Yellow Fever Virus Transmission Research Articles

Mechanisms of Flavivirus Cross-Protection against Yellow Fever in a Mouse Model.

The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector Aedes (Stegomyia.) aegypti is an enigma. An immunologically naïve population of over 2 billion resides in Asia, with most regions infested with the urban YF vector. One hypothesis for the lack of Asian YF, and absence of urban YF in the Americas for over 80 years, is that prior immunity to related flaviviruses like dengue (DENV) or Zika virus (ZIKV) modulates YFV infection and transmission dynamics. Here we utilized an interferon α/β receptor knock-out mouse model to determine the role of pre-existing dengue-2 (DENV-2) and Zika virus (ZIKV) immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice, but may or may not protect relative to disease outcomes. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance of re-assessing the risks associated with YF outbreak while accounting for prior immunity from flaviviruses that are endemic.

Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens

Background Because of yellow fever’s serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Methods Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). Results In total, five mothers (62.5%) were positive for YFV and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. Conclusions YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination.

Genomic epidemiology unveils the dynamics and spatial corridor behind the Yellow Fever virus outbreak in Southern Brazil.

Despite the considerable morbidity and mortality of yellow fever virus (YFV) infections in Brazil, our understanding of disease outbreaks is hampered by limited viral genomic data. Here, through a combination of phylogenetic and epidemiological models, we reconstructed the recent transmission history of YFV within different epidemic seasons in Brazil. A suitability index based on the highly domesticated Aedes aegypti was able to capture the seasonality of reported human infections. Spatial modeling revealed spatial hotspots with both past reporting and low vaccination coverage, which coincided with many of the largest urban centers in the Southeast. Phylodynamic analysis unraveled the circulation of three distinct lineages and provided proof of the directionality of a known spatial corridor that connects the endemic North with the extra-Amazonian basin. This study illustrates that genomics linked with eco-epidemiology can provide new insights into the landscape of YFV transmission, augmenting traditional approaches to infectious disease surveillance and control.

Ecological drivers of sustained enzootic yellow fever virus transmission in Brazil, 2017-2021.

Beginning December 2016, sylvatic yellow fever (YF) outbreaks spread into southeastern Brazil, and Minas Gerais state experienced two sylvatic YF waves (2017 and 2018). Following these massive YF waves, we screened 187 free-living non-human primate (NHPs) carcasses collected throughout the state between January 2019 and June 2021 for YF virus (YFV) using RTqPCR. One sample belonging to a Callithrix, collected in June 2020, was positive for YFV. The viral strain belonged to the same lineage associated with 2017-2018 outbreaks, showing the continued enzootic circulation of YFV in the state. Next, using data from 781 NHPs carcasses collected in 2017-18, we used generalized additive mixed models (GAMMs) to identify the spatiotemporal and host-level drivers of YFV infection and intensity (an estimation of genomic viral load in the liver of infected NHP). Our GAMMs explained 65% and 68% of variation in virus infection and intensity, respectively, and uncovered strong temporal and spatial patterns for YFV infection and intensity. NHP infection was higher in the eastern part of Minas Gerais state, where 2017-2018 outbreaks affecting humans and NHPs were concentrated. The odds of YFV infection were significantly lower in NHPs from urban areas than from urban-rural or rural areas, while infection intensity was significantly lower in NHPs from urban areas or the urban-rural interface relative to rural areas. Both YFV infection and intensity were higher during the warm/rainy season compared to the cold/dry season. The higher YFV intensity in NHPs in warm/rainy periods could be a result of higher exposure to vectors and/or higher virus titers in vectors during this time resulting in the delivery of a higher virus dose and higher viral replication levels within NHPs. Further studies are needed to better test this hypothesis and further compare the dynamics of YFV enzootic cycles between different seasons.

Vertical Distribution of Oviposition and Temporal Segregation of Arbovirus Vector Mosquitoes (Diptera: Culicidae) in a Fragment of the Atlantic Forest, State of Rio de Janeiro, Brazil.

