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Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus.

ABSTRACT: Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined including host range, host-virus interactions and correlates of host immunity and pathogenicity. In this article, we review the current state of YFV research, focusing on the viral lifecycle, host responses to infection, species tropism and the success and associated limitations of the YFV-17D vaccine. In addition, we highlight the current lack of available treatments and use publicly available sequence and structural data to assess global patterns of YFV sequence diversity and identify potential drug targets. Finally, we discuss how technological advances, including real-time epidemiological monitoring of outbreaks using next-generation sequencing and CRISPR/Cas9 modification of vector species, could be utilized in future battles against this re-emerging pathogen which continues to cause devastating disease.

SUBMITTER: Kleinert RDV

PROVIDER: S-EPMC6832525 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus.

Kleinert Robin D V RDV Montoya-Diaz Eduardo E Khera Tanvi T Welsch Kathrin K Tegtmeyer Birthe B Hoehl Sebastian S Ciesek Sandra S Brown Richard J P RJP

Viruses 20191017 10

Yellow fever virus (YFV) represents a re-emerging zoonotic pathogen, transmitted by mosquito vectors to humans from primate reservoirs. Sporadic outbreaks of YFV occur in endemic tropical regions, causing a viral hemorrhagic fever (VHF) associated with high mortality rates. Despite a highly effective vaccine, no antiviral treatments currently exist. Therefore, YFV represents a neglected tropical disease and is chronically understudied, with many aspects of YFV biology incompletely defined includ ...[more]

PMID: 31627415

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Project description:BackgroundTraditional government policies suggest that upstream investment in scientific research is necessary and sufficient to generate technological innovations. The expected downstream beneficial socio-economic impacts are presumed to occur through non-government market mechanisms. However, there is little quantitative evidence for such a direct and formulaic relationship between public investment at the input end and marketplace benefits at the impact end. Instead, the literature demonstrates that the technological innovation process involves a complex interaction between multiple sectors, methods, and stakeholders.DiscussionThe authors theorize that accomplishing the full process of technological innovation in a deliberate and systematic manner requires an operational-level model encompassing three underlying methods, each designed to generate knowledge outputs in different states: scientific research generates conceptual discoveries; engineering development generates prototype inventions; and industrial production generates commercial innovations. Given the critical roles of engineering and business, the entire innovation process should continuously consider the practical requirements and constraints of the commercial marketplace.The Need to Knowledge (NtK) Model encompasses the activities required to successfully generate innovations, along with associated strategies for effectively communicating knowledge outputs in all three states to the various stakeholders involved. It is intentionally grounded in evidence drawn from academic analysis to facilitate objective and quantitative scrutiny, and industry best practices to enable practical application.SummaryThe Need to Knowledge (NtK) Model offers a practical, market-oriented approach that avoids the gaps, constraints and inefficiencies inherent in undirected activities and disconnected sectors. The NtK Model is a means to realizing increased returns on public investments in those science and technology programs expressly intended to generate beneficial socio-economic impacts.

Project description:Despite the government and global health initiatives toward yellow fever epidemic control in Ghana, the country continues to witness sporadic outbreaks of yellow fever mostly among the unvaccinated population and suspected migrates(nomadic) who enter the country. Little is known about nomadic knowledge, attitudes and practice regarding this communicable disease in Ghana. We conducted a community-based cross-sectional survey in 22 yellow fever outbreak communities to assess nomadic household heads' knowledge, attitudes and practices (KAP) regarding yellow fever after an outbreak in November 2021 outbreak. Our study results were analyzed using descriptive statistics, bivariate and multivariate logistics regression with dichotomous outcomes. Significant statistics were obtained from multivariate analysis. About 90% of the nomadic had poor knowledge of the signs and symptoms of yellow with only 16% knowing the vector that transmits yellow fever. The most common source of information on yellow fever was the health campaign. Over 80% of household heads surveyed had positive attitudes regarding yellow fever with about 84% worried about the disease outbreak in their community. In a multivariate logistic regression model, age group(AOR = 2.79; 95% CI: 1.31, 5.98, p = 0.008)., gender ideology(AOR = 2.27; 95% CI: 1.14-4.51, p = 0.019), occupation(AOR = 15.65; 95% CI: 7.02, 34.87, p<0.001), source of health information(AOR = 0.27; 95% CI: 0.07, 0.96, p = 0.043), duration of stay in the community(AOR = 1.11; 95% CI: 1.31, 5.98, p = 0.008) and nationality (AOR = 0.22; 95% CI:0.47, 0.47, p<0.001) were associated with positive attitudes towards yellow fever. Close to 74% have a positive practice, with 97.3% controlling mosquitoes in their household. Nationality (AOR = 3.85; 95% CI: 2.26, 6.56, p<0.001), duration of stay in the community (AOR = 1.06; 95% CI: 1.03, 1.10, p = 0.001), and age group(AOR = 040; 95% CI: 0.22, 0.73, p = 0.003) were associated with positive practices. Our findings show that yellow fever KAP was variable with clear knowledge gaps. Regular locally-tailored education and health promotion campaigns should be considered to improve knowledge and preventive practices against this infectious disease.

