ABSTRACT
The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8+ T cells, the marked reduction of circulating CD4+ T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. On the other hand, when evaluating the impact of the co-infection on the parasitic burden, co-infected mice presented a marked decrease in the total number of migrating Ascaris lung-stage larvae in comparison with Ascaris mono-infection. Taken together, our major findings suggest that Ascaris and VACV co-infection may potentiate the virus-associated pathology by the downmodulation of the VACV-specific immune response. Moreover, this study provides new evidence of how helminth parasites may influence the course of a coincident viral infection.
Subject(s)
Ascariasis/virology , Ascaris/immunology , Coinfection/immunology , Pneumonia/parasitology , Vaccinia virus/immunology , Vaccinia/etiology , Animals , Ascariasis/immunology , CD8-Positive T-Lymphocytes/immunology , Coinfection/parasitology , Coinfection/virology , Cytokines/immunology , Disease Models, Animal , Female , Interferon-gamma/immunology , Larva/parasitology , Lung/immunology , Lung/parasitology , Lung/pathology , Lung/virology , Mice , Mice, Inbred BALB C , Pneumonia/immunology , Pneumonia/virology , Swine , Vaccinia/immunology , Vaccinia/pathology , Vaccinia/virology , Viral LoadABSTRACT
OBJECTIVE: Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression. DESIGN: To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. METHODS: A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (ClinicalTrials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. RESULTS: Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrollment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. CONCLUSION: Treatment of A. lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.