Phase I of the DiaVACCS screening trial: Study design, methods, population demographics and baseline results.

BACKGROUND: Human papillomavirus (HPV)-based primary screening guidelines are based on screening test performance and prevalence data generated in high-resource areas with low HIV infection rates. There is an urgent need for local data on infection and disease prevalence, as well as screening test performance, among both HIV-positive and HIV-negative South African (SA) women, in order to inform updated screening guidelines. Objectives. This study describes the baseline characteristics of participants in the cross-sectional phase of the multicentric DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) screening trial. The objective was to determine the prevalence of positive screening and pre-invasive disease using different tests and strategies in the SA HIV-positive and HIV-negative population. METHODS: A total of 1  104 women aged 25 - 65 years and eligible for screening were included, 465 HIV positive and 639 HIV negative. Visual inspection and molecular and cytological screening tests were done on self-sampled and healthcare worker-collected specimens. All participants who screened positive and 49.1% of those who screened negative were invited for colposcopy and biopsy, and those qualifying for treatment were recalled for large loop excision of the transformation zone as part of the trial. The worst histology result for each participant was used, and for untested women, multiple imputation was used to estimate verification biasadjusted histology values. RESULTS: Visual inspection was positive in 50.4% of HIV-positive v. 20.9% of HIV-negative women, cytology (atypical squamous cells of undetermined significance) in 39.9% v. 17.0%, and high-risk HPV DNA in 41.2% v. 19.6%. Overall, high-grade squamous intraepithelial lesion-positive cytology peaked in the age group 30 - 39 years at 16.7%. After adjustment for verification bias, histological diagnosis of cervical intraepithelial neoplasia (CIN)2+ was suspected in 44.7% v. 23.5% and CIN3+ in 23.3% v. 10.2% of HIV-positive and negative women, respectively. Invasive cancer was diagnosed in 15 women (1.95% of histological studies performed), and verification bias adjustment suggested 20 cases (1.8% of the study population). CONCLUSION: The baseline findings from the DiaVACCS trial confirm a high prevalence of HPV-related cervical pathology in the SA HIV-negative screening population, showing a clear need to reach these women with a screening programme. Among HIV-positive women, prevalence values were almost doubled. The prevalence of existing invasive cervical cancer was 1 - 2% of all women. Further analysis of the performance of single and multiple screening tests between the two subgroups will contribute to the choice of the most effective strategies to identify women at risk of developing invasive cancer.

Assessment and management of venous thrombo-embolism risk during pregnancy and the puerperium (SAVE): The South African cohort.

BACKGROUND: Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Pregnancy and the puerperium are hypercoagulable states and increase the risk of VTE. There is a paucity of South African (SA) data related to use of thromboprophylaxis during pregnancy and the puerperium. OBJECTIVES: To evaluate local practice of VTE risk stratification among SA pregnant women and senior doctors' attitudes to VTE prophylaxis. METHODS: This was a cross-sectional descriptive study of conveniently sampled sites in the private and public health sectors. Patients with confirmed pregnancy and an underlying medical condition were enrolled after giving informed consent. Assessments were made based on the participating doctors' questionnaires and case report forms. In essence, this was a local evaluation of a specific group of patients by a specific group of doctors. RESULTS: Two hundred and twenty patients were enrolled at six sites. In the participating doctors' opinion, 126/220 women assessed (57.2%) were at risk of VTE during pregnancy and the postpartum period (information was missing for 1 woman during the postpartum period). Of the women at risk of VTE, 23/126 (18.3%) were at high risk, 59/126 (46.8%) at moderate risk and 44/126 (34.9%) at low risk. Of the women identified as at risk of VTE, 104/127 (81.9%) received some form of VTE prophylaxis; 94/127 (74.0%) were at risk during pregnancy and 32/126 (25.4%) during the postpartum period. Of those who received pharmacological treatment, 15/15 received low-molecular-weight heparin during pregnancy and before delivery and 87/100 during the puerperium. Thirty-four patients received thromboprophylaxis for only 5 - 10 days after caesarean delivery, and 2 received mechanical thromboprophylaxis during pregnancy. CONCLUSIONS: Doctors participating in the study were generally aware of VTE risk during pregnancy and the puerperium. Pharmacological thromboprophylaxis was the most commonly used intervention to reduce VTE risk. Mechanical thromboprophylaxis was underutilised. Adherence to VTE guidelines, specifically in terms of duration of thromboprophylaxis and its utilisation during pregnancy, was suboptimal.

