Effect of female genital schistosomiasis and anti-schistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract

BACKGROUND: Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. Design The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. METHODS: Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). RESULTS: FGS was associated with a higher frequency of CD14 + cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4 + cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14 + cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). CONCLUSIONS: The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this

POLD2 and KSP37 (FGFBP2) Correlate Strongly with Histology, Stage and Outcome in Ovarian Carcinomas

BACKGROUND:Epithelial ovarian cancer (EOC) constitutes more than 90% of ovarian cancers and is associated with high mortality. EOC comprises a heterogeneous group of tumours, and the causes and molecular pathology are essentially unknown. Improved insight into the molecular characteristics of the different subgroups of EOC is urgently needed, and should eventually lead to earlier diagnosis as well as more individualized and effective treatments. Previously, we reported a limited number of mRNAs strongly upregulated in human osteosarcomas and other malignancies, and six were selected to be tested for a possible association with three subgroups of ovarian carcinomas and clinical parameters. METHODOLOGY/PRINCIPAL FINDINGS:The six selected mRNAs were quantified by RT-qPCR in biopsies from eleven poorly differentiated serous carcinomas (PDSC, stage III-IV), twelve moderately differentiated serous carcinomas (MDSC, stage III-IV) and eight clear cell carcinomas (CCC, stage I-IV) of the ovary. Superficial scrapings from six normal ovaries (SNO), as well as biopsies from three normal ovaries (BNO) and three benign ovarian cysts (BBOC) were analyzed for comparison. The gene expression level was related to the histological and clinical parameters of human ovarian carcinoma samples. One of the mRNAs, DNA polymerase delta 2 small subunit (POLD2), was increased in average 2.5- to almost 20-fold in MDSC and PDSC, respectively, paralleling the degree of dedifferentiation and concordant with a poor prognosis. Except for POLD2, the serous carcinomas showed a similar transcription profile, being clearly different from CCC. Another mRNA, Killer-specific secretory protein of 37 kDa (KSP37) showed six- to eight-fold higher levels in CCC stage I compared with the more advanced staged carcinomas, and correlated positively with an improved clinical outcome. CONCLUSIONS/SIGNIFICANCE:We have identified two biomarkers which are markedly upregulated in two subgroups of ovarian carcinomas and are also associated with stage and outcome. The results suggest that POLD2 and KSP37 might be potential prognostic biomarkers

Cervical ectopy: associations with sexually transmitted infections and HIV. A cross-sectional study of high school students in rural South Africa

Objectives It has been hypothesised that ectopy may be associated with increased susceptibility to sexually transmitted infections (STIs). In this cross-sectional study, we wanted to explore the association between STIs (including HIV) and cervical ectopy. Methods We included 700 sexually active young women attending randomly selected high schools in a rural district in KwaZulu-Natal, South Africa. The district is endemic of HIV and has a high prevalence of STIs. We did computer-assisted measurements of the ectocervical area covered by columnar epithelium (ectopy) in colposcopic images and STI analyses on cervicovaginal lavage and serum samples. All participating women answered a questionnaire about sexual behaviour and use of contraceptives. Results The mean age was 19.1 years. Ectopy was found in 27.2%, HIV in 27.8%, chlamydia in 25.3% and gonorrhoea in 15.6%. We found that age, parity, chlamydia and gonorrhoea, years since menarche, years since sexual debut and number of sexual partners were associated with ectopy. In multivariate analysis with chlamydia infection as the dependent variable, women with ectopy had increased odds of having chlamydia infection (adjusted OR 1.78, p=0.033). In women under 19 years of age, we found twofold higher odds of being HIV-positive for those with ectopy (OR 2.19, p=0.014). Conclusions In conclusion, cervical ectopy is associated with Chlamydia trachomatis infection and HIV in the youngest women

Genital schistosomiasis and its unacknowledged role on HIV transmission in the STD intervention studies

Treatment of sexually transmitted infections (STIs) has been hypothesised to decrease HIV transmission. Although observational studies show an association between STIs and HIV, only one prospective randomised controlled trial (RCT) has confirmed this. Female genital schistosomiasis can cause genital lesions, accompanied by bloody discharge, ulcers or malodorous discharge. Genital schistosomiasis is common, starts before puberty and symptoms can be mistaken for STIs. Three observational studies have found an association between schistosomiasis and HIV. Genital lesions that develop in childhood are chronic. This paper sought to explore the possible effects of schistosomiasis on the RCTs of STI treatment for HIV prevention. In the study sites, schistosomiasis was a likely cause of genital lesions. The studies recruited women that may have had genital schistosomal lesions established in childhood. Schistosomiasis endemic areas with different prevalence levels may have influenced HIV incidence in intervention and control sites differently, and some control group interventions may have influenced the impact of schistosomiasis on the study results. Schistosomiasis is a neglected cause of genital tract disease. It may have been an independent cause of HIV incidence in the RCTs of STI treatment for HIV prevention and may have obscured the findings of these trials. </jats:p

