Schistosoma haematobium infection in the female genital mucosa: Immunohistochemical and clinicopathological analyses with respect to HIV target cells and vascularity in cervicovaginal tissue. Cross-sectional studies in Malawi and Madagascar.

Schistosomiasis is, after malaria, the most important parasite disease in terms of public health impact. Schistosoma haematobium infects millions of people through fresh water contact, especially in sub-Saharan Africa. Recent knowledge of the genital manifestations of schistosomiasis and the possible association with human immunodeficiency virus (HIV) infection, has led to increased focus on this common but neglected tropical disease. Antischistosomal treatment could potentially become an intervention point against HIV transmission. It is therefore imperative that the possible mechanisms by which female genital S. haematobium infection might influence HIV transmission is explored. S. haematobium infection is a frequent cause of mucosal pathology in the female genital tract. To our knowledge, this is the first study to perform systematic immunohistochemical analyses on S. haematobium infected female genital mucosa. This thesis presents the results of up-to-date immunohistochemical and image analyses of periovular mucosal blood vessels and HIV target cells, and of clinicopathological correlates in women with cervicovaginal S. haematobium infection in two cross-sectional studies in Malawi and Madagascar. In line with previous reports, we found a variety of tissue reactions to S. haematobium ova. Female genital mucosa infected with S. haematobium contained a higher density of HIV target cells, i.e. CD4+ T lymphocytes and CD68+ macrophages than uninfected mucosa. The infected genital mucosa was significantly more vascularised compared to healthy tissue. Clinicopathological analyses suggest that characteristic, abnormal mucosal blood vessels might be suggestive of a persistent tissue reaction to female genital S. haematobium ova, and that thrombosis might contribute to the pathogenesis. Finally, we developed a simple model for precise and efficient computer-assisted image analysis of immunostained tissue. In conclusion, the findings show that S. haematobium infected female genital mucosa may contain a higher density of HIV target cells and blood vessels than uninfected mucosa. Pathological changes in both acute and chronic tissue reactions to genital mucosal S. haematobium infection could facilitate cervicovaginal HIV transmission in women. Further studies are needed to explore the findings, and to provide clinical advice on the risks and effect of anti-schistosomal treatment on female genital schistosomiasis