Electron Microscopy Department
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Item T7 expression plasmids for producing a recombinant human G1P[8] rotavirus comprising RIX4414 sequences of the RV1 (Rotarix , GSK) vaccine strain(Microbiology Resource Announcements, 2023) Philip, A.A.; Agbemabiese, C.A.; Patton, J.T.; et al.The live oral rotavirus RV1 (Rotarix) vaccine is formulated from the human G1P[8] RIX4414 virus. Based on RIX4414 sequences, T7 expression plasmids were constructed that supported recovery of recombinant RIX4414-like viruses by reverse genetics. These plasmids will advance the study of the RV1 vaccine, possibly allowing improvements to its efficacy.Item Vaccine value profile for norovirus(Vaccine, 2023) Armah, G.; Vinjé, J.; Lopman, B.A.; et al.Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in devel oping countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroen teritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internal izes, and induces disease.Item Prevalence, Awareness, and Control of Hypertensive Disorders amongst Pregnant Women Seeking Healthcare in Ghana(Hindawi Journal of Pregnancy, 2023) Boachie-Ansah, P; Anto, B.P.; Asiamah, M.; et al.Hypertensive disorders in pregnancy (HDPs) are no longer seen as “transitory diseases cured by delivery.” It accounts for up to 50% of maternal deaths. Information concerning HDPs is less in developing countries like Ghana. This study was conducted to find out the prevalence, awareness, risk factors, control, and the birth outcomes of HDPs. This was a retrospective cohort study conducted among pregnant women seeking care in selected health facilities in the Ashanti Region. Data on demographics, HDPs, and its associated birth outcomes were collected. Logistic regression models were used to examine the association of the independent variables with HDPs. The burden of HDPs was 37.2% among the 500 mothers enrolled with chronic hypertension superimposed with preeclampsia accounting for 17.6%, chronic hypertension, 10.2%, and preeclampsia 6.8% whilst gestational hypertension was 2.6%. It was observed that 44% (220) of the mothers had excellent knowledge on HDPs. Oral nifedipine and methyldopa were frequently used for HDP management, and it resulted in a significant reduction in HDP burden from 37.2% to 26.6%. Factors that influenced the increased risk of HDPs were grand multigravida (AOR = 4 53; CI = 1 42–14.42), family history of hypertension (AOR = 3 61; CI = 1 89–6.90), and the consumption of herbal preparations (AOR = 2 92; CI = 1 15–7.41) and alcohol (AOR = 4 10; CI = 1 34-12.62) during pregnancy. HDPs increased the risk of preterm delivery (AOR = 2 66; CI = 1 29–5.89), stillbirth (AOR = 12 47; CI = 2 72–57.24), and undergoing caesarean section (AOR = 1 70; CI = 1 10–2.61) amongst mothers during delivery. The burden of HDPs is high amongst pregnant mothers seeking care in selected facilities. There is the need for intensified campaign on HDPs in the Ashanti Region of Ghana.Item Prevalence, Awareness, and Control of Hypertensive Disorders amongst Pregnant Women Seeking Healthcare in Ghana(Journal of Pregnancy, 2023) Boachie-Ansah, P.; Anto, B.P.; Asiamah, M.; et al.Hypertensive disorders in pregnancy (HDPs) are no longer seen as “transitory diseases cured by delivery.” It accounts for up to 50% of maternal deaths. Information concerning HDPs is less in developing countries like Ghana. This study was conducted to find out the prevalence, awareness, risk factors, control, and the birth outcomes of HDPs. This was a retrospective cohort study conducted among pregnant women seeking care in selected health facilities in the Ashanti Region. Data on demographics, HDPs, and its associated birth outcomes were collected. Logistic regression models were used to examine the association of the independent variables with HDPs. The burden of HDPs was 37.2% among the 500 mothers enrolled with chronic hypertension superimposed with preeclampsia accounting for 17.6%, chronic hypertension, 10.2%, and preeclampsia 6.8% whilst gestational hypertension was 2.6%. It was observed that 44% (220) of the mothers had excellent knowledge on HDPs. Oral nifedipine and methyldopa were frequently used for HDP management, and it resulted in a significant reduction in HDP burden from 37.2% to 26.6%. Factors that influenced the increased risk of HDPs were grand multigravida (AOR = 4 53; CI = 1 42–14.42), family