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This introductory paper gives the readers a brief description of the scope and contents of this Special Issue that consists of papers devoted to Sustainable Transport Interchanges and intermodal networks. The issue depicts the results of the EU project ALLIANCE, which addresses the topic of intermodal interconnections and presents the results of the international collaboration teams, which were established within the context of the project.

Abstract Background Breeding of fire blight resistant scions and rootstocks is a goal of several international apple breeding programs, as options are limited for management of this destructive disease caused by the bacterial pathogen Erwinia amylovora. A broad, large-effect quantitative trait locus (QTL) for fire blight resistance has been reported on linkage group 3 of Malus ‘Robusta 5’. In this study we identified markers derived from putative fire blight resistance genes associated with the QTL by integrating further genetic mapping studies with bioinformatics analysis of transcript profiling data and genome sequence databases. Results When several defined E.amylovora strains were used to inoculate three progenies from international breeding programs, all with ‘Robusta 5’ as a common parent, two distinct QTLs were detected on linkage group 3, where only one had previously been mapped. In the New Zealand ‘Malling 9’ X ‘Robusta 5’ population inoculated with E. amylovora ICMP11176, the proximal QTL co-located with SNP markers derived from a leucine-rich repeat, receptor-like protein ( MxdRLP1) and a closely linked class 3 peroxidase gene. While the QTL detected in the German ‘Idared’ X ‘Robusta 5’ population inoculated with E. amylovora strains Ea222_JKI or ICMP11176 was approximately 6 cM distal to this, directly below a SNP marker derived from a heat shock 90 family protein gene ( HSP90). In the US ‘Otawa3’ X ‘Robusta5’ population inoculated with E. amylovora strains Ea273 or E2002a, the position of the LOD score peak on linkage group 3 was dependent upon the pathogen strains used for inoculation. One of the five MxdRLP1 alleles identified in fire blight resistant and susceptible cultivars was genetically associated with resistance and used to develop a high resolution melting PCR marker. A resistance QTL detected on linkage group 7 of the US population co-located with another HSP90 gene-family member and a WRKY transcription factor previously associated with fire blight resistance. However, this QTL was not observed in the New Zealand or German populations. Conclusions The results suggest that the upper region of ‘Robusta 5’ linkage group 3 contains multiple genes contributing to fire blight resistance and that their contributions to resistance can vary depending upon pathogen virulence and other factors. Mapping markers derived from putative fire blight resistance genes has proved a useful aid in defining these QTLs and developing markers for marker-assisted breeding of fire blight resistance.

Background: Cervical cancer screening strategies should ideally be informed by population-specific data. Strategies recommended for secondary prevention, are often inadequately studied in populations with high cervical disease burdens. This report describes the test performance measured against CIN2 + /CIN3 + histology in HIV-positive women (HPW) and HIV-negative women (HNW) with the aim to determine the most effective strategies to identify South African women at risk., Methods: Primary screening using visual inspection, cytology and HPV DNA (cobas®) was performed in two South African provinces on 456 HPW and 639 HNW participating in the multicentric DiaVACCS trial. Histology was obtained for 91.7% screen-positive and 42.7% screen-negative participants, and unavailable histology was determined by multiple imputation to adjust for verification bias. Cross-sectional test performance was calculated for single and combination test strategies with and without intermediate risk categories using different cut-offs. Minimum acceptability for sensitivity and specificity, treatment and follow-up numbers were considered to evaluate strategies., Results: The only single test to reach acceptability in HPW was cytology (LSIL) [sensitivity 71.2%; specificity 90.5%; treatment 33.4%]; in HNW only HPV (hr) qualified [sensitivity 68.2%; specificity 85.2%; treatment 23.5%]. The universally best performing strategy which also resulted in smaller treatment numbers without intermediate risk group was primary HPV(hr), with treatment of both HPV(16/18) and cytology (ASCUS +) [HPW: sensitivity 73.6%; specificity 89.7%; treatment 34.7%. HNW: sensitivity 59.1%; specificity 93.6%; treatment 13.9%]. DNA testing for hrHPV (any) and hrHPV (16/18) was the best universally acceptable strategy with an intermediate risk category (early follow-up) in HPW [sensitivity 82.1%; specificity 96.4%; treatment 17.1%; follow-up 31.4%] and HNW [sensitivity 68.2%; specificity 96.7%; treatment 7.6%; follow-up 15.9%]. In comparison, using both HPV (16/18) and cytology (ASCUS +) as secondary tests in hrHPV positive women, decreased follow-up [HPW 13.8%, HNW 9.6%], but increased treatment [HPW 34.7%, HNW 13.9%]., Conclusion: Using hrHPV (any) as primary and both HPV16/18 and cytology as secondary tests, was universally acceptable without an intermediate risk group. Strategies with follow-up groups improved screening performance with smaller treatment numbers, but with effective management of the intermediate risk group as prerequisite., (© 2024. The Author(s).)

