progression to active TB were associated with eosinophil counts > or = 0.4 x 10(9)/L at enrolment. Eosinophilia at enrolment was associated with male gender, low socio-economic status, high CD4+ T cell counts, and schistosomiasis, but adjusting for these factors did not explain the association of eosinophilia with progression to active TB (adjusted rate ratio = 2.76, P = 0.004). Eosinophilia is most likely to be indicative of a type 2 immune response induced by helminth infection in this Ugandan cohort, but the mechanism of the observed association between eosinophilia and risk of TB remains to be determined.

It has been proposed that helminth infection may exacerbate HIV progression by promoting activation of 'type 2' immune responses. To examine this hypothesis, we investigated helminth infection in a cohort of HIV-1-seropositive adults in Entebbe, Uganda, during November 1999 to January 2000. Individuals with helminths were treated. At enroLlment, after 5 weeks and after 4 months, CD4+ and CD8+ T cell counts and viral load were measured. Cytokine responses (interferon [IFN]-gamma, interleukin [IL]-2, IL-4 and IL-5) to Schistosoma mansoni adult worm antigen (SWA), Mycobacterium tuberculosis culture filtrate proteins (CFPs) and phytohaemagglutinin (PHA) were measured in a whole blood assay. At baseline, CD4+ T cell counts and CD4+: CD8+ ratios were higher in individuals with helminths than in those without (median CD4+ T cell counts 467/microL and 268/microL, respectively, P = 0.005). Viral load was lower among those with helminths but this was not statistically significant. During follow-up, CD4+ T cell counts and cytokine responses to PHA fell among individuals without helminths. Among those treated for helminths, CD4+ counts remained stable. Viral loads showed a transient increase at 5 weeks, which was more marked among those treated for helminths, but the levels at 4 months were similar to baseline in both groups. Among those with schistosomiasis, IFN-gamma and IL-2 responses to CFP, and IL-2 and IL-4 responses to PHA declined but there was a sustained increase in cytokine responses to SWA following treatment. These data do not support the hypothesis that helminth infection exacerbates HIV infection. The possibility that chronic helminth infection may suppress HIV replication and that effects on HIV replication may vary during helminth infection and treatment should be considered.