Genital schistosomiasis

This page is under construction

= WOMEN =

Manifestations of genital schistosomiasis - mucosal findings in women
Mucosal grainy sandy patches seem to be pathognomonic for S. haematobium infection in the female genitals [1,2]. S. haematobium infection probably also causes mucosal bleeding and inflammation. Grainy sandy patches are significantly associated with S. haematobium ova only (OR 4.89, 95%CI 2.14-11.17, p<0.001). Genital S. haematobium ova are also significantly associated with homogenous yellow sandy patches in genital mucosa (OR 2.94, 95%CI 1.35-6.44, p=0.007), mucosal bleeding (OR 8.13, 95%CI 2.01-32.9, p=0.003), and abnormal blood vessels (OR 5.16, 95%CI 2.04-13.07, p=0.001). The three latter phenomena are however also associated with other reproductive tract diseases. Ova presence is not a predictor for ulcers, papillomata, leukoplakia, polyps, or cell atypia. The findings are the same in all adult age groups indicating that genital lesions do not undergo a change with age, or that women by the age of 20 have already passed into a chronic state of infection. The full clinical significance of genital schistosomiasis is yet to be established. The concomitant blood vessel friability and inflammation may give weight to the circumstantial evidence for bi-directional transmission of HIV.

Epidemiology of gynecological schistosomiasis
It has been estimated that 9-13 million women have genital schistosomiasis [44-46]. Up to 75% of the women excreting S. haematobium ova in the urine may have schistosome ova in the uterine cervix, vagina or vulva [5-12, 47, 48]. Furthermore, women reportedly have genital schistosomiasis, even without urinary schistosomiasis [17, 18]. Studies in Tanzania and Zimbabwe have shown that up to 41% of women may have involvement of the lower reproductive tract without schistosome ova in the urine [36, 48, 49]. However, genital schistosomiasis, as a cause of morbidity, is only rarely accounted for in overview publications, although there are a few exceptions [37, 50].

Localisation in the genital tract
S. haematobium oviposition may be distributed in pathophysiologically vital areas in the pelvis [9, 51]. Post mortem studies and histopathological material from surgery in the reproductive tract, have shown that S. haematobium may be distributed in all the pelvic organs. As shown in Table 1 ova are most commonly found in the cervix [52, 53], followed by the vagina, ovaries [54-57], Fallopian tubes [52, 58], vulva, and also, albeit rarely, in the uterus [6-10, 52, 59, 60]. There are only a few case reports of severe acute disease such as ascites with ovarian schistosomiasis, ectopic pregnancy, and heavy infestation of the uterus in pregnancy [56, 57, 61-65].

Laboratory diagnosis in lower genital tract
The crushed biopsy of genital tissue is deemed to be the golden standard for the parasitological diagnosis of genital S. haematobium [41, 193]. However, the ova are located in highly focal clusters and one may miss them, especially with histological sectioning of a biopsy [8, 12, 16]. Moreover, women in parts of the schistosomiasis and HIV endemic areas might neither have a choice of whether to have intercourse nor the courage to suggest use of a barrier contraceptive method [194]. Hence, taking a biopsy for the diagnosis of genital S. haematobium remains an HIV transmission risk for the patient and her partner until the inflicted wound has healed, raising ethical concern [192].

Wet smears and PAP smears make a contribution to the diagnosis but the sensitivity is low [193]. In a cytology laboratory in Harare, Zimbabwe 44/1901 Pap smears were found positive, whilst in Kampala, Uganda only 1/30.000 smears were found to be S. haematobium ova positive [12, 16, 42, 195-197]. Urinary filtration [198] or dipsticks [199] are insensitive indicators for genital S. haematobium. Moreover, the techniques themselves have been proven to be of poor value, or not tested, in females of fertile age [199, 200]. Increased levels of eosinophil cationic protein, Neopterin or IgA in cervico-vaginal lavage have only limited value in the diagnosis of female genital schistosomiasis [30, 42, 47, 72, 75, 201-203].

The tricky topic of treatment
For clearance of urinary ova excretion and reduction of morbidity, a single oral dose of praziquantel 40 mg/kg, or 60mg/kg in 2 divided doses is recommended, with food and drink in order to minimise gastrointestinal side effects [204-208]. Based on a number of reports, WHO has decided to also recommend praziquantel to pregnant and lactating women [208-211]. Treatment for urinary schistosomiasis has been found equally effective in HIV positive and negative [212]. Praziquantel does not seem to influence plasma HIV viral load in S. mansoni infected individuals [213].

Only one study has directly explored treatment of genital schistosomiasis [214]. Although urinary ova excretion decreased following treatment (OR, 10.3 95% CI 3.8-27.8, p<0.001), praziquantel was not associated with a significant reduction in genital lesions or contact bleeding (p=0.31-0.94). Sandy patches remained strongly associated with contact bleeding and vessel abnormalities even after treatment. Findings were independent of HIV status. Such lesions, common, and apparently refractory to treatment for at least 12 months, may be an important risk factor for both the acquisition and transmission of the human immunodeficiency virus in sexually active women.