Management of recurrent cervical cancer.

Treatment for cervical cancer is very successful, especially in early stages. However, most patients presenting in late stages of disease will experience recurrence. The prognosis of recurrent disease is very poor and treatment options are limited. The diagnosis of recurrence may be apparent or difficult, but determining the extent of disease is always complex. Routine follow-up of asymptomatic patients has other objectives and is not a reliable way to detect recurrences. Symptomatic patients require extensive investigation to detect the extent of the disease. For patients with central pelvic recurrences, exenteration offers the prospect of survival in more than one-third of cases. Newer developments include laterally extended endopelvic resection that may become an option for patients with more extensive pelvic recurrence. For patients with recurrences of cervical cancer, the roles of second-time radiotherapy or postradiation chemotherapy are very limited. Palliative treatment is important for all patients with untreatable disease. Pain relief forms a central part of palliative care. Caregivers also experience emotional feelings and probably function best in a system offering strong colleageal support.

The Vaccine and Cervical Cancer Screen project 2 (VACCS 2): Linking cervical cancer screening to a two-dose HPV vaccination schedule in the South-West District of Tshwane, Gauteng, South Africa.

BACKGROUND: Cervical cancer is a preventable disease with a high prevalence in South Africa (SA), where screening is opportunistic. Primary prevention is now possible through HPV vaccination. In VACCS 1 the feasibility of linking cervical cancer with HPV vaccination was demonstrated. OBJECTIVES: To investigate the feasibility of linking HPV self-testing with a two-dose HPV vaccination schedule and to compare results with VACCS 1. METHODS: The project was conducted in five schools in the South-West District of Tshwane, Gauteng, SA. Leaflet information on cervical cancer and screening was provided, with requests for consent and assent for a two-dose HPV vaccination of schoolgirls. Female caregivers were invited to take part in HPV self-screening. RESULTS: Of 965 girls invited for vaccination, 519 (53.7%) had full consent and 518 (99.8%) received at least one vaccine dose. The invited uptake rate was 53.7% and 495 girls received both doses, giving a completion rate of 95.4% v. 82.6% in VACCS 1. Of 1 135 self-screen kits handed out, 560 (49.3%) were not returned. The mean age (standard deviation) of the 160 women who participated in self-screening was 38.7 (7.7) years. HPV testing was negative in 116 women (72.5%), 15 women (9.4%) tested positive for HPV 16 and/or 18, and 27 (16.9%) were positive for non-16/18 oncogenic HPV. CONCLUSION: Data from the VACCS projects suggest that school-based vaccine programmes can be successfully implemented. A two-dose schedule allowed for higher completion rates. Linking self-collected HPV screening to HPV vaccination is feasible, is a promising and viable screening strategy, and reached the appropriate age group for screening.

The vaccine and cervical cancer screen (VACCS) project: acceptance of human papillomavirus vaccination in a school-based programme in two provinces of South Africa.

BACKGROUND: The incidence of cervical cancer in South Africa (SA) remains high, and the current screening programme has had limited success. New approaches to prevention and screening tactics are needed. OBJECTIVES: To investigate acceptance of school-based human papillomavirus (HPV) vaccination, as well as the information provided, methods of obtaining consent and assent, and completion rates achieved. METHODS: Information on cervical cancer and HPV vaccination was provided to 19 primary schools in Western Cape and Gauteng provinces participating in the study. Girls with parental consent and child assent were vaccinated during school hours at their schools. RESULTS: A total of 3 465 girls were invited to receive HPV vaccine, of whom 2 046 provided written parental consent as well as child assent. At least one dose of vaccine was delivered to 2 030 girls (99.2% of the consented cohort), while a total of 1 782 girls received all three doses. Sufficient vaccination was achieved in 91.6% of the vaccinated cohort. Of all invited girls, 56.9% in Gauteng and 50.7% in the Western Cape were sufficiently vaccinated. CONCLUSION: This implementation project demonstrated that HPV vaccination is practical and safe in SA schools. Political and community acceptance was good, and positive attitudes towards vaccination were encountered. During the study, which mimicked a governmental vaccine roll-out programme, high completion rates were achieved in spite of several challenges encountered.

