Addressing the Threat of Emerging Viral Infections.

Emerging infections are caused when microorganisms that are maintained in a reservoir where they cause no harm, transmit from the reservoir to a new host. I have been studying the replication, molecular basis for pathogenesis, and host responses to emerging viruses, including influenza virus, Ebola virus, and SARS-CoV-2, and using the knowledge gained from these studies to develop antivirals and vaccines.Influenza viruses cause epidemics every winter, but occasionally new influenza viruses emerge and spread worldwide (pandemic). We established a technique that allows us to make influenza viruses artificially. This technique is now widely used for basic research and for the development of vaccines against highly pathogenic avian influenza virus for pandemic preparedness and live attenuated influenza vaccines. Using this technique, we elucidated the mechanisms of emergence of pandemic viruses, viral replication, and the molecular mechanism of pathogenesis.Ebola virus causes severe disease with a mortality rate of up to 90%. In 2013, a major outbreak of Ebola virus began in West Africa that led to nearly 30,000 people being infected and a death toll of over 10,000 people. During the outbreak, we established a laboratory in Sierra Leone and used samples from Ebola patients to study host responses and identify biomarkers for severe infection. We also established a technology to artificially make Ebola virus and used this technology to make an Ebola virus that grows only in a particular cell line. Using this virus, we produced an inactivated Ebola vaccine, which was shown to be safe and effective in a Phase I clinical trial.Late in 2019, SARS-CoV-2 emerged in Wuhan, China and has since caused unprecedented damage globally. In our laboratory, we established an animal model for this infection and have used it to evaluate pathogenicity, efficacy of therapeutic monoclonal antibodies and antivirals, and to develop vaccines.In my presentation, I will discuss our findings regarding these emerging viral infections.

Advancing detection and response capacities for emerging and re-emerging pathogens in Africa.

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa.

Sustainable strategies for Ebola virus disease outbreak preparedness in Africa: a case study on lessons learnt in countries neighbouring the Democratic Republic of the Congo.

BACKGROUND: From May 2018 to September 2022, the Democratic Republic of Congo (DRC) experienced seven Ebola virus disease (EVD) outbreaks within its borders. During the 10th EVD outbreak (2018-2020), the largest experienced in the DRC and the second largest and most prolonged EVD outbreak recorded globally, a WHO risk assessment identified nine countries bordering the DRC as moderate to high risk from cross border importation. These countries implemented varying levels of Ebola virus disease preparedness interventions. This case study highlights the gains and shortfalls with the Ebola virus disease preparedness interventions within the various contexts of these countries against the background of a renewed and growing commitment for global epidemic preparedness highlighted during recent World Health Assembly events. MAIN TEXT: Several positive impacts from preparedness support to countries bordering the affected provinces in the DRC were identified, including development of sustained capacities which were leveraged upon to respond to the subsequent coronavirus disease 2019 (COVID-19) pandemic. Shortfalls such as lost opportunities for operationalizing cross-border regional preparedness collaboration and better integration of multidisciplinary perspectives, vertical approaches to response pillars such as surveillance, over dependence on external support and duplication of efforts especially in areas of capacity building were also identified. A recurrent theme that emerged from this case study is the propensity towards implementing short-term interventions during active Ebola virus disease outbreaks for preparedness rather than sustainable investment into strengthening systems for improved health security in alignment with IHR obligations, the Sustainable Development Goals and advocating global policy for addressing the larger structural determinants underscoring these outbreaks. CONCLUSIONS: Despite several international frameworks established at the global level for emergency preparedness, a shortfall exists between global policy and practice in countries at high risk of cross border transmission from persistent Ebola virus disease outbreaks in the Democratic Republic of Congo. With renewed global health commitment for country emergency preparedness resulting from the COVID-19 pandemic and cumulating in a resolution for a pandemic preparedness treaty, the time to review and address these gaps and provide recommendations for more sustainable and integrative approaches to emergency preparedness towards achieving global health security is now.

The Evolution of the National Special Pathogen System of Care.

