Gabriele Poggensee

FEMALE GENITAL SCHISTOSOMIASIS: FACTS AND HYPOTHESES

In this paper we summarise the parasitological, clinical and epidemiological characteristics of female genital schistosomiasis (FGS), a frequent manifestation of the infection with Schistosoma haematobium. Means to diagnose and treat lesions in the lower and upper genital tract are discussed. Based on clinical findings and available pathophysiological as well as immunological data it is conceivable that FGS of the cervix and vagina not only facilitates the infection with agents of sexually transmitted diseases, but presumably also alters the natural history of such infections. Two infectious agents are of particular concern: the Human Immunodeficiency Virus and the oncogenic Human Papilloma Viruses. Possible interactions and their consequences are discussed and research areas which should be addressed are outlined.

Female Genital Schistosomiasis of the Lower Genital Tract: Prevalence and Disease-Associated Morbidity in Northern Tanzania

Female genital schistosomiasis (FGS) is a neglected disease manifestation of schistosomiasis. A cross-sectional study was carried out to assess in a schistosomiasis-endemic area the proportion of women affected by FGS of the lower reproductive tract and to compare the frequency of symptoms and signs possibly associated with FGS between women with proven FGS (n=134), endemic referents (n=225, women living in an endemic site), and referents (n=75, women living in a nonendemic site). Urinary schistosomiasis was diagnosed in 36% (239/657) and FGS in 37% (134/359) of the women. Cervical lesions occurred in 75% of the FGS cases, in 48% of endemic referents, and in 36% of nonendemic referents. The high prevalence of FGS in all age groups and the high levels of pathologic cervical alterations such as swollen and disrupted epithelium support the hypothesis that FGS might be a risk factor for the transmission of human immunodeficiency virus.

Schistosomiasis of the Female Genital Tract: Public Health Aspects

In this paper Gabriele Poggensee, Hermann Feldmeier and Ingela Krantz discuss the public health relevance of female genital schistosomiasis (FGS). Some of the stated hypotheses are supported only by clinical observations and/or circumstantial evidence as valid epidemiological and immunological data of this disease entity are still very scanty. Morbidity caused by the presence of schistosome eggs in the lower and upper genital tract have been almost completely neglected during the past two decades. This has been acknowledged by the WHO and, in 1997, the Gender Task Force of the WHOs Tropical Disease Research Programme (TDR) included FGS in a list of scientific areas that deserve high research priority.

Seroepidemiology of TT virus, GBC-C/HGV, and hepatitis viruses B, C, and E among women in a rural area of Tanzania.

The seroprevalence and determinants of hepatitis B, C, and E virus infection, and of GBV‐C/hepatitis G virus and TT virus infection were investigated among women from a rural area of northeastern Tanzania. High seroprevalence rates were found for TTV (74%), HBV (74%), and GBV‐C/HGV (35%), whereas 7% of the women had evidence of HCV and HEV infection. The majority of TTV DNA sequences in the study population belonged to the genotypes 1 or 2. One sequence seems to represent a new subtype of genotype 4. The GBV‐C/HGV sequences either belonged to the genomic Group 1b or to the recently described Group 4. In multivariate analysis, the detection of TTV DNA was associated significantly with a larger number of children in the household and with older age. A history of injections of contraceptive hormones was an independent risk factor for HCV infection. The findings on TTV are consistent with fecal‐oral transmission, and recurrent infections may occur in adults. J. Med. Virol. 62:524–530, 2000.

