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Background Aedes -borne diseases as dengue, zika, chikungunya and yellow fever are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes albopictus . Lack of up to date information about the distribution of Aedes species hampers surveillance and control. Global databases have been compiled but these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any models built using these datasets fail to identify highly suitable areas where one or both species may occur. The first objective of this study was therefore to update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895) compendia and the second objective was to generate species distribution models targeted to the EMR. A final objective was to engage the WHO points of contacts within the region to provide feedback and hence validate all model outputs. Methods The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al. (Sci Data 2:150035, 2015 ; Dryad Digit Repos, 2015 ) were used as starting points. These datasets were extended with more recent species and disease data. In the next step, these sets were filtered using the Köppen–Geiger classification and the Mahalanobis distance. The occurrence data were supplemented with pseudo-absence data as input to Random Forests. The resulting suitability and maximum risk of establishment maps were combined into hard-classified maps per country for expert validation. Results The EMR datasets consisted of 1995 presence locations for Ae. aegypti and 2868 presence locations for Ae. albopictus . The resulting suitability maps indicated that there exist areas with high suitability and/or maximum risk of establishment for these disease vectors in contrast with previous model output. Precipitation and host availability, expressed as population density and night-time lights, were the most important variables for Ae. aegypti . Host availability was the most important predictor in case of Ae. albopictus . Internal validation was assessed geographically. External validation showed high agreement between the predicted maps and the experts’ extensive knowledge of the terrain. Conclusion Maps of distribution and maximum risk of establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR. These region-specific maps highlighted data gaps and these gaps will be filled using targeted monitoring and surveillance. This will increase the awareness and preparedness of the different countries for Aedes borne diseases.

IntroductionAn ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre.Methods and analysisAdults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400 mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72 hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days.Ethics and disseminationEthics approval was obtained at the participating sites and at the national research ethics committee (CAAE 82673018.6.1001.0068). The trial has been submitted for ethical approval at additional potential recruiting centres. Results of the study will be published in journals and presented at scientific meetings.Trial registrationBrazilian Clinical Trials Registry (RBR-93dp9n).

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Yellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF–free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016–2019 YF epidemics have been considered the most significant outbreaks of the last 70 years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36 years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF. Haemagogus janthinomys and Haemagogus leucocelaenus were considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.

Arboviruses transmitted mainly by Aedes ( Stegomyia ) aegypti and Ae. albopictus , including dengue, chikungunya, and Zika viruses, and yellow fever virus in urban settings, pose an escalating global threat. Existing risk maps, often hampered by surveillance biases, may underestimate or misrepresent the true distribution of these diseases and do not incorporate epidemiological similarities despite shared vector species. We address this by generating new global environmental suitability maps for Aedes -borne arboviruses using a multi-disease ecological niche model with a nested surveillance model fit to a dataset of over 21,000 occurrence points. This reveals a convergence in suitability around a common global distribution with recent spread of chikungunya and Zika closely aligning with areas suitable for dengue. We estimate that 5.66 (95% confidence interval 5.64-5.68) billion people live in areas suitable for dengue, chikungunya and Zika and 1.54 (1.53-1.54) billion people for yellow fever. We find large national and subnational differences in surveillance capabilities with higher income more accessible areas more likely to detect, diagnose and report viral diseases, which may have led to overestimation of risk in the United States and Europe. When combined with estimates of uncertainty, these suitability maps can be used by ministries of health to target limited surveillance and intervention resources in new strategies against these emerging threats. Arboviruses transmitted by Aedes mosquitoes have an expanding global distribution and identifying areas at risk is important for public health planning. Here, the authors present global disease maps for dengue, chikungunya, Zika and yellow fever through a multi-disease ecological niche modelling approach.

To counter a limited global supply of yellow fever vaccine, the use of a fractional dose of vaccine (one fifth of the standard dose) during an outbreak in the Democratic Republic of Congo resulted in immunogenicity consistent with expected protective titers at 1-month and 1-year follow-up.

