How the yellow fever mosquito found its first human victim.

Aedes aegypti developed a taste for humans at the birth of the Sahara, a new analysis suggests.

Reemergence of yellow fever virus in southeastern Brazil, 2017-2018: What sparked the spread?

BACKGROUND: The 2017-2018 yellow fever virus (YFV) outbreak in southeastern Brazil marked a reemergence of YFV in urban states that had been YFV-free for nearly a century. Unlike earlier urban YFV transmission, this epidemic was driven by forest mosquitoes. The objective of this study was to evaluate environmental drivers of this outbreak. METHODOLOGY/PRINCIPAL FINDINGS: Using surveillance data from the Brazilian Ministry of Health on human and non-human primate (NHP) cases of YFV, we traced the spatiotemporal progression of the outbreak. We then assessed the epidemic timing in relation to drought using a monthly Standardized Precipitation Evapotranspiration Index (SPEI) and evaluated demographic risk factors for rural or outdoor exposure amongst YFV cases. Finally, we developed a mechanistic framework to map the relationship between drought and YFV. Both human and NHP cases were first identified in a hot, dry, rural area in northern Minas Gerais before spreading southeast into the more cool, wet urban states. Outbreaks coincided with drought in all four southeastern states of Brazil and an extreme drought in Minas Gerais. Confirmed YFV cases had an increased odds of being male (OR 2.6; 95% CI 2.2-3.0), working age (OR: 1.8; 95% CI: 1.5-2.1), and reporting any recent travel (OR: 2.8; 95% CI: 2.3-3.3). Based on this data as well as mosquito and non-human primate biology, we created the "Mono-DrY" mechanistic framework showing how an unusual drought in this region could have amplified YFV transmission at the rural-urban interface and sparked the spread of this epidemic. CONCLUSIONS/SIGNIFICANCE: The 2017-2018 YFV epidemic in Brazil originated in hot, dry rural areas of Minas Gerais before expanding south into urban centers. An unusually severe drought in this region may have created environmental pressures that sparked the reemergence of YFV in Brazil's southeastern cities.

Ecological and environmental factors affecting transmission of sylvatic yellow fever in the 2017-2019 outbreak in the Atlantic Forest, Brazil.

BACKGROUND: Yellow fever virus (YFV) is an arbovirus that, despite the existence of a safe and effective vaccine, continues to cause outbreaks of varying dimensions in the Americas and Africa. Between 2017 and 2019, Brazil registered un unprecedented sylvatic YFV outbreak whose severity was the result of its spread into zones of the Atlantic Forest with no signals of viral circulation for nearly 80 years. METHODS: To investigate the influence of climatic, environmental, and ecological factors governing the dispersion and force of infection of YFV in a naïve area such as the landscape mosaic of Rio de Janeiro (RJ), we combined the analyses of a large set of data including entomological sampling performed before and during the 2017-2019 outbreak, with the geolocation of human and nonhuman primates (NHP) and mosquito infections. RESULTS: A greater abundance of Haemagogus mosquitoes combined with lower richness and diversity of mosquito fauna increased the probability of finding a YFV-infected mosquito. Furthermore, the analysis of functional traits showed that certain functional groups, composed mainly of Aedini mosquitoes which includes Aedes and Haemagogus mosquitoes, are also more representative in areas where infected mosquitoes were found. Human and NHP infections were more common in two types of landscapes: large and continuous forest, capable of harboring many YFV hosts, and patches of small forest fragments, where environmental imbalance can lead to a greater density of the primary vectors and high human exposure. In both, we show that most human infections (~ 62%) occurred within an 11-km radius of the finding of an infected NHP, which is in line with the flight range of the primary vectors. CONCLUSIONS: Together, our data suggest that entomological data and landscape composition analyses may help to predict areas permissive to yellow fever outbreaks, allowing protective measures to be taken to avoid human cases.

Mapping environmental suitability of Haemagogus and Sabethes spp. mosquitoes to understand sylvatic transmission risk of yellow fever virus in Brazil.