Objectives: Cervical cancer is preventable and caused by persistent infection with oncogenic human papilloma virus (HPV) types. HPV screening is more sensitive and is the preferred screening test. HPV screening data are mainly from developed settings, and the purpose of this study was to investigate the performance of HPV screening in previously unscreened HIV positive and negative women., Methods: In this cross sectional multicenter study, liquid based cytology and HPV testing were performed on women attending different clinics. Patients with positive screening tests had colposcopy and biopsy or large loop excision of the transformation zone. Some women with normal screening had colposcopy and biopsy. Data of women with histology results, and data of HIV positive and negative women were analyzed for comparison. For women without histology results, data were imputed using a statistical model., Results: In 903 women with known HIV status, 683 (75.6%) had negative cytology, 202 women (22.4%) had abnormal cytology, and in 18 patients (2.0%) the results were uncertain. Mean age was 41.4 years (range 25-65). HPV tests were negative in 621 women (68.8%). In HIV positive women, 54.5% tested negative compared with 79.7% HIV negative women (p<0.0001). HPV screening had higher sensitivity (60.9%), but lower specificity (82.4%), compared with cytology (48.6% and 86.7%) for detection of cervical intraepithelial neoplasia (CIN) 2+ in all women. For detection of CIN 3+, HPV screening had higher sensitivity (70.4%) compared with cytology (62.9%), and specificity (75.5%) was lower compared with cytology at a threshold of atypical squamous cells of undetermined significance (ASCUS+) (82.4%)., Conclusion: HPV screening was more sensitive than cytology in HIV positive and HIV negative women, but specificity was lower. Although HPV screening should be the preferred screening test, cytology is a suitable screening test in HIV positive women in low resource settings., Trial Registration Number: NCT02956031., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH., Methods: In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher., Results: Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003])., Conclusions: Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing., Competing Interests: Potential conflicts of interest. C. J. L. M. M., and R. D. M. S. are minority shareholders of Self-screen, a spin-off company of Amsterdam UMC, location Vrije Universiteit; Self-screen develops, manufactures and licenses high-risk HPV and methylation marker assays for cervical cancer screening and holds patents on these tests. A research use only version of the methylation assay has been made available by Self-screen (www.self-screen.nl). C. J. L. M. M. is the part-time chief executive officer of Self-screen and served occasionally on scientific advisory boards and/or speakers bureaus for GlaxoSmithKline (GSK), Qiagen, Sanofi Pasteur MSD/Merck, and Asieris Pharma/Ismar Healthcare. He also reports consulting fees from Qiagen, GSK, Sanofi Pasteur MSD/Merck, Asieris Pharma/Ismar Healthcare, paid to the author, and support for attending meetings and/or travel, paid to the author, from Qiagen, GSK, Sanofi Pasteur MSD/Merck, and Self-screen. He formerly had a very small number of shares of MDXHealth and Qiagen. R. D. M. S. is an inventor on patents on methylation markers for cervical cancer (patents are licensed to Self-screen). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

Background: National human papillomavirus (HPV) vaccination programs could reduce global cervical cancer morbidity and mortality with support from health care providers. We assessed providers' perceptions of HPV vaccination in 5 countries., Methods: We identified providers from 5 countries where national HPV vaccination programs were at various stages of implementation: Argentina, Malaysia, South Africa, South Korea, and Spain. Providers authorized to administer adolescent vaccines completed an in-depth survey, reporting perceptions of barriers and facilitators to initiating and completing HPV vaccination, and logistical challenges to HPV vaccination., Results: Among 151 providers, common barriers to HPV vaccination initiation across all countries were parents' lack of awareness (39%), concerns about vaccine safety or efficacy (33%), and cost to patients (30%). Vaccination education campaign (70%) was the most commonly cited facilitator of HPV vaccination initiation. Common barriers to series completion included no reminder system or dosing schedule (37%), loss to follow-up or forgetting appointment (29%), and cost to patients (25%). Cited facilitators to completing the vaccine series were education campaigns (45%), affordable vaccination (32%), and reminder/recall systems (22%). Among all countries, high cost of vaccination was the most common logistical challenge to offering vaccination to adolescents (33%)., Conclusions: Incorporating provider insights into future HPV vaccination programs could accelerate vaccine delivery to increase HPV vaccination rates globally., Competing Interests: Conflict of Interest and Sources of Funding: K.L.R. has been a paid speaker and has received travel support from Merck for meetings unrelated to this study. S.d.S. has received institutional grants from Merck for human papillomavirus–related research. J.S.S. has received research grants, served on paid advisory boards, and/or been a paid speaker for GlaxoSmithKline and Merck over the past 5 years. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.)

