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

Kleppa E, Ramsuran V, Zulu S, Karlsen GH, Bere A, Passmore JA, Ndhlovu P, Lillebø K, Holmen SD, Onsrud M, Gundersen SG, Taylor M, Kjetland EF, Ndung’u T Journal title: PloS one PLoS ONE 2014;9(6):e98593 PMID: 24896815 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/24896815 Abstract 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...

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

Kjetland EF, Hegertun IE, Baay MF, Onsrud M, Ndhlovu PD, Taylor M Journal title: International journal of STD & AIDS Int J STD AIDS 2014 Sep;25(10):705-15 PMID: 24621458 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/24621458 Abstract 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....

Real-time polymerase chain reaction for detection of Schistosoma DNA in small-volume urine samples reflects focal distribution of urogenital Schistosomiasis in primary school girls in KwaZulu Natal, South Africa

Pillay P, Taylor M, Zulu SG, Gundersen SG, Verweij JJ, Hoekstra P, Brienen EA, Kleppa E, Kjetland EF, van Lieshout L Journal title: The American journal of tropical medicine and hygiene Am. J. Trop. Med. Hyg. 2014 Mar;90(3):546-52 PMID: 24470560 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/24470560 Abstract Schistosoma haematobium eggs and Schistosoma DNA levels were measured in urine samples from 708 girls recruited from 18 randomly sampled primary schools in South Africa. Microscopic analysis of two 10-mL urine subsamples collected on three consecutive days confirmed high day-to-day variation; 103 (14.5%) girls had positive results at all six examinations, and at least one positive sample was seen in 225 (31.8%) girls. Schistosoma-specific DNA, which was measured in a 200-μL urine subsample by using real-time polymerase chain reaction, was detected in 180 (25.4%) cases, and levels of DNA corresponded significantly with average urine egg excretion. In concordance with microscopic results, polymerase chain reaction results were significantly associated with history of gynecologic symptoms and confirmed highly focal distribution of urogenital schistosomiasis. Parasite-specific DNA detection has a sensitivity comparable to single urine microscopy and could be used as a standardized high-throughput procedure to assess distribution of urogenital schistosomiasis in relatively large study populations by using small sample volumes....

Cost-effectiveness of a community-based intervention for reducing the transmission of Schistosoma haematobium and HIV in Africa

Ndeffo Mbah ML, Kjetland EF, Atkins KE, Poolman EM, Orenstein EW, Meyers LA, Townsend JP, Galvani AP Journal title: Proceedings of the National Academy of Sciences of the United States of America Proc. Natl. Acad. Sci. U.S.A. 2013 May;110(19):7952-7 PMID: 23589884 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/23589884 Abstract Epidemiological studies from sub-Saharan Africa show that genital infection with Schistosoma haematobium [corrected] may increase the risk for HIV infection in young women. Therefore, preventing schistosomiasis has the potential to reduce HIV transmission in sub-Saharan Africa. We developed a transmission model of female genital schistosomiasis and HIV infections that we fit to epidemiological data of HIV and female genital schistosomiasis prevalence and coinfection in rural Zimbabwe. We used the model to evaluate the cost-effectiveness of a multifaceted community-based intervention for preventing schistosomiasis and, consequently, HIV infections in rural Zimbabwe, from the perspective of a health payer. The community-based intervention combined provision of clean water, sanitation, and health education (WSH) with administration of praziquantel to school-aged children. Considering variation in efficacy between 10% and 70% of WSH for reducing S. haematobium [corrected] transmission, our model predicted that community-based intervention is likely to be cost-effective in Zimbabwe at an aggregated WSH cost corresponding to US $725-$1,000 per individual over a 20-y intervention period. These costs compare favorably with empirical measures of WSH provision in developing countries, indicating that integrated community-based intervention for reducing the transmission of S. haematobium [corrected] is an economically attractive strategy for reducing schistosomiasis and HIV transmission in sub-Saharan Africa that would have a powerful impact on averting infections and saving lives....

S. haematobium as a common cause of genital morbidity in girls: a cross-sectional study of children in South Africa

Hegertun IE, Sulheim Gundersen KM, Kleppa E, Zulu SG, Gundersen SG, Taylor M, Kvalsvig JD, Kjetland EF Journal title: PLoS neglected tropical diseases PLoS Negl Trop Dis 2013;7(3):e2104 PMID: 23556009 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/23556009 Abstract BACKGROUND: Schistosoma (S.) haematobium infection is a common cause of genital morbidity in adult women. Ova in the genital mucosal lining may cause lesions, bleeding, pain, discharge, and the damaged surfaces may pose a risk for HIV. In a heterogeneous schistosomiasis endemic area in South Africa, we sought to investigate if young girls had genital symptoms and if this was associated with urinary S. haematobium. METHODOLOGY: In a cross-sectional study of 18 randomly chosen primary schools, we included 1057 schoolgirls between the age of 10 and 12 years. We interviewed assenting girls, whose parents had consented to their participation and examined three urines from each of them for schistosome ova. PRINCIPAL FINDINGS: One third of the girls reported to have a history of genital symptoms. Prior schistosomal infection was reported by 22% (226/1020), this was associated with current genital symptoms...

Pathologic mucosal blood vessels in active female genital schistosomiasis: new aspects of a neglected tropical disease

Jourdan PM, Randrianasolo BS, Feldmeier H, Chitsulo L, Ravoniarimbinina P, Roald B, Kjetland EF Journal title: International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists Int. J. Gynecol. Pathol. 2013 Jan;32(1):137-40 PMID: 23202777 Article on PubMed: http://www.ncbi.nlm.nih.gov/pubmed/23202777 Abstract Female genital schistosomiasis is a frequent, but neglected cause of mucosal pathology in the female genital tract. Moreover, recent studies indicate that genital mucosal lesions may increase the risk of human immunodeficiency virus (HIV) infection. In rural Africa, detailed clinical images are rarely available alongside histologic sections, and further understanding of the pathogenesis of the genital mucosal lesions is needed. These cases represent previously unreported histopathologic photomicrographs and corresponding clinical images in 2 women with genital schistosomiasis. Dilated and tortuous mucosal venules seen in the cervicovaginal mucosa were found to contain viable Schistosoma haematobium eggs surrounded by a thrombus. The presence of abnormal mucosal blood vessels may be an indication of a persistent tissue reaction to S. haematobium ova in the lower female genital tract....