BACKGROUND: Yellow fever (YF) is an arboviral disease which is endemic to Brazil due to a sylvatic transmission cycle maintained by infected mosquito vectors, non-human primate (NHP) hosts, and humans. Despite the existence of an effective vaccine, recent sporadic YF epidemics have underscored concerns about sylvatic vector surveillance, as very little is known about their spatial distribution. Here, we model and map the environmental suitability of YF's main vectors in Brazil, Haemagogus spp. and Sabethes spp., and use human population and NHP data to identify locations prone to transmission and spillover risk. METHODOLOGY/PRINCIPAL FINDINGS: We compiled a comprehensive set of occurrence records on Hg. janthinomys, Hg. leucocelaenus, and Sabethes spp. from 1991-2019 using primary and secondary data sources. Linking these data with selected environmental and land-cover variables, we adopted a stacked regression ensemble modelling approach (elastic-net regularized GLM, extreme gradient boosted regression trees, and random forest) to predict the environmental suitability of these species across Brazil at a 1 km x 1 km resolution. We show that while suitability for each species varies spatially, high suitability for all species was predicted in the Southeastern region where recent outbreaks have occurred. By integrating data on NHP host reservoirs and human populations, our risk maps further highlight municipalities within the region that are prone to transmission and spillover. CONCLUSIONS/SIGNIFICANCE: Our maps of sylvatic vector suitability can help elucidate potential locations of sylvatic reservoirs and be used as a tool to help mitigate risk of future YF outbreaks and assist in vector surveillance. Furthermore, at-risk regions identified from our work could help disease control and elucidate gaps in vaccination coverage and NHP host surveillance.

Survival rate, blood feeding habits and sibling species composition of Aedes simpsoni complex: Implications for arbovirus transmission risk in East Africa.

Aedes simpsoni complex has a wide distribution in Africa and comprises at least three described sub-species including the yellow fever virus (YFV) vector Ae. bromeliae. To date, the distribution and relative contributions of the sub-species and/or subpopulations including bionomic characteristics in relation to YF transmission dynamics remain poorly studied. In this study conducted in two areas with divergent ecosystems: peri-urban (coastal Rabai) and rural (Rift Valley Kerio Valley) in Kenya, survival rate was estimated by parity in Ae. simpsoni s.l. mosquitoes sampled using CO2-baited BG Sentinel traps. We then applied PCR targeting the nuclear internal transcribed spacer 2 (ITS2), region followed by sequencing and phylogenetic analytics to identify the sibling species in the Ae. simpsoni complex among parous and blood fed cohorts. Our results show that Ae. bromeliae was the most dominant sub-species in both areas, exhibiting high survival rates, human blood-feeding, and potentially, high vectorial capacity for pathogen transmission. We document for the first time the presence of Ae. lilii in Kenya and potentially yet-to-be described species in the complex displaying human feeding tendencies. We also infer a wide host feeding range on rodents, reptile, and domestic livestock besides humans especially for Ae. bromeliae. This feeding trend could likely expose humans to various zoonotic pathogens. Taken together, we highlight the utility of genotype-based analyses to generate precision surveillance data of vector populations for enhanced disease risk prediction and to guide cost-effective interventions (e.g. YF vaccinations).

Oviposition activity of Haemagogus leucocelaenus (Diptera: Culicidae) during the rainy and dry seasons, in areas with yellow fever virus circulation in the Atlantic Forest, Rio de Janeiro, Brazil.

The present study aims to analyze the effectiveness of ovitraps in the capture of Hg leucocelaenus eggs and evaluate the influence of the dry and rainy seasons on their abundance and hatching rates. The eggs were collected in the Atlantic Forest of State of Rio de Janeiro, Brazil, an area in which the yellow fever virus is known to circulate. We distributed 15 ovitraps in three sampling points, with five ovitraps per point. We distributed 15 ovitraps in three sampling points on trees within a forested area, which were sequentially numbered, monitored, and replaced every two weeks from October 2016 to April 2018. There was a high dominance of Hg. leucocelaenus eggs (98.4%) and a variation in egg hatching rates between the wet and dry seasons. These rates were 1.5 times higher in the rainy season than in the dry season. The rainy season also showed a greater abundance of eggs and higher values of ovitrap positivity and egg density indexes in the installed ovitraps. The abundances of Hg. leucocelaenus eggs were positively correlated with mean monthly temperature and air humidity but not significantly correlated with accumulated precipitation. These results, as well as their implications for the possible use of ovitraps to monitor vector mosquitoes of yellow fever in the study region, are discussed.

Radio-frequency exposure of the yellow fever mosquito (A. aegypti) from 2 to 240 GHz.