Culicid species, which include potential vectors of yellow fever, are diverse and abundant, with species commonly co-occurring in certain sites. Studying these species can provide important insights into their vector potential and, consequently, epizootic cycles of arboviruses carried about by these vectors. Here, we evaluated the vertical distribution and temporal segregation of mosquito oviposition with emphasis on arbovirus vectors in a fragment of the Atlantic Forest in Casimiro de Abreu, Rio de Janeiro, Brazil. Two sampling points were selected: Fazenda Três Montes and the Reserva Natural de Propriedade Privada Morro Grande. Collections were carried out at two sites using 10 ovitraps installed on the vegetation cover at different heights (0, 2, 4, 6, and 8 m above ground level) and monitored monthly from July 2018 to December 2020. The hypotheses of temporal and vertical stratification were tested through a PERMANOVA, and the relationship of each species with the vertical distribution was evaluated individually through a correlation analysis. We collected a total of 3075 eggs, including four species of medical importance: Haemagogus leucocelaenus (n = 1513), Haemagogus janthinomys (n = 16), Aedes albopictus (n = 1097), and Aedes terrens (n = 449). We found that Hg. leucocelaenus had a positive relationship with height, exhibiting behavior that appears to benefit from higher heights. The abundance of Ae. terrens seemed to follow Hg. leucocelaenus, although we did not find a relationship with height for the former species. On the other hand, Ae. albopictus exhibited a negative relationship with height, becoming absent or outnumbered at higher strata. Our study site has already presented evidence of recent transmission of the wild yellow fever virus, supporting the need to carefully monitor the emergence of febrile diseases among residents in the surrounding areas and the local population.

Human-Biting Activity, Resting Behavior and Yellow Fever Virus Transmission Potential of Aedes Mosquitoes in Southwest Ethiopia

Yellow fever (YF) is an emerging and re-emerging arboviral disease transmitted through the bites of infected Aedes mosquitoes, primarily in the genus Aedes. Several outbreaks of yellow fever have been documented in southern Ethiopia. Four outbreaks have been documented since 2012, suggesting that southern Ethiopia is prone to YF outbreaks. Understanding the transmission cycle is pivotal to managing arboviral disease outbreaks, and the aims of the present study were to investigate the mosquito species that most likely contributed to the recent YF outbreaks and to study their behaviors. Therefore, the present study aimed to evaluate which species of Aedes mosquitoes contribute to the YF virus transmission, the outbreaks that have occurred and their behaviors (biting and resting) in the region. Two districts were selected on the basis of recent YF outbreak history. A longitudinal entomological survey was conducted to collect adult mosquitoes by using human landing catches (HLC), mechanical mouth aspirators and pyrethrum sprays. Collections were conducted twice a month for six months, from February 2019 to July 2020. The mosquitoes were identified by species by using morphological keys and molecular techniques. A total of 1689 mosquitoes were collected, of which 93.7% (1582/1689) were members of the genus Aedes and 6.3% (107/1689) of the genus Culex. A total of 58.7% (991/1689) of the mosquitoes were captured in the Ofa District and 41.3% (698/1689) from the Boko Dawula District. The largest number of mosquitoes, 97.9% (1653/1689), were collected during the wet season. A total of 1582 members of the Aedes simpsoni complex were collected, where 57.7% (913/1582) were from the Ofa District and 42.3% (669/1582) were from the Boko Dawula District. Molecular identification showed that members of the Aedes simpsoni complex accounted for 99.5% (404/406), while Aedes aegypti, detected only in the Ofa District, accounted for only 0.5% (2/406). The mosquitoes were pooled and tested for YFV, dengue virus (DENV, serotype 1–4) and chikungunya virus (CHKV) by using qPCR. None of the 934 Aedes simpsoni tested were positive for any arboviruses. The human-biting activities of Ae. simpsoni complex were peaked between 8:00–9:00 and 16:00–17:00, mostly outdoors, both within the villages and the forests. The largest numbers of Aedes simpsoni complex resting mosquitoes were collected from the leaves of the Abyssinian banana, Ensete ventricosum, suggesting that they are the preferred resting places. Although the tested Ae. simpsoni complex was negative for arboviruses; the morning and afternoon activities of the species complex coincide with peak human outdoor activities in these areas and may therefore pose the highest risk of transmitting YFV to humans. The extremely low abundance of Aedes aegypti suggests a minor role in arbovirus transmission in southern Ethiopia. It is of great importance that expanded surveillance activities of arboviruses to include reservoir hosts and sylvatic vectors to the chances of devising and implementing effective control measures.