Objective: To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV., Design: Post-hoc analysis using data from a South African study cohort., Methods: Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome., Results: Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test)., Conclusion: Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.

Study Objective: To assess adolescent health care providers' recommendations for, and attitudes towards human papillomavirus (HPV) vaccination in 5 countries., Design: In-depth interviews of adolescent health care providers, 2013-2014., Setting: Five countries where HPV vaccination is at various stages of implementation into national programs: Argentina, Malaysia, South Africa, South Korea, and Spain., Participants: Adolescent health care providers (N = 151) who had administered or overseen provision of adolescent vaccinations (N = Argentina: 30, Malaysia: 30, South Africa: 31, South Korea: 30, Spain: 30)., Main Outcome Measures: Frequency of HPV vaccination recommendation, reasons providers do not always recommend the vaccine and facilitators to doing so, comfort level with recommending the vaccine, reasons for any discomfort, and positive and negative aspects of HPV vaccination., Results: Over half of providers 82/151 (54%) recommend HPV vaccination always or most of the time (range: 20% in Malaysia to 90% in Argentina). Most providers 112/151 (74%) said they were comfortable recommending HPV vaccination, although South Korea was an outlier 10/30 (33%). Providers cited protection against cervical cancer 124/151 (83%) and genital warts 56/151 (37%) as benefits of HPV vaccination. When asked about the problems with HPV vaccination, providers mentioned high cost 75/151 (50% overall; range: 26% in South Africa to 77% in South Korea) and vaccination safety 28/151 (19%; range: 7% in South Africa to 33% in Spain). Free, low-cost, or publicly available vaccination 59/151 (39%), and additional data on vaccination safety 52/151 (34%) and efficacy 43/151 (28%) were the most commonly cited facilitators of health provider vaccination recommendation., Conclusion: Interventions to increase HPV vaccination should consider a country's specific provider concerns, such as reducing cost and providing information on vaccination safety and efficacy., (Copyright © 2018 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Purpose: The World Health Organization revised its human papillomavirus (HPV) vaccination recommendations to include a two (2-) dose schedule for girls aged ≤ 15 years. We investigated acceptability of 2- versus 3-dose schedule among adolescent vaccination providers and mothers of adolescent girls in five countries., Methods: Adolescent vaccination providers (N = 151) and mothers of adolescent girls aged 9-14 years (N = 118) were recruited from Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preference for a 2- versus 3-dose HPV vaccination schedule via quantitative surveys. Mothers' attitudes towards a 2-dose schedule were assessed through focus group discussions., Results: Most adolescent providers preferred a 2- over a 3-dose HPV vaccination schedule (overall: 74%), with preference ranging from 45.2% (South Africa) to 90.0% (South Korea). Lower cost, fewer clinic visits, and higher series completion were commonly cited reasons for 2-dose preference among providers and mothers. Safety and efficacy concerns were commonly cited barriers to accepting a 2-dose HPV vaccination schedule among providers and mothers. Mothers generally accepted the reduced schedule, however requested further information from a trusted source., Conclusions: Adolescent vaccination providers and mothers preferred the 2-dose over 3-dose HPV vaccination schedule. Acceptability of a 2-dose HPV vaccination could be improved with additional information to providers and mothers on HPV vaccination safety and efficacy.

