Mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice

It has been shown previously that recombinant virus-like particles (VLPs) of papillomavirus can induce VLP-specific humoral and cellular immune responses following parenteral administration. To test whether mucosal administration of bovine papillomavirus type 1 (BPV1) VLPs could produce mucosal as well as systemic immune responses to VLPs, 50 mu g chimeric BPV1 VLPs containing an HPV16 E7 CTL epitope (BPVL1/E7 VLP) was administered intranasally to mice. After two immunisations, L1-specific serum IgG and IgA were observed. L1-specific IgG and IgA were also found in respiratory and vaginal secretions. Both serum and mucosal antibody inhibited papillomavirus VLP-induced agglutination of RBC, indicating that the antibody induced by mucosal immunisation may recognize conformational determinants associated with virus neutralisation. For comparison, VLPs were given intramuscularly, and systemic and mucosal immune responses were generally comparable following systemic or mucosal delivery. However, intranasal administration of VLP induced significantly higher local IgA response in lung, suggesting that mucosally delivered HPV VLP may be more effective for mediating local mucosal immune responses. Intranasal immunisation with HPV6b L1 VLP produced VLP-specific T proliferative responses in splenocytes, and immunisation with BPVL1 VLP containing an HPV16 E7 CTL epitope induced E7-specific CTL responses. We conclude that immunisation with papillomavirus VLPs via mucosal and intramuscular routes, without adjuvant, can elicit specific antibody at mucosal surfaces and also systemic VLP epitope specific T cell responses. These findings suggest that mucosally delivered VLPs may offer an alternative HPV VLP vaccine strategy for inducing protective humoral immunity to anogenital HPV infection, together with cell-mediated immune responses to eliminate any cells which become infected. (C) 1998 Academic Press.

Unsupervised cell nucleus segmentation with active contours

The task of segmenting cell nuclei from cytoplasm in conventional Papanicolaou (Pap) stained cervical cell images is a classical image analysis problem which may prove to be crucial to the development of successful systems which automate the analysis of Pap smears for detection of cancer of the cervix. Although simple thresholding techniques will extract the nucleus in some cases, accurate unsupervised segmentation of very large image databases is elusive. Conventional active contour models as introduced by Kass, Witkin and Terzopoulos (1988) offer a number of advantages in this application, but suffer from the well-known drawbacks of initialisation and minimisation. Here we show that a Viterbi search-based dual active contour algorithm is able to overcome many of these problems and achieve over 99% accurate segmentation on a database of 20 130 Pap stained cell images. (C) 1998 Elsevier Science B.V. All rights reserved.

Hysterectomy fractions in New South Wales, 1971-2006

Hysterectomy fractions by age group for particular periods are of interest for: estimating proper population denominators for calculation of disease and procedure rates affecting the cervix and uterus; estimating the target population for Pap test programs, and response rates; and as a way of displaying the cumulative consequences of hysterectomies in a population. Hysterectomy fractions for populations can be determined by direct inquiry via a representative sample survey, or, as in this study, from prior hysterectomy rates of the cohorts of women which compose each age bracket. Hysterectomy data 1979-93 were obtained from the hospital In-patients Statistics Collection (ISC) which covers both public and private hospitals in NSW. Annual population denominators of women were obtained from Census data. Data were modelled by Poisson regression, using five.-year age group (15-greater than or equal to 85 years), annual period, and five-year birth cohort (APC model). Forward- and back-projection of the period effects were undertaken. The resultant NSW hysterectomy fractions by age and period are consistent with fractions obtained from modelled hysterectomy rates for Western Australia (1980-84), and fractions from national representative sample surveys (1989/90 and 1995) for younger women, but not for women aged greater than or equal to 70 years in 1995, which revealed higher hysterectomy fractions than modelled hysterectomy data would suggest. Hysterectomy fractions for NSW women by five-year age group for quinquennia centred on 1971 to 2006 are provided.

