COVID-19 vaccines and the pandemic: lessons learnt for other neglected diseases and future threats.

Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while low and middle-income countries (LMICs) were pushed to the back of the queue and relied more heavily on adenoviral vector, inactivated virus and recombinant protein vaccines. To prevent this from occurring in future pandemics, it is essential to expand the scale-up capacity for both traditional and new vaccine technologies at individual or simultaneous hubs in LMICs. In parallel, a process of tech transfer of new technologies to LMIC producers needs to be facilitated and funded, while building LMIC national regulatory capacity, with the aim of several reaching 'stringent regulator' status. Access to doses is an essential start but is not sufficient, as healthcare infrastructure for vaccination and combating dangerous antivaccine programmes both require support. Finally, there is urgency to establish an international framework through a United Nations Pandemic Treaty to promote, support and harmonise a more robust, coordinated and effective global response.

Increasing Local Disease Preparedness and Surveillance Capacity for Global Health Security: A Cluster-Randomised Control Trial (preprint)

Background: Low-income countries are often characterized by poor health infrastructures and lack systems needed to timely detect and control disease outbreaks, such as the 2014-16 Ebola Viral Disease and COVID-19. In such contexts, a “One Health” approach, which involves investing in both human and animal health systems, plausibly improves local health outcomes by enabling early detection of zoonotic diseases before they are transmitted to humans, and by timely triggering a health system response needed to mitigate possible outbreaks. There is an urgent call to translate One Health into action and create inclusive and sustainable policies. There is however limited direct evidence on the gains from One Health approaches. We contribute here by using a randomised intervention to assess the impact of a participatory community-based One Health program.Methods: As part of a cluster-randomised control trial, government and communities recruited, trained and installed Community Animal Health Workers (CAHWs) to work alongside Community Health Workers (CHWs) in 300 randomly selected rural villages in Sierra Leone. Another 63 villages were randomly selected as control sites and had CHWs exclusively. CAHWs provided essential animal health services, disseminated information regarding animal and human health best practices, and actively participated in surveillance efforts by reporting suspected disease symptoms to government supervisors. We investigated program impacts on human health as well as key intermediary outcomes, including animal health, animal and human health-related behaviours, integration into public services, and household wealth. The trial is registered at clinicaltrialregister.nl (# 21660) and OSF (https://osf.io/9xfv3).Findings: In July and August 2017, the community-based One Health program successfully recruited, trained and installed CAHWs across 287 villages. Throughout the program's duration, spanning from July 2017 to July 2019, the CAHWs reported on 17,813 suspected disease-related events. Using survey data from 2,538 respondents, collected in March and April 2020, we found no evidence of impacts on human health (-0.010 standard deviation units (SDU), 95% CI -0.131, 0.111). The program did improve intermediary outcomes including animal health (0.157 SDU, 95% CI 0.022, 0.293), animal husbandry practices (0.127 SDU, 95% CI -0.022, 0.276), human health behaviours (0.137 SDU, 95% CI -0.007, 0.281), integration into public services (0.300 SDU, 95% CI 0.116, 0.484), and households’ attitudes towards disease reporting (0.263 SDU, 95% CI 0.109, 0.418).Interpretation: Participatory community-based One Health interventions can increase preparedness against zoonotic diseases.Trial Registration: The trial is registered at clinicaltrialregister.nl (# 21660) and OSF (https://osf.io/9xfv3).Funding: The study was funded by NWO grant #451-14-001 and #VI.Vidi.191.154, ESRC grant ES/J017620/1, the Royal Netherlands Embassy in Ghana, the International Growth Center, New York University – Abu Dhabi and the World Bank REDISSE program.Declaration of Interest: We declare no competing interests.Ethical Approval: Before the onset of the program, formal approval was obtained from local authorities. We obtained verbal informed consent from all study participants. Ethics approval was obtained from the Office of the Sierra Leone Ethics and Scientific Review Committee (SLERC 16102017) and Columbia University (AAAR5175).

Host antiviral factors hijack furin to block SARS-CoV-2, ebola virus, and HIV-1†glycoproteins cleavage.

