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In the present study 1,709 cattle, including 1,118 Drakensberger (DRB), 377 Nguni (NGI), and 214 Tuli (TUL), were genotyped using the GeneSeek® Genomic Profiler™ 150 K bovine SNP panel. A genomic data set of 122,632 quality-filtered single nucleotide polymorphisms (SNPs) were used to identify selection signatures within breeds based on conserved runs of homozygosity (ROH) and heterozygosity (ROHet) estimated with the detectRUNS R package. The mean number of ROH per animal varied across breeds ranging from 36.09 ± 12.82 (NGI) to 51.82 ± 21.01 (DRB), and the mean ROH length per breed ranged between 2.31 Mb (NGI) and 3.90 Mb (DRB). The smallest length categories i.e., ROH < 4 Mb were most frequent, indicating historic inbreeding effects for all breeds. The ROH based inbreeding coefficients (F ROH ) ranged between 0.033 ± 0.024 (NGI) and 0.081 ± 0.046 (DRB). Genes mapped to candidate regions were associated with immunity (ADAMTS12, LY96, WDPCP) and adaptation (FKBP4, CBFA2T3, TUBB3) in cattle and genes previously only reported for immunity in mice and human (EXOC3L1, MYO1G). The present study contributes to the understanding of the genetic mechanisms of adaptation, providing information for potential molecular application in genetic evaluation and selection programs., Competing Interests: Declarations. Ethics approval: The genotypic data used in the current study was provided by SA Stud Book with consent from the Drakensberger, Nguni, and Tuli Cattle Breeders' Society of South Africa. The study was approved by the Ethics Committee in the Faculty of Natural and Agricultural Sciences at the University of Pretoria (NAS235/2022). Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s).)

Double muscling occurs when the myostatin (MSTN) gene is deactivated due to a series of mutations, leading to uncontrolled muscle growth and excessive muscle fiber accumulation, as the gene can no longer effectively regulate muscle development. This study aimed to assess the impact of MSTN variants and their combinations on growth traits, namely direct birth weight (BW DIR ), direct weaning weight (WW DIR ), average daily gain (ADG) and feed conversion ratio (FCR) in the South African (SA) Bonsmara. Genomically enhanced estimated breeding value (GEBVs) for traits of interest, and MTSN genotypes for SA Bonsmara animals were available for the study. Thirteen MSTN variants (Nt821, Q204X, F94L, E226X, E291X, C313Y, Nt419, S105C, D182N, Nt414, Nt324, Nt267, and Nt748) were routinely genotyped using the IDBv3 SNP array. Genotypic frequencies of MSTN variants ranged from 1.18% for Q204X to 35.02% for Nt748. No association was observed between the Nt267 variant and any growth traits, while both Nt748 and Nt414 variants affected WW DIR , ADG and FCR (p < 0.05). The results of the effect of multiple variants on growth traits indicated that there was an additive effect when more than one MSTN variant was present in an individual. This study is the first study to report the impact of MSTN variants on traits of economic importance in the SA Bonsmara breed., (© 2024. The Author(s).)

Background: Infection with the human papillomavirus (HPV) is a necessary cause of cervical cancer and is one of the most prevalent sexually transmitted infections worldwide. Primary prevention strategies target reducing HPV acquisition through vaccination, limiting exposure (e.g. delayed sexual debut, barrier contraception) and health education focusing on sexual behaviour and tobacco use., Methods: The ImmunoVACCS study, conducted from 2019 to 2022 in two provinces in South Africa, examined sociodemographic characteristics, sexual practices, and knowledge of cervical cancer and the HPV vaccine among young female vaccine recipients. It encompassed participants from the previously conducted vaccine implementation trials, VACCS 1 and VACCS 2 (2011-2014). Recruitment involved telephonic contact with eligible potential participants. Data were collected through self-administered questionnaires., Results: One hundred and eleven participants took part in the current study (median age: 20 years; age range: 16-22 years). Most sexually active participants had their first engagement in secondary school (96.2%), and 77.2% used contraception during their last sexual activity. Knowledge gaps were evident, with only 13.5% recognising cervical cancer's cervix origin and 3.6% attributing it to a virus. Despite this, 70.3% had heard of a vaccine for cervical cancer. Less than half knew about the importance of regular Pap smears (49.5%), vaccine protection (44.1%) or condom use (20.7%) against HPV and cervical cancer., Conclusion: The current study demonstrates that young women still lack complete information on cervical cancer and its risk factors even after receiving health education linked with vaccination.Contribution: This study underscores the necessity of ongoing education about HPV, its risks and preventive measures among young women to combat cervical cancer.

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.)

