Post-epidemic health system recovery: A comparative case study analysis of routine immunization programs in the Republics of Haiti and Liberia.

Large-scale epidemics in resource-constrained settings disrupt delivery of core health services, such as routine immunization. Rebuilding and strengthening routine immunization programs following epidemics is an essential step toward improving vaccine equity and averting future outbreaks. We performed a comparative case study analysis of routine immunization program recovery in Liberia and Haiti following the 2014-16 West Africa Ebola epidemic and 2010s cholera epidemic, respectively. First, we triangulated data between the peer-reviewed and grey literature; in-depth key informant interviews with subject matter experts; and quantitative metrics of population health and health system functioning. We used these data to construct thick descriptive narratives for each case. Finally, we performed a cross-case comparison by applying a thematic matrix based on the Essential Public Health Services framework to each case narrative. In Liberia, post-Ebola routine immunization coverage surpassed pre-epidemic levels, a feat attributable to investments in surveillance, comprehensive risk communication, robust political support for and leadership around immunization, and strong public-sector recovery planning. Recovery efforts in Haiti were fragmented across a broad range of non-governmental agencies. Limitations in funding, workforce development, and community engagement further impeded vaccine uptake. Consequently, Haiti reported significant disparities in subnational immunization coverage following the epidemic. This study suggests that embedding in-country expertise within outbreak response structures, respecting governmental autonomy, aligning post-epidemic recovery plans and policies, and integrating outbreak response assets into robust systems of primary care contribute to higher, more equitable levels of routine immunization coverage in resource-constrained settings recovering from epidemics.

Vírus de Marburg: Brevíssimos apontamentos sobre sua história, classificação científica e saúde pública / Marburg virus: very brief notes on its history, scientific classification and public health / Virus de Marburg: apuntes muy breves sobre su historia, clasificación científica y salud pública

A "febre de Marburg", "febre hemorrágica de Margurg", o "Marburgvirus", o "Vírus de Marburg", o "Vírus de Marburgo" (MARV), ou ainda, a "doença do vírus Marburg" (DVM), são nomenclaturas relacionadas a mesma complexa enfermidade, que possuir elevada virulência e letalidade, sendo pertencente direta da ordem dos "Mononegavirales", da família "Filoviridae" e do gênero "Marburgvirus". 1,2,3,5,9,10,12,13 Conforme identificado junto a literatura científica, um outro termo alternativo e, diretamente relacionado ao DVM é "Marburgvirus do Lago Vitória", sendo ele possuidor de várias linhagens e, o seu gênero, não mostra reatividade antigênica do tipo cruzada, com o conhecido "Ebolavirus"

Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).

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].

Ebola: uma ameaça à Saúde Pública e à fauna silvestre / Ebola: a threat to public health and wildlife

Este artigo de revisão sumariza conhecimentos sobre a sintomatologia, patogenia, fatores epidemiológicos para algumas espécies da fauna silvestre acometidas pela virose, lista espécies silvestres vulneráveis à doença do vírus Ebola (EVD) e espécies de animais domésticos não vulveráveis, evidencia o uso de modelos animais para estudos objetivando a defesa de humanos e de animais contra essa doença e destaca a ameaça à saúde dos animais silvestres representada pela EVD.(AU)

This review article summarizes knowledge about the symptomatology, pathogenesis, epidemiological factors for some wildlife species affected by the virus, lists wild species vulnerable to Ebola virus disease (EVD) and non-vulverable species of domestic animals, highlights the use of animal models for studies aimed at the defense of humans and animals against this disease and highlights the threat to the health of wild animals represented by the EVD.(AU)

Strategies in Medicinal Chemistry to Discover New Hit Compounds against Ebola Virus: Challenges and Perspectives in Drug Discovery.