Ecological, Genetic, and Phylogenetic Aspects of YFV 2017-2019 Spread in Rio de Janeiro State.

In Brazil, a yellow fever (YF) outbreak was reported in areas considered YF-free for decades. The low vaccination coverage and the increasing forest fragmentation, with the wide distribution of vector mosquitoes, have been related to yellow fever virus (YFV) transmission beyond endemic areas since 2016. Aiming to elucidate the molecular and phylogenetic aspects of YFV spread on a local scale, we generated 43 new YFV genomes sampled from humans, non-human primates (NHP), and primarily, mosquitoes from highly heterogenic areas in 15 localities from Rio de Janeiro (RJ) state during the YFV 2016-2019 outbreak in southeast Brazil. Our analysis revealed that the genetic diversity and spatial distribution of the sylvatic transmission of YFV in RJ originated from at least two introductions and followed two chains of dissemination, here named the YFV RJ-I and YFV RJ-II clades. They moved with similar dispersal speeds from the north to the south of the RJ state in parallel directions, separated by the Serra do Mar Mountain chain, with YFV RJ-I invading the north coast of São Paulo state. The YFV RJ-I clade showed a more significant heterogeneity across the entire polyprotein. The YFV RJ-II clade, with only two amino acid polymorphisms, mapped at NS1 (I1086V), present only in mosquitoes at the same locality and NS4A (I2176V), shared by all YFV clade RJ-II, suggests a recent clustering of YFV isolates collected from different hosts. Our analyses strengthen the role of surveillance, genomic analyses of YVF isolated from other hosts, and environmental studies into the strategies to forecast, control, and prevent yellow fever outbreaks.

Usefulness of an in vitro-transcribed RNA control for the detection and quantification of Yellow fever virus through real-time reverse transcription-polymerase chain reaction

IntroductionUnvaccinated individuals in endemic areas with proven enzootic transmission of Yellow fever virus are at risk of infection due to a dramatic shift in the epidemiology of the disease over recent years. For this reason, epidemiological surveillance and laboratory confirmation of cases have become mandatory. ObjectiveTo develop and test a control RNA for YFV detection through real-time RT-PCR. MethodsA 437-bp insert containing the T7 promoter and the target sequences for two different in-house protocols was designed in the context of the pUC57 vector and obtained through gene synthesis. After T7-driven in vitro transcription, standard curves were developed for Log10 serial dilutions of the YFV control RNA with 8 replicates. ResultsA dynamic range of quantification of 10 orders of magnitude was observed with a limit of detection of 6.3 GCE/µL (95% CI, 2.6 to 139.4 GCE/µL). ConclusionThe plasmid construct is available for YFV molecular test validation on clinical, entomological, and epizootic samples.

Back to Where It Was First Described: Vectors of Sylvatic Yellow Fever Transmission in the 2017 Outbreak in Espírito Santo, Brazil.

Evidence of sylvatic yellow fever was first reported in Atlantic Forest areas in Espírito Santo, Brazil, during a yellow fever virus (YFV) outbreak in 1931. An entomological survey was conducted in six forest sites during and after an outbreak reported ~80 years after the last case in the area. Among 10,658 mosquitoes of 78 species, Haemagogus leucocelaenus, and Hg. janthinomys/capricornii were considered the main vectors as they had a relatively high abundance, co-occurred in essentially all areas, and showed high YFV infection rates. Sabethes chloropterus, Sa. soperi, Sa. identicus, Aedes aureolineatus, and Shannoniana fluviatilis may have a secondary role in transmission. This is the first report of Sa. identicus, Ae. aureolineatus, and Sh. fluviatilis infected with YFV. Our study emphasizes the importance of entomological monitoring and maintenance of high vaccination coverage in receptive areas to YFV transmission.