Yellow fever (YF) is a viral, vector-borne, haemorrhagic fever endemic in tropical regions of Africa and South America. The vaccine for YF is considered safe and effective, but intervention strategies need to be optimised; one of the tools for this is mathematical modelling. We refine and expand an existing modelling framework for Africa to account for transmission in South America. We fit to YF occurrence and serology data. We then estimate the subnational forces of infection for the entire endemic region. Finally, using demographic and vaccination data, we examine the impact of vaccination activities. We estimate that there were 109,000 (95% credible interval [CrI] [67,000–173,000]) severe infections and 51,000 (95% CrI [31,000–82,000]) deaths due to YF in Africa and South America in 2018. We find that mass vaccination activities in Africa reduced deaths by 47% (95% CrI [10%–77%]). This methodology allows us to evaluate the effectiveness of vaccination and illustrates the need for continued vigilance and surveillance of YF.

Objectives Arboviruses pose a significant global health challenge. This study investigated the seroprevalence of major human arboviral infections, including yellow fever (YFV), dengue (DENV), Crimean-Congo hemorrhagic fever (CCHF), Rift Valley fever (RVF), West Nile virus (WNV), and chikungunya (CHIK), in Darfur region from September to December 2018. ELISA-IgM was used to detect antibodies. RT‒PCR was used to differentiate YFV infection from vaccine-immuno-response in IgM samples. Results A total of 152 blood samples were collected, with 123 (80.9%) from males and 29 (19.1%) from females. The participants were grouped by age: 50 (32.9%) were under 20 years, 96 (63.2%) were aged 20–45 years, and 6 (3.9%) were over 45 years. The seroprevalence rates for YFV, DENV, and CHIKV were 68 (44.7%), 23 (15.1%), and 5 (3.3%), respectively. There were 11 molecularly-confirmed YFV cases (7.2%). Among these, 3/11 were positive for DENV-IgM, and 1/11 was positive for CHIKV-IgM. Among the 68 YFV-positive individuals, 15 (22.1%) had been exposed to DENV, and 2 (2.9%) had been exposed to CHIKV. Co-exposure to DENV and CHIKV was detected in 3 (1.9%) patients, while 2 (1.3%) patients had triple exposure to YFV, CHIKV, or DENV. No exposure to CCHF, RVFV, or WNV was detected.

Since late 2015, an epidemic of yellow fever has caused more than 7334 suspected cases in Angola and the Democratic Republic of the Congo, including 393 deaths. We sought to understand the spatial spread of this outbreak to optimise the use of the limited available vaccine stock. We jointly analysed datasets describing the epidemic of yellow fever, vector suitability, human demography, and mobility in central Africa to understand and predict the spread of yellow fever virus. We used a standard logistic model to infer the district-specific yellow fever virus infection risk during the course of the epidemic in the region. The early spread of yellow fever virus was characterised by fast exponential growth (doubling time of 5–7 days) and fast spatial expansion (49 districts reported cases after only 3 months) from Luanda, the capital of Angola. Early invasion was positively correlated with high population density (Pearson's r 0·52, 95% CI 0·34–0·66). The further away locations were from Luanda, the later the date of invasion (Pearson's r 0·60, 95% CI 0·52–0·66). In a Cox model, we noted that districts with higher population densities also had higher risks of sustained transmission (the hazard ratio for cases ceasing was 0·74, 95% CI 0·13–0·92 per log-unit increase in the population size of a district). A model that captured human mobility and vector suitability successfully discriminated districts with high risk of invasion from others with a lower risk (area under the curve 0·94, 95% CI 0·92–0·97). If at the start of the epidemic, sufficient vaccines had been available to target 50 out of 313 districts in the area, our model would have correctly identified 27 (84%) of the 32 districts that were eventually affected. Our findings show the contributions of ecological and demographic factors to the ongoing spread of the yellow fever outbreak and provide estimates of the areas that could be prioritised for vaccination, although other constraints such as vaccine supply and delivery need to be accounted for before such insights can be translated into policy. Wellcome Trust.

Yellow fever (YF) is a re-emerging viral zoonosis caused by the Yellow Fever virus (YFV), affecting humans and non-human primates (NHP). YF is endemic in South America and Africa, being considered a burden for public health worldwide despite the availability of an effective vaccine. Acute infectious disease can progress to severe hemorrhagic conditions and has high rates of morbidity and mortality in endemic countries. In 2016, Brazil started experiencing one of the most significant YF epidemics in its history, with lots of deaths being reported in regions that were previously considered free of the disease. Here, we reviewed the historical aspects of YF in Brazil, the epidemiology of the disease, the challenges that remain in Brazil’s public health context, the main lessons learned from the recent outbreaks, and our perspective for facing future YF epidemics.