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

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.DesignThe study followed a case-control design with post treatment follow-up, nested in an on-going field study on FGS.MethodsBlood 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).ResultsFGS 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).ConclusionsThe 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.

Genital inflammation, immune activation and risk of sexual HIV acquisition

“…Other possible causes of genital inflammation that may influence HIV risk include vaginal hygiene practices [80], exposure to seminal proteins [81], lubricants [82], hormone cycling [59], and genital schistosomiasis [83], as well as host genetics [84]. …”

Estrogen-like metabolites and DNA-adducts in urogenital schistosomiasis-associated bladder cancer

“…Indeed, the number of cases of infection with S. haematobium may far exceed that previously predicted so that urogenital schistosomiasis (UGS) may represent the most common infection or even adverse health condition in sub-Saharan Africa [6]. In addition, female genital schistosomiasis increases the risk of transmission of HIV [7][8][9], and a recent outbreak in Corsica confirms its re-emergence in Europe [10,11]. Many cases of UGS result ostensibly in only mild symptoms and disease such as hematuria, dysuria, anemia and inflammation of the genital-urinary tract [6,[12][13][14][15][16].…”

Inflammation and HIV Transmission in Sub-Saharan Africa

“…In addition, other endemic genital infections that are not sexually transmitted may influence regional disparities in HIV transmission. For instance, genitourinary schistosomiasis (which is generally caused by S. haematobium in SSA) causes clinical and immune alterations in the vagina that would be expected to increase HIV susceptibility [74] and that are reversible after specific therapy [75], while gastrointestinal S. mansoni infection clearly increases rectal SHIV transmission in a macaque model [76,77].…”