Role of local or systemic Schistosoma infections in driving inflammation and HIV risk in women enrolled in the CAPRISA 004 cohort.

Abstract

Female genitourinary schistosomiasis (FGS) has been associated with increased HIV susceptibility, presumably through lesions secondary to parasitic eggs in situ in the female genital tract. We determined the prevalence of FGS infection by real-time PCR (indicative of local involvement of parasitic eggs in the genital mucosae) and sero-prevalence of schistosomiasis (indicating prior exposure to parasitic infection) in HIV-uninfected KZN women (n=383) who had participated in the CAPRISA004 trial. The hypothesis for this study was that FGS, and genital tract inflammation are risk factors for HIV-acquisition. DNA PCR was used to confirm the presence of FGS, ELISAs were used for detection of Schistosoma spp IgG and multiplex technology was used to detect genital tract cytokines in the cervicovaginal lavages (CVLs). The median age of the women in this study was 23 years (range 20-26 years). Of the 383 HIV negative women, 52/383 (13.8%) became HIV-infected by study exit with an HIV incidence rate of 9.1 per 100 women-years ( 95% CI: 6.8 – 11.9). Nine of 383 (2.3%) women had a positive DNA PCR for Schistosoma spp indicative of prevalent genital schistosomiasis. Of these 9 women, 4/9 (44%) acquired HIV infection by study exit with a 4.0 times increased risk for HIV-infection (OR of 4.05- 95% CI 1.8-8.9, p=0.01) than PCR-negative women. Schistosoma haematobium, the endemic species in KZN has high sequence homology with S. mansoni antigen which was used to detect IgG in the plasma samples. Of the 383 plasma samples from study entry, 21/383 (5.5%) and 19/383 (4.96%) of study participants had detectable levels of IgG to S. mansoni at study exit. . Only, MCP-3, a chemokine was significantly higher in FGS+ compared to FGS- healthy HIV negative women. Genital tract pro-inflammatory cytokines at study exit were significantly higher in FGS-HIV+ women for IL-1β, MIF, IL-1A & IL-6 compared to FGS-HIV- women (p<0.0001, p=0.0014, p=0.0088, p=0.0069 respectively). Anti-inflammatory cytokine data in FGS-HIV+ women showed higher median levels of IL-1RA & IL-2RA compared to FGS –HIV- women (p<0.0001 & p=0.0012 respectively). Mixed responses of both pro and anti-inflammatory cytokines in the presence or absence of FGS may be an indication that HIV infection is driving these signatures and causing dysregulation. The presence of parasite DNA in the genital tract was significantly associated with increased risk for HIV acquistion. Taken together, these results highlight the importance of understanding the complex interplay of parasitic infections, and host immunity as potential risk factors for HIV acquistion in regions with high HIV and parasite burden.