Infraumbilical-ring capillary abdominocentesis in late presentation ectopic pregnancy: a prospective study.

Infraumbilical-ring capillary abdominocentesis was compared with culdocentesis in 75 cases of suspected ruptured ectopic pregnancy, with patients serving as their own controls. There were 43 proven ectopic cases and the diagnosis was known in the remaining 32. The accuracy of results was equivalent: P greater than 0.15 for false positives and P greater than 0.63 for false negatives. For combined testing the positive predictive value reached 97%. The new method was easier to perform and should be preferred.

Evaluation of a strict protocol approach in managing women with severe disease due to abortion.

AIM: To evaluate whether the introduction of a strict protocol approach based on the systemic evaluation of critically ill pregnant women with complications of abortion affected outcome. SETTING: Indigent South Africans managed in the regional and tertiary hospitals of the Pretoria Academic Complex. METHOD: Since 1997 a standard definition of severe acute maternal morbidity (SAMM) has been used in the Pretoria Academic Complex. All cases of SAMM and maternal deaths were entered on the Maternal Morbidity and Mortality Audit System programme. A comparison of outcome of severely ill women who had complications of abortion was made between 1997-1998 (original protocol) and 2002-2004 (strict protocol). OUTCOME MEASURES: The mortality index and prevalence of organ system failure or dysfunction. RESULTS: In 1997-1998 there were 43 women with SAMM who survived and a further 10 maternal deaths due to complications of abortion, compared with 107 women with SAMM and 7 maternal deaths during 2002-2004. The mortality index declined from 18.9% in 1997-1998 to 6.1% in 2002-2004 (p = 0.02, odds ratio 0.28, 95% confidence limits 0.10 - 0.79). Significantly more women had hypovolaemic shock in 2002-2004 compared with 1997-1998 (54.4% v. 35.8%, p = 0.04), but fewer women had immune system failure including septic shock (18.4% v. 47.2%, p = 0.0002) and metabolic dysfunction (0 v. 5.7%, p = 0.03) and there was a trend to less renal failure (10.5% v. 22.6%, p = 0.06) and cardiac failure (4.4% v. 13.2%, p = 0.08). CONCLUSION: The strict protocol approach based on systemic evaluation in managing critically ill pregnant women with complications of abortion, coupled with an intensive, regular feedback mechanism, has been associated with a reduction in the mortality index.

Urine cytology as a screening test for bladder infiltration in cervical cancer.

Ultrasound is currently used as a screening test for bladder infiltration in patients with advanced-stage cervical cancer at our institution. Cystoscopy is reserved for patients with abnormal bladder ultrasound findings. This study was undertaken to reevaluate this policy and to compare the results of different screening tests. The study was carried out in Pretoria academic complex. All newly diagnosed cervical carcinoma patients stage II and above were included in this study. The standard staging investigations were done on all patients. In addition, urine midstream and catheter specimens were sent for cytology. Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight patients were enrolled into this study. At cystoscopy, 47 patients had bladder mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of 94% and specificity of 82% for bladder mucosa infiltration. The predictive value of a positive test is 31% and for a negative test is 99%. Catheter urine cytology is a very useful screening test for bladder infiltration in patients with cervical cancer. Cystoscopy should be reserved for patients with abnormal urine cytology in resource-poor settings with a large burden of disease.

A novel nonsense mutation in the EYA1 gene associated with branchio-oto-renal/branchiootic syndrome in an Afrikaner kindred.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the associations of hearing loss, branchial arch defects and renal anomalies. Branchiootic (BO) syndrome is a related disorder that presents without the highly variable characteristic renal anomalies of BOR syndrome. Dominant mutations in the human homologue of the Drosophila eyes absent gene (EYA1) are frequently the cause of both BOR and BO syndromes. We report a South African family of Afrikaner descent with affected individuals presenting with pre-auricular abnormalities and either hearing loss or bilateral absence of the kidneys. Genetic analysis of the pedigree detected a novel EYA1 heterozygous nonsense mutation in affected family members but not in unaffected family members or a random DNA panel. Through mutational analysis, we conclude that this particular mutation is the cause of BOR/BO syndrome in this family as a result of a truncation of the EYA1 protein that ablates the critical EYA homologous region. To the best of our knowledge, this is the first case of BOR/BO syndrome reported in Africa or in those of the Afrikaner descent.