Viral envelope glycoproteins are crucial for viral infections. In the process of enveloped viruses budding and release from the producer cells, viral envelope glycoproteins are presented on the viral membrane surface as spikes, promoting the virus's next-round infection of target cells. However, the host cells evolve counteracting mechanisms in the long-term virus-host co-evolutionary processes. For instance, the host cell antiviral factors could potently suppress viral replication by targeting their envelope glycoproteins through multiple channels, including their intracellular synthesis, glycosylation modification, assembly into virions, and binding to target cell receptors. Recently, a group of studies discovered that some host antiviral proteins specifically recognized host proprotein convertase (PC) furin and blocked its cleavage of viral envelope glycoproteins, thus impairing viral infectivity. Here, in this review, we briefly summarize several such host antiviral factors and analyze their roles in reducing furin cleavage of viral envelope glycoproteins, aiming at providing insights for future antiviral studies.

Immune correlates of protection for SARS-CoV-2, Ebola and Nipah virus infection.

Correlates of protection (CoP) are biological parameters that predict a certain level of protection against an infectious disease. Well-established correlates of protection facilitate the development and licensing of vaccines by assessing protective efficacy without the need to expose clinical trial participants to the infectious agent against which the vaccine aims to protect. Despite the fact that viruses have many features in common, correlates of protection can vary considerably amongst the same virus family and even amongst a same virus depending on the infection phase that is under consideration. Moreover, the complex interplay between the various immune cell populations that interact during infection and the high degree of genetic variation of certain pathogens, renders the identification of immune correlates of protection difficult. Some emerging and re-emerging viruses of high consequence for public health such as SARS-CoV-2, Nipah virus (NiV) and Ebola virus (EBOV) are especially challenging with regards to the identification of CoP since these pathogens have been shown to dysregulate the immune response during infection. Whereas, virus neutralising antibodies and polyfunctional T-cell responses have been shown to correlate with certain levels of protection against SARS-CoV-2, EBOV and NiV, other effector mechanisms of immunity play important roles in shaping the immune response against these pathogens, which in turn might serve as alternative correlates of protection. This review describes the different components of the adaptive and innate immune system that are activated during SARS-CoV-2, EBOV and NiV infections and that may contribute to protection and virus clearance. Overall, we highlight the immune signatures that are associated with protection against these pathogens in humans and could be used as CoP.

Comment la résilience post-Ebola en Guinée contribue à la gestion de la COVID-19 ?

Introduction : The case of Ebola in Guinea (2013-2016) revealed weaknesses in the resilience of the health system and highlighted the challenge of coordinating all actors in the response. After the epidemic, national authorities and their international partners began to strengthen the health system. In 2021, Guinea faced COVID-19 simultaneously with the resurgence of Ebola and other diseases with epidemic potential.Purpose of research : The objective of this article is to analyze the evolution of the five characteristics of health resilience of Kruk et al. (2015) in the Guinean context. To do this, data triangulation was carried out through a literature review, 41 semi-structured interviews with international, national and local stakeholders, and 37 events observed in the post-Ebola period.Results : Our results show that the characteristic of integration was the most important in our study. This is because of the importance of coordination, communication and information sharing among stakeholders during crises. Then, diversity exposes the need to be able to face several health challenges simultaneously. Efforts were focused on Ebola during the first outbreak, but since the COVID-19 pandemic, Guinea has been able to cope with several health challenges. Raising awareness, on the other hand, necessitates an understanding of the context, its strengths, and weaknesses. Guinea learned lessons from Ebola and implemented a program to strengthen the emergency response system. On self-regulation, the speed of the response relies on mechanisms for early detection, notification, and response. The country is now well resourced and has proven information and response mechanisms. Finally, constant adaptability by taking into account lessons learned allows us to set course and prepare for other potential crises and this is what is being done constantly.Conclusions : Given Guinea’s ubiquitous fragility before Ebola, the health system is still not fully resilient. However, gains in each of the characteristics of resilience improve the response to COVID-19.