Twice-weekly, directly observed treatment for HIV-infected and uninfected tuberculosis patients: cohort study in rural South Africa

Objective: To determine the effectiveness of twice-weekly directly observed therapy (DOT) for tuberculosis (TB) in HIV-infected and uninfected patients, irrespective of their previous treatment history. Also to determine the predictive value of 2-3 month smears on treatment outcome. Methods: Four hundred and sixteen new and 113 previously treated adults with culture positive pulmonary TB (58% HIV infected, 9% combined drug resistance) in Hlabisa, South Africa. Daily isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) given in hospital (median 17 days), followed by HRZE twice a week to 2 months and HR twice a week to 6 months in the community. Results: Outcomes at 6 months among the 416 new patients were: transferred out 2%; interrupted treatment 17%; completed treatment 3%; failure 2%; and cured 71%. Outcomes were similar among HIV-infected and uninfected patients except for death (6 versus 2%; P = 0.03). Cure was frequent among adherent HIV-infected (97%; 95% CI 94-99%) and uninfected (96%; 95% CI 92-99%) new patients. Outcomes were similar among previously treated and new patients, except for death (11 versus 4%; P = 0.01), and cure among adherent previously treated patients 97% (95% CI 92-99%) was high. Smear results at 2 months did not predict the final outcome. Conclusion: A twice-weekly rifampicin-containing drug regimen given under DOT cures most adherent patients irrespective of HIV status and previous treatment history. The 2 month smear may be safely omitted. Relapse rates need to be determined, and an improved system of keeping treatment interrupters on therapy is needed. Simplified TB treatment may aid implementation of the DOTS strategy in settings with high TB caseloads secondary to the HIV epidemic. (C) 1999 Lippincott Williams & Wilkins.

Trial-of-antibiotic algorithm for the diagnosis of tuberculosis in a district hospital in a developing country with high HIV prevalence

OBJECTIVE: To evaluate a diagnostic algorithm for pulmonary tuberculosis based on smear microscopy and objective response to trial of antibiotics. SETTING: Adult medical wards, Hlabisa Hospital, South Africa, 1996-1997. METHODS: Adults with chronic chest symptoms and abnormal chest X-ray had sputum examined for Ziehl-Neelsen stained acid-fast bacilli by light microscopy. Those with negative smears were treated with amoxycillin for 5 days and assessed. Those who had not improved were treated with erythromycin for 5 days and reassessed. Response was compared with mycobacterial culture. RESULTS: Of 280 suspects who completed the diagnostic pathway, 160 (57%) had a positive smear, 46 (17%) responded to amoxycillin, 34 (12%) responded to erythromycin and 40 (14%) were treated as smear-negative tuberculosis. The sensitivity (89%) and specificity (84%) of the full algorithm for culture-positive tuberculosis were high. However, 11 patients (positive predictive value [PPV] 95%) were incorrectly diagnosed with tuberculosis, and 24 cases of tuberculosis (negative predictive value [NPV] 70%) were not identified. NPV improved to 75% when anaemia was included as a predictor. Algorithm performance was independent of human immunodeficiency virus status. CONCLUSION: Sputum smear microscopy plus trial of antibiotic algorithm among a selected group of tuberculosis suspects may increase diagnostic accuracy in district hospitals in developing countries.

High HIV incidence and prevalence among young women in rural South Africa: Developing a cohort for intervention trials

Objective: To measure prevalence and model incidence of HIV infection. Setting: 2013 consecutive pregnant women attending public sector antenatal clinics in 1997 in Hlabisa health district, South Africa. Historical seroprevalence data, 1992-1995. Methods: Serum remaining from syphilis testing was tested anonymously for antibodies to HIV to determine seroprevalence. Two models, allowing for differential mortality between HIV-positive and HIV-negative people, were used. The first used serial seroprevalence data to estimate trends in annual incidence. The second, a maximum likelihood model, took account of changing force of infection and age-dependent risk of infection, to estimate age-specific HIV incidence in 1997. Multiple logistic regression provided adjusted odds ratios (OR) for risk factors for prevalent HIV infection. Results: Estimated annual HIV incidence increased from 4% in 1992/1993 to 10% in 1996/1997. In 1997, highest age-specific incidence was 16% among women aged between 20 and 24 years. in 1997, overall prevalence was 26% (95% confidence interval [CI], 24%-28%) and at 34% was highest among women aged between 20 and 24 years. Young age (<30 years; odds ratio [OR], 2.1; p = .001), unmarried status (OR 2.2; p = .001) and living in less remote parts of the district (OR 1.5; p = .002) were associated with HIV prevalence in univariate analysis. Associations were less strong in multivariate analysis. Partner's migration status was not associated with HIV infection. Substantial heterogeneity of HIV prevalence by clinic was observed (range 17%-31%; test for trend, p = .001). Conclusions: This community is experiencing an explosive HIV epidemic. Young, single women in the more developed parts of the district would form an appropriate cohort to test, and benefit from, interventions such as vaginal microbicides and HIV vaccines.