In southern Africa, the Nguni cattle breed is classified as an indigenous and transboundary animal genetic resource (AnGR) that manifests unique adaptation abilities across distinct agroecological zones. The genetic integrity of various ecotypes is under potential threat due to both indiscriminate crossbreeding and uncontrolled inbreeding. The aim of this study was to assess the genetic diversity and autozygosity that exist both across countries (ES: eSwatini; SA: South Africa) and within countries (SA), between purebred stud animals (SA-S) and research herds (SA-R). Subsets of 96 ES, 96 SA-S, and 96 SA-R genotyped for 40,930 common SNPs were used to study genome-wide profiles of runs of homozygosity (ROH) and heterozygosity (ROHet) as well as inbreeding levels and population structure. The highest percentage (39.8%) of the 2168 ROH segments was 4-8 Mbp in length, whereas 65% of the 935 ROHet segments fell within the 0.5-1 Mbp length category. Inbreeding coefficients indicated positive but low inbreeding (F ROH>1Mbp range: 0.025 for SA-S to 0.029 for SA-R). Principal component (PCA) and population structure analyses illustrated genome-level distinctness of (1) the Nguni from global indicine (Boran) and taurine (Hereford) breeds (K = 3), (2) the SA Nguni populations from the ES Nguni population (K = 4), and (3) different Nguni ecotypes within countries (K = 8). Furthermore, greater admixture was observed for the SA-R population compared to purebred SA-S population (shared ancestry = 0.631 ± 0.353 compared to 0.741 ± 0.123), and fewer genomics-defined ES ecotypes were observed than phenotypically (pre)defined. Overall, the results illustrated that genetic uniqueness within the sampled Nguni cattle resulted from both geographic isolation and exposure to different breeding strategies (and, selection pressures). A further loss of genetic variability should be monitored to prevent the endangerment of unique and beneficial ecotypes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

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.

Objective: The platform provided by human papillomavirus (HPV) vaccination for linked public health interventions to improve cervical cancer prevention remains incompletely explored. The Vaccine And Cervical Cancer Screen (VACCS) cross-sectional observation trials aimed to evaluate the efficacy of school-based HPV vaccination linked with maternal cervical cancer screening., Methods: Girls from 29 schools in two provinces in South Africa were invited in writing to receive HPV vaccination. Two approaches to informed consent were compared, namely an audiovisual presentation (VACCS1) and in written format (VACCS2). Markers of vaccine uptake and coverage were calculated, namely uptake among the invited and consented cohorts, and rates of completion and sufficient vaccination. Mothers and female guardians received educational material about cervical cancer, and either a self-sampling device or an invitation to attend existing screening facilities. Knowledge was assessed via structured questionnaires (before and after), and screening uptake was self-reported and directly assessed and compared between these approaches., Results: Vaccine acceptance among 5137 invited girls was similar for the two methods of consent; 99.3% of consented girls received a first dose; overall completion rate was 90.5%. More girls were vaccinated using a two-dose (974/1016 (95.9%)) than a three-dose regimen (1859/2030 (91.6%)). The questionnaire (n=906) showed poor maternal knowledge which improved significantly (p<0.05) after health education; only 54% of mothers reported any previous screening. The offer of a self-sampling device (n=2247) was accepted by 43.9% of mothers, but only 26% of those invited to screen at existing facilities (n=396) reported subsequent screening., Conclusions: Successful linking of primary health interventions to control cervical cancer was demonstrated. School-based HPV vaccination, linked to health education, self-sampling, and molecular screening resulted in significant improvements in knowledge and screening., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Poor knowledge about cervical cancer plays a role in limiting screening uptake. HPV vaccination provides an untested platform to distribute information that could possibly improve knowledge and screening coverage., Objective: To measure changes in knowledge and screening uptake when information and screening opportunities were provided to mothers of adolescent HPV vaccine recipients., Methods: During an HPV vaccine implementation project in the Western Cape (WC) and Gauteng Province (GP), South Africa, information about cervical cancer was provided to parents during a lecture, written information was distributed, and mothers were then invited to either screen at their clinic (WC) or use a self-screening kit (GP). A structured questionnaire was used to test cervical cancer knowledge and screening practices, comparing these before and after the project and between the two screening groups., Results: Complete data for both questionnaires were available for 777 of 906 recruited women. Initial knowledge was poor, but on retesting 6 months later, knowledge about symptoms (p&lt;0.005), screening (p&lt;0.005) and vaccination (p&lt;0.05) improved significantly after the information session and school-based HPV vaccination. In the second questionnaire, women reported significantly more screening and the last reported screening test was more recent. This improvement was more favourable in GP than in the WC (41% v. 26% reporting screening in the past 12 months)., Conclusion: These results demonstrate how adolescent HPV vaccine programmes can help to control cervical cancer among mothers by offering information and screening. It is important not to lose this opportunity to educate mothers and their daughters and offer effective methods to prevent cervical cancer in both generations.

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 Namaqua Afrikaner is an endangered sheep breed indigenous to South Africa, primarily used in smallholder farming systems. Genetic characterization is essential for the breed's conservation and utilization. In this study, a genetic characterization was performed on 144 Namaqua Afrikaner sheep kept at the Karakul Experimental Station (KES), Carnarvon Experimental Station (CES), and a private farm Welgeluk (WGK) using 22 microsatellite markers. The mean number of alleles observed was low (3.7 for KES, 3.9 for CES, and 4.2 for WGK). Expected heterozygosity values across loci ranged between 46 % for WGK, 48 % for KES, and 55 % for CES, indicating low to moderate genetic variation. The analysis of molecular variance revealed that 89.5 % of the genetic variation was due to differences within populations. The population structure confirmed the differentiation of three clusters with high relationships between the CES and WGK populations. In the population structure comparison with Pedi and South African Mutton Merino sheep, limited hybridization between the Namaqua Afrikaner sheep and both of these breeds was observed. The results of this study will serve as a reference for genetic management and conservation of Namaqua Afrikaner sheep.