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1.
J Virol ; 2019 Dec 04.
Article in English | MEDLINE | ID: mdl-31801869

ABSTRACT

The Amazon basin is home to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these, Oropouche orthobunyavirus (OROV) is a relatively understudied member of the genus Orthobunyavirus, family Peribunyaviridae, that causes periodic outbreaks in human populations in Brazil and other South American countries. Although several studies have described the genetic diversity of the virus, the evolutionary processes that shape the OROV genome remain poorly understood. Here we present a comprehensive study of the genomic dynamics of OROV that encompasses phylogenetic analysis, evolutionary rate estimates, inference of natural selective pressures, recombination and reassortment, and structural analysis of OROV variants. Our study includes all available published sequences, as well as a set of new OROV genomes sequences obtained from patients in Ecuador, representing the first set of genomes from this country. Our results show differing evolutionary processes on the three segments that comprise the viral genome. We infer differing times of the most recent common ancestors (TMRCAs) of the genome segments and propose this can be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites, and codons that evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of OROV through a combined phylogenetic and structural approach.Importance The emergence and re-emergence of pathogens such as Zika virus (ZIKV), Chikungunya virus (CHIKV) and yellow fever virus (YFV) have drawn attention towards other co-circulating arboviruses in South America. Oropouche virus (OROV) is a poorly-studied pathogen responsible for over a dozen outbreaks since the early 1960s, and represents a public health burden to countries such as Brazil, Panama and Peru. OROV is likely underreported as its symptomatology can be easily confounded with other febrile illnesses (e.g. dengue fever and leptospirosis), and point-of-care testing for the virus is still uncommon. With limited data, there is a need to optimise the information currently available. Analysis of OROV genomes can help us understand how the virus circulates in nature and can reveal the evolutionary forces that shape the genetic diversity of the virus, which has implications for molecular diagnostics and the design of potential vaccines.

2.
Pediatr Infect Dis J ; 2019 Nov 07.
Article in English | MEDLINE | ID: mdl-31725551

ABSTRACT

Yellow fever is an endemic disease in tropical areas in America and Africa. We report a case where the wild-type yellow fever virus was detected in a breast milk sample of a 33-year-old woman, from a rural area in the municipality of São Paulo, thus highlighting a potential risk for transmission of yellow fever virus through breast-feeding.

3.
Hum Vaccin Immunother ; : 1-4, 2019 Nov 14.
Article in English | MEDLINE | ID: mdl-31634051

ABSTRACT

Yellow fever has been recently described in nonurban areas of Brazil despite 80 years of commercial vaccine use. Although the disease does not spread fear in the general population as it did in the past, yellow fever virus continues to cause many cases of severe disease. Persistence of the virus in the host is a new mechanism to be considered in the pathology of the disease. Immunization with a fractional dose of vaccine during emergency situations needs to be evaluated for antibody duration, and new and improved vaccines should be considered.

4.
J Virol ; 2019 Oct 09.
Article in English | MEDLINE | ID: mdl-31597773

ABSTRACT

The recent re-emergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the virus' rapid dissemination in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil we generated 18 complete and near-complete genomes from the peak of the epidemic curve from non-human primates (NHPs) and human infected cases across Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic YFV was re-introduced from Minas Gerais to Espírito Santo and Rio de Janeiro states multiple times between 2016 to 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in the understanding arbovirus epidemics.IMPORTANCE Arbovirus infections in Brazil including yellow fever, dengue, zika and chikungunya result in considerable morbidity and mortality and are pressing public health concerns. However, our understanding of these outbreaks is hampered by limited availability genomic data. In this study, we investigated the genetic diversity and spatial distribution of YFV during the current outbreak by analyzing genomic data from areas in southeastern Brazil not covered by other previous studies. To gain insights into the routes of YFV introduction and dispersion, we tracked the virus by sequencing YFV genomes sampled from non-human primates and infected patients from the southeastern region. Our study provides an understanding of how YFV initiates transmission in new Brazilian regions and illustrates that genomics in field can augment traditional approaches to infectious disease surveillance and control.

5.
Sci Rep ; 9(1): 13047, 2019 Sep 10.
Article in English | MEDLINE | ID: mdl-31506595

ABSTRACT

In an attempt to control the mosquito-borne diseases yellow fever, dengue, chikungunya, and Zika fevers, a strain of transgenically modified Aedes aegypti mosquitoes containing a dominant lethal gene has been developed by a commercial company, Oxitec Ltd. If lethality is complete, releasing this strain should only reduce population size and not affect the genetics of the target populations. Approximately 450 thousand males of this strain were released each week for 27 months in Jacobina, Bahia, Brazil. We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27-30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes.