Cervical screening in migrants to Australia

Objective: To examine differentials and time trends in self-reported Pap test rates by migrant status from the 1989/90 and 1995 Australian National Health Surveys (NHS). Method: Unit record data for females with the variables of interest were extracted from the 1989/90 and 1995 NHS and combined. The dichotomous outcome variables were 'ever had a Pap test and 'had a Pap test within three years'. The principal study factor was country-of-birth, but language spoken at home (English or not) was also examined. The indirect age-standardised screening ratio was used to calculate proportions of 'ever had a Pap test' and 'had a Pap test within three years' and differences were tested statistically using logistic regression analysis for each year of survey by migrant status. Results: Odds ratios for rates of reporting 'ever had a Pap test' were significantly lower in women born in southern Europe, Italy, other countries, southern Asia, Middle East, Greece and South-East Asia compared with Australian-born. Reported rates of 'ever had a Pap test' were significantly higher in the 1995 NHS (p

Contraction of the pelvic floor muscles during abdominal maneuvers

Objective: To determine whether voluntary abdominal muscle contraction is associated with pelvic floor muscle activity. Design: Pelvic floor muscle activity was recorded during contractions of the abdominal muscles at 3 different intensities in supine and standing positions. Setting: Research laboratory. Participants: Six women and 1 man with no histories of lower back pain. Interventions: Not applicable. Main Outcome Measures: Electromyographic activity of the pelvic floor muscles was recorded with surface electrodes inserted into the anus and vagina. These recordings were corroborated by measurements of anal and vaginal pressures. Gastric pressure was recorded in 2 subjects. Results: Pelvic floor muscle electromyography increased with contraction of the abdominal muscles. With strong abdominal contraction, pelvic floor muscle activity did not differ from that recorded during a maximal pelvic floor muscle effort. The pressure recordings confirmed these data. The increase in pressure recorded in the anus and vagina preceded the pressure in the abdomen. Conclusions: In healthy subjects, voluntary activity in the abdominal muscles results in increased pelvic floor muscle activity. The increase in pelvic floor pressure before the increase in the abdomen pressure indicates that this response is preprogrammed. Dysfunction of the pelvic floor muscles can result in urinary and fecal incontinence. Abdominal muscle training to rehabilitate those muscles may be useful in treating these conditions.

Trichomonas vaginalis is associated with pelvic inflammatory disease in women infected with human immunodeficiency virus

We assessed the association between the causative agents of vaginal discharge and pelvic inflammatory disease (PID) among women attending a rural sexually transmitted disease clinic in South Africa; the role played by coinfection with human immunodeficiency virus type 1 (HIV-1) was studied. Vaginal and cervical specimens were obtained to detect Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis. HIV-1 infection was established by use of serum antibody tests. A total of 696 women with vaginal discharge were recruited, 119 of whom had clinical PID. Patients with trichomoniasis had a significantly higher risk of PID than did women without trichomoniasis (P = .03). PID was not associated with any of the other pathogens. When the patients were stratified according to HIV-1 status, the risk of PID in HIV-1-infected patients with T. vaginalis increased significantly (P = .002); no association was found in patients without HIV-1. T. vaginalis infection of the lower genital tract is associated with a clinical diagnosis of PID in HIV-1-infected women.

Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer

We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% Cl 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% Cl 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents. (C) 1997 Wiley-Liss, Inc.