history of hypertension (AOR = 3 61; CI = 1 89–6.90), and the consumption of herbal preparations (AOR = 2 92; CI = 1 15–7.41) and alcohol (AOR = 4 10; CI = 1 34-12.62) during pregnancy. HDPs increased the risk of preterm delivery (AOR = 2 66; CI = 1 29–5.89), stillbirth (AOR = 12 47; CI = 2 72–57.24), and undergoing caesarean section (AOR = 1 70; CI = 1 10–2.61) amongst mothers during delivery. The burden of HDPs is high amongst pregnant mothers seeking care in selected facilities. There is the need for intensified campaign on HDPs in the Ashanti Region of Ghana.Item Comparative whole genome analysis reveals re-emergence of human Wa-like and DS-1-like G3 rotaviruses after Rotarix vaccine introduction in Malawi(Oxford University Press., 2023) Dennis, F. E.; Chimwemwe, M.; Akuzike, B.; et al.Abstract G3 rotaviruses rank among the most common rotavirus strains worldwide in humans and animals. However, despite a robust long term rotavirus surveillance system from 1997 at Queen Elizabeth Central Hospital in Blantyre, Malawi, these strains were only detected from 1997 to 1999 and then disappeared and re-emerged in 2017, 5 years after the introduction of the Rotarix rotavirus vaccine. Here, we analysed representative twenty-seven whole genome sequences (G3P[4], n = 20; G3P[6], n = 1; and G3P[8], n = 6) randomly selected each month between November 2017 and August 2019 to understand how G3 strains re-emerged in Malawi. We found four geno type constellations that were associated with the emergent G3 strains and co-circulated in Malawi post-Rotarix vaccine introduction: G3P[4] and G3P[6] strains with the DS-1-like genetic backbone genes (G3-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2 and G3-P[6]-I2-R2-C2-M2-A2- N2-T2-E2-H2), G3P[8] strains with the Wa-like genetic backbone genes (G3-P[8]-I1-R1-C1-M1-A1-N1-T1-E1-H1), and reassortant G3P[4] strains consisting of the DS-1-like genetic backbone genes and a Wa-like NSP2 (N1) gene (G3-P[4]-I2-R2-C2-M2-A2-N1-T2-E2-H2). Time resolved phylogenetic trees demonstrated that the most recent common ancestor for each ribonucleic acid (RNA) segment of the emer gent G3 strains was between 1996 and 2012, possibly through introductions from outside the country due to the limited genetic similarity with G3 strains which circulated before their disappearance in the late 1990s. Further genomic analysis revealed that the reassortant DS-1-like G3P[4] strains acquired a Wa-like NSP2 genome segment (N1 genotype) through intergenogroup reassortment; an artiodactyl like VP3 through intergenogroup interspecies reassortment; and VP6, NSP1, and NSP4 segments through intragenogroup reassortment likely before importation into Malawi. Additionally, the emergent G3 strains contain amino acid substitutions within the antigenic regions of the VP4 proteins which could potentially impact the binding of rotavirus vaccine–induced antibodies. Altogether, our fnd ings show that multiple strains with either Wa-like or DS-1-like genotype constellations have driven the re-emergence of G3 strains. The fndings also highlight the role of human mobility and genome reassortment events in the cross-border dissemination and evolution of rotavirus strains in Malawi necessitating the need for long-term genomic surveillance of rotavirus in high disease–burden settings to inform disease prevention and controlItem The Full Impact of Rotavirus Vaccines in Africa Has Yet to Be Realized(Clinical Infectious Diseases, 2023) Steele, A.D.; Armah, G.E.; Mwenda, J.M.; Kirkwood, C.D.Africa bears the brunt of diarrheal mortality globally. Rotavirus vaccination rates are high across the continent and demonstrate impact on diarrheal disease reduction. Nevertheless, there is room for significant improvement in managing rotavirus vaccine coverage, in access to recognized public services such as appropriate medical care, including oral rehydration therapy and improved water and sanitation.Item Evolutionary changes between pre- and post-vaccine South African group A G2P[4] rotavirus strains, 2003–2017(Microbiology Society, 2022) Mwangi, P.N.; Page, N.A.; Seheri, M.L.; Mphahlele, M.J.; Nadan, S.; Esona, M.D.; Kumwenda, B.; Kamng’ona, A.W.; Donato, C.M.; Steele, D.A.; Ndze, V.N.; Dennis, F.E.; Jere, K.C.; Nyaga, M.M.