Risk Of Yellow Fever Research Articles

Yellow fever in Ghana: Predicting emergence and ecology from historical outbreaks.

Understanding the epidemiology and ecology of yellow fever in endemic regions is critical for preventing future outbreaks. Ghana is a high-risk country for yellow fever. In this study we estimate the disease burden, ecological cycles, and areas at risk for yellow fever in Ghana based on historical outbreaks. We identify 2387 cases and 888 deaths (case fatality rate 37.7%) from yellow fever reported in Ghana from 1910 to 2022. During the approximately 30-year periods before and after implementation of routine childhood vaccination in 1992, the reported mean annual number of cases decreased by 80%. The geographic distribution of yellow fever cases has also changed over the past century. While there have been multiple large historical outbreaks of yellow fever in regions throughout Ghana, recent outbreaks have originated in northern regions. Comparing the locations where yellow fever outbreaks have emerged, we find patterns with seasons and different ecological transmission cycles. Using an ecological niche modeling framework, we predict areas in Ghana that are similar to where prior yellow fever outbreaks have originated based on temperature, precipitation, vegetation, and human population density. We find that these predictions differ depending on the ecological cycles of outbreaks. Ultimately, these findings and methods could be used to inform further subnational risk assessments for yellow fever in Ghana and other high-risk countries.

Knowledge and Attitudes Regarding the Vaccination of Brazilian Immigrants in Portugal: Risks When Returning to Their Country of Origin?

Vaccination is one of the main advancements in public health in the prophylaxis of infectious diseases. We intend to describe the general knowledge about vaccines/vaccination among Brazilian immigrants in Portugal, characterize their attitudes toward vaccination, and describe their knowledge of the yellow fever (YF) vaccine. A cross-sectional study was conducted using a self-completion questionnaire (face-to-face or remote). A total of 542 people participated in the study; the mean age was 36.81 years; 40.1% were male; 44.8% had their 12th year of schooling; and 27.0% had resided for ≥10 years in Portugal. Regarding general knowledge about vaccination, 53.8% answered at least 6/8 questions correctly. A total of 37.1% tended to have a favorable attitude toward vaccination. Concerning traveling, 76.7% attributed the risk of disease at the destination as the main reason for accepting vaccines. A total of 89.3% knew that there was a risk of YF in Brazil. A total of 40% answered correctly only one question about the YF vaccine; 21.6% did not answer any questions correctly. Thus, most of the Brazilian immigrants in this study have high general knowledge about vaccines/vaccination, few have a favorable attitude, and their knowledge about the YF vaccine is scarce. This could limit vaccination adherence when visiting Brazil, making health education actions necessary to increase knowledge and prevent YF risks.

Weekly Forecasting of Yellow Fever Occurrence and Incidence via Eco-Meteorological Dynamics.

Yellow Fever (YF), a mosquito-borne disease, requires ongoing surveillance and prevention due to its persistence and ability to cause major epidemics, including one that began in Brazil in 2016. Forecasting based on factors influencing YF risk can improve efficiency in prevention. This study aimed to produce weekly forecasts of YF occurrence and incidence in Brazil using weekly meteorological and ecohydrological conditions. Occurrence was forecast as the probability of observing any cases, and incidence was forecast to represent morbidity if YF occurs. We fit gamma hurdle models, selecting predictors from several meteorological and ecohydrological factors, based on forecast accuracy defined by receiver operator characteristic curves and mean absolute error. We fit separate models for data before and after the start of the 2016 outbreak, forecasting occurrence and incidence for all municipalities of Brazil weekly. Different predictor sets were found to produce most accurate forecasts in each time period, and forecast accuracy was high for both time periods. Temperature, precipitation, and previous YF burden were most influential predictors among models. Minimum, maximum, mean, and range of weekly temperature, precipitation, and humidity contributed to forecasts, with optimal lag times of 2, 6, and 7weeks depending on time period. Results from this study show the use of environmental predictors in providing regular forecasts of YF burden and producing nationwide forecasts. Weekly forecasts, which can be produced using the forecast model developed in this study, are beneficial for informing immediate preparedness measures.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry

ObjectivesPretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). MethodsClients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. ResultsIn total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80–0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14–0.63) were significantly associated with YFV. ConclusionsPreventive interventions other than YFV should be offered to older adults.

