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Sample records for yellow fever epidemic

  1. Yellow fever cases in Asia: primed for an epidemic.

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    Wasserman, Sean; Tambyah, Paul Anantharajah; Lim, Poh Lian

    2016-07-01

    There is currently an emerging outbreak of yellow fever in Angola. Cases in infected travellers have been reported in a number of other African countries, as well as in China, representing the first ever documented cases of yellow fever in Asia. There is a large Chinese workforce in Angola, many of whom may be unvaccinated, increasing the risk of ongoing importation of yellow fever into Asia via busy commercial airline routes. Large parts of the region are hyperendemic for the related Flavivirus dengue and are widely infested by Aedes aegypti, the primary mosquito vector of urban yellow fever transmission. The combination of sustained introduction of viraemic travellers, an ecology conducive to local transmission, and an unimmunized population raises the possibility of a yellow fever epidemic in Asia. This represents a major global health threat, particularly in the context of a depleted emergency vaccine stockpile and untested surveillance systems in the region. In this review, the potential for a yellow fever outbreak in Asia is discussed with reference to the ecological and historical forces that have shaped global yellow fever epidemiology. The limitations of surveillance and vector control in the region are highlighted, and priorities for outbreak preparedness and response are suggested. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  2. Yellow fever cases in Asia: primed for an epidemic

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    Sean Wasserman

    2016-07-01

    Full Text Available There is currently an emerging outbreak of yellow fever in Angola. Cases in infected travellers have been reported in a number of other African countries, as well as in China, representing the first ever documented cases of yellow fever in Asia. There is a large Chinese workforce in Angola, many of whom may be unvaccinated, increasing the risk of ongoing importation of yellow fever into Asia via busy commercial airline routes. Large parts of the region are hyperendemic for the related Flavivirus dengue and are widely infested by Aedes aegypti, the primary mosquito vector of urban yellow fever transmission. The combination of sustained introduction of viraemic travellers, an ecology conducive to local transmission, and an unimmunized population raises the possibility of a yellow fever epidemic in Asia. This represents a major global health threat, particularly in the context of a depleted emergency vaccine stockpile and untested surveillance systems in the region. In this review, the potential for a yellow fever outbreak in Asia is discussed with reference to the ecological and historical forces that have shaped global yellow fever epidemiology. The limitations of surveillance and vector control in the region are highlighted, and priorities for outbreak preparedness and response are suggested.

  3. Investigation of a possible yellow fever epidemic and serosurvey for flavivirus infections in northern Cameroon, 1984

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    Tsai, T. F.; Lazuick, J. S.; Ngah, R. W.; Mafiamba, P. C.; Quincke, G.; Monath, T. P.

    1987-01-01

    A cluster of fatal hepatitis cases in northern Cameroon in 1984 stimulated a field investigation to rule out an epidemic of yellow fever. A serosurvey of villages in the extreme north of the country, in a Sudan savanna (SS) phytogeographical zone, disclosed no evidence of recent yellow fever infection. However, further south, in a Guinea savanna (GS) phytogeographical zone, serological evidence was found of endemic yellow fever virus transmission. The results indicate a potential for epidemic...

  4. Yellow Fever

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    ... Testing Vaccine Information Testing for Vaccine Adverse Events Yellow fever Vaccine Continuing Education Course Yellow Fever Home Prevention Vaccine Vaccine Recommendations Reactions to Yellow Fever Vacine Yellow Fever Vaccine, Pregnancy, & ... Transmission Symptoms, Diagnosis, & Treatment Maps Africa ...

  5. Investigation of a possible yellow fever epidemic and serosurvey for flavivirus infections in northern Cameroon, 1984.

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    Tsai, T F; Lazuick, J S; Ngah, R W; Mafiamba, P C; Quincke, G; Monath, T P

    1987-01-01

    A cluster of fatal hepatitis cases in northern Cameroon in 1984 stimulated a field investigation to rule out an epidemic of yellow fever. A serosurvey of villages in the extreme north of the country, in a Sudan savanna (SS) phytogeographical zone, disclosed no evidence of recent yellow fever infection. However, further south, in a Guinea savanna (GS) phytogeographical zone, serological evidence was found of endemic yellow fever virus transmission. The results indicate a potential for epidemic spread of yellow fever virus from the southern GS zone to the nothern SS zone of Cameroon, where immunity in the population was low.

  6. Yellow fever

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    ... to thrive. Blood tests can confirm the diagnosis. Treatment There is no specific treatment for yellow fever. ... SJ, Endy TP, Rothman AL, Barrett AD. Flaviviruses (dengue, yellow fever, Japanese encephalitis, West Nile encephalitis, St. ...

  7. Epidemics which never came: yellow fever (1883) and bubonic plague (1902-1903) in Baja California

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    Fierros-Hernández, Arturo; Ayala-Zúñiga, Alejandro

    2018-01-01

    This paper seeks to clarify the epidemic panorama that was generated in Baja California in the late nineteenth and early twentieth 20 th century’s, specifically that occurred in 1883 and 1902, years in which it is claimed occurred epidemics of yellow fever and bubonic plague respectively. However, as demonstrated in our study they never occurred due to social-demographic conditions in the area. Copyright: © 2018 SecretarÍa de Salud.

  8. The yellow Fever epidemic in Western mali, september-november 1987: why did epidemiological surveillance fail?

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    Kurz, X

    1990-03-01

    Recent yellow fever epidemics in West Africa have underlined the discrepancy between the official number of cases and deaths and those estimated by a retrospective epidemiological investigation. During the yellow fever epidemic that broke out in western Mali in September 1987, a total of 305 cases and 145 deaths were officially notified, but estimates revealed true figures abut five times higher. This paper attempts to discuss the factors that hindered early case detection and more complete reporting. They were, first, the insufficient training on the clinical diagnosis, the blood sampling method for laboratory confirmation, and the curative treatment of patients (resulting in low utilization of services); second, the lack of an action plan to prepare in advance a quick response to the epidemic, affecting reporting procedures at the peripheral level and active case-finding during the outbreak; and third, the lack of laboratory facilities for a quick confirmation of the disease. The difficulties experienced during the yellow fever epidemic in Mali demonstrated the importance of a preparedness strategy for epidemic control, based on an integrated approach of epidemiological surveillance within basic health service activities. The need for regional collaboration and for institutionalized funds in the donor community that could be mobilized for epidemic preparedness activities is also emphasized.

  9. Assessment of yellow fever epidemic risk: an original multi-criteria modeling approach.

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    Sylvie Briand

    Full Text Available BACKGROUND: Yellow fever (YF virtually disappeared in francophone West African countries as a result of YF mass vaccination campaigns carried out between 1940 and 1953. However, because of the failure to continue mass vaccination campaigns, a resurgence of the deadly disease in many African countries began in the early 1980s. We developed an original modeling approach to assess YF epidemic risk (vulnerability and to prioritize the populations to be vaccinated. METHODS AND FINDINGS: We chose a two-step assessment of vulnerability at district level consisting of a quantitative and qualitative assessment per country. Quantitative assessment starts with data collection on six risk factors: five risk factors associated with "exposure" to virus/vector and one with "susceptibility" of a district to YF epidemics. The multiple correspondence analysis (MCA modeling method was specifically adapted to reduce the five exposure variables to one aggregated exposure indicator. Health districts were then projected onto a two-dimensional graph to define different levels of vulnerability. Districts are presented on risk maps for qualitative analysis in consensus groups, allowing the addition of factors, such as population migrations or vector density, that could not be included in MCA. The example of rural districts in Burkina Faso show five distinct clusters of risk profiles. Based on this assessment, 32 of 55 districts comprising over 7 million people were prioritized for preventive vaccination campaigns. CONCLUSION: This assessment of yellow fever epidemic risk at the district level includes MCA modeling and consensus group modification. MCA provides a standardized way to reduce complexity. It supports an informed public health decision-making process that empowers local stakeholders through the consensus group. This original approach can be applied to any disease with documented risk factors.

  10. Three-dimensional visualization of cultural clusters in the 1878 yellow fever epidemic of New Orleans

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    Curtis Andrew J

    2008-08-01

    Full Text Available Abstract Background An epidemic may exhibit different spatial patterns with a change in geographic scale, with each scale having different conduits and impediments to disease spread. Mapping disease at each of these scales often reveals different cluster patterns. This paper will consider this change of geographic scale in an analysis of yellow fever deaths for New Orleans in 1878. Global clustering for the whole city, will be followed by a focus on the French Quarter, then clusters of that area, and finally street-level patterns of a single cluster. The three-dimensional visualization capabilities of a GIS will be used as part of a cluster creation process that incorporates physical buildings in calculating mortality-to-mortality distance. Including nativity of the deceased will also capture cultural connection. Results Twenty-two yellow fever clusters were identified for the French Quarter. These generally mirror the results of other global cluster and density surfaces created for the entire epidemic in New Orleans. However, the addition of building-distance, and disease specific time frame between deaths reveal that disease spread contains a cultural component. Same nativity mortality clusters emerge in a similar time frame irrespective of proximity. Italian nativity mortalities were far more densely grouped than any of the other cohorts. A final examination of mortalities for one of the nativity clusters reveals that further sub-division is present, and that this pattern would only be revealed at this scale (street level of investigation. Conclusion Disease spread in an epidemic is complex resulting from a combination of geographic distance, geographic distance with specific connection to the built environment, disease-specific time frame between deaths, impediments such as herd immunity, and social or cultural connection. This research has shown that the importance of cultural connection may be more important than simple proximity, which in

  11. Three-dimensional visualization of cultural clusters in the 1878 yellow fever epidemic of New Orleans.

    Science.gov (United States)

    Curtis, Andrew J

    2008-08-22

    An epidemic may exhibit different spatial patterns with a change in geographic scale, with each scale having different conduits and impediments to disease spread. Mapping disease at each of these scales often reveals different cluster patterns. This paper will consider this change of geographic scale in an analysis of yellow fever deaths for New Orleans in 1878. Global clustering for the whole city, will be followed by a focus on the French Quarter, then clusters of that area, and finally street-level patterns of a single cluster. The three-dimensional visualization capabilities of a GIS will be used as part of a cluster creation process that incorporates physical buildings in calculating mortality-to-mortality distance. Including nativity of the deceased will also capture cultural connection. Twenty-two yellow fever clusters were identified for the French Quarter. These generally mirror the results of other global cluster and density surfaces created for the entire epidemic in New Orleans. However, the addition of building-distance, and disease specific time frame between deaths reveal that disease spread contains a cultural component. Same nativity mortality clusters emerge in a similar time frame irrespective of proximity. Italian nativity mortalities were far more densely grouped than any of the other cohorts. A final examination of mortalities for one of the nativity clusters reveals that further sub-division is present, and that this pattern would only be revealed at this scale (street level) of investigation. Disease spread in an epidemic is complex resulting from a combination of geographic distance, geographic distance with specific connection to the built environment, disease-specific time frame between deaths, impediments such as herd immunity, and social or cultural connection. This research has shown that the importance of cultural connection may be more important than simple proximity, which in turn might mean traditional quarantine measures should be

  12. Yellow fever

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    Marcelo Nóbrega Litvoc

    Full Text Available Summary The yellow fever (YF virus is a Flavivirus, transmitted by Haemagogus, Sabethes or Aedes aegypti mosquitoes. The disease is endemic in forest areas in Africa and Latin America leading to epizootics in monkeys that constitute the reservoir of the disease. There are two forms of YF: sylvatic, transmitted accidentally when approaching the forests, and urban, which can be perpetuated by Aedes aegypti. In Brazil, the last case of urban YF occurred in 1942. Since then, there has been an expansion of transmission areas from the North and Midwest regions to the South and Southeast. In 2017, the country faced an important outbreak of the disease mainly in the states of Minas Gerais, Espírito Santo and Rio de Janeiro. In 2018, its reach extended from Minas Gerais toward São Paulo. Yellow fever has an incubation period of 3 to 6 days and sudden onset of symptoms with high fever, myalgia, headache, nausea/vomiting and increased transaminases. The disease ranges from asymptomatic to severe forms. The most serious forms occur in around 15% of those infected, with high lethality rates. These forms lead to renal, hepatic and neurological impairment, and bleeding episodes. Treatment of mild and moderate forms is symptomatic, while severe and malignant forms depend on intensive care. Prevention is achieved by administering the vaccine, which is an effective (immunogenicity at 90-98% and safe (0.4 severe events per 100,000 doses measure. In 2018, the first transplants in the world due to YF were performed. There is also an attempt to evaluate the use of active drugs against the virus in order to reduce disease severity.

  13. Human Genetic Variation and Yellow Fever Mortality during 19th Century U.S. Epidemics

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    2014-01-01

    ABSTRACT We calculated the incidence, mortality, and case fatality rates for Caucasians and non-Caucasians during 19th century yellow fever (YF) epidemics in the United States and determined statistical significance for differences in the rates in different populations. We evaluated nongenetic host factors, including socioeconomic, environmental, cultural, demographic, and acquired immunity status that could have influenced these differences. While differences in incidence rates were not significant between Caucasians and non-Caucasians, differences in mortality and case fatality rates were statistically significant for all epidemics tested (P < 0.01). Caucasians diagnosed with YF were 6.8 times more likely to succumb than non-Caucasians with the disease. No other major causes of death during the 19th century demonstrated a similar mortality skew toward Caucasians. Nongenetic host factors were examined and could not explain these large differences. We propose that the remarkably lower case mortality rates for individuals of non-Caucasian ancestry is the result of human genetic variation in loci encoding innate immune mediators. PMID:24895309

  14. Yellow fever in the Americas: the growing concern about new epidemics [version 2; referees: 2 approved

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    Yeimer Ortiz-Martínez

    2017-04-01

    Full Text Available Yellow fever (YF is a haemorrhagic viral disease with a high case fatality rate. It is considered a reemerging infectious disease of remarkable importance. During the last outbreaks in Brazil (2016-2017, many cases of YF emerged despite high YF vaccination coverage in some areas. However, there are many areas and populations worldwide where vaccination coverage has been low for years (e.g. Nigeria, which increases the risk of major epidemics in such areas, as would be the case in many of the American territories. Several factors, including the vast border and migratory status of Brazil, the widespread distribution of Aedes mosquitoes and the lack of efficient health policies and surveillance systems, favor this complex epidemiological scenario of reemergence. Therefore, mass vaccination of the population at risk, public health awareness and preparedness are urgently needed in this region. This opinion article describes the current global epidemiological situation of YF, focusing especially on the Americas, as well the risk and vulnerabilities in the region that would be of concern for major expansion to other countries apart from Brazil. Also, imported risk from endemic area outside of Americas (i.e. Africa are of current concern.

  15. Epidemic yellow fever in Borno State of Nigeria: characterisation of hospitalised patients.

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    Ekenna, O; Chikwem, J O; Mohammed, I; Durojaiye, S O

    2010-01-01

    In 1990, an outbreak of a febrile illness with high mortality was reported in border villages, later spreading to other areas of Borno State of Nigeria. To present a report of the investigation of that outbreak, with emphasis on the characterisation of hospitalised patients. Selected centres reporting cases of acute febrile illness during the months of August to December, 1990 were visited, to establish surveillance. Case investigation forms were used to obtain clinical and demographic data; and blood samples were obtained from patients for analyses. Only hospitalised patients with adequate clinical information from three centres were included in the analysis. The outbreak, which involved five of the six health zones in the state, and spread into adjoining Gongola state and the Cameroun Republic, was caused by the yellow fever virus. Fever, central nervous system (CNS) involvement, jaundice and haemorrhage were the most common clinical manifestations of 102 hospitalised patients. Eighty -three (81%) of hospitalised patients died and most within two days of admission. CNS manifestations were more common in dying patients than in survivors. The reasons for this rare outbreak of yellow fever in the dry Savannah belt of Borno State remain unclear. Improved surveillance and more effective prevention strategies are needed to avert the recurrence of such outbreaks.

  16. Febre amarela Yellow fever

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    Pedro Fernando da Costa Vasconcelos

    2003-04-01

    Full Text Available A febre amarela é doenca infecciosa não-contagiosa causada por um arbovírus mantido em ciclos silvestres em que macacos atuam como hospedeiros amplificadores e mosquitos dos gêneros Aedes na África, e Haemagogus e Sabethes na América, são os transmissores. Cerca de 90% dos casos da doença apresentam-se com formas clínicas benignas que evoluem para a cura, enquanto 10% desenvolvem quadros dramáticos com mortalidade em torno de 50%. O problema mostra-se mais grave em África onde ainda há casos urbanos. Nas Américas, no período de 1970-2001, descreveram-se 4.543 casos. Os países que mais diagnosticaram a doença foram o Peru (51,5%, a Bolívia (20,1% e o Brasil (18,7%. Os métodos diagnósticos utilizados incluem a sorologia (IgM, isolamento viral, imunohistoquímica e RT-PCR. A zoonose não pode ser erradicada, mas, a doença humana é prevenível mediante a vacinação com a amostra 17D do vírus amarílico. A OMS recomenda nova vacinação a cada 10 anos. Neste artigo são revistos os principais conceitos da doença e os casos de mortes associados à vacina.Yellow fever is an infectious and non-contagious disease caused by an arbovirus, the yellow fever virus. The agent is maintained in jungle cycles among primates as vertebrate hosts and mosquitoes, especially Aedes in Africa, and Haemagogus and Sabethes in America. Approximately 90% of the infections are mild or asymptomatic, while 10% course to a severe clinical picture with 50% case-fatality rate. Yellow fever is largely distributed in Africa where urban epidemics are still reported. In South America, between 1970-2001, 4,543 cases were reported, mostly from Peru (51.5%, Bolivia (20.1% and Brazil (18.7%. The disease is diagnosed by serology (detection of IgM, virus isolation, immunohistochemistry and RT-PCR. Yellow fever is a zoonosis and cannot be eradicated, but it is preventable in man by using the 17D vaccine. A single dose is enough to protect an individual for at least

  17. Yellow fever: an update.

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    Monath, T P

    2001-08-01

    Yellow fever, the original viral haemorrhagic fever, was one of the most feared lethal diseases before the development of an effective vaccine. Today the disease still affects as many as 200,000 persons annually in tropical regions of Africa and South America, and poses a significant hazard to unvaccinated travellers to these areas. Yellow fever is transmitted in a cycle involving monkeys and mosquitoes, but human beings can also serve as the viraemic host for mosquito infection. Recent increases in the density and distribution of the urban mosquito vector, Aedes aegypti, as well as the rise in air travel increase the risk of introduction and spread of yellow fever to North and Central America, the Caribbean and Asia. Here I review the clinical features of the disease, its pathogenesis and pathophysiology. The disease mechanisms are poorly understood and have not been the subject of modern clinical research. Since there is no specific treatment, and management of patients with the disease is extremely problematic, the emphasis is on preventative vaccination. As a zoonosis, yellow fever cannot be eradicated, but reduction of the human disease burden is achievable through routine childhood vaccination in endemic countries, with a low cost for the benefits obtained. The biological characteristics, safety, and efficacy of live attenuated, yellow fever 17D vaccine are reviewed. New applications of yellow fever 17D virus as a vector for foreign genes hold considerable promise as a means of developing new vaccines against other viruses, and possibly against cancers.

  18. [An epidemic risk of yellow fever in Burkina Faso despite a rapid immunisation riposte: role of a multidisciplinary investigation team].

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    Barennes, H; Baldet, T; Cassel, A-M; Kabiré, C; Kambou, C

    2002-01-01

    On October 8, 1999, one yellow fever (YF) case is confirmed in the South West of Burkina Faso by the Centre Muraz' virology unit. Epidemic extension is suspected as large movements of population are occurring due to troubles in Côte d'Ivoire nearby and as the Aedes vector is endemic in the region. On October 23, the Gaoua's Health Regional Head immunizes 1,000 people around the detected YF case, i.e. 70% of the estimated population and requests an epidemiological investigation. A multidisciplinary team (epidemiologist, entomologist, virologist) from the Centre Muraz, a medical research centre based in Bobo Dioulasso investigate in order to answer the following questions: are there any other or asymptomatic cases of YF? How far is the epidemic risk? Is a paper filter a valuable method for collecting blood samples? What benefit can be gained from a multidisciplinary team? An epidemiological analysis of the patient, a research of asymptomatic or ignored patient is performed (Health Centre registers, interview of the population). This includes the research of people missing the immunisation campaign. Blood samples are collected through 5 ml EDTA glass tubes or through filter paper in order to measure immunoglobuline M. A classical entomological prospecting completes the investigation. Two possible cases are suspected in the patient's home. History of the patient's is in agreement with a local contamination. In the village 110 people missed the immunisation campaign and samples were collected in 58 people including 26 children. Among them, four (15.3%) were positive with immunoglobuline M, while there were none in the adults. Aedes Luteocephalus, a potential vector is collected through night-captures but is absent of home-water collection. Paper filter assays shows a 100% concordance with classical method. The team could determine the persistency of a yellow fever epidemic risk in the region despite a rapid and adequate immunisation riposte. Due to iterative sporadic

  19. Yellow Fever Vaccine: What You Need to Know

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    ... How can I prevent yellow fever? Yellow fever vaccine Yellow fever vaccine can prevent yellow fever. Yellow fever vaccine ... such as those containing DEET. 3 Yellow fever vaccine Yellow fever vaccine is a live, weakened virus. It is ...

  20. Yellow fever: epidemiology and prevention.

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    Barnett, Elizabeth D

    2007-03-15

    Yellow fever continues to occur in regions of Africa and South America, despite the availability of effective vaccines. Recently, some cases of severe neurologic disease and multiorgan system disease have been described in individuals who received yellow fever vaccine. These events have focused attention on the need to define criteria for judicious use of yellow fever vaccine and to describe the spectrum of adverse events that may be associated with yellow fever vaccine. Describing host factors that would increase risk of these events and identifying potential treatment modalities for yellow fever and yellow fever vaccine-associated adverse events are subjects of intense investigation.

  1. An epidemic of sylvatic yellow fever in the southeast region of Maranhao State, Brazil, 1993-1994: epidemiologic and entomologic findings.

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    Vasconcelos, P F; Rodrigues, S G; Degallier, N; Moraes, M A; da Rosa, J F; da Rosa, E S; Mondet, B; Barros, V L; da Rosa, A P

    1997-08-01

    Yellow fever virus transmission was very active in Maranhao State in Brazil in 1993 and 1994. An investigation was carried out to evaluate the magnitude of the epidemic. In 1993, a total of 932 people was examined for yellow fever from Maranhao: 70 were positive serologically, histopathologically, and/or by virus isolation, and another four cases were diagnosed clinically and epidemiologically. In Mirador (17,565 inhabitants), the incidence was 3.5 per 1,000 people (case fatality rate [number of deaths/number of cases diagnosed] = 16.4%), while in a rural yellow fever risk area (14,659 inhabitants), the incidence was 4.2 and the case-fatality rate was 16.1% (10 of 62). A total of 45.2% (28 of 62) asymptomatic infections were registered. In 1994, 49 serum samples were obtained and 16 cases were confirmed (two by virus isolation, two by seroconversion, and 12 by serology). No fatal cases were reported. In 1993, 936 potential yellow fever vectors were captured in Mirador and a single strain was isolated from a pool of Haemagogus janthinomys (infection rate = 0.16%). In 1994, 16 strains were isolated from 1,318 Hg. janthinomys (infection rate = 1.34%) and one Sabethes chloropterus (infection rate = 1.67%). Our results suggest that this was the most extensive outbreak of yellow fever in the last 20 years in Brazil. It is also clear that the lack of vaccination was the principal reason for the epidemic, which occurred between April and June, during the rainy season, a period in which the mosquito population in the forest increases.

  2. Shortage of vaccines during a yellow fever outbreak in Guinea.

    OpenAIRE

    Nathan, N; Barry, M; Van Herp, M; Zeller, H

    2001-01-01

    A yellow fever epidemic erupted in Guinea in September, 2000. From Sept 4, 2000, to Jan 7, 2001, 688 instances of the disease and 225 deaths were reported. The diagnosis was laboratory confirmed by IgM detection in more than 40 patients. A mass vaccination campaign was limited by insufficient international stocks. After the epidemic in Guinea, the International Coordinating Group on Vaccine Provision for Epidemic Meningitis Control decided that 2 million doses of 17D yellow fever vaccine, bei...

  3. Need yellow fever vaccine? Plan ahead

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    ... Submit What's this? Submit Button Past Emails Need yellow fever vaccine? Plan ahead. Language: English (US) Español (Spanish) ... none were from the United States). What is yellow fever? Yellow fever is caused by a virus that ...

  4. [Management of the yellow fever epidemic in 2010 in Séguéla (Côte d'Ivoire): value of multidisciplinary investigation].

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    Konan, Yao Lucien; Coulibaly, Zanakoungo Ibrahima; Allali, Kouadio Bernard; Tétchi, Sopi Mathilde; Koné, Atioumounan Blaise; Coulibaly, Daouda; Ekra, Kouadio Daniel; Doannio, Julien Marie Christian; Oudéhouri-Koudou, Paul

    2014-01-01

    In August 2010, five positive cases of yellow fever were reported in the region of Séguéla, in the northwest of Côte d'Ivoire, affected by an armed conflict since 2002. In order to evaluate the extent of yellow fever virus circulation and the risk for local people, a multidisciplinary investigation was carried out by the Côte-d'Ivoire Ministry of Health and Public Hygiene. Theses investigations were conducted in the villages of confirmed cases and the outpatient and hospitalization centers attended by infected patients, two weeks after the reactive immunization campaign performed in order to stop the spread of the epidemic. The search for suspects identified 16 cases, including 4 cases and 2 deaths in hospital registers and 12 cases during community interviews, including 6 deaths. Stegomyiens indices were relatively low. Aedes aegypti was present among adult mosquitoes. In addition, three wild vectors, varying in number from one locality to another, were detected: Ae. africanus, Ae. luteocephalus and Ae. vittatus with average biting rates of 0.3; 0.1 and 0.05 bite/man/twilight, respectively, at Soba, Ae. africanus and Ae. vittatus with average biting rates of 0.25 and 0.3 bite/man/twilight, respectively, at Yaokro and Ae. luteocephalus with one bite/man/twilight at Kaborékro. Unfortunately, the vaccine response conducted before investigations did not stop progression of the epidemic which broke out three months later in the Worofla health area, close to the Magrékros encampment.

  5. Phylogeny of Yellow Fever Virus, Uganda, 2016.

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    Hughes, Holly R; Kayiwa, John; Mossel, Eric C; Lutwama, Julius; Staples, J Erin; Lambert, Amy J

    2018-08-17

    In April 2016, a yellow fever outbreak was detected in Uganda. Removal of contaminating ribosomal RNA in a clinical sample improved the sensitivity of next-generation sequencing. Molecular analyses determined the Uganda yellow fever outbreak was distinct from the concurrent yellow fever outbreak in Angola, improving our understanding of yellow fever epidemiology.

  6. 17DD yellow fever vaccine

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    Martins, Reinaldo M.; Maia, Maria de Lourdes S.; Farias, Roberto Henrique G.; Camacho, Luiz Antonio B.; Freire, Marcos S.; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C.; Lima, Sheila Maria B.; Nogueira, Rita Maria R.; Sá, Gloria Regina S.; Hokama, Darcy A.; de Carvalho, Ricardo; Freire, Ricardo Aguiar V.; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-01-01

    Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. International Register ISRCTN 38082350. PMID:23364472

  7. Perinatal Yellow Fever: A Case Report.

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    Diniz, Lilian Martins Oliveira; Romanelli, Roberta Maia Castro; de Carvalho, Andréa Lucchesi; Teixeira, Daniela Caldas; de Carvalho, Luis Fernando Andrade; Cury, Verônica Ferreira; Filho, Marcelo Pereira Lima; Perígolo, Graciele; Heringer, Tiago Pires

    2018-04-09

    An outbreak of yellow fever in Brazil made it possible to assess different presentations of disease such as perinatal transmission. A pregnant woman was admitted to hospital with yellow fever symptoms. She was submitted to cesarean section and died due to fulminant hepatitis. On the 6th day the newborn developed liver failure and died 13 days later. Yellow fever PCR was positive for both.

  8. Yellow fever, Asia and the East African slave trade.

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    Cathey, John T; Marr, John S

    2014-05-01

    Yellow fever is endemic in parts of sub-Saharan Africa and South America, yet its principal vectors--species of mosquito of the genus Aedes--are found throughout tropical and subtropical latitudes. Phylogenetic analyses indicate that yellow fever originated in Africa and that its spread to the New World coincided with the slave trade, but why yellow fever has never appeared in Asia remains a mystery. None of several previously proposed explanations for its absence there is considered satisfactory. We contrast the trans-Atlantic slave trade, and trade across the Sahara and to the Arabian Peninsula and Mesopotamia, with that to Far East and Southeast Asian ports before abolition of the African slave trade, and before the scientific community understood the transmission vector of yellow fever and the viral life cycle, and the need for shipboard mosquito control. We propose that these differences in slave trading had a primary role in the avoidance of yellow fever transmission into Asia in the centuries before the 20(th) century. The relatively small volume of the Black African slave trade between Africa and East and Southeast Asia has heretofore been largely ignored. Although focal epidemics may have occurred, the volume was insufficient to reach the threshold for endemicity.

  9. STUDIES ON SOUTH AMERICAN YELLOW FEVER

    Science.gov (United States)

    Davis, Nelson C.; Shannon, Raymond C.

    1929-01-01

    Yellow fever virus from M. rhesus has been inoculated into a South American monkey (Cebus macrocephalus) by blood injection and by bites of infected mosquitoes. The Cebus does not develop the clinical or pathological signs of yellow fever. Nevertheless, the virus persists in the Cebus for a time as shown by the typical symptoms and lesions which develop when the susceptible M. rhesus is inoculated from a Cebus by direct transfer of blood or by mosquito (A. aegypti) transmission. PMID:19869607

  10. Facing up to re-emergence of urban yellow fever.

    Science.gov (United States)

    Monath, T P

    1999-05-08

    Transmitted from person to person by Aedes aegypti, urban yellow fever was eliminated in the first half of this century, with the eradication of its mosquito vector from most of South America. However, reinfestation began in the 1970s is now almost complete, and vector control is considerably more difficult now than before. The threat of urban yellow fever is greatest in towns such as Santa Cruz, Bolivia, near the forest, but improved transport links increase the likelihood of spread by viremic people to nonendemic areas. Van der Stuyft et al. have reported the first instance of urban transmission of yellow fever in the Americas in 44 years. Since residents of the densely populated cities and much visited areas in coastal South America have never been vaccinated, an outbreak there would facilitate widespread dissemination of the disease, even to other continents. While urban yellow fever is a significant threat, carrying a case-fatality rate of about 20%, the constrained dynamics of transmission, early recognition of the striking clinical presentation, and efforts to control the infection should limit the impact of the disease. Laboratory-based surveillance, together with the prevention and control strategies outlined by van der Stuyft et al. are the key defensive measures against the future threat of urban epidemics.

  11. Samuel Holden Parsons Lee (1772-1863): American physician, entrepreneur and selfless fighter of the 1798 Yellow Fever epidemic of New London, Connecticut.

    Science.gov (United States)

    Mattie, James K; Desai, Sukumar P

    2015-02-01

    Samuel Holden Parsons Lee practised medicine at a time when the germ theory of disease had not yet been proposed and antibiotics remained undiscovered. In 1798 he served selflessly as the only physician in town who was willing to battle the Yellow Fever outbreak of New London, Connecticut. Because he practised at the dawn of the age of patent medicine, unfortunately his name also came to be associated with medical quackery. We argue that his contributions have been grossly underestimated. He compounded and vended medications - including bilious pills and bitters - that were gold standards of the day. Moreover, one preparation for treatment of kidney stones led to his sub-specialization in this field and was met with such success that its sale continued for nearly 100 years after his death. While a talented medical man, Lee also had a knack for business, finding success in trading, whaling and real estate. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Estimating the number of unvaccinated Chinese workers against yellow fever in Angola.

    Science.gov (United States)

    Wilder-Smith, A; Massad, E

    2018-04-17

    A yellow fever epidemic occurred in Angola in 2016 with 884 laboratory confirmed cases and 373 deaths. Eleven unvaccinated Chinese nationals working in Angola were also infected and imported the disease to China, thereby presenting the first importation of yellow fever into Asia. In Angola, there are about 259,000 Chinese foreign workers. The fact that 11 unvaccinated Chinese workers acquired yellow fever suggests that many more Chinese workers in Angola were not vaccinated. We applied a previously developed model to back-calculate the number of unvaccinated Chinese workers in Angola in order to determine the extent of lack of vaccine coverage. Our models suggest that none of the 259,000 Chinese had been vaccinated, although yellow fever vaccination is mandated by the International Health Regulations. Governments around the world including China need to ensure that their citizens obtain YF vaccination when traveling to countries where such vaccines are required in order to prevent the international spread of yellow fever.

  13. [The fourth horseman: The yellow fever].

    Science.gov (United States)

    Vallejos-Parás, Alfonso; Cabrera-Gaytán, David Alejandro

    2017-01-01

    Dengue virus three, Chikunguya and Zika have entered the national territory through the south of the country. Cases and outbreaks of yellow fever have now been identified in the Americas where it threatens to expand. Although Mexico has a robust epidemiological surveillance system for vector-borne diseases, our country must be alert in case of its possible introduction into the national territory. This paper presents theoretical assumptions based on factual data on the behavior of yellow fever in the Americas, as well as reflections on the epidemiological surveillance of vector-borne diseases.

  14. International travel between global urban centres vulnerable to yellow fever transmission.

    Science.gov (United States)

    Brent, Shannon E; Watts, Alexander; Cetron, Martin; German, Matthew; Kraemer, Moritz Ug; Bogoch, Isaac I; Brady, Oliver J; Hay, Simon I; Creatore, Maria I; Khan, Kamran

    2018-05-01

    To examine the potential for international travel to spread yellow fever virus to cities around the world. We obtained data on the international flight itineraries of travellers who departed yellow fever-endemic areas of the world in 2016 for cities either where yellow fever was endemic or which were suitable for viral transmission. Using a global ecological model of dengue virus transmission, we predicted the suitability of cities in non-endemic areas for yellow fever transmission. We obtained information on national entry requirements for yellow fever vaccination at travellers' destination cities. In 2016, 45.2 million international air travellers departed from yellow fever-endemic areas of the world. Of 11.7 million travellers with destinations in 472 cities where yellow fever was not endemic but which were suitable for virus transmission, 7.7 million (65.7%) were not required to provide proof of vaccination upon arrival. Brazil, China, India, Mexico, Peru and the United States of America had the highest volumes of travellers arriving from yellow fever-endemic areas and the largest populations living in cities suitable for yellow fever transmission. Each year millions of travellers depart from yellow fever-endemic areas of the world for cities in non-endemic areas that appear suitable for viral transmission without having to provide proof of vaccination. Rapid global changes in human mobility and urbanization make it vital for countries to re-examine their vaccination policies and practices to prevent urban yellow fever epidemics.

  15. Serologic assessment of yellow fever immunity in the rural population of a yellow fever-endemic area in Central Brazil

    Directory of Open Access Journals (Sweden)

    Vanessa Wolff Machado

    2013-04-01

    Full Text Available Introduction The yellow fever epidemic that occurred in 1972/73 in Central Brazil surprised the majority of the population unprotected. A clinical-epidemiological survey conducted at that time in the rural area of 19 municipalities found that the highest (13.8% number of disease cases were present in the municipality of Luziânia, State of Goiás. Methods Thirty-eight years later, a new seroepidemiological survey was conducted with the aim of assessing the degree of immune protection of the rural population of Luziânia, following the continuous attempts of public health services to obtain vaccination coverage in the region. A total of 383 volunteers, aged between 5 and 89 years and with predominant rural labor activities (75.5%, were interviewed. The presence of antibodies against the yellow fever was also investigated in these individuals, by using plaque reduction neutralization test, and correlated to information regarding residency, occupation, epidemiological data and immunity against the yellow fever virus. Results We found a high (97.6% frequency of protective titers (>1:10 of neutralizing antibodies against the yellow fever virus; the frequency of titers of 1:640 or higher was 23.2%, indicating wide immune protection against the disease in the study population. The presence of protective immunity was correlated to increasing age. Conclusions This study reinforces the importance of surveys to address the immune state of a population at risk for yellow fever infection and to the surveillance of actions to control the disease in endemic areas.

  16. Enzootic transmission of yellow fever virus, Venezuela.

    Science.gov (United States)

    Auguste, Albert J; Lemey, Philippe; Bergren, Nicholas A; Giambalvo, Dileyvic; Moncada, Maria; Morón, Dulce; Hernandez, Rosa; Navarro, Juan-Carlos; Weaver, Scott C

    2015-01-01

    Phylogenetic analysis of yellow fever virus (YFV) strains isolated from Venezuela strongly supports YFV maintenance in situ in Venezuela, with evidence of regionally independent evolution within the country. However, there is considerable YFV movement from Brazil to Venezuela and between Trinidad and Venezuela.

  17. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  18. The Yellow Fever Vaccine: A History

    OpenAIRE

    Frierson, J. Gordon

    2010-01-01

    After failed attempts at producing bacteria-based vaccines, the discovery of a viral agent causing yellow fever and its isolation in monkeys opened new avenues of research. Subsequent advances were the attenuation of the virus in mice and later in tissue culture; the creation of the seed lot system to avoid spontaneous mutations; the ability to produce the vaccine on a large scale in eggs; and the removal of dangerous contaminants. An important person in the story is Max Theiler, who was Prof...

  19. Longitudinal myelitis associated with yellow fever vaccination.

    Science.gov (United States)

    Chaves, M; Riccio, P; Patrucco, L; Rojas, J I; Cristiano, E

    2009-07-01

    Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever vaccine-associated neurotropic disease. This terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. The objective of this communication is to report a patient who received a YF vaccine in Argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. A 56-year-old man began with progressive paraparesia, urinary retention, and constipation 48 h previous to admission. The patient received YF vaccine 45 days prior to the onset of the symptoms. There was no history of other immunization or relevant condition. MR of the spine showed longitudinal intramedullary hyperintense signal (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests for other flavivirus were negative. A diagnosis of longitudinal myelitis without encephalitis associated with YF vaccine was performed and symptoms improved 5 days later. This is the first report dealing with longitudinal myelitis as a serious adverse event associated with YF vaccination in which confirmation of the presence of antibodies in CSF was found. To date, it is also the first report with serological confirmation in Argentina and in South America. We consider that the present investigation will raise awareness in the region in the reporting of adverse events related to YF vaccine and improve our knowledge of adverse reactions to the vaccine.

  20. The thermal stability of yellow fever vaccines

    Directory of Open Access Journals (Sweden)

    Ricardo Ishak

    1990-09-01

    Full Text Available The assessment of yellow fever vaccine thermostability both in lyophilized form and after reconstitution were analyzed. Two commercial yellow fever vaccines were assayed for their thermal stability. Vaccines were exposed to test temperatures in the range of 8 (graus C to 45 (graus C. Residual infectivity was measured by a plaque assay using Vero cells. The titre values were used in an accelerated degradation test that follows the Arrhenius equation and the minimum immunizing dose was assumed to be 10 (ao cubo particles forming unit (pfu/dose. Some of the most relevant results include that (i regular culture medium show the same degradation pattern of a reconstituted 17D-204 vaccine; (ii reconstituted YF-17D-204 showed a predictable half life of more than six days if kept at 0 (graus C; (iii there are differences in thermostability between different products that are probably due to both presence of stabilizers in the preparation and the modernization in the vaccine production; (iv it is important to establish a proper correlation between the mouse infectivity test and the plaque assay since the last appears to be more simple, economical, and practical for small laboratories to assess the potency of the vaccine, and (v the accelerated degradation test appears to be the best procedure to quantify the thermostability of biological products.

  1. Impact of yellow fever on the developing world.

    Science.gov (United States)

    Tomori, O

    1999-01-01

    Yellow fever (YF) has remained a disease of public health importance since it was first described in the fifteenth century. At different periods in human history, YF has caused untold hardship and indescribable misery among populations in the Americas, Europe, and Africa. It brought economic disaster in its wake, constituting a stumbling block to development. Yellow fever is an arboviral infection with three epidemiological transmission cycles between monkeys, mosquitoes, and humans. It is an acute infectious disease characterized by sudden onset, with two phases of development separated by a short period of remission. The clinical spectrum of YF varies from a very mild, nonspecific, febrile illness to a fulminating, sometimes fatal disease with pathognomonic features. In severe cases, jaundice and bleeding diathesis with hepatorenal involvement are common. The fatality rate of severe YF is 50% or higher. Despite landmark achievements in the understanding of the epidemiology of YF and the availability of a safe, efficacious vaccine, YF remains a major public health problem in both Africa and South America, where annually the disease affects an estimated 200,000 persons, causing an estimated 30,000 deaths. Since the 1980s epidemics of YF in Africa have affected predominantly children under the age of 15 years. The failure to control YF arises from a misapplication of public health strategies and insufficient political commitment by governments in YF endemic areas, especially in Africa, to control the disease.

  2. Traveling Abroad: Latest Yellow Fever Vaccine Update | Poster

    Science.gov (United States)

    Earlier this month, the U.S. Centers for Disease Control and Prevention (CDC) released its list of clinics that are administering the yellow fever vaccine Stamaril, which has been made available to address the total depletion of the United States’ primary yellow fever vaccine, YF-VAX. These clinics will provide the vaccine to individuals preparing for international travel,

  3. Fatal Yellow Fever in Travelers to Brazil, 2018.

    Science.gov (United States)

    Hamer, Davidson H; Angelo, Kristina; Caumes, Eric; van Genderen, Perry J J; Florescu, Simin A; Popescu, Corneliu P; Perret, Cecilia; McBride, Angela; Checkley, Anna; Ryan, Jenny; Cetron, Martin; Schlagenhauf, Patricia

    2018-03-23

    Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination.

  4. What a rheumatologist needs to know about yellow fever vaccine.

    Science.gov (United States)

    Oliveira, Ana Cristina Vanderley; Mota, Licia Maria Henrique da; Santos-Neto, Leopoldo Luiz Dos; Tauil, Pedro Luiz

    2013-04-01

    Patients with rheumatic diseases are more susceptible to infection, due to the underlying disease itself or to its treatment. The rheumatologist should prevent infections in those patients, vaccination being one preventive measure to be adopted. Yellow fever is one of such infectious diseases that can be avoided.The yellow fever vaccine is safe and effective for the general population, but, being an attenuated live virus vaccine, it should be avoided whenever possible in rheumatic patients on immunosuppressive drugs. Considering that yellow fever is endemic in a large area of Brazil, and that vaccination against that disease is indicated for those living in such area or travelling there, rheumatologists need to know that disease, as well as the indications for the yellow fever vaccine and contraindications to it. Our paper was aimed at highlighting the major aspects rheumatologists need to know about the yellow fever vaccine to decide about its indication or contraindication in specific situations. 2013 Elsevier Editora Ltda. All rights reserved.

  5. Yellow Fever Outbreaks in Unvaccinated Populations, Brazil, 2008–2009

    Science.gov (United States)

    Romano, Alessandro Pecego Martins; Costa, Zouraide Guerra Antunes; Ramos, Daniel Garkauskas; Andrade, Maria Auxiliadora; Jayme, Valéria de Sá; de Almeida, Marco Antônio Barreto; Vettorello, Kátia Campomar; Mascheretti, Melissa; Flannery, Brendan

    2014-01-01

    Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43%) in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39%) in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered) and 45 cases of acute neurotropic disease (5.6 per million doses administered). Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever. PMID:24625634

  6. Viscerotropic disease following yellow fever vaccination in Peru.

    Science.gov (United States)

    Whittembury, Alvaro; Ramirez, Gladys; Hernández, Herminio; Ropero, Alba Maria; Waterman, Steve; Ticona, María; Brinton, Margo; Uchuya, Jorge; Gershman, Mark; Toledo, Washington; Staples, Erin; Campos, Clarense; Martínez, Mario; Chang, Gwong-Jen J; Cabezas, Cesar; Lanciotti, Robert; Zaki, Sherif; Montgomery, Joel M; Monath, Thomas; Hayes, Edward

    2009-10-09

    Five suspected cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) clustered in space and time following a vaccination campaign in Ica, Peru in 2007. All five people received the same lot of 17DD live attenuated yellow fever vaccine before their illness; four of the five died of confirmed YEL-AVD. The surviving case was classified as probable YEL-AVD. Intensive investigation yielded no abnormalities of the implicated vaccine lot and no common risk factors. This is the first described space-time cluster of yellow fever viscerotropic disease involving more than two cases. Mass yellow fever vaccination should be avoided in areas that present extremely low risk of yellow fever.

  7. Present status of yellow fever: Memorandum from a PAHO Meeting

    OpenAIRE

    1986-01-01

    An international seminar on the treatment and laboratory diagnosis of yellow fever, sponsored by the Pan American Health Organization (PAHO) and held in 1984, differed from previous meetings on yellow fever because of its emphasis on the care and management of patients and because the participants included specialists from several branches of medicine, such as hepatology, haematology, cardiology, infectious diseases, pathology and nephrology. The meeting reviewed the current status of yellow ...

  8. The centennial of the Yellow Fever Commission and the use of informed consent in medical research

    Directory of Open Access Journals (Sweden)

    Güereña-Burgueño Fernando

    2002-01-01

    Full Text Available The year 2000 marked the centennial of the discovery of the mode of transmission of yellow fever. Informed consent was systematically used for the first time in research. This process was the result of a complex social phenomenon involving the American Public Health Association, the US and Spanish Governments, American and Cuban scientists, the media, and civilian and military volunteers. The public health and medical communities face the AIDS pandemic at the beginning of the 21st Century, as they faced the yellow fever epidemic at the beginning of the 20th Century. Current medical research dilemmas have fueled the debate about the ethical conduct of research in human subjects. The AIDS pandemic is imposing enormous new ethical challenges on the conduct of medical research, especially in the developing world. Reflecting on the yellow fever experiments of 1900, lessons can be learned and applied to the current ethical challenges faced by the international public health research community.

  9. Dengue and the risk of urban yellow fever reintroduction in São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Massad Eduardo

    2003-01-01

    Full Text Available OBJECTIVE: To propose a mathematical method for the estimation of the Basic Reproduction Number, R0, of urban yellow fever in a dengue-infested area. METHODS: The method is based on the assumption that, as the same vector (Aedes aegypti causes both infections, all the quantities related to the mosquito, estimated from the initial phase of dengue epidemic, could be applied to yellow fever dynamics. It is demonstrated that R0 for yellow fever is, on average, 43% lower than that for dengue. This difference is due to the longer dengue viremia and its shorter extrinsic incubation period. RESULTS: In this study the analysis was expanded to the epidemiological situation of dengue in São Paulo in the year 2001. The total number of dengue cases increased from 3,582 in 2000 to 51,348 in 2001. It was then calculated R0 for yellow fever for every city which have shown R0 of dengue greater than 1. It was also estimated the total number of unprotected people living in highly risky areas for urban yellow fever. CONCLUSIONS: Currently there is a great number of non-vaccinated people living in Aedes aegypti infested area in the state of São Paulo.

  10. 42 CFR 71.3 - Designation of yellow fever vaccination centers; Validation stamps.

    Science.gov (United States)

    2010-10-01

    ... safe, potent, and pure yellow fever vaccine. Medical facilities of Federal agencies are authorized to obtain yellow fever vaccine without being designated as a yellow fever vaccination center by the Director..., storage, and administration of yellow fever vaccine. If a designated center fails to comply with such...

  11. [Control discourses and power relations of yellow fever: Philadelphia in 1793].

    Science.gov (United States)

    Kim, Seohyung

    2014-12-01

    1793 Yellow fever in Philadelphia was the most severe epidemics in the late 18th century in the United States. More than 10% of the population in the city died and many people fled to other cities. The cause of yellow fever in the United States had close relationship with slaves and sugar in Philadelphia. Sugarcane plantation had needed many labors to produce sugar and lots of Africans had to move to America as slaves. In this process, Aëdes aegypti, the vector of yellow fever had migrated to America and the circumstances of ships or cities provided appropriate conditions for its breeding. In this period, the cause of yellow fever could not be established exactly, so suggestions of doctors became entangled in political and intellectual discourses in American society. There was a critical conflict between Jeffersonian Republicanism and Federalism about the origin and treatment of yellow fever. Benjamin Rush, a Jeffersonian Republican, suggested urban sanitation reform and bloodletting. He believed the infectious disease happened because of unsanitary city condition, so he thought the United States could be a healthy nation by improvement of the public health and sanitation. He would like to cope with national crisis and develop American society on the basis of republicanism. While Rush suggested the improvement of public health and sanitation, the city government of Philadelphia suggested isolation of yellow fever patients and quarantine. City government isolated the patients from healthy people and it reconstructed space of hospital. Also, it built orphanages to take care of children who lost their parents during the epidemic and implemented power to control people put in the state of exception. Of course, city government tried to protect the city and nation by quarantine of every ship to Philadelphia. Control policies of yellow fever in 1793 showed different conflicts and interactions. Through the yellow fever, Jeffersonian Republicanism and Federalism had

  12. Is it time for a new yellow fever vaccine?

    Science.gov (United States)

    Hayes, Edward B

    2010-11-29

    An inexpensive live attenuated vaccine (the 17D vaccine) against yellow fever has been effectively used to prevent yellow fever for more than 70 years. Interest in developing new inactivated vaccines has been spurred by recognition of rare but serious, sometimes fatal adverse events following live virus vaccination. A safer inactivated yellow fever vaccine could be useful for vaccinating people at higher risk of adverse events from the live vaccine, but could also have broader global health utility by lowering the risk-benefit threshold for assuring high levels of yellow fever vaccine coverage. If ongoing trials demonstrate favorable immunogenicity and safety compared to the current vaccine, the practical global health utility of an inactivated vaccine is likely to be determined mostly by cost. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Yellow fever vectors' surveillance in three satellite communities of ...

    African Journals Online (AJOL)

    Outbreaks of yellow fever have continued to occur in various parts of Nigeria. ... easily render themselves to vector and environmental management strategies. ... vectors, while locally adapted CDC (Centre for Disease Control) ovitraps were ...

  14. An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine

    OpenAIRE

    Wauters, Robert H.; Hernandez, Camellia L.; Petersen, Maureen M.

