The production of health news by the press: the context of the coverage of the 2007/2008 yellow fever epidemic. / A produção de notícias de saúde pela imprensa: o contexto da cobertura da epizootia da febre amarela 2007/2008.

The COVID-19 pandemic scenario raises the amplification of the debate around the production and circulation of information about epidemics. In this sense, the objective of this article is to discuss how social contexts shape the news, taking as an example the case of the news coverage that transformed an epizootic of yellow fever, in the summer of 2007/2008, into an epidemic of urban yellow fever. This is a qualitative research with journalists who worked in two large circulation newspapers and actively participated in the coverage of the event. The interviews were recorded, transcribed and submitted to discourse analysis, which allowed the identification of three factors that influenced the production of a media epidemic of yellow fever: the working conditions and the modus operandi of the newsrooms; the political-ideological dimension of the newspapers; and the difficulties of translation of technical-scientific information. A critical understanding of the production process of the journalistic text can contribute to the construction of communication strategies that minimize the circulation of misinformation on public health in traditional media (newspapers, magazines, radio, TV and news portals).

O cenário da pandemia de COVID-19 suscita a ampliação do debate em torno da produção e circulação de informações sobre epidemias. Nesse sentido, o objetivo deste artigo é discutir como os contextos sociais configuram as notícias, tomando como exemplo o caso da cobertura jornalística que transformou uma epizootia de febre amarela, no verão 2007/2008, em uma epidemia de febre amarela urbana. Trata-se de uma pesquisa qualitativa com jornalistas que trabalhavam em dois jornais de grande circulação e participaram ativamente da cobertura do evento. As entrevistas foram gravadas, transcritas e submetidas à análise de discurso, o que permitiu identificar três fatores que influenciaram a produção de uma epidemia midiática de febre amarela: as condições de trabalho e o modus operandi das redações; a dimensão político-ideológica dos jornais; e as dificuldades de tradução das informações técnico-científicas. A compreensão crítica do processo de produção do texto jornalístico pode contribuir para a construção de estratégias comunicacionais que minimizem a circulação de desinformação em saúde pública nas mídias tradicionais (jornais, revistas, rádio, tevê e portais de notícias).

A Perspective on Current Flavivirus Vaccine Development: A Brief Review.

The flavivirus genus contains several clinically important pathogens that account for tremendous global suffering. Primarily transmitted by mosquitos or ticks, these viruses can cause severe and potentially fatal diseases ranging from hemorrhagic fevers to encephalitis. The extensive global burden is predominantly caused by six flaviviruses: dengue, Zika, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitis. Several vaccines have been developed, and many more are currently being tested in clinical trials. However, flavivirus vaccine development is still confronted with many shortcomings and challenges. With the use of the existing literature, we have studied these hurdles as well as the signs of progress made in flavivirus vaccinology in the context of future development strategies. Moreover, all current licensed and phase-trial flavivirus vaccines have been gathered and discussed based on their vaccine type. Furthermore, potentially relevant vaccine types without any candidates in clinical testing are explored in this review as well. Over the past decades, several modern vaccine types have expanded the field of vaccinology, potentially providing alternative solutions for flavivirus vaccines. These vaccine types offer different development strategies as opposed to traditional vaccines. The included vaccine types were live-attenuated, inactivated, subunit, VLPs, viral vector-based, epitope-based, DNA and mRNA vaccines. Each vaccine type offers different advantages, some more suitable for flaviviruses than others. Additional studies are needed to overcome the barriers currently faced by flavivirus vaccine development, but many potential solutions are currently being explored.

Yellow fever vaccination before and during the covid-19 pandemic in Brazil.