Wicked Problems in Risk Assessment: Mapping Yellow Fever and Constructing Risk as an Embodied Experience

In this article, the author theorizes the process that a World Health Organization work group used to update yellow fever risk maps published in the Yellow Book, a handbook created by the Centers for Disease Control and Prevention for international travelers, from a “wicked problems” perspective. She argues that using this model highlights the complexity of nonexperts’ risk assessment practices in this context and that the work group's decision to create vaccination maps demonstrates an increased awareness of the embodied decision-making practices that nonexperts perform, aligning with and contributing to the growing emphasis on creating user-centered risk information that can be seen in some risk communication.

Enhanced safety surveillance of STAMARIL® yellow fever vaccine provided under the expanded access investigational new drug program in the USA.

YF-VAX® (Sanofi, Swiftwater, PA), a live, attenuated vaccine based on the yellow fever (YF) substrain 17D-204, is the only YF vaccine licensed in the USA. Manufacturing disruption of YF-VAX and anticipated depletion of the US supply by mid-2017 led to the importation of another YF vaccine, STAMARIL® (Sanofi, France), into the USA under an expanded access investigational new drug program (EAP) to fulfil the public health need for YF vaccination. As part of this program, Sanofi collected enhanced safety surveillance data following vaccination with STAMARIL. Here, we report the results of the enhanced safety surveillance. STAMARIL vaccine was offered to those aged ≥9months at high risk of YF. Vaccine recipients (or parents/guardians) were instructed to report suspected adverse reactions, any serious adverse events (SAEs) including adverse events of special interest [AESI] occurring after vaccination regardless of suspected relationship, and any inadvertent exposure in pregnancy or breastfeeding within 14days of vaccination. The AESIs monitored were anaphylaxis, neurotropic disease (YEL-AND) and viscerotropic disease (YEL-AVD). Overall, 627 079 individuals received STAMARIL from May 2017 through June 2021; of these, 1308 (0.2%) reported at least one AE, of which 122 reported at least one SAE. There were seven cases of YEL-AND and three cases of YEL-AVD reported, for reporting rates of 1.1 and 0.5 per 100 000 vaccine recipients, respectively. One vaccine recipient developed an anaphylactic reaction (reporting rate: 0.16 per 100 000). No safety concerns were identified from inadvertent vaccine exposure during pregnancy (41 pregnant women) or potential neonatal exposure via breast milk (four exposed infants). This study supports the utility of STAMARIL in the EAP as an alternative solution for the YF vaccine shortage in the USA. SAEs were very rare and consistent with the known safety profile of STAMARIL.

Yellow fever outbreak in Ebonyi State, Nigeria, May-August 2019

An outbreak of yellow fever (YF) occurred in Ebonyi State, Nigeria in the year 2019 and a Rapid Response Team (RRT) from the Nigeria Centre for Disease Control, Abuja was deployed to investigate and characterize the outbreak and institute control measures. All suspected cases were identified, line-listed and analyzed. Between May and August 2019, 78 suspected YF cases were identified from 5 LGAs in Ebonyi State. Of these, 17 (21.8%) confirmed YF cases [including 4 deaths (case fatality rate (CFR): 23.5%)] were reported in 4 LGAs, with majority 13 (76.5%) from Izzi LGA. Age groups mostly affected were 0-9 years 5(29.4%) and 20-29 years 5(29.4%) with mean age 19 ±12 years. Majority were males 10 (58.8%). Overall, 50 eligible children participated in the YF VCS, 36(72.0%) had their vaccination cards available and only 24 (48.0%) of the cards had a record of YF vaccination. Aedes larva was found in 9(90.0%) of 10 households surveyed and adult species Aedes simpsoni complex emerged from the collections. The 2019 YF outbreak in Ebonyi state was as a result of an abundance of Aedes mosquitoes and low vaccination coverage. We recommend a Statewide YF risk assessment, mass YF vaccination campaign, vector control and enhanced YF surveillance is important to prevent future outbreaks and mortality.

Yellow fever in Asia-a risk analysis.

