Medicine Infectious Diseases

Viral Infections and Outbreaks Research

Description

This cluster of papers encompasses research on the Ebola virus, including its transmission, pathogenesis, genomic surveillance, vaccine development, and the impact of public health measures. It also covers topics related to outbreaks, reservoirs of the virus, and the immune response to Ebola infection.

Keywords

Ebola Virus; Outbreak; Vaccine; Transmission; Reservoirs; Pathogenesis; Genomic Surveillance; Public Health Measures; Immune Response; Zoonotic Origin

In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and … In a study of Lassa fever in Sierra Leone, West Africa, we identified two variables associated with a high risk of death, and we evaluated the efficacy of ribavirin and Lassa virus-convalescent plasma for the treatment of Lassa fever. A serum aspartate aminotransferase level greater than or equal to 150 IU per liter at the time of hospital admission was associated with a case-fatality rate of 55 percent (33 of 60). Patients with the same risk factor who were treated for 10 days with intravenous ribavirin, begun within the first 6 days after the onset of fever, had a case-fatality rate of 5 percent (1 of 20) (P = 0.0002 by Fisher's exact test). Patients whose treatment began seven or more days after the onset of fever had a case-fatality rate of 26 percent (11 of 43) (P = 0.01). Viremia with levels greater than or equal to 10(3.6) TCID50 per milliliter on admission was associated with a case-fatality rate of 76 percent (35 of 46). Patients with this risk factor who were treated with intravenous ribavirin within the first six days after onset of fever had a case-fatality rate of 9 percent (1 of 11) (P = 0.006), whereas those treated after seven days or more of illness had a fatality rate of 47 percent (9 of 19) (P = 0.035). Oral ribavirin was also effective in patients at high risk of death. Lassa-convalescent plasma did not significantly reduce mortality in any of the high-risk groups. We conclude that ribavirin is effective in the treatment of Lassa fever and that it should be used at any point in the illness, as well as for postexposure prophylaxis.
Journal Article QUANTITATIVE METHODS IN THE REVIEW OF EPIDEMIOLOGIC LITERATURE Get access SANDER GREENLAND SANDER GREENLAND Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic … Journal Article QUANTITATIVE METHODS IN THE REVIEW OF EPIDEMIOLOGIC LITERATURE Get access SANDER GREENLAND SANDER GREENLAND Search for other works by this author on: Oxford Academic PubMed Google Scholar Epidemiologic Reviews, Volume 9, Issue 1, 1987, Pages 1–30, https://doi.org/10.1093/oxfordjournals.epirev.a036298 Published: 01 March 1987
Infectious diseases are responsible for millions of deaths worldwide every year. News on outbreaks of infectious diseases like Ebola, Marburg, Lassa fever, which have high death rates, are often the … Infectious diseases are responsible for millions of deaths worldwide every year. News on outbreaks of infectious diseases like Ebola, Marburg, Lassa fever, which have high death rates, are often the focus of exaggerated press scare stories. 30 years ago the prevailing viewpoint in the USA and Europe was that infectious diseases were conquered and had become a problem of the past. This irresponsible and complacent view changed dramatically after the unexpected emergence and rapid spread of the epidemic of HIV/AIDS in the 1990s.
In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× … In its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.
In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these … In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild.
The third edition of this book has been completely revised and updated, and new chapters have been added on Hantanvirus by Karl Johnson, on retroviruses by William Blattner, and on … The third edition of this book has been completely revised and updated, and new chapters have been added on Hantanvirus by Karl Johnson, on retroviruses by William Blattner, and on hepatocellular carcinoma by Joseph Melnick. New authors have replaced previous authors for several chapters. These include Karl Johnson on arenaviruses, Stephen Hadler and Harold Margolin on viral hepatitis, Paul Glezen and Robert Couch on influenza, Alfred S. Evans and Guy de-The on Burkitt lymphoma, and Joseph Melnick, William Rawls, and Ervin Adam on cervical cancer. A summary of the major advances since the last edition in 1982 has been provided by each contributor as given below. Overall, it is clear that the rapid advances in molecular virology, monoclonal antibody, and rapid diagnostic techniques dominate the progress since the last edition and provide a better understanding of pathogenesis, newer tools for epidemiologic investigation, and new methods for vac cine production. Although there is repetition in mention of these advances as written by each contributor, the editor has let these stand to let the reader know how each interprets the impact of these new developments. I. Introduction and Concepts Chapter 1. Epidemiologic Concepts and Methods: The sections on control of infectious diseases has been much expanded to cover progress and problems in both developed and developing countries, the concepts of eradication and elimination, and the means to assess the need and effectiveness of immuniza tion programs.
A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be α-dystroglycan (α-DG). … A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be α-dystroglycan (α-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified α-DG protein. Soluble α-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, α-DG is a cellular receptor for both LCMV and LFV.
Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by … Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stomatitis viruses bearing the EboV glycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs.
Ebola virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity, which … Ebola virus causes hemorrhagic fever in humans and nonhuman primates, resulting in mortality rates of up to 90%. Studies of this virus have been hampered by its extraordinary pathogenicity, which requires biosafety level 4 containment. To circumvent this problem, we developed a novel complementation system for functional analysis of Ebola virus glycoproteins. It relies on a recombinant vesicular stomatitis virus (VSV) that contains the green fluorescent protein gene instead of the receptor-binding G protein gene (VSVDeltaG*). Herein we show that Ebola Reston virus glycoprotein (ResGP) is efficiently incorporated into VSV particles. This recombinant VSV with integrated ResGP (VSVDeltaG*-ResGP) infected primate cells more efficiently than any of the other mammalian or avian cells examined, in a manner consistent with the host range tropism of Ebola virus, whereas VSVDeltaG* complemented with VSV G protein (VSVDeltaG*-G) efficiently infected the majority of the cells tested. We also tested the utility of this system for investigating the cellular receptors for Ebola virus. Chemical modification of cells to alter their surface proteins markedly reduced their susceptibility to VSVDeltaG*-ResGP but not to VSVDeltaG*-G. These findings suggest that cell surface glycoproteins with N-linked oligosaccharide chains contribute to the entry of Ebola viruses, presumably acting as a specific receptor and/or cofactor for virus entry. Thus, our VSV system should be useful for investigating the functions of glycoproteins from highly pathogenic viruses or those incapable of being cultured in vitro.
In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus … In July and September 2007, miners working in Kitaka Cave, Uganda, were diagnosed with Marburg hemorrhagic fever. The likely source of infection in the cave was Egyptian fruit bats (Rousettus aegyptiacus) based on detection of Marburg virus RNA in 31/611 (5.1%) bats, virus-specific antibody in bat sera, and isolation of genetically diverse virus from bat tissues. The virus isolates were collected nine months apart, demonstrating long-term virus circulation. The bat colony was estimated to be over 100,000 animals using mark and re-capture methods, predicting the presence of over 5,000 virus-infected bats. The genetically diverse virus genome sequences from bats and miners closely matched. These data indicate common Egyptian fruit bats can represent a major natural reservoir and source of Marburg virus with potential for spillover into humans.
In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic … In March 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Full-length genome sequencing and phylogenetic analysis showed that EBOV from Guinea forms a separate clade in relationship to the known EBOV strains from the Democratic Republic of Congo and Gabon. Epidemiologic investigation linked the laboratory-confirmed cases with the presumed first fatality of the outbreak in December 2013. This study demonstrates the emergence of a new EBOV strain in Guinea.