Fifth generation networks (5G) will be associated with a partial shift to higher carrier frequencies, including wavelengths comparable in size to insects. This may lead to higher absorption of radio frequency (RF) electromagnetic fields (EMF) by insects and could cause dielectric heating. The yellow fever mosquito (Aedes aegypti), a vector for diseases such as yellow and dengue fever, favors warm climates. Being exposed to higher frequency RF EMFs causing possible dielectric heating, could have an influence on behavior, physiology and morphology, and could be a possible factor for introduction of the species in regions where the yellow fever mosquito normally does not appear. In this study, the influence of far field RF exposure on A. aegypti was examined between 2 and 240 GHz. Using Finite Difference Time Domain (FDTD) simulations, the distribution of the electric field in and around the insect and the absorbed RF power were found for six different mosquito models (three male, three female). The 3D models were created from micro-CT scans of real mosquitoes. The dielectric properties used in the simulation were measured from a mixture of homogenized A. aegypti. For a given incident RF power, the absorption increases with increasing frequency between 2 and 90 GHz with a maximum between 90 and 240 GHz. The absorption was maximal in the region where the wavelength matches the size of the mosquito. For a same incident field strength, the power absorption by the mosquito is 16 times higher at 60 GHz than at 6 GHz. The higher absorption of RF power by future technologies can result in dielectric heating and potentially influence the biology of this mosquito.

Real-Time Genomic Surveillance during the 2021 Re-Emergence of the Yellow Fever Virus in Rio Grande do Sul State, Brazil.

The 2021 re-emergence of yellow fever in non-human primates in the state of Rio Grande do Sul (RS), southernmost Brazil, resulted in the death of many howler monkeys (genus Alouatta) and led the state to declare a Public Health Emergency of State Importance, despite no human cases reported. In this study, near-complete genomes of yellow fever virus (YFV) recovered from the outbreak were sequenced and examined aiming at a better understanding of the phylogenetic relationships and the spatio-temporal dynamics of the virus distribution. Our results suggest that the most likely sequence of events involved the reintroduction of YFV from the state of São Paulo to RS through the states of Paraná and Santa Catarina, by the end of 2020. These findings reinforce the role of genomic surveillance in determining the pathways of distribution of the virus and in providing references for the implementation of preventive measures for populations in high risk areas.

Suppressing mosquito populations with precision guided sterile males.

The mosquito Aedes aegypti is the principal vector for arboviruses including dengue/yellow fever, chikungunya, and Zika virus, infecting hundreds of millions of people annually. Unfortunately, traditional control methodologies are insufficient, so innovative control methods are needed. To complement existing measures, here we develop a molecular genetic control system termed precision-guided sterile insect technique (pgSIT) in Aedes aegypti. PgSIT uses a simple CRISPR-based approach to generate flightless females and sterile males that are deployable at any life stage. Supported by mathematical models, we empirically demonstrate that released pgSIT males can compete, suppress, and even eliminate mosquito populations. This platform technology could be used in the field, and adapted to many vectors, for controlling wild populations to curtail disease in a safe, confinable, and reversible manner.

Yellow Fever Outbreak in Eastern Senegal, 2020-2021.

Yellow fever virus remains a major threat in low resource countries in South America and Africa despite the existence of an effective vaccine. In Senegal and particularly in the eastern part of the country, periodic sylvatic circulation has been demonstrated with varying degrees of impact on populations in perpetual renewal. We report an outbreak that occurred from October 2020 to February 2021 in eastern Senegal, notified and managed through the synergistic effort yellow fever national surveillance implemented by the Senegalese Ministry of Health in collaboration with the World Health Organization, the countrywide 4S network set up by the Ministry of Health, the Institut Pasteur de Dakar, and the surveillance of arboviruses and hemorrhagic fever viruses in human and vector populations implemented since mid 2020 in eastern Senegal. Virological analyses highlighted the implication of sylvatic mosquito species in virus transmission. Genomic analysis showed a close relationship between the circulating strain in eastern Senegal, 2020, and another one from the West African lineage previously detected and sequenced two years ago from an unvaccinated Dutch traveler who visited the Gambia and Senegal before developing signs after returning to Europe. Moreover, genome analysis identified a 6-nucleotide deletion in the variable domain of the 3'UTR with potential impact on the biology of the viral strain that merits further investigations. Integrated surveillance of yellow fever virus but also of other arboviruses of public health interest is crucial in an ecosystem such as eastern Senegal.

[Recrudescence of yellow fever in Chad: case report of the last confirmed case in the health district of Lai-Chad]. / Recrudescence de la fièvre jaune au Tchad: à propos du dernier cas confirmé dans le district sanitaire de Lai-Tchad.