BackgroundThere is concern about the risk of yellow fever (YF) establishment in Asia, owing to rising numbers of urban outbreaks in endemic countries and globalisation. Following an outbreak in Angola in 2016, YF cases were introduced into China. Prior to this, YF had never been recorded in Asia, despite climatic suitability and the presence of mosquitoes. An outbreak in Asia could result in widespread fatalities and huge economic impact. Therefore, quantifying the potential risk of YF outbreaks in Asia is a public health priority.MethodsUsing international flight data and YF incidence estimates from 2016, we quantified the risk of YF introduction via air travel into Asia. In locations with evidence of a competent mosquito population, the potential for autochthonous YF transmission was estimated using a temperature-dependent model of the reproduction number and a branching process model assuming a negative binomial distribution.ResultsIn total, 25 cities across Asia were estimated to be at risk of receiving at least one YF viraemic traveller during 2016. At their average temperatures, we estimated the probability of autochthonous transmission to be <50% in all cities, which was primarily due to the limited number of estimated introductions that year.ConclusionDespite the rise in air travel, we found low support for travel patterns between YF endemic countries and Asia resulting in autochthonous transmission during 2016. This supports the historic absence of YF in Asia and suggests it could be due to a limited number of introductions in previous years. Future increases in travel volumes or YF incidence can increase the number of introductions and the risk of autochthonous transmission. Given the high proportion of asymptomatic or mild infections and the challenges of YF surveillance, our model can be used to estimate the introduction and outbreak risk and can provide useful information to surveillance systems.

Laboratory capacity assessments in 25 African countries at high risk of yellow fever, August-December 2018.

Introductionaccurate and timely laboratory diagnosis of yellow fever (YF) is critical to the Eliminate Yellow Fever Epidemics (EYE) strategy. Gavi, the Vaccine Alliance recognized the need to support and build capacity in the national and regional laboratories in the Global YF Laboratory Network (GYFLN) as part of this strategy.Methodsto better understand current capacity, gaps and needs of the GYFLN laboratories in Africa, assessments were carried out in national and regional reference laboratories in the 25 African countries at high risk for YF outbreaks that were eligible for new financial support from Gavi.Resultsthe assessments found that the GYFLN in Africa has high capacity but 21% of specimens were not tested due to lack of testing kits or reagents and approximately 50% of presumptive YF cases were not confirmed at the regional reference laboratory due to problems with shipping.Conclusionthe laboratory assessments helped to document the baseline capacities of these laboratories prior to Gavi funding to support strengthening YF laboratories.

Vaccine usage and wastage in a designated Yellow Fever Vaccination Centre in North India.

PurposeYellow fever is a viral hemorrhagic fever transmitted through the bite of mosquitoes. World Health Organization guidelines advocate a single dose of vaccine for life-long protective immunity against yellow fever. Yellow fever vaccine is included in routine childhood immunization schedules in countries at medium or high risk of yellow fever. For some travelers, visiting endemic countries, yellow fever vaccination is recommended to protect the travelers. We calculated the yellow fever vaccine wastage rate at a designated center in North India.Materials and MethodsThis is a record-based study. The data for the study was obtained from the immunization center of Government Medical College, Srinagar, Jammu and Kashmir. The particulars for every vaccine recipient were present in the register. The vaccine wastage rate was calculated. The analysis was done in IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA) and results were presented as numbers and frequencies.ResultsA total of 136 doses were issued out of which 111 doses were administered from November 2017 till October 2020. The maximum number of travelers was young adults (26.1%). In 83.7% of cases, the area of the visit was Africa. The vaccine wastage rate was 18.4%.ConclusionThe vaccine wastage rate was not very high and was within that recommended for vaccines in routine immunization.

Eliminating yellow fever epidemics in Africa: Vaccine demand forecast and impact modelling.

