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Masters Degrees (Medical Microbiology)

Permanent URI for this collectionhttps://hdl.handle.net/10413/9620

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Browsing Masters Degrees (Medical Microbiology) by Author "Archary, Derseree."

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    Characterization of immunoglobulin (Ig) isotypes, IgG subclasses and cytokines in the blood and genital tracts of HIV infected and healthy women from an observational cohort study (CAPRISA 082)
    (2020) Zuma, Mandisa Nokukhanya.; Archary, Derseree.; Sorbia, Parveen.
    Background: Heterosexual transmission remains the dominant route of HIV infections in women. Immune responses that predict HIV acquisition during pre-exposure prophylaxis (PrEP) remain undefined. We hypothesized that increased genital tract antibodies and cytokines pre-HIV infection predict HIV acquisition in seroconverters compared to non-seroconverters irrespective of PrEP use. Methods: Plasma and Softcup specimens were collected from n=12 seroconverters (cases) and n=48 non-seroconverters (controls) in the CAPRISA 082 study at five time points. Of 12 cases-, nine took PrEP, while 29 of 48 controls took PrEP. IgG1, IgG2, IgG3, IgG4, IgM and IgA, and nine cytokines: MIP-1􀄮, MIP-1􀈕, IP-10, MCP-1, and IL-8, TNF-􀄮, IL-1􀄮, IL-1􀈕, and IL-6 pre- and post-HIV infection, were measured using multiplexed technology. Results: Baseline levels of IgG subclasses, Ig isotypes, and mucosal cytokines were similar between cases and controls. Over time within the cases, plasma IgA significantly declined, in controls, plasma IgG2, IgG3, and IgM significantly declined over time (p<0.05). In cases and controls on PrEP, plasma IgG3 trended higher compared to no PrEP (p<0.1). Relative to baseline, only within the controls, mucosal IgG1, IgG2, IgG3, IgG4, IgM, and IgA declined significantly. Mucosal IgM significantly predicted four-fold increased HIV risk (p=0.01). Eight of nine cytokines in the genital tract were significantly elevated in the cases compared to controls (all p<0.05). In cases and controls who used PrEP relative to no PrEP, IP-10 was significantly lower (p=0.04 and p=0.009). Baseline mucosal IL-8 significantly correlated with mucosal IgG1, IgG2, total IgG, and IgM (p<0.001 for all). Conclusions: Although no significant elevated genital antibodies or cytokines pre-HIV infection were found, significantly different patterns of antibodies and cytokines were observed in this cohort. Plasma IgG3, one of the most effective of the IgG􀂶s eliciting diverse antibod􀁜 functions, was increased in PrEP users. Mucosal IgM was associated with increased HIV-acquisition risk, while pleiotropic IP-10, a reported risk factor was modulated in PrEP users among cases. Collectively, these data suggest that PrEP use may modulate or preserve specific immune responses that can modify HIV risk. As PrEP uptake increases, its effect on mucosal and systemic immunity is important for informing on prevention strategies where PrEP may be given alone or in combination with HIV vaccine for added efficacy.
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    The effect of genital tract inflammation on HIV-specific binding antibodies, IgG subclass and Isotype transudation.
    (2019) Pillay, Thevani.; Archary, Derseree.; Baxter, Cheryl.
    Abstract available in PDF file.
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    Role of local or systemic Schistosoma infections in driving inflammation and HIV risk in women enrolled in the CAPRISA 004 cohort.
    (2016) Tulsi, Sahil.; Archary, Derseree.; Horsnell, William.; Passmore, Jo-Ann Shelley.
    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.