Low seroprevalence of hepatitis E virus in pregnant women in an urban area near Pretoria, South Africa

OBJECTIVES : Hepatitis E virus (HEV) infection is a globally neglected health problem with a high burden in resource-poor communities. Pregnant women are at increased risk of complications. This pilot study sought to assess the seroprevalence of HEV infection in pregnant women at Dr George Mukhari Academic Hospital, South Africa. METHODS : Stored serum samples from 384 HIV-uninfected pregnant women attending the antenatal clinic were initially screened for HEV total antibody. Positive samples were further evaluated for the presence of IgG and IgM antibody isotypes, using commercial ELISA assays. HEV RNA was assessed in antibody-positive samples utilizing qRT-PCR assay. RESULTS : The sample consisted of women with a median age of 31 years (interquartile range: 28–35 years). Total HEV antibody was detected in 12/384 (3.13%, 95% CI: 1.80–5.38) of these pregnant women. All 12 samples were IgG HEV antibody positive, but none tested positive for IgM antibody or for HEV RNA, demonstrating a lack of current or recent exposure. CONCLUSIONS : Our study revealed a low seroprevalence of HEV among pregnant women from an urban area north of Pretoria. This observation warrants further attention to the circulation of HEV in this population, and a greater understanding of the epidemiology of the infection in South Africa.The South African Ministry of Higher Education, Science and Innovation, and the National Research Foundation.http://www.elsevier.com/locate/ijregihj2023Medical Virolog

Genetic characterisation of South African and Mozambican bovine rotaviruses reveals a typical bovine-like artiodactyl constellation derived through multiple reassortment events

This study presents whole genomes of seven bovine rotavirus strains from South Africa and Mozambique. Double-stranded RNA, extracted from stool samples without prior adaptation to cell culture, was used to synthesise cDNA using a self-annealing anchor primer ligated to dsRNA and random hexamers. The cDNA was subsequently sequenced using an Illumina MiSeq platform without prior genome amplification. All strains exhibited bovine-like artiodactyl genome constellations (G10/G6-P[11]/P[5]-I2-R2-C2-M2-A3/A11/A13-N2-T6-E2-H3). Phylogenetic analysis revealed relatively homogenous strains, which were mostly related to other South African animal strains or to each other. It appears that these study strains represent a specific bovine rotavirus population endemic to Southern Africa that was derived through multiple reassortment events. While one Mozambican strain, MPT307, was similar to the South African strains, the second strain, MPT93, was divergent from the other study strains, exhibiting evidence of interspecies transmission of the VP1 and NSP2 genes. The data presented in this study not only contribute to the knowledge of circulating African bovine rotavirus strains, but also emphasise the need for expanded surveillance of animal rotaviruses in African countries in order to improve our understanding of rotavirus strain diversity.Deutsche Forschungsgemeinschaft (DFG); European Foundation Initiative for African Research into Neglected Tropical Diseases (EFINTD); South African Medical Research Council (SAMRC); Australian National Health and Medical Research Council.http://www.mdpi.com/journal/pathogenspm2022Medical Virolog

Rotavirus group : a genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018

Background Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010–June 2014) and post- (July 2014–December 2018) RVA vaccine introduction. Methods Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. Results We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. Conclusion Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity

Whole Genome In-Silico Analysis of South African G1P[8] Rotavirus Strains before and after Vaccine Introduction over a Period of 14 Years

Rotavirus G1P[8] strains account for more than half of the group A rotavirus (RVA) infections in children under five years of age, globally. A total of 103 stool samples previously characterized as G1P[8] and collected seven years before and seven years after introducing the Rotarix® vaccine in South Africa were processed for whole-genome sequencing. All the strains analyzed had a Wa-like constellation (G1-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1). South African pre- and post-vaccine G1 strains were clustered in G1 lineage-I and II while the majority (84.2%) of the P[8] strains were grouped in P[8] lineage-III. Several amino acid sites across ten gene segments with the exception of VP7 were under positive selective pressure. Except for the N147D substitution in the antigenic site of eight post-vaccine G1 strains when compared to both Rotarix® and pre-vaccine strains, most of the amino acid substitutions in the antigenic regions of post-vaccine G1P[8] strains were already present during the pre-vaccine period. Therefore, Rotarix® did not appear to have an impact on the amino acid differences in the antigenic regions of South African post-vaccine G1P[8] strains. However, continued whole-genome surveillance of RVA strains to decipher genetic changes in the post-vaccine period remains imperative

Evolutionary changes between pre- and post- vaccine South African group A G2P[4] rotavirus strains, 2003-2017