BackgroundTo counter the increasing global risk of Yellow fever (YF), the World Health Organisation initiated the Eliminate Yellow fever Epidemics (EYE) strategy. Estimating YF burden, as well as vaccine impact, while accounting for the features of urban YF transmission such as indirect benefits of vaccination, is key to informing this strategy.Methods and findingsWe developed two model variants to estimate YF burden in sub-Saharan Africa, assuming all infections stem from either the sylvatic or the urban cycle of the disease. Both relied on an ecological niche model fitted to the local presence of any YF reported event in 34 African countries. We calibrated under-reporting using independent estimates of transmission intensity provided by 12 serological surveys performed in 11 countries. We calculated local numbers of YF infections, deaths and disability-adjusted life years (DALYs) lost based on estimated transmission intensity while accounting for time-varying vaccination coverage. We estimated vaccine demand and impact of future preventive mass vaccination campaigns (PMVCs) according to various vaccination scenarios.Vaccination activities conducted in Africa between 2005 and 2017 were estimated to prevent from 3.3 (95% CI 1.2–7.7) to 6.1 (95% CI 2.4–13.2) millions of deaths over the lifetime of vaccinees, representing extreme scenarios of none or maximal herd effects, respectively. By prioritizing provinces based on the risk of urban YF transmission in future PMVCs, an average of 37.7 million annual doses for PMVCs over eight years would avert an estimated 9,900,000 (95% CI 7,000,000–13,400,000) infections and 480,000 (180,000–1,140,000) deaths over the lifetime of vaccinees, corresponding to 1.7 (0.7–4.1) deaths averted per 1,000 vaccine doses.ConclusionsBy estimating YF burden and vaccine impact over a range of spatial and temporal scales, while accounting for the specificity of urban transmission, our model can be used to inform the current EYE strategy.

Yellow Fever Vaccination in a Mouse Model Is Associated With Uninterrupted Pregnancies and Viable Neonates Except When Administered at Implantation Period.

The potential risk of yellow fever (YF) infection in unvaccinated pregnant women has aroused serious concerns. In this study, we evaluated the effect of the YF vaccine during gestation using a mouse model, analyzing placental structure, immunolocalization of the virus antigen, and viral activity at the maternal-fetal barrier and in the maternal liver and fetus. The YF vaccine (17DD) was administered subcutaneously at a dose of 2.0 log10 PFU to CD-1 mice on gestational days (gd) 0.5, 5.5, and 11.5 (n = 5–10/group). The control group received sterile saline (n = 5–10/group). Maternal liver, implantation sites with fetus, and placentas were collected on gd18.5. The numbers of implantation sites, reabsorbed embryos, and stillborn fetuses were counted, and placentas and live fetuses were weighed. Tissues (placenta, fetuses, and liver) of vaccinated pregnant mice on gd5.5 (n = 15) were paraffin-embedded in 10% buffered-formalin and collected in TRIzol for immunolocalization of YF vaccine virus and PCR, respectively. PCR products were also subjected to automated sequence analysis. Fetal growth restriction (p < 0.0001) and a significant decrease in fetal viability (p < 0.0001) occurred only when the vaccine was administered on gd5.5. In stillbirths, the viral antigen was consistently immunolocalized at the maternal-fetal barrier and in fetal organs, suggesting a transplacental transfer. In stillbirths, RNA of the vaccine virus was also detected by reverse transcriptase-PCR indicating viral activity in the maternal liver and fetal tissues. In conclusion, the findings of this study in the mouse suggest that vaccination did not cause adverse outcomes with respect to fetal development except when administered during the early gestational stage, indicating the implantation period as a susceptible period in which the YF vaccine virus might interfere with pregnancy.

2774. Impact of Yellow Fever Vaccine and Recombinant Zoster Vaccine Shortages on Patients Presenting to a Travel Clinic

BackgroundIn 2017, the United States experienced a national shortage of the yellow fever vaccine (YF-Vax). In response to this, the US Food and Drug Administration (FDA) approved the use of Stamaril in a limited number of clinics across the country. This was soon followed by a shortage of the recently approved recombinant zoster vaccine (RZV) in 2018. This project describes the impact of both vaccine shortages on patients presenting to the Travel Health Clinic at Froedtert and the Medical College of Wisconsin.MethodsA retrospective review of Travel Health Clinic medical records between January and December of 2018 was performed. Information regarding patient demographics, travel destination, vaccination rates, reasons for not vaccinating, and referral information was obtained.ResultsOf the 306 patients seen in 2018, 98 were traveling to countries with active yellow fever transmission. Due to the YF-Vax shortage, 59.2% of these patients were referred to another clinic for Stamaril and 7.1% were unable to get the vaccine before departure. The remaining patients qualified for a medical exemption, had an itinerary that was lower risk for yellow fever, or their subsequent vaccine history was unknown. Additional cost for Stamaril at referral locations ranged from $169.50-$315.00 per person with a travel distance of 15–272 miles to the referred clinic. Regarding RZV, 134 clinic patients were qualified to receive the vaccine. 57.5% did not receive RZV due to vaccine shortage, 15.7% were referred to another clinic for RZV, while 15.7% were able to receive the vaccine during their appointment. Of these patients, 31.3% were covered under Medicare, thus necessitating referral to a pharmacy for vaccine coverage.ConclusionWe encountered high rates of unvaccinated travelers who would have qualified for and benefitted from YF-Vax and RZV in 2018. Even among those who could receive the recommended vaccines, there was substantial additional cost and inconvenience. This illustrates the considerable negative impact of the YF-Vax and RZV vaccine shortages. Further efforts are necessary to make these vaccines more accessible to the community.Disclosures All authors: No reported disclosures.

