Insights from the fifth International One Health Congress, 2018, Saskatoon, Canada

The recent outbreaks of diseases including Ebola reemergence in the Democratic Republic of Congo (DRC), Nipah virus outbreak in India, Lassa virus in Nigeria and the continued Influenza pandemic shows that we cannot predict outbreaks, however, developing response plans could help alleviate the burden of diseases. Developing response plans involves strategies such as creating a repository of microbial agents as well as the implementation of the plans. In addition, zoonotic experts and policy makers should work together in order to succeed in fighting against any disease outbreaks. We should also not forget about the importance of vaccination because of the benefits it has brought to humankind preventing disease occurrence. Furthermore, the challenges that come with vaccination including vaccine delivery and vaccine uptake needs to be overcome to make sure that this public health tool continues to be effective. Overcoming these vaccination challenges would play a significant role in decreasing the overuse of antimicrobials, hence avoiding resistance. The One Health Community (OHC) therefore has the responsibility to advocate for the use of vaccines and show that it has costs benefits; this strategy has the potential to fight against antimicrobial resistance

Investigating the relationship between miRNA expression and epithelial mesenchymal transition in colorectal cancer

Introduction: Epithelial-mesenchymal transition (EMT) is characterized by the loss of an epithelial phenotype and gain of a mesenchymal phenotype, i.e., migratory and metastatic properties. The EMT process is therefore characterized by a low expression of E-cadherin and high expression of mesenchymal markers (e.g., N-cadherin, snail and vimentin). It is stated that cells which have undergone EMT also gain stem cell features. Therefore, both EMT and stem cell phenotypes have been implicated in carcinogenesis and metastasis of tumour cells. Furthermore, EMT is regulated by small non-coding molecules (miRNAs) that either function as tumour suppressors or oncogenes (oncomirs). Tumour suppressor miRNAs reverse EMT while oncomirs activate it. Therefore, investigating the relationship between miRNAs and EMT is important in addressing metastasis of colorectal cancers (CRC). Aims and Objectives: The aim of the study was to determine the association between miRNA (miRNA-21 and miRNA-34a) expression levels and EMT in CRC. In addition, this investigation aimed to correlate miRNA and EMT data with clinicopathologic features of the study cohort. Methodology: A total of 100 CRC (including 8 known HNPCC cases) Formalin Fixed Paraffin Embedded (FFPE) tissue blocks and their corresponding H&E slides were collected from the archives of the Division of Anatomical Pathology at the University of Cape Town. Subsequently, the FFPE tissue blocks were sectioned at 3μm and IHC analysis of 4 EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) and 1 stem cell marker (CD44V6) was performed. The stains were then evaluated and scored by a pathologist. The IHC data were then correlated with clinicopathologic features. Furthermore, 59 cases (FFPE tissues and corresponding H&E slides) which included the 8 HNPCCs were randomly selected for miRNA analysis. The H&Es were examined by a pathologist to demarcate normal and tumour regions. RNA was then extracted from 59 tumours and 12 normal tissues using a High Pure FFPET Isolation Kit (Roche). Subsequently, cDNA was synthesized and qRT-PCR was performed to determine the expression levels of miRNA-21 and miRNA-34a. MiRNA-21 and miRNA-34a expression levels were ascertained using the relative quantification method. Moreover, the clinical significance of the two miRNAs was evaluated in relation to MSI status. Therefore, IHC analysis of MLH1, MSH2 and MSH6 mismatch repair proteins was performed on the Ventana platform. Statistical analysis was performed using Fisher's and Pearson's Chi Square tests in Stata 12 to correlate EMT and clinicopathologic data. Additionally, the Mann-Whitney non-parametric test in GraphPad prism 6 was used to determine miRNA-21 and miRNA-34a expression in relation to EMT and MSI data. Results: Our results showed low expression of E-cadherin in 77% of cases. In addition, there was decreased expression of N-cadherin and vimentin in 98% whilst snail-1 expression was decreased in 65% of the cases. Low expression of CD44v6 was also seen in 78% of the cases. There was no correlation between EMT/stem cell markers and clinicopathologic data. Furthermore, increased miRNA-21 expression was significantly associated with grade, lymph node metastasis and age of patients. There was a significant correlation between high miRNA- 21 expression and down-regulated snail-1 and N-cadherin expression. MiRNA-34a expression was not associated with any of the clinicopathologic features. In addition, high miRNA-34a expression was linked with low expression of snail-1 and CD44v6. Increased miRNA-21 expression was related with MSS tumours, whereas there was no relationship between miRNA- 34a and MSI status. Conclusion: Our investigation shows that there is an inverse association between miRNA (miRNA-21 and miRNA-34a) expression and two EMT (N-cadherin and snail-1) markers in our colorectal cancer cohort. Our data also show that both miRNA-21 and miRNA-34a cannot be used as biomarkers to determine progression of the cancer. Contrary to previous studies, our findings indicate that miRNA-21 does not activate EMT in this CRC cohort. However, similar to other studies our results confirm that miRNA-34a may be repressing snail-1 expression, thereby inhibiting EMT in the cancer