Sphingosine Kinases Promote Ebola Virus Infection and Can Be Targeted to Inhibit Filoviruses, Coronaviruses, and Arenaviruses Using Late Endocytic Trafficking to Enter Cells.

Entry of enveloped viruses in host cells requires the fusion of viral and host cell membranes, a process that is facilitated by viral fusion proteins protruding from the viral envelope. These viral fusion proteins need to be triggered by host factors, and for some viruses, this event occurs inside endosomes and/or lysosomes. Consequently, these 'late-penetrating viruses' must be internalized and delivered to entry-conducive intracellular vesicles. Because endocytosis and vesicular trafficking are tightly regulated cellular processes, late-penetrating viruses also depend on specific host proteins for efficient delivery to the site of fusion, suggesting that these could be targeted for antiviral therapy. In this study, we investigated a role for sphingosine kinases (SKs) in viral entry and found that chemical inhibition of sphingosine kinase 1 (SK1) and/or SK2 and knockdown of SK1/2 inhibited entry of Ebola virus (EBOV) into host cells. Mechanistically, inhibition of SK1/2 prevented EBOV from reaching late-endosomes and lysosomes that contain the EBOV receptor, Niemann Pick C1 (NPC1). Furthermore, we present evidence that suggests that the trafficking defect caused by SK1/2 inhibition occurs independently of sphingosine-1-phosphate (S1P) signaling through cell-surface S1P receptors. Lastly, we found that chemical inhibition of SK1/2 prevents entry of other late-penetrating viruses, including arenaviruses and coronaviruses, and inhibits infection by replication-competent EBOV and SARS-CoV-2 in Huh7.5 cells. In sum, our results highlight an important role played by SK1/2 in endocytic trafficking, which can be targeted to inhibit entry of late-penetrating viruses and could serve as a starting point for the development of broad-spectrum antiviral therapeutics.

The lasting influence of Ebola: a qualitative study of community-level behaviors, trust, and perceptions three years after the 2014-16 Ebola epidemic in Liberia.

The majority of disease transmission during the 2014-16 West Africa Ebola epidemic was driven by community-based behaviors that proved difficult to change in a social paradigm of misinformation, denial, and deep-seated distrust of government representatives and institutions. In Liberia, perceptions and beliefs about Ebola during and since the epidemic can provide insights useful to public health strategies aimed at improving community preparedness. In this 2018 study, we conducted nine focus groups with Liberians from three communities who experienced Ebola differently, to evaluate behaviors, attitudes, and trust during and after the epidemic. Focus group participants reported that some behaviors adopted during Ebola have persisted (e.g. handwashing and caretaking practices), while others have reverted (e.g. physical proximity and funeral customs); and reported ongoing distrust of the government and denial of the Ebola epidemic. These findings suggest that a lack of trust in the biomedical paradigm and government health institutions persists in Liberia. Future public health information campaigns may benefit from community engagement addressed at understanding beliefs and sources of trust and mistrust in the community to effect behavior change and improve community-level epidemic preparedness.

Approaches to demonstrating the effectiveness of filovirus vaccines: Lessons from Ebola and COVID-19.

Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Marburg virus (MARV), are members of the Filoviridae family that can cause severe disease and death in humans and animals. The reemergence of Ebola, Sudan and Marburg virus disease highlight the need for continued availability of safe and effectives vaccines as well as development of new vaccines. While randomized controlled trials using disease endpoints provide the most robust assessment of vaccine effectiveness, challenges to this approach include the unpredictable size, location, occurrence and duration of filovirus disease outbreaks. Thus, other approaches to demonstrating vaccine effectiveness have been considered. These approaches are discussed using examples of preventive vaccines against other infectious diseases. In addition, this article proposes a clinical immunobridging strategy using licensed EBOV vaccines as comparators for demonstrating the effectiveness of filovirus vaccine candidates that are based on the same licensed vaccine platform technology.

Magnetic biosensors for identification of SARS-CoV-2, Influenza, HIV, and Ebola viruses: a review.

