Biomedical subjects
Publications and source records attributed to H Feldmeier.
Detection of Schistosoma haematoblum eggs in 43% of semen samples with Increased levels of eosinophil cationic protein suggests that the genital organs of men are frequently affected with schistosomiasis.
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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.
OBJECTIVE: To determine if human growth hormone (hGH) replacement therapy alters pharmacokinetics of hydrocortisone (CS) substitution in hypopituitary adults. DESIGN: To this aim, we analysed serum and salivary CS profiles 270 min after oral CS administration at baseline and 6 and 12 months after initiation of hGH replacement therapy. METHODS: Serum IGF-I, cortisol-binding globulin (CBG), thyroxine-binding globulin (TBG) and sex hormone-binding hormone (SHBG) were measured using commercially available radioimmunoassays. In-house immunofluorometric assays were employed for measurements of CS and hGH. RESULTS: hGH replacement did not change total serum CS bioavailability (area under the serum cortisol profile curve). Interference of orally administered CS with salivary measurement of free CS (fCS) caused significant bias. Therefore, fCS levels were calculated from their total CS and cortisol-binding globulin (CBG) levels. CBG decreased by approximately 30% after both 6 and 12 months of hGH replacement therapy (n=20, P<0.01). A significant negative correlation between deltaCBG (CBG6months-CBGbaseline) and deltaIGF-I (IGF-I6months-IGF-Ibaseline) was observed (P=0.04). The calculated values of free CS tended to increase with physiological hGH replacement, but this effect was marginal and did not reach statistical significance. In contrast to the CBG concentrations, plasma levels of sex hormone-binding globulin and thyroxine-binding globulin were essentially stable. CONCLUSION: Given that no clinically relevant alterations in pharmacokinetics of CS were evoked by initiation of hGH replacement in hypopituitary adults, we conclude that CS substitution does not require dose adjustment after initiation of hGH replacement.
The screening of women of childbearing age for haematuria, leukocyturia and proteinuria to detect urinary schistosomiasis can be confounded by several factors such as menstruation, pregnancy and genitourinary infections. We therefore undertook a study in an area endemic for Schistosoma haematobium in the United Republic of Tanzania to carry out the following: assess the sensitivity, specificity and predictive values--in women of childbearing age--of indirect indicators of urinary schistosomiasis, as measured by urine reagent strip readings; assess the predictive values of self-reported symptoms; and finally to estimate the morbidity attributable to S. haematobium. A total of 303 women (128 and 175, respectively, living in high- and low-risk sites) participated in the study. Haematuria was more frequent among women excreting S. haematobium eggs than among those who did not (65% versus 32%). The predictive potential of all indirect disease markers was poor in the highly endemic site, while in the sites with low endemicity the negative predictive values were high. Among infected women, 54% of haematuria could be attributed to S. haematobium, but for patients with more than 10 eggs/10 ml the attributable fraction rose to 70%. Symptoms of "bloody urine" and "pain while urinating" were recalled significantly more often by women living in the highly endemic site. On a population level, one-third of the self-reported cases with bloody urine could be attributed to urinary schistosomiasis. Screening of women of childbearing age for urinary schistosomiasis using urine reagent strips can be biased in two directions. The prevalence of S. haematobium will be overestimated if other causes of haematuria, such as reproductive tract infections, are highly endemic. On the other hand, women with light or very light infections will be missed and will not be treated. This is of concern because genital schistosomiasis, a possible risk factor for the transmission of HIV, occurs among women even with light infections.
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 WHO's Tropical Disease Research Programme (TDR) included FGS in a list of scientific areas that deserve high research priority.
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A systematic analysis of the existing literature has been undertaken to compare the therapeutic and operational profiles of metrifonate (CAS 52-68-6), and praziquantel (CAS 55-268-74-1), two anti-schistosomal compounds. The criteria evaluated were therapeutic efficacy against Schistosoma haematobium and other helminths, impact on pathology commonly associated with S. haematobium infection, frequency, type and duration of adverse reactions, health risk associated with inadvertent overdosage, applicability and practicality of treatment in various medical settings, tolerance and resistance, pharmacological properties, toxicity and economic aspects. It is concluded that both medical and operational criteria indicate that praziquantel is superior to metrifonate for the treatment of schistosomiasis caused by S. haematobium. Since, compared to praziquantel, metrifonate has a number of disadvantages, future antischistosomal chemotherapy can do without this drug.