Schistosoma haematobium Infection and CD4+ T-cell levels: A cross-sectional study of young South African women

Schistosoma (S.) haematobium causes urogenital schistosomiasis and has been hypothesized to adversely impact HIV transmission and progression. On the other hand it has been hypothesized that HIV could influence the manifestations of schistosomiasis. In this cross-sectional study, we explored the association between urogenital S. haematobium infection and CD4 cell counts in 792 female high-school students from randomly selected schools in rural KwaZulu-Natal, South Africa. We also investigated the association between low CD4 cell counts in HIV positive women and the number of excreted schistosome eggs in urine. Sixteen percent were HIV positive and 31% had signs of urogenital schistosomiasis (as determined by genital sandy patches and / or abnormal blood vessels on ectocervix / vagina by colposcopy or presence of eggs in urine). After stratifying for HIV status, participants with and without urogenital schistosomiasis had similar CD4 cell counts. Furthermore, there was no significant difference in prevalence of urogenital schistosomiasis in HIV positive women with low and high CD4 cell counts. There was no significant difference in the number of eggs excreted in urine when comparing HIV positive and HIV negative women. Our findings indicate that urogenital schistosomiasis do not influence the number of circulating CD4 cells

Colourimetric image analysis as a diagnostic tool in female genital schistosomiasis

Female genital schistosomiasis (FGS) is a highly prevalent waterborne disease in some of the poorest areas of sub-Saharan Africa. Reliable and affordable diagnostics are unavailable. We explored colourimetric image analysis to identify the characteristic, yellow lesions caused by FGS. We found that the method may yield a sensitivity of 83% and a specificity of 73% in colposcopic images. The accuracy was also explored in images of simulated inferior quality, to assess the possibility of implementing such a method in simple, electronic devices. This represents the first step towards developing a safe and affordable aid in clinical diagnosis, allowing for a point-of-care approach

Effect of Female Genital Schistosomiasis and Anti-Schistosomal Treatment on Monocytes, CD4+ T-Cells and CCR5 Expression in the Female Genital Tract

Background Schistosoma haematobium is a waterborne parasite that may cause female genital schistosomiasis (FGS), characterized by genital mucosal lesions. There is clinical and epidemiological evidence for a relationship between FGS and HIV. We investigated the impact of FGS on HIV target cell density and expression of the HIV co-receptor CCR5 in blood and cervical cytobrush samples. Furthermore we evaluated the effect of anti-schistosomal treatment on these cell populations. Design The study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS. Methods Blood and cervical cytobrush samples were collected from FGS negative and positive women for flow cytometry analyses. Urine samples were investigated for schistosome ova by microscopy and polymerase chain reaction (PCR). Results FGS was associated with a higher frequency of CD14+ cells (monocytes) in blood (11.5% in FGS+ vs. 2.2% in FGS-, p = 0.042). Frequencies of CD4+ cells expressing CCR5 were higher in blood samples from FGS+ than from FGS- women (4.7% vs. 1.5%, p = 0.018). The CD14+ cell population decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043). Although the frequency of CD4+ cells did not change after treatment, frequencies of CCR5 expression by CD4+ cells decreased significantly in both compartments (from 3.4% to 0.5% in blood, p = 0.036; and from 42.4% to 5.6% in genital samples, p = 0.025). Conclusions The results support the hypothesis that FGS may increase the risk of HIV acquisition, not only through damage of the mucosal epithelial barrier, but also by affecting HIV target cell populations, and that anti-schistosomal treatment can modify this

Characteristics of Blood Vessels in Female Genital Schistosomiasis: Paving the Way for Objective Diagnostics at the Point of Care

Background The mucosal changes associated with female genital schistosomiasis (FGS) encompass abnormal blood vessels. These have been described as circular, reticular, branched, convoluted and having uneven calibre. However, these characteristics are subjective descriptions and it has not been explored which of them are specific to FGS. Methods In colposcopic images of young women from a schistosomiasis endemic area, we performed computerised morphologic analyses of the cervical vasculature appearing on the mucosal surface. Study participants where the cervix was classified as normal served as negative controls, women with clinically diagnosed FGS and presence of typical abnormal blood vessels visible on the cervical surface served as positive cases. We also included women with cervical inflammatory conditions for reasons other than schistosomiasis. By automating morphological analyses, we explored circular configurations, vascular density, fractal dimensions and fractal lacunarity as parameters of interest. Results We found that the blood vessels typical of FGS are characterised by the presence of circular configurations (p < 0.001), increased vascular density (p = 0.015) and increased local connected fractal dimensions (p = 0.071). Using these features, we were able to correctly classify 78% of the FGS-positive cases with an accuracy of 80%. Conclusions The blood vessels typical of FGS have circular configurations, increased vascular density and increased local connected fractal dimensions. These specific morphological features could be used diagnostically. Combined with colourimetric analyses, this represents a step towards making a diagnostic tool for FGS based on computerised image analysis