Ebola Virus (EBOV) is an infectious disease that mainly affects the cardiovascular system. It belongs to the Filoviridae family, consisting of filamentous envelopes and non-segmented negative RNA genome. EBOV was initially identified in Sudan and Zaire (now named the Democratic Republic of Congo) around 1967. It is transmitted mainly by contact with secretions (blood, sweat, saliva, and tears) from infected wild animals, such as non-human primates and bats. It has gained more prominence in recent years due to the recent EBOV outbreaks that occurred from 2013 to 2016, resulting in approximately 28,000 infected individuals, with a mortality rate of 40- 70%, affecting mainly Liberia, Guinea, and Sierra Leone. Despite these alarming levels, there is still no FDA-approved drug for the effective treatment of these diseases. The most advanced drug to treat EBOV is remdesivir. However, it is a high-cost drug and is available only for intravenous use. In this sense, more investments are needed in the research focused on the development of new antiviral drugs. In this context, medicinal chemistry strategies have been improving and increasingly discovering new hits that can be used in the future as a treatment against these diseases. Thus, this review will address the main advances in medicinal chemistry, such as drug discovery through computational techniques (virtual screening and virtual high throughput screening), drug repurposing, phenotypic screening assays, and employing classical medicinal chemistry, such as bioisosterism, metabolism-based drug design, and the discovery of new inhibitors through natural products, thereby presenting several promising compounds that may contain the advance of these pathogens.

Rapid diagnostic tests versus RT­PCR for Ebola virus infections: a systematic review and meta-analysis

Objective To evaluate the clinical accuracy of rapid diagnostic tests for the detection of Ebola virus. Methods We searched MEDLINE®, Embase® and Web of Science for articles published between 1976 and October 2021 reporting on clinical studies assessing the performance of Ebola virus rapid diagnostic tests compared with reverse transcription polymerase chain reaction (RT­PCR). We assessed study quality using the QUADAS-2 criteria. To estimate the pooled sensitivity and specificity of these rapid diagnostic tests, we used a bivariate random-effects meta-analysis. Findings Our search identified 113 unique studies, of which nine met the inclusion criteria. The studies were conducted in the Democratic Republic of the Congo, Guinea, Liberia and Sierra Leone and they evaluated 12 rapid diagnostic tests. We included eight studies in the meta-analysis. The pooled sensitivity and specificity of the rapid tests were 86% (95% confidence interval, CI: 80­91) and 95% (95% CI: 91­97), respectively. However, pooled sensitivity decreased to 83% (95% CI: 77­88) after removing outliers. Pooled sensitivity increased to 90% (95% CI: 82­94) when analysis was restricted to studies using the RT­PCR from altona Diagnostics as gold standard. Pooled sensitivity increased to 99% (95% CI: 67­100) when the analysis was restricted to studies using whole or capillary blood specimens. Conclusion The included rapid diagnostic tests did not detect all the Ebola virus disease cases. While the sensitivity and specificity of these tests are moderate, they are still valuable tools, especially useful for triage and detecting Ebola virus in remote areas.

Protocolo de vigilancia en salud pública: Ébola / Public health surveillance protocol

La enfermedad producida por el virus del Ébola (EVE), antes llamada fiebre hemorrágica del Ébola es una enfermedad grave, a menudo mortal en el ser humano. Es transmitida por animales salvajes y se propaga en las poblaciones humanas por transmisión secundaria de persona a persona. Esta enfermedad es endémica en el continente africano; los brotes de EVE tienen una tasa de letalidad aproximadamente del 50%, según documentación de las regiones de África occidental. En brotes anteriores de EVE (1976-2014), las tasas fueron del 25% al 90%

Ebola virus disease (EVD), formerly called Ebola hemorrhagic fever is a disease serious, often fatal in humans. It is transmitted by wild animals and spreads in human populations by secondary transmission from person to person. Is disease is endemic on the African continent; sprouts of EVD have a fatality rate of approximately 50%, according to documentation from the African regions western. In previous EVD outbreaks (1976-2014), rates were from 25% to 90%

On the effectiveness of communication strategies as non-pharmaceutical interventions to tackle epidemics.

When pharmaceutical interventions are unavailable to deal with an epidemic outbreak, adequate management of communication strategies can be key to reduce the contagion risks. On the one hand, accessibility to trustworthy and timely information, whilst on the other, the adoption of preventive behaviors may be both crucial. However, despite the abundance of communication strategies, their effectiveness has been scarcely evaluated or merely circumscribed to the scrutiny of public affairs. To study the influence of communication strategies on the spreading dynamics of an infectious disease, we implemented a susceptible-exposed-infected-removed-dead (SEIRD) epidemiological model, using an agent-based approach. Agents in our systems can obtain information modulating their behavior from two sources: (i) through the local interaction with other neighboring agents and, (ii) from a central entity delivering information with a certain periodicity. In doing so, we highlight how global information delivered from a central entity can reduce the impact of an infectious disease and how informing even a small fraction of the population has a remarkable impact, when compared to not informing the population at all. Moreover, having a scheme of delivering daily messages makes a stark difference on the reduction of cases, compared to the other evaluated strategies, denoting that daily delivery of information produces the largest decrease in the number of cases. Furthermore, when the information spreading relies only on local interactions between agents, and no central entity takes actions along the dynamics, then the epidemic spreading is virtually independent of the initial amount of informed agents. On top of that, we found that local communication plays an important role in an intermediate regime where information coming from a central entity is scarce. As a whole, our results highlight the importance of proper communication strategies, both accurate and daily, to tackle epidemic outbreaks.