Infectious disease outbreaks and pandemics have repeatedly threatened public health and have severely strained healthcare delivery systems throughout the past century. Pathogens causing respiratory illness, such as influenza viruses and coronaviruses, as well as the highly communicable viral hemorrhagic fevers, pose a large threat to the healthcare delivery system in the United States and worldwide. Through the Hospital Preparedness Program, within the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, a nationwide Regional Ebola Treatment Network (RETN) was developed, building upon a state- and jurisdiction-based tiered hospital approach. This network, spearheaded by the National Emerging Special Pathogens Training and Education Center, developed a conceptual framework and plan for the evolution of the RETN into the National Special Pathogen System of Care (NSPS). Building the NSPS strategy involved reviewing the literature and the initial framework used in forming the RETN and conducting an extensive stakeholder engagement process to identify gaps and develop solutions. From this, the NSPS strategy and implementation plan were formed. The resulting NSPS strategy is an ambitious but critical effort that will have impacts on the mitigation efforts of special pathogen threats for years to come.

COVID-19 Response Among US Hospitals with Emerging Special Pathogen Programs.

In February 2015, the US Department of Health and Human Services developed a tiered hospital network to deliver safe and effective care to patients with Ebola virus disease (EVD) and other special pathogens. The tiered network consisted of regional special pathogen treatment centers, state- or jurisdiction-designated treatment centers, assessment hospitals able to safely isolate a patient until a diagnosis of EVD was confirmed and transfer the patient, and frontline healthcare facilities able to identify and isolate patients with EVD and facilitate transport to higher-tier facilities. The National Emerging Special Pathogens Training and Education Center (NETEC) was established in tandem to support the development of healthcare facility special pathogen management capabilities. In August 2020, 20 hospitals that previously received an onsite readiness consultation by NETEC were surveyed to assess how special pathogen programs were leveraged for COVID-19 response. All surveyed facilities indicated their programs were leveraged for COVID-19 response in at least 1 of the following ways: NETEC-sponsored resources and training, utilization of patient isolation spaces, specially trained staff, and supplies. Personal protective equipment shortages were experienced by 95% of facilities, with 80% of facilities reporting that special pathogens program personal protective equipment was used to support facility response to COVID-19 admissions. More than half of facilities (63%) reported leveraging biocontainment unit staff to provide training and education to frontline staff during initial response to COVID-19. These findings have implications for planning and investments to avoid the panic-then-forget cycle that hinders sustained preparedness for future special pathogens.

The global failure of facing the pandemic.

The COVID-19 pandemic outbreak in late 2019 has had social, political, and economic consequences worldwide. However, its emergence was not a surprise. In 2015, a Panel organised by the World Health Organization highlighted the importance of learning about the crisis caused by the Ebola epidemic. In 1992, the Committee on Emerging Microbial Threats to Health of the US Institute of Medicine warned of the possibility of an emerging global microbial threat. In this text, we point out five arguments that reveal the global failure in facing the pandemic: (1) deficiency in the global alert system and the fragility of the International Health Regulations (IHR-2005), (2) problems of the international response to the pandemic, related to global health governance, (3) the dispersed global adoption of the elimination strategy (zero Covid) widely seen as a policy of restriction of freedom instead as a strategy of inequities reduction, (4) fragile control of the disease with a narrow reading of the associated problems, and (5) global setbacks in achieving the Sustainable Development Goals in the context of ongoing neoliberal national policies. Finally, we argue that overcoming the weaknesses discussed requires strengthening health systems in all their components and expanding social welfare policies.[Figure: see text].

Exploring inactivation of SARS-CoV-2, MERS-CoV, Ebola, Lassa, and Nipah viruses on N95 and KN95 respirator material using photoactivated methylene blue to enable reuse.

BACKGROUND: The COVID-19 pandemic resulted in a worldwide shortage of N95 respirators, prompting the development of decontamination methods to enable limited reuse. Countries lacking reliable supply chains would also benefit from the ability to safely reuse PPE. Methylene blue (MB) is a light-activated dye with demonstrated antimicrobial activity used to sterilize blood plasma. Decontamination of respirators using photoactivated MB requires no specialized equipment, making it attractive for use in the field during outbreaks. METHODS: We examined decontamination of N95 and KN95 respirators using photoactivated MB and 3 variants of SARS-CoV-2, the virus that causes COVID-19; and 4 World Health Organization priority pathogens: Ebola virus, Middle East respiratory syndrome coronavirus, Nipah virus, and Lassa virus. Virus inactivation by pretreating respirator material was also tested. RESULTS: Photoactivated MB inactivated all tested viruses on respirator material, albeit with varying efficiency. Virus applied to respirator material pre-treated with MB was also inactivated, thus MB pretreatment may potentially protect respirator wearers from virus exposure in real-time. CONCLUSIONS: These results demonstrate that photoactivated MB represents a cost-effective, rapid, and widely deployable method to decontaminate N95 respirators for reuse during supply shortages.