Ebola virus is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. Here we show that the primate lentiviral binding C-type lectins DC-SIGN and L-SIGN act as cofactors … Ebola virus is a highly lethal pathogen responsible for several outbreaks of hemorrhagic fever. Here we show that the primate lentiviral binding C-type lectins DC-SIGN and L-SIGN act as cofactors for cellular entry by Ebola virus. Furthermore, DC-SIGN on the surface of dendritic cells is able to function as a trans receptor, binding Ebola virus-pseudotyped lentiviral particles and transmitting infection to susceptible cells. Our data underscore a role for DC-SIGN and L-SIGN in the infective process and pathogenicity of Ebola virus infection.
Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by … Several human and animal Ebola outbreaks have occurred over the past 4 years in Gabon and the Republic of Congo. The human outbreaks consisted of multiple simultaneous epidemics caused by different viral strains, and each epidemic resulted from the handling of a distinct gorilla, chimpanzee, or duiker carcass. These animal populations declined markedly during human Ebola outbreaks, apparently as a result of Ebola infection. Recovered carcasses were infected by a variety of Ebola strains, suggesting that Ebola outbreaks in great apes result from multiple virus introductions from the natural host. Surveillance of animal mortality may help to predict and prevent human Ebola outbreaks.
Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, … Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, but policy makers, clinicians, and the public frequently fail to understand that diagnosis is essential to the prevention and treatment of disease. Access to reliable diagnostic testing is severely limited in this region, and misdiagnosis commonly occurs. Understandably, allocation of resources to diagnostic laboratory testing has not been a priority for resource-limited health care systems, but unreliable and inaccurate laboratory diagnostic testing leads to unnecessary expenditures in a region already plagued by resource shortages, promotes the perception that laboratory testing is unhelpful, and compromises patient care. We explore the barriers to implementing consistent testing within this region and illustrate the need for a more comprehensive approach to the diagnosis of infectious diseases, with an emphasis on making laboratory testing a higher priority.
Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. … Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP1,2) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression.
ObjectiveTo develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population.ParticipantsThe Working … ObjectiveTo develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population.ParticipantsThe Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions.EvidenceMEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed.Consensus ProcessThree formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft.ConclusionsWeapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs.
Journal Article A Prospective Study of the Epidemiology and Ecology of Lassa Fever Get access Joseph B. McCormick, Joseph B. McCormick From the Division of Viral Diseases, Center for Infectious … Journal Article A Prospective Study of the Epidemiology and Ecology of Lassa Fever Get access Joseph B. McCormick, Joseph B. McCormick From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; and the Peace Corps, Sierra Leone Please address requests for reprints to Dr. Joseph B. McCormick, Chief, Special Pathogens Branch, Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, 1600 Clifton Road NE, Atlanta, Georgia 30333. Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia A. Webb, Patricia A. Webb From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; and the Peace Corps, Sierra Leone Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Krebs, John W. Krebs From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; and the Peace Corps, Sierra Leone Search for other works by this author on: Oxford Academic PubMed Google Scholar Karl M. Johnson, Karl M. Johnson From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; and the Peace Corps, Sierra Leone Search for other works by this author on: Oxford Academic PubMed Google Scholar Ethleen S. Smith Ethleen S. Smith From the Division of Viral Diseases, Center for Infectious Diseases, Centers for Disease Control, Atlanta, Georgia; and the Peace Corps, Sierra Leone Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 155, Issue 3, March 1987, Pages 437–444, https://doi.org/10.1093/infdis/155.3.437 Published: 01 March 1987 Article history Received: 12 April 1985 Revision received: 23 December 1985 Published: 01 March 1987
The west African Ebola epidemic that began in 2013 exposed deep inadequacies in the national and international institutions responsible for protecting the public from the far-reaching human, social, economic, and … The west African Ebola epidemic that began in 2013 exposed deep inadequacies in the national and international institutions responsible for protecting the public from the far-reaching human, social, economic, and political consequences of infectious disease outbreaks. The Ebola epidemic raised a crucial question: what reforms are needed to mend the fragile global system for outbreak prevention and response, rebuild confidence, and prevent future disasters? To address this question, the Harvard Global Health Institute and the London School of Hygiene & Tropical Medicine jointly launched the Independent Panel on the Global Response to Ebola. Panel members from academia, think tanks, and civil society have collectively reviewed the worldwide response to the Ebola outbreak. After difficult and lengthy deliberation, we concluded that major reforms are both warranted and feasible. The Panel's conclusions offer a roadmap of ten interrelated recommendations across four thematic areas: All countries need a minimum level of core capacity to detect, report, and respond rapidly to outbreaks. The shortage of such capacities in Guinea, Liberia, and Sierra Leone enabled Ebola to develop into a national, and worldwide, crisis. •Recommendation 1: The global community must agree on a clear strategy to ensure that governments invest domestically in building such capacities and mobilise adequate external support to supplement efforts in poorer countries. This plan must be supported by a transparent central system for tracking and monitoring the results of these resource flows. Additionally, all governments must agree to regular, independent, external assessment of their core capacities.•Recommendation 2: WHO should promote early reporting of outbreaks by commending countries that rapidly and publicly share information, while publishing lists of countries that delay reporting. Funders should create economic incentives for early reporting by committing to disburse emergency funds rapidly to assist countries when outbreaks strike and compensating for economic losses that might result. Additionally, WHO must confront governments that implement trade and travel restrictions without scientific justification, while developing industry-wide cooperation frameworks to ensure private firms such as airlines and shipping companies continue to provide crucial services during emergencies. When preventive measures do not succeed, outbreaks can cross borders and surpass national capacities. Ebola exposed WHO as unable to meet its responsibility for responding to such situations and alerting the global community. •Recommendation 3: A dedicated centre for outbreak response with strong technical capacity, a protected budget, and clear lines of accountability should be created at WHO, governed by a separate Board.•Recommendation 4: A transparent and politically protected WHO Standing Emergency Committee should be delegated with the responsibility for declaring public health emergencies.•Recommendation 5: An independent UN Accountability Commission should be created to do system-wide assessments of worldwide responses to major disease outbreaks. Rapid knowledge production and dissemination are essential for outbreak prevention and response, but reliable systems for sharing epidemiological, genomic, and clinical data were not established during the Ebola outbreak. •Recommendation 6: Governments, the scientific research community, industry, and non-governmental organisations must begin to develop a framework of norms and rules operating both during and between outbreaks to enable and accelerate research, govern the conduct of research, and ensure access to the benefits of research.•Recommendation 7: Additionally, research funders should establish a worldwide research and development financing facility for outbreak-relevant drugs, vaccines, diagnostics, and non-pharmaceutical supplies (such as personal protective equipment) when commercial incentives are not appropriate. An effective worldwide response to major outbreaks needs leadership, clarity about roles and responsibilities, and robust measures for accountability, all of which were delayed or absent during the Ebola epidemic. •Recommendation 8: For a more timely response in the future, we recommend the creation of a Global Health Committee as part of the UN Security Council to expedite high-level leadership and systematically elevate political attention to health issues, recognising health as essential to human security.•Recommendation 9: Additionally, decisive, time-bound governance reforms will be needed to rebuild trust in WHO in view of its failings during the Ebola epidemic. With respect to outbreak response, WHO should focus on four core functions: supporting national capacity building through technical advice; rapid early response and assessment of outbreaks (including potential emergency declarations); establishing technical norms, standards, and guidance; and convening the global community to set goals, mobilise resources, and negotiate rules. Beyond outbreaks, WHO should maintain its broad definition of health but substantially scale back its expansive range of activities to focus on core functions (to be defined through a process launched by the WHO Executive Board).•Recommendation 10: The Executive Board should mandate good governance reforms, including establishing a freedom of information policy, an Inspector General's office, and human resource management reform, all to be implemented by an Interim Deputy for Managerial Reform by July 2017. In exchange for successful reforms, governments should finance most of the budget with untied funds in a new deal for a more focused WHO. Finally, member states should insist on a Director-General with the character and capacity to challenge even the most powerful governments when necessary to protect public health. These ten recommendations are concrete, actionable, and measurable. High-level political leadership is now needed to translate this roadmap into enduring systemic reform so that the catastrophe of the Ebola outbreak will never be repeated.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine … The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome (MERS)-CoV underscores the threat of cross-species transmission events leading to outbreaks in humans. Here we examine the disease potential of a SARS-like virus, SHC014-CoV, which is currently circulating in Chinese horseshoe bat populations. Using the SARS-CoV reverse genetics system, we generated and characterized a chimeric virus expressing the spike of bat coronavirus SHC014 in a mouse-adapted SARS-CoV backbone. The results indicate that group 2b viruses encoding the SHC014 spike in a wild-type backbone can efficiently use multiple orthologs of the SARS receptor human angiotensin converting enzyme II (ACE2), replicate efficiently in primary human airway cells and achieve in vitro titers equivalent to epidemic strains of SARS-CoV. Additionally, in vivo experiments demonstrate replication of the chimeric virus in mouse lung with notable pathogenesis. Evaluation of available SARS-based immune-therapeutic and prophylactic modalities revealed poor efficacy; both monoclonal antibody and vaccine approaches failed to neutralize and protect from infection with CoVs using the novel spike protein. On the basis of these findings, we synthetically re-derived an infectious full-length SHC014 recombinant virus and demonstrate robust viral replication both in vitro and in vivo. Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.