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To assess the morbidity of S. haematobium infection in women of reproductive age (15-49 years) in the western part of Madagascar, the village of Betalatala with a prevalence of urinary schistosomiasis in women of 75.6% (95% confidence limit 69.3 to 81.9%) was compared with a neighbouring village with similar socio-economic characteristics and a prevalence of 5.0% (95% confidence limit 0 to 11.75%). The women were questioned in Malagasy about obstetrical history and urogynecological symptoms. They were examined gynaecologically, parasitologically and by ultrasonography. Important STDs were excluded by appropriate diagnostics. In Betalatala significantly more women reported a history of spontaneous abortion (P < 0.01), complaints of irregular menstruation (P < 0.001), pelvic pain (<0.05), vaginal discharge (P < 0.0001), dysuria (P < 0.05) and haematuria (P < 0.01) than in the control village. Biopsies were obtained from the cervix of 36 women with macroscopical lesions, and in 12 cases S. haematobium eggs were found by histological sectioning (33.3%). In the control village no eggs were detected in the histological sections of biopsies taken from 14 women. (P < 0.05). Infections with Candida albicans, Trichomonas vaginalis, Gardnerella vaginalis and Treponema pallidum were found in similar frequencies in both villages. In 9.8% of the women in Betalatala abnormalities of the upper reproductive tract were revealed by ultrasonography versus none in the women from the control village (P < 0.05). Echographic abnormalities of the urinary tract were present in 24% and 3% of the women in the study village and in the control village, respectively (P < 0.0001). These findings were accompanied by an elevated frequency of haematuria (55% versus 20%) and proteinuria (70.4% versus 25%) in the study population (P < 0.0001). Our study indicates that S. haematobium infection in women may not only cause symptoms in the urinary tract, but also frequently in the lower and upper reproductive tract.
Several studies have shown that the characteristic hepatic abnormalities induced by Schistosoma mansoni detectable by ultrasound correlate with the degree of oesophageal varices. So far the value of ultrasound for predicting variceal haemorrhage has not been assessed. Fifty Brazilian patients with schistosomal periportal fibrosis from Alagoas State, 18 of whom had already bled from oesophageal varices, were enrolled in a combined cross-sectional and longitudinal study and investigated clinically, by endoscopy and by ultrasound. Twenty-seven of the patients were monitored until another bleeding episode, death or for a minimum of 28 months. Eight of these patients could be followed up for a further three years. A sonographic score, which accounts for the degree of echogenic periportal thickening and of portal vein dilatation, was calculated for all patients. A highly significant correlation (P < 0.0001) existed between the sonographic score and the occurrence of previous variceal haemorrhage, paralleled by a similar correlation between the sonographic score and the degree of oesophageal varices (P < 0.001). In the 27 patients monitored longitudinally, the sonographic score indicated the risk of future variceal bleeding (P < 0.0001). The sonographic score reliably predicts the risk of variceal bleeding in individual patients with periportal fibrosis. Hence, the application of endoscopy, if available at all in endemic areas, may be restricted to the patients at risk of future variceal bleeding, as determined by ultrasound. Since portable devices can be carried even to remote areas, the application of the proposed score in community surveys could provide a new means for the identification of high-risk patients in S. mansoni-infected populations.
Egg-induced lesions in the upper and the lower female reproductive tract are important complications of the infection with Schistosoma mansoni. The understanding of the pathophysiology and pathology of genital lesions is only rudimentary, simple and reliable diagnostic tools are not at hand, epidemiological data do not exist and how to treat best the women affected, is not known. In view of recent advances in the understanding of genital lesions induced by S. haematobium the existing literature is critically analyzed and possible consequences of female genital schistosomiasis are outlined. We estimate that 6 to 27% girls and women with intestinal schistosomiasis, at least temporarily, suffer from pathology induced by eggs sequestered somewhere in their genital organs. This is a matter of concern and warrants more research into the epidemiology, pathology, diagnosis and therapy of this disease entity.
The individual and public health impact of female genital schistosomiasis (FGS) has been studied and FGS as a risk factor for acquiring human immunodeficiency virus is discussed. In a community-based study in Tanzania, 40% of the women of child-bearing age (n=543) showed excretion of Schistosoma haematobium eggs in the urine (median=2.2 eggs/10 ml of urine) and 32% (n=263) had S. haematobium eggs in their cervical tissue. Urinary and genital schistosomiasis coexisted in 62% of the women, but S. haematobium eggs were found in the cervix without detectable egg excretion in the urine in 23%. Only 43% of the FGS cases had hematuria. Since FGS frequently exists in women with scanty or no egg excretion in the urine and because this disease manifestation is a considerable individual and public health hazard in S. haematobium-endemic areas, mass treatment targeted to women of child-bearing age should be considered.
Female genital schistosomiasis, FGS, was investigated in a gynaecological study as part of an overall community based morbidity survey, including parasitological and ultrasonographical examination, of a Schistosoma haematobium endemic area in Madagascar. Women (103), of childbearing age (15-49 years), were included for a gynaecological examination and visible lesions of vagina and cervix were biopsied in order to determine the origin of the lesion. Furthermore all women were screened for the presence of schistosome ova using PAP smears from the vagina and the endo/exo cervix. In total 15 women showed schistosome ova in the vagina and/or cervix (median age 24 years and range 15-36 years). Of 36 women with cervical abnormalities, 12 eggs were detected by cervical biopsy (33%). In addition, two of the 12 presented vaginal induration, which contained eggs. Six women had eggs in their PAP smears of which three were egg negative by cervical biopsy. The prevalence of positive S. haematobium egg excretion in the urine among the 103 women was 69% and the geometric mean egg count of positive individuals was 51 eggs/10 ml of urine. Five of the 15 women with confirmed FGS had < or = 1 egg/10 ml of urine. Bladder lesions and congestive changes in the kidneys were demonstrated by ultrasonographic examination in 33 and 9% of the 103 women, respectively. None of the 15 women with confirmed FGS had renal congestion. Our study demonstrates that FGS is a common manifestation of the infection with S. haematobium, even in lightly infected individuals.