Yellow fever (YF) is a viral haemorrhagic fever caused by yellow fever virus transmitted by Aedes mosquitoes. Since 2013, in Chad, four cases of yellow fever have been detected and confirmed as part of the national fever surveillance program. We here report the last clinical case confirmed in the health district of Lai. The patient was a 57-year-old man with no significant medical and surgical history and unknown immunisation status. He consulted on April 21st, 2020 for fever, moderate to low abundance jaundice and epistaxis (nosebleed) and painful hepatomegaly. Paraclinical examinations, such as RT-PCR, objectified yellow fever virus in post-mortem tissue sample. Thus, confirmed yellow fever cases in this district, the low level of vaccination coverage, the circulation of the virus and the presence of vector in the country should warn of a real threat of reemergence of yellow fever in Chad.

Mosquito-Associated Viruses and Their Related Mosquitoes in West Africa.

Mosquito-associated viruses (MAVs), including mosquito-specific viruses (MSVs) and mosquito-borne (arbo)viruses (MBVs), are an increasing public, veterinary, and global health concern, and West Africa is projected to be the next front for arboviral diseases. As in-depth knowledge of the ecologies of both western African MAVs and related mosquitoes is still limited, we review available and comprehensive data on their diversity, abundance, and distribution. Data on MAVs' occurrence and related mosquitoes were extracted from peer-reviewed publications. Data on MSVs, and mosquito and vertebrate host ranges are sparse. However, more data are available on MBVs (i.e., dengue, yellow fever, chikungunya, Zika, and Rift Valley fever viruses), detected in wild and domestic animals, and humans, with infections more concentrated in urban areas and areas affected by strong anthropogenic changes. Aedes aegypti, Culex quinquefasciatus, and Aedes albopictus are incriminated as key arbovirus vectors. These findings outline MAV, related mosquitoes, key knowledge gaps, and future research areas. Additionally, these data highlight the need to increase our understanding of MAVs and their impact on host mosquito ecology, to improve our knowledge of arbovirus transmission, and to develop specific strategies and capacities for arboviral disease surveillance, diagnostic, prevention, control, and outbreak responses in West Africa.

Database of Sabethes and Haemagogus (Diptera: Culicidae) in Argentina: Sylvatic Vectors of the Yellow Fever Virus.

Yellow fever is an endemic disease in America caused by an arbovirus that circulates in the sylvatic cycle between nonhuman primates and mosquitoes of the genera Sabethes Robineau-Desvoidy and Haemagogus Williston. The main goal of this work is to report the distribution patterns of these genera in Argentina through an updated database built from published records as well as from own sample collections. These genera are represented in Argentina by a total of 18 species distributed in 14 provinces and 10 ecoregions. The ecoregions with greatest biodiversity were Paranense Forest, Yungas, Campos and Malezales. This database will also allow generating distribution maps for these mosquito genera, and their respective species in Argentina, to establish areas with high probability of viral circulation that are an essential input for vector surveillance, as a tool for public health decision-makers.

Incidence, drivers and global health implications of the 2019/2020 yellow fever sporadic outbreaks in Sub-Saharan Africa.

The 2019 and 2020 sporadic outbreaks of yellow fever (YF) in Sub-Saharan African countries had raised a lot of global health concerns. This article aims to narratively review the vector biology, YF vaccination program, environmental factors and climatic changes, and to understand how they could facilitate the reemergence of YF. This study comprehensively reviewed articles that focused on the interplay and complexity of YF virus (YFV) vector diversity/competence, YF vaccine immunodynamics and climatic change impacts on YFV transmission as they influence the 2019/2020 sporadic outbreaks in Sub-Saharan Africa (SSA). Based on available reports, vectorial migration, climatic changes and YF immunization level could be reasons for the re-mergence of YF at the community and national levels. Essentially, the drivers of YFV infection due to spillover are moderately constant. However, changes in land use and landscape have been shown to influence sylvan-to-urban spillover. Furthermore, increased precipitation and warmer temperatures due to climate change are likely to broaden the range of mosquitoes' habitat. The 2019/2020 YF outbreaks in SSA is basically a result of inadequate vaccination campaigns, YF surveillance and vector control. Consequently, and most importantly, adequate immunization coverage must be implemented and properly achieved under the responsibility of the public health stakeholders.

Oviposition behavior of wild yellow fever vector mosquitoes (Diptera: Culicidae) in an Atlantic Forest fragment, Rio de Janeiro state, Brazil.