    2017-01-01

    Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

  15. An Atypical Local Vesicular Reaction to the Yellow Fever Vaccine.

    Science.gov (United States)

    Wauters, Robert H; Hernandez, Camellia L; Petersen, Maureen M

    2017-09-19

    Yellow fever vaccine is a live attenuated viral inoculation indicated for patients traveling to endemic areas. The vaccine is generally well tolerated with minimal adverse effects. Typical side effects include malaise, pain at the injection site, and, albeit rarely, immediate hypersensitivity reactions. We present a case of a rare adverse reaction to yellow fever vaccine in which a patient developed vesicular lesions resulting in bullae and circumferential hyperpigmentation.

  16. An inactivated yellow fever 17DD vaccine cultivated in Vero cell cultures.

    Science.gov (United States)

    Pereira, Renata C; Silva, Andrea N M R; Souza, Marta Cristina O; Silva, Marlon V; Neves, Patrícia P C C; Silva, Andrea A M V; Matos, Denise D C S; Herrera, Miguel A O; Yamamura, Anna M Y; Freire, Marcos S; Gaspar, Luciane P; Caride, Elena

    2015-08-20

    Yellow fever is an acute infectious disease caused by prototype virus of the genus Flavivirus. It is endemic in Africa and South America where it represents a serious public health problem causing epidemics of hemorrhagic fever with mortality rates ranging from 20% to 50%. There is no available antiviral therapy and vaccination is the primary method of disease control. Although the attenuated vaccines for yellow fever show safety and efficacy it became necessary to develop a new yellow fever vaccine due to the occurrence of rare serious adverse events, which include visceral and neurotropic diseases. The new inactivated vaccine should be safer and effective as the existing attenuated one. In the present study, the immunogenicity of an inactivated 17DD vaccine in C57BL/6 mice was evaluated. The yellow fever virus was produced by cultivation of Vero cells in bioreactors, inactivated with β-propiolactone, and adsorbed to aluminum hydroxide (alum). Mice were inoculated with inactivated 17DD vaccine containing alum adjuvant and followed by intracerebral challenge with 17DD virus. The results showed that animals receiving 3 doses of the inactivated vaccine (2 μg/dose) with alum adjuvant had neutralizing antibody titers above the cut-off of PRNT50 (Plaque Reduction Neutralization Test). In addition, animals immunized with inactivated vaccine showed survival rate of 100% after the challenge as well as animals immunized with commercial attenuated 17DD vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Typhus, yellow fever and Medicine in Mexico during the French intervention

    Science.gov (United States)

    Gerardo-Ramírez, Monserrat; Zavaleta-Castro, Jesús; Gómez-Quiroz, Luis Enrique

    2018-01-01

    French intervention in Mexico (1861-1867) is particularly full of episodes of patriotic heroism in terms of military, politic and, even, religious affairs, however this history is also rich in episodes related to diseases and the evolution of Mexican scientific medicine practice, epidemics such as typhus (nowadays knows as rickettsiosis), yellow fever, or cholera. Principally, this context outlined the Mexican history and influenced the course of the nation. The epidemics served as fertile land for the development of medicine science leading by prominent physicians, particularly by doctor Miguel Francisco Jiménez. Copyright: © 2018 SecretarÍa de Salud.

  18. Epidemiological, Clinical and Entomological Characteristics of Yellow Fever Outbreak in Darfur 2012

    Directory of Open Access Journals (Sweden)

    Hamdi Abdulwahab Alhakimi

    2015-03-01

    Full Text Available The study aims at analyzing the epidemiological, clinical and entomological characteristics of Darfur yellow fever epidemic. It is a descriptive, cross-sectional study. According to operational case definition, suspected yellow fever cases are included in case spread sheet with variables like age, sex, locality, occupation, status of vaccination, onset of symptoms, presenting symptoms, date of blood sampling and confirmation of diagnosis either by laboratory results or epidemiological link. Data about important entomological indices were collected by surveys conducted in 17 localities of 3 Darfur states (Central, West and south Darfur. All Darfur states (especially Central Darfur have been affected by Yellow Fever outbreak. There is a need to review the non-specific case definition of Yellow Fever which seems to overwhelm the system during outbreaks with cases of other endemic diseases. The significant risk factors of this outbreak included male sex, adult age, outdoor occupation and traditional mining. The fatality rate was significantly associated with vaccination status. The highest fatality rate was recorded by children less than 2 years old (42.9%. Generally, increase in certain entomological indices was followed by increase in number of reported cases 7 days later. Central Darfur state was significantly higher in most studied entomological indices.

  19. Epidemiological, Clinical and Entomological Characteristics of Yellow Fever Outbreak in Darfur 2012.

    Science.gov (United States)

    Alhakimi, Hamdi Abdulwahab; Mohamed, Omima Gadalla; Khogaly, Hayat Salah Eldin; Arafa, Khalid Ahmad Omar; Ahmed, Waled Amen

    2015-01-01

    The study aims at analyzing the epidemiological, clinical and entomological characteristics of Darfur yellow fever epidemic. It is a descriptive, cross-sectional study. According to operational case definition, suspected yellow fever cases are included in case spread sheet with variables like age, sex, locality, occupation, status of vaccination, onset of symptoms, presenting symptoms, date of blood sampling and confirmation of diagnosis either by laboratory results or epidemiological link. Data about important entomological indices were collected by surveys conducted in 17 localities of 3 Darfur states (Central, West and south Darfur). All Darfur states (especially Central Darfur) have been affected by Yellow Fever outbreak. There is a need to review the non-specific case definition of Yellow Fever which seems to overwhelm the system during outbreaks with cases of other endemic diseases. The significant risk factors of this outbreak included male sex, adult age, outdoor occupation and traditional mining. The fatality rate was significantly associated with vaccination status. The highest fatality rate was recorded by children less than 2 years old (42.9%). Generally, increase in certain entomological indices was followed by increase in number of reported cases 7 days later. Central Darfur state was significantly higher in most studied entomological indices.

  20. Yellow Fever outbreaks in unvaccinated populations, Brazil, 2008-2009.

    Directory of Open Access Journals (Sweden)

    Alessandro Pecego Martins Romano

    2014-03-01

    Full Text Available Due to the risk of severe vaccine-associated adverse events, yellow fever vaccination in Brazil is only recommended in areas considered at risk for disease. From September 2008 through June 2009, two outbreaks of yellow fever in previously unvaccinated populations resulted in 21 confirmed cases with 9 deaths (case-fatality, 43% in the southern state of Rio Grande do Sul and 28 cases with 11 deaths (39% in Sao Paulo state. Epizootic deaths of non-human primates were reported before and during the outbreak. Over 5.5 million doses of yellow fever vaccine were administered in the two most affected states. Vaccine-associated adverse events were associated with six deaths due to acute viscerotropic disease (0.8 deaths per million doses administered and 45 cases of acute neurotropic disease (5.6 per million doses administered. Yellow fever vaccine recommendations were revised to include areas in Brazil previously not considered at risk for yellow fever.

  1. Yellow fever risk assessment in the Central African Republic.

    Science.gov (United States)

    Ramos Junior, Alberto Novaes; Heukelbach, Jorg

    2015-04-01

    Yellow fever still causes high burden in several areas of sub-Saharan Africa and Latin America. There are few well-designed epidemiological studies and limited data about yellow fever in Africa. Staples et al., in a recently published paper in Transactions of the Royal Society of Tropical Medicine & Hygiene, performed a nationwide study in the Central African Republic (CAR) assessing infection risk and the operational impact of preventive measures. The rapid assessment of human, non-human and mosquito data call attention to the potential risk of future yellow fever outbreaks in the CAR and elsewhere. The study reinforces the need for intensified applied and operational research to address problems and human capacity needs in the realm of neglected tropical diseases in the post-2015 agenda. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. [Long term persistence of yellow fever neutralising antibodies in elderly persons].

    Science.gov (United States)

    Coulange Bodilis, H; Benabdelmoumen, G; Gergely, A; Goujon, C; Pelicot, M; Poujol, P; Consigny, P H

    2011-10-01

    The activity of the yellow fever virus is reemerging in areas without recent transmission history, such as northern Argentina and Paraguay, and persists in an epidemic mode in other countries in Africa and Latin America. Thus more and more travelers are at risk of being exposed to this disease. The population is becoming older, sometimes suffering from multiple pathologies. Moreover, the risk of serious adverse events associated with live-attenuated YF17D vaccine, such as multiple organ failure (YEL-AVD), reaches 1/50,000 vaccines in people over 65 versus 1/200,000 in the general population. We analyzed, in a retrospective study, the results of neutralizing antibody titers against yellow fever in people aged 60 and older, who had been previously vaccinated against yellow fever and had visited the International Vaccination Centre of the Institut Pasteur between January 2005 and February 2009. In this population of 84 persons (median age 69 years), the date of the last vaccination was always more than 10 years: it was precisely known in 68 subjects and alleged in 16 subjects. The median time since the previous vaccination was 14 years, with a maximum of 60 years. The indications of serology were: immunosuppressive therapy (19% of cases), cancer (32%), hemopathy (10.7%), HIV infection (3.6%), chronic hepatitis/chronic renal failure/dialysis (2.4%), autoimmune diseases (2.4%), and in 29.8% of cases, age alone was the indication of serology. The antibody titer was at a protective level in 95.2% of cases. The four individuals with negative serology had no formal documented proof of a previous vaccination against yellow fever. This serological study was able to show a persistent protective antibody titer, after a previous vaccination, even going back 60 years, allowing patients to travel in a yellow-fever endemic area despite a contraindication, and without requiring any vaccine booster.

  3. Yellow fever vaccine: worthy friend or stealthy foe?

    Science.gov (United States)

    Seligman, Stephen J; Casanova, Jean-Laurent

    2016-06-01

    Recognition that the live yellow fever vaccine may rarely be associated with viscerotropic disease (YEL-AVD) has diminished its safety status. However, the vaccine remains the principal tool for limiting the occurrence of yellow fever, making large portions of Africa and South America more habitable. The subject has previously been exhaustively reviewed. Novel concepts in the current report include the description of a systematic method for deciding whom to vaccinate, recommendations for obtaining data helpful in making that decision, and suggestions for additional study. The vaccine is indeed a worthy friend, but its adverse reactions need to be recognized.

  4. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report:

    OpenAIRE

    Štuhec, Matej

    2014-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

  5. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate

    OpenAIRE

    Štuhec, Matej

    2015-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were noadverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. ...

  6. EXPERIMENTAL STUDIES ON YELLOW FEVER IN NORTHERN PERU.

    Science.gov (United States)

    Noguchi, H; Kligler, I J

    1921-01-31

    Fourteen typical cases of yellow fever were studied in northern Peru during an epidemic occurring in 1920, nine in Payta in March and April, and five in Morropon and Piura in April and May. The method of investigation was similar to that previously employed, but as the laboratory facilities were very meager certain changes were required. Although in Payta the work was handicapped by the lack of electric light, the scarcity of water and animal food, the unsuitability of the guinea pigs for inoculation, and the changes in culture media due to age, the results obtained under these adverse conditions were by no means negative. While in no instance was there a typical infection produced in animals, either by direct inoculation of blood or with culture materials, yet certain guinea pigs in each series showed temporary febrile reactions or definite hemorrhagic lesions of the lungs indicative of a mild leptospira infection. Direct search for Leptospira icteroides in the blood of patients or in culture materials was not made because the dark-field microscope could not be used. Subsequently, at Piura, the laboratory facilities were vastly, improved, the use of the dark-field microscope was made possible by means of a storage battery, and a fresh stock of young healthy guinea pigs was received from New York, and fresh rabbit serum obtained in Piura. In the study of the materials obtained from five cases of yellow fever in Morropon all these added facilities were taken advantage of, with the result that the outcome was positive and convincing. Cultures from the five cases were examined after 11, 12, and 13 days, and in those from three cases living leptospiras were found. By inoculation into suitable guinea pigs of culture material from these five cases, irrespective of whether or not leptospiras were detected under the dark-field microscope, a typical Leptospira icteroides infection was produced from four of the five cases. In one of these no leptospira had been detected in

  7. Serious adverse events associated with yellow fever vaccine.

    Science.gov (United States)

    de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

    2015-01-01

    Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

  8. How Brazil joined the quest for a yellow fever vaccine

    OpenAIRE

    2013-01-01

    Brazil recently announced an agreement between its Bio-Manguinhos vaccine unit and two US companies to research and develop a new yellow fever vaccine. Claudia Jurberg and Julia D’Aloisio talk to Jaime Benchimol about the controversial history of the development of the vaccine that benefits millions of people today.

  9. Suspected YF-AND after yellow fever vaccination in Finland.

    Science.gov (United States)

    Jääskeläinen, Anne J; Huhtamo, Eili; Kivioja, Reetta; Domingo, Cristina; Vene, Sirkka; Kallio-Kokko, Hannimari; Niedrig, Matthias; Tienari, Pentti J; Vapalahti, Olli

    2014-11-01

    Yellow fever (YF) vaccine is considered safe but vaccine-associated complications have also been encountered. We report neurological symptoms after YF-vaccination in a previously healthy Finnish male. Other concomitant infections or causes for the symptoms could not be identified. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Oral receptivity of Aedes aegypti from Cape Verde for yellow fever, dengue, and chikungunya viruses.

    Science.gov (United States)

    Vazeille, Marie; Yébakima, André; Lourenço-de-Oliveira, Ricardo; Andriamahefazafy, Barrysson; Correira, Artur; Rodrigues, Julio Monteiro; Veiga, Antonio; Moreira, Antonio; Leparc-Goffart, Isabelle; Grandadam, Marc; Failloux, Anna-Bella

    2013-01-01

    At the end of 2009, 21,313 cases of dengue-3 virus (DENV-3) were reported in the islands of Cape Verde, an archipelago located in the Atlantic Ocean 570 km from the coast of western Africa. It was the first dengue outbreak ever reported in Cape Verde. Mosquitoes collected in July 2010 in the city of Praia, on the island of Santiago, were identified morphologically as Aedes aegypti formosus. Using experimental oral infections, we found that this vector showed a moderate ability to transmit the epidemic dengue-3 virus, but was highly susceptible to chikungunya and yellow fever viruses.

  11. Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report.

    Science.gov (United States)

    Stuhec, Matej

    2014-01-01

    The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

  12. The centennial of the Yellow Fever Commission and the use of informed consent in medical research.

    Science.gov (United States)

    Güereña-Burgueño, Fernando

    2002-01-01

    The year 2000 marked the centennial of the discovery of the mode of transmission of yellow fever. Informed consent was systematically used for the first time in research. This process was the result of a complex social phenomenon involving the American Public Health Association, the US and Spanish Governments, American and Cuban scientists, the media, and civilian and military volunteers. The public health and medical communities face the AIDS pandemic at the beginning of the 21st Century, as they faced the yellow fever epidemic at the beginning of the 20th Century. Current medical research dilemmas have fueled the debate about the ethical conduct of research in human subjects. The AIDS pandemic is imposing enormous new ethical challenges on the conduct of medical research, especially in the developing world. Reflecting on the yellow fever experiments of 1900, lessons can be learned and applied to the current ethical challenges faced by the international public health research community. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.

  13. Yellow fever vaccine-associated neurological disease, a suspicious case.

    Science.gov (United States)

    Beirão, Pedro; Pereira, Patrícia; Nunes, Andreia; Antunes, Pedro

    2017-03-02

    A 70-year-old man with known cardiovascular risk factors, presented with acute onset expression aphasia, agraphia, dyscalculia, right-left disorientation and finger agnosia, without fever or meningeal signs. Stroke was thought to be the cause, but cerebrovascular disease investigation was negative. Interviewing the family revealed he had undergone yellow fever vaccination 18 days before. Lumbar puncture revealed mild protein elevation. Cultural examinations, Coxiella burnetti, and neurotropic virus serologies were negative. Regarding the yellow fever virus, IgG was identified in serum and cerebrospinal fluid (CSF), with negative IgM and virus PCR in CSF. EEG showed an encephalopathic pattern. The patient improved gradually and a week after discharge was his usual self. Only criteria for suspect neurotropic disease were met, but it's possible the time spent between symptom onset and lumbar puncture prevented a definite diagnosis of yellow fever vaccine-associated neurological disease. This gap would have been smaller if the vaccination history had been collected earlier. 2017 BMJ Publishing Group Ltd.

  14. Yellow fever virus: genetic and phenotypic diversity and implications for detection, prevention and therapy.

    Science.gov (United States)

    Beasley, David W C; McAuley, Alexander J; Bente, Dennis A

    2015-03-01

    Yellow fever virus (YFV) is the prototypical hemorrhagic fever virus, yet our understanding of its phenotypic diversity and any molecular basis for observed differences in disease severity and epidemiology is lacking, when compared to other arthropod-borne and haemorrhagic fever viruses. This is, in part, due to the availability of safe and effective vaccines resulting in basic YFV research taking a back seat to those viruses for which no effective vaccine occurs. However, regular outbreaks occur in endemic areas, and the spread of the virus to new, previously unaffected, areas is possible. Analysis of isolates from endemic areas reveals a strong geographic association for major genotypes, and recent epidemics have demonstrated the emergence of novel sequence variants. This review aims to outline the current understanding of YFV genetic and phenotypic diversity and its sources, as well as the available animal models for characterizing these differences in vivo. The consequences of genetic diversity for detection and diagnosis of yellow fever and development of new vaccines and therapeutics are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Yellow fever vaccine-associated viscerotropic disease: current perspectives

    OpenAIRE

    Thomas, Roger E

    2016-01-01

    Roger E Thomas Department of Family Medicine, Faculty of Medicine, University of Calgary, Research Office, G012, Health Sciences Centre, Calgary, AB, Canada Purpose: To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Literature search: Ten electronic databases were searched with no restriction of date or language and r...

  16. The phylogeny of yellow fever virus 17D vaccines.

    Science.gov (United States)

    Stock, Nina K; Boschetti, Nicola; Herzog, Christian; Appelhans, Marc S; Niedrig, Matthias

    2012-02-01

    In recent years the safety of the yellow fever live vaccine 17D came under scrutiny. The focus was on serious adverse events after vaccinations that resemble a wild type infection with yellow fever and whose reasons are still not known. Also the exact mechanism of attenuation of the vaccine remains unknown to this day. In this context, the standards of safety and surveillance in vaccine production and administration have been discussed. Therein embodied was the demand for improved documentation of the derivation of the seed virus used for yellow fever vaccine production. So far, there was just a historical genealogy available that is based on source area and passage level. However, there is a need for a documentation based on molecular information to get better insights into the mechanisms of pathology. In this work we sequenced the whole genome of different passages of the YFV-17D strain used by Crucell Switzerland AG for vaccine production. Using all other publically available 17D full genome sequences we compared the sequence variance of all vaccine strains and oppose a phylogenetic tree based on full genome sequences to the historical genealogy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Narcolepsy following yellow fever vaccination: A case report

    Directory of Open Access Journals (Sweden)

    Richard Ewald Rosch

    2016-08-01

    Full Text Available Narcolepsy with cataplexy is a rare, but important differential diagnosis for daytime sleepiness and atonic paroxysms in an adolescent. A recent increase in incidence in the paediatric age-group probably linked to the use of the Pandremix influenza vaccine in 2009, has increased awareness that different environmental factors can ‘trigger’ narcolepsy with cataplexy in a genetically susceptible population.Here we describe the case of a 13 year-old boy with narcolepsy following yellow-fever vaccination. He carries the HLA DQB1*0602 haplotype strongly associated with narcolepsy and cataplexy. Polysomnography showed rapid sleep onset with rapid eye movement (REM latency of 47 minutes, significant sleep fragmentation and a mean sleep latency of 1.6 minutes with sleep onset REM in 4 out of 4 nap periods. Together with the clinical history, these findings are diagnostic of narcolepsy type 1. The envelope protein E of the yellow fever vaccine strain 17D has significant amino acid sequence overlap with both hypocretin and the hypocretin receptor 2 receptors in protein regions that are predicted to act as epitopes for antibody production. These findings raise the question whether the yellow fever vaccine strain may, through a potential molecular mimicry mechanism, be another infectious trigger for this neuro-immunological disorder.

  18. Identification of insecticidal principals from cucumber seed oil against the yellow fever mosquito, Aedes aegypti

    Science.gov (United States)

    The yellow fever mosquito, Aedes aegypti, is one of the most medically important mosquito species due to its ability to spread viruses of yellow fever, dengue fever and Zika in humans. In this study, the insecticidal activity of seventeen plant essential oils were evaluated to toxicity by topical a...

  19. Epidemia midiática: produção de sentidos e configuração social da febre amarela na cobertura jornalística, 2007-2008 Media epidemics: sense production and social configuration of yellow fever in the journalistic coverage, 2007-2008

    Directory of Open Access Journals (Sweden)

    Cláudia Malinverni

    2012-01-01

    sense production in daily life and the hypothesis of agenda-setting and framing of the news, all material on yellow fever issued by the newspaper "Folha de São Paulo" were analyzed during the period comprised between 12/21/07 to 02/29/08 as well as all official documentation on the epizooty issued by the Brazilian authorities on public health during the period comprised between 01/03 and 02/28/08. Finding indicate that discursive strategies of the journalistic coverage rendered relative the discourse of public health authorities; prioritized divulgation of the number of cases; emphasized vaccination as the limit between life and death, refraining to inform the risks of the indiscriminate use of the product and propagated the imminence of a major epidemics of yellow fever. These strategies attributed new senses to the disease, dislodging the event from the wild form, restrict in space and limited in severity, to the urban form, characterized by epidemics and with a more severe potential. Secondarily, this study allowed to identify the impact of this media discourse on the national immunization system and the risks to which the population was exposed due to the senses produced: in 2008, eight cases of serious reactions to the vaccine were registered, and six of these cases resulted in deaths.

  20. Yellow Fever Vaccine Booster Doses: Recommendations of the Advisory Committee on Immunization Practices, 2015.

    Science.gov (United States)

    Staples, J Erin; Bocchini, Joseph A; Rubin, Lorry; Fischer, Marc

    2015-06-19

    On February 26, 2015, the Advisory Committee on Immunization Practices (ACIP) voted that a single primary dose of yellow fever vaccine provides long-lasting protection and is adequate for most travelers. ACIP also approved recommendations for at-risk laboratory personnel and certain travelers to receive additional doses of yellow fever vaccine (Box). The ACIP Japanese Encephalitis and Yellow Fever Vaccines Workgroup evaluated published and unpublished data on yellow fever vaccine immunogenicity and safety. The evidence for benefits and risks associated with yellow fever vaccine booster doses was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This report summarizes the evidence considered by ACIP and provides the updated recommendations for yellow fever vaccine booster doses.

  1. An inactivated cell-culture vaccine against yellow fever.

    Science.gov (United States)

    Monath, Thomas P; Fowler, Elizabeth; Johnson, Casey T; Balser, John; Morin, Merribeth J; Sisti, Maggie; Trent, Dennis W

    2011-04-07

    Yellow fever is a lethal viral hemorrhagic fever occurring in Africa and South America. A highly effective live vaccine (17D) is widely used for travelers to and residents of areas in which yellow fever is endemic, but the vaccine can cause serious adverse events, including viscerotropic disease, which is associated with a high rate of death. A safer, nonreplicating vaccine is needed. In a double-blind, placebo-controlled, dose-escalation, phase 1 study of 60 healthy subjects between 18 and 49 years of age, we investigated the safety and immunogenicity of XRX-001 purified whole-virus, β-propiolactone-inactivated yellow fever vaccine produced in Vero cell cultures and adsorbed to aluminum hydroxide (alum) adjuvant. On two visits 21 days apart, subjects received intramuscular injections of vaccine that contained 0.48 μg or 4.8 μg of antigen. Levels of neutralizing antibodies were measured at baseline and on days 21, 31, and 42. The vaccine induced the development of neutralizing antibodies in 100% of subjects receiving 4.8 μg of antigen in each injection and in 88% of subjects receiving 0.48 μg of antigen in each injection. Antibody levels increased by day 10 after the second injection, at which time levels were significantly higher with the 4.8-μg formulation than with the 0.48-μg formulation (geometric mean titer, 146 vs. 39; Pvaccine groups than in the placebo group: mild pain, tenderness, and (much less frequently) itching at the injection site. One case of urticaria was observed on day 3 after the second dose of 4.8 μg of vaccine. A two-dose regimen of the XRX-001 vaccine, containing inactivated yellow fever antigen with an alum adjuvant, induced neutralizing antibodies in a high percentage of subjects. XRX-001 has the potential to be a safer alternative to live attenuated 17D vaccine. (Funded by Xcellerex; ClinicalTrials.gov number, NCT00995865.).

  2. Dengue-yellow fever sera cross-reactivity; challenges for diagnosis

    OpenAIRE

    Houghton-Triviño, Natalia; Montaña, Diana; Castellanos, Jaime

    2008-01-01

    Objective The Flavivirus genera share epitopes inducing cross-reactive antibodies leading to great difficulty in differentially diagnosing flaviviral infections. This work was aimed at evaluating the complexity of dengue and yellow fever serological differential diagnosis. Material and methods Dengue antibody capture ELISA and a yellow fever neutralisation test were carried out on 13 serum samples obtained from yellow fever patients, 20 acute serum samples from dengue patients and 19 voluntan...

  3. Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis

    OpenAIRE

    Shearer, Freya M; Longbottom, Joshua; Browne, Annie J; Pigott, David M; Brady, Oliver J; Kraemer, Moritz U G; Marinho, Fatima; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Fullman, Nancy; Ray, Sarah E; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S

    2018-01-01

    Summary: Background: Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity t...

  4. [Culicidae insect fauna from rural zone in Amazonas State with incidence of sylvatic yellow fever].

    Science.gov (United States)

    Fé, Nelson Ferreira; Barbosa Md, Maria das Graças Vale; Fé, Flávio Augusto Andrade; Guerra, Marcus Vinitius de Farias; Alecrim, Wilson Duarte

    2003-01-01

    After the occurrence of 14 sylvatic yellow fever cases in 10 cities in the State of Amazonas during 1996, an investigation into the presence of sylvatic yellow fever vectors was carried out. The material of larvae and adult insects was collected around residences and canopy trees within forests, using a light trap (CDC) and human bait. A total of 424 insects was collected. Thirty seven species were identified, some of which were sylvatic yellow fever vectors: Haemagogus janthinomys, Ha. leucocelaenus, Aedes fulvus.

  5. Control of African swine fever epidemics in industrialized swine populations

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2016-01-01

    , it is important to explore strategies that can effectively control an epidemic of ASF. In this study, the epidemiological and economic effects of strategies to control the spread of ASF between domestic swine herds were examined using a published model (DTU-DADS-ASF). The control strategies were the basic EU...... and national strategy (Basic), the basic strategy plus pre-emptive depopulation of neighboring swine herds, and intensive surveillance of herds in the control zones, including testing live or dead animals. Virus spread via wild boar was not modelled. Under the basic control strategy, the median epidemic......African swine fever (ASF) is a notifiable infectious disease with a high impact on swine health. The disease is endemic in certain regions in the Baltic countries and has spread to Poland constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning...

  6. Yellow Fever Remains a Potential Threat to Public Health.

    Science.gov (United States)

    Vasconcelos, Pedro F C; Monath, Thomas P

    2016-08-01

    Yellow fever (YF) remains a serious public health threat in endemic countries. The recent re-emergence in Africa, initiating in Angola and spreading to Democratic Republic of Congo and Uganda, with imported cases in China and Kenya is of concern. There is such a shortage of YF vaccine in the world that the World Health Organization has proposed the use of reduced doses (1/5) during emergencies. In this short communication, we discuss these and other problems including the risk of spread of YF to areas free of YF for decades or never before affected by this arbovirus disease.

  7. Ocular manifestations of dengue fever in an East Indian epidemic.

    Science.gov (United States)

    Kapoor, Harpreet K; Bhai, Saloni; John, Mary; Xavier, Jai

    2006-12-01

    The incidence and geographic distribution of dengue has increased dramatically in recent years. Previously, ocular findings in dengue fever were considered rare. We report a spectrum of ocular manifestations of this potentially fatal disease and its association with laboratory parameters. 134 patients hospitalized with a diagnosis of dengue fever during an epidemic were included. Systemic and ophthalmic examinations were completed on all patients. The mean age was 31.3 years and 63.4% were males. All patients presented with fever. Six (4.5%) patients had retrobulbar pain and none of the patients presented with any visual complaints. Ocular findings were present in 54 (40.3%) patients. Subconjunctival haemorrhage was the commonest eye finding seen in 50 patients, of whom 84% had characteristic petechial type of haemorrhages. Fundus findings present in 10 (7.5%) patients included dilatation and tortuosity of vessels, superficial retinal haemorrhages, cotton-wool spots, and hard exudates; the macula, however, was spared in all patients. Only 6 of the patients with posterior segment involvement returned for follow-up examination and it was found that retinal changes had resolved without any specific treatment within 2 to 8 weeks time. Of all laboratory parameters evaluated, marked thrombocytopenia (platelet count petechial type, are a common manifestation of dengue infection. Dengue fever patients with marked thrombocytopenia are predisposed to spontaneous ocular haemorrhages.

  8. First recorded outbreak of yellow fever in Kenya, 1992-1993. II. Entomologic investigations.

    Science.gov (United States)

    Reiter, P; Cordellier, R; Ouma, J O; Cropp, C B; Savage, H M; Sanders, E J; Marfin, A A; Tukei, P M; Agata, N N; Gitau, L G; Rapuoda, B A; Gubler, D J

    1998-10-01

    The first recorded outbreak of yellow fever in Kenya occurred from mid-1992 through March 1993 in the south Kerio Valley, Rift Valley Province. We conducted entomologic studies in February-March 1993 to identify the likely vectors and determine the potential for transmission in the surrounding rural and urban areas. Mosquitoes were collected by landing capture and processed for virus isolation. Container surveys were conducted around human habitation. Transmission was mainly in woodland of varying density, at altitudes of 1,300-1,800 m. The abundance of Aedes africanus in this biotope, and two isolations of virus from pools of this species, suggest that it was the principal vector in the main period of the outbreak. A third isolate was made from a pool of Ae. keniensis, a little-known species that was collected in the same biotope. Other known yellow fever vectors that were collected in the arid parts of the valley may have been involved at an earlier stage of the epidemic. Vervet monkeys and baboons were present in the outbreak area. Peridomestic mosquito species were absent but abundant at urban sites outside the outbreak area. The entomologic and epidemiologic evidence indicate that this was a sylvatic outbreak in which human cases were directly linked to the epizootic and were independent of other human cases. The region of the Kerio Valley is probably subject to recurrent wandering epizootics of yellow fever, although previous episodes of scattered human infection have gone unrecorded. The risk that the disease could emerge as an urban problem in Kenya should not be ignored.

  9. Transmission of yellow fever vaccine virus through breast-feeding - Brazil, 2009.

    Science.gov (United States)

    2010-02-12

    In April, 2009, the state health department of Rio Grande do Sul, Brazil, was notified by the Cachoeira do Sul municipal health department of a case of meningoencephalitis requiring hospitalization in an infant whose mother recently had received yellow fever vaccine during a postpartum visit. The Field Epidemiology Training Program of the Secretariat of Surveillance in Health of the Brazilian Ministry of Health assisted state and municipal health departments with an investigation. This report summarizes the results of that investigation, which determined that the infant acquired yellow fever vaccine virus through breast-feeding. The mother reported 2 days of headache, malaise, and low fever occurring 5 days after receipt of yellow fever vaccine. The infant, who was exclusively breast-fed, was hospitalized at age 23 days with seizures requiring continuous infusion of intravenous anticonvulsants. The infant received antimicrobial and antiviral treatment for meningoencephalitis. The presence of 17DD yellow fever virus was detected by reverse transcription--polymerase chain reaction (RT-PCR) in the infant's cerebrospinal fluid (CSF); yellow fever--specific immunoglobulin M (IgM) antibodies also were present in serum and CSF. The infant recovered completely, was discharged after 24 days of hospitalization, and has had normal neurodevelopment and growth through age 6 months. The findings in this report provide documentation that yellow fever vaccine virus can be transmitted via breast-feeding. Administration of yellow fever vaccine to breast-feeding women should be avoided except in situations where exposure to yellow fever viruses cannot be avoided or postponed.

  10. What Does the Future Hold for Yellow Fever Virus? (I

    Directory of Open Access Journals (Sweden)

    Raphaëlle Klitting

    2018-06-01

    Full Text Available The recent resurgence of yellow fever virus (YFV activity in the tropical regions of Africa and South America has sparked renewed interest in this infamous arboviral disease. Yellow fever virus had been a human plague for centuries prior to the identification of its urban transmission vector, the Aedes (Stegomyia aegypti (Linnaeus mosquito species, and the development of an efficient live-attenuated vaccine, the YF-17D strain. The combination of vector-control measures and vaccination campaigns drastically reduced YFV incidence in humans on many occasions, but the virus never ceased to circulate in the forest, through its sylvatic invertebrate vector(s and vertebrate host(s. Outbreaks recently reported in Central Africa (2015–2016 and Brazil (since late 2016, reached considerable proportions in terms of spatial distribution and total numbers of cases, with multiple exports, including to China. In turn, questions about the likeliness of occurrence of large urban YFV outbreaks in the Americas or of a successful import of YFV to Asia are currently resurfacing. This two-part review describes the current state of knowledge and gaps regarding the molecular biology and transmission dynamics of YFV, along with an overview of the tools that can be used to manage the disease at individual, local and global levels.

  11. Yellow fever vaccine: an effective vaccine for travelers.

    Science.gov (United States)

    Verma, Ramesh; Khanna, Pardeep; Chawla, Suraj

    2014-01-01

    Yellow fever (YF) is an acute viral communicable disease transmitted by an arbovirus of the Flavivirus genus. It is primarily a zoonotic disease, especially the monkeys. Worldwide, an estimated 200,000 cases of yellow fever occurred each year, and the case-fatality rate is ~15%. Forty-five endemic countries in Africa and Latin America, with a population of close to 1 billion, are at risk. Up to 50% of severely affected persons from YF die without treatment. During 2009, 55 cases and 18 deaths were reported from Brazil, Colombia, and Peru. Brazil reported the maximum number of cases and death, i.e., 42 cases with 11 deaths. From January 2010 to March 2011, outbreaks of YF were reported to the WHO by Cameroon, Democratic Republic of Congo, Cote d'Ivoire, Guinea, Sierra Leone, Senegal, and Uganda. Cases were also reported in three northern districts of Abim, Agago, and Kitugun near the border with South Sudan. YF usually causes fever, muscle pain with prominent backache, headache, shivers, loss of appetite, and nausea or vomiting. Most patients improve, and their symptoms disappear after 3 to 4 d. Half of the patients who enter the toxic phase die within 10-14 d, while the rest recover without significant organ damage. Vaccination has been the single most important measure for preventing YF. The 17D-204 YF vaccine is a freeze-dried, live attenuated, highly effective vaccine. It is available in single-dose or multi-dose vials and should be stored at 2-8 °C. It is reconstituted with normal saline and should be used within 1 h of reconstitution. The 0.5 mL dose is delivered subcutaneously. Revaccination is recommended every 10 y for people at continued risk of exposure to yellow fever virus (YFV). This vaccine is available worldwide. Travelers, especially to Africa or Latin America from Asia, must have a certificate documenting YF vaccination, which is required by certain countries for entry under the International Health Regulations (IHR) of the WHO.

  12. Yellow Fever Outbreak - Kongo Central Province, Democratic Republic of the Congo, August 2016.

    Science.gov (United States)

    Otshudiema, John O; Ndakala, Nestor G; Mawanda, Elande-Taty K; Tshapenda, Gaston P; Kimfuta, Jacques M; Nsibu, Loupy-Régence N; Gueye, Abdou S; Dee, Jacob; Philen, Rossanne M; Giese, Coralie; Murrill, Christopher S; Arthur, Ray R; Kebela, Benoit I

    2017-03-31

    On April 23, 2016, the Democratic Republic of the Congo's (DRC's) Ministry of Health declared a yellow fever outbreak. As of May 24, 2016, approximately 90% of suspected yellow fever cases (n = 459) and deaths (45) were reported in a single province, Kongo Central Province, that borders Angola, where a large yellow fever outbreak had begun in December 2015. Two yellow fever mass vaccination campaigns were conducted in Kongo Central Province during May 25-June 7, 2016 and August 17-28, 2016. In June 2016, the DRC Ministry of Health requested assistance from CDC to control the outbreak. As of August 18, 2016, a total of 410 suspected yellow fever cases and 42 deaths were reported in Kongo Central Province. Thirty seven of the 393 specimens tested in the laboratory were confirmed as positive for yellow fever virus (local outbreak threshold is one laboratory-confirmed case of yellow fever). Although not well-documented for this outbreak, malaria, viral hepatitis, and typhoid fever are common differential diagnoses among suspected yellow fever cases in this region. Other possible diagnoses include Zika, West Nile, or dengue viruses; however, no laboratory-confirmed cases of these viruses were reported. Thirty five of the 37 cases of yellow fever were imported from Angola. Two-thirds of confirmed cases occurred in persons who crossed the DRC-Angola border at one market city on the DRC side, where ≤40,000 travelers cross the border each week on market day. Strategies to improve coordination between health surveillance and cross-border trade activities at land borders and to enhance laboratory and case-based surveillance and health border screening capacity are needed to prevent and control future yellow fever outbreaks.

  13. Yellow Fever Virus Vaccine–associated Deaths in Young Women 1

    OpenAIRE

    Seligman, Stephen J.

    2011-01-01

    Yellow fever vaccine–associated viscerotropic disease is a rare sequela of live-attenuated virus vaccine. Elderly persons and persons who have had thymectomies have increased susceptibility. A review of published and other data suggested a higher than expected number of deaths from yellow fever vaccine–associated viscerotropic disease among women 19–34 years of age without known immunodeficiency.

  14. Lineage-Specific Real-Time RT-PCR for Yellow Fever Virus Outbreak Surveillance, Brazil.

    Science.gov (United States)

    Fischer, Carlo; Torres, Maria C; Patel, Pranav; Moreira-Soto, Andres; Gould, Ernest A; Charrel, Rémi N; de Lamballerie, Xavier; Nogueira, Rita Maria Ribeiro; Sequeira, Patricia C; Rodrigues, Cintia D S; Kümmerer, Beate M; Drosten, Christian; Landt, Olfert; Bispo de Filippis, Ana Maria; Drexler, Jan Felix

    2017-11-01

    The current yellow fever outbreak in Brazil prompted widespread yellow fever virus (YFV) vaccination campaigns, imposing a responsibility to distinguish between vaccine- and wild-type YFV-associated disease. We developed novel multiplex real-time reverse transcription PCRs that differentiate between vaccine and American wild-type YFV. We validated these highly specific and sensitive assays in an outbreak setting.

  15. Lineage-Specific Real-Time RT-PCR for Yellow Fever Virus Outbreak Surveillance, Brazil

    OpenAIRE

    Fischer, Carlo; Torres, Maria C.; Patel, Pranav; Moreira-Soto, Andres; Gould, Ernest A.; Charrel, Rémi N.; de Lamballerie, Xavier; Nogueira, Rita Maria Ribeiro; Sequeira, Patricia C.; Rodrigues, Cintia D.S.; Kümmerer, Beate M.; Drosten, Christian; Landt, Olfert; Bispo de Filippis, Ana Maria; Drexler, Jan Felix

    2017-01-01

    The current yellow fever outbreak in Brazil prompted widespread yellow fever virus (YFV) vaccination campaigns, imposing a responsibility to distinguish between vaccine- and wild-type YFV-associated disease. We developed novel multiplex real-time reverse transcription PCRs that differentiate between vaccine and American wild-type YFV. We validated these highly specific and sensitive assays in an outbreak setting.

  16. Anamnestic immune response to dengue and decreased severity of yellow fever

    Directory of Open Access Journals (Sweden)

    Ricardo O Izurieta

    2009-01-01

    Full Text Available A protective immunity against yellow fever, from cross-reactive dengue antibodies, has been hypothesized as an explanation for the absence of yellow fever in Southern Asia where dengue immunity is almost universal. This study evaluates the association between protective immunity from cross-reactive dengue antibodies with yellow fever infection and severity of the disease. The study population consisted of military personnel of a jungle garrison and its detachments located in the Ecuadorian Amazonian rainforest. The cross-sectional study employed interviews as well as seroepidemiological methods. Humoral immune response to yellow fever, Mayaro, Venezuelan equine encephalitis, Oropouche, and dengue 2 infections was assessed by evaluating IgM and IgG specific antibodies. Log-linear regression analysis was used to evaluate age and presence of antibodies, against dengue type 2 virus, as predictors of yellow fever infection or severe disease. During the seroepidemiological survey, presence of dengue antibodies among yellow fever cases were observed in 77.3% cases from the coastal region, where dengue is endemic, 14.3% cases from the Amazon and 16.7 % cases from the Andean region. Dengue cross-reactive antibodies were not significantly associated with yellow fever infection but significantly associated with severity of the disease. The findings of this study suggest that previous exposure to dengue infection may have induced an anamnestic immune response that did not prevent yellow fever infection but greatly reduced the severity of the disease.

  17. First case of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in Hong Kong.

    Science.gov (United States)

    Leung, Wai Shing; Chan, Man Chun; Chik, Shiu Hong; Tsang, Tak Yin

    2016-04-01

    Yellow fever is an important and potentially fatal infection in tropical regions of Africa, South America, eastern Panama in Central America and Trinidad in the Caribbean. Yellow fever vaccination is not only crucial to reduce the disease risk and mortality in individuals travelling to these areas, but also an important public health measure to prevent the spread of the disease. Despite generally considered as a safe vaccine, yellow fever vaccine can rarely be associated with severe adverse reactions including yellow fever vaccine-associated viscerotropic disease (YEL-AVD). Here, we report the first case of YEL-AVD in Hong Kong. Clinicians should alert to the possibility of YEL-AVD in vaccinees presenting with compatible symptoms after yellow fever vaccination, particularly in people at higher risk of adverse events. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

  18. PREDICTION OF DENGUE FEVER EPIDEMIC SPREADING USING DYNAMICS TRANSMISSION VECTOR MODEL

    Directory of Open Access Journals (Sweden)

    Retno Widyaningrum

    2014-05-01

    Full Text Available Increasing number of dengue cases in Surabaya shows that its city has high potential of dengue fever epidemic. Although some policies were designed by Surabaya Health Department, such as fogging and mosquito’s nest eradication, but these efforts still out of target because of inaccurate predictions. Ineffectiveness eradication of dengue fever epidemic is caused by lack of information and knowledge on environmental conditions in Surabaya. Developing spread and prediction system to minimize dengue fever epidemic is necessary to be conducted immediately. Spread and prediction system can improve eradication and prevention accuracy. The transmission dynamics vector simulation will be used as an approach to draw a complex system ofmosquito life cycle in which involve a lot offactors. Dynamics transmission model used to build model in mosquito model (oviposition rate and pre adult mosquito, infected and death cases in dengue fever. The model of mosquito and infected population can represent system. The output of this research is website of spread and prediction system of dengue fever epidemics to predict growth rate of Aedes Aegypti mosquito, infected, and death population because of dengue fever epidemics. The deviation of infected population is 0,519. The model of death cases in dengue fever is less precision with the deviation 1,229. Death cases model need improvement by adding some variables that influence to dengue fever death cases. Spread ofdengue fever prediction will help the government, health department to decide the best policies in minimizing the spread ofdengue fever epidemics.

  19. Geographic patterns and environmental factors associated with human yellow fever presence in the Americas.

    Science.gov (United States)

    Hamrick, Patricia Najera; Aldighieri, Sylvain; Machado, Gustavo; Leonel, Deise Galan; Vilca, Luz Maria; Uriona, Sonia; Schneider, Maria Cristina

    2017-09-01

    In the Americas, yellow fever virus transmission is a latent threat due to the proximity between urban and wild environments. Although yellow fever has nearly vanished from North and Central America, there are still 13 countries in the Americas considered endemic by the World Health Organization. Human cases usually occur as a result of the exposure to sylvatic yellow fever in tropical forested environments; but urban outbreaks reported during the last decade demonstrate that the risk in this environment still exists. The objective of this study was to identify spatial patterns and the relationship between key geographic and environmental factors with the distribution of yellow fever human cases in the Americas. An ecological study was carried out to analyze yellow fever human cases reported to the Pan American Health Organization from 2000 to 2014, aggregated by second administrative level subdivisions (counties). Presence of yellow fever by county was used as the outcome variable and eight geo-environmental factors were used as independent variables. Spatial analysis was performed to identify and examine natural settings per county. Subsequently, a multivariable logistic regression model was built. During the study period, 1,164 cases were reported in eight out of the 13 endemic countries. Nearly 83.8% of these cases were concentrated in three countries: Peru (37.4%), Brazil (28.1%) and Colombia (18.4%); and distributed in 57 states/provinces, specifically in 286 counties (3.4% of total counties). Yellow fever presence was significantly associated with altitude, rain, diversity of non-human primate hosts and temperature. A positive spatial autocorrelation revealed a clustered geographic pattern in 138/286 yellow fever positive counties (48.3%). A clustered geographic pattern of yellow fever was identified mostly along the Andes eastern foothills. This risk map could support health policies in endemic countries. Geo-environmental factors associated with presence

  20. Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017.

    Science.gov (United States)

    Wouthuyzen-Bakker, Marjan; Knoester, Marjolein; van den Berg, Aad P; GeurtsvanKessel, Corine H; Koopmans, Marion Pg; Van Leer-Buter, Coretta; Oude Velthuis, Bob; Pas, Suzan D; Ruijs, Wilhelmina Lm; Schmidt-Chanasit, Jonas; Vreden, Stephen Gs; van der Werf, Tjip S; Reusken, Chantal Bem; Bierman, Wouter Fw

    2017-03-16

    A Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q)RT-PCR and sequencing. During hospital stay, the patient's condition deteriorated and she developed hepatic encephalopathy requiring transfer to the intensive care. Although yellow fever has not been reported in the last four decades in Suriname, vaccination is recommended by the World Health Organization for visitors to this country. This article is copyright of The Authors, 2017.

  1. Fractional dosing of yellow fever vaccine to extend supply: a modelling study.

    Science.gov (United States)

    Wu, Joseph T; Peak, Corey M; Leung, Gabriel M; Lipsitch, Marc

    2016-12-10

    The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines. We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a

  2. Interim Canadian recommendations for the use of a fractional dose of yellow fever vaccine during a vaccine shortage

    Science.gov (United States)

    2016-01-01

    Summary This statement outlines interim recommendations intended for use during yellow fever vaccine shortages only. The recommendations differ from the standard recommendations for yellow fever vaccination in the Canadian Immunization Guide and in the Committee to Advise on Tropical Medicine and Travel (CATMAT) Statement for Travellers and Yellow Fever. PMID:29770023

  3. Dutch Q fever epidemic in a ‘One Health’ context: outbreaks, seroprevalence and occupational risks

    NARCIS (Netherlands)

    Schimmer, Barbara

    2018-01-01

    Q fever is a worldwide zoonosis caused by the bacterium Coxiella burnetii (C. burnetii). Small ruminants, in particular sheep and goats, have been associated with community Q fever outbreaks in other countries. Just prior to the Dutch Q fever epidemic, a nationwide survey indicated that only 2.4% of

  4. Current status and future prospects of yellow fever vaccines.

    Science.gov (United States)

    Beck, Andrew S; Barrett, Alan D T

    2015-01-01

    Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized historically for its immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be lifelong. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease.

  5. Current Status and Future Prospects of Yellow Fever Vaccines

    Science.gov (United States)

    Beck, Andrew S.; Barrett, Alan D.T.

    2017-01-01

    Summary Yellow fever 17D vaccine is one of the oldest live-attenuated vaccines in current use that is recognized for historically immunogenic and safe properties. These unique properties of 17D are presently exploited in rationally designed recombinant vaccines targeting not only flaviviral antigens but also other pathogens of public health concern. Several candidate vaccines based on 17D have advanced to human trials, and a chimeric recombinant Japanese encephalitis vaccine utilizing the 17D backbone has been licensed. The mechanism(s) of attenuation for 17D are poorly understood; however, recent insights from large in silico studies have indicated particular host genetic determinants contributing to the immune response to the vaccine, which presumably influences the considerable durability of protection, now in many cases considered to be life-long. The very rare occurrence of severe adverse events for 17D is discussed, including a recent fatal case of vaccine-associated viscerotropic disease. PMID:26366673

  6. Yellow fever vaccine-associated viscerotropic disease: current perspectives

    Directory of Open Access Journals (Sweden)

    Thomas RE

    2016-10-01

    Full Text Available Roger E Thomas Department of Family Medicine, Faculty of Medicine, University of Calgary, Research Office, G012, Health Sciences Centre, Calgary, AB, Canada Purpose: To assess those published cases of yellow fever (YF vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Literature search: Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles. Methods: All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers. Results: All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People’s Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died. Conclusion: Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published. Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF

  7. Yellow fever vaccination status and safety in hemodialysis patients.

    Science.gov (United States)

    Facincani, Tila; Guimarães, Maia Nogueira Crown; De Sousa Dos Santos, Sigrid

    2016-07-01

    The adverse effects of yellow fever (YF) vaccine in dialysis patients are not well known. There is concern about the risks and benefits of the vaccine in immunocompromised patients living in endemic areas, particularly given the risk of resurgence of urban YF with the spread of Aedes aegypti mosquitoes. The purpose of this study was to assess the coverage and safety of YF vaccine in chronic dialysis patients. A cross-sectional study of 130 chronic dialysis patients was performed. Data were collected on clinical characteristics and YF vaccine status. Patients not vaccinated against YF or without a booster vaccination within the last 10 years were referred to receive the vaccine, and adverse effects were monitored. Previous vaccination was verified in 44 patients within the last 10 years and in 26 patients at more than 10 years ago, with no mention of adverse effects. Thirty-six patients had never been vaccinated and 24 had an unknown vaccination status. Of the total 86 patients referred for immunization, 45 actually received the YF vaccine, with 24.4% experiencing mild local adverse effects and 4.4% experiencing fever. No serious adverse effects attributable to YF vaccine were observed (anaphylaxis, neurological or viscerotropic disease). YF vaccine coverage among hemodialysis patients is low, and the vaccine appeared to be safe in this population with a small sample size. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

    Science.gov (United States)

    Rüddel, J; Schleenvoigt, B T; Schüler, E; Schmidt, C; Pletz, M W; Stallmach, A

    2016-09-01

    We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Association of IDDM and attenuated response of 2',5'-oligoadenylate synthetase to yellow fever vaccine

    DEFF Research Database (Denmark)

    Bonnevie-Nielsen, V; Larsen, M L; Frifelt, J J

    1989-01-01

    Basal and yellow fever vaccination-induced 2',5'-oligoadenylate synthetase (2',5'A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine...... represented a primary stimulus in all subjects. First, basal 2',5'A activity increased severalfold in response to yellow fever vaccination. In IDDM subjects, this increase was significantly lower (P = .025). Second, the 2',5'A activity increased proportionately to the higher basal 2',5'A activity in IDDM...