Mosquito and primate ecology predict human risk of yellow fever virus spillover in Brazil.

Many (re)emerging infectious diseases in humans arise from pathogen spillover from wildlife or livestock, and accurately predicting pathogen spillover is an important public health goal. In the Americas, yellow fever in humans primarily occurs following spillover from non-human primates via mosquitoes. Predicting yellow fever spillover can improve public health responses through vector control and mass vaccination. Here, we develop and test a mechanistic model of pathogen spillover to predict human risk for yellow fever in Brazil. This environmental risk model, based on the ecology of mosquito vectors and non-human primate hosts, distinguished municipality-months with yellow fever spillover from 2001 to 2016 with high accuracy (AUC = 0.72). Incorporating hypothesized cyclical dynamics of infected primates improved accuracy (AUC = 0.79). Using boosted regression trees to identify gaps in the mechanistic model, we found that important predictors include current and one-month lagged environmental risk, vaccine coverage, population density, temperature and precipitation. More broadly, we show that for a widespread human viral pathogen, the ecological interactions between environment, vectors, reservoir hosts and humans can predict spillover with surprising accuracy, suggesting the potential to improve preventive action to reduce yellow fever spillover and avert onward epidemics in humans.This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.

Differences between coverage of yellow fever vaccine and the first dose of measles-containing vaccine: A desk review of global data sources

IntroductionThe strategy to Eliminate Yellow Fever Epidemics (EYE) is a global initiative that includes all countries with risk of yellow fever (YF) virus transmission. Of these, 40 countries (27 in Africa and 13 in the Americas) are considered high-risk and targeted for interventions to increase coverage of YF vaccine. Even though the World Health Organization (WHO) recommends that YF vaccine be given concurrently with the first dose of measles-containing vaccine (MCV1) in YF-endemic settings, estimated coverage for MCV1 and YF vaccine have varied widely. The objective of this study was to review global data sources to assess discrepancies in YF vaccine and MCV1 coverage and identify plausible reasons for these discrepancies. MethodsWe conducted a desk review of data from 34 countries (22 in Africa, 12 in Latin America), from 2006 to 2016, with national introduction of YF vaccine and listed as high-risk by the EYE strategy. Data reviewed included procured and administered doses, immunization schedules, routine coverage estimates and reported vaccine stock-outs. In the 30 countries included in the comparitive analysis, differences greater than 3 percentage points between YF vaccine and MCV1 coverage were considered meaningful. ResultsIn America, there were meaningful differences (7–45%) in coverage of the two vaccines in 6 (67%) of the 9 countries. In Africa, there were meaningful differences (4–27%) in coverage of the two vaccines in 9 (43%) of the 21 countries. Nine countries (26%) reported MVC1 stock-outs while sixteen countries (47%) reported YF vaccine stock-outs for three or more years during 2006–2016. ConclusionIn countries reporting significant differences in coverage of the two vaccines, differences may be driven by different target populations and vaccine availability. However,these were not sufficient to completely explain observed differences. Further follow-up is needed to identify possible reasons for differences in coverage rates in several countries where these could not fully be explained.

Epidemiological monitoring of the last outbreak of yellow fever in Brazil - An outlook from Portugal.