Sequence analysis of the E-cadherin (CDH1) gene in a cohort of gastric cancers seen in the Western Cape

Includes abstract.Includes bibliographical references.Gastric cancer is commonly seen in the Western Cape. There are numerous factors that contribute to the development of this cancer and these include both environmental and genetic factors. Amongst the genetic factors, the E-cadherin (CDH1) gene is said to play a major role in the development of gastric cancer. Both germline and somatic mutations have been identified in the CDH1 gene. The germline mutations span the entire exon of this gene and are seen in approximately 29% to 56% of familial gastric cancers. On the other hand, CDH1 somatic mutations are seen in approximately 31% of sporadic cancers. These mutations have been identified in exons 7 to 10, with exons 8 and 9 being the commonly mutated regions. The primary objective of this study was to determine the prevalence of CDH1 genetic mutations in gastric cancer in the Western Cape and to correlate these findings with the demographic/clinicopathologic data

Taking stock of vaccine hesitancy among migrants: a scoping review protocol.

INTRODUCTION: At the 72nd World Health Assembly of May 2019, WHO member states prioritised a global action plan to promote migrant and refugee health. Five months earlier, WHO had declared vaccine hesitancy-the reluctance to vaccinate despite the availability of vaccination services-as one of the top 10 threats to global health. Although vaccination is often a requirement for immigration, repeated outbreaks of vaccine-preventable diseases within certain immigrant communities in some host nations suggest that vaccine hesitancy could be a factor in their susceptibility to vaccine-preventable diseases. Studies of the prevalence and determinants of vaccine hesitancy among migrants globally seem to be lacking. This scoping review will (1) identify articles on vaccine hesitancy among migrants; (2) examine the extent and nature of the extant evidence; and (3) determine the value of undertaking a full systematic review. METHODS AND ANALYSIS: The framework for the scoping review proposed by the Joanna Briggs Institute will be used. The reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. Studies published in English or French between January 1999 and December 2019 will be drawn from most or all of the following multidisciplinary databases: Africa-Wide Information, Allied and Complementary Medicine, Cochrane Library, Cumulative Index of Nursing and Allied Health Literature, Embase, Index Medicus for the Eastern Mediterranean Region, International Bibliography of Social Sciences, Literature in the Health Sciences in Latin America and the Caribbean, Medline, Proquest Theses/Dissertations, PsycInfo and Web of Science. The search will include an extensive list of keywords to capture multiple dimensions of confidence and hesitancy vis-à-vis vaccines among migrants. Findings will be reported through summary narratives, tables, flowcharts and evidence maps. ETHICS AND DISSEMINATION: This review is exempted from ethical approval and will be published in a peer-reviewed open-access journal to ensure wide dissemination

Protocol for a systematic review of the effects of interventions for vaccine stock management

Abstract Background Inadequate vaccine stock management in health facilities leads to vaccine stock-outs. The latter threatens the success of immunisation programmes. Countries have used various approaches to reduce stock-outs and improve vaccine availability, but we are not aware of a systematic review of these interventions. This protocol describes the methods we will use to assess the effects of existing approaches for improving vaccine stock management. Methods We include randomised and non-randomised studies identified through a compehensive search of peer-reviewed and grey literature databases. We will search PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science, PDQ-Evidence and Scopus. We will also search websites of the World Health Organisation (WHO), Global Alliance for Vaccine and Immunisation, PATH Vaccine Resources Library and United Nations Children’s Fund. In addition, we will search the WHO International Clinical Trials Registry Platform and reference lists of included studies and relevant reviews. Finally, we plan to do a citation search for included studies. We will use Cochrane recommended methods to screen search outputs, assess study eligibility and risk of bias, extract and analyse study results. We will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to assess the certainty of the evidence on the effects of the interventions. Discussion We believe that the findings of this review will serve as valuable information for policy makers on ways to improve vaccine stock management and vaccine availability. When vaccine availability is improved, those who need them, especially children, will be adequately protected from vaccine-preventable diseases. Systematic review registration PROSPERO CRD4201809221

Pandemic influenza preparedness in the WHO African region: are we ready yet?