Marburg virus disease: A deadly rare virus is coming.

Two cases of the deadly Marburgvirus were reported in Ghana, which might be a new global virus alert following COVID-19 and novel monkeypox. Thus far, there is no vaccine or treatment for Marburg virus disease, which is a disease with a mortality rate as high as that of Ebola. Although now human infections with Marburgvirus occurred mainly in Africa, outbreaks were twice reported in Europe over the past 55 years. A concern is that globalization might promote its global viral transmission, just like what happened with COVID-19. The current study has briefly summarized the etiology, epidemiology, and clinical symptoms of the Marburgvirus as well as vaccine development and experimental treatments in order to prevent and control this virus.

"Are You Sure It's Not the Corona Vaccine?" An Ebola Vaccine Trial During COVID-19 in DRC.

The COVID-19 pandemic began as an Ebola epidemic was unfolding in the Democratic Republic of the Congo. In this article, we examine how COVID-19 influenced experiences of an Ebola vaccine trial and attitudes towards medical research in Goma. First, critical debates about vaccine research became a forum in which to contest ineffective local governance and global inequality. Second, discussions about new COVID-19 therapeutics reignited critique of Western biomedical colonialism. Third, rumors were made powerful through everyday observations of the unexpected adaption of Ebola trial procedures in the pandemic. This illustrates the difficulties of maintaining participants' trust, when circumstances dictate protocol alterations mid-trial.

Effect of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Vaccination on Ebola Virus Disease Illness and Death, Democratic Republic of the Congo.

We conducted a retrospective cohort study to assess the effect vaccination with the live-attenuated recombinant vesicular stomatitis virus-Zaire Ebola virus vaccine had on deaths among patients who had laboratory-confirmed Ebola virus disease (EVD). We included EVD-positive patients coming to an Ebola Treatment Center in eastern Democratic Republic of the Congo during 2018-2020. Overall, 25% of patients vaccinated before symptom onset died compared with 63% of unvaccinated patients. Vaccinated patients reported fewer EVD-associated symptoms, had reduced time to clearance of viral load, and had reduced length of stay at the Ebola Treatment Center. After controlling for confounders, vaccination was strongly associated with decreased deaths. Reduction in deaths was not affected by timing of vaccination before or after EVD exposure. These findings support use of preexposure and postexposure recombinant vesicular stomatitis virus-Zaire Ebola virus vaccine as an intervention associated with improved death rates, illness, and recovery time among patients with EVD.

Interactions Among Cross-Border Contiguous Communities and Implications for Managing Pandemics - The case of Ghana and Burkina Faso During the Ebola Outbreak in West Africa: A Qualitative Study.

Introduction: In sub-Saharan Africa, extensive migratory activities and interactions exist especially amongst unmanned cross-border communities between countries sharing common borders which complicate emergency public health interventions. Understanding the nature of these activities and interactions will help strengthen public health interventions and control of pandemics such as the Ebola outbreak and COVID-19. Objective: The study aimed to understand the nature of contiguous border communities' interactions and to seek community solutions for building efficient and resilient health systems to combat a possible Ebola outbreak in Ghana and Burkina Faso and the control of future pandemics. Methods: A qualitative cross sectional study design using focused group discussions and key informant interviews involving six focused groups and forty-six key informants were conducted amongst six Kasem-speaking contiguous border communities, three-each in Ghana and Burkina Faso. Findings: Findings of interactions consisted of social interactions such as marriage ceremonies; traditional and religious practices; informal trade; and health seeking behavior in the study communities. Collaborative disease surveillance systems; constructive dialogue involving community traditional leaders; incorporation of health education into social, traditional and religious activities; retraining of health personnel; effective communication including networking; and inter-governmental collaborations were identified as solutions to the effective control of the Ebola outbreak and for future public health interventions in general. Conclusion: Understanding community interactions and seeking community solutions were identified to be crucial in building efficient health systems that are resilient and responsive to the Ebola outbreak and for future pandemics in contiguous border communities in sub-Saharan Africa.