Yellow Fever (YF) is a high fatality rate disease (30-50%) caused by Flavivirus, present in some African and South American countries. In order to determine the magnitude and epidemiological distribution of YF cases, vaccination coverage and most affected regions in Brazil, a descriptive epidemiological study monitoring the last outbreak was undertaken in Portugal. The Brazilian database "Portal da Saude" was used to collect data on cases of YF. We used Microsoft Excel on a weekly basis to update the suspected, confirmed and mortality cases as well as the case fatality rate and epizootics in non-human primates. Case Fatality Rate was 33.6%. A total and 82% of confirmed cases were males. The outbreak predominantly affected two south-eastern states, Minas Gerais and Espírito Santo, both with a very low vaccination coverage. The last outbreak of YF was by far the largest observed over the last few decades! Until the emergence of this outbreak, Espírito Santo, Bahia and Rio de Janeiro were states of low risk for YF and the vaccine not previously recommended. The World Health Organization's "Global Strategy to Eliminate Yellow Fever Epidemic" (EYE) should be on the way, to prevent YF outbreaks in Brazil and other countries in Africa and South America.

The vulnerability of New Orleans’ black and foreign-born populations in the 1878 yellow fever outbreak: a reassessment

Since the nineteenth century, medical researchers and social scientists have debated whether persons of African descent have comparative immunity to yellow fever. Studies have mainly used social science methodologies, notably the career-long but still-controversial research of Sheldon Watts and Kenneth Kiple. This case study, in contrast, applied epidemiological methodology to new data about the 1878 New Orleans’ yellow fever outbreak and, using a retrospective cohort study, concluded that Blacks did indeed have a much lower mortality rate than several other non-African groups. Foreign-born residents, Africans, and African-Americans were examined as exposed groups in the outbreak. The 1880 Census was used to measure the yellow fever risk for people born in Europe and for the entire Black population. Yellow fever deaths data came primarily from the records of the New Orleans Board of Health report but was here augmented by records from the Charity Hospital, Cemetery Burial, Coroner’s Office, obituaries, and prisons, creating a more accurate death figure of 4775. Results show that the relative risk (RR) of dying from yellow fever among the foreign-born population exposed to the disease is higher compared to Blacks. The figures are RR 6.28 (Italy), RR 2.55 (France), RR 1.47 (Great Britain), and RR 1.26 (German Empire), and Blacks (RR 0.25). Besides presenting a case in which Blacks were clearly shown as less vulnerable to the disease, the study also showed that contemporary epidemiological statistics and methods could achieve meaningful results regarding vulnerability to yellow fever even using incomplete data from the distant past.

Spatio-temporal spillover risk of yellow fever in Brazil

BackgroundYellow fever virus is a mosquito-borne flavivirus that persists in an enzoonotic cycle in non-human primates (NHPs) in Brazil, causing disease in humans through spillover events. Yellow fever (YF) re-emerged in the early 2000s, spreading from the Amazon River basin towards the previously considered low-risk, southeastern region of the country. Previous methods mapping YF spillover risk do not incorporate the temporal dynamics and ecological context of the disease, and are therefore unable to predict seasonality in spatial risk across Brazil. We present the results of a bagged logistic regression predicting the propensity for YF spillover per municipality (administrative sub-district) in Brazil from environmental and demographic covariates aggregated by month. Ecological context was incorporated by creating National and Regional models of spillover dynamics, where the Regional model consisted of two separate models determined by the regions’ NHP reservoir species richness (high vs low).ResultsOf the 5560 municipalities, 82 reported YF cases from 2001 to 2013. Model accuracy was high for the National and low reservoir richness (LRR) models (AUC = 0.80), while the high reservoir richness (HRR) model accuracy was lower (AUC = 0.63). The National model predicted consistently high spillover risk in the Amazon, while the Regional model predicted strong seasonality in spillover risk. Within the Regional model, seasonality of spillover risk in the HRR region was asynchronous to the LRR region. However, the observed seasonality of spillover risk in the LRR Regional model mirrored the national model predictions.ConclusionsThe predicted risk of YF spillover varies with space and time. Seasonal trends differ between regions indicating, at times, spillover risk can be higher in the urban coastal regions than the Amazon River basin which is counterintuitive based on current YF risk maps. Understanding the spatio-temporal patterns of YF spillover risk could better inform allocation of public health services.