Human growth hormone (GH) and insulin-like growth factor I (IGF-I) are known to bind to, and exert modulatory effects on, different immunocompetent cells, including CD16+/CD3- natural killer (NK) cells. NK cells are involved in various non-major-histocompatibility-complex-restricted actions of the immune system. Although no clinically significant defect in tumour or virus defence has been reported in GH-deficient patients, the data available indicate decreased NK cell activity in these patients. In most studies, the absolute number and percentage of NK cells have been found to be normal. Substitution with GH has been reported to normalize the decreased NK cell activity in GH-deficient patients. In a cross-sectional study in GH-deficient adults, decreased basal and interferon-beta (IFN-beta)-stimulated NK cell activity in vitro. Preliminary data on GH binding to NK cells indicate enhanced binding in GH-deficient patients when compared with normal controls.
Female genital schistosomiasis (FGS) is a neglected disease entity which may give rise to considerable suffering among women of child-bearing age in areas where schistosomiasis (especially due to Schistosoma haematobium) is prevalent. The close relation between the vessels in genital organs and the urinary bladder enables the parasite to easily change location to virtually any organs in the female pelvic area. Symptoms concur with the anatomical location of worm pairs and their ova. Lesions of the lower female genital tract can easily be investigated by cytology, histology or direct demonstration of eggs in scrapings or biopsies whereas schistosomiasis of the upper genital tract is clinically indecipherable and less accessible for examination. In the literature there are references to FGS as a cause of infertility, complications of pregnancy, menstrual disorders, problems related to sexual intercourse, diagnostic similarities to STDs and cancer, unspecified complaints related to blood loss, chronic abdominal pain, social segregation and related psychological problems. The diagnosis of female upper genital schistosomiasis is difficult and the authors point out possible diagnostic procedures which might be helpful for further understanding of this complex entity.
A total of 51 women with urinary schistosomiasis haematobium were examined in order to identify diagnostic indicators for female genital schistosomiasis (FGS). Patients were selected at random from the outpatient department of the Mangochi District Hospital, Malawi. The medical histories were recorded according to a pre-designed questionnaire and the women were subjected to a thorough gynaecological examination including colposcopy and photographic documentation of lesions. Microscopy of genital biopsies revealed that 33 of the 51 women had S. haematobium ova in cervix, vagina and/or vulva in addition to the presence of ova in urine. The most sensitive diagnostic procedure was beside microscopic examination of a wet cervix biopsy crushed between two glass slides, which revealed 25 of the 33 genital infections. There was a significant correlation between the size of genital lesions and the number of ova counted per mm2 of crushed tissue. Women with FGS had significantly more tumours in the vulva than women with schistosomiasis limited to the urinary tract. Most of the observed genital pathology could easily be identified by the naked eye, but colposcopic examination yielded valuable additional information like the demonstration of neovascularisation around cervical sandy patches. Few of the symptoms previously regarded as indicators for FGS could be linked to the presence of schistosome ova in genital tissue. Husbands of infertile women with FGS had children with other women significantly more often than husbands of women who only had urinary schistosomiasis. This, together with the finding that the majority of the divorced women had FGS, indicates that the manifestation of this disease may have implications for the marital and sexual life of the affected women.
Schistosomiasis of the lower female reproductive tract manifests itself in a broad spectrum of clinical features. However, clinical and histopathological findings have never been studied in a synoptic manner. Based on the assumption that any type of pathology present in the female reproductive tract is the expression of a complex pathophysiological reaction towards eggs sequestered in the genital tissues, we decided to analyze colposcopic and histopathological findings in a comprehensive manner. Thirty-three women in Malawi with urinary and genital schistosomiasis were examined parasitologically and gynecologically. A thorough colposcopic examination with photodocumentation was performed and biopsies were taken from the cervix, the vagina and/or the vulva for histological sectioning and immunohistochemistry. The predominant colposcopic findings were sandy patches on the cervical surface similar to those seen in the bladder and polypous/papillomatous tumors with irregular surface on the vaginal wall and in the vulvar area. The histopathological sections of sandy-patch-like lesions demonstrated only a small cellular reaction around S. haematobium eggs in various stages of disintegration. In contrast, in the case of polyps the histology revealed a more pronounced immunological reaction characterized by a heavy cellular infiltrate. One case of invasive squamous cell carcinoma of the cervix was diagnosed. We conclude that colposcopy is a useful tool in the detection of FGS related pathology in the lower female reproductive tract and that the synoptic assessment of surface and of corresponding histological sections helped to understand the pathophysiology of S. haematobium associated disease in genital tissue.