6.
J Med Entomol ; 2019 Sep 27.
Article in English | MEDLINE | ID: mdl-31559435

ABSTRACT

Dengue, yellow fever, Zika, and chikungunya arboviruses are endemic in tropical countries and are transmitted by Aedes aegypti. Resistant populations of this mosquito against chemical insecticides are spreading worldwide. This study aimed to evaluate the biological effects of exposure of pesticide-sensitive Ae. aegypti larvae (Rockefeller) to conidia of the entomopathogen, Metarhizium brunneum, laboratory strains ARSEF 4556 and V275, and any synergistic activity of phenylthiourea (PTU). In addition, to investigate the nature of any cross-resistance mechanisms, these M. brunneum strains were tested against the Rockefeller larvae and two temephos- and deltamethrin-resistant wild mosquito populations from Rio de Janeiro. Treatment of Rockefeller larvae with 106 conidia/ml of ARSEF 4556 and V275 fungal strains resulted in significant decreased survival rates to 40 and 53.33%, respectively (P < 0.0001), compared with untreated controls. In contrast, exposure to 104 or 105 conidia/ml showed no such significant survival differences. However, the addition of PTU to the conidia in the bioassays significantly increased mortalities in all groups and induced a molt block. Experiments also showed no differences in Ae. aegypti mortalities between the fungal treated, wild pesticide-resistant populations and the Rockefeller sensitive strain. The results show the efficacy of M. brunneum in controlling Ae. aegypti larvae and the synergistic role of PTU in this process. Importantly, there was no indication of any cross-resistance mechanisms between Ae. aegypti sensitive or resistant to pesticides following treatment with the fungi. These results further support using M. brunneum as an alternative biological control agent against mosquito populations resistant to chemical insecticides.

7.
Mem Inst Oswaldo Cruz ; 114: e190098, 2019.
Article in English | MEDLINE | ID: mdl-31411310

ABSTRACT

BACKGROUND: Dengue virus (DENV) has circulated in Brazil for over 30 years. During this time, one serotype has cyclically replaced the other, until recently, when all four distinct serotypes began to circulate together. Persistent circulation of DENV for long time periods makes sequential infections throughout a person's life possible. After primary DENV infection, life-long immunity is developed for the infecting serotype. Since DENV and Zika virus (ZIKV) are antigenically similar, the possibility of cross-reactions has attracted attention and has been demonstrated in vitro. OBJECTIVE: The aim of this study was to investigate whether immune-sera from DENV and ZIKV infected patients would cross-react in vitro with other Flaviviridae family members. METHODS: Cross-reaction of the studied samples with yellow fever virus (YFV), West Nile virus (WNV), Rocio virus (ROCV), Saint Louis virus (SLEV) and Ilheus virus (ILHV) has been investigated by plaque reduction neutralisation test (PRNT) and the antibody-dependent enhancement (ADE) by flow-cytometry. FINDINGS: Antibodies against ZIKV and DENV virus cross-reacted with other flaviviruses either neutralising or enhancing the infection. Thus, viral entrance into FcRFcɣRII-expressing cells were influenced by the cross-reactive antibodies. ZIKV or DENV immune sera enhanced cellular infection by WNV, ILHV, ROCV and SLEV. Finally, DENV immune sera presented higher neutralising activity for YFV and SLEV. While ZIKV immune sera neutralised WNV, ILHV and ROCV with high frequencies of positivity. MAIN CONCLUSIONS: The co-circulation of those viruses in the same area represents a risk for the development of severe infections if they spread throughout the country. Successive flavivirus infections may have an impact on disease pathogenesis, as well as on the development of safe vaccine strategies.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Dengue Virus/immunology , Zika Virus/immunology , Cross Reactions/immunology , Flavivirus/classification , Flavivirus/immunology , Flow Cytometry , Humans , Neutralization Tests
8.
PLoS One ; 14(8): e0220773, 2019.
Article in English | MEDLINE | ID: mdl-31374109

ABSTRACT

Aedes albopictus is an invasive mosquito species that has spread globally and can transmit several arboviruses, including dengue, chikungunya and yellow fever. The species was first reported in Brazil in 1986 and since then has been found in 24 of the 27 Brazilian states, often in peri-urban environments close to highly urbanized areas. To date, population genetics of this important mosquito in areas in the city of São Paulo has not been investigated. In this study, we used 12 microsatellite loci to investigate the microgeographic population genetics of Ae. albopictus, which is present throughout the city of São Paulo. All the analyses revealed structuring of the populations studied, divided into two groups with restricted gene flow between them and without evidence of isolation by distance. We propose two hypotheses to explain the results: (i) low dispersal capability-limited gene flow between populations is due to the low dispersal capability inherent to Ae. albopictus; and (ii) multiple introductions-the structure identified here results from multiple introductions, which led to different dispersal patterns within the city and more genetic heterogeneity. The ability of Ae. albopictus to invade new areas and expand may explain why these mosquito populations appear to be well established and thriving in the city of São Paulo.

9.
Article in English | MEDLINE | ID: mdl-31380302

ABSTRACT

The present study shows that the most prominent human arboviruses worldwide (dengue viruses 1, 2, 3, and 4, Chikungunya virus, and Zika virus) can infect wild animals and transfer from urban to sylvatic maintenance cycles in South America, as did the yellow fever virus (YFV) in the past. All these viruses are transmitted by the anthropophilic mosquito Aedes aegypti and cause epidemics throughout Brazil. The YFV is the oldest example of an urban arbovirus that became sylvatic in South America. Currently, the disease is a zoonosis of non-human primates that moves like a wave through the forests of the Brazilian countryside, traveling thousands of kilometers, killing many animals and eventually infecting man. However, since 2016, this zoonotic wave has reached the highly populated areas of Southeast Brazil, producing the largest human outbreak in the past 60 years. As with the YFV, sylvatic cycles may occur with dengue, Chikungunya, and Zika. In order to become sylvatic, arboviruses require an apparently unlikely conjunction of factors to unexpectedly take place. These arboviruses could start to infect sylvatic primates and be transmitted by Haemagogus mosquitoes that inhabit tree canopies. We mention here publications reporting evidence of sylvatic cycles of dengue, Chikungunya, and Zika virus in South America. Indeed, it is almost unfeasible to control these cycles of arboviruses since it is impossible to know where, when or why an arboviral spill-over would occur in wild animals. The sylvatic maintenance cycle could preclude the eradication of an arbovirus. Moreover, an arbovirus in a sylvatic cycle could re-emerge anytime, infecting humans and producing outbreaks. In case of the reemergence of an arbovirus, it is crucial to prevent the occurrence of an urban cycle as a spill-back from the sylvatic cycle.

10.
Philos Trans R Soc Lond B Biol Sci ; 374(1782): 20180335, 2019 Sep 30.
Article in English | MEDLINE | ID: mdl-31401964

ABSTRACT

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'.

11.
Washington, D. C.; OPS; 2019-07-21.
in Spanish | PAHO-IRIS | ID: phr-51376

ABSTRACT

[Introducción]. La historia del control de las enfermedades transmitidas por vectores en las Américas es muy extensa y las evidencias muestran lo exitosos que fueron varios programas en el pasado. El control de la fiebre amarilla y el paludismo en Cuba y Panamá bajo la dirección de William Gorgas (1901-1910), la eliminación de Anopheles gambiae en el Brasil (1940), la eliminación de Aedes aegypti entre 1950 y 1960 auspiciada por la OPS y dirigida por Fred Soper, la eliminación de la transmisión de la enfermedad de Chagas por Triatoma infestans en el Brasil y el Uruguay y la reciente eliminación de la oncocercosis de 11 de los 13 focos endémicos en Colombia, Ecuador, México y Guatemala (2013-2016) son ejemplos recientes de intervenciones que combinaron el uso de insecticidas, la ingeniería sanitaria y la disponibilidad de vacunas o medicamentos efectivos, apoyados por la participación comunitaria y otros métodos de control…


Subject(s)
Aedes , Mosquito Vectors , Wolbachia , Mosquito Control , Vector Control , Pest Control, Biological
12.
Washington, D. C.; PAHO; 2019-07-21.
in English | PAHO-IRIS | ID: phr-51375

ABSTRACT

[Introduction]. The Region of the Americas has a long history of vector-borne disease control. The evidence reveals the success of various programs in the past. The control of yellow fever and malaria in Cuba and Panama under the direction of William Gorgas (1901–1910), the elimination of Anopheles gambiae in Brazil (1940), the elimination of Aedes aegypti between 1950 and 1960 led by Fred Soper under the auspices of PAHO, the elimination of transmission of Chagas disease by Triatoma infestans in Brazil and Uruguay, and the recent elimination of onchocerciasis from 11 of the 13 endemic foci in Colombia, Ecuador, Mexico, and Guatemala (2013–2016) are recent examples of interventions that have combined the use of insecticides, sanitary engineering, and effective vaccines or medicines, supported by community participation and other control methods… It is estimated that nearly half the world’s current population lives in areas at risk for dengue. Transmission is occurring in more than 100 countries and between 300 and 500 million people are infected annually, 96 million of whom have clinical manifestations and 500,000 have severe cases, with around 25,000 deaths. The infection is endemic in the Americas and in the Southeast Asia, Western Pacific, Africa, and Eastern Mediterranean regions. In the last 50 years the incidence has increased thirtyfold, a trend that shows no sign of abating. The epidemiological scenario reveals that the number of cases is increasing, that outbreaks are larger and longer-lasting, and that the affected areas and populations are continually expanding. Achieving the WHO goal of reducing mortality by 50% and morbidity by 25% by 2020 will be a challenge, given the lack of good surveillance systems that can correctly quantify the burden of disease and the deficiencies of vector control programs in the endemic countries…


Subject(s)
Aedes , Mosquito Vectors , Mosquito Control , Dengue , Wolbachia , Epidemiology
13.
Washington, D. C.; OPAS; 2019-07-21.
in Portuguese | PAHO-IRIS | ID: phr-51374

ABSTRACT

[Introdução]. A história do controle das doenças transmitidas por vetores nas Américas é muito extensa, e as evidências mostram que, no passado, vários programas foram exitosos. O controle da febre amarela e do paludismo em Cuba e no Panamá, sob a direção de William Gorgas (1901-1910); a eliminação de Anopheles gambiae no Brasil (1940); a eliminação de Aedes aegypti entre 1950 e 1960, promovida pela OPAS e dirigida por Fred Soper; a eliminação da transmissão da doença de Chagas por Triatoma infestans no Brasil e no Uruguai; e a recente erradicação da oncocercose de 11 dos 13 focos endêmicos na Colômbia, no Equador, no México e na Guatemala (2013-2016) são exemplos recentes de intervenções que combinaram o uso de inseticidas, da engenharia sanitária e a disponibilidade de vacinas ou medicamentos efetivos, apoiados pela participação comunitária e outros métodos de controle... Hoje em dia, estima-se que cerca de metade da população mundial viva em áreas em risco de dengue. Além disso, mais de 100 países apresentam transmissão e são produzidas entre 300 e 500 milhões de infecções anuais, das quais 96 milhões apresentam manifestações clínicas e 500.000 são casos severos, com aproximadamente 25.000 mortes. A infecção é endêmica nas regiões das Américas, Ásia Sul-Oriental, Pacífico Ocidental, África e Mediterrâneo Oriental, e nos últimos 50 anos a incidência cresceu 30 vezes, sem que haja sinais de reversão dessa tendência. O cenário epidemiológico mostra que o número de casos vem aumentando, que os surtos apresentam maior duração e magnitude e que as áreas afetadas e as populações expostas se encontram em constante expansão. A meta da OMS, para o 2020, de reduzir a mortalidade em 50% e a morbidade em 25% é considerada um desafio diante da carência de bons sistemas de vigilância que quantifiquem corretamente a carga de doença e as deficiências dos programas de controle de vetores nos países endêmicos...


Subject(s)
Aedes , Mosquito Vectors , Mosquito Control , Dengue , Wolbachia , Zika Virus , Chikungunya virus , Yellow Fever
14.
Article in English | MEDLINE | ID: mdl-31262759

ABSTRACT

Yellow fever virus (YFV) is a human Flavivirus reemerging in parts of the world. While a vaccine is available, large outbreaks have recently occurred in Brazil and certain African countries. Development of an effective antiviral against YFV is crucial, as there is no available effective drug against YFV. We have identified several novel nucleoside analogs with potent antiviral activity against YFV with 50% effective concentration (EC50) values between 0.25 and 1 µM with selectivity indices over 100 in culture.

15.
Sci Rep ; 9(1): 9951, 2019 Jul 09.
Article in English | MEDLINE | ID: mdl-31289325

ABSTRACT

Zika virus (ZIKV) is a re-emerged flavivirus transmitted by Aedes spp mosquitoes that has caused outbreaks of fever and rash on islands in the Pacific and in the Americas. These outbreaks have been associated with neurologic complications that include congenital abnormalities and Guillain-Barré syndrome (GBS). The pathogenesis of ZIKV-associated GBS, a potentially life-threatening peripheral nerve disease, remains unclear. Because Schwann cells (SCs) play a central role in peripheral nerve function and can be the target for damage in GBS, we characterized the interactions of ZIKV isolates from Africa, Asia and Brazil with human SCs in comparison with the related mosquito-transmitted flaviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2). SCs supported sustained replication of ZIKV and YFV, but not DENV. ZIKV infection induced increased SC expression of IL-6, interferon (IFN)ß1, IFN-λ, IFIT-1, TNFα and IL-23A mRNAs as well as IFN-λ receptors and negative regulators of IFN signaling. SCs expressed baseline mRNAs for multiple potential flavivirus receptors and levels did not change after ZIKV infection. SCs did not express detectable levels of cell surface Fcγ receptors. This study demonstrates the susceptibility and biological responses of SCs to ZIKV infection of potential importance for the pathogenesis of ZIKV-associated GBS.

16.
Internet resource in Portuguese | LIS -Health Information Locator, LIS-bvsms | ID: lis-LISBR1.1-46582

ABSTRACT

Pesquisadores da Universidade Federal do Rio de Janeiro (UFRJ) descobriram que outra arbovirose, com sintomas parecidos com os da febre chikungunya, circulou em Niterói, na região metropolitana do Rio, em 2016. A descoberta dos cientistas acendeu o alerta para a possibilidade de outros casos diagnosticados como chikungunya serem, na verdade, do vírus Mayaro, que também pode ser transmitido pela picada dos mosquitos Aedes aegypti e Aedes albopictus [vetores da dengue, zika e chikungunya], além do Cúlex [pernilongo] e do Haemagogus [transmissor da febre amarela].


Subject(s)
Arbovirus Infections , Dengue , Chikungunya Fever , Aedes , Culex , Yellow Fever , Polymerase Chain Reaction
17.
J Virol ; 93(14)2019 Jul 15.
Article in English | MEDLINE | ID: mdl-31043530

ABSTRACT

The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/ß) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/ß-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication in vivo These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.IMPORTANCE Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/ß) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/ß-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.

18.
Transfusion ; 59(7): 2223-2227, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31050821

ABSTRACT

BACKGROUND: Yellow fever virus (YFV) is endemic to tropical and subtropical areas in South America and Africa, and is currently a major public health threat in Brazil. Transfusion transmission of the yellow fever vaccine virus has been demonstrated, which is indicative of the potential for viral transfusion transmission. An approach to manage the potential YFV transfusion transmission risk is the use of pathogen inactivation (PI) technology systems, such as THERAFLEX MB-Plasma and THERAFLEX UV-Platelets (Macopharma). We aimed to investigate the efficacy of these PI technology systems to inactivate YFV in plasma or platelet concentrates (PCs). STUDY DESIGN AND METHODS: YFV spiked plasma units were treated using THERAFLEX MB-Plasma system (visible light doses: 20, 40, 60, and 120 [standard] J/cm2 ) in the presence of methylene blue (approx. 0.8 µmol/L) and spiked PCs were treated using THERAFLEX UV-Platelets system (ultraviolet C doses: 0.05, 0.10, 0.15, and 0.20 [standard] J/cm2 ). Samples were taken before the first and after each illumination dose and tested for residual virus using a modified plaque assay. RESULTS: YFV infectivity was reduced by an average of 4.77 log or greater in plasma treated with the THERAFLEX MB-Plasma system and by 4.8 log or greater in PCs treated with THERAFLEX UV-Platelets system. CONCLUSIONS: Our study suggests the THERAFLEX MB-Plasma and the THERAFLEX UV-Platelets systems can efficiently inactivate YFV in plasma or PCs to a similar degree as that for other arboviruses. Given the reduction levels observed in this study, these PI technology systems could be an effective option for managing YFV transfusion-transmission risk in plasma and PCs.

19.
Mem Inst Oswaldo Cruz ; 114: e180509, 2019.
Article in English | MEDLINE | ID: mdl-31066755

ABSTRACT

BACKGROUND: The outbreak of sylvatic Yellow Fever (SYF) in humans during 2016-2017 in Brazil is one of the greatest in the history of the disease. The occurrence of the disease in areas with low vaccination coverage favoured the dissemination of the disease; therefore, it is necessary to identify the areas vulnerability to the YF virus (YFV) to assist in the adoption of preventive measures. OBJECTIVE: To correlate the physical-environmental elements associated with the occurrence of SYF in humans via a multicriteria analysis. METHODS: For the multicriteria analysis, preponderant elements related to SYF occurrences, including soil usage and coverage, temperature, precipitation, altitude, mosquito transmitters, and non-human primate occurrence areas, were considered. The results were validated by assessing the correlation between the incidence of SYF and the vulnerable areas identified in the multicriteria analysis. RESULTS: Two regions with different vulnerability to the occurrence of the disease were identified in the multicriteria analysis, with emphasis on the southern areas of the state of São Paulo northeast areas of Minas Gerais, and the entire states of Rio de Janeiro and Espírito Santo. The map of SYF vulnerability obtained in the multicriteria analysis coincides with the areas in which cases of the disease have been recorded. The regions that presented the greatest suitability were in fact the municipalities with the highest incidence. MAIN CONCLUSIONS: The multicriteria analysis revealed that the elements that were used are suited for and consistent in the prediction of the areas that are vulnerable to SYF. The results obtained indicate the proximity of the areas that are most vulnerable to the disease to densely populated areas where an Aedes aegypti infestation was observed, which confers a high risk of re-urbanisation of YF.


Subject(s)
Aedes/virology , Yellow Fever/transmission , Animals , Brazil/epidemiology , Endemic Diseases/prevention & control , Geographic Information Systems , Humans , Population Density , Population Surveillance , Risk Assessment , Urbanization , Yellow Fever/epidemiology , Yellow Fever/prevention & control , Yellow Fever Vaccine
20.
Mem Inst Oswaldo Cruz ; 114: e190076, 2019.
Article in English | MEDLINE | ID: mdl-31038550

ABSTRACT

BACKGROUND: In Brazil, the Yellow Fever virus (YFV) is endemic in the Amazon, from where it eventually expands into epidemic waves. Coastal south-eastern (SE) Brazil, which has been a YFV-free region for eight decades, has reported a severe sylvatic outbreak since 2016. The virus spread from the north toward the south of the Rio de Janeiro (RJ) state, causing 307 human cases with 105 deaths during the 2016-2017 and 2017-2018 transmission seasons. It is unclear, however, whether the YFV would persist in the coastal Atlantic Forest of RJ during subsequent transmission seasons. OBJECTIVES: To conduct a real-time surveillance and assess the potential persistence of YFV in the coastal Atlantic Forest of RJ during the 2018-2019 transmission season. METHODS: We combined epizootic surveillance with fast diagnostic and molecular, phylogenetic, and evolutionary analyses. FINDINGS: Using this integrative strategy, we detected the first evidence of YFV re-emergence in the third transmission season (2018-2019) in a dying howler monkey from the central region of the RJ state. The YFV detected in 2019 has the molecular signature associated with the current SE YFV outbreak and exhibited a close phylogenetic relationship with the YFV lineage that circulated in the same Atlantic Forest fragment during the past seasons. This lineage circulated along the coastal side of the Serra do Mar mountain chain, and its evolution seems to be mainly driven by genetic drift. The potential bridge vector Aedes albopictus was found probing on the recently dead howler monkey in the forest edge, very close to urban areas. MAIN CONCLUSIONS: Collectively, our data revealed that YFV transmission persisted at the same Atlantic Forest area for at least three consecutive transmission seasons without the need of new introductions. Our real-time surveillance strategy permitted health authorities to take preventive actions within 48 h after the detection of the sick non-human primate. The local virus persistence and the proximity of the epizootic forest to urban areas reinforces the concern with regards to the risk of re-urbanisation and seasonal re-emergence of YFV, stressing the need for continuous effective surveillance and high vaccination coverage in the SE region, particularly in RJ, an important tourist location.


Subject(s)
Aedes/virology , Yellow Fever/epidemiology , Yellow Fever/virology , Yellow fever virus/genetics , Alouatta , Animals , Brazil/epidemiology , Disease Outbreaks , Humans , Phylogeography , Seasons , Urban Population , Yellow Fever/transmission
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