Norovirus epidemiology in Africa : a review

Norovirus (NoV) is recognised as a leading cause of gastroenteritis worldwide across all age groups. The prevalence and diversity of NoVs in many African countries is still unknown, although early sero-prevalence studies indicated widespread early infection. Reports on NoVs in Africa vary widely in terms of study duration, population groups and size, inclusion of asymptomatic controls, as well as genotyping information. This review provides an estimate of NoV prevalence and distribution of genotypes of NoVs in Africa. Inclusion criteria for the review were study duration of at least 6 months, population size of >50 and diagnosis by RT-PCR. As regions used for genotyping varied, or genotyping was not always performed, this was not considered as an inclusion criteria. A literature search containing the terms norovirus+Africa yielded 74 publications. Of these 19 studies from 14 out of the 54 countries in Africa met the inclusion criteria. Data from studies not meeting the inclusion criteria, based on sample size or short duration, were included as discussion points. The majority of studies published focused on children, under five years of age, hospitalised with acute gastroenteritis. The mean overall prevalence was 13.5% (range 0.8– 25.5%) in children with gastroenteritis and 9.7% (range 7–31%) in asymptomatic controls, where tested. NoV GII.4 was the predominant genotype identified in most of the studies that presented genotyping data. Other prevalent genotypes detected included GII.3 and GII.6. In conclusion, NoV is a common pathogen in children with diarrhoea in Africa, with considerable carriage in asymptomatic children. There is however, a paucity of data on NoV infection in adults.http://www.plosone.orgam2016Medical Microbiolog

Isolation and preliminary characterization of a caprine rotavirus

Five cytopathic rotavirus strains were isolated in MA 104 cells from stool specimens of kids with diarrhoea. Pre-treatment of the virus with trypsin and incorporation of low levels of trypsin in the maintenance medium were important for the successful cultivation of the strains in these cells. The isolates were shown to be group A rotaviruses by antigenic reactivity with a group A monoclonal antibody. This was confirmed by the migration patterns of the viral RNA genome during polyacrylamide gel electrophoresis, which also confirmed that all five strains had an identical RNA electropherotype. Analysis with monoclonal antibodies to the subgroup-specific VP6 antigen showed that these strains carried the subgroup I epitope.The articles have been scanned in colour with a HP Scanjet 5590; 600dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format.mn201

Molecular epidemiology of group A Rotaviruses in water sources and selected raw vegetables in Southern Africa

Group A rotaviruses (RVs) are the most important cause of acute viral gastroenteritis in infants and young children. In this study raw and treated drinking water supplies at plants in two geographic areas, as well as selected irrigation water and corresponding raw vegetables in three regions of southern Africa, were screened for the presence of RVs using molecular techniques. Group A RVs were detected in 11.8% of partially treated and 1.7% of finally treated drinking water samples and in 14% of irrigation water samples and 1.7% of corresponding raw vegetable samples. Type-specific reverse transcriptase-PCR and sequence analysis revealed the presence of multiple types (G1, G2, G8, and G9) in irrigation water and single types (G1 or G3) in raw and treated drinking water. Group A RVs detected in all samples consisted of mixed P types (P[4], P[6], P[8], and P[9]), with P[6] predominating. The detection of types G8, G9, and P[6] reflects the emergence of these types in clinical infections. The similarity of environmental types to those in patients with clinical RV infections confirms the value of wastewater screening as a tool for assessing RVs circulating in communities, with the benefit of detecting types that cause both clinical and subclinical infections. The results provide new information on RV types in water and related environments and identify the potential risk of waterborne transmission. In addition, the presence of RVs in drinking water underlines shortcomings in quality specifications. These data provide valuable information regarding the prevalence of RVs in environmental sources, with important implications for vaccine development.This study was supported by grants from the Water Research Commission, the Poliomyelitis Research Foundation, and the Research Committee, School of Medicine, University of Pretoria. A postdoctoral fellowship for W.B.V.Z. from the South African Medical Research Council is also gratefully acknowledged

Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons : a randomized, double-blind, placebo-controlled trail