Efficacy of praziquantel against Schistosoma japonicum: field evaluation in an area with repeated chemotherapy compared with a newly identified endemic focus in Hunan, China

This study conducted in 1999/2000 was designed to evaluate the efficacy of praziquantel against Schistosoma japonicum in an area with repeated chemotherapy (Area A) compared with a newly identified endemic focus (Area B) in Hunan Province, China. The population size was 2015 and 2180 in Areas A and B, respectively, of which 1129 and 1298 subjects received stool examination. A total of 230 subjects were identified by the Kato-Katz technique (4 smears per person) as being infected with S. japonicum, 124 in Area A (prevalence 11 %) and 106 in Area B (prevalence 8.2%). They were treated with a single oral dose of praziquantel (40 mg/kg) in the non-transmission season. A follow-up stool examination was made 50 days after treatment. Among the 220 cases followed, 22 were found stool-egg-positive, with an overall cure rate of 90 %, and 99 % reduction of infection intensity (eggs per gram stool). No significant difference was found in cure rates between the 2 areas (89.7% vs 90.3%). The efficacy of the drug in the area with repeated chemotherapy was not significantly different from that in the newly identified endemic focus. This study, therefore, suggests that the efficacy of praziquantel against S. japonicum has not changed in the Dongting Lake region after more than 14 years of mass chemotherapy, and there is no evidence of tolerance or resistance of S. japonicum against praziquantel.

Determinants of hepato- and spleno-megaly in Hunan, China: cross-sectional survey data from areas endemic for schistosomiasis

In order to understand the determinants of schistosome-related hepato- and spleno-megaly better, 14 002 subjects aged 3-60 years (59% male; mean age =32 years) were randomly selected from 43 villages, all in Hunan province, China, where schistosomiasis caused by Schistosoma japonicum is endemic. The abdomen of each subject was examined along the mid-sternal (MSL) and mid-clavicular lines, for evidence of current hepato- and/or spleno-megaly, and a questionnaire was used to collect information on the medical history of each individual. Current infections with S. japonicum were detected by stool examination. Almost all (99.8%) of the subjects were ethnically Han by descent and most (77%) were engaged in farming. Although schistosomiasis appeared common (42% of the subjects claiming to have had the disease), only 45% of the subjects said they had received anti-schistosomiasis drugs. Overall, 1982 (14%) of the subjects had S. japonicum infections (as revealed by miracidium-hatching tests and/or Katon Katz smears) when examined and 22% had palpable hepatomegaly (i.e. enlargement of at least 3 cm along the MSL), although only 2.5% had any form of detectable splenomegaly (i.e. a Hackett's grade of at least 1). Multiple logistic regression revealed that male subjects, fishermen, farmers, subjects aged greater than or equal to 25 years, subjects with a history of schistosomiasis, and subjects who had had bloody stools in the previous 2 weeks were all at relatively high risk of hepato- and/or spleno-megaly. In areas moderately endemic for Schistosoma japonicum, occupational exposure and disease history appear to be good predictors of current disease status among older residents. These results reconfirm those reported earlier in the same region.

Uterine preservation or hysterectomy at sacrospinous colpopexy for uterovaginal prolapse

This study retrospectively compared 34 women who had a sacrospinous hysteropexy and 36 who had a vaginal hysterectomy and sacrospinous fixation for symptomatic uterine prolapse. All women underwent independent review and examination, with a mean follow-up of 36 months in the hysterectomy group and 26 months in the hysteropexy group.  The subjective success rate was 86% in the hysterectomy group and 78% in the hysteropexy group (P = 0.70). The objective success rate was 72% and 74%, respectively (P = 1.00). The patient-determined satisfaction rate was 86% in the hysterectomy group and 85% in the hysteropexy group (P = 1.00). The operating time in the hysterectomy group was 91 minutes, compared to 59 minutes in the hysteropexy group (P

A revision of Benedenia Diesing, 1858 including a redescription of B-sciaenae (van Beneden, 1856) Odhner, 1905 and recognition of Menziesia Gibson, 1976 (Monogenea : Capsalidae)