Many of the devastating pandemics and outbreaks of the 20th and 21st centuries have involved enveloped viruses, including influenza, HIV, SARS, MERS, and Ebola. However, little is known about the … Many of the devastating pandemics and outbreaks of the 20th and 21st centuries have involved enveloped viruses, including influenza, HIV, SARS, MERS, and Ebola. However, little is known about the presence and fate of enveloped viruses in municipal wastewater. Here, we compared the survival and partitioning behavior of two model enveloped viruses (MHV and ϕ6) and two nonenveloped bacteriophages (MS2 and T3) in raw wastewater samples. We showed that MHV and ϕ6 remained infective on the time scale of days. Up to 26% of the two enveloped viruses adsorbed to the solid fraction of wastewater compared to 6% of the two nonenveloped viruses. Based on this partitioning behavior, we assessed and optimized methods for recovering enveloped viruses from wastewater. Our optimized ultrafiltration method resulted in mean recoveries (±SD) of 25.1% (±3.6%) and 18.2% (±9.5%) for the enveloped MHV and ϕ6, respectively, and mean recoveries of 55.6% (±16.7%) and 85.5% (±24.5%) for the nonenveloped MS2 and T3, respectively. A maximum of 3.7% of MHV and 2% of MS2 could be recovered from the solids. These results shed light on the environmental fate of an important group of viruses and the presented methods will enable future research on enveloped viruses in water environments.
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in … rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening … The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model. Once-daily 10 mg/kg iv treatment on days 3-14 postinfection had a significant effect on viremia and mortality, resulting in 100% survival of infected treated animals [ Nature 2016 , 531 , 381 - 385 ]. A phase 2 study (PREVAIL IV) is currently enrolling and will evaluate the effect of 4b on viral shedding from sanctuary sites in EBOV survivors.
The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations … The world has developed an elaborate global health system as a bulwark against known and unknown infectious disease threats. The system consists of various formal and informal networks of organizations that serve different stakeholders; have varying goals, modalities, resources, and accountability; operate at different regional levels (e.g., local, national, and global); and cut across the public, private-for-profit, and private-not-for-profit sectors. The evolving global health system has done much to protect and promote human health. However, the world continues to be confronted by longstanding, emerging, and reemerging infectious disease threats. These threats differ widely in terms of severity and probability. They also have varying consequences for morbidity and mortality, as well as for a complex set of social and economic outcomes. To various degrees, they are also amenable to alternative responses, ranging from clean water provision to regulation to biomedical countermeasures. Whether the global health system as currently constituted can provide effective protection against a dynamic array of infectious disease threats has been called into question by recent outbreaks of Ebola, Zika, dengue, Middle East respiratory syndrome, severe acute respiratory syndrome, and influenza and by the looming threat of rising antimicrobial resistance. The concern is magnified by rapid population growth in areas with weak health systems, urbanization, globalization, climate change, civil conflict, and the changing nature of pathogen transmission between human and animal populations. There is also potential for human-originated outbreaks emanating from laboratory accidents or intentional biological attacks. This paper discusses these issues, along with the need for a (possibly self-standing) multi-disciplinary Global Technical Council on Infectious Disease Threats to address emerging global challenges with regard to infectious disease and associated social and economic risks. This Council would strengthen the global health system by improving collaboration and coordination across organizations (e.g., the WHO, Gavi, CEPI, national centers for disease control, pharmaceutical manufacturers, etc.); filling in knowledge gaps with respect to (for example) infectious disease surveillance, research and development needs, financing models, supply chain logistics, and the social and economic impacts of potential threats; and making high-level, evidence-based recommendations for managing global risks associated with infectious disease.
Remdesivir (GS-5734) is a 1'-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses. This compound is currently under clinical development for the treatment of Ebola … Remdesivir (GS-5734) is a 1'-cyano-substituted adenosine nucleotide analogue prodrug that shows broad-spectrum antiviral activity against several RNA viruses. This compound is currently under clinical development for the treatment of Ebola virus disease (EVD). While antiviral effects have been demonstrated in cell culture and in non-human primates, the mechanism of action of Ebola virus (EBOV) inhibition for remdesivir remains to be fully elucidated. The EBOV RNA-dependent RNA polymerase (RdRp) complex was recently expressed and purified, enabling biochemical studies with the relevant triphosphate (TP) form of remdesivir and its presumptive target. In this study, we confirmed that remdesivir-TP is able to compete for incorporation with adenosine triphosphate (ATP). Enzyme kinetics revealed that EBOV RdRp and respiratory syncytial virus (RSV) RdRp incorporate ATP and remdesivir-TP with similar efficiencies. The selectivity of ATP against remdesivir-TP is ~4 for EBOV RdRp and ~3 for RSV RdRp. In contrast, purified human mitochondrial RNA polymerase (h-mtRNAP) effectively discriminates against remdesivir-TP with a selectivity value of ~500-fold. For EBOV RdRp, the incorporated inhibitor at position i does not affect the ensuing nucleotide incorporation event at position i+1. For RSV RdRp, we measured a ~6-fold inhibition at position i+1 although RNA synthesis was not terminated. Chain termination was in both cases delayed and was seen predominantly at position i+5. This pattern is specific to remdesivir-TP and its 1'-cyano modification. Compounds with modifications at the 2'-position show different patterns of inhibition. While 2'-C-methyl-ATP is not incorporated, ara-ATP acts as a non-obligate chain terminator and prevents nucleotide incorporation at position i+1. Taken together, our biochemical data indicate that the major contribution to EBOV RNA synthesis inhibition by remdesivir can be ascribed to delayed chain termination. The long distance of five residues between the incorporated nucleotide analogue and its inhibitory effect warrant further investigation.
Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a … Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.