Infectious diseases such as novel coronavirus (SARS-CoV-2), Influenza, HIV, Ebola, etc kill many people around the world every year (SARS-CoV-2 in 2019, Ebola in 2013, HIV in 1980, Influenza in 1918). For example, SARS-CoV-2 has plagued higher than 317 000 000 people around the world from December 2019 to January 13, 2022. Some infectious diseases do not yet have not a proper vaccine, drug, therapeutic, and/or detection method, which makes rapid identification and definitive treatments the main challenges. Different device techniques have been used to detect infectious diseases. However, in recent years, magnetic materials have emerged as active sensors/biosensors for detecting viral, bacterial, and plasmids agents. In this review, the recent applications of magnetic materials in biosensors for infectious viruses detection have been discussed. Also, this work addresses the future trends and perspectives of magnetic biosensors.

Contextual determinants of mass drug administration performance: Modelling fourteen years of lymphatic filariasis treatments in West Africa.

BACKGROUND: Effective mass drug administration (MDA) is the cornerstone in the elimination of lymphatic filariasis (LF) and a critical component in combatting all neglected tropical diseases for which preventative chemotherapy is recommended (PC-NTDs). Despite its importance, MDA coverage, however defined, is rarely investigated systematically across time and geography. Most commonly, investigations into coverage react to unsatisfactory outcomes and tend to focus on a single year and health district. Such investigations omit more macro-level influences including sociological, environmental, and programmatic factors. The USAID NTD database contains measures of performance from thousands of district-level LF MDA campaigns across 14 years and 10 West African countries. Specifically, performance was measured as an MDA's epidemiological coverage, calculated as persons treated divided by persons at risk. This analysis aims to explain MDA coverage across time and geography in West Africa using sociological, environmental, and programmatic factors. METHODOLOGY: The analysis links epidemiological coverage data from 3,880 LF MDAs with contextual, non-NTD data via location (each MDA was specific to a health district) and time (MDA month, year). Contextual data included rainfall, temperature, violence or social unrest, COVID-19, the 2014 Ebola outbreak, road access/isolation, population density, observance of Ramadan, and the number of previously completed MDAs. PRINCIPAL FINDINGS: We fit a hierarchical linear regression model with coverage as the dependent variable and performed sensitivity analyses to confirm the selection of the explanatory factors. Above average rainfall, COVID-19, Ebola, violence and social unrest were all significantly associated with lower coverage. Years of prior experience in a district and above average temperature were significantly associated with higher coverage. CONCLUSIONS/SIGNIFICANCE: These generalized and context-focused findings supplement current literature on coverage dynamics and MDA performance. Findings may be used to quantify typically anecdotal considerations in MDA planning. The model and methodology are offered as a tool for further investigation.

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.

Interdisciplinary Collaboration in International Crisis Medical Relief: A Look at the Nepal Earthquake and Ebola Relief Efforts.

OBJECTIVE: This study explores interprofessional collaboration among medical and non-medical personnel planning and implementing international crisis health and medical relief efforts, and how disciplinary and professional background influences these activities. METHODS: This study analyzes semi-structured interviews with individuals involved in organizations medical or health services to the Ebola epidemic in West Africa (2014-2016) or the 2015 Nepal earthquake. RESULTS: Disciplinary background, sometimes coupled with organization role, shaped how relief workers engaged in the process of planning and implementing crisis medical relief. There were 3 thematic areas where these differences emerged: issue focus, problem -solving approaches, and decision-making approaches. Solutions from the field emerged as a fourth theme. CONCLUSIONS: The study demonstrates medical relief required collaboration across medical and non-medical professions and highlights the importance of relief workers' disciplinary background in shaping the planning and implementation of crisis medical relief. Successful collaboration requires that people involved in crisis relief communicate the relevance of their own expertise, identify limits of their own and others' disciplinary perspective(s), seek out strengths in others' expertise, and can identify/ respond appropriately to others who do not see their own disciplinary limits, as well as learn these skills before engaging in relief.

How has Guinea learnt from the response to outbreaks? A learning health system analysis.