Although there are many studies on the control of mosquito vectors of the yellow fever virus (YFV) in tropical forests, there are still few ecological studies regarding abiotic factors effect on these mosquitoes. Here we characterize these effects on oviposition behavior, abundance, and diversity of mosquito vectors of YFV. The study was conducted in Córrego da Luz Municipal Park, in Casimiro de Abreu, Rio de Janeiro state, Brazil, from July 2018 to December 2019. Ovitraps were placed at ground level and 3 m high. The data were tested for normality using the Shapiro-Wilk test, followed by an independent sample analysis, the Mann-Whitney test. The Shannon Diversity Index was used to evaluate the abundance of mosquitos' eggs collected at both ground level and 3 m high. We highlight the presence of Haemagogus janthinomys and Hg. leucocelaenus, primary YFV vectors in forest areas. The abundance of Hg. leucocelaenus (63%), Hg. janthinomys (75%), and Aedes terrens (58%) was higher at the height of 3 m, while Ae. albopictus (52%) was higher at ground level. Aedes albopictus was positively correlated with temperature. Culicidae monitoring is essential for assessing the YFV transmission cycle in Atlantic forest fragments.

The global burden of yellow fever.

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.

Yellow fever in Asia-a risk analysis.

BACKGROUND: There 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. METHODS: Using 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. RESULTS: In 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. CONCLUSION: Despite 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.

Seasonal and inter-annual drivers of yellow fever transmission in South America.

In the last 20 years yellow fever (YF) has seen dramatic changes to its incidence and geographic extent, with the largest outbreaks in South America since 1940 occurring in the previously unaffected South-East Atlantic coast of Brazil in 2016-2019. While habitat fragmentation and land-cover have previously been implicated in zoonotic disease, their role in YF has not yet been examined. We examined the extent to which vegetation, land-cover, climate and host population predicted the numbers of months a location reported YF per year and by each month over the time-period. Two sets of models were assessed, one looking at interannual differences over the study period (2003-2016), and a seasonal model looking at intra-annual differences by month, averaging over the years of the study period. Each was fit using hierarchical negative-binomial regression in an exhaustive model fitting process. Within each set, the best performing models, as measured by the Akaike Information Criterion (AIC), were combined to create ensemble models to describe interannual and seasonal variation in YF. The models reproduced the spatiotemporal heterogeneities in YF transmission with coefficient of determination (R2) values of 0.43 (95% CI 0.41-0.45) for the interannual model and 0.66 (95% CI 0.64-0.67) for the seasonal model. For the interannual model, EVI, land-cover and vegetation heterogeneity were the primary contributors to the variance explained by the model, and for the seasonal model, EVI, day temperature and rainfall amplitude. Our models explain much of the spatiotemporal variation in YF in South America, both seasonally and across the period 2003-2016. Vegetation type (EVI), heterogeneity in vegetation (perhaps a proxy for habitat fragmentation) and land cover explain much of the trends in YF transmission seen. These findings may help understand the recent expansions of the YF endemic zone, as well as to the highly seasonal nature of YF.

Altered gene expression profile of Wolbachia pipientis wAlbB strain following transinfection from its native host Aedes albopictus to Aedes aegypti cells.

Wolbachia is an obligate intracellular bacterial symbiont prevalent among arthropods and nematodes. To survive and reproduce, Wolbachia interacts with and modifies host subcellular structures, while sensing and responding to changes within the cellular environment. In mutualistic associations, Wolbachia may provision the host with metabolites, or help to maintain the chemical homeostasis of the host cell. Some strains can rapidly invade insect populations by manipulating host reproductive biology, while also preventing viral replication, allowing their use in vector control of arthropod-borne viruses. The Aedes albopictus-derived strain wAlbB is promising in this regard. When transinfected into the Yellow fever mosquito, Aedes aegypti, wAlbB reaches high frequencies within wild populations, and strongly inhibits viral transmission. Despite its obvious potential, much is still unknown about the molecular interactions between Wolbachia and host that enable its use in vector control. Furthermore, most Wolbachia transinfection research to date has focused on host effects. In the current study, we used a cell line model to explore the effect of transinfection of wAlbB from Ae. albopictus to Ae. aegypti. Using RNA sequencing, we show that several genes associated with host-symbiont interactions were downregulated by transinfection, with the greatest downregulation exhibited by prophage-associated genes.

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.