  10. Mortality and Morbidity Among Military Personnel and Civilians During the 1930s and World War II From Transmission of Hepatitis During Yellow Fever Vaccination: Systematic Review

    Science.gov (United States)

    Lorenzetti, Diane L.; Spragins, Wendy

    2013-01-01

    During World War II, nearly all US and Allied troops received yellow fever vaccine. Until May 1942, it was both grown and suspended in human serum. In April 1942, major epidemics of hepatitis occurred in US and Allied troops who had received yellow fever vaccine. A rapid and thorough investigation by the US surgeon general followed, and a directive was issued discontinuing the use of human serum in vaccine production. The large number of cases of hepatitis caused by the administration of this vaccine could have been avoided. Had authorities undertaken a thorough review of the literature, they would have discovered published reports, as early as 1885, of postvaccination epidemics of hepatitis in both men and horses. It would take 4 additional decades of experiments and epidemiological research before viruses of hepatitis A, B, C, D, and E were identified, their modes of transmission understood, and their genomes sequenced. PMID:23327242

  11. Mortality and morbidity among military personnel and civilians during the 1930s and World War II from transmission of hepatitis during yellow fever vaccination: systematic review.

    Science.gov (United States)

    Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy

    2013-03-01

    During World War II, nearly all US and Allied troops received yellow fever vaccine. Until May 1942, it was both grown and suspended in human serum. In April 1942, major epidemics of hepatitis occurred in US and Allied troops who had received yellow fever vaccine. A rapid and thorough investigation by the US surgeon general followed, and a directive was issued discontinuing the use of human serum in vaccine production. The large number of cases of hepatitis caused by the administration of this vaccine could have been avoided. Had authorities undertaken a thorough review of the literature, they would have discovered published reports, as early as 1885, of postvaccination epidemics of hepatitis in both men and horses. It would take 4 additional decades of experiments and epidemiological research before viruses of hepatitis A, B, C, D, and E were identified, their modes of transmission understood, and their genomes sequenced.

  12. Multifocal choroiditis following simultaneous hepatitis A, typhoid, and yellow fever vaccination

    Directory of Open Access Journals (Sweden)

    Escott S

    2013-02-01

    Full Text Available Sarah Escott, Ahmad B Tarabishy, Frederick H DavidorfHavener Eye Institute, The Ohio State University, Columbus, OH, USAAbstract: The paper describes the first reported case of multifocal choroiditis following simultaneous hepatitis-A, typhoid, and yellow fever vaccinations. A 33-year-old male developed sudden onset of flashing lights and floaters in his right eye 3 weeks following hepatitis A, typhoid, and yellow fever vaccinations. Fundus examination and angiography confirmed the presence of multiple peripheral chorioretinal lesions. These lesions demonstrated characteristic morphologic changes over a period of 8 weeks which were consistent with a diagnosis of self-resolving multifocal choroiditis. Vaccine-induced intraocular inflammation has been described infrequently. We demonstrate the first case of self-resolving multifocal choroiditis following simultaneous administration of hepatitis A, yellow fever, and typhoid immunizations.Keywords: multifocal choroiditis, vaccination, hepatitis A, typhoid, yellow fever

  13. Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis

    OpenAIRE

    Shearer, FM; Moyes, CL; Pigott, DM; Marinho, F; Deshpande, A; Longbottom, J; Browne, AJ; Kraemer, MUG; O’Reilly, KM; Hombach, J; Yactayo, S; de Araújo, VEM; da Nόbrega, AA; Mosser, JF; Stanaway, JD

    2017-01-01

    Summary Background: Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. Methods: ...

  14. Yellow fever control in Cameroon: Where are we now and where are we going?

    OpenAIRE

    Wiysonge, Charles Shey; Nomo, Emmanuel; Mawo, Jeanne; Ofal, James; Mimbouga, Julienne; Ticha, Johnson; Ndumbe, Peter M

    2008-01-01

    Abstract Background Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan. Methods ...

  15. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Molecular analysis of yellow fever virus 17DD vaccine strain

    Directory of Open Access Journals (Sweden)

    Paulo R. Post

    1991-06-01

    Full Text Available The Oswaldo Cruz Foundation produces most of the yellow fever (YF vaccine prepared world wide. As part of a broader approach to determine the genetic variability in YF l7D seeds and vaccines and its relevance to viral attenuation the 17DD virus was purifed directly from chick embryo homogenates which is the source of virus used for vaccination of millions of people in Brazil and other countries for half a century. Neutralization and hemagglutination tests showed that the purified virus is similar to the original stock. Furthermore, radioimmune precipitation of 35S-methionine-labeled viral proteins using mouse hyperimmune ascitic fluid revealed identical patterns for the purified 17DD virus and the YF l7D-204 strain except for the 17DD E protein which migrated slower on SDS-PAGE. This difference is likely to be due to N-linked glycosylation. Finally, comparison by northern blot nybridization of virion RNAs of purified 17DD with two other strains of YF virus only fenome-sized molecules for all three viruses. These observations suggest that vaccine phenotype is primarily associated with the accumulation of mutations.

  17. Protective and immunological behavior of chimeric yellow fever dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B; Russell, Philip K

    2016-03-29

    Clinical observations from the third year of the Sanofi Pasteur chimeric yellow fever dengue tetravalent vaccine (CYD) trials document both protection and vaccination-enhanced dengue disease among vaccine recipients. Children who were 5 years-old or younger when vaccinated experienced a DENV disease resulting in hospitalization at 5 times the rate of controls. On closer inspection, hospitalized cases among vaccinated seropositives, those at highest risk to hospitalized disease accompanying a dengue virus (DENV) infection, were greatly reduced by vaccination. But, seronegative individuals of all ages after being vaccinated were only modestly protected from mild to moderate disease throughout the entire observation period despite developing neutralizing antibodies at high rates. Applying a simple epidemiological model to the data, vaccinated seronegative individuals of all ages were at increased risk of developing hospitalized disease during a subsequent wild type DENV infection. The etiology of disease in placebo and vaccinated children resulting in hospitalization during a DENV infection, while clinically similar are of different origin. The implications of the observed mixture of DENV protection and enhanced disease in CYD vaccinees are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Yellow fever risk assessment in the Central African Republic.

    Science.gov (United States)

    Staples, J Erin; Diallo, Mawlouth; Janusz, Kristen B; Manengu, Casimir; Lewis, Rosamund F; Perea, William; Yactayo, Sergio; Sall, Amadou A

    2014-10-01

    Starting in 2008, the Central African Republic (CAR) experienced an unprecedented number of reported yellow fever (YF) cases. A risk assessment of YF virus (YFV) activity was conducted to estimate potential disease risk and vaccine needs. A multistage cluster sampling design was used to sample humans, non-human primates, and mosquitoes in distinct ecologic zones. Humans and non-human primates were tested for YFV-specific antibodies; mosquitoes were tested for YFV RNA. Overall, 13.3% (125/938) of humans were found to have naturally-acquired YFV antibodies. Antibody levels were higher in zones in the southern and south central regions of CAR. All sampled non-human primates (n=56) were known YFV reservoirs; one tested positive for YFV antibodies. Several known YF vectors were identified including Aedes africanus, Ae. aegypti, Ae. luteocephalus, and Ae. simpsoni. Several more urban locations were found to have elevated Breateau and Container indices for Ae. aegypti. A country-wide assessment of YF risk found YFV to be endemic in CAR. The potential for future YF cases and outbreaks, however, varied by ecologic zone. Improved vaccination coverage through mass campaign and childhood immunization was recommended to mitigate the YF risk. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Importation of yellow fever into China: assessing travel patterns.

    Science.gov (United States)

    Wilder-Smith, Annelies; Leong, W Y

    2017-07-01

    Rapid increase in trade and a growing air passenger market encourages high travel volume between the regions associated with increasing risks of such importations including China. Eleven Chinese workers infected during the 2016 yellow fever (YF) outbreak in Angola imported YF into China highlighting the potential for spread into Asia. Using outbound and inbound travel data, we assessed travel patterns from and to YF endemic countries in relation to China. Among YF endemic countries, Angola has the second highest number of travellers into China and also receives the second highest number of Chinese visitors. We estimated that China needs around half a million YF vaccine doses to cover their population travelling to YF endemic countries. The recent importation cases into China also unmasked the low YF vaccination coverage among Chinese travellers and workers to Angola, indicating the need to ensure better adherence to the International Health Regulations. © International Society of Travel Medicine, 2017.. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  20. Equilibrium Analysis of a Yellow Fever Dynamical Model with Vaccination

    Directory of Open Access Journals (Sweden)

    Silvia Martorano Raimundo

    2015-01-01

    Full Text Available We propose an equilibrium analysis of a dynamical model of yellow fever transmission in the presence of a vaccine. The model considers both human and vector populations. We found thresholds parameters that affect the development of the disease and the infectious status of the human population in the presence of a vaccine whose protection may wane over time. In particular, we derived a threshold vaccination rate, above which the disease would be eradicated from the human population. We show that if the mortality rate of the mosquitoes is greater than a given threshold, then the disease is naturally (without intervention eradicated from the population. In contrast, if the mortality rate of the mosquitoes is less than that threshold, then the disease is eradicated from the populations only when the growing rate of humans is less than another threshold; otherwise, the disease is eradicated only if the reproduction number of the infection after vaccination is less than 1. When this reproduction number is greater than 1, the disease will be eradicated from the human population if the vaccination rate is greater than a given threshold; otherwise, the disease will establish itself among humans, reaching a stable endemic equilibrium. The analysis presented in this paper can be useful, both to the better understanding of the disease dynamics and also for the planning of vaccination strategies.

  1. Intrathecal antibody production in two cases of yellow fever vaccine associated neurotropic disease in Argentina.

    Science.gov (United States)

    Pires-Marczeski, Fanny Clara; Martinez, Valeria Paula; Nemirovsky, Corina; Padula, Paula Julieta

    2011-12-01

    During the period 2007-2008 several epizootics of Yellow fever with dead of monkeys occurred in southeastern Brasil, Paraguay, and northeastern Argentina. In 2008 after a Yellow fever outbreak an exhaustive prevention campaign took place in Argentina using 17D live attenuated Yellow fever vaccine. This vaccine is considered one of the safest live virus vaccines, although serious adverse reactions may occur after vaccination, and vaccine-associated neurotropic disease are reported rarely. The aim of this study was to confirm two serious adverse events associated to Yellow fever vaccine in Argentina, and to describe the analysis performed to assess the origin of specific IgM against Yellow fever virus (YFV) in cerebrospinal fluid (CSF). Both cases coincided with the Yellow fever vaccine-associated neurotropic disease case definition, being clinical diagnosis longitudinal myelitis (case 1) and meningoencephalitis (case 2). Specific YFV antibodies were detected in CSF and serum samples in both cases by IgM antibody-capture ELISA. No other cause of neurological disease was identified. In order to obtain a conclusive diagnosis of central nervous system (CNS) infection the IgM antibody index (AI(IgM) ) was calculated. High AI(IgM) values were found in both cases indicating intrathecal production of antibodies and, therefore, CNS post-vaccinal YFV infection could be definitively associated to YFV vaccination. Copyright © 2011 Wiley Periodicals, Inc.

  2. Spread of yellow fever virus outbreak in Angola and the Democratic Republic of the Congo 2015-16: a modelling study.

    Science.gov (United States)

    Kraemer, Moritz U G; Faria, Nuno R; Reiner, Robert C; Golding, Nick; Nikolay, Birgit; Stasse, Stephanie; Johansson, Michael A; Salje, Henrik; Faye, Ousmane; Wint, G R William; Niedrig, Matthias; Shearer, Freya M; Hill, Sarah C; Thompson, Robin N; Bisanzio, Donal; Taveira, Nuno; Nax, Heinrich H; Pradelski, Bary S R; Nsoesie, Elaine O; Murphy, Nicholas R; Bogoch, Isaac I; Khan, Kamran; Brownstein, John S; Tatem, Andrew J; de Oliveira, Tulio; Smith, David L; Sall, Amadou A; Pybus, Oliver G; Hay, Simon I; Cauchemez, Simon

    2017-03-01

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

  3. Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, M.; Knoester, M.; Berg, A.P. van den; GeurtsvanKessel, C.H.; Koopmans, M.P.; Leer-Buter, C. Van; Velthuis, B.; Pas, S.D.; Ruijs, W.L.M.; Schmidt-Chanasit, J.; Vreden, S.G.; Werf, T.S. van der; Reusken, C.B.; Bierman, W.F.

    2017-01-01

    A Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q)RT-PCR and sequencing. During hospital stay, the patient's condition deteriorated and she developed hepatic encephalopathy requiring transfer to the

  4. Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, M.; Knoester, M.; van den Berg, A. P.; GeurtsvanKessel, C. H.; Koopmans, M. P.; Van Leer-Buter, C.; Velthuis, B. Oude; Pas, S. D.; Ruijs, W. L.; Schmidt-Chanasit, J.; Vreden, S. G.; van der Werf, T. S.; Reusken, C. B.; Bierman, W. F.

    2017-01-01

    A Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q) RT-PCR and sequencing. During hospital stay, the patient's condition deteriorated and she developed hepatic encephalopathy requiring transfer to the

  5. Yellow fever in a traveller returning from Suriname to the Netherlands, March 2017

    NARCIS (Netherlands)

    M. Wouthuyzen-Bakker (Marjan); M. Knoester; A.P. van den Berg; C.H. Geurts van Kessel (Corine); M.P.G. Koopmans D.V.M. (Marion); C. Van Leer-Buter (Coretta); B. Oude Velthuis; S.D. Pas (Suzan); W.L.M. Ruijs (Wilhelmina L.M.); J. Schmidt-Chanasit (Jonas); S.G. Vreden; T.S. van der Werf; C.B.E.M. Reusken (Chantal); W.F.W. Bierman (Wouter)

    2017-01-01

    textabstractA Dutch traveller returning from Suriname in early March 2017, presented with fever and severe acute liver injury. Yellow fever was diagnosed by (q)RT-PCR and sequencing. During hospital stay, the patient’s condition deteriorated and she developed hepatic encephalopathy requiring

  6. Antibody response to 17D yellow fever vaccine in Ghanaian infants.

    Science.gov (United States)

    Osei-Kwasi, M; Dunyo, S K; Koram, K A; Afari, E A; Odoom, J K; Nkrumah, F K

    2001-01-01

    To assess the seroresponses to yellow fever vaccination at 6 and 9 months of age; assess any possible adverse effects of immunization with the 17D yellow fever vaccine in infants, particularly at 6 months of age. Four hundred and twenty infants who had completed BCG, OPV and DPT immunizations were randomized to receive yellow fever immunization at either 6 or 9 months. A single dose of 0.5 ml of the reconstituted vaccine was administered to each infant by subcutaneous injection. To determine the yellow fever antibody levels of the infants, each donated 1 ml whole blood prior to immunization and 3 months post-immunization. Each serum sample was titred on Vero cells against the vaccine virus. The most common adverse reactions reported were fever, cough, diarrhoea and mild reactions at the inoculation site. The incidences of adverse reactions were not statistically different in both groups. None of the pre-immunization sera in both age groups had detectable yellow fever antibodies. Infants immunized at 6 months recorded seroconversion of 98.6% and those immunized at 9 months recorded 98% seroconversion. The GMT of their antibodies were 158.5 and 129.8, respectively. The results indicate that seroresponses to yellow fever immunization at 6 and 9 months as determined by seroconversion and GMTs of antibodies are similar. The findings of good seroresponses at 6 months without significant adverse effects would suggest that the 17D yellow fever vaccine could be recommended for use in children at 6 months in outbreak situations or in high risk endemic areas.

  7. A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination

    NARCIS (Netherlands)

    Wieten, Rosanne W.; Jonker, Emile F. F.; van Leeuwen, Ester M. M.; Remmerswaal, Ester B. M.; ten Berge, Ineke J. M.; de Visser, Adriëtte W.; van Genderen, Perry J. J.; Goorhuis, Abraham; Visser, Leo G.; Grobusch, Martin P.; de Bree, Godelieve J.

    2016-01-01

    Prompted by recent amendments of Yellow Fever (YF) vaccination guidelines from boost to single vaccination strategy and the paucity of clinical data to support this adjustment, we used the profile of the YF-specific CD8+ T-cell subset profiles after primary vaccination and neutralizing antibodies as

  8. Yellow fever vaccine-associated viscerotropic disease: current perspectives.

    Science.gov (United States)

    Thomas, Roger E

    2016-01-01

    To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles. All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers. All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People's Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died). Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity.

  9. Dissection of antibody specificities induced by yellow fever vaccination.

    Directory of Open Access Journals (Sweden)

    Oksana Vratskikh

    Full Text Available The live attenuated yellow fever (YF vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual

  10. Adverse event reports following yellow fever vaccination, 2007-13.

    Science.gov (United States)

    Lindsey, Nicole P; Rabe, Ingrid B; Miller, Elaine R; Fischer, Marc; Staples, J Erin

    2016-05-01

    Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex-specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for ≥70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons ≤18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers. Published by Oxford University Press on behalf of the International Society of Travel Medicine, 2016. This work is written by US Government employees and is in the public domain in the United States.

  11. A DNA vaccine against yellow fever virus: development and evaluation.

    Directory of Open Access Journals (Sweden)

    Milton Maciel

    2015-04-01

    Full Text Available Attenuated yellow fever (YF virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE, aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

  12. A DNA vaccine against yellow fever virus: development and evaluation.

    Science.gov (United States)

    Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T A; Dhalia, Rafael

    2015-04-01

    Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies.

  13. Molecular characterization of the 17D-204 yellow fever vaccine.

    Science.gov (United States)

    Salmona, Maud; Gazaignes, Sandrine; Mercier-Delarue, Severine; Garnier, Fabienne; Korimbocus, Jehanara; Colin de Verdière, Nathalie; LeGoff, Jerome; Roques, Pierre; Simon, François

    2015-10-05

    The worldwide use of yellow fever (YF) live attenuated vaccines came recently under close scrutiny as rare but serious adverse events have been reported. The population identified at major risk for these safety issues were extreme ages and immunocompromised subjects. Study NCT01426243 conducted by the French National Agency for AIDS research is an ongoing interventional study to evaluate the safety of the vaccine and the specific immune responses in HIV-infected patients following 17D-204 vaccination. As a preliminary study, we characterized the molecular diversity from E gene of the single 17D-204 vaccine batch used in this clinical study. Eight vials of lyophilized 17D-204 vaccine (Stamaril, Sanofi-Pasteur, Lyon, France) of the E5499 batch were reconstituted for viral quantification, cloning and sequencing of C/prM/E region. The average rate of virions per vial was 8.68 ± 0.07 log₁₀ genome equivalents with a low coefficient of variation (0.81%). 246 sequences of the C/prM/E region (29-33 per vials) were generated and analyzed for the eight vials, 25 (10%) being defective and excluded from analyses. 95% of sequences had at least one nucleotide mutation. The mutations were observed on 662 variant sites distributed through all over the 1995 nucleotides sequence and were mainly non-synonymous (66%). Genome variability between vaccine vials was highly homogeneous with a nucleotide distance ranging from 0.29% to 0.41%. Average p-distances observed for each vial were also homogeneous, ranging from 0.15% to 0.31%. This study showed a homogenous YF virus RNA quantity in vaccine vials within a single lot and a low clonal diversity inter and intra vaccine vials. These results are consistent with a recent study showing that the main mechanism of attenuation resulted in the loss of diversity in the YF virus quasi-species. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Yellow fever vaccine-associated viscerotropic disease: current perspectives

    Science.gov (United States)

    Thomas, Roger E

    2016-01-01

    Purpose To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease. Literature search Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles. Methods All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers. Results All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People’s Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died). Conclusion Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity. PMID:27784992

  15. A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

    Science.gov (United States)

    Maciel, Milton; Cruz, Fábia da Silva Pereira; Cordeiro, Marli Tenório; da Motta, Márcia Archer; Cassemiro, Klécia Marília Soares de Melo; Maia, Rita de Cássia Carvalho; de Figueiredo, Regina Célia Bressan Queiroz; Galler, Ricardo; Freire, Marcos da Silva; August, Joseph Thomas; Marques, Ernesto T. A.; Dhalia, Rafael

    2015-01-01

    Attenuated yellow fever (YF) virus 17D/17DD vaccines are the only available protection from YF infection, which remains a significant source of morbidity and mortality in the tropical areas of the world. The attenuated YF virus vaccine, which is used worldwide, generates both long-lasting neutralizing antibodies and strong T-cell responses. However, on rare occasions, this vaccine has toxic side effects that can be fatal. This study presents the design of two non-viral DNA-based antigen formulations and the characterization of their expression and immunological properties. The two antigen formulations consist of DNA encoding the full-length envelope protein (p/YFE) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal, LAMP-1 (pL/YFE), aimed at diverting antigen processing/presentation through the major histocompatibility complex II precursor compartments. The immune responses triggered by these formulations were evaluated in H2b and H2d backgrounds, corresponding to the C57Bl/6 and BALB/c mice strains, respectively. Both DNA constructs were able to induce very strong T-cell responses of similar magnitude against almost all epitopes that are also generated by the YF 17DD vaccine. The pL/YFE formulation performed best overall. In addition to the T-cell response, it was also able to stimulate high titers of anti-YF neutralizing antibodies comparable to the levels elicited by the 17DD vaccine. More importantly, the pL/YFE vaccine conferred 100% protection against the YF virus in intracerebrally challenged mice. These results indicate that pL/YFE DNA is an excellent vaccine candidate and should be considered for further developmental studies. PMID:25875109

  16. Functional requirements of the yellow fever virus capsid protein.

    Science.gov (United States)

    Patkar, Chinmay G; Jones, Christopher T; Chang, Yu-hsuan; Warrier, Ranjit; Kuhn, Richard J

    2007-06-01

    Although it is known that the flavivirus capsid protein is essential for genome packaging and formation of infectious particles, the minimal requirements of the dimeric capsid protein for virus assembly/disassembly have not been characterized. By use of a trans-packaging system that involved packaging a yellow fever virus (YFV) replicon into pseudo-infectious particles by supplying the YFV structural proteins using a Sindbis virus helper construct, the functional elements within the YFV capsid protein (YFC) were characterized. Various N- and C-terminal truncations, internal deletions, and point mutations of YFC were analyzed for their ability to package the YFV replicon. Consistent with previous reports on the tick-borne encephalitis virus capsid protein, YFC demonstrates remarkable functional flexibility. Nearly 40 residues of YFC could be removed from the N terminus while the ability to package replicon RNA was retained. Additionally, YFC containing a deletion of approximately 27 residues of the C terminus, including a complete deletion of C-terminal helix 4, was functional. Internal deletions encompassing the internal hydrophobic sequence in YFC were, in general, tolerated to a lesser extent. Site-directed mutagenesis of helix 4 residues predicted to be involved in intermonomeric interactions were also analyzed, and although single mutations did not affect packaging, a YFC with the double mutation of leucine 81 and valine 88 was nonfunctional. The effects of mutations in YFC on the viability of YFV infection were also analyzed, and these results were similar to those obtained using the replicon packaging system, thus underscoring the flexibility of YFC with respect to the requirements for its functioning.

  17. Evaluating the safety and immunogenicity of yellow fever vaccines: a systematic review

    Directory of Open Access Journals (Sweden)

    Thomas RE

    2015-04-01

    Full Text Available Roger E Thomas Department of Family Medicine, G012 Health Sciences Center, University of Calgary Medical School, Calgary, AB, Canada Purpose: To review the safety and immunogenicity of yellow fever vaccines. Literature search: The Cochrane Library (including the Cochrane CENTRAL Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the NHS Database of Abstracts of Reviews of Effects; MEDLINE; EMBASE; BIOSIS Previews; Global Health; CAB Abstracts; and the Lilacs Database of Latin American and Caribbean literature were searched for individual studies and systematic reviews through January 1, 2015. Results: Six yellow fever vaccines are currently produced, and they are effective against all seven yellow fever virus strains. There is a 99.2% homology of the genome sequences of the six current vaccines. Four systematic reviews identified very small numbers of serious adverse events. A systematic review (updated of all published cases identified 133 serious adverse events that met the Brighton Collaboration criteria: 32 anaphylactic, 42 neurologic (one death, 57 viscerotropic (25 deaths, and two of both neurologic and viscerotropic SAEs. The Sanofi Pasteur Global Pharmacovigilance database reported 276 million doses of Stamaril™ distributed worldwide and identified 12 reports of yellow fever vaccine-associated viscerotropic disease (YEL-AVD, 24 of yellow fever vaccine-associated neurologic disease (YEL-AND, and 33 reports of anaphylaxis (many already published. The Biomanguinhos manufacturer's database reported 110 million doses distributed worldwide between 1999 and 2009, and the rate of YEL-AND was estimated at 0.084/100,000 doses distributed and YEL-AVD at 0.02/100,000 doses distributed. Conclusion: Reports of serious adverse events are mostly from travelers from developed countries, and there is likely serious underreporting for developing countries. On the basis of the published reports, the yellow fever vaccines are

  18. Advice on malaria and yellow fever prevention provided at travel agencies in Cuzco, Peru.

    Science.gov (United States)

    Villanueva-Meyer, Pablo G; Garcia-Jasso, Carlos A; Springer, Chelsea A; Lane, Jenna K; Su, Bonny S; Hidalgo, Idania S; Goodrich, Mary R; Deichsel, Emily L; White, A C; Cabada, Miguel M

    2015-01-01

    Travelers receive medical advice from a variety of sources, including travel agencies. The aim of this study is to describe the quality of pre-travel advice provided by travel agencies in Cuzco to travelers interested in visiting malaria and yellow fever endemic areas. Trained medical students posed as tourists and visited travel agencies in Cuzco requesting travel advice for a trip to the southern Amazon of Peru, recording advice regarding risk and prevention of malaria and yellow fever. A total of 163 registered travel agencies were included in the study. The mean proposed tour duration was 6.8 days (±1.4 days) with a median time to departure of 3 days and a median tour cost of 805 US dollars (USD) [interquartile range (IQR) 580-1,095]. Overall, 45% employees failed to mention the risk for any illness. Eighteen percent of the employees acknowledged risk of malaria and 53% risk of yellow fever. However, 36% denied malaria risk and 2% denied risk of yellow fever in the region. The price of tours from travel agencies that did not mention any health risk was significantly lower [1,009.6 ± 500.5 vs 783.9 ± 402 USD, t (152) = 3, p yellow fever (100%) were able to provide at least one recommendation for prevention. However, advice was not always accurate or spontaneously volunteered. Only 7% of the employees provided both correct scheduling and location information for administration of the yellow fever vaccine. The majority of registered travel agencies in Cuzco did not provide sufficient and accurate information regarding risk and prevention of malaria and yellow fever to travelers inquiring about trips to the southern Amazon of Peru. © 2014 International Society of Travel Medicine.

  19. [Yellow fever virus, dengue 2 and other arboviruses isolated from mosquitos, in Burkina Faso, from 1983 to 1986. Entomological and epidemiological considerations].

    Science.gov (United States)

    Robert, V; Lhuillier, M; Meunier, D; Sarthou, J L; Monteny, N; Digoutte, J P; Cornet, M; Germain, M; Cordellier, R

    1993-01-01

    An arbovirus surveillance was carried out in Burkina Faso from 1983 to 1986. It was based on crepuscular catches of mosquitoes on human bait in some wooded areas and in one town. The total collection was 228 catches with an average of 8 men per catch. The total number of mosquitoes caught was 44,956 among which 32,010 potential vector of yellow fever; all these mosquitoes were analysed for arbovirology. In the south-western part of the country (region of Bobo-Dioulasso), surveillance was conducted each year from August to November, whilst the circulation of Aedes-borne arboviruses is well known to be favoured. In 1983, 1984 and 1986, seven strains of yellow fever virus were isolated in circumstances remarkably similar. They came from selvatic areas and never from the town. They concerned only Aedes (Stegomyia) luteocephalus which is the very predominant potential vector of yellow fever in the region. They were obtained in low figure, between 1 and 4 per year. They occurred from 27th of October to 21th of November. These observations confirm that the southern portion of the Sudan savanna zone of West Africa is the setting of a customary circulation of yellow fever virus and therefore belongs to the endemic emergence zone. In 1986, two strains of dengue 2 virus were isolated. One concerned Ae. luteocephalus from the selvatic area, the other Ae. (St.) aegypti from the heart of town. These data suggest two distinct cycles for dengue 2 virus, one urban and one selvatic, which could coexist simultaneously in the same region. In the south-eastern part of the country (region of Fada-N'Gourma) a yellow fever epidemic occurred between September and December 1983; its study has enable to precise their entomological aspects. The entomological inoculation rate of yellow fever virus has been evaluated to 22 infected bites per man during the month of october, for a man living close to forest gallery. 25 strains of yellow fever virus strains was isolated from Ae. (Diceromyia

  20. Administration of time-expired yellow fever vaccine: public health response and results of a serological investigation.

    Science.gov (United States)

    Allen, K W; Nguyen-Van-Tam, J S; Howells, J

    1999-06-01

    The discovery that a local travel clinic had administered 101 doses of time-expired yellow fever vaccine over a six month period prompted an immediate investigation in order to advise vaccinees about to travel to areas where yellow fever is endemic. No data were available to provide adequate reassurance about the potential efficacy of time-expired vaccine, so a rapid serological investigation was conducted, which provided evidence that the yellow fever vaccine had remained potent beyond its expiry date.

  1. Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

    Science.gov (United States)

    Polonsky, Jonathan A; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J

    2014-01-01

    Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

  2. Case report: probable transmission of vaccine strain of yellow fever virus to an infant via breast milk

    OpenAIRE

    Kuhn, Susan; Twele-Montecinos, Loreto; MacDonald, Judy; Webster, Patricia; Law, Barbara

    2011-01-01

    The 17D yellow fever vaccine is a live-virus vaccine that has been in use since the 1940s. The incidence of encephalitis after yellow fever vaccination among young infants is much higher than among children older than nine months of age. Until recently, avoidance of vaccination by breastfeeding women who have received yellow fever vaccine had been based on theoretical grounds only. We report the probable transmission of vaccine strain of yellow fever virus from a mother to her infant through ...

  3. Yellow fever control in Cameroon: where are we now and where are we going?

    Science.gov (United States)

    Wiysonge, Charles Shey; Nomo, Emmanuel; Mawo, Jeanne; Ofal, James; Mimbouga, Julienne; Ticha, Johnson; Ndumbe, Peter M

    2008-02-08

    Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan. In January 2003, case-based surveillance of suspected yellow fever cases was instituted in the whole country. A year later, yellow fever immunisation at nine months of age (the same age as routine measles immunisation) was introduced. Supplementary immunisation activities (SIAs), both preventive and in response to outbreaks, also formed an integral part of the yellow fever control plan. Each level of the national health system makes a synthesis of its activities and sends this to the next higher level at defined regular intervals; monthly for routine data and daily for SIAs. From 2004 to 2006 the national routine yellow fever vaccination coverage rose from 58.7% to 72.2%. In addition, the country achieved parity between yellow fever and measles vaccination coverage in 2005 and has since maintained this performance level. The number of suspected yellow fever cases in the country increased from 156 in 2003 to 859 in 2006, and the proportion of districts that reported at least one suspected yellow fever case per year increased from 31.4% to 68.2%, respectively. Blood specimens were collected from all suspected cases (within 14 days of onset of symptoms) and tested at a central laboratory for yellow fever IgM antibodies; leading to confirmation of yellow fever outbreaks in the health districts of Bafia, Méri and Ntui in 2003, Ngaoundéré Rural in 2004, Yoko in 2005 and Messamena in 2006. Owing to constraints in rapidly mobilising the necessary resources, reactive SIAs were only conducted in Bafia and M

  4. Yellow fever control in Cameroon: Where are we now and where are we going?

    Directory of Open Access Journals (Sweden)

    Mimbouga Julienne

    2008-02-01

    Full Text Available Abstract Background Cameroon is one of 12 African countries that bear most of the global burden of yellow fever. In 2002 the country developed a five-year strategic plan for yellow fever control, which included strategies for prevention as well as rapid detection and response to outbreaks when they occur. We have used data collected by the national Expanded Programme on Immunisation to assess the progress made and challenges faced during the first four years of implementing the plan. Methods In January 2003, case-based surveillance of suspected yellow fever cases was instituted in the whole country. A year later, yellow fever immunisation at nine months of age (the same age as routine measles immunisation was introduced. Supplementary immunisation activities (SIAs, both preventive and in response to outbreaks, also formed an integral part of the yellow fever control plan. Each level of the national health system makes a synthesis of its activities and sends this to the next higher level at defined regular intervals; monthly for routine data and daily for SIAs. Results From 2004 to 2006 the national routine yellow fever vaccination coverage rose from 58.7% to 72.2%. In addition, the country achieved parity between yellow fever and measles vaccination coverage in 2005 and has since maintained this performance level. The number of suspected yellow fever cases in the country increased from 156 in 2003 to 859 in 2006, and the proportion of districts that reported at least one suspected yellow fever case per year increased from 31.4% to 68.2%, respectively. Blood specimens were collected from all suspected cases (within 14 days of onset of symptoms and tested at a central laboratory for yellow fever IgM antibodies; leading to confirmation of yellow fever outbreaks in the health districts of Bafia, Méri and Ntui in 2003, Ngaoundéré Rural in 2004, Yoko in 2005 and Messamena in 2006. Owing to constraints in rapidly mobilising the necessary resources

  5. Global yellow fever vaccination coverage from 1970 to 2016: an adjusted retrospective analysis.

    Science.gov (United States)

    Shearer, Freya M; Moyes, Catherine L; Pigott, David M; Brady, Oliver J; Marinho, Fatima; Deshpande, Aniruddha; Longbottom, Joshua; Browne, Annie J; Kraemer, Moritz U G; O'Reilly, Kathleen M; Hombach, Joachim; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S; Hay, Simon I; Golding, Nick; Reiner, Robert C

    2017-11-01

    Substantial outbreaks of yellow fever in Angola and Brazil in the past 2 years, combined with global shortages in vaccine stockpiles, highlight a pressing need to assess present control strategies. The aims of this study were to estimate global yellow fever vaccination coverage from 1970 through to 2016 at high spatial resolution and to calculate the number of individuals still requiring vaccination to reach population coverage thresholds for outbreak prevention. For this adjusted retrospective analysis, we compiled data from a range of sources (eg, WHO reports and health-service-provider registeries) reporting on yellow fever vaccination activities between May 1, 1939, and Oct 29, 2016. To account for uncertainty in how vaccine campaigns were targeted, we calculated three population coverage values to encompass alternative scenarios. We combined these data with demographic information and tracked vaccination coverage through time to estimate the proportion of the population who had ever received a yellow fever vaccine for each second level administrative division across countries at risk of yellow fever virus transmission from 1970 to 2016. Overall, substantial increases in vaccine coverage have occurred since 1970, but notable gaps still exist in contemporary coverage within yellow fever risk zones. We estimate that between 393·7 million and 472·9 million people still require vaccination in areas at risk of yellow fever virus transmission to achieve the 80% population coverage threshold recommended by WHO; this represents between 43% and 52% of the population within yellow fever risk zones, compared with between 66% and 76% of the population who would have required vaccination in 1970. Our results highlight important gaps in yellow fever vaccination coverage, can contribute to improved quantification of outbreak risk, and help to guide planning of future vaccination efforts and emergency stockpiling. The Rhodes Trust, Bill & Melinda Gates Foundation, the

  6. Persistence of yellow fever vaccine-induced antibodies after solid organ transplantation.

    Science.gov (United States)

    Wyplosz, B; Burdet, C; François, H; Durrbach, A; Duclos-Vallée, J C; Mamzer-Bruneel, M-F; Poujol, P; Launay, O; Samuel, D; Vittecoq, D; Consigny, P H

    2013-09-01

    Immunization using live attenuated vaccines represents a contra-indication after solid organ transplantation (SOT): consequently, transplant candidates planning to travel in countries where yellow fever is endemic should be vaccinated prior to transplantation. The persistence of yellow fever vaccine-induced antibodies after transplantation has not been studied yet. We measured yellow-fever neutralizing antibodies in 53 SOT recipients vaccinated prior to transplantation (including 29 kidney recipients and 18 liver recipients). All but one (98%) had protective titers of antibodies after a median duration of 3 years (min.: 0.8, max.: 21) after transplantation. The median antibody level was 40 U/L (interquartile range: 40-80). For the 46 patients with a known or estimated date of vaccination, yellow-fever antibodies were still detectable after a median time of 13 years (range: 2-32 years) post-immunization. Our data suggest there is long-term persistence of antibodies to yellow fever in SOT recipients who have been vaccinated prior to transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  7. Reemergence of yellow fever in Ethiopia after 50 years, 2013: epidemiological and entomological investigations.

    Science.gov (United States)

    Lilay, Abrham; Asamene, Negga; Bekele, Abyot; Mengesha, Mesfin; Wendabeku, Milliyon; Tareke, Israel; Girmay, Abiy; Wuletaw, Yonas; Adossa, Abate; Ba, Yamar; Sall, Amadou; Jima, Daddi; Mengesha, Debritu

    2017-05-15

    Yellow Fever (YF) is a viral hemorrhagic disease transmitted by aedes mosquito species. Approximately, 200,000 cases and 30,000 deaths occur worldwide every year. In Ethiopia, the last outbreak was reported in 1966 with 2200 cases and 450 deaths. A number of cases with deaths from unknown febrile illness reported from South Ari district starting from November 2012. This investigation was conducted to identify the causative agent, source of the outbreak and recommend appropriate interventions. Medical records were reviewed and Patients and clinicians involved in managing the case were interviewed. Descriptive data analysis was done by time, person and place. Serum samples were collected for serological analysis it was done using Enzyme-linked Immunosorbent Assay for initial screening and confirmatory tests were done using Plaque Reduction and Neutralization Test. Breteau and container indices were used for the entomological investigation to determine the risk of epidemic. A total of 141 Suspected YF cases with 43 deaths (CFR = 30.5%) were reported from November 2012 to October 2013 from South Omo Zone. All age groups were affected (mean 27.5, Range 1-75 Years). Of the total cases, 85.1% cases had jaundice and 56.7% cases had fever. Seven of the 21 samples were IgM positive for YF virus. Aedes bromeliae and Aedes aegypti were identified as responsible vectors of YF in affected area. The Breteau indices of Arkisha and Aykamer Kebeles were 44.4% and 33.3%, whereas the container indices were 12.9% and 22.2%, respectively. The investigation revealed that YF outbreak was reemerged after 50 years in Ethiopia. Vaccination should be given for the affected and neighboring districts and Case based surveillance should be initiated to detect every case.

  8. Safety of the yellow Fever vaccine: a retrospective study.

    Science.gov (United States)

    Nordin, James D; Parker, Emily D; Vazquez-Benitez, Gabriela; Kharbanda, Elyse O; Naleway, Allison; Marcy, S Michael; Molitor, Beth; Kuckler, Leslie; Baggs, James

    2013-01-01

    Yellow fever (YF) vaccine is considered safe; however, severe illness and death following vaccination have been reported. Vaccine Safety Datalink (VSD) and US Department of Defense (DoD) data were used to identify adverse reactions following YF vaccination. Within the VSD, YF-vaccine-exposed subjects were compared to age-, site-, and gender-matched unexposed subjects. YF-vaccine-exposed DoD subjects were studied using a risk-interval design. For both cohorts, ICD-9 codes were analyzed for allergic and local reactions, mild systemic reactions, and possible visceral and neurologic adverse events (AEs). The VSD cohort received 47,159 doses from 1991 through 2006. The DoD cohort received 1.12 million doses from 1999 through 2007. Most subjects received other vaccines simultaneously. In the VSD cohort, rates of allergic, local, and mild systemic reactions were not statistically different between YF-vaccine-exposed and -unexposed subjects. In the DoD, there was an increased risk for outpatient allergic events in the period following vaccination with YF and other vaccines rate ratios [RR 3.85, 95% confidence interval (CI) 3.35-4.41] but with no increased risk for inpatient allergic reactions. In both cohorts, inpatient ICD-9 codes for visceral events were significantly less common following vaccination; inpatient codes for neurologic events were less common in the VSD YF-vaccine-exposed adult cohort, but did not differ between exposed and unexposed periods in the DoD. In the DoD, one fatal case of YF-vaccine-associated viscerotropic disease (YF-vaccine-AVD) was detected. The estimated death rate was 0.89 for 1,000,000 YF vaccine doses (95% CI 0.12-6.31/1,000,000 doses). No YF vaccine-associated deaths occurred in the VSD. In these closed cohorts we did not detect increased risk for visceral or neurologic events following YF vaccination. The death rate following YF vaccine was consistent with previous reports. These data support current recommendations for use of YF

  9. Yellow fever vaccine for patients with HIV infection.

    Science.gov (United States)

    Barte, Hilary; Horvath, Tara H; Rutherford, George W

    2014-01-23

    Yellow fever (YF) is an acute viral haemorrhagic disease prevalent in tropical Africa and Latin America. The World Health Organization (WHO) estimates that there are 200,000 cases of YF and 30,000 deaths worldwide annually. Treatment for YF is supportive, but a live attenuated virus vaccine is effective for preventing infection. WHO recommends immunisation for all individuals > 9 months living in countries or areas at risk. However, the United States Advisory Committee on Immunization Practices (ACIP) advises that YF vaccine is contraindicated in individuals with HIV. Given the large populations of HIV-infected individuals living in tropical areas where YF is endemic, YF vaccine may be an important intervention for preventing YF in immunocompromised populations. To assess the risk and benefits of YF immunisation for people infected with HIV. We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Randomised controlled trials and cohort studies of individuals with HIV infection who received YF vaccine (17DD or 17D-204). Two authors screened abstracts of references identified by electronic or bibliographic searches according to inclusion and exclusion criteria as detailed in the protocol. We identified 199 references and examined 19 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Three cohort studies were included in the review. They examined 484 patients with HIV infection who received YF immunisation. Patients with HIV infection developed significantly lower concentrations of neutralising antibodies in the first year post immunisation compared to uninfected patients, though decay patterns were similar for recipients regardless of HIV infection. No study patient with HIV infection suffered serious adverse events as a result of YF vaccination. YF vaccination can produce protective levels of neutralising antibodies in

  10. Differentiation of strains of yellow fever virus in γ-irradiated mice

    International Nuclear Information System (INIS)

    Fitzgeorge, R.; Bradish, C.J.

    1980-01-01

    The mouse sensitized by optimal, sub-lethal γ-irradiation has been used for the differentiation of strains of yellow fever virus and for the resolution of their immunogenicity and pathogenicity as distinct characteristics. For different strains of yellow fever virus, the patterns of antibody-synthesis, regulatory immunity (pre-challenge) and protective immunity (post-challenge) are differentially sensitive to γ-irradiation. These critical differentiations of strains of yellow fever virus in γ-irradiated mice have been compared with those shown in normal athymic and immature mice in order to elucidate the range of quantifiable in vivo characteristics and the course of the virus-host interaction. This is discussed as a basis for the comparisons of the responses of model and principal hosts to vaccines and pathogens. (author)

  11. Yellow fever and Hajj: with all eyes on Zika, a familiar flavivirus remains a threat.

    Science.gov (United States)

    Ahmed, Qanta A; Memish, Ziad A

    2016-12-01

    Hajj is among the world's largest mass gatherings, drawing between 2 and 3.5 million Muslims from 183 nations annually to perform pilgrimage in Mecca, Saudi Arabia. Infectious disease outbreaks can be imported both into the Hajj population and exported internationally by returning pilgrims. The domestic Saudi population can also be at risk of outbreaks traveling amid this mass migration. With yellow fever reported for the first time in China following the infection of expatriate Chinese workers in Angola and a full blown outbreak underway in wider West Africa, the prospect of yellow fever outbreaks in Asia threatens to impact Saudi Arabia, both during and beyond the Hajj season. With global focus trained on Zika, the rising threat of yellow fever cannot be overlooked. Strategies to mitigate risk to Saudi Arabia and the global population are thereby suggested.

  12. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models.

    Science.gov (United States)

    Watson, Alan M; Klimstra, William B

    2017-04-11

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus.

  13. Serological reactions in Rhesus monkeys inoculated with the 17D strain of yellow fever virus.

    Science.gov (United States)

    GROOT, H

    1962-01-01

    Haemagglutination-inhibition tests, which depend on the appearance of haemagglutination-inhibiting antibodies in the serum in virus infections, are in common use in the study of arthropod-borne diseases. This paper contains the results of an investigation into the appearance and pattern of haemagglutination-inhibiting antibodies in the serum of rhesus monkeys inoculated intracerebrally with the 17D strain of yellow fever virus during the testing of seed lots of yellow fever vaccine. These antibodies appeared on the tenth day after inoculation, and were still demonstrable four years later. In all of the eight monkeys tested complement-fixing and neutralizing antibodies against yellow fever antigens also developed, and in six out of the eight heterologous antigens developed.

  14. T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models

    Science.gov (United States)

    Watson, Alan M.; Klimstra, William B.

    2017-01-01

    The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. PMID:28398253

  15. Yellow fever in Brazil: thoughts and hypotheses on the emergence in previously free areas

    Directory of Open Access Journals (Sweden)

    Pedro Fernando da Costa Vasconcelos

    2010-12-01

    Full Text Available This article describes and discusses factors associated to the reemergence of yellow fever and its transmission dynamics in the states of São Paulo (Southeastern Brazil and Rio Grande do Sul (Southern during 2008 and 2009. The following factors have played a pivotal role for the reemergence of yellow fever in these areas: large susceptible human population; high prevalence of vectors and primary hosts (non-human primates; favorable climate conditions, especially increased rainfall; emergence of a new genetic lineage; and circulation of people and/or monkeys infected by virus. There is a need for an effective surveillance program to prevent the reemergence of yellow fever in other Brazilian states.

  16. Geographical distribution of the red howler monkey (Alouatta seniculus) and yellow fever in Colombia.

    Science.gov (United States)

    Piedrahita-Cortés, Juan; Soler-Tovar, Diego

    2016-02-11

    Colombia is a country with an important diversity of non-human primates, of which the red howler monkey (Alouatta seniculus) stands out because of its distribution and the role it plays in the occurrence of yellow fever.  To describe the geographic co-occurrence of Alouatta seniculus and the reported presence of yellow fever.  We conducted a descriptive study. The reported presence of yellow fever in Colombia was obtained from the reports and bulletins issued by the Instituto Nacional de Salud, and the study by Segura, et al. (2013). The occurrence of A. seniculus was determined based on the data from the Global Biodiversity Information Facility and the Colombian Biodiversity Information System. A map of the occurrence was developed using the DIVA-GIS program, and the ecological niche model under current conditions was created with the Maxent program.  The departments with the highest occurrence of A. seniculus were Antioquia, Meta and Casanare; 69.5% of the departments with reported history of yellow fever had co-occurrence with A. seniculus. The ecological niche model showed that Antioquia, Bolívar, La Guajira, Magdalena, Meta, Santander, Norte de Santander and Vichada had geographical portions with a probability rate nearing to 0.9 (90%).  In 69.5% of the departments with a history of yellow fever there was co-occurrence with A. seniculus, which is relevant because non-human primates play a well-known role as natural reservoirs of the virus, and they might contribute to the occurrence of the yellow fever, which makes them very useful as sentinels.

  17. The 2007-2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming.

    NARCIS (Netherlands)

    Dijkstra, F.; Hoek, W. van der; Wijers, N.; Schimmer, B.; Rietveld, A.; Wijkmans, C.J.; Vellema, P.; Schneeberger, P.M.

    2012-01-01

    We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most

  18. International team with Virginia Tech participation maps genome of dengue and yellow fever mosquito

    OpenAIRE

    Trulove, Susan

    2007-01-01

    Developing new strategies to prevent and control yellow fever and dengue fever has become more possible with the completion of the first draft of the genome sequence of Aedes aegypti mosquito by scientists led by Vishvanath Nene at The Institute for Genomic Research (TIGR) and David Severson at the University of Notre Dame. The genome is the complete set of genetic material including genes and other segments of DNA in an organism.

  19. Dengue fever/dengue haemorrhagic fever in Filipino children: clinical experience during the 1983-1984 epidemic.

    Science.gov (United States)

    Songco, R S; Hayes, C G; Leus, C D; Manaloto, C O

    1987-09-01

    A total of 377 Filipino children out of a total of 5,427 admissions from October 31, 1983 to March 31, 1984 were found to have dengue fever/dengue haemorrhagic fever The present clinical presentation of these infections was basically similar to that in previous epidemics but hepatomegaly and pleural effusion were less frequent and cardiac involvement, more frequent. The discrepancies between the clinical syndromes and HI antibody responses were evident; thus, the values used for the interpretation of the antibody titers must be reassessed.

  20. Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis.