A Novel Coronavirus Emerging in China A novel coronavirus, designated as 2019-nCoV, emerged in Wuhan, China, at the end of 2019. Although many details of the emergence of this virus … A Novel Coronavirus Emerging in China A novel coronavirus, designated as 2019-nCoV, emerged in Wuhan, China, at the end of 2019. Although many details of the emergence of this virus remain unknown,...
On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to … On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern."
The viral hemorrhagic fevers Ebola and Lassa fever are endemic to Sub-Saharan Africa. Both viruses are characterized by high case fatality risk and lifelong debilitating sequelae including blindness and deafness. … The viral hemorrhagic fevers Ebola and Lassa fever are endemic to Sub-Saharan Africa. Both viruses are characterized by high case fatality risk and lifelong debilitating sequelae including blindness and deafness. However, despite these findings the mechanisms of disease and pathogenesis through which these viruses act remain poorly understood. The objective of this systematic review was to synthesize known data regarding both acute and chronic immune-inflammatory dysfunction. A comprehensive search strategy was conducted from July 2022- August 2024. A total of 1,587 articles were identified and evaluated for inclusion. In total 49 Ebola specific and 31 Lassa fever articles were included in this review. The results of this study found considerable dysregulation in immune-inflammatory homeostasis. Specifically, Ebola was found to induce increased concentrations of molecules associated with immune cell recruitment and migration during acute disease. In addition, the virus led to reduction in innate cell populations and expansion of T-cell population frequencies across disease outcomes. Studies of Lassa fever also demonstrated considerable immune dysregulation. However, given the relative lack of studies the exact mechanism of disease is unclear. Among disease survivors, both viruses demonstrate persistent chronic immune dysregulation years following disease onset. However, associating these findings with post-viral syndromes is controversial.
Introduction In a vaccine trial conducted between 2019 and 2022 in Boende, a remote, resource-constrained area of the Democratic Republic of the Congo, our research team developed an ancillary care … Introduction In a vaccine trial conducted between 2019 and 2022 in Boende, a remote, resource-constrained area of the Democratic Republic of the Congo, our research team developed an ancillary care (AC) policy to provide adequate care and follow-up for concomitant adverse events (AE), whether study-related or not. The trial aimed to assess the safety and immunogenicity of an Ebola vaccine regimen among approximately 700 healthcare providers and frontliners to strengthen outbreak preparedness in this Ebola-endemic region, where access to healthcare is severely limited by poverty, weak infrastructure, and an overstretched health system. Methods A mixed-methods approach was used to assess participants’ acceptability of the AC policy. First, participants with AE completed a questionnaire (1-–5 scale; 6 questions on AC policy support, 4 on the consequences of no support, and an open comment field). Second, a telephone survey (1-–3 scale; 3 questions evaluating the AC policy, 1 on unsupported AE and an open comment field) was conducted with participants, both with and without AE. Descriptive statistics were used for quantitative data analysis, while open comments were coded qualitatively. Third, semi-structured interviews were conducted with participants who experienced a (serious) AE and either benefited from or did not benefit from the policy. Participants were selected using purposive and convenience sampling, and thematic analysis was performed. Results Of 185 individuals with AE, 290 surveys were collected, with 93.5% expressing (very) strong appreciation for the AC policy. In the telephone survey, all 311 respondents supported the AC policy and emphasized its importance, 88.1% indicated it addressed their medical needs, and 35.7% reported experiencing an AE not covered by the policy. The 17 interviews revealed three major themes: 1) Experiences with AE management and AC support; 2) Financial impact of (non-) support; 3) Expectations of AC support. Participants who received AC reported personal, medical, and financial benefits, but noted limitations, such as the scope and duration of support, variations in local healthcare practices, and administrative hurdles. Conclusion Both quantitative and qualitative findings show high endorsement for the AC policy support, regardless of participants’ personal use. This acceptability study highlights the importance of AC in clinical trials and comprehensive participant care in research.
The Ebola Virus Disease (EVD) is associated with significant mental health and psychosocial problems among patients/survivors. Effective strategies for addressing these problems necessitate an in-depth understanding of the sociocultural, economic … The Ebola Virus Disease (EVD) is associated with significant mental health and psychosocial problems among patients/survivors. Effective strategies for addressing these problems necessitate an in-depth understanding of the sociocultural, economic and political context of the outbreaks, and survivors’ own experiences of the disease. Yet, such context and survivors’ experiences remain inadequately understood. We explore the pre- and post-diagnosis/treatment and post-recovery experiences of survivors of the 2022 EVD outbreak in Mubende District (Uganda) and draw lessons for better management of future outbreaks. A qualitative study was undertaken in Mubende District to explore the lived experiences of various categories of persons affected by the outbreak. Participants were sampled purposively. In-depth interviews were held with 15 EVD survivors. A thematic analysis of data was done. Our findings reveal that across the entire spectrum of their encounter with EVD, patients had a range of overwhelmingly stressful experiences that, according to the participants, took a toll on their mental health. These included stigma during evacuation and on return to their communities upon discharge, perceived inhuman treatment from health workers, lack of epidemic preparedness at the EVD facilities, witnessing frequent EVD deaths due to the EVD Treatment Unit’s open/unpartitioned ward, delayed removal of dead bodies from the shared ward, systemic lapses in health services and EVD-induced livelihoods challenges. In conclusion, EVD patients’/survivors’ experiences across the entire spectrum of their illness – from the period before diagnosis to their treatment at the EVD Treatment Unit and, later, their re-integration into their communities – are characterised with high levels of unattended, self-reported psychological distress. We propose a holistic person-centred approach to healthcare for EVD suspects, confirmed cases and survivors. Additionally, EVD education and sensitisation programs need to target health workers, among other population groups.
The Marburg virus (MARV) is a dangerous infection that causes a deadly sickness known as MARV disease. This severe hemorrhagic fever is a major concern for people all over the … The Marburg virus (MARV) is a dangerous infection that causes a deadly sickness known as MARV disease. This severe hemorrhagic fever is a major concern for people all over the world. Since the initial identification in 1967 during simultaneous outbreaks in Germany and Serbia, MARV has caused recurrent epidemics predominantly in sub-Saharan Africa with fatality rates ranging from 24% to 90% as a result of differences in virus strains, healthcare infrastructure, and the quality of patient treatment. Like Ebola virus, MARV causes a viral hemorrhagic fever identified in some of the same principles of clinical and epidemiological concern. However, MARV has unique biologic characteristics that require specialized research and response by public health and among researchers. Diagnosis relies on molecular tools such as real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, as well as clinical and epidemiological assessments. Despite advancements in understanding MARV biology, no vaccines or antiviral therapies have been approved, with treatment limited to supportive care. Experimental therapeutics, monoclonal antibodies, RNA-based drugs, and adenovirus-based vaccines, show promise but require further validation. Current efforts in outbreak containment include surveillance, rapid diagnostics, case isolation, and safe burial practices. However, gaps in understanding MARV pathogenesis, limited diagnostic tools, and the absence of regulatory-approved vaccines underscore the urgent need for global collaboration and investment in research. Bridging these gaps is critical to mitigating the public health impact of MARV, ensuring effective response strategies for future outbreaks.