INTRODUCTION: Learning is a key attribute of a resilient health system and, therefore, is central to health system strengthening. The main objective of this study was to analyse how Guinea's health system has learnt from the response to outbreaks between 2014 and 2021. METHODS: We used a retrospective longitudinal single embedded case study design, applying the framework conceptualised by Sheikh and Abimbola for analysing learning health systems. Data were collected employing a mixed methods systematic review carried out in March 2022 and an online survey conducted in April 2022. RESULTS: The 70 reports included in the evidence synthesis were about the 2014-2016 Ebola virus disease (EVD), Measles, Lassa Fever, COVID-19, 2021 EVD and Marburg virus disease. The main lessons were from 2014 to 2016 EVD and included: early community engagement in the response, social mobilisation, prioritising investment in health personnel, early involvement of anthropologists, developing health infrastructure and equipment and ensuring crisis communication. They were learnt through information (research and experts' opinions), action/practice and double-loop and were progressively incorporated in the response to future outbreaks through deliberation, single-loop, double-loop and triple-loop learning. However, advanced learning aspects (learning through action, double-loop and triple-loop) were limited within the health system. Nevertheless, the health system successfully controlled COVID-19, the 2021 EVD and Marburg virus disease. Survey respondents' commonly reported that enablers were the creation of the national agency for health security and support from development partners. Barriers included cultural and political issues and lack of funding. Common recommendations included establishing a knowledge management unit within the Ministry of Health with representatives at regional and district levels, investing in human capacities and improving the governance and management system. CONCLUSION: Our study highlights the importance of learning. The health system performed well and achieved encouraging and better outbreak response outcomes over time with learning that occurred.

Potential use of the cholesterol transfer inhibitor U18666A as an antiviral drug for research on various viral infections.

Cholesterol plays critical functions in arranging the biophysical attributes of proteins and lipids in the plasma membrane. For various viruses, an association with cholesterol for virus entrance and/or morphogenesis has been demonstrated. Therefore, the lipid metabolic pathways and the combination of membranes could be targeted to selectively suppress the virus replication steps as a basis for antiviral treatment. U18666A is a cationic amphiphilic drug (CAD) that affects intracellular transport and cholesterol production. A robust tool for investigating lysosomal cholesterol transfer and Ebola virus infection is an androstenolone derived termed U18666A that suppresses three enzymes in the cholesterol biosynthesis mechanism. In addition, U18666A inhibited low-density lipoprotein (LDL)-induced downregulation of LDL receptor and triggered lysosomal aggregation of cholesterol. According to reports, U18666A inhibits the reproduction of baculoviruses, filoviruses, hepatitis, coronaviruses, pseudorabies, HIV, influenza, and flaviviruses, as well as chikungunya and flaviviruses. U18666A-treated viral infections may act as a novel in vitro model system to elucidate the cholesterol mechanism of several viral infections. In this article, we discuss the mechanism and function of U18666A as a potent tool for studying cholesterol mechanisms in various viral infections.

The PA profession in Liberia: A case study in pioneering innovation and resiliency.

ABSTRACT: In Liberia, the physician assistant (PA) profession began in the mid-1960s. PAs have had a major role in providing access to healthcare for patients, many of whom live in poverty and reside in remote areas where access to physicians may be severely limited. In 1964, representatives from UNICEF selected Agnes N. Dagbe, MS, RN, to be the first director of a new PA program to be developed at the Tubman National Institute of Medical Arts. Dagbe was sent to Russia to learn about their feldsher profession, which served as a significant source of inspiration for the newly emerging PA profession in Liberia. To date, Liberia has faced extreme shortages of physicians, the ravages of two brutal civil wars over a 14-year period (1989-2003), as well as outbreaks of the Ebola and COVID-19 viruses. Now, more than 54 years since the first class graduated, PAs are vital for the delivery of essential healthcare services for the citizens of Liberia.

Effects of therapies for Ebola virus disease: a systematic review and network meta-analysis.