    Science.gov (United States)

    Shearer, Freya M; Longbottom, Joshua; Browne, Annie J; Pigott, David M; Brady, Oliver J; Kraemer, Moritz U G; Marinho, Fatima; Yactayo, Sergio; de Araújo, Valdelaine E M; da Nóbrega, Aglaêr A; Fullman, Nancy; Ray, Sarah E; Mosser, Jonathan F; Stanaway, Jeffrey D; Lim, Stephen S; Reiner, Robert C; Moyes, Catherine L; Hay, Simon I; Golding, Nick

    2018-03-01

    Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the disease's contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa). We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the Congo, and South Sudan, where vaccination coverage in 2016

  1. Existing and potential infection risk zones of yellow fever worldwide: a modelling analysis

    Directory of Open Access Journals (Sweden)

    Freya M Shearer, BSc

    2018-03-01

    Full Text Available Summary: Background: Yellow fever cases are under-reported and the exact distribution of the disease is unknown. An effective vaccine is available but more information is needed about which populations within risk zones should be targeted to implement interventions. Substantial outbreaks of yellow fever in Angola, Democratic Republic of the Congo, and Brazil, coupled with the global expansion of the range of its main urban vector, Aedes aegypti, suggest that yellow fever has the propensity to spread further internationally. The aim of this study was to estimate the disease's contemporary distribution and potential for spread into new areas to help inform optimal control and prevention strategies. Methods: We assembled 1155 geographical records of yellow fever virus infection in people from 1970 to 2016. We used a Poisson point process boosted regression tree model that explicitly incorporated environmental and biological explanatory covariates, vaccination coverage, and spatial variability in disease reporting rates to predict the relative risk of apparent yellow fever virus infection at a 5 × 5 km resolution across all risk zones (47 countries across the Americas and Africa. We also used the fitted model to predict the receptivity of areas outside at-risk zones to the introduction or reintroduction of yellow fever transmission. By use of previously published estimates of annual national case numbers, we used the model to map subnational variation in incidence of yellow fever across at-risk countries and to estimate the number of cases averted by vaccination worldwide. Findings: Substantial international and subnational spatial variation exists in relative risk and incidence of yellow fever as well as varied success of vaccination in reducing incidence in several high-risk regions, including Brazil, Cameroon, and Togo. Areas with the highest predicted average annual case numbers include large parts of Nigeria, the Democratic Republic of the

  2. Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

    Science.gov (United States)

    Gershman, Mark D; Angelo, Kristina M; Ritchey, Julian; Greenberg, David P; Muhammad, Riyadh D; Brunette, Gary; Cetron, Martin S; Sotir, Mark J

    2017-05-05

    Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

  3. Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication

    NARCIS (Netherlands)

    Wieten, Rosanne W.; Jonker, Emile F. F.; Pieren, Daan K. J.; Hodiamont, Caspar J.; van Thiel, Pieter P. A. M.; van Gorp, Eric C. M.; de Visser, Adriëtte W.; Grobusch, Martin P.; Visser, Leo G.; Goorhuis, Abraham

    2016-01-01

    The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice. In this study we compare two antibody tests (the Immune Fluorescence Assay and

  4. Access to yellow fever travel vaccination centres in England, Wales, and Northern Ireland: A geographical study.

    Science.gov (United States)

    Petersen, Jakob; Simons, Hilary; Patel, Dipti

    More than 700,000 trips were made by residents in England, Wales, and Northern Ireland (EWNI) in 2015 to tropical countries endemic for yellow fever, a potentially deadly, yet vaccine-preventable disease transmitted by mosquitoes. The aim of this study was to map the geographical accessibility of yellow fever vaccination centres (YFVC) in EWNI. The location of 3208 YFVC were geocoded and the average geodetic distance to nearest YFVC was calculated for each population unit. Data on trips abroad and centres were obtained regionally for EWNI and nationally for the World Top20 countries in terms of travel. The mean distance to nearest YFVC was 2.4 km and only 1% of the population had to travel more than 16.1 km to their nearest centre. The number of vaccines administered regionally in EWNI was found correlated with the number of trips to yellow fever countries. The number of centres per 100,000 trips was 6.1 in EWNI, which was below United States (12.1) and above the rest of Top20 countries. The service availability was in line with demand regionally. With the exception of remote, rural areas, yellow fever vaccination services were widely available with only short distances to cover for the travelling public. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  5. Clinical and laboratory features of dengue virus-infected travellers previously vaccinated against yellow fever

    NARCIS (Netherlands)

    Teichmann, Dieter; Göbels, Klaus; Niedrig, Matthias; Grobusch, Martin P.

    2003-01-01

    Dengue is a mosquito-borne viral infection endemic throughout the tropics and subtropics. The global prevalence of dengue has grown dramatically in recent years and it has become a major international public health concern. The close taxonomic relationships between yellow fever and dengue viruses

  6. Investigations into yellow fever virus and other arboviruses in the northern regions of Kenya.

    Science.gov (United States)

    Henderson, B E; Metselaar, D; Kirya, G B; Timms, G L

    1970-01-01

    Previous studies having shown an appreciable level of yellow fever immunity to exist in northern Kenya, further epidemiological and serological surveys were carried out there in 1968 in an attempt to define more clearly the distribution of yellow fever and to locate possible vector and reservoir hosts of the disease; these surveys also provided information on a number of other arboviruses.Altogether 436 sera from 5 areas in northern Kenya were screened by haemagglutination-inhibition tests with 8 antigens, and 107 of these sera by neutralization tests for Group-B arboviruses. Small numbers of yellow-fever-immune adults were found in Ileret, Garissa, Loglogo and Mikona. At Marsabit high proportions of immune adults and children were found among the Burgi tribe. As the Burgi are permanent agricultural workers on Marsabit Mountain, an entomological investigation was made, over 15 000 mosquitos being collected. From these, 13 strains of Pongola virus, 1 strain of Semliki Forest virus and an unidentified virus were isolated, but no yellow fever strains. Aedes africanus and Aedes simpsoni were not found at Marsabit; small numbers of Aedes aegypti were collected biting man. The vector potential of other mosquitos collected (particularly Mansonia africana, which is present throughout the year) is discussed.

  7. Resurgence of Yellow Fever in Angola, 2015–2016

    Centers for Disease Control (CDC) Podcasts

    2016-10-12

    Sarah Gregory reads an abridged version of an article on the resurgence of yellow fever in Angola.  Created: 10/12/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 10/12/2016.

  8. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

    Science.gov (United States)

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

    2016-09-21

    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever. Yellow fever is an acute viral hemorrhagic disease which threatens approximately one billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than seven decades, the low vaccination rate fails to prevent outbreaks in at

  9. Development of a membrane adsorber based capture step for the purification of yellow fever virus.

    Science.gov (United States)

    Pato, Tânia P; Souza, Marta Cristina O; Silva, Andréa N M R; Pereira, Renata C; Silva, Marlon V; Caride, Elena; Gaspar, Luciane P; Freire, Marcos S; Castilho, Leda R

    2014-05-19

    Yellow fever (YF) is an endemic disease in some tropical areas of South America and Africa that presents lethality rate between 20 and 50%. There is no specific treatment and to control this disease a highly effective live-attenuated egg based vaccine is widely used for travelers and residents of areas where YF is endemic. However, recent reports of rare, sometimes fatal, adverse events post-vaccination have raised concerns. In order to increase safety records, alternative strategies should be considered, such as developing a new inactivated vaccine using a cell culture based technology, capable of meeting the demands in cases of epidemic. With this goal, the production of YF virus in Vero cells grown on microcarriers and its subsequent purification by chromatographic techniques was studied. In this work we investigate the capture step of the purification process of the YF virus. At first, virus stability was studied over a wide pH range, showing best results for the alkaline region. Considering this result and the pI of the envelope protein previously determined in silico, a strong anion exchanger was considered most suitable. Due to the easy scalability, simplicity to handle, absence of diffusional limitations and suitability for virus handling of membrane adsorbers, a Q membrane was evaluated. The amount of antigen adsorbed onto the membrane was investigated within the pH range for virus stability, and the best pH for virus adsorption was considered to be 8.5. Finally, studies on gradient and step elution allowed to determine the most adequate salt concentration for washing (0.15M) and virus elution (0.30 M). Under these operating conditions, it was shown that this capture step is quite efficient, showing high product recovery (93.2±30.3%) and efficient DNA clearance (0.9±0.3 ng/dose). Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. A qualitatively validated mathematical-computational model of the immune response to the yellow fever vaccine.

    Science.gov (United States)

    Bonin, Carla R B; Fernandes, Guilherme C; Dos Santos, Rodrigo W; Lobosco, Marcelo

    2018-05-25

    Although a safe and effective yellow fever vaccine was developed more than 80 years ago, several issues regarding its use remain unclear. For example, what is the minimum dose that can provide immunity against the disease? A useful tool that can help researchers answer this and other related questions is a computational simulator that implements a mathematical model describing the human immune response to vaccination against yellow fever. This work uses a system of ten ordinary differential equations to represent a few important populations in the response process generated by the body after vaccination. The main populations include viruses, APCs, CD8+ T cells, short-lived and long-lived plasma cells, B cells and antibodies. In order to qualitatively validate our model, four experiments were carried out, and their computational results were compared to experimental data obtained from the literature. The four experiments were: a) simulation of a scenario in which an individual was vaccinated against yellow fever for the first time; b) simulation of a booster dose ten years after the first dose; c) simulation of the immune response to the yellow fever vaccine in individuals with different levels of naïve CD8+ T cells; and d) simulation of the immune response to distinct doses of the yellow fever vaccine. This work shows that the simulator was able to qualitatively reproduce some of the experimental results reported in the literature, such as the amount of antibodies and viremia throughout time, as well as to reproduce other behaviors of the immune response reported in the literature, such as those that occur after a booster dose of the vaccine.

  11. Fractional Dosing of Yellow Fever Vaccine to Extend Supply: A Modeling Study

    Science.gov (United States)

    Peak, Corey M.; Leung, Gabriel M.

    2016-01-01

    Background The ongoing yellow fever (YF) epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa in July–August 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidating the conditions under which dose fractionation would reduce transmission. Methods We estimate the effective reproductive number for YF in Angola using disease natural history and case report data. With simple mathematical models of YF transmission, we calculate the infection attack rate (IAR, the proportion of population infected over the course of an epidemic) under varying levels of transmissibility and five-fold fractional-dose vaccine efficacy for two vaccination scenarios: (i) random vaccination in a hypothetical population that is completely susceptible; (ii) the Kinshasa vaccination campaign in July–August 2016 with different age cutoff for fractional-dose vaccines. Findings We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (i.e. a proportion VE of vaccinees receives complete and the remainder receive no protection), n-fold fractionation can dramatically reduce IAR as long as efficacy VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (i.e. the susceptibility of each vaccinee is reduced by a factor that is equal to the vaccine efficacy VE). The age cutoff for fractional-dose vaccines chosen by the WHO for the Kinshasa vaccination campaign (namely, 2 years) provides the largest reduction in IAR if the efficacy of five-fold fractional-dose vaccines exceeds 20%. Interpretation Dose fractionation is a very effective strategy for reducing infection attack rate that would be robust with a large margin for error in case

  12. Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact of vaccination.

    Science.gov (United States)

    Zhao, Shi; Stone, Lewi; Gao, Daozhou; He, Daihai

    2018-01-01

    Yellow fever (YF), transmitted via bites of infected mosquitoes, is a life-threatening viral disease endemic to tropical and subtropical regions of Africa and South America. YF has largely been controlled by widespread national vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF resurged in Angola, quickly spread and became the largest YF outbreak for the last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there is an urgent need to gain better understanding of the transmission pattern of YF. The present study provides a refined mathematical model, combined with modern likelihood-based statistical inference techniques, to assess and reconstruct important epidemiological processes underlying Angola's YF outbreak. This includes the outbreak's attack rate, the reproduction number ([Formula: see text]), the role of the mosquito vector, the influence of climatic factors, and the unusual but noticeable appearance of two-waves in the YF outbreak. The model explores actual and hypothetical vaccination strategies, and the impacts of possible human reactive behaviors (e.g., response to media precautions). While there were 73 deaths reported over the study period, the model indicates that the vaccination campaign saved 5.1-fold more people from death and saved from illness 5.6-fold of the observed 941 cases. Delaying the availability of the vaccines further would have greatly worsened the epidemic in terms of increased cases and deaths. The analysis estimated a mean [Formula: see text] and an attack rate of 0.09-0.15% (proportion of population infected) over the whole period from December 2015 to August 2016. Our estimated lower and upper bounds of [Formula: see text] are in line with previous studies. Unusually, [Formula: see text] oscillated in a manner that was "delayed" with the reported deaths. High recent number of deaths were associated (followed) with periods of relatively low disease transmission and low [Formula

  13. Fatal yellow fever in a traveler returning from Venezuela, 1999.

    Science.gov (United States)

    2000-04-14

    On September 28, 1999, a previously healthy 48-year-old man from California sought care at a local emergency department (ED) and was hospitalized with a 2-day history of fever (102 F [38.9 C]), chills, headache, photophobia, diffuse myalgias, joint pains, nausea, vomiting, constipation, upper abdominal discomfort, and general weakness. On September 26, he had returned from a 10-day trip to Venezuela. On September 29, an infectious disease physician from the ED contacted the Marin County Health Department (MCHD) about the patient's symptoms; MCHD reported his illness to the California Department of Health Services (CDHS) as a suspected case of viral hemorrhagic fever. This report describes the investigation of the case.

  14. CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles.

    Science.gov (United States)

    Goujon, Catherine; Gougeon, Marie-Lise; Tondeur, Laura; Poirier, Béatrice; Seffer, Valérie; Desprès, Philippe; Consigny, Paul-Henri; Vray, Muriel

    2017-10-27

    For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area. A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27

  15. Historical analysis of the records of sylvan yellow fever in the State of Amazonas, Brazil, from 1996 to 2009

    Directory of Open Access Journals (Sweden)

    Maria das Graças Gomes Saraiva

    2013-04-01

    Full Text Available Introduction Yellow fever is a non-contagious infectious disease, highly lethal, transmitted by the Aedes, Haemagogus and Sabethes. Methods Descriptive retrospective study of the yellow fever cases in Amazonas, between 1996 and 2009. Results Forty two cases of yellow fever were confirmed, with 30 deaths, 10% of which were foreigners. Conclusions The presence of Aedes aegypti and Aedes albopictus in both rural Amazonas and its capital demonstrates the dispersion of these vectors and underscores the need for better and continuous epidemiological and entomological control.

  16. [Yellow fever in Western Africa, 1973-1987. Observed facts--studies realized, campaign, prevention and forecast].

    Science.gov (United States)

    Cordellier, R

    1990-01-01

    This global analysis of the situation is based on a review of notifications, observations and studies concerning yellow fever in 16 of 17 countries of the West African subregion (Algeria is not affected for the years 1973-1987). In view of this analysis and the epidemiological picture, the author proposes a plan of concerted action to confine yellow fever to its monkey-to-monkey cycle in the wild. Official notifications vary greatly from one country to the next. Any of five major causes could explain this: ecological and ethological conditions that favour circulation of the virus in the wild and man-to-man transmission to different extents; the immune status of the populations; the difficulty of diagnosing especially isolated cases; lack of means for investigation; and negligence. The quantity and gravity of human cases are systematically underestimated, sometimes to a great extent. Lack of resources and difficulty of diagnosis, but also in many instances the attitude of the population, can account for this. Modern means of investigation, faster intervention by specialists, and better knowledge of how the virus is transmitted, have shown recently an increasing gap between notifications and the actual situation. Research and monitoring programmes are particularly important. The programmes under way in Senegal and Côte d'Ivoire have already resulted in considerable improvement in the action against epidemics. Because of these programmes, our knowledge of the very complex pattern of viral circulation is improving, thereby helping us develop systems for prevention and enabling us to forecast epidemics. Priority areas for study and research are: (i) Basic programmes for detailed study of all the topotypes of the virus, and identification of the viral amplification cycles that recur over several years. Such studies are under way in Senegal and Côte d'Ivoire. They would be particularly useful in Ghana and in Nigeria, where the taxonomy and bioecology of A. africanus s

  17. Neurological adverse events temporally associated to mass vaccination against yellow fever in Juiz de Fora, Brazil, 1999-2005.

    Science.gov (United States)

    Fernandes, Guilherme Côrtes; Camacho, Luiz Antonio Bastos; Sá Carvalho, Marilia; Batista, Maristela; de Almeida, Sonia Maria Rodrigues

    2007-04-20

    The identification of adverse events following immunization (AEFI) and their prompt investigation are important to allow a timely and scientifically based response to the users of immunization services. This article presents an analysis of notified AEFI cases between 1999 and 2005 and their temporal association with 2001 yellow fever vaccination campaign, AEFI notification attributed to yellow fever vaccination rose from 0.06 to 1.32 per 100,000 vaccinees in Brazil, between 1998 and 2000. During the 2001 yellow fever mass vaccination campaign held in Juiz de Fora, Brazil, 12 cases of aseptic meningitis were temporally associated to yellow fever vaccination, but clinical and laboratory data were not available to confirm nor deny causality. Epidemiological studies associated to enhanced surveillance and standardized protocols should take advantage of public health interventions like mass vaccination campaigns and implementation of new vaccination strategies in order to assess and investigate vaccine safety.

  18. A case suspected for yellow fever vaccine-associated viscerotropic disease in the Netherlands.

    Science.gov (United States)

    van de Pol, Eva M; Gisolf, Elizabeth H; Richter, Clemens

    2014-01-01

    Yellow fever (YF) 17D vaccine is one of the most successful vaccines ever developed. Since 2001, 56 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been published in the peer-reviewed literature. Here, we report a new case suspected for YEL-AVD in the Netherlands. Further research is needed to determine the true incidence of YEL-AVD and to clarify host and vaccine-associated factors in the pathogenesis of YEL-AVD. Because of the potential adverse events, healthcare providers should carefully consider vaccination only in people who are truly at risk for YF infection, especially in primary vaccine recipients. © 2014 International Society of Travel Medicine.

  19. Single shot of 17D vaccine may not confer life-long protection against yellow fever.

    Science.gov (United States)

    Vasconcelos, Pedro Fc

    2018-02-01

    The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.

  20. NMOSD triggered by yellow fever vaccination - An unusual clinical presentation with segmental painful erythema.

    Science.gov (United States)

    Schöberl, F; Csanadi, E; Eren, O; Dieterich, M; Kümpfel, T

    2017-01-01

    Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Detection of yellow fever virus genomes from four imported cases in China.

    Science.gov (United States)

    Cui, Shujuan; Pan, Yang; Lyu, Yanning; Liang, Zhichao; Li, Jie; Sun, Yulan; Dou, Xiangfeng; Tian, Lili; Huo, Da; Chen, Lijuan; Li, Xinyu; Wang, Quanyi

    2017-07-01

    Yellow fever virus (YFV), as the first proven human-pathogenic virus, is still a major public health problem with a dramatic upsurge in recent years. This is a report on four imported cases of yellow fever virus into China identified by whole genome sequencing. Phylogenetic analysis was performed and the results showed that these four viruses were highly homologous with Angola 71 strains (AY968064). In addition, effective mutations of amino acids were not observed in the E protein domain of four viruses, thus confirming the effectiveness of the YFV-17D vaccine (X03700). Although there is low risk of local transmission in most part of China, the increasing public health risk of YF caused by international exchange should not be ignored. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Viscerotropic and neurotropic disease following vaccination with the 17D yellow fever vaccine, ARILVAX.

    Science.gov (United States)

    Kitchener, Scott

    2004-06-02

    Yellow fever vaccine associated viscerotropic (YFV-AVD) and neurotropic (YFV-AND) diseases have been recently identified in various countries. Previously post-vaccination multiple organ system failure was recognised as a rare serious adverse event of yellow fever vaccination and 21 cases of post-vaccinal (YFV) encephalitis had been recorded. Incidence data is not available. On investigation of vaccine surveillance reports from Europe following distribution of more than 3 million doses of ARILVAX trade mark, four cases each of YFV-AVD and YFV-AND were found (each 1.3 cases per million doses distributed) for the period 1991 to 2003. The incidence for each is higher after 1996 (2.5 cases per million doses distributed). The incidence of these adverse events appears to be very low with ARILVAX trade mark. Similar incidence data is required from other countries for comparison.

  3. The Aquaporin Gene Family of the Yellow Fever Mosquito, Aedes aegypti

    OpenAIRE

    Drake, Lisa L.; Boudko, Dmitri Y.; Marinotti, Osvaldo; Carpenter, Victoria K.; Dawe, Angus L.; Hansen, Immo A.

    2010-01-01

    Background The mosquito, Aedes aegypti, is the principal vector of the Dengue and yellow fever viruses. During feeding, an adult female can take up more than its own body weight in vertebrate blood. After a blood meal females excrete large amounts of urine through their excretion system, the Malpighian tubules (MT). Diuresis starts within seconds after the mosquito starts feeding. Aquaporins (AQPs) are a family of membrane transporters that regulate the flow of water, glycerol and other small...

  4. Neglect and not forgetting produces shameful diseases such as yellow fever

    Directory of Open Access Journals (Sweden)

    Salim Mattar V

    2017-05-01

    Full Text Available Yellow fever (YF is a disease caused by a flavivirus that bears its name, is a disease with haemorrhagic manifestations and high lethality that compromises the central nervous system. YF has two cycles; one in the jungle and another urban, epizootics precede outbreaks before migrating to urban areas. The vectors are the mosquitoes Aedes aegypti, Aedes albopictus, Haemogogus janthinomys and Sabethes sp, which have a wide geographical distribution in Colombia and South America.

  5. [Yellow fever: reemerging in the state of Sao Paulo, Brazil, 2009].

    Science.gov (United States)

    Mascheretti, Melissa; Tengan, Ciléa H; Sato, Helena Keiko; Suzuki, Akemi; de Souza, Renato Pereira; Maeda, Marina; Brasil, Roosecelis; Pereira, Mariza; Tubaki, Rosa Maria; Wanderley, Dalva M V; Fortaleza, Carlos Magno Castelo Branco; Ribeiro, Ana Freitas

    2013-10-01

    To describe the investigation of a sylvatic yellow fever outbreak in the state of Sao Paulo and the main control measures undertaken. This is a descriptive study of a sylvatic yellow fever outbreak in the Southwestern region of the state from February to April 2009. Suspected and confirmed cases in humans and in non-human primates were evaluated. Entomological investigation in sylvatic environment involved capture at ground level and in the tree canopy to identify species and detect natural infections. Control measures were performed in urban areas to control Aedes aegypti . Vaccination was directed at residents living in areas with confirmed viral circulation and also at nearby cities according to national recommendation. Twenty-eight human cases were confirmed (39.3% case fatality rate) in rural areas of Sarutaiá, Piraju, Tejupá, Avaré and Buri. The deaths of 56 non-human primates were also reported, 91.4% were Allouatta sp. Epizootics was confirmed in two non-human primates in the cities of Itapetininga and Buri. A total of 1,782 mosquitoes were collected, including Haemagogus leucocelaenus , Hg. janthinomys/capricornii , and Sabethes chloropterus, Sa. purpureus and Sa. undosus . Yellow fever virus was isolated from a group of Hg. Leucocelaenus from Buri. Vaccination was carried out in 49 cities, with a total of 1,018,705 doses. Nine serious post-vaccination adverse events were reported. The cases occurred between February and April 2009 in areas with no recorded yellow fever virus circulation in over 60 years. The outbreak region occurred outside the original recommended vaccination area with a high percentage of susceptible population. The fast adoption of control measures interrupted the human transmission within a month and the confirmation of viral circulation in humans, monkeys and mosquitoes. The results allowed the identification of new areas of viral circulation but further studies are required to clarify the dynamics of the spread of this disease.

  6. Yellow fever disease: density equalizing mapping and gender analysis of international research output.

    Science.gov (United States)

    Bundschuh, Matthias; Groneberg, David A; Klingelhoefer, Doris; Gerber, Alexander

    2013-11-18

    A number of scientific papers on yellow fever have been published but no broad scientometric analysis on the published research of yellow fever has been reported.The aim of the article based study was to provide an in-depth evaluation of the yellow fever field using large-scale data analysis and employment of bibliometric indicators of production and quantity. Data were retrieved from the Web of Science database (WoS) and analyzed as part of the NewQis platform. Then data were extracted from each file, transferred to databases and visualized as diagrams. Partially by means of density-equalizing mapping makes the findings clear and emphasizes the output of the analysis. In the study period from 1900 to 2012 a total of 5,053 yellow fever-associated items were published by 79 countries. The United States (USA) having the highest publication rate at 42% (n = 751) followed by far from Brazil (n = 203), France (n = 149) and the United Kingdom (n = 113). The most productive journals are the "Public Health Reports", the "American Journal of Tropical Medicine and Hygiene" and the "Journal of Virology". The gender analysis showed an overall steady increase of female authorship from 1950 to 2011. Brazil is the only country of the five most productive countries with a higher proportion of female scientists. The present data shows an increase in research productivity over the entire study period, in particular an increase of female scientists. Brazil shows a majority of female authors, a fact that is confirmed by other studies.

  7. Oral infection of Aedes aegypti with yellow fever virus: geographic variation and genetic considerations.

    Science.gov (United States)

    Tabachnick, W J; Wallis, G P; Aitken, T H; Miller, B R; Amato, G D; Lorenz, L; Powell, J R; Beaty, B J

    1985-11-01

    Twenty-eight populations representing a worldwide distribution of Aedes aegypti were tested for their ability to become orally infected with yellow fever virus (YFV). Populations had been analyzed for genetic variations at 11 isozyme loci and assigned to one of 8 genetic geographic groups of Ae. aegypti. Infection rates suggest that populations showing isozyme genetic relatedness also demonstrate similarity to oral infection rates with YFV. The findings support the hypothesis that genetic variation exists for oral susceptibility to YFV in Ae. aegypti.

  8. Vaccines and vaccination against yellow fever: WHO Position Paper, June 2013--recommendations.

    Science.gov (United States)

    2015-01-01

    This article presents the World Health Organizations (WHO) evidence and recommendations for the use of yellow fever (YF) vaccination from "Vaccines and vaccination against yellow fever: WHO Position Paper - June 2013" published in the Weekly Epidemiological Record. This position paper summarizes the WHO position on the use of YF vaccination, in particular that a single dose of YF vaccine is sufficient to confer sustained life-long protective immunity against YF disease. A booster dose is not necessary. The current document replaces the position paper on the use of yellow fever vaccines and vaccination published in 2003. Footnotes to this paper provide a number of core references. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. This paper reflects the recommendations of WHO's Strategic Advisory Group of Experts (SAGE) on immunization. These recommendations were discussed by SAGE at its April 2013 meeting. Evidence presented at the meeting can be accessed at http://www.who.int/immunization/sage/previous/en/index.html. Copyright © 2014. Published by Elsevier Ltd.

  9. Screening test for neutralizing antibodies against yellow fever virus, based on a flavivirus pseudotype.

    Directory of Open Access Journals (Sweden)

    Séverine Mercier-Delarue

    Full Text Available Given the possibility of yellow fever virus reintroduction in epidemiologically receptive geographic areas, the risk of vaccine supply disruption is a serious issue. New strategies to reduce the doses of injected vaccines should be evaluated very carefully in terms of immunogenicity. The plaque reduction test for the determination of neutralizing antibodies (PRNT is particularly time-consuming and requires the use of a confinement laboratory. We have developed a new test based on the use of a non-infectious pseudovirus (WN/YF17D. The presence of a reporter gene allows sensitive determination of neutralizing antibodies by flow cytometry. This WN/YF17D test was as sensitive as PRNT for the follow-up of yellow fever vaccinees. Both tests lacked specificity with sera from patients hospitalized for acute Dengue virus infection. Conversely, both assays were strictly negative in adults never exposed to flavivirus infection or vaccination, and in patients sampled some time after acute Dengue infection. This WN/YF17D test will be particularly useful for large epidemiological studies and for screening for neutralizing antibodies against yellow fever virus.

  10. Adverse events following yellow fever immunization: Report and analysis of 67 neurological cases in Brazil.

    Science.gov (United States)

    Martins, Reinaldo de Menezes; Pavão, Ana Luiza Braz; de Oliveira, Patrícia Mouta Nunes; dos Santos, Paulo Roberto Gomes; Carvalho, Sandra Maria D; Mohrdieck, Renate; Fernandes, Alexandre Ribeiro; Sato, Helena Keico; de Figueiredo, Patricia Mandali; von Doellinger, Vanessa Dos Reis; Leal, Maria da Luz Fernandes; Homma, Akira; Maia, Maria de Lourdes S

    2014-11-20

    Neurological adverse events following administration of the 17DD substrain of yellow fever vaccine (YEL-AND) in the Brazilian population are described and analyzed. Based on information obtained from the National Immunization Program through passive surveillance or intensified passive surveillance, from 2007 to 2012, descriptive analysis, national and regional rates of YFV associated neurotropic, neurological autoimmune disease, and reporting rate ratios with their respective 95% confidence intervals were calculated for first time vaccinees stratified on age and year. Sixty-seven neurological cases were found, with the highest rate of neurological adverse events in the age group from 5 to 9 years (2.66 per 100,000 vaccine doses in Rio Grande do Sul state, and 0.83 per 100,000 doses in national analysis). Two cases had a combination of neurotropic and autoimmune features. This is the largest sample of YEL-AND already analyzed. Rates are similar to other recent studies, but on this study the age group from 5 to 9 years of age had the highest risk. As neurological adverse events have in general a good prognosis, they should not contraindicate the use of yellow fever vaccine in face of risk of infection by yellow fever virus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Entomological investigation of a sylvatic yellow fever area in São Paulo State, Brazil.

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    Camargo-Neves, Vera L F de; Poletto, Daniela W; Rodas, Lílian A C; Pachioli, Márcio L; Cardoso, Rubens P; Scandar, Sirle A S; Sampaio, Susy M P; Koyanagui, Paulo H; Botti, Mauricio V; Mucci, Luis F; Gomes, Almério de C

    2005-01-01

    Following reports of two autochthonous cases of sylvatic yellow fever in the State of São Paulo, Brazil, in 2000, entomological surveys were conducted with the objective of verifying the occurrence of vector species in forest environments close to or associated with riparian areas located in the western and northwestern regions of the State. Culicidae were captured in 39 sites distributed in four regions. Haemagogus leucocelaenus and Aedes albopictus were the most abundant species and were captured in all the regions studied. H. leucocelaenus was the most abundant species in the municipalities of Santa Albertina and Ouroeste, where the two cases of sylvatic yellow fever had been reported. Mosquitoes from the janthinomys/capricornii group were only found at eight sites in the São José do Rio Preto region, while Sabethes chloropterus was found at one site in Ribeirão Preto. H. leucocelaenus showed its capacity to adapt to a secondary and degraded environment. Our results indicate a wide receptive area for yellow fever transmission in the State of São Paulo, with particular emphasis on the possibility of H. leucocelaenus being involved in the maintenance of this sylvatic focus of the disease.

  12. Low frequency of side effects following an incidental 25 times concentrated dose of yellow fever vaccine

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    Rabello Ana

    2002-01-01

    Full Text Available In August/1999, a group of 14 adults from the staff of a private hospital in Contagem -- Minas Gerais State, Brazil, received unintentionally a 25 times concentrated dose of the 17-DD yellow fever vaccine (Bio-Manguinhos, due to a mistake at the reconstitution step. All patients were clinically and laboratorially evaluated at days 5, 13 and 35 post vaccination. Frequency of side effects and clinical observations of this group of individuals were not different from the observed in recipients immunized with normal doses of the vaccine. At the second and third evaluation none of the subjects reported symptoms. None of the patients presented abnormalities at the physical examination at none of the time points and in all cases the blood examination was normal, except for a reduced number of platelets that was detected in one subject at the first and second evaluation and reverted to normal at third evaluation. At the first evaluation point, 8 subjects were serum negative and 6 serum positive for yellow fever at the plaque reduction neutralization test. In 5 subjects the observed titre was 10 times higher as the baseline of 2.36 Log10 mUI/ml. The samples collected at second and third evaluation (13th and 35th days demonstrated that all subjects responded to the vaccination with the exception of one that did not present a positive result in any of the samples collected. This evaluation confirms the safety of the 17-DD yellow fever vaccine.

  13. [YEL-AND meningoencephalitis in a 4-year-old boy consecutive to a yellow-fever vaccine].

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    Gerin, M; Wroblewski, I; Bost-Bru, C; N'guyen, M-A; Debillon, T

    2014-04-01

    Yellow fever is a vector-borne disease transmitted by an endemic mosquito in sub-Saharan Africa and tropical South America. It causes fever and possibly liver and renal failure with hemorrhagic signs, which may be fatal. The yellow-fever vaccine is an attenuated vaccine that is recommended for all travelers over the age of 9 months in high-risk areas. Adverse effects have been reported: minor symptoms (such as viral syndrome), hypersensitivity reactions, and major symptoms such as viscerotropic disease (YEL-AVD) and neurotropic disease (YEL-AND). The yellow-fever vaccine-associated autoimmune disease with central nervous system involvement (such as acute disseminated encephalomyelitis) associates fever and headaches, neurologic dysfunction, seizures, cerebrospinal fluid (CSF) pleocytosis, and elevated protein, with neuroimaging consistent with multifocal areas of demyelization. The presence of antibodies or virus in CSF, within 1-30 days following vaccination, and the exclusion of other causes is necessary for diagnosis. We describe herein the case of a 4-year-old child who presented with severe encephalitis consecutive to a yellow-fever vaccine, with favorable progression. Diagnosis is based on the chronology of clinical and paraclinical signs and the presence of yellow-fever-specific antibodies in CSF. The treatment consists of symptomatic treatment and immunoglobulin injection. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. [Severe Yellow fever vaccine-associated disease: a case report and current overview].

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    Slesak, Günther; Gabriel, Martin; Domingo, Cristina; Schäfer, Johannes

    2017-08-01

    History and physical examination  A 56-year-old man developed high fever with severe headaches, fatigue, impaired concentration skills, and an exanthema 5 days after a yellow fever (YF) vaccination. Laboratory tests  Liver enzymes and YF antibody titers were remarkably elevated. YF vaccine virus was detected in urine by PCR. Diagnosis and therapy  Initially, severe YF vaccine-associated visceral disease was suspected and treated symptomatically. Clinical Course  His fever ceased after 10 days in total, no organ failure developed. However, postencephalitic symptoms persisted with fatigue and impaired concentration, memory, and reading skills and partly incapability to work for over 3 months. A diagnosis was made of suspected YF vaccine-associated neurotropic disease. Conclusion  Severe vaccine-derived adverse effects need to be considered in the indication process for YF vaccination. © Georg Thieme Verlag KG Stuttgart · New York.

  15. First dengue haemorrhagic fever epidemic in the Americas, 1981: insights into the causative agent.

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    Rodriguez-Roche, Rosmari; Hinojosa, Yoandri; Guzman, Maria G

    2014-12-01

    Historical records describe a disease in North America that clinically resembled dengue haemorrhagic fever during the latter part of the slave-trading period. However, the dengue epidemic that occurred in Cuba in 1981 was the first laboratory-confirmed and clinically diagnosed outbreak of dengue haemorrhagic fever in the Americas. At that time, the presumed source of the dengue type 2 strain isolated during this epidemic was considered controversial, partly because of the limited sequence data and partly because the origin of the virus appeared to be southern Asia. Here, we present a molecular characterisation at the whole-genome level of the original strains isolated at different time points during the epidemic. Phylogenetic trees constructed using Bayesian methods indicated that 1981 Cuban strains group within the Asian 2 genotype. In addition, the study revealed that viral evolution occurred during the epidemic - a fact that could be related to the increasing severity from month to month. Moreover, the Cuban strains exhibited particular amino acid substitutions that differentiate them from the New Guinea C prototype strain as well as from dengue type 2 strains isolated globally.

  16. Collaborative study to assess the suitability of a candidate International Standard for yellow fever vaccine.

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    Ferguson, Morag; Heath, Alan

    2004-12-01

    Yellow fever vaccines are routinely assayed by plaque assay. However, the results of these assays are then converted into mouse LD(50) using correlations/conversion factors which, in many cases, were established many years ago. The minimum required potency in WHO Recommendations is 10(3) LD(50)/dose. Thirteen participants from 8 countries participated in a collaborative study whose aim was to assess the suitability of two candidate preparations to serve as an International Standard for yellow fever vaccine. In addition, the study investigated the relationship between the mouse LD(50) test and plaque forming units with a view to updating the WHO recommendations. Plaque assays were more reproducible than mouse assays, as expected. Differences in sensitivities of plaque assays were observed between laboratories but these differences appear to be consistent within a laboratory for all samples and the expression of potency relative to the candidate standard vaccine improved the reproducibility of assays between laboratories. However, the use of potencies had little effect on the between laboratory variability in mouse LD(50) assays. There appears to be a consistent relationship between overall mean LD(50) and plaques titre for all study preparations other than sample E. The slope of the correlation curve is >1 and it would appear that 10(3) LD(50) is approximately equivalent to 10(4) plaque forming units (PFU), based on the overall means of all laboratory results. The First International Standard for yellow fever vaccine, NIBSC Code 99/616, has been established as the First International Standard for yellow fever vaccine by the Expert Committee of Biological Standards of the World Health Organisation. The International Standard has been arbitrarily assigned a potency of 10(4.5) International Units (IU) per ampoule. Manufacturers and National Control Laboratories are including the First International Standard for yellow fever vaccine in routine assays so that the minimum

  17. Yellow Rust Epidemics Worldwide Were Caused by Pathogen Races from Divergent Genetic Lineages

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    Ali, Sajid; Rodriguez-Algaba, Julian; Thach, Tine; Sørensen, Chris K.; Hansen, Jens G.; Lassen, Poul; Nazari, Kumarse; Hodson, David P.; Justesen, Annemarie F.; Hovmøller, Mogens S.

    2017-01-01

    We investigated whether the recent worldwide epidemics of wheat yellow rust were driven by races of few clonal lineage(s) or populations of divergent races. Race phenotyping of 887 genetically diverse Puccinia striiformis isolates sampled in 35 countries during 2009–2015 revealed that these epidemics were often driven by races from few but highly divergent genetic lineages. PstS1 was predominant in North America; PstS2 in West Asia and North Africa; and both PstS1 and PstS2 in East Africa. PstS4 was prevalent in Northern Europe on triticale; PstS5 and PstS9 were prevalent in Central Asia; whereas PstS6 was prevalent in epidemics in East Africa. PstS7, PstS8 and PstS10 represented three genetic lineages prevalent in Europe. Races from other lineages were in low frequencies. Virulence to Yr9 and Yr27 was common in epidemics in Africa and Asia, while virulence to Yr17 and Yr32 were prevalent in Europe, corresponding to widely deployed resistance genes. The highest diversity was observed in South Asian populations, where frequent recombination has been reported, and no particular race was predominant in this area. The results are discussed in light of the role of invasions in shaping pathogen population across geographical regions. The results emphasized the lack of predictability of emergence of new races with high epidemic potential, which stresses the need for additional investments in population biology and surveillance activities of pathogens on global food crops, and assessments of disease vulnerability of host varieties prior to their deployment at larger scales. PMID:28676811

  18. Yellow Rust Epidemics Worldwide Were Caused by Pathogen Races from Divergent Genetic Lineages

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    Sajid Ali

    2017-06-01

    Full Text Available We investigated whether the recent worldwide epidemics of wheat yellow rust were driven by races of few clonal lineage(s or populations of divergent races. Race phenotyping of 887 genetically diverse Puccinia striiformis isolates sampled in 35 countries during 2009–2015 revealed that these epidemics were often driven by races from few but highly divergent genetic lineages. PstS1 was predominant in North America; PstS2 in West Asia and North Africa; and both PstS1 and PstS2 in East Africa. PstS4 was prevalent in Northern Europe on triticale; PstS5 and PstS9 were prevalent in Central Asia; whereas PstS6 was prevalent in epidemics in East Africa. PstS7, PstS8 and PstS10 represented three genetic lineages prevalent in Europe. Races from other lineages were in low frequencies. Virulence to Yr9 and Yr27 was common in epidemics in Africa and Asia, while virulence to Yr17 and Yr32 were prevalent in Europe, corresponding to widely deployed resistance genes. The highest diversity was observed in South Asian populations, where frequent recombination has been reported, and no particular race was predominant in this area. The results are discussed in light of the role of invasions in shaping pathogen population across geographical regions. The results emphasized the lack of predictability of emergence of new races with high epidemic potential, which stresses the need for additional investments in population biology and surveillance activities of pathogens on global food crops, and assessments of disease vulnerability of host varieties prior to their deployment at larger scales.

  19. ETIOLOGY OF YELLOW FEVER : VII. DEMONSTRATION OF LEPTOSPIRA ICTEROIDES IN THE BLOOD, TISSUES, AND URINE OF YELLOW FEVER PATIENTS AND OF ANIMALS EXPERIMENTALLY INFECTED WITH THE ORGANISM.

    Science.gov (United States)

    Noguchi, H

    1919-08-01

    Examinations of fresh blood from yellow fever patients by means of the dark-field microscope, made in more than twenty-seven cases, revealed in three cases the presence of Leptospira icteroides. In no instance was a large number of organisms found, a long search being required before one was encountered. The injection of the blood into guinea pigs from two of the three positive cases induced in the animals a fatal infection, while the blood from the third positive case failed to infect the guinea pigs fatally. Careful but by no means exhaustive dark-field searches for the leptospira with fresh specimens of blood from the remaining cases of yellow fever ended without positive findings, although four of the specimens, when injected into guinea pigs, caused a fatal leptospira infection. Stained blood film preparations from the corresponding cases were also examined, but the percentage showing the leptospira in the blood was no greater than that found by examination in the fresh state with the dark-field microscope. In fact, owing to the defective stains that were available at the time of the investigation a great many slides did not take the proper coloration with Giemsa's or Wright's stain and could not be relied upon. Regarding the presence of Leptospira icteroides in various organs both dark-field and stained films were examined. In only one instance so far a few organisms were detected in the emulsion of liver taken shortly after death from a case dying on the 4th day of yellow fever. This part of the work will be reported later upon completion. Examinations of the urine from different cases of yellow fever were made both by dark-field microscope and by inoculation into guinea pigs. The results were totally negative in thirteen cases, including many convalescents, but in one case one of the guinea pigs inoculated with 10 cc. of the urine came down on the 15th day with suggestive symptoms (suspicion of jaundice, and some hemorrhagic and parenchymatous lesions of

  20. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control.

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    Matua, Gerald Amandu; Van der Wal, Dirk Mostert; Locsin, Rozzano C

    2015-01-01

    Ebola hemorrhagic fever, caused by the highly virulent RNA virus of the filoviridae family, has become one of the world's most feared pathogens. The virus induces acute fever and death, often associated with hemorrhagic symptoms in up to 90% of infected patients. The known sub-types of the virus are Zaire, Sudan, Taï Forest, Bundibugyo and Reston Ebola viruses. In the past, outbreaks were limited to the East and Central African tropical belt with the exception of Ebola Reston outbreaks that occurred in animal facilities in the Philippines, USA and Italy. The on-going outbreak in West Africa that is causing numerous deaths and severe socio-economic challenges has resulted in widespread anxiety globally. This panic may be attributed to the intense media interest, the rapid spread of the virus to other countries like United States and Spain, and moreover, to the absence of an approved treatment or vaccine. Informed by this widespread fear and anxiety, we analyzed the commonly used strategies to manage and control Ebola outbreaks and proposed new approaches that could improve epidemic management and control during future outbreaks. We based our recommendations on epidemic management practices employed during recent outbreaks in East, Central and West Africa, and synthesis of peer-reviewed publications as well as published "field" information from individuals and organizations recently involved in the management of Ebola epidemics. The current epidemic management approaches are largely "reactive", with containment efforts aimed at halting spread of existing outbreaks. We recommend that for better outcomes, in addition to "reactive" interventions, "pre-emptive" strategies also need to be instituted. We conclude that emphasizing both "reactive" and "pre-emptive" strategies is more likely to lead to better epidemic preparedness and response at individual, community, institutional, and government levels, resulting in timely containment of future Ebola outbreaks. Copyright

  1. Yellow fever vaccine-associated neurotropic disease (YEL-AND) - A case report.

    Science.gov (United States)

    Florczak-Wyspiańska, Jolanta; Nawotczyńska, Ewa; Kozubski, Wojciech

    Yellow fever (YF) is a mosquito-borne viral hemorrhagic fever, which is a serious and potentially fatal disease with no specific antiviral treatment that can be effectively prevented by an attenuated vaccine (YEL). Despite the long history of safe and efficacious YF vaccination, sporadic case reports of serious adverse events (SAEs) have been reported, including yellow fever vaccine-associated neurotropic disease (YEL-AND). YEL-AND usually appears within one month of YF vaccination, manifesting as meningoencephalitis, Guillain-Barré syndrome (GBS) or acute disseminated encephalomyelitis (ADEM). We report a case of YEL-AND with meningitis presentation in a 39-year-old Caucasian man without evidence of significant risk factors, which was confirmed by the presence of the YF virus and specific immunoglobulin G (IgG) antibodies in the cerebrospinal fluid (CSF). In conclusion, we should stress the importance of balancing the risk of SAEs associated with the vaccine and the benefits of YF vaccination for each patient individually. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  2. Yellow Fever outbreak in Darfur, Sudan in October 2012; the initial outbreak investigation report

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    Mohammed A. Soghaier

    2013-10-01

    Full Text Available Summary: Introduction: Sudan is subject to repeated outbreaks, including Viral Hemorrhagic Fever (VHF, which is considered to be a very serious illness. Yellow Fever (YF outbreaks in Sudan have been reported from the 1940s through 2005. In 2012, a new outbreak of YF occurred in the Darfur region. Objective: To identify the potential for an outbreak, to diagnose the disease and to be able to recognize its cause among the initial reported cases. Methodology: >This is a descriptive and investigative field study that applies standard communicable disease outbreak investigation steps. The study involved clinical, serological, entomological and environmental surveys. Results: The field investigation confirmed the outbreak and identified its cause to be YF. Conclusion: National surveillance systems should be strong enough to detect VHFs in a timely manner. Local health facilities should be prepared to promptly treat the initial cases because the case fatality ratios (CFRs are usually very high among the index cases. Keywords: Yellow Fever, Sudan, Darfur, VHFs, Soghaier

  3. Seroprevalence of yellow fever virus in selected health facilities in Western Kenya from 2010 to 2012.

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    Kwallah, Allan ole; Inoue, Shingo; Thairu-Muigai, Anne Wangari; Kuttoh, Nancy; Morita, Kouichi; Mwau, Matilu

    2015-01-01

    Yellow fever (YF), which is caused by a mosquito-borne virus, is an important viral hemorrhagic fever endemic in equatorial Africa and South America. Yellow fever virus (YFV) is the prototype of the family Flaviviridae and genus Flavivirus. The aim of this study was to determine the seroprevalence of YFV in selected health facilities in Western Kenya during the period 2010-2012. A total of 469 serum samples from febrile patients were tested for YFV antibodies using in-house IgM-capture ELISA, in-house indirect IgG ELISA, and 50% focus reduction neutralization test (FRNT50). The present study did not identify any IgM ELISA-positive cases, indicating absence of recent YFV infection in the area. Twenty-eight samples (6%) tested positive for YFV IgG, because of either YFV vaccination or past exposure to various flaviviruses including YFV. Five cases were confirmed by FRNT50; of these, 4 were either vaccination or natural infection during the YF outbreak in 1992-1993 or another period and 1 case was confirmed as a West Nile virus infection. Domestication and routine performance of arboviral differential diagnosis will help to address the phenomenon of pyrexia of unknown origin, contribute to arboviral research in developing countries, and enhance regular surveillance.

  4. Risk groups for yellow fever vaccine-associated viscerotropic disease (YEL-AVD).

    Science.gov (United States)

    Seligman, Stephen J

    2014-10-07

    Although previously considered as the safest of the live virus vaccines, reports published since 2001 indicate that live yellow fever virus vaccine can cause a severe, often fatal, multisystemic illness, yellow fever vaccine-associated viscerotropic disease (YEL-AVD), that resembles the disease it was designed to prevent. This review was prompted by the availability of a listing of the cumulative cases of YEL-AVD, insights from a statistical method for analyzing risk factors and re-evaluation of previously published data. The purpose of this review is to identify and analyze risk groups based on gender, age, outcome and predisposing illnesses. Using a passive surveillance system in the US, the incidence was reported as 0.3 to 0.4 cases per 100,000. However, other estimates range from 0 to 12 per 100,000. Identified and potential risk groups for YEL-AVD include elderly males, women between the ages of 19 and 34, people with a variety of autoimmune diseases, individuals who have been thymectomized because of thymoma, and infants and children ≤11 years old. All but the last group are supported by statistical analysis. The confirmed risk groups account for 77% (49/64) of known cases and 76% (32/42) of the deaths. The overall case fatality rate is 66% (42/64) with a rate of 80% (12/15) in young women, in contrast to 50% (13/26) in men ≥56 years old. Recognition of YEL-AVD raises the possibility that similar reactions to live chimeric flavivirus vaccines that contain a yellow fever virus vaccine backbone could occur in susceptible individuals. Delineation of risk groups focuses the search for genetic mutations resulting in immune defects associated with a given risk group. Lastly, identification of risk groups encourages concentration on measures to decrease both the incidence and the severity of YEL-AVD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Vaccinating in disease-free regions: a vaccine model with application to yellow fever.

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    Codeço, Claudia T; Luz, Paula M; Coelho, Flavio; Galvani, Alison P; Struchiner, Claudio

    2007-12-22

    Concerns regarding natural or induced emergence of infectious diseases have raised a debate on the pros and cons of pre-emptive vaccination of populations under uncertain risk. In the absence of immediate risk, ethical issues arise because even smaller risks associated with the vaccine are greater than the immediate disease risk (which is zero). The model proposed here seeks to formalize the vaccination decision process looking from the perspective of the susceptible individual, and results are shown in the context of the emergence of urban yellow fever in Brazil. The model decomposes the individual's choice about vaccinating or not into uncertain components. The choice is modelled as a function of (i) the risk of a vaccine adverse event, (ii) the risk of an outbreak and (iii) the probability of receiving the vaccine or escaping serious disease given an outbreak. Additionally, we explore how this decision varies as a function of mass vaccination strategies of varying efficiency. If disease is considered possible but unlikely (risk of outbreak less than 0.1), delay vaccination is a good strategy if a reasonably efficient campaign is expected. The advantage of waiting increases as the rate of transmission is reduced (low R0) suggesting that vector control programmes and emergency vaccination preparedness work together to favour this strategy. The opposing strategy, vaccinating pre-emptively, is favoured if the probability of yellow fever urbanization is high or if expected R0 is high and emergency action is expected to be slow. In summary, our model highlights the nonlinear dependence of an individual's best strategy on the preparedness of a response to a yellow fever outbreak or other emergent infectious disease.