OBJECTIVE: To analyze the number of yellow fever vaccine doses administered before and during the covid-19 pandemic in Brazil. METHODS: This is an ecological, time series study based on data from the National Immunization Program. Differences between the median number of yellow fever vaccine doses administered in Brazil and in its regions before (from April/2019 to March/2020) and after (from April/2020 to March/2021) the implementation of social distancing measures in the country were assessed via the Mann-Whitney test. Prais-Winsten regression models were used for time series analyses. RESULTS: We found a reduction in the median number of yellow fever vaccine doses administered in Brazil and in its regions: North (-34.71%), Midwest (-21.72%), South (-63.50%), and Southeast (-34.42%) (p < 0.05). Series showed stationary behavior in Brazil and in its five regions during the covid-19 pandemic (p > 0.05). Brazilian states also showed stationary trends, except for two states which recorded an increasing trend in the number of administered yellow fever vaccine doses, namely: Alagoas State (before: ß = 64, p = 0.081; after: ß = 897, p = 0.039), which became a yellow fever vaccine recommendation zone, and Roraima State (before: ß = 68, p = 0.724; after: ß = 150, p = 0.000), which intensified yellow fever vaccinations due to a yellow fever case confirmation in a Venezuelan State in 2020. CONCLUSION: The reduced number of yellow fever vaccine doses administered during the covid-19 pandemic in Brazil may favor the reemergence of urban yellow fever cases in the country.

Leveraging Lessons Learned from Yellow Fever and Polio Immunization Campaigns during COVID-19 Pandemic, Ghana, 2021.

Ghana is a yellow fever-endemic country and experienced a vaccine-derived polio outbreak in July 2019. A reactive polio vaccination campaign was conducted in September 2019 and preventive yellow fever campaign in November 2020. On March 12, 2020, Ghana confirmed its first COVID-19 cases. During February-August 2021, Ghana received 1,515,450 COVID-19 vaccines through the COVID-19 Vaccines Global Access initiative and other donor agencies. We describe how systems and infrastructure used for polio and yellow fever vaccine deployment and the lessons learned in those campaigns were used to deploy COVID-19 vaccines. During March-August 2021, a total of 1,424,008 vaccine doses were administered in Ghana. By using existing vaccination and health systems, officials in Ghana were able to deploy COVID-19 vaccines within a few months with <5% vaccine wastage and minimal additional resources despite the short shelf-life of vaccines received. These strategies were essential in saving lives in a resource-limited country.

Epidemiological description of and response to a large yellow fever outbreak in Edo state Nigeria, September 2018 - January 2019.

BACKGROUND: Edo State Surveillance Unit observed the emergence of a disease with "no clear-cut-diagnosis", which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State. METHODS: A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as "Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019". Our response involved active case search in health facilities and communities, retrospective review of patients' records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made. RESULTS: A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented. CONCLUSION: Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.

Live-attenuated YF17D-vectored COVID-19 vaccine protects from lethal yellow fever virus infection in mouse and hamster models.

BACKGROUND: The live-attenuated yellow fever vaccine YF17D holds great promise as alternative viral vector vaccine platform, showcased by our previously presented potent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate YF-S0. Besides protection from SARS-CoV-2, YF-S0 also induced strong yellow fever virus (YFV)-specific immunity, suggestive for full dual activity. A vaccine concomitantly protecting from SARS-CoV-2 and YFV would be of great benefit for those living in YFV-endemic areas with limited access to current SARS-CoV-2 vaccines. However, for broader applicability, pre-existing vector immunity should not impact the potency of such YF17D-vectored vaccines. METHODS: The immunogenicity and efficacy of YF-S0 against YFV and SARS-CoV-2 in the presence of strong pre-existing YFV immunity were evaluated in mouse and hamster challenge models. FINDINGS: Here, we show that a single dose of YF-S0 is sufficient to induce strong humoral and cellular immunity against YFV as well as SARS-CoV-2 in mice and hamsters; resulting in full protection from vigorous YFV challenge in either model; in mice against lethal intracranial YF17D challenge, and in hamsters against viscerotropic infection and liver disease following challenge with highly pathogenic hamster-adapted YFV-Asibi strain. Importantly, strong pre-existing immunity against the YF17D vector did not interfere with subsequent YF-S0 vaccination in mice or hamsters; nor with protection conferred against SARS-CoV-2 strain B1.1.7 (Alpha variant) infection in hamsters. INTERPRETATION: Our findings warrant the development of YF-S0 as dual SARS-CoV-2 and YFV vaccine. Contrary to other viral vaccine platforms, use of YF17D does not suffer from pre-existing vector immunity. FUNDING: Stated in the acknowledgments.