Preparedness Tested: Severe Cerebral Malaria Presenting as a High-Risk Person Under Investigation for Ebola Virus Disease at a US Hospital.

In 2019, a 42-year-old African man who works as an Ebola virus disease (EVD) researcher traveled from the Democratic Republic of Congo (DRC), near an ongoing EVD epidemic, to Philadelphia and presented to the Hospital of the University of Pennsylvania Emergency Department with altered mental status, vomiting, diarrhea, and fever. He was classified as a "wet" person under investigation for EVD, and his arrival activated our hospital emergency management command center and bioresponse teams. He was found to be in septic shock with multisystem organ dysfunction, including circulatory dysfunction, encephalopathy, metabolic lactic acidosis, acute kidney injury, acute liver injury, and diffuse intravascular coagulation. Critical care was delivered within high-risk pathogen isolation in the ED and in our Special Treatment Unit until a diagnosis of severe cerebral malaria was confirmed and EVD was definitively excluded.This report discusses our experience activating a longitudinal preparedness program designed for rare, resource-intensive events at hospitals physically remote from any active epidemic but serving a high-volume international air travel port-of-entry.

Factores pronósticos clínicos determinantes en la supervivencia de pacientes con el virus Ébola / Clinical prognostic factors determining the survival of patients with the Ebola virus

Introducción: La enfermedad por el virus del Ébola presenta una elevada letalidad, por lo cual resulta de gran interés la realización de investigaciones que aborden las manifestaciones clínicas que pudieran ser factores pronósticos de supervivencia. Objetivo: Evaluar factores pronósticos de los pacientes enfermos de ébola. Métodos: El universo lo constituyó la totalidad (n = 350) de pacientes ingresados. Se emplearon medidas de resumen para variables cualitativas, estimaciones puntuales y por intervalos para las cuantitativas, así como las pruebas de significación Kaplan-Meier, regresión de Cox y Odds Ratio. Se trabajó con un nivel de confiabilidad del 95 por ciento. Resultados: La supervivencia global fue del 42,5 por ciento. La media de supervivencia, de aproximadamente 10 días (IC: 9 - 11 días). Los pacientes que ingresaron en estado grave (OR = 3,76), que tuvieron dolor lumbar (OR = 2,24), que refirieron cefalea (OR = 2,22), que presentaron fiebre (OR=2,16), que aquejaron de dolor abdominal (OR=1,95) y a quienes se les constató inyección conjuntival (OR = 1,86), tuvieron mayor probabilidad de fallecer, que quienes ingresaron sin estos síntomas y signos. Conclusiones: La supervivencia fue elevada, pese a las complicaciones presentadas. Los síntomas y signos predictores de muerte en los pacientes fueron: la gravedad del paciente al momento del ingreso, la presencia de dolor lumbar, cefalea, fiebre, dolor abdominal e inyección conjuntival(AU)

Introduction: Ebola virus disease has a high lethality, which is why it is of great interest to carry out research that addresses clinical manifestations that could be prognostic factors for survival. Objective: To evaluate prognostic factors of Ebola patients. Methods: the universe was constituted by the totality (n = 350) of admitted patients. Summary measures were used for qualitative variables, point and interval estimates for quantitative variables, as well as Kaplan-Meier significance tests, Cox regression and Odds Ratio. We worked with a 95% level of reliability. Results: The overall survival was 42.5 por ciento. The average survival, approximately 10 days (CI: 9-11 days). Patients who were admitted in serious condition (OR = 3.76), who had low back pain (OR = 2.24), who reported headache (OR = 2.22), who presented fever (OR = 2.16), who they suffered from abdominal pain (OR = 1.95) and who were found to have conjunctival injection (OR = 1.86), were more likely to die than those who entered without these symptoms and signs. Conclusions: Survival was high, despite the complications presented. The symptoms and predictive signs of death in the patients were: the severity of the patient at admission, the presence of low back pain, headache, fever, abdominal pain and conjunctival injection(AU)

Mental Models of Infectious Diseases and Public Understanding of COVID-19 Prevention.