Editorial: Male genital schistosomiasis and haemospermia

Haemospermia, the presence of blood in the ejaculate, is caused by a variety of conditions involving the accessory sexual glands or their ducts, the urethra or the bladder. The more common causes of haemospermia include prostatitis, seminal vesiculitis, calculi, varices or cysts of the prostate or of the seminal vesicles, benign prostatic hyperplasia, hypertension, trauma and, rarely, prostatic cancer (Jones 1991; Amano et al. 1994; Mulhall & Albertsen 1995; Munkelwitz et al. 1997). In younger men, haemospermia is often due to infection or inflammatory processes of the prostate or seminal vesicles (Jones 1991; Mulhall & Albertsen 1995). Although causing great anxiety, it is usually a benign and transient condition. Conversely, the presence of haemospermia in older men may indicate a more serious pathology which warrants extensive investigations (Jones 1991; Mulhall & Albertsen 1995). Presumably, the epidemiology of haemospermia is different in other parts of the world, especially in sub-Saharan Africa. Here, genito-urinary schistosomiasis due to S. haematobium and, to a lesser extent, S. mansoni, is a common infection in both males and females. An estimated 200 million people are affected in 48 countries in Africa alone (WHO 1993). Male genital schistosomiasis (MGS) was first described in 1911 in a patient presenting with haemospermia as the predominent symptom (Madden 1911). In 1944, Claude Barlow (who had earlier auto-infected himself with Fasciolopsis buski) performed a self-experiment with S. haematobium. Over 21 days he placed 224 cercariae on his forearm. Eleven weeks later, Barlow developed fever, eggs appeared in his seminal fluid, the ejaculate turned brownish and spermatozoa were present in his urine (Barlow & Meleney 1949). Since then, MGS has been observed by clinicians and pathologists in many S. haematobium-endemic areas. Accordingly, in the 1960s the disease caused by S. haematobium was referred to as genito-urinary schistosomiasis, reflecting the importance of genital involvement induced by this species (Manson-Bahr 1967). Thereafter, this aspect of schistosomal infection seems to have lost medical importance and awareness. Some recent data exist on the morbidity due to female genital schistosomiasis (FGS), but only one systematic study on the infection of genital organs in men has been conducted (Feldmeier et al. 1996, 1997; Leutscher et al. 1999; Poggensee et al. 1999, 2000). Moreover, FGS was recently acknowledged as a potential risk factor for the transmission of HIV, while the role of MGS regarding HIV transmission has not yet been defined (Feldmeier et al. 1994, 1995). Postmortem histopathological studies have shown that in patients infected with S. haematobium the seminal vesicles and the prostate are as frequently affected by egg-induced lesions as the urinary bladder (Edington et al. 1970; Gelfand et al. 1970; Patil & Elem 1988). The intensity of infection, however, as reflected by the number of schistosomal eggs per gram of tissue, was higher in the bladder than in other organs of the genito-urinary tract (Gelfand et al. 1970). Using extensive histological sectioning, Patil and Elem (1988) concluded that in the prostate eggs were predominantly scattered in the stroma, whereas in the seminal vesicles all layers were similarly affected and eggs were even present in the lumen. The seminal vesicles showed signs of inflammation more often than the prostate and the spermatic cord was affected by sclerosing endophlebitis, conditions which may lead to haemospermia (Gelfand et al. 1970; El Badawi et al. 1979). At a relatively young age (14–30 years) inflammatory reactions were observed in up to 36% of autopsy cases, whereas in older patients local infiltration by inflammatory cells occurred in only 13% (Gelfand et al. 1970). Using ultrasonography, morphological alterations of the prostate and the seminal vesicles such as enlargement, fibrosis and calcification may easily be visualized (Fataar et al. 1990; Corachan et al. 1994; Vilana et al. 1997). Interestingly, the symptom of haemospermia has never been reported from morbidity studies in S. haematobiumendemic areas and is not even mentioned in current textbooks on tropical medicine. The simple explanation may be that haemospermia, in contrast to haematuria, usually occurs unnoticed and can only be diagnosed when it is TMIH511

