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

The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa

This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas. In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews.publishedVersio

Evaluating diagnostic indicators of urogenital Schistosoma haematobium infection in young women: A cross sectional study in rural South Africa.

BACKGROUND: Urine microscopy is the standard diagnostic method for urogenital S. haematobium infection. However, this may lead to under-diagnosis of urogenital schistosomiasis, as the disease may present itself with genital symptoms in the absence of ova in the urine. Currently there is no single reliable and affordable diagnostic method to diagnose the full spectrum of urogenital S. haematobium infection. In this study we explore the classic indicators in the diagnosis of urogenital S. haematobium infection, with focus on young women. METHODS: In a cross-sectional study of 1237 sexually active young women in rural South Africa, we assessed four diagnostic indicators of urogenital S. haematobium infection: microscopy of urine, polymerase chain reaction (PCR) of cervicovaginal lavage (CVL), urogenital symptoms, and sandy patches detected clinically in combination with computerised image analysis of photocolposcopic images. We estimated the accuracy of these diagnostic indicators through the following analyses: 1) cross tabulation (assumed empirical gold standard) of the tests against the combined findings of sandy patches and/or computerized image analysis and 2) a latent class model of the four indicators without assuming any gold standard. RESULTS: The empirical approach showed that urine microscopy had a sensitivity of 34.7% and specificity of 75.2% while the latent class analysis approach (LCA) suggested a sensitivity of 81.0% and specificity of 85.6%. The empirical approach and LCA showed that Schistosoma PCR in CVL had low sensitivity (14.1% and 52.4%, respectively) and high specificity (93.0% and 98.0, respectively). Using LCA, the presence of sandy patches showed a sensitivity of 81.6 and specificity of 42.4%. The empirical approach and LCA showed that urogenital symptoms had a high sensitivity (89.4% and 100.0%, respectively), whereas specificity was low (10.6% and 12.3%, respectively). CONCLUSION: All the diagnostic indicators used in the study had limited accuracy. Using urine microscopy or Schistosoma PCR in CVL would only confirm a fraction of the sandy patches found by colposcopic examination

Association of urogenital symptoms with history of water contact in young women in areas endemic for <i>S. haematobium</i>:a cross-sectional study in rural South Africa

Female genital schistosomiasis is a neglected tropical disease caused by Schistosoma haematobium. Infected females may suffer from symptoms mimicking sexually transmitted infections. We explored if self-reported history of unsafe water contact could be used as a simple predictor of genital schistosomiasis. In a cross-sectional study in rural South Africa, 883 sexually active women aged 16–22 years were included. Questions were asked about urogenital symptoms and water contact history. Urine samples were tested for S. haematobium ova. A score based on self-reported water contact was calculated and the association with symptoms was explored while adjusting for other genital infections using multivariable logistic regression analyses. S. haematobium ova were detected in the urine of 30.5% of subjects. Having ova in the urine was associated with the water contact score (p &lt; 0.001). Symptoms that were associated with water contact included burning sensation in the genitals (p = 0.005), spot bleeding (p = 0.012), abnormal discharge smell (p = 0.018), bloody discharge (p = 0.020), genital ulcer (p = 0.038), red urine (p &lt; 0.001), stress incontinence (p = 0.001) and lower abdominal pain (p = 0.028). In S. haematobium endemic areas, self-reported water contact was strongly associated with urogenital symptoms. In low-resource settings, a simple history including risk of water contact behaviour can serve as an indicator of urogenital schistosomiasis

Mapping Schistosoma haematobium for Novel Interventions against Female Genital Schistosomiasis and Associated HIV Risk in KwaZulu-Natal, South Africa

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HIV susceptibility related to HIV target cells and cervical ectopy. A study of young South African women living in a rural area endemic of urogenital schistosomiasis

More than 110 million Africans are estimated to be infected with Schistosoma (S.) haematobium, but it is still one of the so-called “neglected tropical diseases”. Poor countries bear the majority of the disease burden, contributing to the maintenance of the cycle of poverty. In Africa, women are at a higher risk of human immunodeficiency virus (HIV) infection than men, and this cannot be explained by behavioural factors alone. Biological risk factors seem to contribute to the differences in HIV prevalence between geographical regions and genders. This thesis will focus on female genital schistosomiasis and cervical ectopy, both factors hypothesised to facilitate the transmission of HIV through the genital mucosa. Genital schistosomiasis in women is characterized by lesions referred to as “sandy patches” that appear grainy or homogenous and are thought to be caused by the deposition of ova in the genital tissues. Sandy patches are often associated with abnormal mucosal blood vessels and contact bleeding due to the fragile mucosa. Cervical ectopy and female genital schistosomiasis (FGS) may be diagnosed by photocolposcopic examination, and both conditions are likely to be present before sexual debut. In addition to increased susceptibility to HIV infection, S. haematobium infection has been suggested to accelerate the progression of HIV infection, possibly through increased immune activation. In this study, South African women attending high schools in KwaZulu-Natal were included. Blood, urine and cervical lavage samples were collected and a photocolposcopic examination performed. We found that FGS was associated with a higher frequency of HIV target cells and HIV co-receptor expression in the genital compartment (the proportion of CD14+CCR5+ cells was higher in FGSpositive (FGS+) than FGS-negative (FGS-), p = 0.036) and in blood (both the proportions of CD14+ cells (p = 0.042), and CD4+CCR5+ cells (p = 0.018) were higher in FGS+). Furthermore, praziquantel treatment decreased the proportion of HIV target cells in FGS-positive women. Both the CD14+ cell population and CCR5 expression by CD4+ cells decreased significantly in both compartments after anti-schistosomal treatment (p = 0.043 and 0.025, respectively). We found no significant difference in CD4 cell counts in women with or without S. haematobium infection. Furthermore, we found that cervical ectopy was associated with the prevalence of chlamydia infection (adjusted OR 1.78, p = 0.033) and with HIV infection in the youngest study subjects (OR 2.19, p = 0.014). Future studies are needed to show whether treatment of schistosomiasis and/or intervention against cervical ectopy may become tools in the battle against the HIV epidemic

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

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