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 step-wise 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.Item Enterotoxigenic Escherichia coli (ETEC) vaccines: Priority activities to enable product development, licensure, and global access(Elsevier, 2021) Khalil, I.; Walker, R.; Porter, C.K.; Muhib, F.; Chilengi, R.; Cravioto, A.; Guerrant, R.; Svennerholm, A.; Qadri, F.; Baqar, S.; Kosek, M.; Kang, G.; Lanata, C.; Armah, G.; Wierzba, T.; Hasso-Agopsowicz, M.; Giersing, B.; Bourgeois, L.A.Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interven tions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the associa tion between ETEC infection and physical and cognitive stunting as well as delayed educational attain ment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further eluci dation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of address ing globally unmet data needs in the areas of research, product development, and policy, as well as com mercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently neededItem Report of the 1st African Enteric Viruses Genome Initiative data and Bioiniformatics workshop on whole genome analysis of some African rotavirus strains held in Bloemfontein, South Africa(Vaccine, 2020-07-22) Dennis, F.E.; Nyaga, M.M.; Sabiu, S.; Ndze, V.N.; Jere, K.C.The University of the Free State - Next Generation Sequencing (NGS) Unit, Bloemfontein, South Africa, hosted a data and bioinformatics workshop from 19 to 22 June 2018. The workshop was coordinated by the African Enteric Viruses Genome Initiative (AEVGI) with support from the Bill & Melinda Gates Foundation. The event introduced technologies in NGS and data analysis with focus on the rotavirus (RV) genome. The workshop fostered interactions and networking between professionals, scientific experts, technicians and students. The courses provided an overview of RV diarrhoea and its burden in Africa, while highlighting the key resources and methodologies in NGS and advanced bioinformatics in deciphering vaccine impact. It was concluded that, despite the reported significant decline in RV associated-diarrhoea mortality and morbidity in Africa due to RV vaccine impact, the need for continuous surveillance and genomic characterization to better understand the ever-changing dynamics of RV strains is imperative.Item Modeling of rotavirus transmission dynamics and impact of vaccination in Ghana(Vaccine, 2020-06-05) Armah, G.E.; Asare, E.O.; Al-Mamun, M.A.; Lopman, B.A.; Parashar, U.D.; Binka, F.; Pitzer, V.E.Background: Rotavirus incidence remains relatively high in low-income countries (LICs) compared to high-income countries (HICs) after vaccine introduction. Ghana introduced monovalent rotavirus vaccine in April 2012 and despite the high coverage, vaccine performance has been modest compared to developed countries. The predictors of low vaccine effectiveness in LICs are poorly understood, and the drivers of subnational heterogeneity in rotavirus vaccine impact are unknown. Methods: We used mathematical models to investigate variations in rotavirus incidence in children <5 years old in Ghana. We fit models to surveillance and case-control data from three different hospitals: Korle-Bu Teaching Hospital in Accra, Komfo Anokye Teaching Hospital in Kumasi, and War Memorial Hospital in Navrongo. The models were fitted to both pre- and post-vaccine data to estimate parameters describing the transmission rate, waning of maternal immunity, and vaccine response rate. Results: The seasonal pattern and age distribution of rotavirus cases varied among the three study sites in Ghana. Our model was able to capture the spatio-temporal variations in rotavirus incidence across the three sites and showed good agreement with the age distribution of observed cases. The rotavirus transmission rate was highest in Accra and lowest in Navrongo, while the estimated duration of maternal immunity was longer (~5 months) in Accra and Kumasi and shorter (~3 months) in Navrongo. The proportion of infants who responded to the vaccine was estimated to be high in Accra and Kumasi and low in Navrongo. Conclusions: Rotavirus vaccine impact varies within Ghana. A low vaccine response rate was estimated for Navrongo, where rotavirus is highly seasonal and incidence limited to a few months of the year. Our findings highlight the need to further explore the relationship between rotavirus seasonality, maternal immunity, and vaccine response rate to determine how they influence vaccine effectiveness and to develop strategies to improve vaccine impact.