  6. Immunogenicity of WHO-17D and Brazilian 17DD yellow fever vaccines: a randomized trial

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    Camacho Luiz Antonio Bastos

    2004-01-01

    Full Text Available OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots. METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind. Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

  7. The 17D-204 and 17DD yellow fever vaccines: an overview of major similarities and subtle differences.

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    Ferreira, Clarissa de Castro; Campi-Azevedo, Ana Carolina; Peruhype-Magalhāes, Vanessa; Costa-Pereira, Christiane; Albuquerque, Cleandro Pires de; Muniz, Luciana Feitosa; Yokoy de Souza, Talita; Oliveira, Ana Cristina Vanderley; Martins-Filho, Olindo Assis; da Mota, Licia Maria Henrique

    2018-01-01

    The yellow fever vaccine is a live attenuated virus vaccine that is considered one of the most efficient vaccines produced to date. The original 17D strain generated the substrains 17D-204 and 17DD, which are used for the current production of vaccines against yellow fever. The 17D-204 and 17DD substrains present subtle differences in their nucleotide compositions, which can potentially lead to variations in immunogenicity and reactogenicity. We will address the main changes in the immune responses induced by the 17D-204 and 17DD yellow fever vaccines and report similarities and differences between these vaccines in cellular and humoral immunity . This is a relevant issue in view of the re-emergence of yellow fever in Uganda in 2016 and in Brazil in the beginning of 2017. Areas covered: This article will be divided into 8 sections that will analyze the innate immune response, adaptive immune response, humoral response, production of cytokines, immunity in children, immunity in the elderly, gene expression and adverse reactions. Expert commentary: The 17D-204 and 17DD yellow fever vaccines present similar immunogenicity, with strong activation of the cellular and humoral immune responses. Additionally, both vaccines have similar adverse effects, which are mostly mild and thus are considered safe.

  8. Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever

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    Ana Cristina Vanderley Oliveira

    2014-01-01

    Full Text Available Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache and severe (visceral and neurotropic disease related to vaccine. However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance.

  9. Identification of Dengue and Chikungunya Cases Among Suspected Cases of Yellow Fever in the Democratic Republic of the Congo.

    Science.gov (United States)

    Makiala-Mandanda, Sheila; Ahuka-Mundeke, Steve; Abbate, Jessica L; Pukuta-Simbu, Elisabeth; Nsio-Mbeta, Justus; Berthet, Nicolas; Leroy, Eric Maurice; Becquart, Pierre; Muyembe-Tamfum, Jean-Jacques

    2018-05-16

    For more than 95% of acute febrile jaundice cases identified through surveillance for yellow fever, a reemerging arthropod-borne viral disease, no etiological exploration is ever done. The aim of this study was to test for other arthropod-borne viruses that can induce the same symptoms in patients enrolled in the yellow fever surveillance in the Democratic Republic of the Congo (DRC). Of 652 patients included in the surveillance of yellow fever in DRC from January 2003 to January 2012, 453 patients that tested negative for yellow fever virus (YFV) immunoglobulin M (IgM) antibodies were selected for the study. Real-time polymerase chain reaction was performed for the detection of dengue, West Nile, Chikungunya, O'nyong-nyong, Rift Valley fever, Zika, and YFV. The average age of patients was 22.1 years. We reported 16 cases (3.5%; confidence interval [CI]: 0.8-5.2) of dengue (serotypes 1 and 2) and 2 cases (0.4%; CI: 0.0-1.0) of Chikungunya. Three patients were co-infected with the two serotypes of dengue virus. Three cases of dengue were found in early July 2010 from the city of Titule (Oriental province) during a laboratory-confirmed outbreak of yellow fever, suggesting simultaneous circulation of dengue and yellow fever viruses. This study showed that dengue and Chikungunya viruses are potential causes of acute febrile jaundice in the DRC and highlights the need to consider dengue and Chikungunya diagnosis in the integrated disease surveillance and response program in the DRC. A prospective study is necessary to establish the epidemiology of these diseases.

  10. Persistence of Yellow Fever vaccine-induced antibodies after cord blood stem cell transplant.

    Science.gov (United States)

    Avelino-Silva, Vivian Iida; Freire, Marcos da Silva; Rocha, Vanderson; Rodrigues, Celso Arrais; Novis, Yana Sarkis; Sabino, Ester C; Kallas, Esper Georges

    2016-04-02

    We report the case of a cord blood haematopoietic stem cell transplant recipient who was vaccinated for Yellow Fever (YF) 7 days before initiating chemotherapy and had persistent YF antibodies more than 3 years after vaccination. Since the stem cell donor was never exposed to wild YF or to the YF vaccine, and our patient was not exposed to YF or revaccinated, this finding strongly suggests the persistence of recipient immunity. We briefly discuss potential consequences of incomplete elimination of recipient's leukocytes following existing haematopoietic cancer treatments.

  11. Guiding dengue vaccine development using knowledge gained from the success of the yellow fever vaccine.

    Science.gov (United States)

    Liang, Huabin; Lee, Min; Jin, Xia

    2016-01-01

    Flaviviruses comprise approximately 70 closely related RNA viruses. These include several mosquito-borne pathogens, such as yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), which can cause significant human diseases and thus are of great medical importance. Vaccines against both YFV and JEV have been used successfully in humans for decades; however, the development of a DENV vaccine has encountered considerable obstacles. Here, we review the protective immune responses elicited by the vaccine against YFV to provide some insights into the development of a protective DENV vaccine.

  12. Development and applications of transgenesis in the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Adelman, Zachary N; Jasinskiene, Nijole; James, Anthony A

    2002-04-30

    Transgenesis technology has been developed for the yellow fever mosquito, Aedes aegypti. Successful integration of exogenous DNA into the germline of this mosquito has been achieved with the class II transposable elements, Hermes, mariner and piggyBac. A number of marker genes, including the cinnabar(+) gene of Drosophila melanogaster, and fluorescent protein genes, can be used to monitor the insertion of these elements. The availability of multiple elements and marker genes provides a powerful set of tools to investigate basic biological properties of this vector insect, as well as the materials for developing novel, genetics-based, control strategies for the transmission of disease.

  13. Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data

    Science.gov (United States)

    Garske, Tini; Van Kerkhove, Maria D.; Yactayo, Sergio; Ronveaux, Olivier; Lewis, Rosamund F.; Staples, J. Erin; Perea, William; Ferguson, Neil M.

    2014-01-01

    Background Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. Methods and Findings Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns

  14. Yellow Fever in Africa: estimating the burden of disease and impact of mass vaccination from outbreak and serological data.

    Science.gov (United States)

    Garske, Tini; Van Kerkhove, Maria D; Yactayo, Sergio; Ronveaux, Olivier; Lewis, Rosamund F; Staples, J Erin; Perea, William; Ferguson, Neil M

    2014-05-01

    Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods. Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone. The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000-380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000-180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the

  15. Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Ravn, Henrik Bylling; Rodrigues, Amabelia

    2014-01-01

    is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar......Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine...

  16. Mutual interference on the immune response to yellow fever vaccine and a combined vaccine against measles, mumps and rubella.

    Science.gov (United States)

    Nascimento Silva, Juliana Romualdo; Camacho, Luiz Antonio B; Siqueira, Marilda M; Freire, Marcos de Silva; Castro, Yvone P; Maia, Maria de Lourdes S; Yamamura, Anna Maya Y; Martins, Reinaldo M; Leal, Maria de Luz F

    2011-08-26

    A randomized trial was conducted to assess the immunogenicity and reactogenicity of yellow fever vaccines (YFV) given either simultaneously in separate injections, or 30 days or more after a combined measles-mumps-rubella (MMR) vaccine. Volunteers were also randomized to YFV produced from 17DD and WHO-17D-213 substrains. The study group comprised 1769 healthy 12-month-old children brought to health care centers in Brasilia for routine vaccination. The reactogenicity was of the type and frequency expected for the vaccines and no severe adverse event was associated to either vaccine. Seroconversion and seropositivity 30 days or more after vaccination against yellow fever was similar across groups defined by YFV substrain. Subjects injected YFV and MMR simultaneously had lower seroconversion rates--90% for rubella, 70% for yellow fever and 61% for mumps--compared with those vaccinated 30 days apart--97% for rubella, 87% for yellow fever and 71% for mumps. Seroconversion rates for measles were higher than 98% in both comparison groups. Geometric mean titers for rubella and for yellow fever were approximately three times higher among those who got the vaccines 30 days apart. For measles and mumps antibodies GMTs were similar across groups. MMR's interference in immune response of YFV and YFV's interference in immune response of rubella and mumps components of MMR had never been reported before but are consistent with previous observations from other live vaccines. These results may affect the recommendations regarding primary vaccination with yellow fever vaccine and MMR. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Infection of Mosquito Cells (C6/36) by Dengue-2 Virus Interferes with Subsequent Infection by Yellow Fever Virus.

    Science.gov (United States)

    Abrao, Emiliana Pereira; da Fonseca, Benedito Antônio Lopes

    2016-02-01

    Dengue is one of the most important diseases caused by arboviruses in the world. Yellow fever is another arthropod-borne disease of great importance to public health that is endemic to tropical regions of Africa and the Americas. Both yellow fever and dengue viruses are flaviviruses transmitted by Aedes aegypti mosquitoes, and then, it is reasonable to consider that in a given moment, mosquito cells could be coinfected by both viruses. Therefore, we decided to evaluate if sequential infections of dengue and yellow fever viruses (and vice-versa) in mosquito cells could affect the virus replication patterns. Using immunofluorescence and real-time PCR-based replication assays in Aedes albopictus C6/36 cells with single or sequential infections with both viruses, we demonstrated the occurrence of viral interference, also called superinfection exclusion, between these two viruses. Our results show that this interference pattern is particularly evident when cells were first infected with dengue virus and subsequently with yellow fever virus (YFV). Reduction in dengue virus replication, although to a lower extent, was also observed when C6/36 cells were initially infected with YFV followed by dengue virus infection. Although the importance that these findings have on nature is unknown, this study provides evidence, at the cellular level, of the occurrence of replication interference between dengue and yellow fever viruses and raises the question if superinfection exclusion could be a possible explanation, at least partially, for the reported lack of urban yellow fever occurrence in regions where a high level of dengue transmission occurs.

  18. Construction and characterization of a recombinant yellow fever virus stably expressing Gaussia luciferase

    Directory of Open Access Journals (Sweden)

    TELISSA C. KASSAR

    Full Text Available ABSTRACT Yellow fever is an arthropod-borne viral disease that still poses high public health concerns, despite the availability of an effective vaccine. The development of recombinant viruses is of utmost importance for several types of studies, such as those aimed to dissect virus-host interactions and to search for novel antiviral strategies. Moreover, recombinant viruses expressing reporter genes may greatly facilitate these studies. Here, we report the construction of a recombinant yellow fever virus (YFV expressing Gaussia luciferase (GLuc (YFV-GLuc. We show, through RT-PCR, sequencing and measurement of GLuc activity, that stability of the heterologous gene was maintained after six passages. Furthermore, a direct association between GLuc expression and viral replication was observed (r2=0.9967, indicating that measurement of GLuc activity may be used to assess viral replication in different applications. In addition, we evaluated the use of the recombinant virus in an antiviral assay with recombinant human alfa-2b interferon. A 60% inhibition of GLuc expression was observed in cells infected with YFV-GLuc and incubated with IFN alfa-2b. Previously tested on YFV inhibition by plaque assays indicated a similar fold-decrease in viral replication. These results are valuable as they show the stability of YFV-GLuc and one of several possible applications of this construct.

  19. Risk of yellow fever vaccine-associated viscerotropic disease among the elderly: a systematic review.

    Science.gov (United States)

    Rafferty, Ellen; Duclos, Philippe; Yactayo, Sergio; Schuster, Melanie

    2013-12-02

    Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a rare and serious adverse event of the yellow fever (YF) vaccine that mimics wild-type YF. Research shows there may be an increased risk of YEL-AVD among the elderly population (≥ 60-65 years old), however this research has yet to be accumulated and reviewed in order to make policy recommendations to countries currently administering the YF vaccine. This paper systematically reviewed all information available on YEL-AVD to determine if there is an increased risk among the elderly, for both travelers and endemic populations. Age-specific reporting rates (RRs) were re-calculated from the literature using the Brighton Collaboration case definition for YEL-AVD and were then analyzed to determine if there was a significant difference between the RRs of younger and older age groups. Two out of the five studies found a significantly higher rate of YEL-AVD among the elderly population. Our findings suggest unexposed elders may be at an increased risk of developing YEF-AVD, however the evidence remains limited. Therefore, our findings for YF vaccination of elderly populations support the recommendations made by the Strategic Advisory Group of Experts (SAGE) in their April 2013 meeting, mainly vaccination of the elderly should be based on a careful risk-benefit analysis. Copyright © 2013 World Health Organization (WHO). Published by Elsevier Ltd.. All rights reserved.

  20. Animal models of yellow fever and their application in clinical research.

    Science.gov (United States)

    Julander, Justin G

    2016-06-01

    Yellow fever virus (YFV) is an arbovirus that causes significant human morbidity and mortality. This virus has been studied intensively over the past century, although there are still no treatment options for those who become infected. Periodic and unpredictable yellow fever (YF) outbreaks in Africa and South America continue to occur and underscore the ongoing need to further understand this viral disease and to develop additional countermeasures to prevent or treat cases of illness. The use of animal models of YF is critical to accomplishing this goal. There are several animal models of YF that replicate various aspects of clinical disease and have provided insight into pathogenic mechanisms of the virus. These typically include mice, hamsters and non-human primates (NHP). The utilities and shortcomings of the available animal models of YF are discussed. Information on recent discoveries that have been made in the field of YFV research is also included as well as important future directions in further ameliorating the morbidity and mortality that occur as a result of YFV infection. It is anticipated that these model systems will help facilitate further improvements in the understanding of this virus and in furthering countermeasures to prevent or treat infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication.

    Science.gov (United States)

    Wieten, Rosanne W; Jonker, Emile F F; Pieren, Daan K J; Hodiamont, Caspar J; van Thiel, Pieter P A M; van Gorp, Eric C M; de Visser, Adriëtte W; Grobusch, Martin P; Visser, Leo G; Goorhuis, Abraham

    2016-03-04

    The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice. In this study we compare two antibody tests (the Immune Fluorescence Assay and the Plaque Reduction Neutralization Test) in a group of Dutch immune-compromised travellers with a median of 33 days (IQR [28-49]) after primary YF vaccination. We collected samples of 15 immune-compromised vaccinees vaccinated with the 17D yellow fever vaccine between 2004 and 2012. All samples measured in the plaque reduction neutralization test yielded positive results (>80% virus neutralization with a 1:10 serum dilution). Immune Fluorescence Assay sensitivity was 28% (95% CI [0.12-0.49]). No adverse events were reported. All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. [Vaccination against yellow fever among patients on immunosuppressors with diagnoses of rheumatic diseases].

    Science.gov (United States)

    Mota, Licia Maria Henrique da; Oliveira, Ana Cristina Vanderley; Lima, Rodrigo Aires Corrêa; Santos-Neto, Leopoldo Luiz dos; Tauil, Pedro Luiz

    2009-01-01

    Yellow fever is endemic in some countries. The anti-yellow fever vaccine is the only effective means of protection but is contraindicated for immunocompromised patients. The aim of this paper was to report on a case series of rheumatological patients who were using immunosuppressors and were vaccinated against this disease. This was a retrospective study by means of a questionnaire applied to these patients, who were vaccinated 60 days before the investigation. Seventy patients of mean age 46 years were evaluated. Most of them were female (90%). There were cases of rheumatoid arthritis (54), systemic lupus erythematosus (11), spondyloarthropathy (5) and systemic sclerosis (2). The therapeutic schemes included methotrexate (42), corticosteroids (22), sulfasalazine (26), leflunomide (18), cyclophosphamide (3) and immunobiological agents (9). Sixteen patients (22.5%) reported some minor adverse effect. Among the eight patients using immunobiological agents, only one presented a mild adverse effect. Among these patients using immunosuppressors, adverse reactions were no more frequent than among immunocompetent individuals. This is the first study on this topic.

  3. [Entomological investigations conducted around ten cases of yellow fever in 2009 in the Denguélé sanitary region, Côte-d'Ivoire].

    Science.gov (United States)

    Konan, Y L; Fofana, D; Coulibaly, Z I; Diallo, A; Koné, A B; Doannio, J M C; Ekra, K D; Odéhouri-Koudou, P

    2011-10-01

    In November 2009, ten suspicious cases of yellow fever, including six deaths, were notified in the region of Denguélé, in the northwest of Côte-d'Ivoire. In order to evaluate the extent of yellow fever virus circulation and the risk for local people, a mission of entomological investigation was carried out by the Ministry of Health and Public Hygiene of Côte-d'Ivoire. Entomological investigations were conducted in the villages of confirmed cases (Banakoro and Tron-Touba) and the centers of consultation and hospitalization of cases during illness. Breteau index and recipient index were quasi nil. Aedes aegypti was absent among the captured mosquitoes. On the other hand, Aedes luteocephalus and Aedes opok were present at Banakoro and Tron-Touba with respective average biting rates of 0.8 and 0.6 bite/man/twilight. This situation of epidemic in the northwest of Côte-d'Ivoire could be explained by the deterioration of Denguélé region's health system which is a consequence of the war started in the country in 2002 and which has lowered the immunity of the population.

  4. Analysis of Impact of Geographical Environment and Socio-economic Factors on the Spatial Distribution of Kaohsiung Dengue Fever Epidemic

    Science.gov (United States)

    Hsu, Wei-Yin; Wen, Tzai-Hung; Yu, Hwa-Lung

    2013-04-01

    Taiwan is located in subtropical and tropical regions with high temperature and high humidity in the summer. This kind of climatic condition is the hotbed for the propagation and spread of the dengue vector mosquito. Kaohsiung City has been the worst dengue fever epidemic city in Taiwan. During the study period, from January 1998 to December 2011, Taiwan CDC recorded 7071 locally dengue epidemic cases in Kaohsiung City, and the number of imported case is 118. Our research uses Quantile Regression, a spatial infection disease distribution, to analyze the correlation between dengue epidemic and geographic environmental factors and human society factors in Kaohsiung. According to our experiment statistics, agriculture and natural forest have a positive relation to dengue fever(5.5~34.39 and 3.91~15.52). The epidemic will rise when the ratio for agriculture and natural forest increases. Residential ratio has a negative relation for quantile 0.1 to 0.4(-0.005~-0.78), and a positive relation for quantile 0.5 to0.9(0.01~18.0) . The mean income is also a significant factor in social economy field, and it has a negative relation to dengue fever(-0.01~-0.04). Conclusion from our research is that the main factor affecting the degree of dengue fever in predilection area is the residential proportion and the ratio of agriculture and natural forest plays an important role affecting the degree of dengue fever in non predilection area. Moreover, the serious epidemic area located by regression model is the same as the actual condition in Kaohsiung. This model can be used to predict the serious epidemic area of dengue fever and provide some references for the Health Agencies

  5. An online spatiotemporal prediction model for dengue fever epidemic in Kaohsiung (Taiwan).

    Science.gov (United States)

    Yu, Hwa-Lung; Angulo, José M; Cheng, Ming-Hung; Wu, Jiaping; Christakos, George

    2014-05-01

    The emergence and re-emergence of disease epidemics is a complex question that may be influenced by diverse factors, including the space-time dynamics of human populations, environmental conditions, and associated uncertainties. This study proposes a stochastic framework to integrate space-time dynamics in the form of a Susceptible-Infected-Recovered (SIR) model, together with uncertain disease observations, into a Bayesian maximum entropy (BME) framework. The resulting model (BME-SIR) can be used to predict space-time disease spread. Specifically, it was applied to obtain a space-time prediction of the dengue fever (DF) epidemic that took place in Kaohsiung City (Taiwan) during 2002. In implementing the model, the SIR parameters were continually updated and information on new cases of infection was incorporated. The results obtained show that the proposed model is rigorous to user-specified initial values of unknown model parameters, that is, transmission and recovery rates. In general, this model provides a good characterization of the spatial diffusion of the DF epidemic, especially in the city districts proximal to the location of the outbreak. Prediction performance may be affected by various factors, such as virus serotypes and human intervention, which can change the space-time dynamics of disease diffusion. The proposed BME-SIR disease prediction model can provide government agencies with a valuable reference for the timely identification, control, and prevention of DF spread in space and time. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.

    Science.gov (United States)

    Mweya, Clement N; Mboera, Leonard E G; Kimera, Sharadhuli I

    2017-07-01

    Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

  7. Travel characteristics and yellow fever vaccine usage among US Global TravEpiNet travelers visiting countries with risk of yellow fever virus transmission, 2009-2011.

    Science.gov (United States)

    Jentes, Emily S; Han, Pauline; Gershman, Mark D; Rao, Sowmya R; LaRocque, Regina C; Staples, J Erin; Ryan, Edward T

    2013-05-01

    Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27-5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37-6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk-benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations.

  8. Travel Characteristics and Yellow Fever Vaccine Usage Among US Global TravEpiNet Travelers Visiting Countries with Risk of Yellow Fever Virus Transmission, 2009–2011

    Science.gov (United States)

    Jentes, Emily S.; Han, Pauline; Gershman, Mark D.; Rao, Sowmya R.; LaRocque, Regina C.; Staples, J. Erin; Ryan, Edward T.

    2013-01-01

    Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27–5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37–6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk–benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations. PMID:23458961

  9. Dengue Fever in American Military Personnel in the Philippines: Clinical Observations on Hospitalized Patients during a 1984 Epidemic

    Science.gov (United States)

    1989-03-01

    the mean maximum temperature was Hypotenson 15 (62.5) 102.0 + 1.3 F. A "saddle back" or dip- Rash (Non- Petechial ) 13 (54.2) hasic fever pattern was not...DENGUE FEVER IN AMERICAN MILITARY PERSONNEL IN THE PHILIPPINES: CLINICAL OBSERVATIONS ON HOSPITALIZED PATIENS DURING A 1984 EPIDEMIC C.G. Hayes, T.F...Accession Tr~I Jti ti DENGUE FEVER IN AMERICAN MILITARY PERSONNEL IN THE PHILIPPINES: CLINICAL OBSERVATIONS ON HOSPITALIZED PATIENTS DURING A 1984

  10. THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

    Science.gov (United States)

    Moysidis, Stavros N; Koulisis, Nicole; Patel, Vivek R; Kashani, Amir H; Rao, Narsing A; Humayun, Mark S; Rodger, Damien C

    2017-01-01

    To describe a case of small retinal vessel vasculopathy postvaccination. We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary

  11. Intradermally Administered Yellow Fever Vaccine at Reduced Dose Induces a Protective Immune Response: A Randomized Controlled Non-Inferiority Trial

    NARCIS (Netherlands)

    M.G. Roukens (Guy); A.C.Th.M. Vossen (Ann); P.J. Bredenbeek (Peter); J.T. van Dissel (Jaap); L.G. Visser (Leo)

    2008-01-01

    textabstractBackground:Implementation of yellow fever vaccination is currently hampered by limited supply of vaccine. An alternative route of administration with reduced amounts of vaccine but without loss of vaccine efficacy would boost vaccination programmes.Methods and Findings:A randomized,

  12. How Brazil joined the quest for a yellow fever vaccine. Interview by Claudia Jurberg and Julia D'Aloisio..

    Science.gov (United States)

    Benchimol, Jaime

    2013-03-01

    Brazil recently announced an agreement between its Bio-Manguinhos vaccine unit and two US companies to research and develop a new yellow fever vaccine. Claudia Jurberg and Julia D'Aloisio talk to Jaime Benchimol about the controversial history of the development of the vaccine that benefits millions of people today.

  13. 17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients

    NARCIS (Netherlands)

    Wieten, R. W.; Goorhuis, A.; Jonker, E. F. F.; de Bree, G. J.; de Visser, A. W.; van Genderen, P. J. J.; Remmerswaal, E. B. M.; ten Berge, I. J. M.; Visser, L. G.; Grobusch, M. P.; van Leeuwen, E. M. M.

    2016-01-01

    The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen

  14. The single kinin receptor signals to separate and independent physiological pathways in Malpighian tubules of the yellow fever mosquito

    Science.gov (United States)

    In the past we have used the leucokinins, the kinins of the cockroach Leucophaea, to evaluate the mechanism of diuretic action of kinin peptides in Malpighian tubules of the yellow fever mosquito Aedes aegypti. Now using aedeskinins, the kinins of Aedes, are available, we find that in isolated Aede...

  15. Toxicity of compounds isolated from white snakeroot (Ageratina altissima) to adult and larval yellow fever mosquitoes (Aedes aegypti)

    Science.gov (United States)

    Because of increasing insecticide resistance, new pesticides are needed. Flowering plants have been the source of useful pesticides in the past. We studied 15 chemicals isolated from a poisonous pasture plant for activity against the yellow fever mosquito. We found that dehydrotremetone was effectiv...

  16. Gustatory receptor neuron responds to DEET and other insect repellents in the yellow fever mosquito, aedes aegypti

    Science.gov (United States)

    Three gustatory receptor neurons were characterized for contact chemoreceptive sensilla on the labella of female yellow fever mosquitoes, Aedes aegypti. The neuron with the smallest amplitude spike responded to the feeding deterrent, quinine, as well as DEET and other insect repellents. Two other ...

  17. Simulated epidemiological and economic effects of measures to reduce piglet supply during a classical swine fever epidemic in the Netherlands

    NARCIS (Netherlands)

    Mangen, M.J.J.; Nielen, M.; Burrell, A.M.

    2003-01-01

    The effects of additional measures adopted during a classical swine fever (CSF) epidemic to reduce piglet supply, namely, an insemination ban, abortion of sows and killing of young piglets, are studied using a stochastic, spatial, dynamic epidemiological simulation model of the pig sector in the

  18. Yellow fever vaccination coverage following massive emergency immunization campaigns in rural Uganda, May 2011: a community cluster survey

    Science.gov (United States)

    2013-01-01

    Background Following an outbreak of yellow fever in northern Uganda in December 2010, Ministry of Health conducted a massive emergency vaccination campaign in January 2011. The reported vaccination coverage in Pader District was 75.9%. Administrative coverage though timely, is affected by incorrect population estimates and over or under reporting of vaccination doses administered. This paper presents the validated yellow fever vaccination coverage following massive emergency immunization campaigns in Pader district. Methods A cross sectional cluster survey was carried out in May 2011 among communities in Pader district and 680 respondents were indentified using the modified World Health Organization (WHO) 40 × 17 cluster survey sampling methodology. Respondents were aged nine months and above. Interviewer administered questionnaires were used to collect data on demographic characteristics, vaccination status and reasons for none vaccination. Vaccination status was assessed using self reports and vaccination card evidence. Our main outcomes were measures of yellow fever vaccination coverage in each age-specific stratum, overall, and disaggregated by age and sex, adjusting for the clustered design and the size of the population in each stratum. Results Of the 680 survey respondents, 654 (96.1%, 95% CI 94.9 – 97.8) reported being vaccinated during the last campaign but only 353 (51.6%, 95% CI 47.2 – 56.1) had valid yellow fever vaccination cards. Of the 280 children below 5 years, 269 (96.1%, 95% CI 93.7 – 98.7) were vaccinated and nearly all males 299 (96.9%, 95% CI 94.3 – 99.5) were vaccinated. The main reasons for none vaccination were; having travelled out of Pader district during the campaign period (40.0%), lack of transport to immunization posts (28.0%) and, sickness at the time of vaccination (16.0%). Conclusions Our results show that actual yellow fever vaccination coverage was high and satisfactory in Pader district since it was above the

  19. CD8+ T Cells Complement Antibodies in Protecting against Yellow Fever Virus

    DEFF Research Database (Denmark)

    Bassi, Maria R; Kongsgaard, Michael; Steffensen, Maria A

    2015-01-01

    The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model...... of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune...... response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination...

  20. Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate

    DEFF Research Database (Denmark)

    Ekenberg, C.; Friis-Møller, N.; Ulstrup, Thomas

    2016-01-01

    We present a case of a 56-year-old woman with Crohn's disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated...... in patients treated with immunosuppressive drugs. Following vaccination, the patient fell ill with influenza-like illness. Elevated transaminase levels and YF viremia were detected. Despite being immunocompromised, the patient did not develop more severe adverse effects. Neutralising antibodies to YF virus...... were detected on day 14 following vaccination and remained protective at least 10 months after vaccination. Limited data is available on outcomes of YFV in patients receiving immunosuppressive therapy, including biologics, and we report this case as a reminder of vigilance of vaccine recommendations...

  1. Efficient, trans-complementing packaging systems for chimeric, pseudoinfectious dengue 2/yellow fever viruses

    International Nuclear Information System (INIS)

    Shustov, Alexandr V.; Frolov, Ilya

    2010-01-01

    In our previous studies, we have stated to build a new strategy for developing defective, pseudoinfectious flaviviruses (PIVs) and applying them as a new type of vaccine candidates. PIVs combined the efficiency of live vaccines with the safety of inactivated or subunit vaccines. The results of the present work demonstrate further development of chimeric PIVs encoding dengue virus 2 (DEN2V) glycoproteins and yellow fever virus (YFV)-derived replicative machinery as potential vaccine candidates. The newly designed PIVs have synergistically functioning mutations in the prM and NS2A proteins, which abolish processing of the latter proteins and make the defective viruses capable of producing either only noninfectious, immature and/or subviral DEN2V particles. The PIV genomes can be packaged to high titers into infectious virions in vitro using the NS1-deficient YFV helper RNAs, and both PIVs and helpers can then be passaged as two-component genome viruses at an escalating scale.

  2. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  3. Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day.

    Science.gov (United States)

    Collins, Natalie D; Barrett, Alan D T

    2017-03-01

    Live attenuated 17D vaccine is considered one of the safest and efficacious vaccines developed to date. This review highlights what is known and the gaps in knowledge of vaccine-induced protective immunity. Recently, the World Health Organization modifying its guidance from 10-year booster doses to one dose gives lifelong protection in most populations. Nonetheless, there are some data suggesting immunity, though protective, may wane over time in certain populations and more research is needed to address this question. Despite having an effective vaccine to control yellow fever, vaccine shortages were identified during outbreaks in 2016, eventuating the use of a fractional-dosing campaign in the Democratic Republic of the Congo. Limited studies hinder identification of the underlying mechanism(s) of vaccine longevity; however, concurrent outbreaks during 2016 provide an opportunity to evaluate vaccine immunity following fractional dosing and insights into vaccine longevity in populations where there is limited information.

  4. RESPONSE OF VOLTA CHILDREN TO JET INOCULATION OF COMBINED LIVE MEASLES, SMALLPOX AND YELLOW FEVER VACCINES.

    Science.gov (United States)

    MEYER, H M; HOSTETLER, D D; BERNHEIN, B C; ROGERS, N G; LAMBIN, P; CHASSARY, A; LABUSQUIERE, R; SMADEL, J E

    1964-01-01

    An earlier study established that Upper Volta children respond to vaccination with the Enders live attenuated measles strain in the same general fashion as do children in the USA. The present report describes a second pilot project carried out in Ouagadougou, Upper Volta. During this investigation various mixtures of live measles, smallpox and 17D yellow fever vaccines were introduced into susceptible infants by jet injection. Combining the attenuated virus vaccines did not alter or accentuate the characteristic clinical reactions elicited by the individual components, nor was there evidence of significant immunological interference. From this experience it is concluded that combined vaccination with these agents may be safely and effectively employed in larger programmes as the need dictates.

  5. Dynamic behavior of sylvatic yellow fever in Brazil (1954-2008

    Directory of Open Access Journals (Sweden)

    Fernando Portela Câmara

    2011-06-01

    Full Text Available INTRODUCTION: Sylvatic yellow fever (SYF is enzootic in Brazil, causing periodic outbreaks in humans living near forest borders or in rural areas. In this study, the cycling patterns of this arbovirosis were analyzed. METHODS: Spectral Fourier analysis was used to capture the periodicity patterns of SYF in time series. RESULTS: SYF outbreaks have not increased in frequency, only in the number of cases. There are two dominant cycles in SYF outbreaks, a seven year cycle for the central-western region and a 14 year cycle for the northern region. Most of the variance was concentrated in the central-western region and dominated the entire endemic region. CONCLUSIONS: The seven year cycle is predominant in the endemic region of the disease due the greater contribution of variance in the central-western region; however, it was possible identify a 14 cycle that governs SYF outbreaks in the northern region. No periodicities were identified for the remaining geographical regions.

  6. Tropheryma whipplei as a Cause of Epidemic Fever, Senegal, 2010-2012.

    Science.gov (United States)

    Bassene, Hubert; Mediannikov, Oleg; Socolovschi, Cristina; Ratmanov, Pavel; Keita, Alpha K; Sokhna, Cheikh; Raoult, Didier; Fenollar, Florence

    2016-07-01

    The bacterium Tropheryma whipplei, which causes Whipple disease in humans, is commonly detected in the feces of persons in Africa. It is also associated with acute infections. We investigated the role of T. whipplei in febrile patients from 2 rural villages in Senegal. During June 2010-March 2012, we collected whole-blood finger-prick samples from 786 febrile and 385 healthy villagers. T. whipplei was detected in blood specimens from 36 (4.6%) of the 786 febrile patients and in 1 (0.25%) of the 385 apparently healthy persons. Of the 37 T. whipplei cases, 26 (70.2%) were detected in August 2010. Familial cases and a potential new genotype were observed. The patients' symptoms were mainly headache (68.9%) and cough (36.1%). Our findings suggest that T. whipplei is a cause of epidemic fever in Senegal.

  7. Simulating the epidemiological and economic effects of an African swine fever epidemic in industrialized swine populations

    DEFF Research Database (Denmark)

    Hisham Beshara Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2016-01-01

    to simulate the spread of ASF virus between domestic swine herds exemplified by the Danish swine population. ASF was simulated to spread via animal movement, low- or medium-risk contacts and local spread. Each epidemic was initiated in a randomly selected herd – either in a nucleus herd, a sow herd......African swine fever (ASF) is a notifiable infectious disease with a considerable impact on animal health and is currently one of the most important emerging diseases of domestic pigs. ASF was introduced into Georgia in 2007 and subsequently spread to the Russian Federation and several Eastern...... European countries. Consequently, there is a non-negligible risk of ASF spread towards Western Europe. Therefore it is important to develop tools to improve our understanding of the spread and control of ASF for contingency planning. A stochastic and dynamic spatial spread model (DTU-DADS) was adjusted...

  8. Risk assessment for yellow fever in western and North-Western provinces of Zambia

    Directory of Open Access Journals (Sweden)

    Olusegun A Babaniyi

    2015-01-01

    Full Text Available Background: North-Western and Western provinces of Zambia were reclassified as low-risk areas for yellow fever (YF. However, the current potential for YF transmission in these areas is unclear. Aims: To determine the current potential risk of YF infection. Setting and Design: A cross sectional study was conducted in North-Western and Western provinces of Zambia. Materials and Methods: Samples were tested for both YF virus-specific IgG and IgM antibodies by the ELISA and YF virus confirmation was done using Plaque Reduction Neutralization Test. The samples were also tested for IgG and IgM antibodies against other flaviviruses. Results: Out of the 3625 respondents who participated in the survey, 46.7% were males and 9.4% were aged less than 5 years. Overall, 58.1% of the participants slept under an impregnated insecticide-treated net and 20.6% reported indoor residual spraying of insecticides. A total of 616 (17.0% samples were presumptive YF positive. The prevalence for YF was 0.3% for long-term infection and 0.2% for recent YF infection. None of the YF confirmed cases had received YF vaccine. Prevalence rates for other flaviviruses were 149 (4.1% for Dengue, 370 (10.2% for West Nile and 217 (6.0% for Zika. Conclusion: There is evidence of past and recent infection of YF in both provinces. Hence, they are at a low risk for YF infection. Yellow fever vaccination should be included in the EPI program in the two provinces and strengthen surveillance with laboratory confirmation.

  9. Rapid molecular assays for the detection of yellow fever virus in low-resource settings.

    Science.gov (United States)

    Escadafal, Camille; Faye, Oumar; Sall, Amadou Alpha; Faye, Ousmane; Weidmann, Manfred; Strohmeier, Oliver; von Stetten, Felix; Drexler, Josef; Eberhard, Michael; Niedrig, Matthias; Patel, Pranav

    2014-03-01

    Yellow fever (YF) is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV), is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control. The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA) assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay) to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal. The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction) and rapid processing time (<20 min). Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for YFV detection in low-resource settings.

  10. The seasonal influence of climate and environment on yellow fever transmission across Africa.

    Science.gov (United States)

    Hamlet, Arran; Jean, Kévin; Perea, William; Yactayo, Sergio; Biey, Joseph; Van Kerkhove, Maria; Ferguson, Neil; Garske, Tini

    2018-03-01

    Yellow fever virus (YFV) is a vector-borne flavivirus endemic to Africa and Latin America. Ninety per cent of the global burden occurs in Africa where it is primarily transmitted by Aedes spp, with Aedes aegypti the main vector for urban yellow fever (YF). Mosquito life cycle and viral replication in the mosquito are heavily dependent on climate, particularly temperature and rainfall. We aimed to assess whether seasonal variations in climatic factors are associated with the seasonality of YF reports. We constructed a temperature suitability index for YFV transmission, capturing the temperature dependence of mosquito behaviour and viral replication within the mosquito. We then fitted a series of multilevel logistic regression models to a dataset of YF reports across Africa, considering location and seasonality of occurrence for seasonal models, against the temperature suitability index, rainfall and the Enhanced Vegetation Index (EVI) as covariates alongside further demographic indicators. Model fit was assessed by the Area Under the Curve (AUC), and models were ranked by Akaike's Information Criterion which was used to weight model outputs to create combined model predictions. The seasonal model accurately captured both the geographic and temporal heterogeneities in YF transmission (AUC = 0.81), and did not perform significantly worse than the annual model which only captured the geographic distribution. The interaction between temperature suitability and rainfall accounted for much of the occurrence of YF, which offers a statistical explanation for the spatio-temporal variability in transmission. The description of seasonality offers an explanation for heterogeneities in the West-East YF burden across Africa. Annual climatic variables may indicate a transmission suitability not always reflected in seasonal interactions. This finding, in conjunction with forecasted data, could highlight areas of increased transmission and provide insights into the occurrence of

  11. Rapid molecular assays for the detection of yellow fever virus in low-resource settings.

    Directory of Open Access Journals (Sweden)

    Camille Escadafal

    2014-03-01

    Full Text Available BACKGROUND: Yellow fever (YF is an acute viral hemorrhagic disease transmitted by Aedes mosquitoes. The causative agent, the yellow fever virus (YFV, is found in tropical and subtropical areas of South America and Africa. Although a vaccine is available since the 1930s, YF still causes thousands of deaths and several outbreaks have recently occurred in Africa. Therefore, rapid and reliable diagnostic methods easy to perform in low-resources settings could have a major impact on early detection of outbreaks and implementation of appropriate response strategies such as vaccination and/or vector control. METHODOLOGY: The aim of this study was to develop a YFV nucleic acid detection method applicable in outbreak investigations and surveillance studies in low-resource and field settings. The method should be simple, robust, rapid and reliable. Therefore, we adopted an isothermal approach and developed a recombinase polymerase amplification (RPA assay which can be performed with a small portable instrument and easy-to-use lyophilized reagents. The assay was developed in three different formats (real-time with or without microfluidic semi-automated system and lateral-flow assay to evaluate their application for different purposes. Analytical specificity and sensitivity were evaluated with a wide panel of viruses and serial dilutions of YFV RNA. Mosquito pools and spiked human plasma samples were also tested for assay validation. Finally, real-time RPA in portable format was tested under field conditions in Senegal. CONCLUSION/SIGNIFICANCE: The assay was able to detect 20 different YFV strains and demonstrated no cross-reactions with closely related viruses. The RPA assay proved to be a robust, portable method with a low detection limit (<21 genome equivalent copies per reaction and rapid processing time (<20 min. Results from real-time RPA field testing were comparable to results obtained in the laboratory, thus confirming our method is suitable for

  12. High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo.

    Science.gov (United States)

    Makiala-Mandanda, Sheila; Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Bivigou-Mboumba, Berthold; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques; Becquart, Pierre

    2017-05-01

    The majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 10 5 IU/ml for HBV (range, 769 to 9.82 × 10 9 IU/ml) and 1.4 × 10 6 IU/ml for HDV (range, 3.1 × 10 2 to 2.9 × 10 8 IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC. Copyright © 2017 Makiala-Mandanda et al.

  13. Rift Valley fever virus epidemic in Kenya, 2006/2007: the entomologic investigations.

    Science.gov (United States)

    Sang, Rosemary; Kioko, Elizabeth; Lutomiah, Joel; Warigia, Marion; Ochieng, Caroline; O'Guinn, Monica; Lee, John S; Koka, Hellen; Godsey, Marvin; Hoel, David; Hanafi, Hanafi; Miller, Barry; Schnabel, David; Breiman, Robert F; Richardson, Jason

    2010-08-01

    In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa.

  14. Concomitant outbreaks of yellow fever and hepatitis E virus in Darfur States, Sudan, 2012.

    Science.gov (United States)

    Ahmed, Sarah S; Soghaier, Mohammed A; Mohammed, Sozan; Khogali, Hayat S; Osman, Muntasir M; Abdalla, Abdalla M

    2016-01-31

    Yellow fever (YF) is a vector-borne disease transmitted to humans by infected Aedes mosquitoes, while hepatitis E virus (HEV) is a waterborne disease that is transmitted through the fecal-oral route. Both diseases have very close clinical presentation, namely fever, jaundice, malaise, and dark urine; they differ in severity and outcome. In this cross-sectional, laboratory-based study, an attempt was made to measure the correlation of concomitant YF and HEV infection in Darfur States during the previous YF outbreak in 2012. Results found concomitant outbreaks of YF and HEV at the same time with very weak statistical correlation between the two infections during the outbreak period, with Cramer's V correlation 0.05 and insignificant p value of 0.86. This correlation indicates that clinicians and care providers in tropical areas have to deal with clinical case definitions used for disease surveillance very carefully since prevalence of HEV infection is relatively common and this increases the possibility of misclassification and missing YF cases, particularly initial index cases, in a season or outbreak.

  15. Yellow Fever outbreak in Darfur, Sudan in October 2012; the initial outbreak investigation report.

    Science.gov (United States)

    Soghaier, Mohammed A; Hagar, Ahmed; Abbas, Mohammed A; Elmangory, Mutasim M; Eltahir, Khalid M; Sall, Amadou A

    2013-10-01

    Sudan is subject to repeated outbreaks, including Viral Hemorrhagic Fever (VHF), which is considered to be a very serious illness. Yellow Fever (YF) outbreaks in Sudan have been reported from the 1940s through 2005. In 2012, a new outbreak of YF occurred in the Darfur region. To identify the potential for an outbreak, to diagnose the disease and to be able to recognize its cause among the initial reported cases. >This is a descriptive and investigative field study that applies standard communicable disease outbreak investigation steps. The study involved clinical, serological, entomological and environmental surveys. The field investigation confirmed the outbreak and identified its cause to be YF. National surveillance systems should be strong enough to detect VHFs in a timely manner. Local health facilities should be prepared to promptly treat the initial cases because the case fatality ratios (CFRs) are usually very high among the index cases. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  16. A fatal yellow fever virus infection in China: description and lessons

    Science.gov (United States)

    Chen, Zhihai; Liu, Lin; Lv, Yanning; Zhang, Wei; Li, Jiandong; Zhang, Yi; Di, Tian; Zhang, Shuo; Liu, Jingyuan; Li, Jie; Qu, Jing; Hua, Wenhao; Li, Chuan; Wang, Peng; Zhang, Quanfu; Xu, Yanli; Jiang, Rongmeng; Wang, Qin; Chen, Lijuan; Wang, Shiwen; Pang, Xinghuo; Liang, Mifang; Ma, Xuejun; Li, Xingwang; Wang, Quanyi; Zhang, Fujie; Li, Dexin

    2016-01-01

    Yellow fever (YF) is a viral disease endemic to the tropical regions of Africa and South America. An outbreak of YF has been occurring in Angola, since the beginning of 2016. In March 2016, a 32-year-old Chinese man who returned from Angola was hospitalized and diagnosed with the first case of imported YF in China. Clinical observations, blood viral RNA detection, serological testing and treatments for the patient were performed daily. The virus was isolated in Vero cells, and the complete viral genome was sequenced and analyzed using the next-generation genomic sequencing platform. The patient presented with hemorrhagic fever, jaundice and oliguria at day 3 after onset, which rapidly progressed to multisystem organ failure with extremely elevated liver, pancreatic and myocardial enzymes. The patient died despite the intensive supportive treatments that were performed. A liver biopsy showed severe and multilobular necrosis. Viral RNA was detectable throughout the clinical course of the disease. Whole-genomic sequence analysis revealed that the virus belongs to the Angola71 genotype. Although the virus has been circulating in Angola for 45 years, only 14 amino-acid substitutions and no amino-acid changes were observed in the membrane and envelope proteins compared with the virus collected in 1971. The presence of this imported YF case in China indicated that with the increase in business travel among countries, YF outbreaks in Africa can lead to the international spread of the disease. The production and use of YF vaccines is, therefore, an urgent issue. PMID:27406389

  17. Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010-January 2011.

    Science.gov (United States)

    Wamala, Joseph F; Malimbo, Mugagga; Okot, Charles L; Atai-Omoruto, Ann D; Tenywa, Emmanuel; Miller, Jeffrey R; Balinandi, Stephen; Shoemaker, Trevor; Oyoo, Charles; Omony, Emmanuel O; Kagirita, Atek; Musenero, Monica M; Makumbi, Issa; Nanyunja, Miriam; Lutwama, Julius J; Downing, Robert; Mbonye, Anthony K

    2012-07-01

    In November 2010, following reports of an outbreak of a fatal, febrile, hemorrhagic illness in northern Uganda, the Uganda Ministry of Health established multisector teams to respond to the outbreak. This was a case-series investigation in which the response teams conducted epidemiological and laboratory investigations on suspect cases. The cases identified were line-listed and a data analysis was undertaken regularly to guide the outbreak response. Overall, 181 cases met the yellow fever (YF) suspected case definition; there were 45 deaths (case fatality rate 24.9%). Only 13 (7.5%) of the suspected YF cases were laboratory confirmed, and molecular sequencing revealed 92% homology to the YF virus strain Couma (Ethiopia), East African genotype. Suspected YF cases had fever (100%) and unexplained bleeding (97.8%), but jaundice was rare (11.6%). The overall attack rate was 13 cases/100000 population, and the attack rate was higher for males than females and increased with age. The index clusters were linked to economic activities undertaken by males around forests. This was the largest YF outbreak ever reported in Uganda. The wide geographical case dispersion as well as the male and older age preponderance suggests transmission during the outbreak was largely sylvatic and related to occupational activities around forests. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  18. The 2007–2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming.

    Science.gov (United States)

    Dijkstra, Frederika; van der Hoek, Wim; Wijers, Nancy; Schimmer, Barbara; Rietveld, Ariene; Wijkmans, Clementine J; Vellema, Piet; Schneeberger, Peter M

    2012-02-01

    We describe the Q fever epidemic in the Netherlands with emphasis on the epidemiological characteristics of acute Q fever patients and the association with veterinary factors. Data from 3264 notifications for acute Q fever in the period from 2007 through 2009 were analysed. The patients most affected were men, smokers and persons aged 40–60 years. Pneumonia was the most common clinical presentation (62% in 2007 and 2008). Only 3.2% of the patients were working in the agriculture sector and 0.5% in the meat-processing industry including abattoirs. Dairy goat farms with Coxiella burnetii-induced abortion waves were mainly located in the same area where human cases occurred. Airborne transmission of contaminated dust particles from commercial dairy goat farms in densely populated areas has probably caused this epidemic. In 2010, there was a sharp decline in the number of notified cases following the implementation of control measures on dairy goat and sheep farms such as vaccination, hygiene measures and culling of pregnant animals on infected farms. In combination with a rise in the human population with antibodies against C. burnetii, these have most likely ended the outbreak. Development of chronic Q fever in infected patients remains an important problem for years to come.

  19. [Entomological investigation following the re-emergence of yellow fever in 2008 in Abidjan area (Côte d'Ivoire)].

    Science.gov (United States)

    Konan, Y L; Koné, A B; Ekra, K D; Doannio, J M C; Odéhouri, K P

    2009-06-01

    In April 2008, Abidjan was again faced with another case of yellow fever after the epidemic of 2001 causing mass immunization campaign. In order to evaluate the extent of amaril virus circulation and the risk for local people, an entomological investigation was carried out by the Ministry of Health and Public Hygiene of Côte d'Ivoire. At "Entent" area of Treichville, Breteau index was estimated at 34, recipient index at 20% and house index at 25%. Those indexes were respectively 53, 21 and 31% at "Vridi canal" of Port Bouet. In the both neighborhood, Aedes aegypti accounted for more than 80% of mosquitoes caught and more than 90% of mosquitoes adults obtained from larval breeding. This new situation of epidemic risk could be explained by several factors including the reception of 70% of forced migration people caused by the crisis in the country occurred in 2002, the probable drop of preventive immunization, the environment deterioration creating of more breeding sites of Ae. aegypti.

  20. [Surveillance system for adverse events following immunization against yellow fever in Burkina Faso in 2008. Good practice recommendations].