Yellow fever virus investigation in tissues of vampire bats Desmodus rotundus during a wild yellow fever outbreak in Brazilian Atlantic Forest

In the last decade a large outbreak of Yellow Fever (YF) has been observed in Brazilian Atlantic Forest region, traditionally a non-endemic area. In this scenario, the role of wild mammal species as YF reservoirs can be questioned, especially the hematophagous bat, Desmodus rotundus. So, the objective of this study was to analyze molecularly the presence of the YF virus (YFV) in hematophagous bats during a YF outbreak in Brazil. Twenty-one samples were collected from seven adult male hematophagous bats D. rotundus. As YFV is considered a viscerotropic and neurotropic virus, samples of liver, kidney and brain were collected and molecularly analyzed using the RT qPCR technique. The animals were captured according to ethical protocols during a YF outbreak in Brazil in 2017, from a region of the Brazilian Atlantic Forest. The results revealed that the analyzed tissue samples were not infected with the YFV. The negative results for this bat species allow us to infer that other animals may be reservoirs of this virus in this ecosystem and they probably have not been identified yet. Therefore, health surveillance actions are essential to monitor the role of wild animals in the YF dissemination in Brazilian Atlantic Forest and alert to the possibility of new geographic amplification of areas where YF occurs. This research encourages the new search about the role of wild animals on YFV transmission and reinforces the importance of epidemiological surveillance in the transmission of human infectious diseases.

Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens.

Because of yellow fever's serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). In total, five mothers (62.5%) were positive for YFV and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother's YF vaccination.

Categorization by Score of Mosquito Species (Diptera: Culicidae) Related to Yellow Fever Epizootics in Argentina.

The mosquito-borne yellow fever virus (YFV) is the cause of a zoonotic disease, with both sylvatic and urban cycles. Some mosquito species have been associated directly with transmission of the virus in South America, although the importance given to each species varies depending on the bibliography, geographical location, or year of publication. For Argentina, few publications have assessed the involvement of mosquito species, especially those included in the sylvatic cycle. Therefore, the goal of our paper was to gather all the information available in South America and categorize all mosquito species potentially involved in the YFV transmission cycle in Argentina according to incriminating vector criteria. Based on three main characteristics ('Hosts', 'Mosquito vector', and 'YF outbreak'), we generated scales of importance by species, one exclusively for Argentina and another for all of South America, Sabethes albiprivus Theobald, 1903 was the most important species in Argentina; whereas the most important species in South America were Haemagogus janthinomys Dyar 1921, Hg. leucocelaenus Dyar and Shannon, 1924, and Sa. chloropterus Von Humboldt, 1819. Our review highlights the lack of research that evaluates the importance of these species for YFV transmission in Argentina, while serving as a starting point to establish priorities for research on the bionomics and vector status of these species.

An ecological niche model to predict the geographic distribution of Haemagogus janthinomys, Dyar, 1921 a yellow fever and Mayaro virus vector, in South America.

Yellow fever virus (YFV) has a long history of impacting human health in South America. Mayaro virus (MAYV) is an emerging arbovirus of public health concern in the Neotropics and its full impact is yet unknown. Both YFV and MAYV are primarily maintained via a sylvatic transmission cycle but can be opportunistically transmitted to humans by the bites of infected forest dwelling Haemagogus janthinomys Dyar, 1921. To better understand the potential risk of YFV and MAYV transmission to humans, a more detailed understanding of this vector species’ distribution is critical. This study compiled a comprehensive database of 177 unique Hg. janthinomys collection sites retrieved from the published literature, digitized museum specimens and publicly accessible mosquito surveillance data. Covariate analysis was performed to optimize a selection of environmental (topographic and bioclimatic) variables associated with predicting habitat suitability, and species distributions modelled across South America using a maximum entropy (MaxEnt) approach. Our results indicate that suitable habitat for Hg. janthinomys can be found across forested regions of South America including the Atlantic forests and interior Amazon.

Bacterial diversity in Haemagogus leucocelaenus (Diptera: Culicidae) from Vale do Ribeira, São Paulo, Brazil

IntroductionMosquitoes (Diptera: Culicidae) are vectors that transmit numerous pathogens to humans and other vertebrates. Haemagogus leucocelaenus is a mosquito associated with transmission of yellow fever virus. The insect gut harbors a variety of microorganisms that can live and multiply within it, thus contributing to digestion, nutrition, and development of its host. The composition of bacterial communities in mosquitoes can be influenced by both biotic and abiotic factors. The goal of this study was to investigate the bacterial diversity of Hg. leucocelaenus and verify the differences between the bacterial communities in Hg. leucocelaenus from three different locations in the Atlantic tropical rain forest and southeastern state of São Paulo State, Brazil.ResultsThe phylum Proteobacteria was found in mosquitoes collected from the three selected study sites. More than 50% of the contigs belong to Wolbachia, followed by 5% Swaminathania, and 3% Acinetobacter. The genus Serratia was found in samples from two locations.ConclusionsWolbachia was reported for the first time in this species and may indicates that the vector competence of the populations of the species can vary along its geographical distribution area. The presence of Serratia might facilitate viral invasion caused by the disruption of the midgut barrier via action of the SmEnhancin protein, which digests the mucins present in the intestinal epithelium.

Risk assessment of urban yellow fever virus transmission in Kenya: is Aedes aegypti an efficient vector?

ABSTRACT The absence of urban yellow fever epidemics in East Africa remains a mystery amidst the proliferation of Aedes aegypti in this region. To understand the transmission dynamics of the disease, we tested urban (Mombasa, Kisumu, and Nairobi) Aedes mosquito populations in Kenya for their susceptibility to an East African yellow fever virus (YFV) genotype. Overall, 22% (n = 805) of the Ae. aegypti that were orally challenged with an infectious dose of YFV had a midgut infection, with comparable rates for Mombasa and Kisumu (χ2 = 0.35, df = 1, P = 0.55), but significantly lower rates for Nairobi (χ2 ≥ 11.08, df = 1, P ≤ 0.0009). Variations in YFV susceptibility (midgut infection) among Ae. aegypti subspecies were not associated with discernable cytochrome c oxidase subunit 1 gene haplotypes. Remarkably, no YFV dissemination or transmission was observed among the orally challenged Ae. aegypti populations. Moreover, Ae. aegypti mosquitoes that were intrathoracically inoculated with YFV failed to transmit the virus via capillary feeding. In contrast, dissemination (oral exposure) and transmission (intrathoracic inoculation) of YFV was observed among a few peri-domestic Ae. bromeliae mosquitoes (n = 129) that were assessed from these urban areas. Our study highlights an inefficient urban Ae. aegypti population, and the potential for Ae. bromeliae in sustaining an urban YFV transmission in Kenya. An assessment of urban Ae. aegypti susceptibility to other YFV genotypes, and vector potential of urban Ae. bromeliae populations in Kenya is recommended to guide cost-effective vaccination.

Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens

Background: Because of yellow fever’s serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Methods: Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). Results: In total, five mothers (62.5%) were positive for YFV IgM and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. Conclusions: YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination.

Diversity of Mosquitoes (Diptera: Culicidae) in an Atlantic Forest Urban Park, Salvador, Brazil.

We identified mosquito species (Diptera: Culicidae) in an Atlantic Forest fragment located in a large urban park in Salvador, Brazil, one year after a citywide epizootic of yellow fever virus (YFV). Between May 2 and August 2, 2018, adult mosquitoes were collected using the human attraction method, followed by trapping with hand-nets, and CO2-baited light traps placed at ground level and in the canopy. We collected a total of 11,914 mosquitoes, which belonged to three tribes, five genera, and at least seven species. The most abundant taxa captured by CO2-baited light traps were Culex quinquefasciatus (Say, Diptera: Culicidae) Limatus spp. (Diptera: Culicidae), and Wyeomyia spp. (Diptera: Culicidae), while by human attraction, Cx. quinquefasciatus, Wyeomyia spp., and Aedes albopictus (Skuse, Diptera: Culicidae) were captured most often. The diversity of mosquitoes by species was greater in the park area with restinga vegetation compared to the area with dense rainforest. Although vectors commonly associated with sylvatic YFV transmission were not captured, we collected several species capable of transmission of other arboviruses. Given the high likelihood of encounters between mosquitoes and human visitors in environments, such as the one studied, periodic entomological surveys to determine the risk of arbovirus transmission in these settings are warranted.

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

BackgroundThe 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 findingsUsing 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/SignificanceThe 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.

Transmission of yellow fever vaccine virus from breast feeding mothers to their infants: reporting of yellow fever virus (YFV) RNA detection in milk specimens

Background: Because of yellow fever’s serious impact on health, vaccination is the principal strategy to control the disease. Administration of the yellow fever vaccine to breastfeeding women should be before they complete 9 months post-delivery, in order to prevent transmission of the yellow fever vaccine virus to their infants through breast feeding. This study aimed to confirm whether the excretion of yellow fever vaccine virus is in milk of vaccinated breastfeeding mothers and to confirm the probable transmission to their infants through breast milk. Methods: Samples were taken as follows: one serum specimen was taken 3-14 days after the date of the vaccination, and breast milk specimens were taken at four different time points between 3-4 days apart. Specimens were obtained from eight nursing mothers, who received the YVF vaccine (17DD). Mothers were asymptomatic before and after the vaccine administration but their infants developed symptoms after administration. Maternal serum samples were tested for YFV specific IgM antibodies through immuno-fluorescent assay (IFA). RNA was extracted from serum and breast milk specimens and YFV RNA screened using real-time polymerase chain reaction (RT-PCR). Results: In total, five mothers (62.5%) were positive for YFV and two mothers (25%) had YFV RNA in serum. Among milk specimens, YFV RNA was detected during the four different mentioned collection times as follows (positive milk specimens/total milk specimens): 3/8 (37.5 %), 4/6 (66.6%) and 1/4(25%). RNA was completely undetectable in the last collection time. Conclusions: YFV transmission from mothers to their babies through breast-feeding was highly probable indicated by the temporal relationship to mother’s YF vaccination.

Epizootic dynamics of yellow fever in forest fragments: An agent-based model to explore the influence of vector and host parameters

Yellow fever (YF) is an acute infectious hemorrhagic disease caused by the yellow fever virus (YFV) and transmitted to humans by infected mosquitoes. In Brazil and other South American countries, the disease has been restricted to the sylvatic cycle, in which the virus circulates among mosquitoes and non-human primates in forested areas. Frequent outbreaks in the Amazon basin that spread to other Brazilian ecoregions have been observed in recent years. The most recent started in 2014 and spread to forests in densely populated areas on the Brazilian Atlantic Coast, resulting in the death of hundreds of humans and thousands of monkeys. However, the underlying ecological mechanisms that support YFV amplification and the severity of an epizootic and persistence of the virus on a microgeographic scale in these forest patches are still poorly understood. Here, we developed an agent-based model that simulates the dynamics of YFV transmission in a hypothetical forest fragment. The proposed model contains individual agents representing mosquitoes, breeding sites, howler monkeys (Alouatta) and other vertebrate species living and interacting in an environment where the YFV has emerged. The model simulations aimed to investigate the isolated and interaction effects of important input parameters linked to mosquitoes, monkeys, the environment and hypothetical alternative hosts on the following outcomes: (1) maximum proportion of infected mosquitoes, (2) proportion of dead monkeys and (3) YFV persistence in the environment. Local and global sensitivity analyses were used to assess the influence of different sets of input parameter values on the outputs. The model simulations indicated that mosquito abundance had the greatest influence on the outputs and made a major contribution to monkey mortality. Additionally, most of the variation in the outputs was due to complex and indirect effects of the different input parameters. These results suggest that mosquito density is one of the main factors responsible for YFV amplification during epizootics and reinforce the hypothesis that the severity and persistence of an outbreak depend on a complex web of interactions between different factors associated with vectors, hosts and the environment.