Benedenia Diesing, 1858, a genus of capsalid (benedeniine) monogeneans, is redefined. The generic diagnosis is amended to include: the path of tendons in the haptor from extrinsic muscles in the body; presence and form of the marginal valve; a penis occupying a penis canal with weakly muscular wall; a weakly muscular accessory gland reservoir proximal to the penis and enclosed by a proximal extension of the wall of the penis canal; male and female genital apertures usually common, rarely separate; vagina with pore usually close to the common genital pore but may open in mid body between the germarium and the common genital pore, or anterior to the common genital pore. A conservative approach is adopted and the generic diagnosis is clarified and broadened to accommodate species that display some variation in reproductive anatomy, especially of the female system. We argue against potential alternative actions such as defining Benedenia strictly to contain species with separate male and female genital apertures and against recognition of a separate genus, Tareenia Hussey, 1986, for species with a vaginal pore anterior to the common genital pore. Under our conception, Benedenia comprises 21 species: B. sciaenae (van Beneden, 1856) Odhner, 1905 (type species); B. acanthopagri (Hussey, 1986) comb. nov.; B. anticavaginata Byrnes, 1986; B. bodiani Yamaguti, 1968; B. elongata (Yamaguti, 1968) Egorova, 1997; B. epinepheli (Yamaguti, 1937) Meserve, 1938; B. hawaiiensis Yamaguti, 1968; B. hendorffi(von Linstow, 1889) Odhner, 1905; B. hoshinai Ogawa, 1984; B. innobilitata Burhnheim Gomes and Varela, 1973: B. jaliscana Bravo-Hollis, 1952; B. lolo Yamaguti, 1968; B. lutjani Whittington and Kearn, 1993: B. monticellii (Parona and Perugia, 1895) Johnston, 1929; B. ovata (Goto, 1894) Johnston. 1929: B. pompatica Burhnheim, Gomes and Varela, 1973; B. rohdei Whittington, Kearn and Beverley-Burton, 1994; B. scari Yamaguti, 1968; B. sekii (Yamaguti, 1937) Meserve, 1938; B, seriolae (Yamaguti, 1934) Meserve, 1938; and B. synagris Yamaguti, 1953. The type species, B. sciaenae, is redescribed based on new material from Australia. No types for this taxon were designated and we have assigned a series of voucher specimens. Tareenia acanthopagri Hussey, 1986 becomes B. acanthopagri (Hussey, 1986) comb. nov. and T. anticavaginata (Byrnes, 1986) Egorova, 1997 and T. lutjani (Whittington and Kearn, 1993) Egorova, 1997 are returned to Benedenia as B. anticavaginata and B. lutjani Benedenia akaisaki Iwata, 1990 is considered a synonym of B. ovata and B. kintoki Iwata, 1990 is considered a synonym of B. elongata. Two species, B, madai Ishii and Sawada, 1938 and B. pagrosomi Ishii and Sawada, 1938, are considered species inquirendae. Based on the redefinition of Benedenia, the diagnosis for the Benedeniinae is amended. Tareenia is synonymized with Benedenia but Menziesia Gibson, 1976 is recognized and its generic diagnosis amended to include: anterior attachment organs tending to form a 'hooded' appearance; prominent anterior gland cells between the pharynx and the anterior margin of the body: long penis, tapering proximally, occupying a penis canal with weakly muscular wall: penis canal and penis describe a sigmoid; accessory gland reservoir dorsal and alongside, or posterior and lateral to, proximal end of the penis and enclosed by a proximal extension of the wall of the penis canal. Under this conception. Menziesia comprises: M. noblei (Menzies. 1946) Gibson, 1976 (type species); M. malaboni (Velasquez. 1982) comb. nov.: M. merinthe (Yamaguti, 1968) Gibson. 1976: M. ovalis (Yamaguti, 1968) Gibson, 1976: and M. sebastodis (Yamaguti, 1934) comb, nov. A key to valid species of Benedenia and Menziesia is provided and a list is presented of published records of undescribed or unattributed species of Benedenia. Some protocols are suggested for preparation of benedeniine material to enhance future taxonomic studies and comparisons. The host-specificity and geographic distribution of species in these revised genera are discussed. The composition of the Capsalidae is discussed and some difficulties in defining and distinguishing between its different subfamilies are considered.