Introduction: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa., Methods: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects., Results: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3 + ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3 + sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers., Conclusions: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3 + , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Objective: Cervical cancer is the leading cause of cancer-related death in women in South Africa. This study evaluates DNA methylation levels in cervical (pre)cancer and aims to assess the value of high-risk human papillomavirus (hrHPV) testing and methylation analysis, alone or in combination, on physician-taken cervical scrapes to detect cervical cancer, and cervical intraepithelial neoplasia grade 3 (CIN3) in an HIV-infected South African population., Design: Prospective observational multicentre cohort study., Methods: Women from a cohort of women living with HIV (n = 355) and a referral cohort (n = 109, 60% HIV seropositive) were included. Cervical scrapes were collected for hrHPV testing and methylation analysis of cell adhesion molecule 1, T-lymphocyte maturation-associated protein, and microRNA124-2 genes. Histologic endpoints were available for all participants. Performance for detection of CIN3 or worse (CIN3+) was determined in the cohort of women living with HIV and different testing strategies were compared., Results: HrHPV and methylation positivity rates increased with severity of cervical disease in the two study cohorts, each reaching 100% in samples of women with carcinoma. HrHPV testing showed a sensitivity for CIN3+ of 83.6%, at a specificity of 67.7%. Methylation analysis showed a comparable CIN3+ sensitivity of 85.2%, but a significantly lower specificity of 49.6%. HrHPV testing with reflex methylation analysis showed a CIN3+ sensitivity of 73.8%, at a specificity of 81.5%., Conclusion: In this HIV-infected South African population, stratifying hrHPV-positive women with reflex methylation analysis detects all cervical carcinomas and yields an acceptable sensitivity and specificity for CIN3+.

Introduction: Multipurpose vaccines (MPVs) could be formulated to prevent multiple sexually transmitted infections simultaneously. Little is known about acceptability of MPVs among vaccine health care providers (HCPs) or mothers of adolescent girls., Methods: 151 adolescent vaccine providers and 118 mothers of adolescent girls aged 9-14 were recruited from five geographically-diverse countries: Argentina, Malaysia, South Africa, South Korea, and Spain. We assessed providers' preferences for single-purpose human papillomavirus (HPV) vaccine versus MPVs (including HPV+herpes simplex virus (HSV)-2, HPV+HIV, or HPV+HSV-2+HIV) via quantitative surveys. Maternal MPV attitudes were assessed in four focus group discussions (FGDs) in each country., Results: Most providers preferred MPVs over single-purpose HPV vaccination, with preference ranging from 61% in Malaysia to 96% in South Africa. HPV+HSV-2+HIV was the most preferred MPV formulation (56-82%). Overall, 53% of the mothers preferred MPVs over single-purpose HPV vaccines, with strongest support in South Africa (90%) and lowest support in South Korea (29%). Convenience and trust in the health care system were commonly-cited reasons for MPV acceptability. Safety and efficacy concerns were common barriers to accepting MPVs, though specific concerns differed by country. Across FGDs, additional safety and efficacy information on MPVs were requested, particularly from trusted sources like HCPs., Conclusions: Though maternal acceptability of MPVs varied by country, MPV acceptability would be enhanced by having HCPs provide parents with additional MPV vaccine safety and efficacy information. While most providers preferred MPVs, future health behavior research should identify acceptability barriers, and targeted provider interventions should equip providers to improve vaccination discussions with parents., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Occupational injuries in medical students are concerning, especially in countries with a high prevalence of bloodborne infections. With more HIV-infected patients on antiretroviral treatment, appropriate post-exposure prophylaxis (PEP) depends on knowledge of source patients' infection status and treatment response. This study determined the number and type of exposure incidents, reporting practices, and PEP use among medical students at the University of Pretoria, South Africa., Methodology: Data were collected from an anonymous voluntary questionnaire completed by medical students from years 1 to 6 of study as well as from incident records archived at the Department of Family Medicine. Data were described and tests of association performed in Stata 11., Results: Thirteen percent of students overall and 21% of senior students reported an incident in the preceding year. The majority of incidents occurred during phlebotomy, with fatigue and work pressure found to be major contributing factors. Underreporting was common and many students displayed a lack of risk awareness and a preference for managing the incident privately. Although 59% knew the HIV-status of the source patient, less than a third knew the viral load and only 16.9% the regimen. Side-effects on antiretroviral treatment used for PEP were common and only about three-quarters of the students completed the course., Conclusions: We recommend targeted training, especially in the senior years, together with improving the work environment through attention to working hours, sharps disposal and ready availability of safety devices, improved reporting systems, individualised PEP, and possibly the implementation of an occupational injury support line.