In the urinary tract the effect of praziquantel has largely been determined by resolution of lesions detectable by ultra sound scan and decreased ova excretion in urine [180]. Sandy patches in the bladder have been found post-mortem, in surgical specimens or as seen by cystoscopy [15, 184, 187, 188, 214, 215], but there have been no large-scale cystoscopic studies on the natural course of sandy patches or effect of praziquantel on the clinical morphology of bladder lesion [180, 186]. The outcome of treatment in the urinary tract may be variable, depending on four factors: (1) the age of patient, (2) the pre-treatment intensity of infection, (3) the degree of fibrosis or calcification, and (4) the site of the lesion. The urinary tract lesions in younger patients are more responsive to treatment [21, 176, 216], this may be so in the genital tract as well [179]. However as mentioned previously, given the same age group and exposure rates, lesions in the bladder decrease faster than lesions in the upper ureteres after treatment [174-177, 183]. Hence, effect of treatment in the urinary tract cannot automatically be extrapolated to the genital tract.

Praziquantel, which kills the mature worm, is standard treatment for all types of schistosomiasis and there will be a decrease in S. haematobium ova excretion in urine 4-26 weeks after treatment [169, 217]. Occasionally repeated courses are be necessary to cure S. haematobium in the urinary tract, even in children and sometimes in returned travellers long after the worm should have matured [175, 218, 219]. Case reports indicate that praziquantel may have an immunomodulatory effect on lesions so that lesions resolve [220, 221]. However, although praziquantel kills the egg-laying worms, lesions – not yet visible – may develop around ova already deposited in tissues. Once ova deposition has occurred in the cervix, ova excretion and lesion development are two independent processes, praziquantel affecting the former almost immediately, but possibly not the latter [15, 20, 176, 188].

Egg excretion in urine of lesions in genital mucosa are not directly comparable and little is known about the effect of treatment in the genital tract [180]. Prior to the current Zimbabwean study, there had been no longitudinal study and only some few case reports on effect of treatment of genital schistosomiasis [57, 86, 189]. The case reports describe regression of sandy patches in the lower genital tract schistosomiasis after treatment with praziquantel, in the course of 1 week to 6 months. After less than 2 years, treatment has been described to resolve schistosomal infertility (with pregnancy) in up to 6 of 13 infertile women [97, 222].

It has been hypothesised (and debated) that the release of worm fragments upon death enhances immunological protection against reinfection, and possibly also removes the immunosuppressive effect of the adult worm [223-227]. Moreover, there is a second effect on transmission. By interfering with the cycle (Figure 2), there will be decreased infection of the snails and decreased excretion of cercaria and infection of humans, especially if mass chemotherapy is carried out in the low transmission season [205, 228, 229].

Other forms of treatment such as arthemeter (recently tested), metrifonate (for S. haematobium, recently withdrawn from the market), niridazole, oxamniquine, hycanthone, amoscanate, and antimony (no longer in use for schistosomiasis) will not be discussed here [217, 230, 231].

WHO has recommended mass treatment for women and children in schistosomiasis-endemic areas in order to prevent long-term morbidity [175, 208]. This is often done through schools, most often with the active participation of the teaching staff. Mass treatment has been recommended for 6-months to 3-years intervals depending whether there is a continuous high or seasonal low transmission, more often with the former [183, 208, 228, 232, 233]. However, studies have found that prevalence of schistosomiasis is higher in non-enrolled children [234]. Moreover, girls are often underrepresented in schools and in an Egyptian study it was estimated that 59% of the boys, but only 18% of the infected girls were reached through the school programmes [208].

Travelling women and genital schistosomiasis
Travellers are defined as coming from non-endemic areas, exposed for a limited time whereupon they return to a non-endemic site. Schistosomiasis, and in particular genital schistosomiasis, have been neglected in travellers, despite the risk of infection with certain types of increasingly common travels such as rafting, and other forms of so-called eco-tourism [92-95]. Eighteen percent of asymptomatic travellers to Africa, exposed to freshwater and subsequently screened at The Hospital for Tropical Diseases in London, were found to have schistosomiasis [96]. Katayama fever, fatigue, and dysuria are the commonest presentations in symptomatic travellers. There are, however, a few case reports where genital schistosomiasis has been found, years after reasonably short exposure.

''The manifestations of schistosomal disease in ‘non-genital’ organs, immunological considerations, immunodiagnosis, S. haematobium parasite adeptness, snail control, and schistosomiasis’ relationship with cancer are beyond the scope of this article. Although S. mansoni, S. intercalatum, S. japonica and S. matthei may affect the genital organs, the magnitude of the problem is not known, and they will not be discussed in this manuscript [26-32].''