Travel vaccines throughout history.

Vaccinations are an important component of travel medicine. Beyond protection of travelers, vaccines are administered to prevent the importation of vaccine-preventable diseases at home and at destination. Proof of immunization to travel dates back to the first smallpox vaccine, developed by Edward Jenner in 1796. However, it took one century to generate the next vaccines against cholera, rabies, and typhoid fever. During the 20th century the armamentarium of vaccines used in travelers largely expanded with yellow fever, poliomyelitis, tetravalent meningococcal, and hepatitis A vaccines. The International Certificate of Inoculation and Vaccination was implemented in 1933. Currently there are vaccines administered to travelers following risk assessment, but also vaccines required according to the 2005 International Health Regulations and vaccines required at certain countries. Finally, within less than one year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic, the first COVID-19 vaccines were launched and approved for emergency use to control the pandemic. Despite practical and ethical challenges, COVID-19 vaccine verifications have been widely used since spring 2021 in many activities, including international travel. In this article, we review the course of development of travel vaccines focusing on those for which a proof of vaccination has been or is required.

'Learn from the lessons and don't forget them': identifying transferable lessons for COVID-19 from meningitis A, yellow fever and Ebola virus disease vaccination campaigns.

INTRODUCTION: COVID-19 vaccines are now being distributed to low- and middle-income countries (LMICs), with global urgency surrounding national vaccination plans. LMICs have significant experience implementing vaccination campaigns to respond to epidemic threats but are often hindered by chronic health system challenges. We sought to identify transferable lessons for COVID-19 vaccination from the rollout of three vaccines that targeted adult groups in Africa and South America: MenAfriVac (meningitis A); 17D (yellow fever) and rVSV-ZEBOV (Ebola virus disease). METHODS: We conducted a rapid literature review and 24 semi-structured interviews with technical experts who had direct implementation experience with the selected vaccines in Africa and South America. We identified barriers, enablers, and key lessons from the literature and from participants' experiences. Interview data were analysed thematically according to seven implementation domains. RESULTS: Participants highlighted multiple components of vaccination campaigns that are instrumental for achieving high coverage. Community engagement is an essential and effective tool, requiring dedicated time, funding and workforce. Involving local health workers is a key enabler, as is collaborating with community leaders to map social groups and tailor vaccination strategies to their needs. Vaccination team recruitment and training strategies need to be enhanced to support vaccination campaigns. Although recognised as challenging, integrating vaccination campaigns with other routine health services can be highly beneficial if well planned and coordinated across health programmes and with communities. CONCLUSION: As supplies of COVID-19 vaccines become available to LMICs, countries need to prepare to efficiently roll out the vaccine, encourage uptake among eligible groups and respond to potential community concerns. Lessons from the implementation of these three vaccines that targeted adults in LMICs can be used to inform best practice for COVID-19 and other epidemic vaccination campaigns.

A Systematic, Unbiased Mapping of CD8+ and CD4+ T Cell Epitopes in Yellow Fever Vaccinees.

Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified and tetramer-validated 92 CD8+ and 50 CD4+ T cell epitopes, many inducing strong and prevalent (i.e., immunodominant) T cell responses. Restricted by 40 and 14 HLA-class I and II allotypes, respectively, these responses have wide population coverage and might be of considerable academic, diagnostic and therapeutic interest. The broad coverage of epitopes and HLA overcame the otherwise confounding effects of HLA diversity and non-HLA background providing the first evidence of T cell immunodomination in humans. Also, double-staining of CD4+ T cells with tetramers representing the same HLA-binding core, albeit with different flanking regions, demonstrated an extensive diversification of the specificities of many CD4+ T cell responses. We suggest that this could reduce the risk of pathogen escape, and that multi-tetramer staining is required to reveal the true magnitude and diversity of CD4+ T cell responses. Our T cell epitope discovery approach uses a combination of (1) overlapping peptides representing the entire Yellow Fever virus proteome to search for peptides containing CD4+ and/or CD8+ T cell epitopes, (2) predictors of peptide-HLA binding to suggest epitopes and their restricting HLA allotypes, (3) generation of peptide-HLA tetramers to identify T cell epitopes, and (4) analysis of ex vivo T cell responses to validate the same. This approach is systematic, exhaustive, and can be done in any individual of any HLA haplotype. It is all-inclusive in the sense that it includes all protein antigens and peptide epitopes, and encompasses both CD4+ and CD8+ T cell epitopes. It is efficient and, importantly, reduces the false discovery rate. The unbiased nature of the T cell epitope discovery approach presented here should support the refinement of future peptide-HLA class I and II predictors and tetramer technologies, which eventually should cover all HLA class I and II isotypes. We believe that future investigations of emerging pathogens (e.g., SARS-CoV-2) should include population-wide T cell epitope discovery using blood samples from patients, convalescents and/or long-term survivors, who might all hold important information on T cell epitopes and responses.

Impact of COVID-19-related disruptions to measles, meningococcal A, and yellow fever vaccination in 10 countries.

Background: Childhood immunisation services have been disrupted by the COVID-19 pandemic. WHO recommends considering outbreak risk using epidemiological criteria when deciding whether to conduct preventive vaccination campaigns during the pandemic. Methods: We used two to three models per infection to estimate the health impact of 50% reduced routine vaccination coverage in 2020 and delay of campaign vaccination from 2020 to 2021 for measles vaccination in Bangladesh, Chad, Ethiopia, Kenya, Nigeria, and South Sudan, for meningococcal A vaccination in Burkina Faso, Chad, Niger, and Nigeria, and for yellow fever vaccination in the Democratic Republic of Congo, Ghana, and Nigeria. Our counterfactual comparative scenario was sustaining immunisation services at coverage projections made prior to COVID-19 (i.e. without any disruption). Results: Reduced routine vaccination coverage in 2020 without catch-up vaccination may lead to an increase in measles and yellow fever disease burden in the modelled countries. Delaying planned campaigns in Ethiopia and Nigeria by a year may significantly increase the risk of measles outbreaks (both countries did complete their supplementary immunisation activities (SIAs) planned for 2020). For yellow fever vaccination, delay in campaigns leads to a potential disease burden rise of >1 death per 100,000 people per year until the campaigns are implemented. For meningococcal A vaccination, short-term disruptions in 2020 are unlikely to have a significant impact due to the persistence of direct and indirect benefits from past introductory campaigns of the 1- to 29-year-old population, bolstered by inclusion of the vaccine into the routine immunisation schedule accompanied by further catch-up campaigns. Conclusions: The impact of COVID-19-related disruption to vaccination programs varies between infections and countries. Planning and implementation of campaigns should consider country and infection-specific epidemiological factors and local immunity gaps worsened by the COVID-19 pandemic when prioritising vaccines and strategies for catch-up vaccination. Funding: Bill and Melinda Gates Foundation and Gavi, the Vaccine Alliance.

Measurement of Cellular Immune Response to Viral Infection and Vaccination.

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

BACKGROUND: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. METHODS AND FINDINGS: We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. CONCLUSIONS: In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.

The obscurance of the greatest sylvatic yellow fever epidemic and the cooperation of the Pan American Health Organization during the COVID-19 pandemic.