Background: Although the use of highly active antiretroviral therapy in HIV positive individuals has proved to be effective in suppressing the virus to below detection limits of commonly used assays, virological failure associated with drug resistance is still a major challenge in some settings. The prevalence and effect of pre-treatment resistance associated variants on virological outcomes may also be underestimated because of reliance on conventional population sequencing data which excludes minority species. We investigated long term virological outcomes and the prevalence and pattern of pre-treatment minority drug resistance mutations in individuals initiating HAART at a local HIV clinic., Methods: Patient's records of viral load results and CD4 cell counts from routine treatment monitoring were used and additional pre-treatment blood samples for Sanger sequencing were obtained. A selection of pre-treatment samples from individuals who experienced virological failure were evaluated for minority resistance associated mutations to 1 % prevalence and compared to individuals who achieved viral suppression., Results: At least one viral load result after 6 months or more of treatment was available for 65 out of 78 individuals followed for up to 33 months. Twenty (30.8 %) of the 65 individuals had detectable viremia and eight (12.3 %) of them had virological failure (viral load > 1000 RNA copies/ml) after at least 6 months of HAART. Viral suppression, achieved by month 8 to month 13, was followed by low level viremia in 10.8 % of patients and virological failure in one patient after month 20. There was potentially reduced activity to Emtricitabine or Tenofovir in three out of the eight cases in which minority drug resistance associated variants were investigated but detectable viremia occurred in one of these cases while the activity of Efavirenz was generally reduced in all the eight cases., Conclusions: Early viral suppression was followed by low level viremia for some patients which may be an indication of failure to sustain viral suppression over time. The low level viremia may also be representing early stages of resistance development. The mutation patterns detected in the minority variants showed potential reduced drug sensitivity which highlights their potential to dominate after treatment initiation., Trial Registration: Not applicable.

Background: In Africa, data on the relationship between oncogenic human papillomavirus (HPV) types, immune status and cervical preinvasive lesions are lacking., Methods:  We investigated low-risk (lrHPV) and high-risk (hrHPV) HPV types in a cohort of women with cervical intraepithelial neoplasia (CIN) II/III confirmed on histological examination, in an urban setting with a high prevalence of HIV infection., Results:  Of 270 women with confirmed CIN II/III, 45 were HIV-negative and 225 HIV-positive. HIV-infected women had significantly more HPV type infections, including all HPV (p&lt;0.001) and hrHPV (p=0.014) types. The prevalences of one or more hrHPV type/s were 93.3% and 92.9% in HIV-negative and positive patients, respectively. The most prevalent hrHPV type among HIV-negative women was HPV 16, followed by HPV 52, 31, 35 and 58. Among HIV-positive women, HPV 16 was followed by HPV 58, 35, 51 and 52. Not yet qualifying qualify for highly active antiretroviral therapy (HAART) (CD4 count &gt;350 cells/μL) or having received HAART for ≥12 months were negatively associated with HPV 18, 33, 45, 51, 52, 59 and 82., Conclusions:  In South Africa, burdened by the HIV pandemic, high numbers of high- and low-risk HPV type infections are present in women with cervical preneoplasia. HPV type distribution differs among varying levels of HIV-induced immune depletion.

Objectives: Cervical cancer is the most common cause of cancer-related deaths among South African women. Viral types associated with cervical cancer may differ not only between countries and regions, but possibly also between human immunodeficiency virus (HIV)-infected and noninfected women., Methods: In a population with high HIV prevalence, human papillomavirus (HPV)-type infections detected with DNA analyses were reported in a cohort of 299 women diagnosed with invasive cervical cancer., Results: One hundred fifty-four women tested HIV negative, 77 tested HIV positive, and HIV status was unknown for 68 women. The mean age for HIV-positive women was 41.3 years, and that for HIV-negative women was 55.8 years (P < 0.001). Ninety-two percent of women tested HPV-DNA positive. Human papillomavirus types 16 and/or 18 were present in 62% of HIV-negative women and 65% of HIV-positive women. The 5 most common HPV types in HIV-positive women were, in decreasing frequency, HPV 16, 18, 45, 33, and 58. In HIV-negative women, the most common HPV types were HPV 16, 18, 35, and 45, followed by HPV 33 and 52. Human papillomavirus type 45 was more likely in the HIV positive compared with the HIV negative (odds ratio, 3.07; 95% confidence interval, 1.07-8.77). The HIV-positive women had more multiple high-risk HPV-type infections than did the HIV-negative women (27% vs 8%, P = 0.001)., Conclusions: A high number of women in South Africa with cervical cancer are HIV positive. Without viral cross-protection, HPV vaccines should prevent around 65% of cervical cancers in this population. Human papillomavirus type 45 infection is significantly linked to HIV and important for future vaccine developments.