In January 2022, a number of Yellow Fever cases were identified in Kenya's Isiolo County for the first time, triggering a national-level response centred on vaccinating residents. 181,000 people were … In January 2022, a number of Yellow Fever cases were identified in Kenya's Isiolo County for the first time, triggering a national-level response centred on vaccinating residents. 181,000 people were vaccinated in July, around 72% of the eligible population. In the face of this ostensible success, this article explores the continuing coloniality, that is, long-standing patterns of domination, operating within disease control in Kenya's northeast, whereby punitive encounters with the state loom large. Despite health matters being devolved, top-down implementation from nationally-controlled actors exacerbated local distrust, resulting in contention around the roll-out and of the authorities behind it. This article, drawing on ethnography supplemented by in-depth interviews and Focus Group Discussions over 12 months 2022-2023, centres the experiences of Community Health Volunteers (CHVs) over the ten-day campaign. We adopt a Fanonian lens to interpret our findings, historicizing the contention CHVs faced from their communities, in a region where governmental approaches oscillate between neglect and heavy-handed remedial action. We operationalise Fanon's 'psychoexistential complex', whereby CHVs internalise the conflict between their roles of community representative and state-enforcer, exacerbated by their precarity and invisibility to others. We conclude with a call for CHVs' place to be protected, capacitated and seen within outbreak response.
Countries with the highest potential exposure to viral haemorrhagic fever viruses are also those with low expenditure on health services, limiting the capacity for surveillance and detection of these viruses, … Countries with the highest potential exposure to viral haemorrhagic fever viruses are also those with low expenditure on health services, limiting the capacity for surveillance and detection of these viruses, and effective treatment and outbreak containment. The COVID-19 pandemic further limited travel and in-person collaborative training opportunities for researchers, laboratory and public health professionals. Digital learning offers the prospect of addressing some of the shortfall in training needs. In this short report, we describe our experiences in the development of effective laboratory training tools using digital learning methods. We describe the teaching methodology, list barriers to successful implementation and offer some potential solutions.
Introduction Tanzania declared a Marburg Virus Disease (MVD) outbreak on March 21, 2023, reporting nine cases and six deaths (case fatality rate (CFR) 66.7%). Detection began when a Community Health … Introduction Tanzania declared a Marburg Virus Disease (MVD) outbreak on March 21, 2023, reporting nine cases and six deaths (case fatality rate (CFR) 66.7%). Detection began when a Community Health Worker (CHW) reported unexplained illness via the electronic EBS (e-EBS) system, triggering a national outbreak response. This study documents the Early Warning, Alert and Response (EWAR) interventions carried out during the MVD outbreak response in the Kagera region to identify strengths and bottlenecks for strengthening future outbreak preparedness and response efforts. Method We documented EWAR interventions using retrospective surveillance document review. MVD outbreak detection and reporting timeliness were compared with Tanzania’s EBS indicators and the 7-1-7 target. Surveillance interventions included additional staff deployment, equipment addition, and tool adoption. Community sensitization efforts utilized Swahili-translated informational cards to facilitate early detection and reporting of signals through multiple channels, including the 199-hotline number, EBS desk numbers and via e-EBS and verified using the standard case definition (SCD). Signals were compiled in Microsoft Excel, where descriptive analysis using frequencies to show trends was conducted. Suspected MVD cases were sent for laboratory confirmation. Findings On March 15, 2023, a CHW reported a signal in the e-EBS system within 24 hours. However, a community member and HCWs missed unusual signs of the MVD index case. Five additional members were deployed to support data management using the equipment provided, including three laptops, ten smartphones, and adapted tools. A total of 6,260 informational cards were distributed during community sensitization; 176 MVD signals were reported, where 48 (27.3%) met the SCD, and 37 were sent for laboratory confirmation, of which 2.7% tested positive for the virus. Most signals, 107 (60.8%), were reported in April. Conclusions and recommendations The government should adopt the 7-1-7 target and strengthen community and health facility EBS through ongoing mentorship for EWAR.
Community-based surveillance (CBS) refers to a structured process whereby community members systematically detect and report events of public health significance occurring within their communities. In response to the COVID-19 pandemic, … Community-based surveillance (CBS) refers to a structured process whereby community members systematically detect and report events of public health significance occurring within their communities. In response to the COVID-19 pandemic, the Government of Indonesia has taken steps to enhance national preparedness for future health threats, focussing on expanding the use of CBS. Given the novelty of CBS's use in Indonesia, we undertook this research to provide evidence-based advice to guide its implementation across the country's diverse communities and operational contexts. We employed three strategies to gather data: a content analysis of policy documents related to CBS implementation in Indonesia, site visits, and interviews with purposefully selected key informants from the animal, wildlife and human health sectors, planning agencies, village leadership, and inter-government coordination bodies. We conducted additional interviews with staff from the United Nations and donor development assistance agencies involved in CBS implementation in Indonesia. A semi-structured tool guided the interviews, and we analysed the data using an inductive approach. We identified eight policy documents, visited six CBS project sites, and interviewed 120 key stakeholders. Key themes that emerged included the need for greater clarity on the scope, purpose, and function of CBS and how data collected intersect with and is used within Indonesia's broader early warning disease surveillance architecture, a need to harmonisation CBS legislation and implementation guidance across and within ministries, and that ongoing investment in essential health system building blocks - workforce, data systems, and analytical capacity - is required to ensure the scalability and sustainability of CBS across the country. Although CBS holds promise for strengthening public health security in Indonesia, key challenges related to common understanding, workforce capacity, data flow, and system governance must be addressed if the strategy is to make a meaningful contribution. Effective collaboration among government ministries, administrative levels, and community stakeholders is crucial for adapting CBS to balance local and national health security priorities, while ensuring stability, sustainability, and scalability across Indonesia's diverse contexts.
Background The 2014–2016 Ebola outbreak in West Africa showed that multiple response strategies are necessary to contain disease outbreaks in resource-constrained settings. A critical component of these response strategies was … Background The 2014–2016 Ebola outbreak in West Africa showed that multiple response strategies are necessary to contain disease outbreaks in resource-constrained settings. A critical component of these response strategies was the involvement of community members and women’s groups in leading them. While women’s groups actively participated in Ebola containment strategies in various communities, there is a dearth of research on their role or how their presence in communities affected the deployment of Ebola response strategies. In contributing to bridging this knowledge gap, we ask: How did the presence of women’s groups influence perceptions of Ebola response strategies in Ebola-affected communities in Liberia?. Methods We fitted multivariate multinomial logistic regression models to cross-sectional data (n = 1,340) collected in five counties in Liberia. We built a composite model from community response strategies that participants reported witnessing. These responses were then categorized into no response, single-response, and multiple-response strategies. Response strategies included Ebola education and sensitisation campaigns, community surveillance, lobbying for personal protective equipment (PPEs), and other measures (e.g., prayer). Single responses pertain to participants choosing only one response strategy, while multiple responses indicate the selection of two or more response strategies. Results Overall, we found that knowledge about the presence of women’s groups was associated with an increased likelihood of participants reporting having witnessed a community response during the Ebola outbreak. Specifically, participants who reported having women’s groups in their communities had 89% and 98% higher odds of reporting a single Ebola response (RRR = 1.89, p ≤ 0.001) and multiple responses (RRR = 1.98, p ≤ 0.001), respectively. We also found some demographic, socioeconomic, and place-based variables to be associated with Ebola response strategies. Conclusion We provide relevant policy recommendations necessary to center women’s groups and other community organisations in Liberia’s strategic health plan toward a pandemic-ready future. We believe that strengthening local, national, and international collaborations is critical to achieving this future and can help the country reach its SDG 3.3 goal of ending infectious diseases by 2030.