    Science.gov (United States)

    Yaméogo, T M; Breugelmans, J G; Kambou, J L; Badolo, O; Tiendrebéogo, S; Traoré, E; Avokey, F; Yactayo, S

    2009-08-01

    Yellow fever (YF) remains a public health problem in Africa. In 2007 and 2008, Togo, Senegal, Mali and Burkina Faso became the first countries to implement mass YF immunization campaigns within the framework of the Yellow Fever Initiative. The goal of this initiative led by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) with the support of The Global Alliance for Vaccines and Immunization (GAVI) is to organize mass YF immunization campaigns in 12 African countries at high risk forYF transmission between 2006 and 2013. A total of 290 million USD have been allocated for vaccination of 180 million people with the highly effective attenuated 17DYF vaccine. Working in partnership with the WHO, the 12 member states are to identify and target high risk areas with the dual aim of preventing epidemics and increasing immunization coverage. Surveillance of adverse events following immunization (AEFI) is a mandatory component for organization of these campaigns. Purpose. The purpose of this article is to describe the AEFI surveillance system implemented in Burkina Faso in 2008. Methods. The strategy used in Burkina Faso was based on a combination of regular passive surveillance and active surveillance. General guidelines and related operational processes were established including reporting forms, investigation forms, and procedures for collection, storage and transport of biological specimens. Classification of cases was based on clearly defined criteria. Any patient meeting the defined criteria and requiring hospitalization was considered as a serious case. In addition to case definition criteria, serious cases were tracked according to presented signs and symptoms using a line-listing form at two university hospital centers in Ouagadougou and one regional hospital center. Emergency room admission records and patient charts were examined during the surveillance period (30 days after the end of the immunization campaign) and on

  1. Duration of post-vaccination immunity against yellow fever in adults.

    Science.gov (United States)

    2014-09-03

    Available scientific evidence to recommend or to advise against booster doses of yellow fever vaccine (YFV) is inconclusive. A study to estimate the seropositivity rate and geometric mean titres (GMT) of adults with varied times of vaccination was aimed to provide elements to revise the need and the timing of revaccination. Adults from the cities of Rio de Janeiro and Alfenas located in non-endemic areas in the Southeast of Brazil, who had one dose of YFV, were tested for YF neutralising antibodies and dengue IgG. Time (in years) since vaccination was based on immunisation cards and other reliable records. From 2011 to 2012 we recruited 691 subjects (73% males), aged 18-83 years. Time since vaccination ranged from 30 days to 18 years. Seropositivity rates (95%C.I.) and GMT (International Units/mL; 95%C.I.) decreased with time since vaccination: 93% (88-96%), 8.8 (7.0-10.9) IU/mL for newly vaccinated; 94% (88-97), 3.0 (2.5-3.6) IU/mL after 1-4 years; 83% (74-90), 2.2 (1.7-2.8) IU/mL after 5-9 years; 76% (68-83), 1.7 (1.4-2.0) IU/mL after 10-11 years; and 85% (80-90), 2.1 (1.7-2.5) IU/mL after 12 years or more. YF seropositivity rates were not affected by previous dengue infection. Eventhough serological correlates of protection for yellow fever are unknown, seronegativity in vaccinated subjects may indicate primary immunisation failure, or waning of immunity to levels below the protection threshold. Immunogenicity of YFV under routine conditions of immunisation services is likely to be lower than in controlled studies. Moreover, infants and toddlers, who comprise the main target group in YF endemic regions, and populations with high HIV infection rates, respond to YFV with lower antibody levels. In those settings one booster dose, preferably sooner than currently recommended, seems to be necessary to ensure longer protection for all vaccinees. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Lymphocyte subset analyses in healthy adults vaccinated with yellow fever 17DD virus

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    Ana Paula dos Santos

    2005-05-01

    Full Text Available In this study the kinetics of humoral and cellular immune responses in first-time vaccinees and re-vaccinees with the yellow fever 17DD vaccine virus was analyzed. Flow cytometric analyses were used to determine percentual values of T and B cells in parallel to the yellow fever neutralizing antibody production. All lymphocyte subsets analyzed were augmented around the 30th post vaccination day, both for first-time vaccinees and re-vaccinees. CD3+ T cells increased from 30.8% (SE ± 4% to 61.15% (SE ± 4.2%, CD4+ T cells from 22.4% (SE ± 3.6% to 39.17% (SE ± 2% with 43% of these cells corresponding to CD4+CD45RO+ T cells, CD8+ T cells from 15.2% (SE ± 2.9% to 27% (SE ± 3% with 70% corresponding to CD8+CD45RO+ T cells in first-time vaccinees. In re-vaccinees, the CD3+ T cells increased from 50.7% (SE ± 3% to 80% (SE ± 2.3%, CD4+ T cells from 24.9% (SE ± 1.4% to 40% (SE ± 3% presenting a percentage of 95% CD4+CD45RO+ T cells, CD8+ T cells from 19.7% (SE ± 1.8% to 25% (SE ± 2%. Among CD8+CD38+ T cells there could be observed an increase from 15 to 41.6% in first-time vaccinees and 20.7 to 62.6% in re-vaccinees. Regarding neutralizing antibodies, the re-vaccinees presented high titers even before re-vaccination. The levels of neutralizing antibodies of first-time vaccinees were similar to those presented by re-vaccinees at day 30 after vaccination, indicating the success of primary vaccination. Our data provide a basis for further studies on immunological behavior of the YF 17DD vaccine.

  3. A network-based meta-population approach to model Rift Valley fever epidemics.

    Science.gov (United States)

    Xue, Ling; Scott, H Morgan; Cohnstaedt, Lee W; Scoglio, Caterina

    2012-08-07

    Rift Valley fever virus (RVFV) has been expanding its geographical distribution with important implications for both human and animal health. The emergence of Rift Valley fever (RVF) in the Middle East, and its continuing presence in many areas of Africa, has negatively impacted both medical and veterinary infrastructures and human morbidity, mortality, and economic endpoints. Furthermore, worldwide attention should be directed towards the broader infection dynamics of RVFV, because suitable host, vector and environmental conditions for additional epidemics likely exist on other continents; including Asia, Europe and the Americas. We propose a new compartmentalized model of RVF and the related ordinary differential equations to assess disease spread in both time and space; with the latter driven as a function of contact networks. Humans and livestock hosts and two species of vector mosquitoes are included in the model. The model is based on weighted contact networks, where nodes of the networks represent geographical regions and the weights represent the level of contact between regional pairings for each set of species. The inclusion of human, animal, and vector movements among regions is new to RVF modeling. The movement of the infected individuals is not only treated as a possibility, but also an actuality that can be incorporated into the model. We have tested, calibrated, and evaluated the model using data from the recent 2010 RVF outbreak in South Africa as a case study; mapping the epidemic spread within and among three South African provinces. An extensive set of simulation results shows the potential of the proposed approach for accurately modeling the RVF spreading process in additional regions of the world. The benefits of the proposed model are twofold: not only can the model differentiate the maximum number of infected individuals among different provinces, but also it can reproduce the different starting times of the outbreak in multiple locations

  4. Adaptive immune responses to booster vaccination against yellow fever virus are much reduced compared to those after primary vaccination

    DEFF Research Database (Denmark)

    Kongsgaard, Michael; Bassi, Maria Rosaria; Rasmussen, Michael

    2017-01-01

    Outbreaks of Yellow Fever occur regularly in endemic areas of Africa and South America frequently leading to mass vaccination campaigns straining the availability of the attenuated Yellow Fever vaccine, YF-17D. The WHO has recently decided to discontinue regular booster-vaccinations since a single...... vaccination is deemed to confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) and cellular (CD8 and CD4 T cell) immune responses in primary and booster vaccinees (the latter spanning 8 to 36 years after primary vaccination). After primary vaccination, we observed strong...... cellular immune responses with T cell activation peaking ≈2 weeks and subsiding to background levels ≈ 4 weeks post-vaccination. The number of antigen-specific CD8+ T cells declined over the following years. In >90% of vaccinees, in vitro expandable T cells could still be detected >10 years post-vaccination...

  5. Spatiotemporal trends and climatic factors of hemorrhagic fever with renal syndrome epidemic in Shandong Province, China.

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    Li-Qun Fang

    Full Text Available BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS is a rodent-borne disease caused by Hantaviruses. It is endemic in all 31 provinces, autonomous regions, and metropolitan areas in mainland China where human cases account for 90% of the total global cases. Shandong Province is among the most serious endemic areas. HFRS cases in Shandong Province were first reported in Yutai County in 1968. Since then, the disease has spread across the province, and as of 2005, all 111 counties were reported to have local human infections. However, causes underlying such rapid spread and wide distribution remain less well understood. METHODS AND FINDINGS: Here we report a spatiotemporal analysis of human HFRS cases in Shandong using data spanning 1973 to 2005. Seasonal incidence maps and velocity vector maps were produced to analyze the spread of HFRS over time in Shandong Province, and a panel data analysis was conducted to explore the association between HFRS incidence and climatic factors. Results show a rapid spread of HFRS from its epicenter in Rizhao, Linyi, Weifang Regions in southern Shandong to north, east, and west parts of the province. Based on seasonal shifts of epidemics, three epidemic phases were identified over the 33-year period. The first phase occurred between 1973 and 1982 during which the foci of HFRS was located in the south Shandong and the epidemic peak occurred in the fall and winter, presenting a seasonal characteristic of Hantaan virus (HTNV transmission. The second phase between 1983 and 1985 was characterized by northward and westward spread of HFRS foci, and increases in incidence of HFRS in both fall-winter and spring seasons. The human infections in the spring reflected a characteristic pattern of Seoul virus (SEOV transmission. The third phase between 1986 and 2005 was characterized by the northeast spread of the HFRS foci until it covered all counties, and the HFRS incidence in the fall-winter season decreased while it

  6. Inter-epidemic acquisition of Rift Valley fever virus in humans in Tanzania.

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    Robert David Sumaye

    2015-02-01

    Full Text Available BACKGROUND: In East Africa, epidemics of Rift Valley fever (RVF occur in cycles of 5-15 years following unusually high rainfall. RVF transmission during inter-epidemic periods (IEP generally passes undetected in absence of surveillance in mammalian hosts and vectors. We studied IEP transmission of RVF and evaluated the demographic, behavioural, occupational and spatial determinants of past RVF infection. METHODOLOGY: Between March and August 2012 we collected blood samples, and administered a risk factor questionnaire among 606 inhabitants of 6 villages in the seasonally inundated Kilombero Valley, Tanzania. ELISA tests were used to detect RVFV IgM and IgG antibodies in serum samples. Risk factors were examined by mixed effects logistic regression. FINDINGS: RVF virus IgM antibodies, indicating recent RVFV acquisition, were detected in 16 participants, representing 2.6% overall and in 22.5% of inhibition ELISA positives (n = 71. Four of 16 (25.0% IgM positives and 11/71 (15.5% of individuals with inhibition ELISA sero-positivity reported they had had no previous contact with host animals. Sero-positivity on inhibition ELISA was 11.7% (95% CI 9.2-14.5 and risk was elevated with age (odds ratio (OR 1.03 per year; 95% CI 1.01-1.04, among milkers (OR 2.19; 95% CI 1.23-3.91, and individuals eating raw meat (OR 4.17; 95% CI 1.18-14.66. Households keeping livestock had a higher probability of having members with evidence of past infection (OR = 3.04, 95% CI = 1.42-6.48 than those that do not keep livestock. CONCLUSION: There is inter-epidemic acquisition of RVFV in Kilombero Valley inhabitants. In the wake of declining malaria incidence, these findings underscore the need for clinicians to consider RVF in the differential diagnosis for febrile illnesses. Several types of direct contact with livestock are important risk factors for past infection with RVFV in this study's population. However, at least part of RVFV transmission appears to have occurred

  7. Composition of the Essential Oil of Pink Chablis Bluebeard (Caryopteris x clandonensis ’Durio’) and Its Biological Activity against the Yellow Fever Mosquito Aedes aegypti

    Science.gov (United States)

    2016-04-07

    oil of Pink Chablis™ bluebeard (Caryopteris ×clandonensis ’Durio’) and its biological activity against the yellow fever mosquito Aedes aegypti ARTICLE...bluebeard (Caryopteris ×clandonensis ’Durio’) and its biological activity against the yellow fever mosquito Aedes aegypti Eugene K. Blythe1...mosquito [ Aedes aegypti (L.) (Diptera: Culicidae)]. Essential oil from the aerial parts of this mildly aromatic ornamental species was extracted by water

  8. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania

    OpenAIRE

    Mweya, Clement N.; Kimera, Sharadhuli I.; Mellau, Lesakit S. B.; Mboera, Leonard E. G.

    2015-01-01

    Background: Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. Objective: To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. Methods: A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mos...

  9. A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus.

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    Erika Hammarlund

    Full Text Available Primary clinical isolates of yellow fever virus can be difficult to quantitate by standard in vitro methods because they may not form discernable plaques or induce a measurable cytopathic effect (CPE on cell monolayers. In our hands, the Dakar strain of yellow fever virus (YFV-Dakar could not be measured by plaque assay (PA, focus-forming assay (FFA, or by measurement of CPE. For these reasons, we developed a YFV-specific monoclonal antibody (3A8.B6 and used it to optimize a highly sensitive flow cytometry-based tissue culture limiting dilution assay (TC-LDA to measure levels of infectious virus. The TC-LDA was performed by incubating serial dilutions of virus in replicate wells of C6/36 cells and stained intracellularly for virus with MAb 3A8.B6. Using this approach, we could reproducibly quantitate YFV-Dakar in tissue culture supernatants as well as from the serum of viremic rhesus macaques experimentally infected with YFV-Dakar. Moreover, the TC-LDA approach was >10-fold more sensitive than standard plaque assay for quantitating typical plaque-forming strains of YFV including YFV-17D and YFV-FNV (French neurotropic vaccine. Together, these results indicate that the TC-LDA technique is effective for quantitating both plaque-forming and non-plaque-forming strains of yellow fever virus, and this methodology may be readily adapted for the study and quantitation of other non-plaque-forming viruses.

  10. Duration of post-vaccination immunity to yellow fever in volunteers eight years after a dose-response study.

    Science.gov (United States)

    de Menezes Martins, Reinaldo; Maia, Maria de Lourdes S; de Lima, Sheila Maria Barbosa; de Noronha, Tatiana Guimarães; Xavier, Janaina Reis; Camacho, Luiz Antonio Bastos; de Albuquerque, Elizabeth Maciel; Farias, Roberto Henrique Guedes; da Matta de Castro, Thalita; Homma, Akira

    2018-06-27

    In 2009, Bio-Manguinhos conducted a dose-response study with the yellow fever vaccine, administering the vaccine in the usual mean dose of 27,476 IU (full dose, reference) and in tapered doses (10,447 IU, 3013 IU, 587 IU, 158 IU, and 31 IU) by the usual subcutaneous route and usual volume (0.5 mL). Tapered doses were obtained by dilution in the manufacturer's laboratory, and the test batches presented industrial quality. Doses down to 587 IU showed similar immunogenicity to the full dose (27,476, reference), while the 158 IU and 31 IU doses displayed lower immunogenicity. Seropositivity was maintained at 10 months, except in the group that received the 31 IU dose. The current study aims to determine whether yellow fever seropositivity was maintained eight years after YF vaccination in non-revaccinated individuals. According to the current study's results, seropositivity was maintained in 85% of 318 participants and was similar across groups. The findings support the use of the yellow fever vaccine in fractional doses during outbreaks, but each fractional dose should have at least 587 IU. This study also supports the minimum dose required by WHO, 1000 IU. Clinicaltrials.gov NCT 03338231. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. MEK/ERK activation plays a decisive role in yellow fever virus replication: implication as an antiviral therapeutic target.

    Science.gov (United States)

    Albarnaz, Jonas D; De Oliveira, Leonardo C; Torres, Alice A; Palhares, Rafael M; Casteluber, Marisa C; Rodrigues, Claudiney M; Cardozo, Pablo L; De Souza, Aryádina M R; Pacca, Carolina C; Ferreira, Paulo C P; Kroon, Erna G; Nogueira, Maurício L; Bonjardim, Cláudio A

    2014-11-01

    Exploiting the inhibition of host signaling pathways aiming for discovery of potential antiflaviviral compounds is clearly a beneficial strategy for the control of life-threatening diseases caused by flaviviruses. Here we describe the antiviral activity of the MEK1/2 inhibitor U0126 against Yellow fever virus 17D vaccine strain (YFV-17D). Infection of VERO cells with YFV-17D stimulates ERK1/2 phosphorylation early during infection. Pharmacological inhibition of MEK1/2 through U0126 treatment of VERO cells blockades not only the YFV-stimulated ERK1/2 phosphorylation, but also inhibits YFV replication by ∼99%. U0126 was also effective against dengue virus (DENV-2 and -3) and Saint-Louis encephalitis virus (SLEV). Levels of NS4AB, as detected by immunofluorescence, are diminished upon treatment with the inhibitor, as well as the characteristic endoplasmic reticulum membrane invagination stimulated during the infection. Though not protective, treatment of YFV-infected, adult BALB/c mice with U0126 resulted in significant reduction of virus titers in brains. Collectively, our data suggest the potential targeting of the MEK1/2 kinase as a therapeutic tool against diseases caused by flaviviruses such as yellow fever, adverse events associated with yellow fever vaccination and dengue. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Municipalities of higher vulnerability to Sylvatic Yellow Fever occurrence in the São Paulo State, Brazil

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    Eduardo Stramandinoli Moreno

    2011-12-01

    Full Text Available Until 1999 the endemic cases of Sylvatic Yellow Fever were located in the states of northern, midwestern and pre-Amazon regions. Since then, the disease progressively expanded its territory of occurrence, cases being registered beyond the traditional boundaries of endemism. The São Paulo State is considered to be part of this context, since after decades without registration of autochthonous cases of the disease, it reported, in 2000 and 2008-2009, epizootic occurrence in non-human primates and 30 cases in humans. Facts like these, added to the increase in incidences of serious adverse effects resulting from the Yellow Fever vaccination, have highlighted the importance of defining priority municipalities for vaccination against the disease in the state. Two groups of municipalities, some affected and some non-affected by YF, were compared for environmental variables related to the eco-epidemiology of the disease according to literature. The Multiple Correspondence Analysis (MCA was used to pinpoint the factor able to differentiate the two groups of municipalities and define the levels of risk. The southeast region of the São Paulo State was considered to be the area with a higher number of municipalities classified as high risk and should be considered a priority for the application of prevention measures against Yellow Fever.

  13. International Health Regulations in practice: Focus on yellow fever and poliomyelitis.

    Science.gov (United States)

    Simons, H; Patel, D

    2016-10-02

    ASBTRACT The spread of infectious disease represents a global threat and therefore remains a priority on the international public health agenda. The International Health Regulations (IHR) (2005) came into effect in June 2007 and provide a legal framework to which the 196 member states of the World Health Assembly agree to abide. 1 These regulations include implementation of protective, control and response measures at points of entry to a country (i.e. land borders, sea and airports), and of notification measures, all of which aim to prevent or limit the spread of disease while minimising disruption to international trade. The World Health Organization can apply and enforce IHR (2005) to any disease considered to pose a significant threat to international public health. This short paper focuses on 2 diseases; yellow fever and poliomyelitis, both of which have the potential to spread internationally. It will discuss the measures applied under IHR (2005) to minimize the threat, and explore the implications for both travelers and travel health advisors.

  14. Genome analysis of yellow fever virus of the ongoing outbreak in Brazil reveals polymorphisms

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    Myrna C Bonaldo

    Full Text Available The current yellow fever outbreak in Brazil is the most severe one in the country in recent times. It has rapidly spread to areas where YF virus (YFV activity has not been observed for more than 70 years and vaccine coverage is almost null. Here, we sequenced the whole YFV genome of two naturally infected howler-monkeys (Alouatta clamitans obtained from the Municipality of Domingos Martins, state of Espírito Santo, Brazil. These two ongoing-outbreak genome sequences are identical. They clustered in the 1E sub-clade (South America genotype I along with the Brazilian and Venezuelan strains recently characterised from infections in humans and non-human primates that have been described in the last 20 years. However, we detected eight unique amino acid changes in the viral proteins, including the structural capsid protein (one change, and the components of the viral replicase complex, the NS3 (two changes and NS5 (five changes proteins, that could impact the capacity of viral infection in vertebrate and/or invertebrate hosts and spreading of the ongoing outbreak.

  15. Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity.

    Science.gov (United States)

    Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W

    2010-05-14

    In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age 60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (Pvaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.

  16. Questions regarding the safety and duration of immunity following live yellow fever vaccination.

    Science.gov (United States)

    Amanna, Ian J; Slifka, Mark K

    2016-12-01

    The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered.

  17. Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos.

    Science.gov (United States)

    Manso, Pedro Paulo de Abreu; Dias de Oliveira, Barbara C E P; de Sequeira, Patrícia Carvalho; Maia de Souza, Yuli Rodrigues; Ferro, Jessica Maria dos Santos; da Silva, Igor José; Caputo, Luzia Fátima Gonçalves; Guedes, Priscila Tavares; dos Santos, Alexandre Araujo Cunha; Freire, Marcos da Silva; Bonaldo, Myrna Cristina; Pelajo-Machado, Marcelo

    2015-01-01

    The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system.

  18. YELLOW FEVER PREVENTION STRATEGIES AWARENESS AMONG HIV-INFECTED PATIENTS IN SÃO PAULO, BRAZIL

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    Vivian Iida Avelino-Silva

    2014-09-01

    Full Text Available Introduction: Vaccination is the main preventive strategy against Yellow Fever (YF, which is a public health concern in Brazil. However, HIV-infected patients might have insufficient knowledge regarding YF, YF prevention, and vaccines in general. Methods: In this questionnaire-based study, data from 158 HIV-infected individuals were addressed in three distinct outpatient clinics in São Paulo. Information was collected on demographic and clinical characteristics, as well as patients' knowledge of vaccines, YF and YF preventive strategies. In addition, individual YF vaccine recommendations and vaccine status were investigated. Results: Although most participants adequately ascertain the vaccine as the main prevention strategy against YF, few participants were aware of the severity and lack of specific treatment for YF. Discrepancy in YF vaccine (patients who should have taken the vaccine, but did not was observed in 18.8% of participants. Conclusion: YF is an important and preventable public health concern, and these results demonstrate that more information is necessary for the HIV-infected population.

  19. Ecdysis triggering hormone signaling in the yellow fever mosquito Aedes aegypti.

    Science.gov (United States)

    Dai, Li; Adams, Michael E

    2009-05-15

    At the end of each developmental stage, the yellow fever mosquito Aedes aegypti performs the ecdysis behavioral sequence, a precisely timed series of behaviors that culminates in shedding of the old exoskeleton. Here we describe ecdysis triggering hormone-immunoreactive Inka cells located at branch points of major tracheal trunks and loss of staining coincident with ecdysis. Peptides (AeaETH1, AeaETH2) purified from extracts of pharate 4th instar larvae have--PRXamide C-terminal amino acid sequence motifs similar to ETHs previously identified in moths and flies. Injection of synthetic AeaETHs induced premature ecdysis behavior in pharate larvae, pupae and adults. Two functionally distinct subtypes of ETH receptors (AeaETHR-A, AeaETHR-B) of A. aegypti are identified and show high sensitivity and selectivity to ETHs. Increased ETHR transcript levels and behavioral sensitivity to AeaETHs arising in the hours preceding the 4th instar larva-to-pupa ecdysis are correlated with rising ecdysteroid levels, suggesting steroid regulation of receptor gene expression. Our description of natural and ETH-induced ecdysis in A. aegypti should facilitate future approaches directed toward hormone-based interference strategies for control of mosquitoes as human disease vectors.

  20. Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos.

    Directory of Open Access Journals (Sweden)

    Pedro Paulo de Abreu Manso

    Full Text Available The yellow fever (YF 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system.

  1. Kinetic Study of Yellow Fever 17DD Viral Infection in Gallus gallus domesticus Embryos.

    Directory of Open Access Journals (Sweden)

    Pedro Paulo de Abreu Manso

    Full Text Available Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos.

  2. Is There a Risk of Yellow Fever Virus Transmission in South Asian Countries with Hyperendemic Dengue?

    Science.gov (United States)

    Agampodi, Suneth B.; Wickramage, Kolitha

    2013-01-01

    The fact that yellow fever (YF) has never occurred in Asia remains an “unsolved mystery” in global health. Most countries in Asia with high Aedes aegypti mosquito density are considered “receptive” for YF transmission. Recently, health officials in Sri Lanka issued a public health alert on the potential spread of YF from a migrant group from West Africa. We performed an extensive review of literature pertaining to the risk of YF in Sri Lanka/South Asian region to understand the probability of actual risk and assist health authorities to form evidence informed public health policies/practices. Published data from epidemiological, historical, biological, molecular, and mathematical models were harnessed to assess the risk of YF in Asia. Using this data we examine a number of theories proposed to explain lack of YF in Asia. Considering the evidence available, we conclude that the probable risk of local transmission of YF is extremely low in Sri Lanka and for other South Asian countries despite a high Aedes aegypti density and associated dengue burden. This does not however exclude the future possibility of transmission in Asia, especially considering the rapid influx travelers from endemic areas, as we report, arriving in Sri Lanka. PMID:24367789

  3. Prevalence and titers of yellow fever virus neutralizing antibodies in previously vaccinated adults.

    Science.gov (United States)

    Miyaji, Karina Takesaki; Avelino-Silva, Vivian Iida; Simões, Marisol; Freire, Marcos da Silva; Medeiros, Carlos Roberto de; Braga, Patrícia Emilia; Neves, Maria Angélica Acalá; Lopes, Marta Heloisa; Kallas, Esper Georges; Sartori, Ana Marli Christovam

    2017-04-03

    The World Health Organization (WHO) recommends one single dose of the Yellow Fever (YF) vaccine based on studies of antibody persistency in healthy adults. We assessed the prevalence and titers of YF virus neutralizing antibodies in previously vaccinated persons aged  60 years, in comparison to younger adults. We also evaluated the correlation between antibody titers and the time since vaccination among participants who received one vaccine dose, and the seropositivity among participants vaccinated prior to or within the past 10 years. previously vaccinated healthy persons aged  18 years were included. YF virus neutralizing antibody titers were determined by means of the 50% Plaque Reduction Neutralization Test. 46 persons aged  60 years and 48 persons aged 18 to 59 years were enrolled. There was no significant difference in the prevalence of YF virus neutralizing antibodies between the two groups (p = 0.263). However, titers were significantly lower in the elderly (p = 0.022). There was no correlation between YF virus neutralizing antibody titers and the time since vaccination. There was no significant difference in seropositivity among participants vaccinated prior to or within the past 10 years. the clinical relevance of the observed difference in YF virus neutralizing antibody titers between the two groups is not clear.

  4. Yellow Fever 17DD Vaccine Virus Infection Causes Detectable Changes in Chicken Embryos

    Science.gov (United States)

    Manso, Pedro Paulo de Abreu; Dias de Oliveira, Barbara C. E. P.; de Sequeira, Patrícia Carvalho; Maia de Souza, Yuli Rodrigues; Ferro, Jessica Maria dos Santos; da Silva, Igor José; Caputo, Luzia Fátima Gonçalves; Guedes, Priscila Tavares; dos Santos, Alexandre Araujo Cunha; Freire, Marcos da Silva; Bonaldo, Myrna Cristina; Pelajo-Machado, Marcelo

    2015-01-01

    The yellow fever (YF) 17D vaccine is one of the most effective human vaccines ever created. The YF vaccine has been produced since 1937 in embryonated chicken eggs inoculated with the YF 17D virus. Yet, little information is available about the infection mechanism of YF 17DD virus in this biological model. To better understand this mechanism, we infected embryos of Gallus gallus domesticus and analyzed their histopathology after 72 hours of YF infection. Some embryos showed few apoptotic bodies in infected tissues, suggesting mild focal infection processes. Confocal and super-resolution microscopic analysis allowed us to identify as targets of viral infection: skeletal muscle cells, cardiomyocytes, nervous system cells, renal tubular epithelium, lung parenchyma, and fibroblasts associated with connective tissue in the perichondrium and dermis. The virus replication was heaviest in muscle tissues. In all of these specimens, RT-PCR methods confirmed the presence of replicative intermediate and genomic YF RNA. This clearer characterization of cell targets in chicken embryos paves the way for future development of a new YF vaccine based on a new cell culture system. PMID:26371874

  5. Kinetic Study of Yellow Fever 17DD Viral Infection in Gallus gallus domesticus Embryos

    Science.gov (United States)

    Manso, Pedro Paulo de Abreu; E. P. Dias de Oliveira, Bárbara Cristina; Carvalho de Sequeira, Patrícia; Rodrigues Maia de Souza, Yuli; dos Santos Ferro, Jessica Maria; da Silva, Igor José; Gonçalves Caputo, Luzia Fátima; Tavares Guedes, Priscila; Araujo Cunha dos Santos, Alexandre; da Silva Freire, Marcos; Bonaldo, Myrna Cristina; Pelajo Machado, Marcelo

    2016-01-01

    Yellow fever continues to be an important epidemiological problem in Africa and South America even though the disease can be controlled by vaccination. The vaccine has been produced since 1937 and is based on YFV 17DD chicken embryo infection. However, little is known about the histopathological background of virus infection and replication in this model. Here we show by morphological and molecular methods (brightfield and confocal microscopies, immunofluorescence, nested-PCR and sequencing) the kinetics of YFV 17DD infection in chicken embryos with 9 days of development, encompassing 24 to 96 hours post infection. Our principal findings indicate that the main cells involved in virus production are myoblasts with a mesenchymal shape, which also are the first cells to express virus proteins in Gallus gallus embryos at 48 hours after infection. At 72 hours post infection, we observed an increase of infected cells in embryos. Many sites are thus affected in the infection sequence, especially the skeletal muscle. We were also able to confirm an increase of nervous system infection at 96 hours post infection. Our data contribute to the comprehension of the pathogenesis of YF 17DD virus infection in Gallus gallus embryos. PMID:27158977

  6. CD8+ T cells complement antibodies in protecting against yellow fever virus.

    Science.gov (United States)

    Bassi, Maria R; Kongsgaard, Michael; Steffensen, Maria A; Fenger, Christina; Rasmussen, Michael; Skjødt, Karsten; Finsen, Bente; Stryhn, Anette; Buus, Søren; Christensen, Jan P; Thomsen, Allan R

    2015-02-01

    The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Biological and phylogenetic characteristics of yellow fever virus lineages from West Africa.

    Science.gov (United States)

    Stock, Nina K; Laraway, Hewád; Faye, Ousmane; Diallo, Mawlouth; Niedrig, Matthias; Sall, Amadou A

    2013-03-01

    The yellow fever virus (YFV), the first proven human-pathogenic virus, although isolated in 1927, is still a major public health problem, especially in West Africa where it causes outbreaks every year. Nevertheless, little is known about its genetic diversity and evolutionary dynamics, mainly due to a limited number of genomic sequences from wild virus isolates. In this study, we analyzed the phylogenetic relationships of 24 full-length genomes from YFV strains isolated between 1973 and 2005 in a sylvatic context of West Africa, including 14 isolates that had previously not been sequenced. By this, we confirmed genetic variability within one genotype by the identification of various YF lineages circulating in West Africa. Further analyses of the biological properties of these lineages revealed differential growth behavior in human liver and insect cells, correlating with the source of isolation and suggesting host adaptation. For one lineage, repeatedly isolated in a context of vertical transmission, specific characteristics in the growth behavior and unique mutations of the viral genome were observed and deserve further investigation to gain insight into mechanisms involved in YFV emergence and maintenance in nature.

  8. Questions regarding the safety and duration of immunity following live yellow fever vaccination

    Science.gov (United States)

    Amanna, Ian J.; Slifka, Mark K.

    2016-01-01

    Introduction The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas Covered We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert Commentary Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered. PMID:27267203

  9. Alterations in the Aedes aegypti transcriptome during infection with West Nile, dengue and yellow fever viruses.

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    Tonya M Colpitts

    2011-09-01

    Full Text Available West Nile (WNV, dengue (DENV and yellow fever (YFV viruses are (reemerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥ 5-fold differentially up-regulated (DUR and 202 genes that were ≥ 10-fold differentially down-regulated (DDR during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses.

  10. Climate Change and the Arboviruses: Lessons from the Evolution of the Dengue and Yellow Fever Viruses.

    Science.gov (United States)

    Tabachnick, Walter J

    2016-09-29

    The impact of anticipated changes in global climate on the arboviruses and the diseases they cause poses a significant challenge for public health. The past evolution of the dengue and yellow fever viruses provides clues about the influence of changes in climate on their future evolution. The evolution of both viruses has been influenced by virus interactions involving the mosquito species and the primate hosts involved in virus transmission, and by their domestic and sylvatic cycles. Information is needed on how viral genes in general influence phenotypic variance for important viral functions. Changes in global climate will alter the interactions of mosquito species with their primate hosts and with the viruses in domestic cycles, and greater attention should be paid to the sylvatic cycles. There is great danger for the evolution of novel viruses, such as new serotypes, that could compromise vaccination programs and jeopardize public health. It is essential to understand (a) both sylvatic and domestic cycles and (b) the role of virus genetic and environmental variances in shaping virus phenotypic variance to more fully assess the impact of global climate change.

  11. Characterization of an enantioselective odorant receptor in the yellow fever mosquito Aedes aegypti.

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    Jonathan D Bohbot

    2009-09-01

    Full Text Available Enantiomers differ only in the left or right handedness (chirality of their orientations and exhibit identical chemical and physical properties. In chemical communication systems, enantiomers can be differentially active at the physiological and behavioral levels. Only recently were enantioselective odorant receptors demonstrated in mammals while their existence in insects has remained hypothetical. Using the two-microelectrode voltage clamp of Xenopus oocytes, we show that the yellow fever mosquito, Aedes aegypti, odorant receptor 8 (AaOR8 acts as a chiral selective receptor for the (R-(--enantiomer of 1-octen-3-ol, which in the presence of other kairomones is an attractant used by blood-sucking insects to locate their hosts. In addition to steric constraints, chain length and degree of unsaturation play important roles in this recognition process. This is the first characterization of an enantioselective odorant receptor in insects and the results demonstrate that an OR alone, without helper proteins, can account for chiral specificity exhibited by olfactory sensory neurons (OSNs.

  12. Molecular Epidemiology of Yellow Fever in Bolivia from 1999 to 2008

    Science.gov (United States)

    Baronti, Cécile; Goitia, Norma Janeth Velasquez; Cook, Shelley; Roca, Yelin; Revollo, Jimmy; Flores, Jorge Vargas

    2011-01-01

    Abstract Yellow fever (YF) is a serious public health problem in Bolivia since at least the 19th century. Surprisingly, very limited information has been made available to date regarding the genetic characterisation and epidemiology of Bolivian YF virus (YFV) strains. Here, we conducted the genetic characterization of 12 human isolates of YFV collected in Bolivia between 1999 and 2008, by sequencing and analysis of two regions of the viral genome: a fragment encoding structural proteins “PrM” (premembrane and envelope) and a distal region “EMF,” spanning the end of the virus genome. Our study reveals a high genetic diversity of YFV strains circulating in Bolivia during the last decade: we identified not only “Peruvian-like” genotype II viruses (related to previously characterized Bolivian strains), but also, for the fist time, “Brazilian-like” genotype I viruses. During the complete period of the study, only cases of “jungle” YF were detected (i.e., circulation of YFV via a sylvatic cycle) with no cluster of urban cases. However, the very significant spread of the Aedes aegypti mosquito across Bolivian cities threatens the country with the reappearance of an urban YFV transmission cycle and thus is required a sustained epidemiological surveillance. PMID:20925524

  13. YouTube videos as a source of medical information during the Ebola hemorrhagic fever epidemic.

    Science.gov (United States)

    Nagpal, Sajan Jiv Singh; Karimianpour, Ahmadreza; Mukhija, Dhruvika; Mohan, Diwakar; Brateanu, Andrei

    2015-01-01

    The content and quality of medical information available on video sharing websites such as YouTube is not known. We analyzed the source and quality of medical information about Ebola hemorrhagic fever (EHF) disseminated on YouTube and the video characteristics that influence viewer behavior. An inquiry for the search term 'Ebola' was made on YouTube. The first 100 results were arranged in decreasing order of "relevance" using the default YouTube algorithm. Videos 1-50 and 51-100 were allocated to a high relevance (HR), and a low relevance (LR) video group, respectively. Multivariable logistic regression models were used to assess the predictors of a video being included in the HR vs. LR groups. Fourteen videos were excluded because they were parodies, songs or stand-up comedies (n = 11), not in English (n = 2) or a remaining part of a previous video (n = 1). Two scales, the video information and quality and index and the medical information and content index (MICI) assessed the overall quality, and the medical content of the videos, respectively. There were no videos from hospitals or academic medical centers. Videos in the HR group had a higher median number of views (186,705 vs. 43,796, p YouTube videos presenting clinical symptoms of infectious diseases during epidemics are more likely to be included in the HR group and influence viewers behavior.

  14. Circulation of antibodies against yellow fever virus in a simian population in the area of Porto Primavera Hydroelectric Plant, São Paulo, Brazil.

    Science.gov (United States)

    Lima, Maura Antonia; Romano-Lieber, Nicolina Silvana; Duarte, Ana Maria Ribeiro de Castro

    2010-01-01

    Yellow fever (YF) is an acute viral infectious disease transmitted by mosquitoes which occurs in two distinct epidemiological cycles: sylvatic and urban. In the sylvatic cycle, the virus is maintained by monkey's infection and transovarian transmission in vectors. Surveillance of non-human primates is required for the detection of viral circulation during epizootics, and for the identification of unaffected or transition areas. An ELISA (enzyme-linked immunosorbent assay) was standardized for estimation of the prevalence of IgG antibodies against yellow fever virus in monkey sera (Alouatta caraya) from the reservoir area of Porto Primavera Hydroelectric Plant, in the state of São Paulo, Brazil. A total of 570 monkey sera samples were tested and none was reactive to antibodies against yellow fever virus. The results corroborate the epidemiology of yellow fever in the area. Even though it is considered a transition area, there were no reports to date of epizootics or yellow fever outbreaks in humans. Also, entomological investigations did not detect the presence of vectors of this arbovirus infection. ELISA proved to be fast, sensitive, an adequate assay, and an instrument for active search in the epidemiological surveillance of yellow fever allowing the implementation of prevention actions, even before the occurrence of epizootics.

  15. ETIOLOGY OF YELLOW FEVER : X. COMPARATIVE IMMUNOLOGICAL STUDIES ON LEPTOSPIRA ICTEROIDES AND LEPTOSPIRA ICTEROHAEMOORRHAGIAE.

    Science.gov (United States)

    Noguchi, H

    1920-01-31

    It has been previously reported that a filterable microorganism belonging to the genus Leptospira has been recovered from the blood or organs of human beings suffering from the disease known as yellow fever in Guayaquil, and that the organism, which has been termed Leptospira icteroides, induces in certain experimental animals the characteristic symptoms and lesions observed in the patients from whom it was isolated. It has also been previously shown that the serum from patients recovering from an attack of yellow fever in Guayaquil had the power to agglutinate and dissolve the organism when introduced into the peritoneal cavity of a normal guinea pig (Pfeiffer phenomenon). Moreover, the guinea pigs which had once been inoculated with the blood of yellow fever patients without succumbing to the infection, notwithstanding the fact that they had shown a definite febrile reaction after 4 to 5 days, were found to be refractory to a subsequent inoculation of a culture of Leptospira icteroides All these observations pointed to the possible relation of this organism to the disease known as yellow fever in Guayaquil. The demonstration of the filterability of the organism and the transmission of the infection with the same organism by Stegomyia calopus have further strengthened the probable etiological significance of the organism in yellow fever. It was by no means a simple problem to determine the relation existing between Leptospira icteroides and Leptospira icterohaemorrhagiae. An experiment reported in a previous paper seemed to justify the view that the two leptospiras are closely related but not identical, yet it was necessary to exhaust various other modes of differentiation before the distinction between them was firmly established. The present paper continues this phase of the inquiry in further detail. There have been taken up here the phenomena of agglutination, the reaction of Pfeiffer, complement fixation, the protective properties of various monovalent and

  16. Long-Term Serological Follow-Up of Acute Q-Fever Patients after a Large Epidemic.

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    Cornelia C H Wielders

    Full Text Available Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007-2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever.A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever.Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6% were included in the analysis. At any time during the four-year follow-up period, 58 (4.5% patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever. Fifty-two (89.7% of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months.A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever.

  17. Evaluation of two yellow fever vaccines for routine immunization programs in Argentina.

    Science.gov (United States)

    Ripoll, Carlos; Ponce, Amalia; Wilson, Mario M; Sharif, Norma; Vides, José B; Armoni, Judith; Teuwen, Dirk E

    2008-01-01

    Although highly effective vaccines have been available for almost 70 years, an estimated 200,000 cases of YF, including 30,000 deaths, still occur annually. This study evaluated the safety of two yellow fever (YF) vaccines [Stamaril and Vacina Contra Febre Amarela (VCFA)]. A total of 2,514 subjects were randomized equally to receive Stamaril or VCFA. Immediate reactions occurring within 30 minutes after vaccination, and solicited local and systemic reactions occurring within eight days, were monitored. Unsolicited local, systemic adverse events and serious adverse events (SAE) were recorded for 21 days after vaccination. Solicited local and systemic adverse reactions were reported by 15.3-17.6% and 30.4-31.6% of the Stamaril and VCFA groups, respectively. Only 56 of the 2,514 study subjects (2.2%) reported a severe solicited adverse reaction, 25 in the Stamaril group (1.99%) and 31 in the VFCA group (2.49%), (p=0.403). Ten subjects (0.8%) in each group reported at least one severe solicited local reaction (p = 0.988). A total of 18 Stamaril subjects (1.43%) and 21 VCFA subjects (1.68%) reported at least one severe solicited systemic reaction (p = 0.617) One SAE considered related to vaccination occurred, polymyalgia in the VCFA group. No immediate reactions to vaccination were seen. Vaccine-related unsolicited events were infrequent, 1.4% in the Stamaril group and 2.0% VCFA group, generally of mild or moderate intensity. We conclude that the safety profiles of Stamaril and VCFA support routine vaccination to prevent YF in residents of and travelers to endemic areas of South America and Africa.

  18. Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline.

    Science.gov (United States)

    Campi-Azevedo, Ana Carolina; de Almeida Estevam, Paula; Coelho-Dos-Reis, Jordana Grazziela; Peruhype-Magalhães, Vanessa; Villela-Rezende, Gabriela; Quaresma, Patrícia Flávia; Maia, Maria de Lourdes Sousa; Farias, Roberto Henrique Guedes; Camacho, Luiz Antonio Bastos; Freire, Marcos da Silva; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando Carvalho; Lima, Sheila Maria Barbosa; Nogueira, Rita Maria Ribeiro; Silva Sá, Gloria Regina; Hokama, Darcy Akemi; de Carvalho, Ricardo; Freire, Ricardo Aguiar Villanova; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira; Teixeira-Carvalho, Andréa; Martins, Reinaldo Menezes; Martins-Filho, Olindo Assis

    2014-07-15

    The live attenuated 17DD Yellow Fever vaccine is one of the most successful prophylactic interventions for controlling disease expansion ever designed and utilized in larger scale. However, increase on worldwide vaccine demands and manufacturing restrictions urge for more detailed dose sparing studies. The establishment of complementary biomarkers in addition to PRNT and Viremia could support a secure decision-making regarding the use of 17DD YF vaccine subdoses. The present work aimed at comparing the serum chemokine and cytokine kinetics triggered by five subdoses of 17DD YF Vaccine. Neutralizing antibody titers, viremia, cytokines and chemokines were tested on blood samples obtained from eligible primary vaccinees. The results demonstrated that a fifty-fold lower dose of 17DD-YF vaccine (587 IU) is able to trigger similar immunogenicity, as evidenced by significant titers of anti-YF PRNT. However, only subdoses as low as 3,013 IU elicit viremia kinetics with an early peak at five days after primary vaccination equivalent to the current dose (27,476 IU), while other subdoses show a distinct, lower in magnitude and later peak at day 6 post-vaccination. Although the subdose of 587 IU is able to trigger equivalent kinetics of IL-8/CXCL-8 and MCP-1/CCL-2, only the subdose of 3,013 IU is able to trigger similar kinetics of MIG/CXCL-9, pro-inflammatory (TNF, IFN-γ and IL-2) and modulatory cytokines (IL-5 and IL-10). The analysis of serum biomarkers IFN-γ and IL-10, in association to PRNT and viremia, support the recommendation of use of a ten-fold lower subdose (3,013 IU) of 17DD-YF vaccine.

  19. Immune activation alters cellular and humoral responses to yellow fever 17D vaccine.

    Science.gov (United States)

    Muyanja, Enoch; Ssemaganda, Aloysius; Ngauv, Pearline; Cubas, Rafael; Perrin, Helene; Srinivasan, Divya; Canderan, Glenda; Lawson, Benton; Kopycinski, Jakub; Graham, Amanda S; Rowe, Dawne K; Smith, Michaela J; Isern, Sharon; Michael, Scott; Silvestri, Guido; Vanderford, Thomas H; Castro, Erika; Pantaleo, Giuseppe; Singer, Joel; Gillmour, Jill; Kiwanuka, Noah; Nanvubya, Annet; Schmidt, Claudia; Birungi, Josephine; Cox, Josephine; Haddad, Elias K; Kaleebu, Pontiano; Fast, Patricia; Sekaly, Rafick-Pierre; Trautmann, Lydie; Gaucher, Denis

    2014-07-01

    Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Registration is not required for observational studies. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases

  20. Neurovirulence of yellow fever 17DD vaccine virus to rhesus monkeys

    International Nuclear Information System (INIS)

    Marchevsky, Renato S.; Freire, Marcos S.; Coutinho, Evandro S.F.; Galler, Ricardo

    2003-01-01

    The yellow fever 17D virus is attenuated and used for human vaccination. Two of its substrains, 17D-204 and 17DD, are used for vaccine production. One of the remarkable properties of this vaccine is limited viral replication in the host but with significant dissemination of the viral mass, yielding a robust and long-lived neutralizing antibody response. The vaccine has excellent records of efficacy and safety and is cheap, used as a single dose, and there are well-established production methodology and quality control procedures which include the monkey neurovirulence test (MNTV). The present study aims at a better understanding of YF 17DD virus attenuation and immunogenicity in the MNVT with special emphasis on viremia, seroconversion, clinical and histological lesions scores, and their intrinsic variability across the tests. Several MNVTs were performed using the secondary seed lot virus 17DD 102/84 totaling 49 rhesus monkeys. Viremia was never higher than the accepted limits established in international requirements, and high levels of neutralizing antibodies were observed in all animals. None of the animals showed visceral lesions. We found that the clinical scores for the same virus varied widely across the tests. There was a direct correlation between the clinical scores in animals with clinical signs of encephalitis and a higher degree of central nervous system (CNS) histological lesions, with an increase of lesions in areas of the CNS such as the substantia nigra, nucleus caudatus, intumescentia cervicalis, and intumescentia ventralis. The histological scores were shown to be less prone to individual variations and had a more homogeneous value distribution among the tests. Since 17DD 102/84 seed virus has been used for human vaccine production and immunization for 16 years with the vaccine being safe and efficacious, it demonstrates that the observed variations across the MNVTs do not influence its effect on humans

  1. The Aquaporin gene family of the yellow fever mosquito, Aedes aegypti.

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    Lisa L Drake

    2010-12-01

    Full Text Available The mosquito, Aedes aegypti, is the principal vector of the Dengue and yellow fever viruses. During feeding, an adult female can take up more than its own body weight in vertebrate blood. After a blood meal females excrete large amounts of urine through their excretion system, the Malpighian tubules (MT. Diuresis starts within seconds after the mosquito starts feeding. Aquaporins (AQPs are a family of membrane transporters that regulate the flow of water, glycerol and other small molecules across cellular membranes in both prokaryotic and eukaryotic cells. Our aim was to identify aquaporins that function as water channels, mediating transcellular water transport in MTs of adult female Ae. aegypti.Using a bioinformatics approach we screened genome databases and identified six putative AQPs in the genome of Ae. aegypti. Phylogenetic analysis showed that five of the six Ae. aegypti AQPs have high similarity to classical water-transporting AQPs of vertebrates. Using microarray, reverse transcription and real time PCR analysis we found that all six AQPs are expressed in distinct patterns in mosquito tissues/body parts. AaAQP1, 4, and 5 are strongly expressed in the adult female MT. RNAi-mediated knockdown of the MT-expressed mosquito AQPs resulted in significantly reduced diuresis.Our results support the notion that AQP1, 4, and 5 function as water transporters in the MTs of adult female Ae. aegypti mosquitoes. Our results demonstrate the importance of these AQPs for mosquito diuresis after blood ingestion and highlight their potential as targets for the development of novel vector control strategies.

  2. The Aquaporin gene family of the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Drake, Lisa L; Boudko, Dmitri Y; Marinotti, Osvaldo; Carpenter, Victoria K; Dawe, Angus L; Hansen, Immo A

    2010-12-29

    The mosquito, Aedes aegypti, is the principal vector of the Dengue and yellow fever viruses. During feeding, an adult female can take up more than its own body weight in vertebrate blood. After a blood meal females excrete large amounts of urine through their excretion system, the Malpighian tubules (MT). Diuresis starts within seconds after the mosquito starts feeding. Aquaporins (AQPs) are a family of membrane transporters that regulate the flow of water, glycerol and other small molecules across cellular membranes in both prokaryotic and eukaryotic cells. Our aim was to identify aquaporins that function as water channels, mediating transcellular water transport in MTs of adult female Ae. aegypti. Using a bioinformatics approach we screened genome databases and identified six putative AQPs in the genome of Ae. aegypti. Phylogenetic analysis showed that five of the six Ae. aegypti AQPs have high similarity to classical water-transporting AQPs of vertebrates. Using microarray, reverse transcription and real time PCR analysis we found that all six AQPs are expressed in distinct patterns in mosquito tissues/body parts. AaAQP1, 4, and 5 are strongly expressed in the adult female MT. RNAi-mediated knockdown of the MT-expressed mosquito AQPs resulted in significantly reduced diuresis. Our results support the notion that AQP1, 4, and 5 function as water transporters in the MTs of adult female Ae. aegypti mosquitoes. Our results demonstrate the importance of these AQPs for mosquito diuresis after blood ingestion and highlight their potential as targets for the development of novel vector control strategies.

  3. Molecular and immunological characterization of a DNA-launched yellow fever virus 17D infectious clone.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Lukashevich, Igor S; Bredenbeek, Peter J; Franco, David

    2015-04-01

    Yellow fever virus (YFV)-17D is an empirically developed, highly effective live-attenuated vaccine that has been administered to human beings for almost a century. YFV-17D has stood as a paradigm for a successful viral vaccine, and has been exploited as a potential virus vector for the development of recombinant vaccines against other diseases. In this study, a DNA-launched YFV-17D construct (pBeloBAC-FLYF) was explored as a new modality to the standard vaccine to combine the commendable features of both DNA vaccine and live-attenuated viral vaccine. The DNA-launched YFV-17D construct was characterized extensively both in cell culture and in mice. High titres of YFV-17D were generated upon transfection of the DNA into cells, whereas a mutant with deletion in the capsid-coding region (pBeloBAC-YF/ΔC) was restricted to a single round of infection, with no release of progeny virus. Homologous prime-boost immunization of AAD mice with both pBeloBAC-FLYF and pBeloBAC-YF/ΔC elicited specific dose-dependent cellular immune response against YFV-17D. Vaccination of A129 mice with pBeloBAC-FLYF resulted in the induction of YFV-specific neutralizing antibodies in all vaccinated subjects. These promising results underlined the potential of the DNA-launched YFV both as an alternative to standard YFV-17D vaccination and as a vaccine platform for the development of DNA-based recombinant YFV vaccines. © 2015.