The risks associated with infection of healthcare workers and students with blood-borne pathogens, specifically HIV, hepatitis B virus and hepatitis C virus, are often neglected. South Africa (SA) currently has no official policies or guidelines in place for the prevention and management of these infections. This article reviews the available data and international guidelines with regard to infected healthcare practitioners and makes minimum recommendations for the SA setting.

Background: Human papillomavirus (HPV) infection is well known to be associated with head and neck cancers (HNCs). HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners, but the epidemiology of oral and oropharyngeal HPV in South African men has not yet been studied., Objectives: To determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa (SA)., Methods: Male factory workers were recruited. Oral rinse and gargle samples were tested for 37 HPV types using the Linear Array HPV Genotyping Test (Roche Molecular Systems). A questionnaire was used to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional., Results: The HPV prevalence was 5.6% among men (N=125) aged 17 - 64 years. High-risk HPV (hrHPV) types 16 and 68 were found in two men. Oral sex seemed to be an uncommon practice in the majority of respondents, but the two respondents with hrHPV did practise oral sex. There was a statistically significant association between HPV infection and an increased number of sexual partners (p=0.027), but not between HPV and substance use, HIV status or clinical mucosal pathology., Conclusion: The prevalence of oral and oropharyngeal HPV was lower than reported in other countries. An association between oral HPV and having multiple sexual partners was found. A larger nationwide study would give a more representative view of the burden of oral and oropharyngeal HPV infection in SA.

Background: To evaluate the prevalence of human papilloma virus (HPV) infection and types in the oral and cervix mucosa of treatment-naïve HIV-1-positive women with CD4 counts less than 300 cells per ml with no HPV-associated oral lesions., Methods: Oral epithelium was harvested from the buccal mucosa and lateral borders of the tongue and cervical samples were collected from the endocervical area of 30 women, 22-64 years old. Cytobrush Plus cell collectors were used for sampling both anatomical areas. Genital pathology, obstetric and gynaecological history, co-morbid disease, hormone therapy, sexual behavior and smoking history were assessed via physical examination and clinical interviews. Special investigations included cervical Papanicolau smears, CD4 counts and HIV-1 viral loads. The linear array HPV test was used to determine HPV genotypes present in the specimens., Results: Oral HPV were identified in 20% (n = 6) of the patients, of which two had infection with two HPV types. Genital HPV was found in 96.7% (n = 29) of the women, of which only 14 had cytological abnormalities on Papanicolau smear. Infection with multiple HPV types were present in 93.1% (n = 27) of the patients, with an average of four HPV types per individual., Conclusions: South African HIV-positive women with CD4 counts less than 300 cells per ml have a significant risk of cervical HPV strains and multiple strain infection of the cervix. The prevalence of HPV in normal oral mucosa was low but high-risk types were present. Limited correlation between oral HPV types and those identified in the cervical mucosa was found.

Objective: Gadolinium neutron capture therapy (GdNCT) is a potential treatment for malignant tumors based on two steps: (1) injection of a tumor-specific (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction can induce cell death provided that Gd is proximate to DNA. Here, we studied the nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two Gd compounds commonly used for magnetic resonance imaging, to evaluate their potential as GdNCT agents., Methods: Using synchrotron X-ray spectromicroscopy, we analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor samples from GBM patients injected with Gd-DTPA., Results: In cell cultures, Gd-DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after single and double injection of Gd-DOTA, respectively. In contrast, in human GBM tumors 6.1% of the cell nuclei contained Gd-DTPA., Discussion: Efficacy of Gd-DTPA and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient number of tumor cell nuclei incorporating Gd. Although multiple administration schedules in vivo might induce Gd penetration into more tumor cell nuclei, a search for new Gd compounds with higher nuclear affinity is warranted before planning GdNCT in animal models or clinical trials.

We present a new differential-thickness coating technique to analyze insulating samples with X-ray PhotoElectron Emission spectroMicroscopy (X-PEEM). X-PEEM is non-destructive, analyzes the chemical composition and crystal structure of minerals and can spatially resolve chemical species with a resolution presently reaching 35 nm. We tested the differential coating by analyzing a 4.4 billion-year-old zircon (ZrSiO(4)) containing silicate inclusions. We observed quartz (SiO(2)) inclusions smaller than 1microm in size that can only be analyzed non-destructively with synchrotron spectromicroscopies. With the removal of charging we greatly extend the range of samples that can be analyzed by X-PEEM.