Modeling the elevated risk of yellow fever among travelers visiting Brazil, 2018

BackgroundUnlike the epidemic of yellow fever from 2016 to 17 in Brazil mostly restricted to the States of Minas Gerais and Espirito Santo, the epidemic from 2017 to 18 mainly involved São Paulo and Rio de Janeiro and resulted in multiple international disseminations. To understand mechanisms behind this observation, the present study analyzed the distribution of imported cases from Brazil, 2018.MethodsA statistical model was employed to capture the risk of importing yellow fever by returning international travelers from Brazil. We estimated the relative risk of importation among travelers by the extent of wealth measured by GDP per capita and the relative risk obtained by random assignment of travelers’ destination within Brazil by the relative population size.ResultsUpper-half wealthier countries had 2.1 to 3.4 times greater risk of importation than remainders. Even among countries with lower half of GDP per capita, the risk of importation was 2.5 to 2.8 times greater than assuming that the risk of travelers’ infection within Brazil is determined by the regional population size.ConclusionsTravelers from wealthier countries were at elevated risk of yellow fever, allowing us to speculate that travelers’ local destination and behavior at high risk of infection are likely to act as a key determinant of the heterogeneous risk of importation. It is advised to inform travelers over the ongoing geographic foci of transmission, and if it appears unavoidable to visit tourist destination that has the history of producing imported cases, travelers must be strongly advised to receive vaccination in advance.

Responding to yellow fever outbreaks in West and Central Africa: Rapid prioritization assessment for the pre-emptive vaccination campaigns

Introduction Recent yellow fever (YF) outbreaks in Africa, such as 2016 in Angola, or 2017 in Nigeria, have demonstrated the ongoing threat of large-scale urban YF outbreaks. Moreover, outbreaks of other mosquito-borne diseases (Zika, chikungunya) have increased awareness of the potential for rapid, international spread of arboviruses. Swift outbreak response, for YF primarily in the form of vaccination, is therefore essential to prevent local and international spread. However, limited global stockpiles means that the prioritization of geographic areas for pre-emptive vaccination campaigns is required (i.e. vaccination campaigns targeting areas that are at risk of disease introduction and spread but as yet unaffected). Conducting a rapid prioritization assessment based on the risk of disease spread is thus highly valuable to inform decisions on vaccination activities in a context of emergency. Objective To develop a method for rapid risk assessment of YF spread to prioritize sub-national administrative units (hereafter called province) for pre-emptive campaigns. Specific requirements for this method are: –speed of implementation in the context of emergency response; –transparent methodology to allow discussions with and feedback from decision-makers. Method We developed a heuristic method to quantify the risk of YF spread by integrating multiple data streams: population sizes, estimates of existing vaccine-induced population-level immunity, recent incidence of yellow fever cases in the province and travel flows between provinces. The resulting risk score primarily reflects the expected absolute number of yellow cases in the respective province, accounting for local cases and the risk of case importation. Based on their risk score, provinces are ranked according to priority for vaccination and target population sizes are estimated. This baseline, quick-to-compute, risk assessment can be refined by integrating additional elements. For example, the presence and population size of large urban centres at the province level may be relevant to characterize the risk of urban outbreaks, and of international spread in the case of highly connected urban centres. Similarly, independent estimates of the local transmission potential of the disease produced by a mathematical model can be combined into this risk metric. Results This heuristic method has been used in collaboration with the World Health Organization in the context of urgent response to yellow fever outbreaks that affected Angola and the Democratic Republic of Congo (DRC) in 2016 and Nigeria in 2017. Results were provided in a form that allowed decision-makers to easily and interactively adjust the relative weights of different factors and visualize the effect on the results. Moreover, the transparency of the method allowed decision-makers to provide feedback and to request the integration of additional elements considered as relevant for outbreak control (for instance: trans-border movements in Angola-DRC). This risk assessment contributed to inform decision for mass vaccination campaigns conducted in the DRC in 2017 and for campaigns (still under consideration) in Nigeria in 2018. Conclusion By integrating different, mostly publicly available, data streams, we developed a risk assessment method that can be quickly implemented in the context of yellow fever outbreak response. The transparency and flexibility of the method enhanced interactions with decision-makers to refine estimates.