INTRODUCTION: Since 2016, Brazil has been in the midst of its largest sylvatic yellow fever epidemic ever, found predominantly outside the Amazon region. Cases originating from Brazil have been reported in France, the Netherlands, Romania, Switzerland, Argentina, and Chile. The epidemic began in the Central-West region of Brazil in 2014, spreading into the Southern region, with significant non-human primate transmission continuing towards Paraguay and Argentina. METHODS: This report is an integrative review of Pan American Health Organization cooperation during a sylvatic yellow fever epidemic. RESULTS: The Pan American Health Organization has played a central role in handling the yellow fever emergency, collaborating with the Ministry of Health and various research groups in supporting interventions of different response areas. The Pan American Health Organization's technical cooperation included: training and workshops to exchange experiences, carrying out technical cooperation in patient management and epidemiological, entomological, laboratory, and epizootic surveillance, organizing the assistance network, and acquiring strategic inputs. The Pan American Health Organization's technical cooperation supported the Ministry of Health's decision to adopt a single-dose vaccine and use fractional doses to support the vaccination needs of more than 39,000,000 people. The coronavirus disease 2019 pandemic contributed to the failure of reaching the yellow fever vaccination goals and made it difficult to integrate the yellow fever vaccine into recommended areas. CONCLUSIONS: Given the ongoing coronavirus disease 2019 pandemic, it is necessary to strengthen measures for the surveillance, prevention, and control of yellow fever with multilateral cooperation between countries.

The Absence of Yellow Fever in Asia: History, Hypotheses, Vector Dispersal, Possibility of YF in Asia, and Other Enigmas.

Since the recent epidemics of yellow fever in Angola and Brazil as well as the importation of cases to China in 2016, there has been an increased interest in the century-old enigma, absence of yellow fever in Asia. Although this topic has been repeatedly reviewed before, the history of human intervention has never been considered a critical factor. A two-stage literature search online for this review, however, yielded a rich history indispensable for the debate over this medical enigma. As we combat the pandemic of COVID-19 coronavirus worldwide today, we can learn invaluable lessons from the historical events in Asia. In this review, I explore the history first and then critically examine in depth major hypotheses proposed in light of accumulated data, global dispersal of the principal vector, patterns of YF transmission, persistence of urban transmission, and the possibility of YF in Asia. Through this process of re-examination of the current knowledge, the subjects for research that should be conducted are identified. This review also reveals the importance of holistic approach incorporating ecological and human factors for many unresolved subjects, such as the enigma of YF absence in Asia, vector competence, vector dispersal, spillback, viral persistence and transmission mechanisms.

Prevention and control of Aedes transmitted infections in the post-pandemic scenario of COVID-19: challenges and opportunities for the region of the Americas.

The coronavirus disease of 2019 (COVID-19) pandemic challenges public health systems around the world. Tropical countries will face complex epidemiological scenarios involving the simultaneous transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with viruses transmitted by Aedes aegypti. The occurrence of arboviral diseases with COVID-19 in the Latin America and the Caribbean (LAC) region presents challenges and opportunities for strengthening health services, surveillance and control programs. Financing of training, equipment and reconversion of hospital spaces will have a negative effect on already the limited resource directed to the health sector. The strengthening of the diagnostic infrastructure reappears as an opportunity for the national reference laboratories. Sharing of epidemiological information for the modeling of epidemiological scenarios allows collaboration between health, academic and scientific institutions. The fear of contagion by COVID-19 is constraining people with arboviral diseases to search for care which can lead to an increase in serious cases and could disrupt the operation of vector-control programs due to the reluctance of residents to open their doors to health personnel. Promoting intense community participation along with the incorporation of long lasting innovations in vector control offers new opportunities for control. The COVID-19 pandemic offers challenges and opportunities that must provoke positive behavioral changes and encourage more permanent self-care actions.