BACKGROUND: Specific treatments targeting Ebola virus are crucial in managing Ebola virus disease. To support the development of clinical practice guidelines on medications for Ebola virus disease, we aimed to evaluate the efficacy and safety of therapies for patients with Ebola virus disease. METHODS: In this systematic review and network meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, Global Health, African Index Medicus, World Health Organization Global Index Medicus, the Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, Epistemonikos, bioRxiv, medRxiv, and SSRN without language restrictions for randomised controlled trials (RCTs) published between database inception and Jan 1, 2022, comparing at least one therapeutic agent for Ebola virus disease against standard care or another therapeutic agent for Ebola virus disease. Two reviewers assessed study eligibility and extracted summary data independently using a standardised form. Our outcomes of interest were mortality, adverse maternal outcomes, risk of onward transmission, duration of admission to a health-care facility, functional status after Ebola virus disease, serious adverse events from medication, adverse perinatal outcomes, time to symptom resolution, and time to viral clearance. We did frequentist network meta-analyses to estimate the effect of all interventions and applied the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of the evidence. We registered the protocol with PROSPERO, CRD42022296539. FINDINGS: We identified 7840 records through database searches, of which two RCTs with a total of 753 patients proved eligible. Only data on mortality, the duration of admission, serious adverse events, and time to viral clearance were available for meta-analysis. Compared with standard care, REGN-EB3 (relative risk [RR] 0·40, 95% CI 0·18 to 0·89; moderate certainty) and mAb114 (0·42, 0·19 to 0·93; moderate certainty) probably reduce mortality. Whether ZMapp (0·60, 0·28 to 1·26; very low certainty) and remdesivir (0·64, 0·29 to 1·39; very low certainty) reduce mortality compared with standard care is uncertain. With high certainty, REGN-EB3 reduces mortality compared with ZMapp (0·67, 0·52 to 0·88) and remdesivir (0·63, 0·49 to 0·82). With high certainty, mAb114 also reduces mortality compared with ZMapp (0·71, 0·55 to 0·91) and remdesivir (0·66, 0·52 to 0·84). Compared with standard care, REGN-EB3, mAb114, ZMapp, and remdesivir might have little or no effect on the time to viral clearance (mean difference ranged from -0·25 days to -1·14 days; low certainty). ZMapp might reduce the duration of admission compared with standard care (mean difference -2·02 days, 95% CI -4·05 to 0·01; low certainty). Findings for all comparisons suggested that there might be little or no difference in the prevalence of serious adverse events, but certainty was low or very low in all comparisons but one. INTERPRETATION: REGN-EB3 and mAb114 separately reduce mortality compared with ZMapp, remdesivir, or standard care in patients with Ebola virus disease. These findings suggest that health-care workers should prioritise the use of REGN-EB3 and mAb114 for patients with Ebola virus disease during future outbreaks. FUNDING: WHO.

Lessons learnt from the applying the Centers for Disease Control and Prevention (CDC) evaluation framework to the measles incident management system response, USA, 2020-2021.

The functionality and performance of public health programmes at all levels of government play a critical role in preventing, detecting, mitigating and responding to public health threats, including infectious disease outbreaks. Multiple and concurrent outbreaks in recent years, such as COVID-19, Ebola and Zika, have highlighted the importance of documenting lessons learnt from public health responses of national and global agencies. In February 2020, the US Centers for Disease Control and Prevention (CDC) Center for Global Health (CGH) activated the Measles Incident Management System (MIMS) to accelerate the ability to detect, mitigate and respond to measles outbreaks globally and advance progress towards regional measles elimination goals. The activation was triggered by a global resurgence in reported measles cases during 2018-2019 and supported emergency response activities conducted by partner organisations and countries. MIMS leadership decided early in the response to form an evaluation team to design and implement an evaluation approach for producing real-time data to document progress of response activities and inform timely decision-making. In this manuscript, we describe how establishing an evaluation unit within MIMS, and engaging MIMS leadership and subject matter experts in the evaluation activities, was critical to monitor progress and document lessons learnt to inform decision making. We also explain the CDC's Framework for Evaluation in Public Health Practice applied to evaluate the dynamic events throughout the MIMS response. Evaluators supporting emergency response should use a flexible framework that can be adaptable in dynamic contexts and document response activities in real-time.