The emergence of viral diseases such as Ebola virus disease, Zika virus disease, and the coronavirus disease (COVID-19) has posed considerable challenges to health care systems around the world. Public health strategy to address emerging infectious diseases has depended in part on human behavior change and yet the perceptions and knowledge motivating that behavior have been at times inconsistent with the latest consensus of peer-reviewed science. Part of that disjuncture likely involves the existence and persistence of past ideas about other diseases. To forecast and prepare for future epidemic and pandemic response, we need to better understand how people approach emerging infectious diseases as objects of public opinion during the periods when such diseases first become salient at a population level. In this essay, we explore two examples of how existing mental models of past infectious diseases appear to have conditioned and constrained public response to novel viral diseases. We review previously reported experiences related to Zika virus in Central America and discuss public opinion data collected in the early months of the COVID-19 pandemic. In the case of Zika virus disease, we assess how thinking about earlier mosquito-borne disease seems to have affected public consideration of the virus in Guatemala. In the case of COVID-19, we assess how previous vaccination behavior for a different disease is associated with intention to obtain vaccination for COVID-19 in the future.

Historical epidemiology and global health history.

The subdiscipline of historical epidemiology holds the promise of creating a more robust and more nuanced foundation for global public health decision-making by deepening the empirical record from which we draw lessons about past interventions. This essay draws upon historical epidemiological research on three global public health campaigns to illustrate this promise: the Rockefeller Foundation's efforts to control hookworm disease (1909-c.1930), the World Health Organization's pilot projects for malaria eradication in tropical Africa (1950s-1960s), and the international efforts to shut down the transmission of Ebola virus disease during outbreaks in tropical Africa (1974-2019).

Historical epidemiology and global health history / Epidemiologia histórica e história global da saúde

Abstract The subdiscipline of historical epidemiology holds the promise of creating a more robust and more nuanced foundation for global public health decision-making by deepening the empirical record from which we draw lessons about past interventions. This essay draws upon historical epidemiological research on three global public health campaigns to illustrate this promise: the Rockefeller Foundation's efforts to control hookworm disease (1909-c.1930), the World Health Organization's pilot projects for malaria eradication in tropical Africa (1950s-1960s), and the international efforts to shut down the transmission of Ebola virus disease during outbreaks in tropical Africa (1974-2019).

Resumo A subdisciplina epidemiologia histórica se propõe a criar um alicerce robusto e refinado para o processo de tomada de decisões em saúde pública global, aprofundando registros empíricos que nos ensinam sobre intervenções passadas. Este artigo se baseia na pesquisa epidemiológica histórica de três campanhas globais de saúde pública para ilustrar essa proposta: os esforços da Fundação Rockefeller para controle da ancilostomose (1909-c.1930), os projetos-piloto da Organização Mundial da Saúde para erradicação da malária na África tropical (décadas de 1950-1960), e os esforços internacionais de interrupção da transmissão do vírus Ebola durante surtos na África tropical (1974-2019).

Ebola virus disease: An emerging and re-emerging viral threat.

The genus Ebolavirus from the family Filoviridae is composed of five species including Sudan ebolavirus, Reston ebolavirus, Bundibugyo ebolavirus, Taï Forest ebolavirus, and Ebola virus (previously known as Zaire ebolavirus). These viruses have a large non-segmented, negative-strand RNA of approximately 19 kb that encodes for glycoproteins (i.e., GP, sGP, ssGP), nucleoproteins, virion proteins (i.e., VP 24, 30,40) and an RNA dependent RNA polymerase. These viruses have become a global health concern because of mortality, their rapid dissemination, new outbreaks in West-Africa, and the emergence of a new condition known as "Post-Ebola virus disease syndrome" that resembles inflammatory and autoimmune conditions such as rheumatoid arthritis, systemic lupus erythematosus and spondyloarthritis with uveitis. However, there are many gaps in the understanding of the mechanisms that may induce the development of such autoimmune-like syndromes. Some of these mechanisms may include a high formation of neutrophil extracellular traps, an uncontrolled "cytokine storm", and the possible formation of auto-antibodies. The likely appearance of autoimmune phenomena in Ebola survivors suppose a new challenge in the management and control of this disease and opens a new field of research in a special subgroup of patients. Herein, the molecular biology, pathogenesis, clinical manifestations, and treatment of Ebola virus disease are reviewed and some strategies for control of disease are discussed.