  4. Unpredictable checks of yellow fever vaccination certificates upon arrival in Tanzania.

    Science.gov (United States)

    Schönenberger, Selina; Hatz, Christoph; Bühler, Silja

    2016-05-01

    Yellow fever (YF) is a mosquito-borne disease, which can be prevented by vaccination. While YF vaccination (YFV) is not generally recommended for travellers to Tanzania, proof of YFV may be required upon arrival. In April 2013, the World Health Organization concluded that one dose of YFV confers lifelong protection and countries have started to adapt their entry requirements. The traveller's consultant has to balance the risk of YFV and the risk of encountering problems when entering a country without a valid YFV, especially because countries are slowly implementing the requirements. We performed a survey among 421 travellers to Tanzania with a pre-travel consultation at the Travel Clinic of the University of Zurich about their experiences with YFV certificate inspections upon arrival in Tanzania between January and November 2015. There were three main findings: (i) most vaccine card checks were done while crossing the land border of Tanzania. Inspections were frequently conducted at Arusha airport, less often in Dar es Salaam and Zanzibar. In the latter a significantly larger percentage of individuals arriving by ferry/boat were checked than those arriving by plane. (ii) Checks appeared to be non-systematic. They were also performed in travellers who did not enter Tanzania from a YF-endemic country. No seasonal or daytime pattern could be identified; the thoroughness of checks varied widely. (iii) In the case of travel without valid YFV, an exemption certificate was always accepted. In travellers with neither a valid YFV nor an exemption certificate, travellers reported forced YF vaccination and fines before entry was granted. We recommend YFV or a YF exemption certificate for all travellers to Tanzania until further notice. The decision of whether to vaccinate against YF or to issue an exemption should be based on exposure risk to YF infection in other countries during travel. © International Society of Travel Medicine, 2016. All rights reserved. Published by

  5. Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice.

    Science.gov (United States)

    Ryman, K D; Xie, H; Ledger, T N; Campbell, G A; Barrett, A D

    1997-04-14

    The live-attenuated yellow fever (YF) vaccine virus, strain 17D-204, has long been known to consist of a heterologous population of virions. Gould et al. (J. Gen. Virol. 70, 1889-1894 (1989)) previously demonstrated that variant viruses exhibiting a YF wild-type-specific envelope (E) protein epitope are present at low frequency in the vaccine pool and were able to isolate representative virus variants with and without this epitope, designated 17D(+wt) and 17D(-wt), respectively. These variants were employed here in an investigation of YF virus pathogenesis in the mouse model. Both the 17D-204 parent and the 17D(+wt) variant viruses were lethal for adult outbred mice by the intracerebral route of inoculation. However, the 17D(-wt) variant was significantly attenuated (18% mortality rate) and replicated to much lower titer in the brains of infected mice. A single amino acid substitution in the envelope (E) protein at E-240 (Ala-->Val) was identified as responsible for the restricted replication of the 17D(-wt) variant in vivo. The 17D(+wt) variant has an additional second-site mutation, believed to encode a reversion to the neurovirulence phenotype of the 17D-204 parent virus. The amino acid substitution in the E protein at E-173 (Thr-->Ile) of the 17D(+wt) variant which results in the appearance of the wild-type-specific epitope or nucleotide changes in the 5' and 3' noncoding regions of the virus are proposed as a candidates.

  6. Transfusion-related transmission of yellow fever vaccine virus--California, 2009.

    Science.gov (United States)

    2010-01-22

    In the United States, yellow fever (YF) vaccination is recommended for travelers and active duty military members visiting endemic areas of sub-Saharan Africa and Central/South America. The American Red Cross recommends that recipients of YF vaccine defer blood product donation for 2 weeks because of the theoretical risk for transmission from a viremic donor. On April 10, 2009, a hospital blood bank supervisor learned that, on March 27, blood products had been collected from 89 U.S. active duty trainees who had received YF vaccine 4 days before donation. This report summarizes the subsequent investigation by the hospital and CDC to identify lapses in donor deferral and to determine whether transfusion-related transmission of YF vaccine virus occurred. The investigation found that a recent change in the timing of trainee vaccination had occurred and that vaccinees had not reported recent YF vaccination status at time of donation. Despite a prompt recall, six units of blood products were transfused into five patients. No clinical evidence or laboratory abnormalities consistent with a serious adverse reaction were identified in four recipients within the first month after transfusion; the fifth patient, who had prostate cancer and end-stage, transfusion-dependent, B-cell lymphoma, died while in hospice care. Three of the four surviving patients had evidence of serologic response to YF vaccine virus. This report provides evidence that transfusion-related transmission of YF vaccine virus can occur and underscores the need for careful screening and deferral of recently vaccinated blood donors.

  7. Attenuation of Recombinant Yellow Fever 17D Viruses Expressing Foreign Protein Epitopes at the Surface

    Science.gov (United States)

    Bonaldo, Myrna C.; Garratt, Richard C.; Marchevsky, Renato S.; Coutinho, Evandro S. F.; Jabor, Alfredo V.; Almeida, Luís F. C.; Yamamura, Anna M. Y.; Duarte, Adriana S.; Oliveira, Prisciliana J.; Lizeu, Jackeline O. P.; Camacho, Luiz A. B.; Freire, Marcos S.; Galler, Ricardo

    2005-01-01

    The yellow fever (YF) 17D vaccine is a live attenuated virus. Three-dimensional (3D) homology modeling of the E protein structure from YF 17D virus and its comparison with that from tick-borne encephalitis virus revealed that it is possible to accommodate inserts of different sizes and amino acid compositions in the flavivirus E protein fg loop. This is consistent with the 3D structures of both the dimeric and trimeric forms in which the fg loop lies exposed to solvents. We demonstrate here that YF 17D viruses bearing foreign humoral (17D/8) and T-cell (17D/13) epitopes, which vary in sequence and length, displayed growth restriction. It is hypothesized that interference with the dimer-trimer transition and with the formation of a ring of such trimers in order to allow fusion compromises the capability of the E protein to induce fusion of viral and endosomal membranes, and a slower rate of fusion may delay the extent of virus production. This would account for the lower levels of replication in cultured cells and of viremia in monkeys, as well as for the more attenuated phenotype of the recombinant viruses in monkeys. Testing of both recombinant viruses (17D/8 and 17D/13) for monkey neurovirulence also suggests that insertion at the 17D E protein fg loop does not compromise the attenuated phenotype of YF 17D virus, further confirming the potential use of this site for the development of new live attenuated 17D virus-based vaccines. PMID:15956601

  8. Rapid Evolution of Ovarian-Biased Genes in the Yellow Fever Mosquito (Aedes aegypti).

    Science.gov (United States)

    Whittle, Carrie A; Extavour, Cassandra G

    2017-08-01

    Males and females exhibit highly dimorphic phenotypes, particularly in their gonads, which is believed to be driven largely by differential gene expression. Typically, the protein sequences of genes upregulated in males, or male-biased genes, evolve rapidly as compared to female-biased and unbiased genes. To date, the specific study of gonad-biased genes remains uncommon in metazoans. Here, we identified and studied a total of 2927, 2013, and 4449 coding sequences (CDS) with ovary-biased, testis-biased, and unbiased expression, respectively, in the yellow fever mosquito Aedes aegypti The results showed that ovary-biased and unbiased CDS had higher nonsynonymous to synonymous substitution rates (dN/dS) and lower optimal codon usage (those codons that promote efficient translation) than testis-biased genes. Further, we observed higher dN/dS in ovary-biased genes than in testis-biased genes, even for genes coexpressed in nonsexual (embryo) tissues. Ovary-specific genes evolved exceptionally fast, as compared to testis- or embryo-specific genes, and exhibited higher frequency of positive selection. Genes with ovary expression were preferentially involved in olfactory binding and reception. We hypothesize that at least two potential mechanisms could explain rapid evolution of ovary-biased genes in this mosquito: (1) the evolutionary rate of ovary-biased genes may be accelerated by sexual selection (including female-female competition or male-mate choice) affecting olfactory genes during female swarming by males, and/or by adaptive evolution of olfactory signaling within the female reproductive system ( e.g. , sperm-ovary signaling); and/or (2) testis-biased genes may exhibit decelerated evolutionary rates due to the formation of mating plugs in the female after copulation, which limits male-male sperm competition. Copyright © 2017 by the Genetics Society of America.

  9. Isolation of yellow fever virus (YFV from naturally infectied Haemagogus (Conopostegus leucocelaenus (diptera, cukicudae in São Paulo State, Brazil, 2009

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    Renato Pereira de Souza

    2011-06-01

    Full Text Available After detecting the death of Howlers monkeys (genus Alouatta and isolation of yellow fever virus (YFV in Buri county, São Paulo, Brazil, an entomological research study in the field was started. A YFV strain was isolated from newborn Swiss mice and cultured cells of Aedes albopictus - C6/36, from a pool of six Haemagogus (Conopostegus leucocelaenus (Hg. leucocelaenus mosquitoes (Dyar & Shannon collected at the study site. Virus RNA fragment was amplified by RT-PCR and sequenced. The MCC Tree generated showed that the isolated strain is related to the South American I genotype, in a monophyletic clade containing isolates from recent 2008-2010 epidemics and epizootics in Brazil. Statistical analysis commonly used were calculated to characterize the sample in relation to diversity and dominance and indicated a pattern of dominance of one or a few species. Hg. leucocelaenus was found infected in Rio Grande do Sul State as well. In São Paulo State, this is the first detection of YFV in Hg. leucocelaenus.

  10. Reemergence of yellow fever: detection of transmission in the State of São Paulo, Brazil, 2008

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    Eduardo Stramandinoli Moreno

    2011-06-01

    Full Text Available INTRODUCTION: Following yellow fever virus (YFV isolation in monkeys from the São José do Rio Preto region and two fatal human autochthonous cases from the Ribeirão Preto region, State of São Paulo, Brazil, two expeditions for entomological research and eco-epidemiological evaluation were conducted. METHODS: A total of 577 samples from humans, 108 from monkeys and 3,049 mosquitoes were analyzed by one or more methods: virus isolation, ELISA-IgM, RT-PCR, histopathology and immunohistochemical. RESULTS: Of the 577 human samples, 531 were tested by ELISA-IgM, with 3 positives, and 235 were inoculated into mice and 199 in cell culture, resulting in one virus isolation. One sample was positive by histopathology and immunohistochemical. Using RT-PCR, 25 samples were processed with 4 positive reactions. A total of 108 specimens of monkeys were examined, 108 were inoculated into mice and 45 in cell culture. Four virus strains were isolated from Alouattacaraya. A total of 931 mosquitoes were captured in Sao Jose do Rio Preto and 2,118 in Ribeirão Preto and separated into batches. A single isolation of YFV was derived from a batch of 9 mosquitoes Psorophoraferox, collected in Urupês, Ribeirão Preto region. A serological survey was conducted with 128 samples from the municipalities of São Carlos, Rincão and Ribeirão Preto and 10 samples from contacts of patients from Ribeirão Preto. All samples were negative by ELISA-IgM for YFV. CONCLUSIONS: The results confirm the circulation of yellow fever, even though sporadic, in the Sao Paulo State and reinforce the importance of vaccination against yellow fever in areas considered at risk.

  11. [Investigation surrounding a fatal case of yellow fever in Côte d'Ivoire in 1999].

    Science.gov (United States)

    Akoua-Koffi, C; Diarrassouba, S; Bénié, V B; Ngbichi, J M; Bozoua, T; Bosson, A; Akran, V; Carnevale, P; Ehouman, A

    2001-08-01

    Côte d'Ivoire is an endemic country for yellow fever, but no case was officially notified in recent years. In July 1999, however, one fatal case was reported. A German citizen was infected in the national park of Comoe, in the north eastern area of the country. In order to evaluate the extent of amaril virus circulation and the risk for local people, a virological, entomological and epidemiological investigation was carried out by the ministry of health, the OCCGE, the Côte d'Ivoire Pasteur Institute (IPCI) and the World Health Organisation in the area where the fatal case had been staying. 18 suspected and 24 confirmed mosquito catchers were identified by interview and a blood specimen was collected from each of them. In addition, 159 batches of mosquitoes from which 94 batches of potential vectors were collected; among the suspected cases, 22% were immunised against yellow fever. Serological and virological analyses were made at IPCI and the Paris Pasteur Institute by ELISA technique and isolation on cells cultures and newborn mice. All the suspicious sera and 87.5% of the catchers were positive for IgG anti-amaril virus. One catcher's serum was positive for IgM anti-amaril virus. 11 suspected sera were positive for IgG anti-dengue virus with 1 positive for IgM. 1 strain of amaril virus and 3 strains of Zika virus were isolated from mosquitoes at IPCI and confirmed by CRORA in Dakar. These results indicated that there is a yellow fever and dengue virus are prevalent among the human and vector populations in the study area. Preventive measures must be adopted to protect human beings at risk for amaril infection.

  12. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    Science.gov (United States)

    Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-04-01

    To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

  13. Becoming an International Scientist in South Korea: Ho Wang Lee’s Research Activity about Epidemic Hemorrhagic Fever

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    Miyoung SHIN

    2017-04-01

    Full Text Available In the 1960-70s, South Korea was still in the position of a science latecomer. Although the scientific research environment in South Korea at that time was insufficient, there was a scientist who achieved outcomes that could be recognized internationally while acting in South Korea. He was Ho Wang Lee(1928~ who found Hantann Virus that causes epidemic hemorrhagic fever for the first time in the world. It became a clue to identify causative viruses of hemorrhagic diseases that were scattered here and there throughout the world. In addition, these outcomes put Ho Wang Lee on the global center of research into epidemic hemorrhagic fever. This paper examines how a Korean scientist who was in the periphery of virology could go into the central area of virology. Also this article shows the process through which the virus found by Ho Wang Lee was registered with the international academia and he proceeded with follow-up research based on this progress to reach the level at which he generalized epidemic hemorrhagic fever related studies throughout the world. While he was conducting the studies, experimental methods that he had never experienced encountered him as new difficulties. He tried to solve the new difficulties faced in his changed status through devices of cooperation and connection. Ho Wang Lee’s growth as a researcher can be seen as well as a view of a researcher that grew from a regional level to an international level and could advance from the area of non-mainstream into the mainstream. This analytic tool is meaningful in that it can be another method of examining the growth process of scientists in South Korea or developing countries.

  14. Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease.

    Science.gov (United States)

    Barrett, Alan D T

    2017-10-20

    Yellow fever (YF) is regarded as the original hemorrhagic fever and has been a major public health problem for at least 250years. A very effective live attenuated vaccine, strain 17D, was developed in the 1930s and this has proved critical in the control of the disease. There is little doubt that without the vaccine, YF virus would be considered a biosafety level 4 pathogen. Significantly, YF is currently the only disease where an international vaccination certificate is required under the International Health Regulations. Despite having a very successful vaccine, there are occasional issues of supply and demand, such as that which occurred in Angola and Democratic Republic of Congo in 2016 when there was insufficient vaccine available. For the first time fractional dosing of the vaccine was approved on an emergency basis. Thus, continued vigilance and improvements in supply and demand are needed in the future. Copyright © 2017. Published by Elsevier Ltd.

  15. Simulation modelling of population dynamics of mosquito vectors for rift valley Fever virus in a disease epidemic setting.

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    Clement N Mweya

    Full Text Available Rift Valley Fever (RVF is weather dependent arboviral infection of livestock and humans. Population dynamics of mosquito vectors is associated with disease epidemics. In our study, we use daily temperature and rainfall as model inputs to simulate dynamics of mosquito vectors population in relation to disease epidemics.Time-varying distributed delays (TVDD and multi-way functional response equations were implemented to simulate mosquito vectors and hosts developmental stages and to establish interactions between stages and phases of mosquito vectors in relation to vertebrate hosts for infection introduction in compartmental phases. An open-source modelling platforms, Universal Simulator and Qt integrated development environment were used to develop models in C++ programming language. Developed models include source codes for mosquito fecundity, host fecundity, water level, mosquito infection, host infection, interactions, and egg time. Extensible Markup Language (XML files were used as recipes to integrate source codes in Qt creator with Universal Simulator plug-in. We observed that Floodwater Aedines and Culicine population continued to fluctuate with temperature and water level over simulation period while controlled by availability of host for blood feeding. Infection in the system was introduced by floodwater Aedines. Culicines pick infection from infected host once to amplify disease epidemic. Simulated mosquito population show sudden unusual increase between December 1997 and January 1998 a similar period when RVF outbreak occurred in Ngorongoro district.Findings presented here provide new opportunities for weather-driven RVF epidemic simulation modelling. This is an ideal approach for understanding disease transmission dynamics towards epidemics prediction, prevention and control. This approach can be used as an alternative source for generation of calibrated RVF epidemics data in different settings.

  16. Simulation modelling of population dynamics of mosquito vectors for rift valley Fever virus in a disease epidemic setting.

    Science.gov (United States)

    Mweya, Clement N; Holst, Niels; Mboera, Leonard E G; Kimera, Sharadhuli I

    2014-01-01

    Rift Valley Fever (RVF) is weather dependent arboviral infection of livestock and humans. Population dynamics of mosquito vectors is associated with disease epidemics. In our study, we use daily temperature and rainfall as model inputs to simulate dynamics of mosquito vectors population in relation to disease epidemics. Time-varying distributed delays (TVDD) and multi-way functional response equations were implemented to simulate mosquito vectors and hosts developmental stages and to establish interactions between stages and phases of mosquito vectors in relation to vertebrate hosts for infection introduction in compartmental phases. An open-source modelling platforms, Universal Simulator and Qt integrated development environment were used to develop models in C++ programming language. Developed models include source codes for mosquito fecundity, host fecundity, water level, mosquito infection, host infection, interactions, and egg time. Extensible Markup Language (XML) files were used as recipes to integrate source codes in Qt creator with Universal Simulator plug-in. We observed that Floodwater Aedines and Culicine population continued to fluctuate with temperature and water level over simulation period while controlled by availability of host for blood feeding. Infection in the system was introduced by floodwater Aedines. Culicines pick infection from infected host once to amplify disease epidemic. Simulated mosquito population show sudden unusual increase between December 1997 and January 1998 a similar period when RVF outbreak occurred in Ngorongoro district. Findings presented here provide new opportunities for weather-driven RVF epidemic simulation modelling. This is an ideal approach for understanding disease transmission dynamics towards epidemics prediction, prevention and control. This approach can be used as an alternative source for generation of calibrated RVF epidemics data in different settings.

  17. Hay fever, a post industrial revolution epidemic: a history of its growth during the 19th century.

    Science.gov (United States)

    Emanuel, M B

    1988-05-01

    Although other forms of allergic disease were described in antiquity, hay fever is surprisingly modern. Very rare descriptions can be traced back to Islamic texts of the 9th century and European texts of the 16th century. It was only in the early 19th century that the disease was carefully described and at that time was regarded as most unusual. By the end of the 19th century it had become commonplace in both Europe and North America. This paper attempts to chart the growth of hay fever through the medical literature of the 19th century. It is hoped that an understanding of the increase in prevalence between 1820 and 1900 may provide an insight for modern researchers and give some clues into possible reasons for the epidemic nature of the disease today.

  18. Estimating the size of Aedes aegypti populations from dengue incidence data: Implications for the risk of yellow fever outbreaks

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    Eduardo Massad

    2017-11-01

    Full Text Available In this paper we present a model to estimate the density of aedes mosquitoes in a community affected by dengue. The method consists in fitting a continuous function to the incidence of dengue infections, from which the density of infected mosquitoes is derived straightforwardly. Further derivations allow the calculation of the latent and susceptible mosquitoes' densities, the sum of the three equals the total mosquitoes' density. The method is illustrated with the case of the risk of urban yellow fever resurgence in dengue infested areas but the same procedures apply for other aedes-transmitted infections like Zika and chikungunya viruses.

  19. International risk of yellow fever spread from the ongoing outbreak in Brazil, December 2016 to May 2017.

    Science.gov (United States)

    Dorigatti, Ilaria; Hamlet, Arran; Aguas, Ricardo; Cattarino, Lorenzo; Cori, Anne; Donnelly, Christl A; Garske, Tini; Imai, Natsuko; Ferguson, Neil M

    2017-07-13

    States in south-eastern Brazil were recently affected by the largest Yellow Fever (YF) outbreak seen in a decade in Latin America. Here we provide a quantitative assessment of the risk of travel-related international spread of YF indicating that the United States, Argentina, Uruguay, Spain, Italy and Germany may have received at least one travel-related YF case capable of seeding local transmission. Mitigating the risk of imported YF cases seeding local transmission requires heightened surveillance globally. This article is copyright of The Authors, 2017.

  20. Gustatory receptor neuron responds to DEET and other insect repellents in the yellow-fever mosquito, Aedes aegypti

    Science.gov (United States)

    Sanford, Jillian L.; Shields, Vonnie D. C.; Dickens, Joseph C.

    2013-03-01

    Three gustatory receptor neurons were characterized for contact chemoreceptive sensilla on the labella of female yellow-fever mosquitoes, Aedes aegypti. The neuron with the smallest amplitude spike responded to the feeding deterrent, quinine, as well as N, N-diethyl-3-methylbenzamide and other insect repellents. Two other neurons with differing spikes responded to salt (NaCl) and sucrose. This is the first report of a gustatory receptor neuron specific for insect repellents in mosquitoes and may provide a tool for screening chemicals to discover novel or improved feeding deterrents and repellents for use in the management of arthropod disease vectors.

  1. T cell Receptor Alpha Variable 12-2 bias in the immunodominant response to Yellow fever virus

    OpenAIRE

    Bovay, Amandine; Zoete, Vincent; Dolton, Garry; Bulek, Anna M.; Cole, David K.; Rizkallah, Pierre J.; Fuller, Anna; Beck, Konrad; Michielin, Olivier; Speiser, Daniel E.; Sewell, Andrew K.; Fuertes Marraco, Silvia A.

    2018-01-01

    The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 javax.xml.bind.JAXBElement@714aac...

  2. Temporal trend and climate factors of hemorrhagic fever with renal syndrome epidemic in Shenyang City, China

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    Liu Xiaodong

    2011-12-01

    Full Text Available Abstract Background Hemorrhagic fever with renal syndrome (HFRS is an important infectious disease caused by different species of hantaviruses. As a rodent-borne disease with a seasonal distribution, external environmental factors including climate factors may play a significant role in its transmission. The city of Shenyang is one of the most seriously endemic areas for HFRS. Here, we characterized the dynamic temporal trend of HFRS, and identified climate-related risk factors and their roles in HFRS transmission in Shenyang, China. Methods The annual and monthly cumulative numbers of HFRS cases from 2004 to 2009 were calculated and plotted to show the annual and seasonal fluctuation in Shenyang. Cross-correlation and autocorrelation analyses were performed to detect the lagged effect of climate factors on HFRS transmission and the autocorrelation of monthly HFRS cases. Principal component analysis was constructed by using climate data from 2004 to 2009 to extract principal components of climate factors to reduce co-linearity. The extracted principal components and autocorrelation terms of monthly HFRS cases were added into a multiple regression model called principal components regression model (PCR to quantify the relationship between climate factors, autocorrelation terms and transmission of HFRS. The PCR model was compared to a general multiple regression model conducted only with climate factors as independent variables. Results A distinctly declining temporal trend of annual HFRS incidence was identified. HFRS cases were reported every month, and the two peak periods occurred in spring (March to May and winter (November to January, during which, nearly 75% of the HFRS cases were reported. Three principal components were extracted with a cumulative contribution rate of 86.06%. Component 1 represented MinRH0, MT1, RH1, and MWV1; component 2 represented RH2, MaxT3, and MAP3; and component 3 represented MaxT2, MAP2, and MWV2. The PCR model

  3. Community knowledge, attitudes and practices on Yellow fever in South Omo area, Southern Ethiopia.

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    Mengistu Legesse

    2018-04-01

    Full Text Available Yellow fever (Yf outbreak was recently reported in South Omo of Southern Ethiopia. This area was also highly affected by Yf outbreak in the 1960s. However, there is no reliable information on the level of community knowledge attitudes and practices about the disease in the area. The objective of the current study was to assess level of community knowledge, attitudes and practices about Yf.Between March and May 2017, a community-based cross-sectional survey was conducted in two districts of the South Omo area. During the survey, 612 randomly selected adults were interviewed about Yf using structured questionnaire.Out of the 612 study participants, 508 (83.0% reported that they heard about Yf which is locally known as "a disease that causes vomiting blood". Most (90.4% of the study participants also said that Yf is different from malaria. Two hundred thirteen (41.9% participants said that Yf can be transmitted from a patient to another person, while only 80 (37.6% mentioned that the disease is transmitted through mosquitoes bite. Out of 333 (65.7% study participants who believed that Yf is a preventable disease, 280 (84.1% mentioned vaccine as a preventive method. The majority believed that the disease is a killer (97.2% and a newly emerging (69.4%. Among the total of 612 study participants, 221(36.1% were considered as having a high level of overall knowledge of Yf. Having educational level above 7th grade (AOR = 3.25, 95% CI: 1.39, 7.57, p = 0.006 and being resident of Bena-Tsemay district (AOR = 1.77, 95% CI: 1.12, 2.78, P = 0.014 were significantly associated with having a high level of overall knowledge of Yf. Agro-pastoralism as an occupation compared to farming was associated with having a low level of overall knowledge of Yf (AOR = 0.51, 95% CI, 0.33, 0.79, P = 0.003.The findings indicate that most of the study community members had a low level of overall knowledge of Yf, especially about its cause, mode of transmission and preventive

  4. A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

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    Kathryn C Meier

    2009-10-01

    Full Text Available Mosquito-borne yellow fever virus (YFV causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129 or the STAT1 signaling molecule (STAT129 were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129

  5. A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

    Science.gov (United States)

    Meier, Kathryn C; Gardner, Christina L; Khoretonenko, Mikhail V; Klimstra, William B; Ryman, Kate D

    2009-10-01

    Mosquito-borne yellow fever virus (YFV) causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta) in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129) or the STAT1 signaling molecule (STAT129) were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129-derived, but not WT

  6. Yellow Rust Epidemics Worldwide Were Caused by Pathogen Races from Divergent Genetic Lineages

    DEFF Research Database (Denmark)

    Ali, Sajid; Rodriguez Algaba, Julian; Thach, Tine

    2017-01-01

    population across geographical regions. The results emphasized the lack of predictability of emergence of new races with high epidemic potential, which stresses the need for additional investments in population biology and surveillance activities of pathogens on global food crops, and assessments of disease...... that these epidemics were often driven by races from few but highly divergent genetic lineages. PstS1 was predominant in North America; PstS2 in West Asia and North Africa; and both PstS1 and PstS2 in East Africa. PstS4 was prevalent in Northern Europe on triticale; PstS5 and PstS9 were prevalent in Central Asia......; whereas PstS6 was prevalent in epidemics in East Africa. PstS7, PstS8 and PstS10 represented three genetic lineages prevalent in Europe. Races from other lineages were in low frequencies. Virulence to Yr9 and Yr27 was common in epidemics in Africa and Asia, while virulence to Yr17 and Yr32 were prevalent...

  7. WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

    Science.gov (United States)

    World Health Organization

    2017-10-13

    This article presents the World Health Organization's (WHO) recommendations on the use of fractional doses of yellow fever vaccines excerpted from the "Yellow fever vaccine: WHO position on the use of fractional doses - June 2017, Addendum to Vaccines and vaccination against yellow fever WHO: Position Paper - June 2013″, published in the Weekly Epidemiological Record [1,2]. This addendum to the 2013 position paper pertains specifically to use of fractional dose YF (fYF) vaccination (fractional dose yellow fever vaccination refers to administration of a reduced volume of vaccine dose, which has been reconstituted as usual per manufacturer recommendations) in the context of YF vaccine supply shortages beyond the capacity of the global stockpile. The current WHO position on the use of yellow fever (YF) vaccine is set out in the 2013 WHO position paper on vaccines and vaccination against YF and those recommendations are unchanged. Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of Yellow Fever vaccines were discussed by SAGE in October 2016; evidence presented at these meetings can be accessed at: www.who.int/immunization/sage/meetings/2016/October/presentations_background_docs/en/. Copyright © 2017. Published by Elsevier Ltd.

  8. Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

    Science.gov (United States)

    Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

    2011-01-01

    Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

  9. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    Directory of Open Access Journals (Sweden)

    Birgit Schäfer

    Full Text Available BACKGROUND: Currently existing yellow fever (YF vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D. Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5 TCID(50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

  10. Vaccination against yellow fever in French Guiana: The impact of educational level, negative beliefs and attitude towards vaccination.

    Science.gov (United States)

    Koïvogui, Akoï; Carbunar, Aurel; Imounga, Laure-Manuella; Laruade, Christelle; Laube, Sylvaine

    Analyze the impact of educational level, negative beliefs and negative attitudes on the yellow fever vaccination coverage (YFVC). This analytical study involved a sample of 2763 people from 866 households. Educational status was described in six levels: No level (Respondent had never attended school), level-1 (respondent left before intermediate school), level-2 (Respondent attended intermediate school), level-3 (respondent attended high school), level-4 (Respondent attended university), Other level (When the level could not be determined). The Attitude towards vaccination was described in terms of person's availability to recommend vaccination to third. The relationships were analyzed by multivariate mixed logistic regression. Among the 2763 peoples, 2039 (73.8%) were vaccinated against yellow fever. People who left high school with or without the French baccalaureate were more likely to be vaccinated against YF than people without any diploma (OR = 1.4; p < 0.05). The probability of being vaccinated among people with negative attitudes was reduced by 40% (OR = 0.6; p < 0.05). Low level of education, negative beliefs and negative attitudes have significant impacts on YFVC. Negatives beliefs and attitudes result often from a major lack of information about the benefits of vaccination. This deficit is exacerbated in persons with low educational level. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Strong alkalinization in the anterior midgut of larval yellow fever mosquitoes (Aedes aegypti): involvement of luminal Na+/K+-ATPase.

    Science.gov (United States)

    Onken, Horst; Patel, Malay; Javoroncov, Margarita; Izeirovski, Sejmir; Moffett, Stacia B; Moffett, David F

    2009-03-01

    Recently, Na(+)/K(+)-ATPase has been detected in the luminal membrane of the anterior midgut of larval yellow fever mosquitoes (Aedes aegypti) with immunohistochemical techniques. In this study, the possible involvement of this ATPase in strong alkalinization was investigated on the level of whole larvae, isolated and perfused midgut preparations and on the molecular level of the Na(+)/K(+)-ATPase protein. Ouabain (5 mM) did not inhibit the capability of intact larval mosquitoes to alkalinize their anterior midgut. Also in isolated and perfused midgut preparations the perfusion of the lumen with ouabain (5 mM) did not result in a significant change of the transepithelial voltage or the capacity of luminal alkalinization. Na(+)/K(+)-ATPase activity was completely abolished when KCl was substituted with choline chloride, suggesting that the enzyme cannot act as an ATP-driven Na(+)/H(+)-exchanger. Altogether the results of the present investigation indicate that apical Na(+)/K(+)-ATPase is not of direct importance for strong luminal alkalinization in the anterior midgut of larval yellow fever mosquitoes.

  12. Imaginal discs--a new source of chromosomes for genome mapping of the yellow fever mosquito Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Maria V Sharakhova

    2011-10-01

    Full Text Available The mosquito Aedes aegypti is the primary global vector for dengue and yellow fever viruses. Sequencing of the Ae. aegypti genome has stimulated research in vector biology and insect genomics. However, the current genome assembly is highly fragmented with only ~31% of the genome being assigned to chromosomes. A lack of a reliable source of chromosomes for physical mapping has been a major impediment to improving the genome assembly of Ae. aegypti.In this study we demonstrate the utility of mitotic chromosomes from imaginal discs of 4(th instar larva for cytogenetic studies of Ae. aegypti. High numbers of mitotic divisions on each slide preparation, large sizes, and reproducible banding patterns of the individual chromosomes simplify cytogenetic procedures. Based on the banding structure of the chromosomes, we have developed idiograms for each of the three Ae. aegypti chromosomes and placed 10 BAC clones and a 18S rDNA probe to precise chromosomal positions.The study identified imaginal discs of 4(th instar larva as a superior source of mitotic chromosomes for Ae. aegypti. The proposed approach allows precise mapping of DNA probes to the chromosomal positions and can be utilized for obtaining a high-quality genome assembly of the yellow fever mosquito.

  13. Genetic structure and phylogeography of Aedes aegypti, the dengue and yellow-fever mosquito vector in Bolivia.

    Science.gov (United States)

    Paupy, Christophe; Le Goff, Gilbert; Brengues, Cécile; Guerra, Mabel; Revollo, Jimmy; Barja Simon, Zaïra; Hervé, Jean-Pierre; Fontenille, Didier

    2012-08-01

    Between the 16th and 18th centuries, Aedes aegypti (Diptera: Culicidae), a mosquito native to Africa, invaded the Americas, where it was successively responsible for the emergence of yellow fever (YF) and dengue (DEN). The species was eradicated from numerous American countries in the mid-20th century, but re-invaded them in the 1970s and 1980s. Little is known about the precise identities of Ae. aegypti populations which successively thrived in South America, or their relation with the epidemiological changes in patterns of YF and DEN. We examined these questions in Bolivia, where Ae. aegypti, eradicated in 1943, re-appeared in the 1980s. We assessed the genetic variability and population genetics of Ae. aegypti samples in order to deduce their genetic structure and likely geographic origin. Using a 21-population set covering Bolivia, we analyzed the polymorphism at nine microsatellite loci and in two mitochondrial DNA regions (COI and ND4). Microsatellite markers revealed a significant genetic structure among geographic populations (F(ST)=0.0627, PBolivia. Analysis of mtDNA sequences revealed the existence of two genetic lineages, one dominant lineage recovered throughout Bolivia, and the second restricted to rural localities in South Bolivia. Phylogenic analysis indicated that this minority lineage was related to West African Ae. aegypti specimens. In conclusion, our results suggested a temporal succession of Ae. aegypti populations in Bolivia, that potentially impacted the epidemiology of dengue and yellow fever. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. AEGY-28 Cell Line of Aedes aegypti (Diptera Culicidae is Infection Refractory to Dengue 2 and Yellow Fever Virus

    Directory of Open Access Journals (Sweden)

    Nadia Y. Castañeda

    2007-07-01

    Full Text Available Mosquito cell derived cultures are useful tools for arbovirus isolation, identification or characterization. For studying dengue (DENV and yellow fever viruses (YFV Aedes albopictus C6/36 or Aedes pseudoscutellaris AP-61 cell lines, are normally used. The Aedes aegypti AEGY-28 cell line was obtained from embryonic tissues and characterized previously by one of us. In order to evaluate its susceptibility to two Flavivirus, AEGY- 28 cells were inoculated with different multiplicity of infection (MOI with type 2 DENV (COL-789, MOI: 1 and 5 and YFV clinical isolates (V-341, MOI 0,02 then processed at different times post infection (p.i.. Immunostai ning and fluorometric cell-ELISA were carried out to identify and quantify viral antigens. C6/36 and Vero cells were used as positive controls. Unexpectedly, immunoreactivity was not found in inoculated AEGY-28 cells, even in higher MOI or late times p.i., therefore antigen quantification using fluorometric cell-ELISA were not  plausible. Reverse transcriptase PCR with specific primers did not detect viral RNA in AEGY-28 inoculated cells. We can conclude that Aedes aegypti AEGY-28 cell line is not susceptible to dengue and yellow fever Flavivirus, a finding possibly related with the lacking of specific molecules at the plasma membrane or absence of cell machinery necessary for viral replication.

  15. Phylodynamics of Yellow Fever Virus in the Americas: new insights into the origin of the 2017 Brazilian outbreak.

    Science.gov (United States)

    Mir, Daiana; Delatorre, Edson; Bonaldo, Myrna; Lourenço-de-Oliveira, Ricardo; Vicente, Ana Carolina; Bello, Gonzalo

    2017-08-07

    Yellow fever virus (YFV) strains circulating in the Americas belong to two distinct genotypes (I and II) that have diversified into several concurrent enzootic lineages. Since 1999, YFV genotype I has spread outside endemic regions and its recent (2017) reemergence in non-endemic Southeastern Brazilian states fuels one of the largest epizootic of jungle Yellow Fever registered in the country. To better understand this phenomenon, we reconstructed the phylodynamics of YFV American genotypes using sequences from nine countries sampled along 60 years, including strains from Brazilian 2017 outbreak. Our analyses reveals that YFV genotypes I and II follow roughly similar evolutionary and demographic dynamics until the early 1990s, when a dramatic change in the diversification process of the genotype I occurred associated with the emergence and dissemination of a new lineage (here called modern). Trinidad and Tobago was the most likely source of the YFV modern-lineage that spread to Brazil and Venezuela around the late 1980s, where it replaced all lineages previously circulating. The modern-lineage caused all major YFV outbreaks detected in non-endemic South American regions since 2000, including the 2017 Brazilian outbreak, and its dissemination was coupled to the accumulation of several amino acid substitutions particularly within non-structural viral proteins.

  16. The risk of blood transfusion-associated Chikungunya fever during the 2009 epidemic in Songkhla Province, Thailand.

    Science.gov (United States)

    Appassakij, Hatsadee; Promwong, Charuporn; Rujirojindakul, Pairaya; Wutthanarungsan, Rochana; Silpapojakul, Khachornsakdi

    2014-08-01

    Asymptomatic Chikungunya fever (CHIKF)-viremic blood donors could be a potential threat of spreading the disease unwittingly through contaminated blood transfusions. The relatively low prevalence of Chikungunya virus antibodies in the population and the records of more than 9000 suspected CHIKF cases raised concern about the potential transfusion-associated CHIKF during the 2009 epidemic. This study assessed the potential transfusion risk for CHIKF and the implementation of blood safety measures to mitigate this risk. A probabilistic model using key variables obtained from local information was used to estimate the weekly risk of transfusion-associated CHIKF during the 2009 epidemic. In addition, other blood safety measure-based strategies involving screening for donors at risk, donor tracing, and a 7-day quarantine of blood components at risk were implemented at the time of the epidemic. The risk of viremic donations per 100,000 ranged from 38.2 (95% confidence interval [CI], 36.5-39.8) to 52.3 (95% CI, 50.4-54.2). The potential risk of transfusion-associated CHIKF per 100,000 was estimated to be 1 in 2429 (0.04%; 95% CI, 1 in 6681 [0.02%]-1 in 1572 [0.06%]) to 1 in 1781 (0.06%; 95% CI, 1 in 3817 [0.03%]-1 in 1214 (0.08%]) donations. Among 26,722 donations, 11 (95% CI, 4-17) to 15 (95% CI, 7-22) donations were predicted to associate with transfusion risk. The implementation of blood safety measure-based strategies for this epidemic period suggested to deter 11 blood donations of transfusion risk. The interventions for blood safety measures applied in this study had mitigated the potential transfusion-associated CHIKF during the 2009 epidemic. © 2014 AABB.

  17. Dengue fever

    African Journals Online (AJOL)

    symptoms and research has been limited to studies ... severity and problems with vaccination (4). History of ... Americas in 1970s reduced the spread of dengue fever. After this .... Reiter P. Yellow fever and dengue: a threat to Europe? 9.

  18. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    OpenAIRE

    Marco A B Almeida; Jader da C Cardoso; Edmilson Dos Santos; Daltro F da Fonseca; Laura L Cruz; Fernando J C Faraco; Marilina A Bercini; Kátia C Vettorello; Mariana A Porto; Renate Mohrdieck; Tani M S Ranieri; Maria T Schermann; Alethéa F Sperb; Francisco Z Paz; Zenaida M A Nunes

    2014-01-01

    Author Summary Yellow fever (YF) is a viral hemorrhagic disease that affects humans as well as several species of non-human primates, especially New World monkeys found in South America. Yellow fever virus (YFV) is maintained in a natural cycle involving tree-hole breeding mosquitoes and non-human primates hosts. Because YF is often fatal in susceptible New World monkey populations, sudden die-offs of New World monkeys or epizootics can signal YFV circulation in an environment where humans ma...

  19. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    International Nuclear Information System (INIS)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S.; Pushko, Peter

    2014-01-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA ® platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice

  20. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States); Jokinen, Jenny; Lukashevich, Igor S. [Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville, KY (United States); Pushko, Peter, E-mail: ppushko@medigen-usa.com [Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701 (United States)

    2014-11-15

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. - Highlights: • The iDNA{sup ®} platform combines advantages of DNA and live attenuated vaccines. • Yellow fever (YF) 17D vaccine was launched from iDNA plasmid in vitro and in vivo. • Safety of iDNA-generated 17D virus was confirmed in AG129 mice. • BALB/c mice seroconverted after a single-dose vaccination with iDNA. • YF virus-neutralizing response was elicited in iDNA-vaccinated mice.

  1. A comparison of clinical diagnosis and serological diagnosis in an epidemic of Crimean-Congo Hemorrhagic Fever

    International Nuclear Information System (INIS)

    Nadeem, M.; Ali, N.; Anwar, M.

    2003-01-01

    Crimean Congo Hemorrhagic Fever (CCHF) is the life-threatening disease caused by Nairovirus of genus Bunya virus caused by tick bite of Hayalomma species or by direct contact of the blood/sera of the patient and animals suffering from this disease. Epidemics have been occurring in Balochistan province of Pakistan and neighboring Afghanistan and Iran from time to time with this mortality. Aim: In the absence of facilities for detection of serological markers of CCHF (IgM Et IgG antibodies and PCR for viral RNA), a study was designed to diagnose and treat cases of CCHF reporting to a specialist unit hospital situated at Quetta, Pakistan. The aim was to compare the clinical features, complications and outcome of both groups of patients: one detecting the disease clinically only and the other depending upon serological tests for the diagnosis. Methods: Thirty-four patients having fever of less than two weeks of duration with features of bleeding from the skin and various orifices were included in this study from June 2001 to September 2001 after hospitalization. Index case and some of the consecutive cases were subjected to detection of serological markers. Rest of the cases were diagnosed on clinical ground and baseline laboratory investigations only. Difference in both the group was noted carefully. All the patients were given Ribavirin and blood products as and when required. Results: Statistically there was no obvious difference in clinical manifestations (fever, body aches, purpuric spots, ecchymosis, epistaxis, gum bleed etc. ) and laboratory findings (blood picture, serum ALT, serum urea and electrolytes, PT, APTT, etc). There was also no difference in mortality of the two groups studied. Conclusion: In an on ongoing outbreak of CCHF, history, clinical findings and supportive baseline, laboratory investigations may be sufficient for early detection and treatment of CCHF cases. However for documentation of start of epidemic, serological markers should be done

  2. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control

    Directory of Open Access Journals (Sweden)

    Gerald Amandu Matua

    2015-05-01

    The current epidemic management approaches are largely “reactive”, with containment efforts aimed at halting spread of existing outbreaks. We recommend that for better outcomes, in addition to “reactive” interventions, “pre-emptive” strategies also need to be instituted. We conclude that emphasizing both “reactive” and “pre-emptive” strategies is more likely to lead to better epidemic preparedness and response at individual, community, institutional, and government levels, resulting in timely containment of future Ebola outbreaks.

  3. Survival and swimming behavior of insecticide-exposed larvae and pupae of the yellow fever mosquito Aedes aegypti

    Science.gov (United States)

    2014-01-01

    Background The yellow fever mosquito Aedes aegypti is essentially a container-inhabiting species that is closely associated with urban areas. This species is a vector of human pathogens, including dengue and yellow fever viruses, and its control is of paramount importance for disease prevention. Insecticide use against mosquito juvenile stages (i.e. larvae and pupae) is growing in importance, particularly due to the ever-growing problems of resistance to adult-targeted insecticides and human safety concerns regarding such use in human dwellings. However, insecticide effects on insects in general and mosquitoes in particular primarily focus on their lethal effects. Thus, sublethal effects of such compounds in mosquito juveniles may have important effects on their environmental prevalence. In this study, we assessed the survival and swimming behavior of A. aegypti 4th instar larvae (L4) and pupae exposed to increasing concentrations of insecticides. We also assessed cell death in the neuromuscular system of juveniles. Methods Third instar larvae of A. aegypti were exposed to different concentrations of azadirachtin, deltamethrin, imidacloprid and spinosad. Insect survival was assessed for 10 days. The distance swam, the resting time and the time spent in slow swimming were assessed in 4th instar larvae (L4) and pupae. Muscular and nervous cells of L4 and pupae exposed to insecticides were marked with the TUNEL reaction. The results from the survival bioassays were subjected to survival analysis while the swimming behavioral data were subjected to analyses of covariance, complemented with a regression analysis. Results All insecticides exhibited concentration-dependent effects on survival of larvae and pupae of the yellow fever mosquito. The pyrethroid deltamethrin was the most toxic insecticide followed by spinosad, imidacloprid, and azadirachtin, which exhibited low potency against the juveniles. All insecticides except azadirachtin reduced L4 swimming speed and

  4. Survival and swimming behavior of insecticide-exposed larvae and pupae of the yellow fever mosquito Aedes aegypti.

    Science.gov (United States)

    Tomé, Hudson Vv; Pascini, Tales V; Dângelo, Rômulo Ac; Guedes, Raul Nc; Martins, Gustavo F

    2014-04-24

    The yellow fever mosquito Aedes aegypti is essentially a container-inhabiting species that is closely associated with urban areas. This species is a vector of human pathogens, including dengue and yellow fever viruses, and its control is of paramount importance for disease prevention. Insecticide use against mosquito juvenile stages (i.e. larvae and pupae) is growing in importance, particularly due to the ever-growing problems of resistance to adult-targeted insecticides and human safety concerns regarding such use in human dwellings. However, insecticide effects on insects in general and mosquitoes in particular primarily focus on their lethal effects. Thus, sublethal effects of such compounds in mosquito juveniles may have important effects on their environmental prevalence. In this study, we assessed the survival and swimming behavior of A. aegypti 4th instar larvae (L4) and pupae exposed to increasing concentrations of insecticides. We also assessed cell death in the neuromuscular system of juveniles. Third instar larvae of A. aegypti were exposed to different concentrations of azadirachtin, deltamethrin, imidacloprid and spinosad. Insect survival was assessed for 10 days. The distance swam, the resting time and the time spent in slow swimming were assessed in 4th instar larvae (L4) and pupae. Muscular and nervous cells of L4 and pupae exposed to insecticides were marked with the TUNEL reaction. The results from the survival bioassays were subjected to survival analysis while the swimming behavioral data were subjected to analyses of covariance, complemented with a regression analysis. All insecticides exhibited concentration-dependent effects on survival of larvae and pupae of the yellow fever mosquito. The pyrethroid deltamethrin was the most toxic insecticide followed by spinosad, imidacloprid, and azadirachtin, which exhibited low potency against the juveniles. All insecticides except azadirachtin reduced L4 swimming speed and wriggling movements. A

  5. Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.

    Science.gov (United States)

    Fisker, Ane Bærent; Ravn, Henrik; Rodrigues, Amabelia; Østergaard, Marie Drivsholm; Bale, Carlito; Benn, Christine Stabell; Aaby, Peter

    2014-01-23

    Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects. In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors. While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4). In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Yellow fever virus envelope protein expressed in insect cells is capable of syncytium formation in lepidopteran cells and could be used for immunodetection of YFV in human sera

    Directory of Open Access Journals (Sweden)

    Nagata Tatsuya

    2011-05-01

    Full Text Available Abstract Background Yellow fever is an haemorrhagic disease caused by a virus that belongs to the genus Flavivirus (Flaviviridae family and is transmitted by mosquitoes. Among the viral proteins, the envelope protein (E is the most studied one, due to its high antigenic potencial. Baculovirus are one of the most popular and efficient eukaryotic expression system. In this study a recombinant baculovirus (vSynYFE containing the envelope gene (env of the 17D vaccine strain of yellow fever virus was constructed and the recombinant protein antigenicity was tested. Results Insect cells infected with vSynYFE showed syncytium formation, which is a cytopathic effect characteristic of flavivirus infection and expressed a polypeptide of around 54 kDa, which corresponds to the expected size of the recombinant E protein. Furthermore, the recombinant E protein expression was also confirmed by fluorescence microscopy of vSynYFE-infected insect cells. Total vSynYFE-infected insect extracts used as antigens detected the presence of antibodies for yellow fever virus in human sera derived from yellow fever-infected patients in an immunoassay and did not cross react with sera from dengue virus-infected patients. Conclusions The E protein expressed by the recombinant baculovirus in insect cells is antigenically similar to the wild protein and it may be useful for different medical applications, from improved diagnosis of the disease to source of antigens for the development of a subunit vaccine.

  7. Chemosensory responses to the repellent nepeta essential oil and its major component nepetalactone by the yellow fever mosquito, aedes aegypti, a vector of zika virus

    Science.gov (United States)

    Nepeta essential oil (Neo) (catnip) and its major component, nepetalactone, have long been known to repel insects including mosquitoes. However, the neural mechanisms through which these repellents are detected by mosquitoes, including the yellow fever mosquito Aedes aegypti, an important vector of...

  8. Ebola hemorrhagic fever outbreaks: strategies for effective epidemic management, containment and control

    OpenAIRE

    Matua, Gerald Amandu; Wal, Dirk Mostert Van der; Locsin, Rozzano C.

    2015-01-01

    Ebola hemorrhagic fever, caused by the highly virulent RNA virus of the filoviridae family, has become one of the world's most feared pathogens. The virus induces acute fever and death, often associated with hemorrhagic symptoms in up to 90% of infected patients. The known sub-types of the virus are Zaire, Sudan, Taï Forest, Bundibugyo and Reston Ebola viruses. In the past, outbreaks were limited to the East and Central African tropical belt with the exception of Ebola Reston outbreaks that o...