Ebola virus (EBOV) infection usually leads to highly lethal EBOV disease (EVD) with associated viraemia. Viraemia is cleared in those that do survive, however, EBOV may remain hidden in the … Ebola virus (EBOV) infection usually leads to highly lethal EBOV disease (EVD) with associated viraemia. Viraemia is cleared in those that do survive, however, EBOV may remain hidden in the testes and other immune privileged niches (IPNs) where it can persist for years during asymptomatic convalescence. Viral shedding into seminal fluid may result in sexual transmission to naive contacts years after EBOV outbreaks have been declared over. This leads to flare-ups of cases, redefining our understanding of the shaping and origin of EBOV outbreaks. Such delayed sexual transmission eliminates the geographical boundaries which typically constrain EBOV outbreaks, thus posing a significant global health security threat. Despite hints of EBOV persistence dating over half a century, it was only until the unprecedented scale of the 2013–2016 Western Africa EBOV epidemic that the true importance of this phenomenon was revealed to scientists, public health officials and policy makers alike. This review summarises the evidence for EBOV persistence, suggests the possible underlying molecular mechanisms and proposes future directions for research in the field. A meta-analysis is presented to further investigate the duration of EBOV shedding in seminal fluid. The ultimate aim is to develop therapeutics that clear sites of persistence. Such therapeutics could prevent the re-emergence of the persistent virus, eliminating the chance of new outbreaks whilst alleviating the severe stigmatisation facing the EBOV survivor population.
Lassa fever, a viral hemorrhagic illness that first came into the limelight as a clinical entity in 1969 when it was discovered in Northern Nigeria, is now found in other … Lassa fever, a viral hemorrhagic illness that first came into the limelight as a clinical entity in 1969 when it was discovered in Northern Nigeria, is now found in other West African countries such as Sierra Leone, Liberia, Guinea, Togo, and the Benin Republic. Over the years, the disease, which is primarily transmitted from contact with infected mastomys rodents to humans, has the capability of secondary human-to-human transmission with significant morbidity and mortality, especially in healthcare settings. The disease is typically characterized by seasonal outbreaks, which peak during the dry season months of December to March. Lassa fever significantly impacts public health and the socioeconomic life of people in affected communities. In Nigeria, the Integrated Disease Surveillance and Response Strategy (IDSR), along with other medical countermeasures, have been employed to curtail the impact of the disease in endemic regions of Nigeria and other West Africa countries. The one-health approach to combat the disease is a promising strategy. This, along with the hope of a safe and effective vaccine, is a ray of hope on the horizon for public health authorities in Nigeria and other West African countries that the battle against Lassa fever might indeed end sooner than later.
Background: This commentary analyzes demographic, clinical, and occupational characteristics associated with Ebola virus disease (EVD) outcomes during the 2018-2020 outbreak in the Democratic Republic of Congo (DRC). Methods: A total … Background: This commentary analyzes demographic, clinical, and occupational characteristics associated with Ebola virus disease (EVD) outcomes during the 2018-2020 outbreak in the Democratic Republic of Congo (DRC). Methods: A total of 3477 EVD cases were included. Descriptive statistics and univariate and multivariate Cox regression analyses were performed to evaluate associations between clinical outcomes and patient characteristics. Comorbidity estimates and healthcare worker (HCW) occupational exposure data were incorporated based on the literature. Results: The median age was 26.5 years (SD = 16.1), with the majority (59.7%) aged 20-59. Males represented 51.3% of the cohort. Most patients (81.8%) worked in occupations that were not disease-exposing. Overall, 450 patients (12.9%) died. Although comorbidities initially appeared predictive of mortality (unadjusted HR: 3.05; 95% CI: 2.41-3.87), their effect was not statistically significant after adjustment (adjusted HR: 1.17; 95% CI: 0.87-1.59; p = 0.301). The strongest predictor of death was clinical status at admission: patients classified as "very sick" had an alarmingly high adjusted hazard ratio (HR) of 236.26 (95% CI: 33.18-1682.21; p < 0.001). Non-disease-exposing occupations were also associated with increased mortality (adjusted HR: 1.75; 95% CI: 1.33-2.31; p < 0.001). Conclusions: Despite improvements in outbreak response, mortality remains disproportionately high among patients presenting in critical condition and those outside the health sector. These findings underscore the importance of early detection strategies and enhanced protection for all occupational groups during EVD outbreaks.
Abstract We organized an Innovation Bootcamp for young people in Nigeria to develop strategies promoting the uptake of the hepatitis B birth dose vaccine among newborns, which remains low, with … Abstract We organized an Innovation Bootcamp for young people in Nigeria to develop strategies promoting the uptake of the hepatitis B birth dose vaccine among newborns, which remains low, with a vaccine coverage of less than 30%. This event was a collaborative, cross-disciplinary capacity-building platform for participants to generate creative solutions addressing barriers to Hepatitis B vaccine uptake. The purpose of this study was to describe the bootcamp activities that address this gap. The mixed-methods design study described the five-week Innovation Bootcamp informed by Participatory Action Research. It comprised a series of activities aimed at building research capacity among young people to support the implementation of their ideas in their respective communities using the PEN-3 cultural model. Qualitative data from the community needs assessment were analyzed using a thematic analysis framework to identify and synthesize emerging themes. Socio-demographic characteristics of the participants were collected, and a pre- and post-survey was administered. The participants’ knowledge of hepatitis B and research skills were compared using the Wilcoxon test. Our results included five teams composed of fifteen participants with a mean age of 25.5 years, originating from the South-West and South-East regions of Nigeria. The post-survey showed significant improvements in participants’ knowledge and research skills, with knowledge increasing by 21.6% (mean score: 39.7 to 48.3, p = 0.010) and research skills by 36.4% (mean score: 56.1 to 76.5, p &lt; 0.001). Each team co-designed implementation strategies, including referral pathways from traditional birth attendants to formal health centers, comprehensive training workshops, and trusted community leaders as vaccination ambassadors. In conclusion, the bootcamp demonstrated its effectiveness in strengthening capacity and increasing knowledge, which contributed to informing the development of implementation strategies. Findings from the pilot studies will ultimately inform future research focused on promoting and sustaining youth-derived vaccination service delivery strategies in Nigeria.
<title>Abstract</title> Climate change is lengthening malaria transmission seasons and driving disease resurgence in southern Africa, especially Zimbabwe. While traditional control measures (nets, spraying, treatment) have reduced malaria, emerging climatic factors … <title>Abstract</title> Climate change is lengthening malaria transmission seasons and driving disease resurgence in southern Africa, especially Zimbabwe. While traditional control measures (nets, spraying, treatment) have reduced malaria, emerging climatic factors are undermining progress. Simultaneously, Zimbabwe’s population is very young – over 60% under 25 years old. Simultaneously, Zimbabwe’s population is very young – over 60% under 25 years old and highly connected by mobile technology . We developed a mobile/web crowdsourcing platform (“Mosquito Hunter”) to engage youth in real-time malaria surveillance and climate data collection. The open-source prototype app (https://mosquito-hunter.vercel.app) allows young volunteers to report mosquito breeding sites, upload photos, log environmental conditions, and access interactive educational modules on malaria–climate. Gamification elements (points, badges, certificates) and school-based outreach were used to motivate participation. We describe the platform’s design, the youth engagement strategy, and initial lessons from prototype development. This youth-driven approach can provide geolocated, contextual data that complements official health surveillance in high-burden, climate-vulnerable settings. By empowering Zimbabwean youth to become citizen-scientists, this initiative aims not only to improve situational awareness of malaria risk, but also to foster local ownership of public health and climate resilience.
Abstract Context : Aotearoa New Zealand's biosecurity system, shaped by colonial and bureaucratic structures, tends to prioritise competition and financial management over environmental outcomes and community involvement. Successful biodiversity protection … Abstract Context : Aotearoa New Zealand's biosecurity system, shaped by colonial and bureaucratic structures, tends to prioritise competition and financial management over environmental outcomes and community involvement. Successful biodiversity protection requires more cooperative, inclusive practices that engage local and Indigenous communities. Despite policies promoting knowledge sharing and collaboration, practical implementation remains a challenge. Approach : We took an action research approach, involving iterative cycles of inquiry, reflection and refinement to explore inclusive biosecurity practices. Through interviews and co‐analysis sessions with biosecurity professionals, including Māori researchers, we identified challenges and opportunities for integrating diverse knowledge systems. By synthesising empirical insights with theoretical frameworks, we co‐developed practical tools to address these challenges and promote more collaborative approaches in biosecurity research, policy and practice. Findings : We identified six dimensions of collective praxis to support those within the biosecurity system to work in a more inclusive, respectful, pluralistic and regenerative manner. Synthesis and application of findings : To help practitioners reimagine their work practices, we developed a rubric with reflective prompts and gave it a more convenient and user‐oriented format as a set of cards. These tools were designed to spark critical thinking and facilitate individual and collective self‐assessment and priority setting (when used as a planning device). These support devices are intended for people working at the nexus between different knowledge systems. They were designed to help people with diverse cultural, disciplinary and professional backgrounds work better together and critically reflect on everyday practices that marginalise, discredit or disempower ways of knowing and doing that differ from mainstream scientific biosecurity. Conclusion : This action research contributes towards decolonisation of the broader research culture, biosecurity system and biodiversity protection goals. The process is also valuable in adapting to changing contexts and highlights the power of reflection in reframing practices across a wide range of situations, beyond biosecurity, to foster collaboration and ensure more equitable decision‐making. Read the free Plain Language Summary for this article on the Journal blog.
Inter-agency networks are believed to be essential to maintaining essential health services during pandemics and to strengthening the resilience of health systems. Focusing on malaria during the COVID-19 pandemic as … Inter-agency networks are believed to be essential to maintaining essential health services during pandemics and to strengthening the resilience of health systems. Focusing on malaria during the COVID-19 pandemic as a case study, this paper investigates the network of organisations fighting malaria in Guinea and Sierra Leone, the changes in their interactions during the pandemic, and their collaboration with organisations addressing the COVID-19 response. We used a mixed-methods approach to analyse data from 36 semi-structured interviews with respondents involved in the COVID-19 response and malaria service provision in Guinea and Sierra Leone, as well as data from a social network survey conducted with a subsample of 21 out of the 36 respondents. Results from the thematic analysis of key informant interviews were used to contextualize the social network data, which was visualized as sociograms. We found that malaria stakeholders worked closely with key stakeholders involved in containing the COVID-19 pandemic. Their ability to support the COVID-19 response and contribute to maintaining essential malaria services was facilitated by the fact that established networks of malaria stakeholders had existed in both countries which comprised a variety of national and international organisations from the public, private and civil society sector working in different areas of malaria elimination. These stakeholders were able to maintain or even intensify their collaboration during the COVID-19 pandemic. The findings suggest that in resource-limited settings, the promotion of coordination mechanisms among stakeholders working on specific issues can strengthen linkages and consistency, thereby contributing to overall health system resilience and pandemic response.
Marburg virus disease is a severe and often fatal hemorrhagic fever that poses a significant threat to global health. Its high transmissibility, incubation period, and nonspecific symptoms hinder early detection … Marburg virus disease is a severe and often fatal hemorrhagic fever that poses a significant threat to global health. Its high transmissibility, incubation period, and nonspecific symptoms hinder early detection and effective containment. Limited public awareness, delayed diagnosis, and restricted access to reliable health information further heighten the risk of widespread outbreaks. This study develops a mathematical model for Marburg virus transmission using a compartmental SEIR (Susceptible, Exposed, Infectious, Recovered) framework. The inclusion of an Exposed compartment captures the latent period before symptom onset, improving the accuracy of disease progression modeling. Key parameters, such as the basic reproduction number ​, are estimated to evaluate the virus's potential for sustained transmission. Sensitivity and stability analyses identify the most critical factors influencing outbreak dynamics and thresholds for containment. To guide intervention efforts, optimal control strategies such as public education, early diagnosis and treatment, case isolation, and vector control are incorporated into the model. Numerical simulations and cost-effectiveness assessments demonstrate that combined strategies can reduce infection rates and lower ​ below the epidemic threshold. Despite data limitations and implementation challenges, this model offers valuable insights for public health decision-making, emphasizing the need for integrated and timely responses to prevent future Marburg virus outbreaks.
Viral Hemorrhagic Fever (VHFs) is a diverse group of systemic diseases mediated by RNA viruses with significant morbidity and mortality rates and represents a major public health concern caused by … Viral Hemorrhagic Fever (VHFs) is a diverse group of systemic diseases mediated by RNA viruses with significant morbidity and mortality rates and represents a major public health concern caused by four families of viruses- Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. It can harm the walls of small blood vessels, making them leak, and it can prevent blood from clotting. VHFs are a disease that is classified into a variety of deadly viral diseases characterized by severe internal or external hemorrhage or bleeding into the skin. Fever, malaise, muscle soreness, vomiting, and shock are common clinical signs of viral hemorrhagic fever, though they might vary depending on the type. Internal bleeding that results is typically not fatal, but the illness itself may be. Viral hemorrhagic fevers (VHFs) represent a group of severe, systemic feverish diseases. This review aims to shed light on viral hemorrhagic fevers in terms of their causes, symptoms, transmission methods, prevention, and available treatment, to raise awareness about their danger and enhance preventive efforts to combat their spread. Hemorrhagic fever is a serious disease that affects humans and causes a high mortality rate due to its pathogenicity. These viruses infect insects or rodents, so the focus is on staying away from rodents or insects that carry the virus. Therefore, it is necessary to adhere to the procedures of Islam and prepare. These procedures allow for preparation for the future. disease outbreaks and preparation reduce the impact of diseases on humans. Scientific research is still ongoing to develop more effective vaccines and treatments that may contribute to reducing the negative effects of these viruses.
Abstract Background Lassa fever, caused by Lassa virus (LASV), is a rodent-borne disease endemic to West Africa. Despite growing interest from the global health community, the overall disease burden remains … Abstract Background Lassa fever, caused by Lassa virus (LASV), is a rodent-borne disease endemic to West Africa. Despite growing interest from the global health community, the overall disease burden remains poorly understood due to persistent underreporting and inadequate diagnostic capacities. This study aimed to assess LASV infection dynamics in rural Guinea, addressing gaps in understanding its epidemiology in endemic settings. Methods A cross-sectional serosurveillance study was conducted across six villages in Faranah, Guinea, involving 1,306 participants. Serum samples were analyzed for LASV-specific antibodies using ELISA, and a subset confirmed via immunofluorescence and neutralization assays. Statistical and mathematical models were used to estimate key epidemiological parameters, including the force of infection, antibody waning rates, and infection prevalence. Results Overall, IgG seroprevalence was 82.3%, while IgM prevalence stood at 1.8%. Seroprevalence exceeded 50% by age five and increased steadily with age, indicating lifelong exposure. Antibody waning rates suggested an average IgG persistence of 58 years. Mathematical analysis showed that halving LASV prevalence would require a tenfold reduction in the force of spillover, highlighting the challenges of effective control measures. Conclusions The seroprevalence observed in this study was markedly higher than reported elsewhere in West Africa, identifying Faranah as a hotspot for LASV transmission. Despite the high seroprevalence and estimated force of infection, the number of reported acute cases is very low, suggesting that LASV may frequently cause pauci- or asymptomatic infections or be commonly misdiagnosed for other diseases. These findings underscore that LASV is more widespread than assumed in rural Guinea.
The pilot implementation of the RTS,S/AS01E (Mosquirix) malaria vaccine marked a significant step in addressing one of Africa’s leading causes of mortality by providing essential data that led to its … The pilot implementation of the RTS,S/AS01E (Mosquirix) malaria vaccine marked a significant step in addressing one of Africa’s leading causes of mortality by providing essential data that led to its approval for use in children under two years old in malaria-endemic regions. However, little attention has been given to the lived experiences of caregivers and how they made decisions about participating in the vaccine pilot implementation. This paper takes an interpretive phenomenological analysis lens to understand caregivers’ process of negotiating participation in the pilot implementation. I conducted 11 in-depth interviews with caregivers in the RTS,S pilot implementation site in the Assin North district in Ghana. Findings reveal that participants engaged in three overarching sense-making processes to negotiate their involvement in the pilot. These were questioning the vaccine , considering political and socio-economic concerns , and biting the bullet. Embodied within these themes are how agency, power, politics, trust in healthcare workers, and knowledge of vaccines undergird respondents’ decision-making regarding the pilot implementation. The study evidenced the need for a holistic approach to engaging community members in pilot sites to guide their vaccine decision-making. By identifying the complex decision-making processes that individuals go through, we can better inform vaccine policy and public messaging to guide vaccine decision-making.
Abstract Hierarchical composite endpoints (HCEs), combining features of simple composite endpoints and conventional ordinal endpoints, are increasingly being used in infectious diseases research. However, many clinicians may be unfamiliar with … Abstract Hierarchical composite endpoints (HCEs), combining features of simple composite endpoints and conventional ordinal endpoints, are increasingly being used in infectious diseases research. However, many clinicians may be unfamiliar with these novel endpoints, including the variety of different target parameters that may be of interest and the methods that can be used to estimate them. In this review, we provide a conceptual overview of HCEs by defining them and providing examples from the infectious diseases literature. We explain different methods for analyzing HCEs, including: (a) the Wilcoxon rank sum approach (often used in studies with a Desirability of Outcome Ranking [DOOR] endpoint); (b) generalized pairwise comparisons (used to estimate a win ratio or win odds); (c) proportional odds model (and the relevance of the proportional odds assumption); and, (d) the probabilistic index model. This review will help infectious disease clinicians and healthcare providers interpret current and future research using such endpoints.
Abhay Singh Chauhan | INTERANTIONAL JOURNAL OF SCIENTIFIC RESEARCH IN ENGINEERING AND MANAGEMENT
Abstract The COVID-19 pandemic exposed critical vulnerabilities in global pandemic preparedness, including fragmented health systems, inequitable resource distribution, and insufficient international coordination. This research employs a qualitative exploratory design to … Abstract The COVID-19 pandemic exposed critical vulnerabilities in global pandemic preparedness, including fragmented health systems, inequitable resource distribution, and insufficient international coordination. This research employs a qualitative exploratory design to analyze pandemic response mechanisms, drawing on literature reviews, case studies, and stakeholder interviews. Findings reveal that countries with robust healthcare infrastructure, proactive surveillance, and equitable vaccine access mitigated pandemic impacts more effectively. Persistent barriers include funding gaps, misinformation, and geopolitical inequities. Recommendations emphasize integrated "One Health" approaches, increased health investments, and strengthened global cooperation. The study underscores pandemic preparedness as a shared responsibility vital for global stability. Global health and pandemic preparedness are about making sure the world is ready to deal with disease outbreaks that can spread across countries and affect millions of people. The COVID-19 pandemic showed how unprepared many countries were and how important it is to work together to stop diseases early and protect people’s health. Good pandemic preparedness starts with early warning systems to detect new diseases quickly. This includes watching for diseases in humans, animals, and the environment, since many viruses come from animals. Health systems must also be strong, with enough trained workers, equipment, and medicine to handle emergencies. Pandemic preparedness and global health are essential for protecting people from infectious diseases that can spread quickly across borders. The COVID-19 pandemic revealed many weaknesses in how the world handles health emergencies, showing that stronger systems and better cooperation are urgently needed
Ebola hemorrhagic fever has increasingly spread beyond its traditional epicenters in Africa to other parts of the world, bearing significant implications for various health and non-health populations. This study examines … Ebola hemorrhagic fever has increasingly spread beyond its traditional epicenters in Africa to other parts of the world, bearing significant implications for various health and non-health populations. This study examines Ebola's prevalence and burden in Africa, Europe, and North America, as well as the risk factors associated with it. A systematic review and meta-analysis were performed following PRISMA guidelines. Literature was searched through PubMed, Google Scholar, and the Cochrane Library, supplemented by manual searches and grey literature from authoritative health organizations. Meta-analysis was conducted using RevMan with a fixed-effects model and 95% confidence intervals (CI). There were 17 outbreaks covered in the included studies. There were 34,527 cases, 17,116 deaths, and an overall case fatality rate (CFR) of 49.57%. Regionally, Africa accounted for 99.96% of the cases and 99.98% of the reported deaths. The meta-analysis showed that the difference in the odds of infected healthcare workers dying from Ebola relative to non-healthcare patients was insignificant [OR=0.66, 95% CI, 0.39-1.12, I2=75%, p=0.12]. There was also no significant difference between the CFR of male and female patients infected by the virus, despite men being at a slightly higher risk of mortality from the infection compared to women [OR=0.88, 95% CI, 0.48-1.62, I2=0%, p=0.69]. This study showed that Africa continues to have the highest number of Ebola cases and deaths while retaining a high CFR. While there is no statistical difference in the odds of death among the non-health population, healthcare workers bear a higher burden of the outbreaks as they have higher odds of dying compared to non-healthcare populations. There is no significant difference in the CFR of male and female patients despite men being more likely to develop infections.
Introduction Malaria is a public health threat in Mali, with high morbidity (37%) and mortality (25%) rates. Malaria risk stratification is needed to identify different transmission zones and prioritize the … Introduction Malaria is a public health threat in Mali, with high morbidity (37%) and mortality (25%) rates. Malaria risk stratification is needed to identify different transmission zones and prioritize the interventions, especially in resource-limited contexts. For the new National Strategic Plan, we updated stratification with World Health Organization (WHO) recommendation. This study presents the selection of interventions based on stratification. Method Data collection covered all the 75 Health Districts (HDs) in the country for the period 2018-2022. This was further supplemented by national survey data on parasitology and entomology in Mali. To estimate the adjusted incidence, the analysis considered health data reporting, malaria diagnostic positivity and health facility attendance rates at health district level to malaria cases estimated. Mixed interventions were defined based on adjusted incidence, prevalence, seasonality, vector resistance to insecticides and parasite distribution by Health Districts or region according to data available. Results Four strata have been defined according to the 2017 WHO Malaria Elimination Framework. Most HDs (54) fall within the highest and moderate transmission areas, covering 84% of the population (about 18 million) located in the southern and central regions. A total of 19 intervention packages were selected and adapted. We identified 61 out of 75 eligible HDs for the LLINs mass distribution campaign, 57 HDs for SMC, 67 for IPTp including community IPTp and 19 HD for vaccination. Conclusion A half of Malian population live in high-risk areas. These districts require a continuous intensification of interventions. Malaria stratification was critical for strategic planning and appropriate deployment of malaria control interventions in Mali.