International Network for Comparison of HIV Neutralization Assays: The NeutNet Report

BACKGROUND: Neutralizing antibody assessments play a central role in human immunodeficiency virus type-1 (HIV-1) vaccine development but it is unclear which assay, or combination of assays, will provide reliable measures of correlates of protection. To address this, an international collaboration (NeutNet) involving 18 independent participants was organized to compare different assays. METHODS: Each laboratory evaluated four neutralizing reagents (TriMab, 447-52D, 4E10, sCD4) at a given range of concentrations against a panel of 11 viruses representing a wide range of genetic subtypes and phenotypes. A total of 16 different assays were compared. The assays utilized either uncloned virus produced in peripheral blood mononuclear cells (PBMCs) (virus infectivity assays, VI assays), or their Env-pseudotyped (gp160) derivatives produced in 293T cells (PSV assays) from molecular clones or uncloned virus. Target cells included PBMC and genetically-engineered cell lines in either a single- or multiple-cycle infection format. Infection was quantified by using a range of assay read-outs that included extracellular or intracellular p24 antigen detection, RNA quantification and luciferase and beta-galactosidase reporter gene expression. FINDINGS: PSV assays were generally more sensitive than VI assays, but there were important differences according to the virus and inhibitor used. For example, for TriMab, the mean IC50 was always lower in PSV than in VI assays. However, with 4E10 or sCD4 some viruses were neutralized with a lower IC50 in VI assays than in the PSV assays. Inter-laboratory concordance was slightly better for PSV than for VI assays with some viruses, but for other viruses agreement between laboratories was limited and depended on both the virus and the neutralizing reagent. CONCLUSIONS: The NeutNet project demonstrated clear differences in assay sensitivity that were dependent on both the neutralizing reagent and the virus. No single assay was capable of detecting the entire spectrum of neutralizing activities. Since it is not known which in vitro assay correlates with in vivo protection, a range of neutralization assays is recommended for vaccine evaluation

The role of household adaptation measures in reducing vulnerability to flooding: A coupled agent-based and flood modelling approach

Flood adaptation measures implemented at the household level play an important role in reducing communities' vulnerability. The aim of this study is to enhance the current modelling practices of human–flood interaction to draw new insights for flood risk management (FRM) policy design. The paper presents a coupled agent-based and flood model for the case of Hamburg, Germany, to explore how individual adaptation behaviour is influenced by flood event scenarios, economic incentives and shared and individual strategies. Simulation results show that a unique trajectory of adaptation measures and flood damages emerges from different flood event series. Another finding is that providing subsidies increases the number of coping households in the long run. Households' social network also has a strong influence on their coping behaviour. The paper also highlights the role of simple measures such as adapted furnishings, which do not incur any monetary cost, in reducing households' vulnerability and preventing millions of euros of contents damages. Generally, we demonstrate that coupled agent-based and flood models can potentially be used as decision support tools to examine the role of household adaptation measures in flood risk management. Although the findings of the paper are case-specific, the improved modelling approach shows the potential to be applied in testing policy levers and strategies considering heterogeneous individual behaviours

Impact of an Educational Clinical Video Combined with Standard Helping Babies Breathe Training on Acquisition and Retention of Knowledge and Skills among Ethiopian Midwives

Helping Babies Breathe (HBB) is an evidence-based neonatal resuscitation program designed for implementation in low-resource settings. While HBB reduces rates of early neonatal mortality and stillbirth, maintenance of knowledge and skills remains a challenge. The extent to which the inclusion of educational clinical videos impacts learners’ knowledge and skills acquisition, and retention is largely unknown. We conducted a cluster-randomized controlled trial at two public teaching hospitals in Addis Ababa, Ethiopia. We randomized small training group clusters of 84 midwives to standard HBB vs. standard HBB training supplemented with exposure to an educational clinical video on newborn resuscitation. Midwives were followed over a 7-month time period and assessed on their knowledge and skills using standard HBB tools. When comparing the intervention to the control group, there was no difference in outcomes across all assessments, indicating that the addition of the video did not influence skill retention. Pass rates for both the control and intervention group on bag and mask skills remained low at 7 months despite frequent assessments. There is more to learn about the use of educational videos along with low-dose, high-frequency training and how it relates to retention of knowledge and skills in learners

Strategic Response to COVID-19 in Ethiopia

COVID-19, the novel coronavirus, has posed a major threat to low- and middle-income countries (LMICs) due to inadequate health infrastructure and human resources. Ethiopia, a low-income country with the second largest population in Africa, has coordinated a strategic response, leveraging existing infrastructure and health systems and mobilizing public health professionals and specialist expert physicians for a multifaceted, unified government approach and adaptive response. Resource limitations, particularly in critical care, have still posed challenges, but the public health and clinical interventions thus far have prevented the catastrophic toll that many predicted. As the pandemic continues, Ethiopia expects to use a triple care model integrated at all levels, consisting of COVID-19 care, isolation care for suspected cases, and essential health services, and urges intensified non-pharmaceutical interventions alongside equitable global vaccine distribution as the ultimate answers to pandemic control. This paper draws on existing data, national planning and guidelines, and expertise from health leadership to describe this response in hopes of providing an example of how future large-scale health challenges might be faced in LMICs, using Ethiopia\u27s successes and challenges in facing the pandemic

Genetic diversity and molecular epidemiology of Middle East Respiratory Syndrome Coronavirus in dromedaries in Ethiopia, 2017–2020

ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels and causes zoonotic infection and disease in humans. Although over 80% of the global population of infected dromedary camels are found in Africa, zoonotic disease had only been reported in the Arabia Peninsula and travel-associated disease has been reported elsewhere. In this study, genetic diversity and molecular epidemiology of MERS-CoV in dromedary camels in Ethiopia were investigated during 2017–2020. Of 1766 nasal swab samples collected, 61 (3.5%) were detected positive for MERS-CoV RNA. Of 484 turbinate swab samples collected, 10 (2.1%) were detected positive for MERS-CoV RNA. Twenty-five whole genome sequences were obtained from these MERS-CoV positive samples. Phylogenetically, these Ethiopian camel-originated MERS-CoV belonged to clade C2, clustering with other East African camel strains. Virus sequences from camel herds clustered geographically while in an abattoir, two distinct phylogenetic clusters of MERS-CoVs were observed in two sequential sampling collections, which indicates the greater genetic diversity of MERS-CoV in abattoirs. In contrast to clade A and B viruses from the Arabian Peninsula, clade C camel-originated MERS-CoV from Ethiopia had various nucleotide insertions and deletions in non-structural gene nsp3, accessory genes ORF3 and ORF5 and structural gene N. This study demonstrates the genetic instability of MERS-CoV in dromedaries in East Africa, which indicates that the virus is still actively adapting to its camel host. The impact of the observed nucleotide insertions and deletions on virus evolution, viral fitness, and zoonotic potential deserves further study