Project description:We evaluated the impact of man-made conflict events and climate change impact in guiding evidence-based community "One Health" epidemiology and emergency response practice against re-/emerging epidemics. Increasing evidence of emerging and re-emerging zoonotic diseases including recent Lassa fever outbreaks in almost 20 states in Nigeria led to 101 deaths and 175 suspected and confirmed cases since August 2015. Of the 75 laboratory confirmed cases, 90 deaths occurred representing 120% laboratory-confirmed case fatality. The outbreak has been imported into neighbouring country such as Benin, where 23 deaths out of 68 cases has also been reported. This study assesses the current trends in re-emerging Lassa fever outbreak in understanding spatio-geographical reservoir(s), risk factors pattern and Lassa virus incidence mapping, inherent gaps and raising challenges in health systems. It is shown that Lassa fever peak endemicity incidence and prevalence overlap the dry season (within January to March) and reduced during the wet season (of May to November) annually in Sierra Leone, Senegal to Eastern Nigeria. We documented a scarcity of consistent data on rodent (reservoirs)-linked Lassa fever outbreak, weak culturally and socio-behavioural effective prevention and control measures integration, weak or limited community knowledge and awareness to inadequate preparedness capacity and access to affordable case management in affected countries. Hence, robust sub/regional leadership commitment and investment in Lassa fever is urgently needed in building integrated and effective community "One Health" surveillance and rapid response approach practice coupled with pest management and phytosanitation measures against Lassa fever epidemic. This offers new opportunities in understanding human-animal interactions in strengthening Lassa fever outbreak early detection and surveillance, warning alerts and rapid response implementation in vulnerable settings. Leveraging on Africa CDC centre, advances in cloud-sourcing and social media tools and solutions is core in developing and integrating evidence-based and timely risk communication, and reporting systems in improving contextual community-based immunization and control decision making policy to effectively defeat Lassa fever outbreak and other emerging pandemics public health emergencies in Africa and worldwide.

Project description:BackgroundYellow fever (Yf) outbreak was recently reported in South Omo of Southern Ethiopia. This area was also highly affected by Yf outbreak in the 1960s. However, there is no reliable information on the level of community knowledge attitudes and practices about the disease in the area. The objective of the current study was to assess level of community knowledge, attitudes and practices about Yf.MethodsBetween March and May 2017, a community-based cross-sectional survey was conducted in two districts of the South Omo area. During the survey, 612 randomly selected adults were interviewed about Yf using structured questionnaire.ResultsOut of the 612 study participants, 508 (83.0%) reported that they heard about Yf which is locally known as "a disease that causes vomiting blood". Most (90.4%) of the study participants also said that Yf is different from malaria. Two hundred thirteen (41.9%) participants said that Yf can be transmitted from a patient to another person, while only 80 (37.6%) mentioned that the disease is transmitted through mosquitoes bite. Out of 333 (65.7%) study participants who believed that Yf is a preventable disease, 280 (84.1%) mentioned vaccine as a preventive method. The majority believed that the disease is a killer (97.2%) and a newly emerging (69.4%). Among the total of 612 study participants, 221(36.1%) were considered as having a high level of overall knowledge of Yf. Having educational level above 7th grade (AOR = 3.25, 95% CI: 1.39, 7.57, p = 0.006) and being resident of Bena-Tsemay district (AOR = 1.77, 95% CI: 1.12, 2.78, P = 0.014) were significantly associated with having a high level of overall knowledge of Yf. Agro-pastoralism as an occupation compared to farming was associated with having a low level of overall knowledge of Yf (AOR = 0.51, 95% CI, 0.33, 0.79, P = 0.003).ConclusionThe findings indicate that most of the study community members had a low level of overall knowledge of Yf, especially about its cause, mode of transmission and preventive methods. Thus, there is a need to increase people's knowledge and practices regarding the cause, mode of transmission and preventive methods like avoiding mosquitoe breeding sites beside vaccination through various strategies like disseminating information through community health extension workers and community leaders in the study area.

Project description:Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR-/-) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR-/-) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR-/- λR-/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the role of type III interferon (IFN)-mediated signaling, a host immune defense mechanism, in controlling YFV-17D infection and attenuation in different mouse models. We uncovered a critical role of type III IFN-mediated signaling in preserving the integrity of the blood-brain barrier and preventing viral brain invasion. Type III IFN also played a major role in regulating the induction of a potent but balanced immune response that prevented viral evasion of the host immune system. An improved understanding of the complex mechanisms regulating YFV-17D attenuation will provide insights into the key virus-host interactions that regulate host immune responses and infection outcomes as well as open novel avenues for the development of innovative vaccine strategies.

Dataset Information

Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus.

Publications

Yellow Fever: Integrating Current Knowledge with Technological Innovations to Identify Strategies for Controlling a Re-Emerging Virus.

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