Background Prior to the 2009 pandemic H1N1, and the unprecedented outbreak of Highly Pathogenic Avian Influenza (HPAI) caused by the H5N1 virus, the World Health Organization (WHO) called upon its Member States to develop preparedness plans in response to a new pandemic in humans. The WHO Member States responded to this call by developing national pandemic plans in accordance with the International Health Regulations (IHR) to strengthen the capabilities of Member States to respond to different pandemic scenarios. In this study, we aim to evaluate the quality of the preparedness plans in the WHO African region since their inception in 2005. Methods A standard checklist with 61 binary indicators (“yes” or “no”) was used to assess the quality of the preparedness plans. The checklist was categorised across seven thematic areas of preparedness: preparation (16 indicators); coordination and partnership (5 indicators); risk communication (8 indicators); surveillance and monitoring (7 indicators); prevention and containment (10 indicators); case investigation and treatment (10 indicators) and ethical consideration (5 indicators). Four assessors independently scored the plans against the checklist. Results Of the 47 countries in the WHO African region, a total of 35 national pandemic plans were evaluated. The composite score for the completeness of the pandemic plans across the 35 countries was 36%. Country-specific scores on each of the thematic indicators for pandemic plan completeness varied, ranging from 5% in Côte d’Ivoire to 79% in South Africa. On average, preparation and risk communication scored 48%, respectively, while coordination and partnership scored the highest with an aggregate score of 49%. Surveillance and monitoring scored 34%, while prevention and containment scored 35%. Case investigation and treatment scored 25%, and ethical consideration scored the lowest of 14% across 35 countries. Overall, our assessment shows that pandemic preparedness plans across the WHO African region are inadequate. Conclusions Moving forward, these plans must address the gaps identified in this study and demonstrate clarity in their goals that are achievable through drills, simulations and tabletop exercises

Improving the availability of vaccines in primary healthcare facilities in South Africa : is the time right for a system redesign process?

An uninterrupted supply of vaccines at different supply chain levels is a basic component of a functional immunization programme and care service. There can be no progress toward achieving universal health coverage and sustainable development without continuous availability of essential medicines and vaccines in healthcare facilities. Shortages of vaccines, particularly at health facility level is an issue of grave concern that requires urgent attention in South Africa. The causes of vaccine stock-outs are multifactorial and may be linked to a broader systems issue. These factors include challenges at higher levels such as delays in the delivery of stock from the pharmaceutical depot; health facility level factors, which include a lack of commitment from healthcare workers and managers; human resource factors, such as, staff shortages, and lack of skilled personnel. Therefore, there is a compelling need to address the factors associated with shortages of vaccines in health facilities. This paper highlights the challenges of vaccine availability in South Africa, the associated factors, the available interventions, and recommended interventions for the expanded programme on immunization in South Africa. We propose a system redesign approach as a potentially useful intervention.World Health Organization Regional Office for Africa (WHO/AFRO) and the Hideyo Noguchi Africa Prize (HNAP).http://www.tandfonline.com/loi/khvi20hj2023School of Health Systems and Public Health (SHSPH

Predictors of COVID-19 Vaccine Hesitancy in South African Local Communities: The VaxScenes Study

South Africa launched a mass COVID-19 vaccination campaign in May 2021, targeting 40 million adults. Understanding predictors of COVID-19 vaccine intentions was required to achieve this goal. We conducted a population-based survey in June–July 2021 using the WHO Behavioral and Social Drivers (BeSD) of COVID-19 Vaccination tool to determine predictors of vaccine hesitancy, defined as intention to refuse or uncertainty whether to accept COVID-19 vaccination. There were 1193 participants, mean age 39 (standard deviation 15) years, and 53% women, of whom 58% trusted information provided by healthcare workers and 32% were vaccine hesitant. Independent predictors of vaccine hesitancy included concerns about side effects (odds ratio (OR) 11.41; 95% confidence interval (CI) 3.5–50.80), lack of access to the online vaccine registration platform (OR 4.75; CI 2.15–10.37), distrust of government (OR 3.0; CI 1.33–6.77), belief in conspiracy theories (OR 3.01; CI 1.32–6.77), having no monthly income (OR 1.84; CI 1.12–3.07), and depending on someone else to make vaccination decision (OR 2.47; CI 1.06–5.77). We identified modifiable predictors of vaccine hesitancy at the start of South Africa’s COVID-19 vaccination rollout. These factors should be addressed by different stakeholders involved in the national immunization program through tailored communication and other effective strategies that increase vaccine literacy, reach low-income households, and engender confidence in government

Preventing and managing antimicrobial resistance in the African region : a scoping review protocol

INTRODUCTION: Antimicrobial resistance (AMR) constitutes a significant threat to global health and food security, typically associated with high morbidity and mortality rate. The high burden of infectious diseases coupled with the weak health systems in most countries of Africa magnifies the risk of increasing AMR and its consequences thereof. This scoping review will be aimed at mapping the evidence on interventions used to prevent and manage antimicrobial resistance in Africa, guided by the “One Health” concept. METHODS: We will consider interventions targeting multiple sectors such as health care systems, the agricultural and veterinary sectors. The outcomes to be considered include reduction of AMR decreased morbidity and mortality due to infectious diseases, increased awareness for rational use of antimicrobials and reduced antibiotic consumption. We will include all types of studies regardless of study designs conducted within the context of the WHO African region. Studies will be excluded if they are not conducted in Africa and if they are literature reviews, only describing the concept of AMR without mentioning interventions. We will include studies identified through a comprehensive search of peer-reviewed and grey literature databases. In addition, we will search the reference lists of included studies and relevant reviews. Finally, we plan to do a citation search for included studies. Findings of this review will be narratively synthesized.http://www.plosone.orgSchool of Health Systems and Public Health (SHSPH

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic