A community-level investigation following a yellow fever virus outbreak in South Omo Zone, South-West Ethiopia

Background Despite the availability of a highly effective vaccine, yellow fever virus (YFV) remains an important public health problem across Africa and South America due to its high case-fatality rate. This study investigated the historical epidemiology and contemporary entomological and social determinants of a YFV outbreak in South Omo Zone (SOZ), Ethiopia. Methods A YFV outbreak occurred in SOZ, Ethiopia in 2012–2014. Historical epidemiological data were retrieved from the SOZ Health Department and analyzed. Entomological sampling was undertaken in 2017, including mosquito species identification and molecular screening for arboviruses to understand mosquito habitat distribution, and finally current knowledge, attitudes and preventative practices within the affected communities were assessed. Results From October 2012 to March 2014, 165 suspected cases and 62 deaths were reported, principally in rural areas of South Ari region (83.6%). The majority of patients were 15–44 years old (75.8%) and most case deaths were males (76%). Between June and August 2017, 688 containers were sampled across 180 households to identify key breeding sites for Aedes mosquitoes. Ensete ventricosum (“false banana”) and clay pots outside the home were the most productive natural and artificial breeding sites, respectively. Entomological risk indices classified most sites as “high risk” for future outbreaks under current World Health Organization criteria. Adult mosquitoes in houses were identified as members of the Aedes simpsoni complex but no YFV or other arboviruses were detected by PCR. The majority of community members had heard of YFV, however few activities were undertaken to actively reduce mosquito breeding sites. Discussion Study results highlight the potential role vector control could play in mitigating local disease transmission and emphasize the urgent need to strengthen disease surveillance systems and in-country laboratory capacity to facilitate more rapid responses to future YFV outbreaks.

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Yellow Fever Outbreak in Eastern Senegal, 2020–2021

Viruses ◽

10.3390/v13081475 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1475

Author(s):

Moussa Moïse Diagne ◽

Marie Henriette Dior Ndione ◽

Alioune Gaye ◽

Mamadou Aliou Barry ◽

Diawo Diallo ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Mosquito Species ◽

Virus Transmission ◽

Genomic Analysis ◽

Hemorrhagic Fever ◽

Fever Virus ◽

World Health ◽

Effective Vaccine ◽

Ministry Of Health

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.

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A community-level investigation of the yellow fever virus outbreak in South Omo Zone, South-West Ethiopia, 2012–2014

10.1101/320317 ◽

2018 ◽

Author(s):

Ranya Mulchandani ◽

Fekadu Massebo ◽

Fekadu Bocho ◽

Claire L Jeffries ◽

Thomas Walker ◽

...

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Mosquito Species ◽

Breeding Site ◽

Fever Virus ◽

Entomological Surveillance ◽

Breeding Sites ◽

South Omo ◽

South West Ethiopia ◽

Aedes Simpsoni

AbstractBackgroundA yellow fever (YF) outbreak occurred in South Omo Zone, Ethiopia in 2012-2014. This study aimed to analyse historical epidemiological data, to assess the risk for future YF outbreaks through entomological surveillance, including mosquito species identification and molecular screening for arboviruses, and finally to determine the knowledge, attitudes and current preventative practices within the affected communities.Methodology/Principal FindingsFrom October 2012 to March 2014, 165 cases and 62 deaths were reported, principally in rural areas of South Ari region (83.6%), south-west Ethiopia. The majority of patients were 15-44 years old (74.5%) and most case deaths were males (76%). Between June and August 2017, 688 containers were sampled from across 177 households to identify key breeding sites forAedesmosquitoes.Ensete ventricosum(“false banana”) was identified as the primary natural breeding site, and clay pots outside the home as the most productive artificial breeding site. Entomological risk indices from the majority of sites were classified as “high risk” for future outbreaks under current World Health Organization criteria. Adult trapping resulted in the identification of members of theAedes simpsonicomplex in and around households. Screening of adult females revealed no detection of yellow fever virus (YFV) or other arboviruses. 88% of 177 participants had heard of YF, however many participants easily confused transmission and symptoms of YF with malaria, which is also endemic in the area.Conclusions/SignificanceStudy results emphasise the need for further entomological studies to improve our understanding of local vector species and transmission dynamics. Disease surveillance systems and in-country laboratory capacity also need to be strengthened to facilitate more rapid responses to future YF outbreaks.Author SummaryDespite the availability of a highly effective vaccine, yellow fever virus (YFV) remains an important public health problem across Africa and South America due to its high case-fatality rate. This study aimed to assess and reduce the risk for future outbreaks. During this study, historical data analysis was conducted to understand the epidemiology of the recent outbreak in 2012-2014. Entomological surveillance was also carried out, including both mosquito species identification and molecular screening for arboviruses, as well as a household survey to understand the knowledge and attitudes towards yellow fever (YF) within the affected areas and to assess community-level practices for YF prevention. We found a high abundance ofAedes simpsonicomplex in the context of low vaccination coverage. Community knowledge and practice levels were low for reducing potential breeding sites, highlighting the need for increased dissemination of information to community members on how to reduce their risk of exposure to mosquito vectors of arboviruses.

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Yellow Fever Virus Down-Regulates mRNA Expression of SOCS1 in the Initial Phase of Infection in Human Cell Lines

Viruses ◽

10.3390/v12080802 ◽

2020 ◽

Vol 12 (8) ◽

pp. 802

Author(s):

Michael B. Yakass ◽

David Franco ◽

Osbourne Quaye

Keyword(s):

Mrna Expression ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Expression Patterns ◽

Fever Virus ◽

Effective Vaccine ◽

Interferon Β ◽

Infected Cells ◽

Insight Into

Flaviviruses are constantly evolving diverse immune evasion strategies, and the exploitation of the functions of suppressors of cytokine signalling (SOCS) and protein inhibitors of activated STATs (PIAS) to favour virus replication has been described for Dengue and Japanese encephalitis viruses but not for yellow fever virus (YFV), which is still of global importance despite the existence of an effective vaccine. Some mechanisms that YFV employs to evade host immune defence has been reported, but the expression patterns of SOCS and PIAS in infected cells is yet to be determined. Here, we show that SOCS1 is down-regulated early in YFV-infected HeLa and HEK 293T cells, while SOCS3 and SOCS5 are not significantly altered, and PIAS mRNA expression appears to follow a rise-dip pattern akin to circadian-controlled genes. We also demonstrate that YFV evades interferon-β application to produce comparable viral titres. This report provides initial insight into the in vitro expression dynamics of SOCS and PIAS upon YFV infection and a basis for further investigation into SOCS/PIAS expression and how these modulate the immune response in animal models.

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AT-752, a double prodrug of a guanosine nucleotide analog, inhibits yellow fever virus in a hamster model

10.1101/2021.10.25.465665 ◽

2021 ◽

Author(s):

Kai Lin ◽

Steven S Good ◽

Justin G. Julander ◽

Abbie Weight ◽

Adel Moussa

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Limit Of Detection ◽

Virus Titer ◽

Fever Virus ◽

Effective Vaccine ◽

Hamster Model ◽

Nucleotide Analog

Yellow fever virus (YFV) is a zoonotic pathogen re-emerging in parts of the world, causing a viral hemorrhagic fever associated with high mortality rates. While an effective vaccine is available, having an effective antiviral against YFV is critical against unexpected outbreaks, or when vaccination is not recommended. We have previously identified AT-281, the free base of AT-752, an orally available double prodrug of a guanosine nucleotide analog, as a potent inhibitor of YFV in vitro , with a 50% effective concentration (EC 50 ) of 0.31 µM. In hamsters infected with YFV (Jimenez strain), viremia rose about 4 log 10 -fold and serum alanine aminotransferase (ALT) 2-fold compared to sham-infected animals. Treatment with 1000 mg/kg AT-752 for 7 days, initiated 4 h prior to viral challenge, reduced viremia to below the limit of detection by day 4 post infection (pi) and returned ALT to normal levels by day 6 pi. When treatment with AT-752 was initiated 2 days pi, the virus titer and ALT dropped >2 log 10 and 53% by day 4 and 6 pi, respectively. In addition, at 21 days pi, 70 – 100% of the infected animals in the treatment groups survived compared to 0% of the untreated group (p<0.001). Moreover, in vivo formation of the active triphosphate metabolite AT-9010 was measured in the animal tissues, with the highest concentrations in liver and kidney, organs that are vulnerable to the virus. The demonstrated in vivo activity of AT-752 suggests that it is a promising compound for clinical development in the treatment of YFV infection.

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Yellow Fever Virus: Diagnostics for a Persistent Arboviral Threat

Journal of Clinical Microbiology ◽

10.1128/jcm.00827-18 ◽

2018 ◽

Vol 56 (10) ◽

Cited By ~ 9

Author(s):

Jesse J. Waggoner ◽

Alejandra Rojas ◽

Benjamin A. Pinsky

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Current Knowledge ◽

Hemorrhagic Fever ◽

Clinical Diagnostics ◽

Fever Virus ◽

Diagnostic Methods ◽

Effective Vaccine ◽

Molecular Testing ◽

Viral Culture

ABSTRACTYellow fever (YF) is the prototypical hemorrhagic fever and results from infection with yellow fever virus (YFV), which is endemic to regions of Africa and South America. Despite the availability of an effective vaccine, YFV continues to cause disease throughout regions where it is endemic, including intermittent large outbreaks among undervaccinated populations. A number of diagnostic methods and assays have been described for the detection of YFV infection, including viral culture, molecular testing, serology, and antigen detection. Commercial diagnostics are not widely available, and testing is generally performed at a small number of reference laboratories. The goal of this article, therefore, is to review available clinical diagnostics for YFV, which may not be familiar to many practitioners outside areas where it is endemic. Additionally, we identify gaps in our current knowledge about YF that pertain to diagnosis and describe interventions that may improve YFV detection.

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What Does the Future Hold for Yellow Fever Virus? (II)

10.20944/preprints201807.0378.v1 ◽

2018 ◽

Author(s):

Raphaëlle Klitting ◽

Carlo Fischer ◽

Jan F. Drexler ◽

Ernest A. Gould ◽

David Roiz ◽

...

Keyword(s):

South America ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Virus Transmission ◽

Fever Virus ◽

Control Measures ◽

World Health ◽

Epidemiological Surveillance ◽

Tropical Regions ◽

Vaccination Recommendation

As revealed by the recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America, YFV control measures need urgent rethinking. Over the last decade, most reported outbreaks occurred in, or eventually reached, areas of low vaccination coverage but suitable for virus transmission, with an unprecedented risk of expansion to densely populated territories in Africa, South America and Asia. As reflected in the World Health Organization’s initiative launched in 2017, it is high time to strengthen epidemiological surveillance to monitor accurately, viral dissemination and redefine vaccination recommendation areas. Vector-control and immunisation measures need to be adapted and vaccine manufacturing must be reconciled with an increasing demand. We will have to face more YF cases in the upcoming years hence, improving disease management through the development of efficient treatments will prove most beneficial. Undoubtedly, these developments will require in-depth descriptions of YFV biology at molecular, physiological and ecological levels. This second section of the two-part review describes the current state of knowledge and gaps regarding the molecular biology of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

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What Does the Future Hold for Yellow Fever Virus? (II)

Genes ◽

10.3390/genes9090425 ◽

2018 ◽

Vol 9 (9) ◽

pp. 425 ◽

Cited By ~ 6

Author(s):

Raphaëlle Klitting ◽

Carlo Fischer ◽

Jan Drexler ◽

Ernest Gould ◽

David Roiz ◽

...

Keyword(s):

South America ◽

Yellow Fever ◽

Yellow Fever Virus ◽

Virus Transmission ◽

Fever Virus ◽

Control Measures ◽

World Health ◽

Epidemiological Surveillance ◽

Tropical Regions ◽

Vaccination Recommendation

As revealed by the recent resurgence of yellow fever virus (YFV) activity in the tropical regions of Africa and South America, YFV control measures need urgent rethinking. Over the last decade, most reported outbreaks occurred in, or eventually reached, areas with low vaccination coverage but that are suitable for virus transmission, with an unprecedented risk of expansion to densely populated territories in Africa, South America and Asia. As reflected in the World Health Organization’s initiative launched in 2017, it is high time to strengthen epidemiological surveillance to monitor accurately viral dissemination, and redefine vaccination recommendation areas. Vector-control and immunisation measures need to be adapted and vaccine manufacturing must be reconciled with an increasing demand. We will have to face more yellow fever (YF) cases in the upcoming years. Hence, improving disease management through the development of efficient treatments will prove most beneficial. Undoubtedly, these developments will require in-depth descriptions of YFV biology at molecular, physiological and ecological levels. This second section of a two-part review describes the current state of knowledge and gaps regarding the molecular biology of YFV, along with an overview of the tools that can be used to manage the disease at the individual, local and global levels.

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Haemagogus leucocelaenus (Diptera: Culicidae), the potential wild vector of yellow fever in the border zone of northern Misiones, Argentina

Revista de la Sociedad Entomológica Argentina ◽

10.25085/rsea.800410 ◽

2021 ◽

Vol 80 (04) ◽

pp. 136-141

Author(s):

Julieta A. SICHES ◽

Pablo E. BERROZPE ◽

Gustavo C. ROSSI ◽

Oscar D. SALOMÓN ◽

Juan J. GARCÍA

Keyword(s):

Yellow Fever ◽

Yellow Fever Virus ◽

Virus Transmission ◽

Distribution Patterns ◽

Fever Virus ◽

Border Zone ◽

Wild Populations ◽

Breeding Sites ◽

In The Wild ◽

Primary Vector

Haemagogus leucocelaenus (Diptera: Culicidae) is considered the primary vector of yellow fever virus (Flaviviridae) in wild environments in South America. Previous research has defined Hg. leucocelaenus as a wild species with phytotelmata-type breeding sites. The objective of this study was to report the temporal and space occurrence of Hg. leucocelaenus at the microscale in the wild-periurban fringe through a systematic and spatially stratified sampling using 81 ovitraps between April 2019 and February 2 020 in the locality of Puerto Iguazú, Argentina. Of the total ovitraps, eight were positive for Hg. leucocelaenus, six in the wild environment and two in the periurban environment. Regarding the time distribution, 98.5% of the occurrence was concentrated in November and December 2019 towards the beginning of the rainy season. The results confirm the habitat plasticity of Hg. leucocelaenus and establish the aptitude of artificial containers as a methodology in monitoring studies, since they illustrate the potential of wild populations to deposit fertile eggs in them at least up to 300 m from the wild-periurban fringe. This work is a contribution to determine the temporal and space risk of yellow fever virus transmission in the region, based on the distribution patterns of this species as a function to the ecotone associated with forest borders and climatic variables.

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