Schistosomiasis is ranked by the WHO as the third most devastating parasitic disease in tropical areas (World Health Organization (WHO), 2010). About 20 million women worldwide have this disease (Friedman et al., 2007; Yirenya-Tawiah et al., 2011). Some postmortem studies found histological evidence of female genital schistosomiasis (FGS) in 3–10% of the cases (Friedman et al., 2007). In Africa, 9–13 million women may be affected (Poggensee and Feldmeier, 2001). Although considerable progress has been achieved in the research of schistosomiasis, FGS had been neglected. The Gender Task Force of WHO’s Tropical Diseases Program (2007) had included FGS in ‘the list of scientific areas which deserve a high research priority.’ The actual morbidity of FGS on maternal health and birth outcomes has still not been estimated properly (Yirenya-Tawiah et al., 2011). FGS represents a significant public health problem affecting sexual, reproductive, and maternal ill-health (World Health Organization (WHO), 2007).
Historical background of bilharzial infestation in Egypt
Schistosomal ova were found in Egyptian mummies dating back to 1200 BC and in the hieroglyphic Kahun and Ebers Papyri dating back to 1900 and 1500 BC (Shokeir and Hussein, 1999). It is believed that Napoleon and his soldiers contracted schistosomiasis during the 3-year French invasion of Egypt (Ayer, 1996). Theodor Bilharz identified the parasite, in Egypt, and was named after him (Fig. 1). The eponymic name bilharziasis is the synonym of schistosomiasis.
Female genital schistosomiasis
FGS was reported for the first time in by Madden (1899) and Petrides (1899). Since then, extensive gynecological and pathological studies have been carried out. Gelfand et al. (1971) previously concluded that ‘if a patient has urinary bilharziasis, the probability is that she will have ova of Schistosoma hematobium in some portion of the genital tract.’
Previous epidemiological studies from Egypt and worldwide have shown that genital lesions as a result of FGS are due to S. hematobium in 50–80% of women (Feldmeier et al., 1998). Some reports have indicated that 74–88% and 12–26% of FGS could be due to S. hematobium and Schistosoma mansoni, respectively (Feldmeier et al., 1998). In a pilot study conducted to identify FGS in an Egyptian hamlet, half of the women studied were found to have FGS with its associated reproductive health morbidity (Talaat et al., 2004). This study confirmed that relatively high levels of S. hematobium infestation still exist in Egypt, with persistent infection in remote areas, continuous transmission, and high levels of re-infection (Talaat et al., 2004). The topographic sites, most commonly, are the vagina and cervix, followed by the ovaries and very rarely the endometrium, tubes, and the pelvic peritoneum (Chitsulo et al., 2000).
The diagnosis of FGS is usually made incidentally by histopathological examination of colposcopic or laparoscopic biopsies (Poggensee and Feldmeier, 2001). It should be suspected after a careful clinical assessment, also taking into consideration the travel history or residence in endemic areas. The gold standard for the diagnosis of FGS is the quantitative compressed biopsy technique (Poggensee and Feldmeier, 2001). Additional supportive laboratory evidence may include peripheral-blood eosinophilia, anemia, or hypergammaglobulinemia with elevated renal function tests (Chitsulo et al., 2000).
The standard of care for the treatment of FGS is a single dose of the antiparasitic drug praziquantel at a dose of 40 mg/kg (Yirenya-Tawiah et al., 2011). However, long-standing cases of FGS with adhesions may need surgery, with or without IVF treatment.
Interaction with other infectious diseases, namely the oncogenic human papillomavirus (HPV) and HIV, is of great scientific interest. FGS seems to favor persistent genital HPV infection either by traumatizing the genital epithelium and/or by local immunosuppression (Mosunjac et al., 2003). Vulval schistosomiasis may also contribute to the transmission of HIV (Mosunjac et al., 2003). Moreover, recently, it has been pointed out that schistosomiasis of the cervix, with or without concomitant HPV infection, has to be considered a risk factor for the development of cancer of the cervix (Mosunjac et al., 2003).
The aim of the current study was to record some cases of FGS with unusual presentations in an attempt to direct attention to this preventable and treatable disease in an endemic area like Egypt.
The first case was that of a 31-year-old housewife who was referred to the outpatient infertility clinic with a history of primary infertility for 10 years. Two years back, the patient had undergone laparoscopy and was diagnosed as having a ‘bilateral distal tubal block, most probably tuberculous in origin.’ No biopsy was taken at that time to confirm this diagnosis. The patient was then given combined antituberculous treatment for 9 months. She had regular ovulatory cycles and a normal hormonal profile. Her husband had a normal semen analysis result and was generally healthy.
A pelvic ultrasonography showed an associated right side unilocular ovarian cyst 8×7 cm in size. Laparoscopy was carried out with the aim of removing the ovarian cyst and confirming the current tubal pathological condition to decide on the expected benefits from surgery versus assisted reproduction techniques.
On laparoscopy, a simple serous ovarian cyst was identified, aspirated, and then removed completely. The fallopian tubes were bilaterally tortuous and kinked with adhesions between the distal ends and the ipsilateral ovary and the pelvic floor. The pelvic peritoneum covering the pouch of Douglas, the broad ligaments, and the tubes were covered with small grayish nodules that were provisionally thought to be tubercles. Multiple peritoneal punch biopsies were taken together with an endometrial biopsy.
The histopathology report indicated a diagnosis of ovarian serous cystadenoma, simple proliferative endometrium, chronic salpingitis, and disseminated bilharzial granulomata of the pelvic peritoneum with evidence of S. hematobium ova in the center. The case was established as disseminated peritoneal S. hematobium associated with salpingitis (Fig. 2).
The second case was that of a 34-year-old housewife who was referred to the Gynecology outpatient clinic with a painless pelvic mass accidentally discovered during infertility workup. She was generally healthy, and had regular and normal menstrual periods. Transvaginal ultrasonography revealed a 9×8 cm pelvic mass with solid components. Her blood count and CA-125 level were normal. Computed tomography revealed a right tubo-ovarian mass, mostly neoplastic. She underwent an exploratory laparotomy and unilateral adnexectomy. The histological examination of the specimen revealed chronic salpingitis with a localized serosal mass composed of a large number of S. hematobium ova in a fibrous stroma surrounded by chronic inflammatory cells. The case was established as right mesenteric bilharzioma (Fig. 3).
The third case was that of a 30-year-old woman who presented to our outpatient infertility clinic with infertility of 5 years’ duration. She had regular periods, with severe dysmenorrhea. Her periods had been progressively becoming lighter over the last 2 years. Her basal hormone profile and hysterosalpingography results were normal but the endometrial thickness on midcycle ultrasound scanning was much thinner than expected for that date. Diagnostic hysteroscopy was carried out and revealed patches of scarring. Endometrial biopsy was taken and was diagnosed histopathologically as schistosomal endometritis (Fig. 4).
The fourth case was that of a 22-year-old, recently married housewife. She presented to the Gynecology outpatient clinic with complaints of vaginal discharge and postcoital bleeding. On ultrasonography, the uterus and ovaries were normal. On hysteroscopy, an endocervical polyp was found and excised. Histopathological examination showed a polyp lined by endocervical epithelium and showing surface ulceration. The fibrovascular core showed numerous ova of S. hematobium and a mild mononuclear cell infiltrate. The case was established as a bilharzial endocervical polyp (Fig. 5).
The fifth case was that of a 26-year-old woman from a rural area in Southern Egypt. She presented to the Gynecology emergency room with a complaint of acute abdominal pain. She was a primigravida, 7 weeks pregnant.
Initial assessment revealed that the patient was normotensive but pale and tachycardic. Abdominal examination revealed rebound tenderness on the left lower quadrant. Pelvic ultrasonography revealed an empty uterine cavity and free fluid in the pouch of Douglas. A decision was made to proceed with a midline exploratory laparotomy.
On laparotomy, 2 l of blood was drained from the abdomen. The left fallopian tube was covered with omental adhesions. It was ruptured because of an ectopic gestational sac and it had to be removed, together with part of the adherent omental layer. Histopathological examination of the sections from mesentery adherent to the fallopian tube revealed a localized mass composed of inflammatory cells, fibrosis, and many bilharizial ova (Fig. 6).
The first case was diagnosed as having disseminated peritoneal S. hematobium associated with chronic salpingitis. Although bilharzial salpingitis has been described in previous case reports (Ekoukou et al., 1995; Schroers et al., 1995; Schanz et al., 2010), this is the first report, to our knowledge, of a case of disseminated peritoneal S. hematobium. Disseminated peritoneal Schistosoma japonicum, but without associated gynecological manifestations, has been reported by Al-Waheeb et al. (2009).
The second case was referred with a provisional diagnosis of ‘ovarian neoplasm’. Histopathological examination confirmed the diagnosis of iliac bilharzioma. A case of a Filipino woman with upper genital schistosomiasis mimicking an ovarian tumor has been previously reported by Al-Waheeb et al. (2009). Although bilharzioma has been previously reported in several sites such as the kidneys (n=2) (Amhajji et al., 2003; Diallo et al., 2011), ureters (n=1) (Fischel, 1973), urinary bladder (n=15) (Pieron et al., 1983; Fievet et al., 1985), epididymis (n=1) (Fievet et al., 1985), verumontanum causing azoospermia (n=1) (Fourcade et al., 1977), lung (n=3) (Thompson et al., 1979; Besson et al., 1982; Rakotovao et al., 2005), small intestine (n=1) (Ali et al., 2003), rectosigmoid (n=3) (Elmasalme et al., 1997; Digray, 1998; Vaid et al., 2011), gall bladder (n=1) (Ibrahim et al., 1977), and the epidural space (n=2) (Ruberti and Saio, 1999; Maia et al., 2007), no cases of mesenteric bilharzioma have been reported.
The third case was diagnosed as bilharzial endometritis. Endometrial scarring is a cause of infertility and its thickness is an important predictor for the success of IVF cycles (Shufaro et al., 2008). In this case, the endometrial thickness was only 5 mm. This demonstrates the heavy burden of a treatable disease such as schistosomiasis on reproductive health. Endometrial schistosomiasis is a rare event. Only five cases have been reported in the medical literature (Sugiyama et al., 1963; Le Guyader et al., 1965; Billy Brissac et al., 1994; Boers et al., 2003). Herein, we report on the sixth case of schistosomal endometritis. As in our case, abdominal hysterectomy was performed in some of these aforementioned cases because of complaints of dysmenorrhea and severe menorrhagia.
The fourth case presented with recurrent contact bleeding, resulting in marital problems. Kjetland et al. (2008) had addressed the importance of childhood antischistosomal treatment in the prevention of gynecologic contact bleeding and genital sandy patches. There is a postulated relationship between schistosomiasis, HPV, HIV, and cervical neoplasia (Mosunjac et al., 2003). Prabhakaran and Brown (2004) recommended a vigilant search for schistosoma ova in the cervical biopsies of patients from endemic areas. The lesions in the lower reproductive tract are not pathognomonic (Prabhakaran and Brown, 2004). FGS may mimic any infectious or malignant condition found in the vagina or the cervix (Poggensee and Feldmeier, 2001). Schistosomiasis of the lower genital tract is usually presented as sandy patches, leukoplakia, and cervical erosion (Poggensee and Feldmeier, 2001). The formation of an endocervical polyp, as in our case, was only reported previously in two case reports (Badiale et al., 2005; Vilar et al., 2007).
The fifth case had a life-threatening peritoneal hemorrhage. Five cases of ectopic pregnancies, associated with FGS, have been previously reported (Bugalho et al., 1991; Mohammed et al., 2004). Furthermore, infestation of the placenta may cause stillbirth, miscarriage, premature labor, or intrauterine growth restriction (Friedman et al., 2007). In a previous study, it was observed that women with urinary schistosomiasis, without necessarily presenting evidence of genital involvement, showed a significantly higher proportion of preterm deliveries and the birthweight of their children was lower than that of noninfected women.
It should always be kept in mind that schistosomal salpingitis and peritonitis are causes of infertility and ectopic pregnancies. In a previous study, 0.9% of 434 patients who had undergone videolaparoscopy for infertility had FGS (Schanz et al., 2010).
It is evident from our reported cases that the clinical manifestations of FGS are nonspecific. They can include otherwise unexplained infertility, ectopic pregnancy, irregular bleeding, or discharge, dyspareunia, pelvi-abdominal pain or tenderness, and/or tubo-ovarian masses. The signs and symptoms of chronically infested women may be minor or completely subclinical (Yirenya-Tawiah et al., 2011). Symptoms may mimic cervical cancer and sexually transmitted diseases (Yirenya-Tawiah et al., 2011).
Histopathologically, the ova induce perioval granulomas resulting in fibrosis and adhesions. The histopathological sequel of schistosomiasis in the genital tract has not been precisely determined (Feldmeier et al., 1998). Nosny (1963) reviewed histological sections from surgical specimens and concluded that the type of tissue reaction depended on the topographic site affected. In a comprehensive study by Helling Giese et al. (1996) of S. hematobium-infected women, two opposing spectra of inflammatory responses were observed. The first spectrum was characterized by a diffuse infiltration of plasma cells, lymphocytes, eosinophils, and macrophages, mostly around viable ova. The second spectrum was characterized by minimal cellular infiltrate and ‘scar tissue’ predominantly observed around nonviable or calcified ova. Surprisingly, the different histological types may be simultaneously present in the same patient (Helling Giese et al., 1996). In the current study, cases 1, 2, and 5 demonstrated the first spectrum (Figs 2, 3 and 6) and cases 3 and 4 (Figs 4 and 5) demonstrated the second spectrum. Moreover, histopathological studies have reported that the reaction of the genital tissue around S. hematobium and S. mansoni ova differed from the typical perioval granuloma seen in the liver, rectum, or bladder (Helling Giese et al., 1996). This was very typical in the histopathological findings obtained in our cases (Figs 2–6).
FGS is a serious health risk to women of reproductive age living in endemic areas. It may lead to infertility, ectopic pregnancy, poor pregnancy outcome, irregular vaginal bleeding or discharge, dyspareunia, pelvic abdominal pain or tenderness, and/or tubo-ovarian masses. Bilharziasis should be considered as a potential disease of the genital tract and not only as a urinary or an intestinal tract disease. From recent community-based studies, it has been documented that FGS has a high burden of morbidity on female health worldwide.
Conflicts of interest
The authors confirm that this material is totally original; it has not been published or submitted for publication elsewhere. None of the authors have any competing financial interests to disclose or any actual or potential commercial associations that might create a conflict of interest in connection with the submitted manuscript.
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