Puberty and Age-intensity Profiles in Schistosome Infections: Another Hypothesis

In an excellent focus article on puberty and age-related changes in susceptibility to schistosome infection, Fulford et al.[1xFulford, A.J.C. et al. Parasitol. Today. 1998; 14: 23–26Abstract | Full Text | Full Text PDF | PubMed | Scopus (91)See all References[1]provide a new explanation for the characteristic age-intensity profile in areas where schistosomiasis is endemic. An age-dependent host factor seems to override—at least during adolescence—the variation in intensity of infection expected both from the variability of exposure with changing age and from the dynamics of acquired immunity. Fulford and colleagues put forward the hypothesis that physiological changes in the production of sex hormones could be one explanation. The authors explore how sex hormones might exert a regulatory effect on the immune system, eventually leading to an increased resistance to infection. Other modes of action by which sex hormones, particularly in females, may influence parasites are only mentioned briefly, but not commented on.Pelvic vascularization alters when girls enter puberty, resulting in multiple anastomoses between the rectal and the vesical plexus, and between the plexus of external and internal genital organs[2xSee all References, 3xSee all References]. These adaptive changes are accentuated during pregnancy. As adult worms tend to migrate, the adaptive changes in pelvic vascularization add to the chance that parasites reach the adjacent vascular beds, thereby increasing the probability of a settlement in female genital organs. In fact, at least in Schistosoma haematobium infection, involvement of external and internal genital organs is extremely common. Of women infected with this parasite species 40–80% are considered to have manifestations in the lower reproductive tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References, 5xKjetland, E. et al. Acta Trop. 1996; 62: 239–255Crossref | PubMed | Scopus (65)See all References, 6xLeutscher, P. et al. Acta Trop. 1997; 66: 27–34Crossref | PubMed | Scopus (27)See all References]. How many women also have worms located in the internal genital organs is unknown; post-mortem studies in female schistosomiasis patients, however, show that the ovaries, the fallopian tubes and the uterus are affected in 10–80% of cases[7xEdington, G.M. et al. Trans. R. Soc. Trop. Med. Hyg. 1971; 20: 846–849See all References, 8xGelfand, M. and Ross, W. Trans. R. Soc. Trop. Med. Hyg. 1953; 47: 218–220PubMed | Scopus (17)See all References, 9xYoussef, A.F. et al. J. Obstet. Gynaecol. Br. Commonw. 1970; 77: 847–851Crossref | PubMedSee all References].A shift of adult worms to topographic sites from which eggs cannot reach the lumen of the bladder, and thus are not excreted, obviously has an important consequence on age-intensity profiles: even if reinfection rates remain unchanged, egg excretion in urine will diminish and thus create the impression that there is an age-associated decrease of intensity of infection with onset of puberty.Two lines of evidence support this assumption. First, according to the literature, female genital schistosomiasis (FGS) occurs mainly after girls have reached sexual maturity[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4], ie. at an age when intensity of infection—as measured by egg excretion—decreases. Recently, these clinical observations were supported by data from a community-based study in Tanzania; the existence of FGS as measured by the presence of eggs in cervical biopsies and the prevalence/intensity of egg excretion in urine were inversely correlated during adolescence (Poggensee et al., unpublished).Second, if with the beginning of puberty a topographic shift of adult worms, rather than a diminished worm burden, is responsible for a decrease of egg excretion in urine, then the simultaneous measurement of egg excretion and circulating antigens should provide an important clue. Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]examined S. haematobium- or S. mansoni-infected populations for egg excretion as well as circulating anodic antigen (CAA). Schistosoma haematobium egg output relative to serum CAA was significantly reduced with onset of puberty. Nothing like that was observed in patients infected with S. mansoni, a parasite less commonly affecting the genital tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4]. Moreover, the effect observed by Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]was highly significant in women, but not in men, whose genitals are less frequently affected by ectopic schistosomiasis.Taken together, these circumstantial facts favour the hypothesis that in S. haematobium infection in women yet another mechanism may explain the familar age-intensity profile with the typical decline of the curve after onset of puberty. Whether vascular changes induced by sex hormones during puberty and pregnancy and subsequent anatomical compartmentalization of adult worms also have a regulatory effect on protective immune mechanisms is another intriguing question. The dynamics of schistosomiasis are probably much more complex than we still know. Why should it not be different between women and men?

Unreliability of PAP smears to diagnose female genital schistosomiasis

Female genital schistosomiasis (FGS) is a common condition of infection with Schistosoma haematobium. Schistosome eggs of different species have been found in Papanicolaou-stained (Pap) smears either accidentally by the examination of cytological material obtained during screening for cervical malignancy or in patients suspected of having FGS. To assess whether Pap smears may substitute for the examination of cervical tissue a study was conducted with 51 women aged 15-47 years who excreted S. haematobium eggs in urine and presented with various symptoms at Mangochi District Hospital near Lake Malawi Malawi. The biopsy was examined using the quantitative fresh compressed biopsy technique (QCBT) which is derived from a procedure developed for the assessment of cure in intestinal schistosomiasis and which has been successfully applied to biopsies taken from the cervix the vagina and the vulva. Overall results demonstrated that endo/ectocervical smears especially Pap smears cannot substitute for the QCBT in diagnosing FGS. However considering the epithelial atypias frequently associated with genital schistosomiasis endo/exocervical Pap smears are a useful complementary examination in women suspected of having schistosomiasis of the lower reproductive tract.