BACKGROUND: Human rotavirus vaccine (HRV; i.e., Rotarix) reduced the incidence of severe rotavirus gastroenteritis (RVGE) by 77% (95% Conficence interval: 56% to 88%) during the first year of life in South Africa. Persistence of HRV-derived protection against RVGE during subsequent rotavirus seasons, although evident in industrialized settings, remains to be established in African settings. This study reports on the efficacy of HRV against server RGVE over two consecutive rotavirus seasons in South African children. METHODS: A prospective, double-blind, placebo controlled multi-centered trail in South Afria and Malawi randomly assigned infants in a 1:1:1 ration to receive either two (10 and 14 weeks; HRV_2D) or three (6, 10 and 14 weeks; HRV_3D) doses of HRV or placebo. The primary analysis involved pooling of HRV_2D and HRV_3D arms. Episodes of gastroenteritis caused by wild-type rotavirus were identified through active follow-up surveillance and graded by the Vesikari scale. RESULTS: 1,339 infants (447 in the HRV_2D group, 447 in the HRV_3D group and 445 in the placebo group) were enrolled in Year 2 of the study, including 1,035 (77.3%) who were followed up over two consecutive rotavirus seasons (i.e., Cohort 2 subjects). Rotarix was associated with ongoing protection against severe RVGE, preventing 2.5 episodes per 100 vaccinated children over two consecutive rotavirus seasons; vaccine efficacy: 59% (95% Confidence interval: 1 to 83). An exploratory analysis indicated better immunogenicity (among Cohort 1 subjects) and a higher point-efficacy estimate over two seasons in the HRV_3D compared to HRV_2D arms of the study in Cohort 2 subjects. CONCLUSION: Rotarix is associated with significant reductions in servere gastroenteritis episodes through 2 years of life among South African children. Further research is needed to determine the optimal dosing schedule of Rotarix in providing long-term protection against rotavirus illness in African children.GAVI Alliance and GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium.http://www.elsevier.com/locate/vaccin

Local CpG density affects the trajectory and variance of age-associated DNA methylation changes

Acknowledgements We thank Riccardo Marioni, Chris Haley, Ailith Ewing, David Porteous, Chris Ponting, Rob Illingworth, Tamir Chandra, Sara Hagg, Yunzhang Wang, Chantriolnt-Andreas Kapourani, Nick Gilbert, Hannes Becher and members of the Sproul lab for helpful discussions about the study and the manuscript. This work has made use of the resources provided by the University of Edinburgh digital research services and the MRC IGC compute cluster. We are grateful to all the families who took part in the Generation Scotland study along with the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the entire Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants, and nurses. Peer review information Anahita Bishop and Kevin Pang were the primary editors of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. Review history The review history is available as Additional file 3. Funding DS is a Cancer Research UK Career Development fellow (reference C47648/A20837), and work in his laboratory is also supported by an MRC university grant to the MRC Human Genetics Unit. LK is a cross-disciplinary postdoctoral fellow supported by funding from the University of Edinburgh and Medical Research Council (MC_UU_00009/2). S.R.C. and I.J.D. were supported by a National Institutes of Health (NIH) research grant R01AG054628, and S.R.C is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (221890/Z/20/Z). AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). PMV acknowledges support from the Australian National Health and Medical Research Council (1113400) and the Australian Research Council (FL180100072). DMH is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z). We thank the LBC1936 participants and team members who contributed to the study. Further study information can be found at https://www.ed.ac.uk/lothian-birth-cohorts. The LBC1936 is supported by a jointly funded grant from the BBSRC and ESRC (BB/W008793/1), and also by Age UK (Disconnected Mind project), the Medical Research Council (G0701120, G1001245, MR/M013111/1, MR/R024065/1), and the University of Edinburgh. Genotyping of LBC1936 was funded by the BBSRC (BB/F019394/1), and methylation typing of LBC1936 was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. Work on Generation Scotland was supported by a Wellcome Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL; 104036/Z/14/Z) to AMM, KLE, and others, and an MRC Mental Health Data Pathfinder Grant (MC_PC_17209) to AMM. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). DNA methylation profiling and analysis of the GS:SFHS samples was supported by Wellcome Investigator Award 220857/Z/20/Z and Grant 104036/Z/14/Z (PI: AM McIntosh) and through funding from NARSAD (Ref: 27404; awardee: Dr DM Howard) and the Royal College of Physicians of Edinburgh (Sim Fellowship; Awardee: Dr HC Whalley).Peer reviewedPublisher PD

Stock-outs of antiretroviral and tuberculosis medicines in South Africa: A national cross-sectional survey.

BACKGROUND: HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world's largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic. METHODS: We conducted a cross-sectional telephonic survey (October-December 2015) of public health facilities. Facilities were asked about the prevalence of stock-outs on the day of the survey and in the preceding three months, their duration and impact. RESULTS: Nationwide, of 3547 eligible health facilities, 79% (2804) could be reached telephonically. 88% (2463) participated and 4% (93) were excluded as they did not provide ART or TB treatment. Of the 2370 included facilities, 20% (485) reported a stock-out of at least 1 ARV and/or TB-related medicine on the day of contact and 36% (864) during the three months prior to contact, ranging from 74% (163/220) of health facilities in Mpumalanga to 12% (32/261) in the Western Cape province. These 864 facilities reported 1475 individual stock-outs, with one to fourteen different medicines out of stock per facility. Information on impact was provided in 98% (1449/1475) of stock-outs: 25% (366) resulted in a high impact outcome, where patients left the facility without medicine or were provided with an incomplete regimen. Of the 757 stock-outs that were resolved 70% (527) lasted longer than one month. INTERPRETATION: There was a high prevalence of stock-outs nationwide. Large interprovincial differences in stock-out occurrence, duration, and impact suggest differences in provincial ability to prevent, mitigate and cope within the same framework. End-user monitoring of the supply chain by patients and civil society has the potential to increase transparency and complement public sector monitoring systems

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common