The transient upsurge of G2P[4] group A rotavirus (RVA) after Rotarix vaccine introduction in several countries has been a matter of concern. To gain insight into the diversity and evolution of G2P[4] strains in South Africa pre- and post-RVA vaccination introduction, whole-genome sequencing was performed for RVA positive faecal specimens collected between 2003 and 2017 and samples previously sequenced were obtained from GenBank (n=103; 56 pre- and 47 post-vaccine). Pre-vaccine G2 sequences predominantly clustered within sub-lineage IVa-1. In contrast, post-vaccine G2 sequences clustered mainly within sub-lineage IVa-3, whereby a radical amino acid (AA) substitution, S15F, was observed between the two sub-lineages. Pre-vaccine P[4] sequences predominantly segregated within sub-lineage IVa while post-vaccine sequences clustered mostly within sub-lineage IVb, with a radical AA substitution R162G. Both S15F and R162G occurred outside recognised antigenic sites. The AA residue at position 15 is found within the signal sequence domain of Viral Protein 7 (VP7) involved in translocation of VP7 into endoplasmic reticulum during infection process. The 162 AA residue lies within the hemagglutination domain of Viral Protein 4 (VP4) engaged in interaction with sialic acid-containing structure during attachment to the target cell. Free energy change analysis on VP7 indicated accumulation of stable point mutations in both antigenic and non-antigenic regions. The segregation of South African G2P[4] strains into pre- and post-vaccination sub-lineages is likely due to erstwhile hypothesized stepwise lineage/sub-lineage evolution of G2P[4] strains rather than RVA vaccine introduction. Our findings reinforce the need for continuous whole-genome RVA surveillance and investigation of contribution of AA substitutions in understanding the dynamic G2P[4] epidemiology

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

Introduction: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. Methods: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. Results: During 2017–2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). Conclusions: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality

Wie schneiden Sie ab?: Studie über Kontroll- und Prüfungsaktivitäten bei mittelgrossen Unternehmen, Spitälern und Hochschulen in der Schweiz

Kontroll- und Prüfungsaktivitäten unterstützen den Verwaltungsrat und die Geschäftsleitung bei der Steuerung und Kontrolle des Unternehmens. Bei mittelgrossen Unternehmen ist aufgrund der begrenzten personellen und finanziellen Ressourcen ein effektiver und effizienter Einsatz dieser Aktivitäten unerlässlich. Auch bei Spitälern und Hochschulen gewinnen Kontroll- und Prüfungsaktivitäten infolge erhöhter Wettbewerbsintensität und steigenden Kostendrucks sowie zunehmender Unabhängigkeit dieser Organisationen an Bedeutung. Vor diesem Hintergrund haben das Institut für Rechnungswesen und Controlling der Universität Zürich und die PricewaterhouseCoopers AG im Sommer 2008 untersucht, ob und in welchem Ausmass Kontroll- und Prüfungsaktivitäten bei mittelgrossen Unternehmen, Spitälern und Hochschulen vorhanden sind, wie sie ausgestaltet sind und wie die einzelnen Aktivitäten aufeinander abgestimmt werden. Des Weiteren wurden die diesbezüglichen Erwartungen und die gegenwärtigen Herausforderungen der befragten Organisationen eruiert

Rotavirus breakthrough infections responsible for gastroenteritis in vaccinated infants who presented with acute diarrhoea at University Teaching Hospitals, Children's Hospital in 2016, in Lusaka Zambia.

BackgroundIn Zambia, before rotavirus vaccine introduction, the virus accounted for about 10 million episodes of diarrhoea, 63 000 hospitalisations and 15 000 deaths in 2015, making diarrhoea the third leading cause of death after pneumonia and malaria. In Zambia, despite the introduction of the vaccine acute diarrhoea due to rotaviruses has continued to affect children aged five years and below. This study aimed to characterise the rotavirus genotypes which were responsible for diarrhoeal infections in vaccinated infants aged 2 to 12 months and to determine the relationship between rotavirus strains and the severity of diarrhoea in 2016.MethodsStool samples from infants aged 2 to 12 months who presented to the hospital with acute diarrhoea of three or more episodes in 24 hours were tested for group A rotavirus. All positive specimens that had enough sample were genotyped using reverse transcriptase Polymerase Chain Reaction (RT-PCR). A 20-point Vesikari clinical score between 1-5 was considered as mild, 6-10 as moderate and greater or equal to 11 as severe.ResultsA total of 424 stool specimens were tested of which 153 (36%, 95% CI 31.5% to 40.9%) were positive for VP6 rotavirus antigen. The age-specific rotavirus infections decreased significantly (p = 0.041) from 2-4 months, 32.0% (49/118) followed by a 38.8% (70/181) infection rate in the 5-8 months' category and subsequently dropped in the infants aged 9-12 months with a positivity rate of 27.2%. 38.5% of infants who received a single dose, 34.5% of those who received a complete dose and 45.2% (19/42) of the unvaccinated tested positive for rotavirus. The predominant rotavirus genotypes included G2P[6] 36%, G1P[8] 32%, mixed infections 19%, G2P[4] 6%, G1P[6] 4% and G9P[6] 3%.Discussion and conclusionResults suggest breakthrough infection of heterotypic strains (G2P[6] (36%), homotypic, G1P[8] (32%) and mixed infections (19%) raises concerns about the effects of the vaccination on the rotavirus diversity, considering the selective pressure that rotavirus vaccines could exert on viral populations. This data indicates that the rotavirus vaccine has generally reduced the severity of diarrhoea despite the detection of the virus strains