HIV target cells in Schistosoma haematobium-infected female genital mucosa

Abstract

The parasite Schistosoma haematobium frequently causes genital lesions in women and could increase the risk of human immunodeficiency virus (HIV) transmission. This study quantifies the HIV target cells in schistosome-infected female genital mucosa. Cervicovaginal biopsies with and without schistosomiasis were immunostained for quantification of CD4(+) T lymphocytes (CD3, CD8), macrophages (CD68), and dendritic Langerhans cells (S100 protein). We found significantly higher densities of genital mucosal CD4(+) T lymphocytes and macrophages surrounding schistosome ova compared with cervicovaginal mucosa without ova (P = 0.034 and P = 0.018, respectively). We found no increased density of Langerhans cells (P = 0.25). This study indicates that S. haematobium may significantly increase the density of HIV target cells (CD4(+) T lymphocytes and macrophages) in the female genitals, creating a beneficial setting for HIV transmission. Further studies are needed to confirm these findings and to evaluate the effect of anti-schistosomal treatment on female genital schistosomiasis.

Figure 1.

Computer-assisted image analyses of immune cells in genital mucosa. Top row: Low and high magnification of hematoxylin and eosin (HE)-stained female genital mucosa containing Schistosoma haematobium ova. All present ova are calcified (asterisks). Middle row: (1) In a subsequent section of the same biopsy as above, antibodies to CD3 identify mature T lymphocytes adjacent to calcified S. haematobium ova (asterisks). (2) Pixels representing immunohistochemically stained structures are isolated using their color properties. (3) Background noise is then removed to identify structures of interest only. (4) The measured structures are super-imposed on the original image for manual evaluation. The ruler line in picture 2 measures 0.1 mm. Bottom row: As middle row, CD8⁺ cells are identified by immunohistochemistry on the consecutive 3.5 μm thick section.

Figure 2.

Manual count of epithelial dendritic Langerhans cells. Low and high magnification of stratified squamous epithelium of the ectocervix and S100 protein-detected epithelial dendritic Langerhans cells (arrows); b = basal cell layer.

Figure 3.

The density of CD4⁺ T lymphocytes in each study group. The density of CD4⁺ T lymphocytes/mm² cervicovaginal stroma was significantly higher surrounding calcified Schistosoma haematobium ova compared with endemic and non-endemic tissue without ova (asterisk, P < 0.05). The whiskers represent the minimum and maximum values < 1.5 times the interquartile range (IQR), whereas the circles represent outliers (values > 1.5 times IQR). The most representative area for each biopsy was carefully selected by an experienced pathologist. In biopsies containing ova, the most representative high-power field surrounding the ova was analyzed. (1) Non-endemic = Norwegian (N = 45). (2) Endemic = Malawian (N = 29). (3) There were no significant differences between specimens with viable schistosome ova (N = 2) and the other study groups.