  9. Defining risk groups to yellow fever vaccine-associated viscerotropic disease in the absence of denominator data.

    Science.gov (United States)

    Seligman, Stephen J; Cohen, Joel E; Itan, Yuval; Casanova, Jean-Laurent; Pezzullo, John C

    2014-02-01

    Several risk groups are known for the rare but serious, frequently fatal, viscerotropic reactions following live yellow fever virus vaccine (YEL-AVD). Establishing additional risk groups is hampered by ignorance of the numbers of vaccinees in factor-specific risk groups thus preventing their use as denominators in odds ratios (ORs). Here, we use an equation to calculate ORs using the prevalence of the factor-specific risk group in the population who remain well. The 95% confidence limits and P values can also be calculated. Moreover, if the estimate of the prevalence is imprecise, discrimination analysis can indicate the prevalence at which the confidence interval results in an OR of ∼1 revealing if the prevalence might be higher without yielding a non-significant result. These methods confirm some potential risk groups for YEL-AVD and cast doubt on another. They should prove useful in situations in which factor-specific risk group denominator data are not available.

  10. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: systematic review.

    Science.gov (United States)

    Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

    2011-06-20

    To identify the rate of serious adverse events attributable to yellow fever vaccination with 17D and 17DD strains reported in active and passive surveillance data. We conducted a systematic review of published literature on adverse events associated with yellow fever. We searched 9 electronic databases for peer reviewed and grey literature in all languages. There were no restrictions on date of publication. Reference lists of key studies were also reviewed to identify additional studies. We identified 66 relevant studies: 24 used active, 17 a combination of passive and active (15 of which were pharmacovigilance databases), and 25 passive surveillance. ACTIVE SURVEILLANCE: A total of 2,660,929 patients in general populations were followed for adverse events after vaccination, heavily weighted (97.7%) by one large Brazilian study. There were no observed cases of viscerotropic or neurotropic disease, one of anaphylaxis and 26 cases of urticaria (hypersensitivity). We also identified four studies of infants and children (n=2199), four studies of women (n=1334), and one study of 174 HIV+, and no serious adverse events were observed. PHARMACOVIGILANCE DATABASES: 10 of the 15 databases contributed data to this review, with 107,621,154 patients, heavily weighted (94%) by the Brazilian database. The estimates for Australia were low at 0/210,656 for "severe neurological disease" and 1/210,656 for YEL-AVD, and also low for Brazil with 9 hypersensitivity events, 0.23 anaphylactic shock events, 0.84 neurologic syndrome events and 0.19 viscerotropic events cases/million doses. The five analyses of partly overlapping periods for the US VAERS database provided an estimate of 6.6 YEL-AVD and YEL-AND cases per million, and estimates between 11.1 and 15.6 of overall "serious adverse events" per million. The estimates for the UK were higher at 34 "serious adverse events" and also for Switzerland with 14.6 "neurologic events" and 40 "serious events not neurological"/million doses

  11. The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

    Directory of Open Access Journals (Sweden)

    Galler R.

    1997-01-01

    Full Text Available The yellow fever (YF virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed

  12. Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

    Science.gov (United States)

    Silva, José V J; Lopes, Thaísa R R; Oliveira-Filho, Edmilson F de; Oliveira, Renato A S; Durães-Carvalho, Ricardo; Gil, Laura H V G

    2018-06-01

    Emerging and re-emerging viral infections transmitted by insect vectors (arthopode-borne viruses, arbovirus) are a serious threat to global public health. Among them, yellow fever (YFV), dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses are particularly important in tropical and subtropical regions. Although vector control is one of the most used prophylactic measures against arboviruses, it often faces obstacles, such as vector diversity, uncontrolled urbanization and increasing resistance to insecticides. In this context, vaccines may be the best control strategy for arboviral diseases. Here, we provide a general overview about licensed vaccines and the most advanced vaccine candidates against YFV, DENV, CHIKV and ZIKV. In particular, we highlight vaccine difficulties, the current status of the most advanced strategies and discuss how the molecular characteristics of each virus can influence the choice of the different vaccine formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Efficacy and Duration of Immunity after Yellow Fever Vaccination: Systematic Review on the Need for a Booster Every 10 Years

    Science.gov (United States)

    Gotuzzo, Eduardo; Yactayo, Sergio; Córdova, Erika

    2013-01-01

    Current regulations stipulate a yellow fever (YF) booster every 10 years. We conducted a systematic review of the protective efficacy and duration of immunity of YF vaccine in residents of disease-endemic areas and in travelers to assess the need for a booster in these two settings and in selected populations (human immunodeficiency virus–infected persons, infants, children, pregnant women, and severely malnourished persons). Thirty-six studies and 22 reports were included. We identified 12 studies of immunogenicity, 8 of duration of immunity, 8 of vaccine response in infants and children, 7 of human-immunodeficiency virus–infected persons, 2 of pregnant women, and 1 of severely malnourished children. Based on currently available data, a single dose of YF vaccine is highly immunogenic and confers sustained life-long protective immunity against YF. Therefore, a booster dose of YF vaccine is not needed. Special considerations for selected populations are detailed. PMID:24006295

  14. Yellow fever in Pará State, Amazon region of Brazil, 1998-1999: entomologic and epidemiologic findings.

    Science.gov (United States)

    Vasconcelos, P F; Rosa, A P; Rodrigues, S G; Rosa, E S; Monteiro, H A; Cruz, A C; Barros, V L; Souza, M R; Rosa, J F

    2001-01-01

    Yellow fever (YF) is frequently associated with high severity and death rates in the Amazon region of Brazil. During the rainy seasons of 1998 and 1999, 23 (eight deaths) and 34 (eight deaths) human cases of YF were reported, respectively, in different geographic areas of Pará State; most cases were on Marajó Island. Patients were 1 to 46 years of age. Epidemiologic and ecological studies were conducted in Afuá and Breves on Marajó Island; captured insects yielded isolates of 4 and 11 YF strains, respectively, from Haemagogus janthinomys pooled mosquitoes. The cases on Marajó Island in 1999 resulted from lack of vaccination near the focus of the disease and intense migration, which brought many nonimmune people to areas where infected vectors were present. We hypothesize that YF virus remains in an area after an outbreak by vertical transmission among Haemagogus mosquitoes.

  15. Medical and Indirect Costs Associated with a Rocky Mountain Spotted Fever Epidemic in Arizona, 2002-2011.

    Science.gov (United States)

    Drexler, Naomi A; Traeger, Marc S; McQuiston, Jennifer H; Williams, Velda; Hamilton, Charlene; Regan, Joanna J

    2015-09-01

    Rocky Mountain spotted fever (RMSF) is an emerging public health issue on some American Indian reservations in Arizona. RMSF causes an acute febrile illness that, if untreated, can cause severe illness, permanent sequelae requiring lifelong medical support, and death. We describe costs associated with medical care, loss of productivity, and death among cases of RMSF on two American Indian reservations (estimated population 20,000) between 2002 and 2011. Acute medical costs totaled more than $1.3 million. This study further estimated $181,100 in acute productivity lost due to illness, and $11.6 million in lifetime productivity lost from premature death. Aggregate costs of RMSF cases in Arizona 2002-2011 amounted to $13.2 million. We believe this to be a significant underestimate of the cost of the epidemic, but it underlines the severity of the disease and need for a more comprehensive study. © The American Society of Tropical Medicine and Hygiene.

  16. Medical and Indirect Costs Associated with a Rocky Mountain Spotted Fever Epidemic in Arizona, 2002–2011

    Science.gov (United States)

    Drexler, Naomi A.; Traeger, Marc S.; McQuiston, Jennifer H.; Williams, Velda; Hamilton, Charlene; Regan, Joanna J.

    2015-01-01

    Rocky Mountain spotted fever (RMSF) is an emerging public health issue on some American Indian reservations in Arizona. RMSF causes an acute febrile illness that, if untreated, can cause severe illness, permanent sequelae requiring lifelong medical support, and death. We describe costs associated with medical care, loss of productivity, and death among cases of RMSF on two American Indian reservations (estimated population 20,000) between 2002 and 2011. Acute medical costs totaled more than $1.3 million. This study further estimated $181,100 in acute productivity lost due to illness, and $11.6 million in lifetime productivity lost from premature death. Aggregate costs of RMSF cases in Arizona 2002–2011 amounted to $13.2 million. We believe this to be a significant underestimate of the cost of the epidemic, but it underlines the severity of the disease and need for a more comprehensive study. PMID:26033020

  17. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Florian Douam

    2017-08-01

    Full Text Available Yellow fever virus (YFV is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β signaling and type II interferon (IFN-γ signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ integrates into this antiviral system. Here, we report that while wild-type (WT and IFN-λ receptor knockout (λR−/− mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR−/− mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB. α/βR−/− λR−/− mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity.

  18. Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients after a preventive immunisation campaign in Mali.

    Science.gov (United States)

    Sidibe, Mariam; Yactayo, Sergio; Kalle, Abdoulaye; Sall, Amadou A; Sow, Samba; Ndoutabe, Modjirom; Perea, William; Avokey, Fenella; Lewis, Rosamund F; Veit, Olivia

    2012-07-01

    The immune response to yellow fever (YF) vaccine and its safety among HIV-infected individuals living in YF endemic areas is not well understood. Following a national YF preventive immunisation campaign in Mali in April 2008, we assessed the immunogenicity and safety of 17D yellow fever vaccine (17DV) among HIV-infected patients in two HIV treatment centres in Bamako, Mali, by testing for neutralising antibodies and identifying serious adverse events following immunisation (AEFI). A YF neutralisation titre (NT) of 1:≥20 was considered to be adequate and protective. A serious AEFI included hospitalisation, any life-threatening condition, or death, occurring within 30 days following 17DV administration. Of 115 HIV-infected patients who reported having received 17DV, 110 (96%) were on combination antiretroviral therapy and 83 patients were tested for neutralising antibodies. Around the time of vaccination, median CD4 cell count was 389 cells/mm(3) (IQR 227-511cells/mm(3)); HIV-RNA was undetectable in 24 of 46 patients tested. Seventy-six (92%) of 83 participants had adequate immune titres 9 months after the immunisation campaign. Previous vaccination or flavivirus exposure could contribute to this finding. No serious AEFI was found in the 115 participants. In this small series, YF vaccine appeared to be immunogenic with a favourable safety profile in HIV-infected patients on antiretroviral therapy. Higher CD4 cell counts and suppressed HIV-RNA were associated with the presence of an adequate immune titre and higher NTs. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  19. Pre-epidemic preparedness and the control of Lassa fever in ...

    African Journals Online (AJOL)

    The country seems not to have learnt from past epidemics most especially the 2014 Ebola Virus Disease (EVD) outbreak. After the declaration of Nigeria EVD free, most control arsenals were relaxed, isolation and quarantine structures were dismantled and preventive efforts such as provision of Personal Protective ...

  20. The 2007-2010 Q fever epidemic in the Netherlands: risk factors and risk groups

    NARCIS (Netherlands)

    van der Hoek, W.

    2012-01-01

    An analysis of 3,264 notifications for acute Q fever show that the patients were mostly men, smokers and persons aged 40–60 years. Pneumonia was the most common clinical presentation in >60% of patients. Fewer than 5% of the notified patients were working in the agriculture sector or meat-processing

  1. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.

    Science.gov (United States)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat; Jokinen, Jenny; Lukashevich, Igor S; Pushko, Peter

    2014-11-01

    Yellow fever (YF) causes an acute hemorrhagic fever disease in tropical Africa and Latin America. To develop a novel experimental YF vaccine, we applied iDNA infectious clone technology. The iDNA represents plasmid that encodes the full-length RNA genome of 17D vaccine downstream from a cytomegalovirus (CMV) promoter. The vaccine was designed to transcribe the full-length viral RNA and to launch 17D vaccine virus in vitro and in vivo. Transfection with 10 ng of iDNA plasmid was sufficient to start replication of vaccine virus in vitro. Safety of the parental 17D and iDNA-derived 17D viruses was confirmed in AG129 mice deficient in receptors for IFN-α/β/γ. Finally, direct vaccination of BALB/c mice with a single 20 μg dose of iDNA plasmid resulted in seroconversion and elicitation of virus-specific neutralizing antibodies in animals. We conclude that iDNA immunization approach combines characteristics of DNA and attenuated vaccines and represents a promising vaccination strategy for YF. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by transpositional insertion of a piggyBac vector.

    Science.gov (United States)

    Lobo, N F; Hua-Van, A; Li, X; Nolen, B M; Fraser, M J

    2002-04-01

    Mosquito-vectored diseases such as yellow fever and dengue fever continue to have a substantial impact on human populations world-wide. Novel strategies for control of these mosquito vectored diseases can arise through the development of reliable systems for genetic manipulation of the insect vector. A piggyBac vector marked with the Drosophila melanogaster cinnabar (cn) gene was used to transform the white-eyed khw strain of Aedes aegypti. Microinjection of preblastoderm embryos resulted in four families of cinnabar transformed insects. An overall transformation frequency of 4%, with a range of 0% to as high as 13% for individual experiments, was achieved when using a heat-shock induced transposase providing helper plasmid. Southern hybridizations indicated multiple insertion events in three of four transgenic lines, while the presence of duplicated target TTAA sites at either ends of individual insertions confirmed characteristic piggyBac transposition events in these three transgenic lines. The transgenic phenotype has remained stable for more than twenty generations. The transformations effected using the piggyBac element establish the potential of this element as a germ-line transformation vector for Aedine mosquitoes.

  3. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania.

    Science.gov (United States)

    Mweya, Clement N; Kimera, Sharadhuli I; Mellau, Lesakit S B; Mboera, Leonard E G

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC) light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. A total of 1,823 mosquitoes were collected, of which 87% (N=1,588) were Culex pipiens complex, 12% (N=226) Aedes aegypti, and 0.5% (N=9) Anopheles species. About two-thirds (67%; N=1,095) of C. pipiens complex and nearly 100% (N=225) of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78%) of C. pipiens complex and most (85%) of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

  4. Inter-epidemic abundance and distribution of potential mosquito vectors for Rift Valley fever virus in Ngorongoro district, Tanzania

    Directory of Open Access Journals (Sweden)

    Clement N. Mweya

    2015-01-01

    Full Text Available Background: Rift Valley fever (RVF is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. Objective: To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. Methods: A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. Results: A total of 1,823 mosquitoes were collected, of which 87% (N=1,588 were Culex pipiens complex, 12% (N=226 Aedes aegypti, and 0.5% (N=9 Anopheles species. About two-thirds (67%; N=1,095 of C. pipiens complex and nearly 100% (N=225 of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78% of C. pipiens complex and most (85% of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. Conclusions: These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

  5. Fever

    Science.gov (United States)

    ... also cause fevers. Some examples are: Arthritis or connective tissue illnesses such as rheumatoid arthritis and systemic lupus erythematosus Ulcerative colitis and Crohn disease Vasculitis or periarteritis nodosa The first symptom of a cancer may be a fever. This is particularly true ...

  6. Fever

    Directory of Open Access Journals (Sweden)

    Tamas Bartfai

    2010-01-01

    Full Text Available Measurement of body temperature remains one of the most common ways to assess health. An increase in temperature above what is considered to be a normal value is inevitably regarded as a sure sign of disease and referred to with one simple word: fever. In this review, we summarize how research on fever allowed the identification of the exogenous and endogenous molecules and pathways mediating the fever response. We also show how temperature elevation is common to different pathologies and how the molecular components of the fever-generation pathway represent drug targets for antipyretics, such as acetylsalicylic acid, the first “blockbuster drug”. We also show how fever research provided new insights into temperature and energy homeostasis, and into treatment of infection and inflammation.

  7. Oropouche Fever: A Review

    Directory of Open Access Journals (Sweden)

    Hercules Sakkas

    2018-04-01

    Full Text Available Oropouche fever is an emerging zoonotic disease caused by Oropouche virus (OROV, an arthropod transmitted Orthobunyavirus circulating in South and Central America. During the last 60 years, more than 30 epidemics and over half a million clinical cases attributed to OROV infection have been reported in Brazil, Peru, Panama, Trinidad and Tobago. OROV fever is considered the second most frequent arboviral febrile disease in Brazil after dengue fever. OROV is transmitted through both urban and sylvatic transmission cycles, with the primary vector in the urban cycle being the anthropophilic biting midge Culicoides paraensis. Currently, there is no evidence of direct human-to-human OROV transmission. OROV fever is usually either undiagnosed due to its mild, self-limited manifestations or misdiagnosed because its clinical characteristics are similar to dengue, chikungunya, Zika and yellow fever, including malaria as well. At present, there is no specific antiviral treatment, and in the absence of a vaccine for effective prophylaxis of human populations in endemic areas, the disease prevention relies solely on vector control strategies and personal protection measures. OROV fever is considered to have the potential to spread across the American continent and under favorable climatic conditions may expand its geographic distribution to other continents. In view of OROV’s emergence, increased interest for formerly neglected tropical diseases and within the One Health concept, the existing knowledge and gaps of knowledge on OROV fever are reviewed.

  8. Oropouche Fever: A Review.

    Science.gov (United States)

    Sakkas, Hercules; Bozidis, Petros; Franks, Ashley; Papadopoulou, Chrissanthy

    2018-04-04

    Oropouche fever is an emerging zoonotic disease caused by Oropouche virus (OROV), an arthropod transmitted Orthobunyavirus circulating in South and Central America. During the last 60 years, more than 30 epidemics and over half a million clinical cases attributed to OROV infection have been reported in Brazil, Peru, Panama, Trinidad and Tobago. OROV fever is considered the second most frequent arboviral febrile disease in Brazil after dengue fever. OROV is transmitted through both urban and sylvatic transmission cycles, with the primary vector in the urban cycle being the anthropophilic biting midge Culicoides paraensis . Currently, there is no evidence of direct human-to-human OROV transmission. OROV fever is usually either undiagnosed due to its mild, self-limited manifestations or misdiagnosed because its clinical characteristics are similar to dengue, chikungunya, Zika and yellow fever, including malaria as well. At present, there is no specific antiviral treatment, and in the absence of a vaccine for effective prophylaxis of human populations in endemic areas, the disease prevention relies solely on vector control strategies and personal protection measures. OROV fever is considered to have the potential to spread across the American continent and under favorable climatic conditions may expand its geographic distribution to other continents. In view of OROV's emergence, increased interest for formerly neglected tropical diseases and within the One Health concept, the existing knowledge and gaps of knowledge on OROV fever are reviewed.

  9. Dengue and the risk of urban yellow fever reintroduction in São Paulo State, Brazil Dengue e risco da reintrodução da febre amarela urbana no Estado de São Paulo

    Directory of Open Access Journals (Sweden)

    Eduardo Massad

    2003-08-01

    Full Text Available OBJECTIVE: To propose a mathematical method for the estimation of the Basic Reproduction Number, R0, of urban yellow fever in a dengue-infested area. METHODS: The method is based on the assumption that, as the same vector (Aedes aegypti causes both infections, all the quantities related to the mosquito, estimated from the initial phase of dengue epidemic, could be applied to yellow fever dynamics. It is demonstrated that R0 for yellow fever is, on average, 43% lower than that for dengue. This difference is due to the longer dengue viremia and its shorter extrinsic incubation period. RESULTS: In this study the analysis was expanded to the epidemiological situation of dengue in São Paulo in the year 2001. The total number of dengue cases increased from 3,582 in 2000 to 51,348 in 2001. It was then calculated R0 for yellow fever for every city which have shown R0 of dengue greater than 1. It was also estimated the total number of unprotected people living in highly risky areas for urban yellow fever. CONCLUSIONS: Currently there is a great number of non-vaccinated people living in Aedes aegypti infested area in the state of São Paulo.OBJETIVO: Propor um modelo matemático para a estimativa da reprodutibilidade basal, R0, para a febre amarela urbana em uma área infestada pela dengue. MÉTODOS: O método utilizado considera que, como ambas as doenças são transmitidas pelo mesmo vetor (Aedes aegypti, poder-se-ia aplicar todos os parâmetros quantitativos relativos ao mosquito, estimados pela fase inicial da curva de crescimento de casos de dengue, à dinâmica da febre amarela. Demonstra-se que o R0 da febre amarela é em média 43% menor que o da dengue. Esta diferença deve-se à viremia mais prolongada da dengue, bem como ao menor período de incubação extrínseco daquele vírus no mosquito. RESULTADOS: Apresenta-se a aplicação desta análise matemática à situação epidemiológica da dengue no estado de São Paulo, para o ano de 2001

  10. The rubber plantation environment and Lassa fever epidemics in Liberia, 2008-2012: a spatial regression.

    Science.gov (United States)

    Olugasa, Babasola O; Dogba, John B; Ogunro, Bamidele; Odigie, Eugene A; Nykoi, Jomah; Ojo, Johnson F; Taiwo, Olalekan; Kamara, Abraham; Mulbah, Charles K; Fasunla, Ayotunde J

    2014-10-01

    As Lassa fever continues to be a public health challenge in West Africa, it is critical to produce good maps of its risk pattern for use in active surveillance and control intervention. We identified eight spatial features related to the rubber plantation environment and used them as explanatory variables for Lassa fever (LF) outbreaks on the Uniroyal Liberian Agricultural Company (LAC) rubber plantation environment in Grand Bassa County, Liberia. We computed classical and spatial lag regression models on all spatial features, including proximity of residential camp to rubber tree-edge, main road in the plantation, LAC hospital, rice farmland, household refuse dump, human population density, post-harvest storage density of rice and density of rodent deterrent on rice storage. We found significant (p=0.0024) spatial autocorrelation between LF cases and the spatial features we have considered. We concluded that the rubber plantation environment influenced Mastomys species' breeding and transmission of Lassa virus along spatial scale to humans. The risk factors identified in this study offered a baseline for more effective surveillance and control of LF in the post-civil conflict Liberia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.

    Science.gov (United States)

    Fernandez-Garcia, Maria Dolores; Meertens, Laurent; Chazal, Maxime; Hafirassou, Mohamed Lamine; Dejarnac, Ophélie; Zamborlini, Alessia; Despres, Philippe; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando; Jouvenet, Nolwenn; Amara, Ali

    2016-02-09

    The live attenuated yellow fever virus (YFV) vaccine 17D stands as a "gold standard" for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation. The yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry

  12. Characterization of recombinant yellow fever-dengue vaccine viruses with human monoclonal antibodies targeting key conformational epitopes.

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    Lecouturier, Valerie; Berry, Catherine; Saulnier, Aure; Naville, Sophie; Manin, Catherine; Girerd-Chambaz, Yves; Crowe, James E; Jackson, Nicholas; Guy, Bruno

    2018-04-26

    The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several dengue-endemic countries. Although the vaccine provides protection against dengue, the level of protection differs by serotype and warrants further investigation. We characterized the antigenic properties of each vaccine virus serotype using highly neutralizing human monoclonal antibodies (hmAbs) that bind quaternary structure-dependent epitopes. Specifically, we monitored the binding of dengue virus-1 (DENV-1; 1F4), DENV-2 (2D22) or DENV-3 (5J7) serotype-specific or DENV-1-4 cross-reactive (1C19) hmAbs to the four chimeric yellow fever-dengue vaccine viruses (CYD-1-4) included in phase III vaccine formulations using a range of biochemical and functional assays (dot blot, ELISA, surface plasmon resonance and plaque reduction neutralization assays). In addition, we used the "classic" live, attenuated DENV-2 vaccine serotype, immature CYD-2 viruses and DENV-2 virus-like particles as control antigens for anti-serotype-2 reactivity. The CYD vaccine serotypes were recognized by each hmAbs with the expected specificity, moreover, surface plasmon resonance indicated a high functional affinity interaction with the CYD serotypes. In addition, the hmAbs provided similar protection against CYD and wild-type dengue viruses in the in vitro neutralization assay. Overall, these findings demonstrate that the four CYD viruses used in clinical trials display key conformational and functional epitopes targeted by serotype-specific and/or cross-reactive neutralizing human antibodies. More specifically, we showed that CYD-2 displays serotype- specific epitopes present only on the mature virus. This indicates that the CYD-TDV has the ability to elicit antibody specificities which are similar to those induced by the wild type DENV. Future investigations will be needed to address the nature of CYD-TDV-induced responses after vaccine administration, and how these

  13. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

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    Douam, Florian; Soto Albrecht, Yentli E; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V; Ploss, Alexander

    2017-08-15

    Yellow fever virus (YFV) is an arthropod-borne flavivirus, infecting ~200,000 people worldwide annually and causing about 30,000 deaths. The live attenuated vaccine strain, YFV-17D, has significantly contributed in controlling the global burden of yellow fever worldwide. However, the viral and host contributions to YFV-17D attenuation remain elusive. Type I interferon (IFN-α/β) signaling and type II interferon (IFN-γ) signaling have been shown to be mutually supportive in controlling YFV-17D infection despite distinct mechanisms of action in viral infection. However, it remains unclear how type III IFN (IFN-λ) integrates into this antiviral system. Here, we report that while wild-type (WT) and IFN-λ receptor knockout (λR -/- ) mice were largely resistant to YFV-17D, deficiency in type I IFN signaling resulted in robust infection. Although IFN-α/β receptor knockout (α/βR -/- ) mice survived the infection, mice with combined deficiencies in both type I signaling and type III IFN signaling were hypersusceptible to YFV-17D and succumbed to the infection. Mortality was associated with viral neuroinvasion and increased permeability of the blood-brain barrier (BBB). α/βR -/- λR -/- mice also exhibited distinct changes in the frequencies of multiple immune cell lineages, impaired T-cell activation, and severe perturbation of the proinflammatory cytokine balance. Taken together, our data highlight that type III IFN has critical immunomodulatory and neuroprotective functions that prevent viral neuroinvasion during active YFV-17D replication. Type III IFN thus likely represents a safeguard mechanism crucial for controlling YFV-17D infection and contributing to shaping vaccine immunogenicity. IMPORTANCE YFV-17D is a live attenuated flavivirus vaccine strain recognized as one of the most effective vaccines ever developed. However, the host and viral determinants governing YFV-17D attenuation and its potent immunogenicity are still unknown. Here, we analyzed the

  14. [Rift Valley fever: sporadic infection of French military personnel outside currently recognized epidemic zones].

    Science.gov (United States)

    Durand, J P; Richecoeur, L; Peyrefitte, C; Boutin, J P; Davoust, B; Zeller, H; Bouloy, M; Tolou, H

    2002-01-01

    For three years the arbovirus surveillance unit of the Tropical Medicine Institute of the French Army Medical Corps (French acronym IMTSSA) in Marseille, France has been investigating causes of benign non-malarial febrile syndromes in French military personnel serving outside mainland France. The methodology used in N'Djamena consisted of sending frozen specimens collected concomitant with viremia, to Marseille for culture. During the rainy season of 2001, specimens were collected from a total of 50 febrile soldiers. Cultures allowed isolation and identification of two strains of Rift Valley virus. The risk of contamination exists not only in the field but also in mainland hospital departments treating infected patients. Routine serological diagnosis for Rift Valley fever must be DISCUSSED for all patients in the field or returning from Africa.

  15. Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

    Science.gov (United States)

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

    2015-01-01

    Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

  16. Innate immunity phenotypic features point toward simultaneous raise of activation and modulation events following 17DD live attenuated yellow fever first-time vaccination.

    Science.gov (United States)

    Martins, Marina Angela; Silva, Maria Luiza; Elói-Santos, Silvana Maria; Ribeiro, José Geraldo Leite; Peruhype-Magalhães, Vanessa; Marciano, Ana Paula Vieira; Homma, Akira; Kroon, Erna Geessien; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2008-02-26

    Detailed multiparametric phenotypic investigation aiming to characterize the kinetics of the innate immune response in the peripheral blood following 17DD yellow fever (17DD-YF) first-time vaccination was performed. Results showed increased frequency of monocytes and NK cell subpopulations besides unexpected up-regulation of granulocytes activation status (CD28+/CD23+ and CD28+/HLA-DR+, respectively). Up-regulation of Fcgamma-R and IL-10-R expression emerge as putative events underlying the mixed pattern of phenotypic features triggered by the 17DD yellow fever (17DD-YF) vaccination. Mixed pattern of chemokine receptors expression further support our hypothesis that a parallel establishment of activation/modulation microenvironment plays a pivotal role in the protective immunity triggered by the 17DD-YF vaccine.

  17. Not a polar island: yellow fever, Spanish medical research, and the struggle for scientific and political hegemony in late nineteenth century Cuba

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    Francisco Javier Martínez

    Full Text Available Abstract: This paper explores questions related to yellow fever and the political destiny of Cuba in the late nineteenth century. A forgotten therapeutic device to treat the disease invented in that period, the “polar chamber” (cámara polar, provides a useful standpoint for reconstructing the tradition of Spanish yellow fever research in Cuba, a topic largely neglected by the medical historiography. The failed history of this device can also illuminate the complex struggle for scientific hegemony between Spanish, Cuban, and US institutions and researchers. Finally, we focus on the politics of the polar chamber by analyzing how this invention intended to provide a particular solution for the complex, threefold struggle for Cuba’s political future.

  18. Building a Species Conservation Strategy for the brown howler monkey (Alouatta guariba clamitans) in Argentina in the context of yellow fever outbreaks

    OpenAIRE

    Agostini, Ilaria; Holzmann, Ingrid; Di Bitetti, Mario Santiago; Oklander, Luciana Inés; Kowalewski, Martín M.; Beldomenico, Pablo Martín; Goenaga, Silvina; Martinez, Mariela; Moreno, Eduardo S.; Lestani, Eduardo; Desbiez, Arnaud L.J.; Miller, Philip

    2017-01-01

    The brown howler monkey (Alouatta guariba clamitans) is endemic to South America’s Atlantic Forest, with a small population extending into the northern portion of Misiones province in northeastern Argentina. In 2012, the species was classified as Critically Endangered in Argentina due to its highly restricted distribution, low population density and dramatic declines from recent Yellow Fever outbreaks. In March 2013, we organized an international workshop in Misiones to evaluate population st...

  19. The early use of yellow fever virus strain 17D for vaccine production in Brazil - a review

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    Paulo Roberto Post

    2001-08-01

    Full Text Available The use of yellow fever (YF virus 17D strain for vaccine production adapted in Brazil since its introduction in 1937 was reviewed. This was possible due to the availability of official records of vaccine production. The retrieved data highlight the simultaneous use of several serially passaged 17D substrain viruses for both inocula and vaccine preparation that allowed uninterrupted production. Substitution of these substrain viruses became possible with the experience gained during quality control and human vaccination. Post-vaccinal complications in humans and the failure of some viruses in quality control tests (neurovirulence for monkeys indicated that variables needed to be reduced during vaccine production, leading to the development of the seed lot system. The 17DD substrain, still used today, was the most frequently used substrain and the most reliable in terms of safety and efficacy. For this reason, it is possible to derive an infectious cDNA clone of this substrain combined with production in cell culture that could be used to direct the expression of heterologous antigens and lead to the development of new live vaccines.

  20. Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

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    Galler R.

    2005-01-01

    Full Text Available A chimeric yellow fever (YF-dengue serotype 2 (dengue 2 virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

  1. Immunogenicity of Yellow Fever Vaccine Coadministered With MenAfriVac in Healthy Infants in Ghana and Mali.

    Science.gov (United States)

    Roy Chowdhury, Panchali; Meier, Christian; Laraway, Hewad; Tang, Yuxiao; Hodgson, Abraham; Sow, Samba O; Enwere, Godwin C; Plikaytis, Brian D; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Niedrig, Matthias

    2015-11-15

    Yellow fever (YF) is still a major public health problem in endemic regions of Africa and South America. In Africa, one of the main control strategies is routine vaccination within the Expanded Programme on Immunization (EPI). A new meningococcal A conjugate vaccine (PsA-TT) is about to be introduced in the EPI of countries in the African meningitis belt, and this study reports on the immunogenicity of the YF-17D vaccines in infants when administered concomitantly with measles vaccine and PsA-TT. Two clinical studies were conducted in Ghana and in Mali among infants who received PsA-TT concomitantly with measles and YF vaccines at 9 months of age. YF neutralizing antibody titers were measured using a microneutralization assay. In both studies, the PsA-TT did not adversely affect the immune response to the concomitantly administered YF vaccine at the age of 9 months. The magnitude of the immune response was different between the 2 studies, with higher seroconversion and seroprotection rates found in Mali vs Ghana. Immunogenicity to YF vaccine is unaffected when coadministered with PsA-TT at 9 months of age. Further studies are warranted to better understand the determinants of the immune response to YF vaccine in infancy. ISRCTN82484612 (PsA-TT-004); PACTR201110000328305 (PsA-TT-007). © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  2. Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA.

    Science.gov (United States)

    Samuel, Glady Hazitha; Wiley, Michael R; Badawi, Atif; Adelman, Zach N; Myles, Kevin M

    2016-11-29

    Mosquito-borne flaviviruses, including yellow fever virus (YFV), Zika virus (ZIKV), and West Nile virus (WNV), profoundly affect human health. The successful transmission of these viruses to a human host depends on the pathogen's ability to overcome a potentially sterilizing immune response in the vector mosquito. Similar to other invertebrate animals and plants, the mosquito's RNA silencing pathway comprises its primary antiviral defense. Although a diverse range of plant and insect viruses has been found to encode suppressors of RNA silencing, the mechanisms by which flaviviruses antagonize antiviral small RNA pathways in disease vectors are unknown. Here we describe a viral suppressor of RNA silencing (VSR) encoded by the prototype flavivirus, YFV. We show that the YFV capsid (YFC) protein inhibits RNA silencing in the mosquito Aedes aegypti by interfering with Dicer. This VSR activity appears to be broadly conserved in the C proteins of other medically important flaviviruses, including that of ZIKV. These results suggest that a molecular "arms race" between vector and pathogen underlies the continued existence of flaviviruses in nature.

  3. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    Science.gov (United States)

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  4. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development.

    Science.gov (United States)

    Franco, David; Li, Wenjing; Qing, Fang; Stoyanov, Cristina T; Moran, Thomas; Rice, Charles M; Ho, David D

    2010-08-09

    The failure to develop an effective vaccine against HIV-1 infection has led the research community to seek new ways of raising qualitatively different antibody and cellular immune responses. Towards this goal, we investigated the yellow fever 17D vaccine strain (YF17D), one of the most effective vaccines ever made, as a platform for HIV-1 vaccine development. A test antigen, HIV-1 p24 (clade B consensus), was inserted near the 5' end of YF17D, in frame and upstream of the polyprotein (YF-5'/p24), or between the envelope and the first non-structural protein (YF-E/p24/NS1). In vitro characterization of these recombinants indicated that the gene insert was more stable in the context of YF-E/p24/NS1. This was confirmed in immunogenicity studies in mice. CD8(+) IFN-gamma T-cell responses against p24 were elicited by the YF17D recombinants, as were specific CD4(+) T cells expressing IFN-gamma and IL-2. A balanced CD4(+) and CD8(+) T-cell response was notable, as was the polyfunctionality of the responding cells. Finally, the protective efficacy of the YF17D recombinants, particularly YF-E/p24/NS1, in mice challenged with a vaccinia expressing HIV-1 Gag was demonstrated. These results suggest that YF17D warrants serious consideration as a live-attenuated vector for HIV-1 vaccine development. Copyright 2010 Elsevier Ltd. All rights reserved.

  5. First report on invasion of yellow fever mosquito, Aedes aegypti, at Narita International Airport, Japan in August 2012.

    Science.gov (United States)

    Sukehiro, Nayu; Kida, Nori; Umezawa, Masahiro; Murakami, Takayuki; Arai, Naoko; Jinnai, Tsunesada; Inagaki, Shunichi; Tsuchiya, Hidetoshi; Maruyama, Hiroshi; Tsuda, Yoshio

    2013-01-01

    The invasion of the yellow fever mosquito Aedes aegypti at Narita International Airport, Japan was detected for the first time. During the course of routine vector surveillance at Narita International Airport, 27 Ae. aegypti adults emerged from larvae and pupae collected from a single larvitrap placed near No. 88 spot at passenger terminal 2 on August 8, 2012. After the appearance of Ae. aegypti in the larvitrap, we defined a 400-m buffer zone and started an intensive vector survey using an additional 34 larvitraps and 15 CO2 traps. International aircraft and passenger terminal 2 were also inspected, and one Ae. aegypti male was collected from the cargo space of an international aircraft from Darwin via Manila on August 28, 2012. Larvicide treatment with 1.5% fenitrothion was conducted in 64 catch basins and one ditch in the 400-m buffer zone. Twenty-four large water tanks were also treated at least once with 0.5% pyriproxyfen, an insect growth regulator. No Ae. aegypti eggs or adults were found during the 1-month intensive vector survey after finding larvae and pupae in the larvitrap. We concluded that Ae. aegypti had failed to establish a population at Narita International Airport.

  6. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  7. A mortality study of the last outbreak of yellow fever in Barcelona City (Spain in 1870 Estudio de la mortalidad del último brote de fiebre amarilla en la ciudad de Barcelona (España en 1870

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    Jaume Canela Soler

    2009-08-01

    Full Text Available Background: The last outbreak of yellow fever in the city of Barcelona, Spain, was caused by a ship arriving from Cuba. The objective of this study was to describe and analyze the epidemic of 1870 by using the available mortality data. Methods: The information on 1,235 deaths identified in the parochial registries was analyzed, using statistical and epidemiological procedures for epidemic outbreaks. Results: Mortality due to yellow fever was 549.7 per 100,000 inhabitants. The temporal distribution of the deaths showed two peaks at the end of September and October with the last fatalities occurring in December 1870. The distribution of the fatalities in the city's neighborhoods was unequal. In La Barceloneta, in particular, more fatalities were found in the streets adjacent to the port than in the most remote streets (r=0.83; pObjetivo: El último brote de fiebre amarilla en la ciudad de Barcelona, España, se originó a partir de un barco que venía de Cuba. El objetivo de este estudio es describir y analizar esa epidemia ocurrida en 1870, utilizando los datos disponibles de mortalidad. Métodos: La información de las 1235 defunciones identificadas en los registros parroquiales se ha analizado utilizando los procedimientos estadísticos y epidemiológicos para brotes epidémicos. Resultados: La tasa de mortalidad por fiebre amarilla fue de 549.7 por 100,000 habitantes. La distribución temporal de las muertes tenía dos modas en el final de septiembre y octubre, y los últimos muertos ocurrieron en diciembre de 1870. La distribución de las defunciones según los barrios de la ciudad fue desigual. En La Barceloneta, en particular, hubo mas muertos en las calles adyacentes al puerto que en las más lejanas (r=0,83; p<0,0001. Conclusiones: Este estudio muestra una distribución bimodal de la mortalidad por fiebre amarilla durante el brote, con un impacto alto en hombres adultos, y en el barrio de La Barceloneta.

  8. Assessment of risk of dengue and yellow fever virus transmission in three major Kenyan cities based on Stegomyia indices

    Science.gov (United States)

    Tchouassi, David P.; Bastos, Armanda D. S.; Sang, Rosemary

    2017-01-01

    Dengue (DEN) and yellow fever (YF) are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia) vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone), and Kisumu and Nairobi Counties (no documented DEN outbreaks). We surveyed water-holding containers for mosquito immature (larvae/pupae) indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season) in each County from October 2014-June 2016. House index (HI), Breteau index (BI) and Container index (CI) estimates based on Aedes (Stegomyia) immature infestations were compared by city and season. Aedes aegypti and Aedes bromeliae were the main Stegomyia species with significantly more positive houses outdoors (212) than indoors (88) (n = 900) (χ2 = 60.52, P < 0.0001). Overall, Ae. aegypti estimates of HI (17.3 vs 11.3) and BI (81.6 vs 87.7) were higher in Kilifi and Kisumu, respectively, than in Nairobi (HI, 0.3; BI,13). However, CI was highest in Kisumu (33.1), followed by Kilifi (15.1) then Nairobi (5.1). Aedes bromeliae indices were highest in Kilifi, followed by Kisumu, then Nairobi with HI (4.3, 0.3, 0); BI (21.3, 7, 0.7) and CI (3.3, 3.3, 0.3), at the respective sites. HI and BI for both species were highest in the long rains, compared to the short rains and dry seasons. We found strong positive correlations between the BI and CI, and BI and HI for Ae. aegypti, with the most productive container types being jerricans, drums, used/discarded containers and tyres. On the basis of established vector index thresholds, our findings suggest low-to-medium risk levels for urban YF and high DEN risk for Kilifi and Kisumu, whereas for Nairobi YF risk was low while DEN risk

  9. Assessment of risk of dengue and yellow fever virus transmission in three major Kenyan cities based on Stegomyia indices.

    Directory of Open Access Journals (Sweden)

    Sheila B Agha

    2017-08-01

    Full Text Available Dengue (DEN and yellow fever (YF are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone, and Kisumu and Nairobi Counties (no documented DEN outbreaks. We surveyed water-holding containers for mosquito immature (larvae/pupae indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season in each County from October 2014-June 2016. House index (HI, Breteau index (BI and Container index (CI estimates based on Aedes (Stegomyia immature infestations were compared by city and season. Aedes aegypti and Aedes bromeliae were the main Stegomyia species with significantly more positive houses outdoors (212 than indoors (88 (n = 900 (χ2 = 60.52, P < 0.0001. Overall, Ae. aegypti estimates of HI (17.3 vs 11.3 and BI (81.6 vs 87.7 were higher in Kilifi and Kisumu, respectively, than in Nairobi (HI, 0.3; BI,13. However, CI was highest in Kisumu (33.1, followed by Kilifi (15.1 then Nairobi (5.1. Aedes bromeliae indices were highest in Kilifi, followed by Kisumu, then Nairobi with HI (4.3, 0.3, 0; BI (21.3, 7, 0.7 and CI (3.3, 3.3, 0.3, at the respective sites. HI and BI for both species were highest in the long rains, compared to the short rains and dry seasons. We found strong positive correlations between the BI and CI, and BI and HI for Ae. aegypti, with the most productive container types being jerricans, drums, used/discarded containers and tyres. On the basis of established vector index thresholds, our findings suggest low-to-medium risk levels for urban YF and high DEN risk for Kilifi and Kisumu, whereas for Nairobi YF risk was low while DEN risk

  10. Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys

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    Gisela F. Trindade

    2008-06-01

    Full Text Available For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4. Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL-1 or 3.29 log10 copies mL-1. Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL-1 or 3.53 log10 copies mL-1. These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.Uma das principais propriedades a serem estabelecidas para o desenvolvimento de vacinas seguras e atenuadas de flavivirus,é a taxa de replicação viral. Neste trabalho, aplicamos a metodologia de amplificação pela reação em cadeia da polimerase em tempo real e titulação viral por plaqueamento para determinação da replicação do vírus 17DD (FA 17DD e recombinantes, expressando proteínas do envelope de dengue sorotipos 2 e 4 (17D-DENV-2 e 17D-DENV-4. As amostras de soros de macacos inoculados por via intracerebral ou subcutânea com FA 17DD ou 17D-DENV foram usadas para determinar e comparar a viremia induzida por estes vírus. A quantificação da carga viral em amostras de macacos inoculados por ambas as vias com FA 17DD sugere restrita capacidade de replicação com

  11. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

    Science.gov (United States)

    Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G

    2016-12-01

    HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

  12. Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study.

    Science.gov (United States)

    Kernéis, Solen; Launay, Odile; Ancelle, Thierry; Iordache, Laura; Naneix-Laroche, Véronique; Méchaï, Frédéric; Fehr, Thierry; Leroy, Jean-Philippe; Issartel, Bertrand; Dunand, Jean; van der Vliet, Diane; Wyplosz, Benjamin; Consigny, Paul-Henri; Hanslik, Thomas

    2013-09-01

    To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy. All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids. Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination. After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results. Copyright © 2013 by the American College of Rheumatology.

  13. 17D yellow fever vaccine elicits comparable long-term immune responses in healthy individuals and immune-compromised patients.

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    Wieten, R W; Goorhuis, A; Jonker, E F F; de Bree, G J; de Visser, A W; van Genderen, P J J; Remmerswaal, E B M; Ten Berge, I J M; Visser, L G; Grobusch, M P; van Leeuwen, E M M

    2016-06-01

    The 17D live attenuated yellow fever (YF) vaccine is contra-indicated in immune-compromised individuals and may elicit a suboptimal immunologic response. The aim of this study is to assess whether long-term immune responses against the YF vaccine are impaired in immune-compromised patients. Fifteen patients using different immunosuppressive drugs and 30 healthy individuals vaccinated 0-22 years ago were included. The serological response was measured using the plaque reduction neutralization test (PRNT). CD8(+) and CD4(+) T-cell responses were measured following proliferation and re-stimulation with YFV peptide pools. Phenotypic characteristics and cytokine responses of CD8(+) T-cells were determined using class I tetramers. The geometric mean titre of neutralizing antibodies was not different between the groups (p = 0.77). The presence of YFV-specific CD4(+) and CD8(+) T-cell did not differ between patients and healthy individuals (15/15, 100.0% vs. 29/30, 96.7%, p = 0.475). Time since vaccination correlated negatively with the number of YFV-specific CD8(+) T-cells (r = -0.66, p = 0.0045). Percentages of early-differentiated memory cells increased (r = 0.67, p = 0.017) over time. These results imply that YF vaccination is effective despite certain immunosuppressive drug regimens. An early-differentiated memory-like phenotype persisted, which is associated with effective expansion upon re-encounter with antigen, suggesting a potent memory T-cell pool remains. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  14. A Systems Vaccinology Approach Reveals Temporal Transcriptomic Changes of Immune Responses to the Yellow Fever 17D Vaccine.

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    Hou, Jue; Wang, Shuhui; Jia, Manxue; Li, Dan; Liu, Ying; Li, Zhengpeng; Zhu, Hong; Xu, Huifang; Sun, Meiping; Lu, Li; Zhou, Zhinan; Peng, Hong; Zhang, Qichen; Fu, Shihong; Liang, Guodong; Yao, Lena; Yu, Xuesong; Carpp, Lindsay N; Huang, Yunda; McElrath, Julie; Self, Steve; Shao, Yiming

    2017-08-15

    In this study, we used a systems vaccinology approach to identify temporal changes in immune response signatures to the yellow fever (YF)-17D vaccine, with the aim of comprehensively characterizing immune responses associated with protective immunity. We conducted a cohort study in which 21 healthy subjects in China were administered one dose of the YF-17D vaccine; PBMCs were collected at 0 h and then at 4 h and days 1, 2, 3, 5, 7, 14, 28, 84, and 168 postvaccination, and analyzed by transcriptional profiling and immunological assays. At 4 h postvaccination, genes associated with innate cell differentiation and cytokine pathways were dramatically downregulated, whereas receptor genes were upregulated, compared with their baseline levels at 0 h. Immune response pathways were primarily upregulated on days 5 and 7, accompanied by the upregulation of the transcriptional factors JUP, STAT1, and EIF2AK2. We also observed robust activation of innate immunity within 2 d postvaccination and a durable adaptive response, as assessed by transcriptional profiling. Coexpression network analysis indicated that lysosome activity and lymphocyte proliferation were associated with dendritic cell (DC) and CD4 + T cell responses; FGL2, NFAM1, CCR1, and TNFSF13B were involved in these associations. Moreover, individuals who were baseline-seropositive for Abs against another flavivirus exhibited significantly impaired DC, NK cell, and T cell function in response to YF-17D vaccination. Overall, our findings indicate that YF-17D vaccination induces a prompt innate immune response and DC activation, a robust Ag-specific T cell response, and a persistent B cell/memory B cell response. Copyright © 2017 by The American Association of Immunologists, Inc.

  15. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

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    Maria Dolores Fernandez-Garcia

    2016-02-01

    Full Text Available The live attenuated yellow fever virus (YFV vaccine 17D stands as a “gold standard” for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation.

  16. Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti.

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    Andrew F van den Hurk

    Full Text Available Incidence of disease due to dengue (DENV, chikungunya (CHIKV and yellow fever (YFV viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 10(4 times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.

  17. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

    Science.gov (United States)

    Hunt, Peter W.; Huang, Yong; Simoes, Marisol; Lima, Sheila B.; Freire, Marcos S.; Caiaffa-Filho, Helio H.; Hong, Marisa A.; Costa, Dayane Alves; Dias, Juliana Zanatta C.; Cerqueira, Natalia B.; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M.; Kallas, Esper G.

    2016-01-01

    Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio. PMID:27941965

  18. Applicability of the Monocyte Activation Test (MAT) in the quality control of the 17DD yellow fever vaccine.

    Science.gov (United States)

    de Mattos, Katherine Antunes; Navega, Elaine Cristina Azevedo; Silva, Vitor Fernandes; Almeida, Alessandra Santos; da Silva, Cristiane Caldeira; Presgrave, Octavio Augusto França; Junior, Daniel da Silva Guedes; Delgado, Isabella Fernandes

    2018-03-01

    The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016-2018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1β levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies. 2018 FRAME.

  19. Amplified fragment length polymorphism mapping of quantitative trait loci for malaria parasite susceptibility in the yellow fever mosquito Aedes aegypti.

    Science.gov (United States)

    Zhong, Daibin; Menge, David M; Temu, Emmanuel A; Chen, Hong; Yan, Guiyun

    2006-07-01

    The yellow fever mosquito Aedes aegypti has been the subject of extensive genetic research due to its medical importance and the ease with which it can be manipulated in the laboratory. A molecular genetic linkage map was constructed using 148 amplified fragment length polymorphism (AFLP) and six single-strand conformation polymorphism (SSCP) markers. Eighteen AFLP primer combinations were used to genotype two reciprocal F2 segregating populations. Each primer combination generated an average of 8.2 AFLP markers eligible for linkage mapping. The length of the integrated map was 180.9 cM, giving an average marker resolution of 1.2 cM. Composite interval mapping revealed a total of six QTL significantly affecting Plasmodium susceptibility in the two reciprocal crosses of Ae. aegypti. Two common QTL on linkage group 2 were identified in both crosses that had similar effects on the phenotype, and four QTL were unique to each cross. In one cross, the four main QTL accounted for 64% of the total phenotypic variance, and digenic epistasis explained 11.8% of the variance. In the second cross, the four main QTL explained 66% of the variance, and digenic epistasis accounted for 16% of the variance. The actions of these QTL were either dominance or underdominance. Our results indicated that at least three new QTL were mapped on chromosomes 1 and 3. The polygenic nature of susceptibility to P. gallinaceum and epistasis are important factors for significant variation within or among mosquito strains. The new map provides additional information useful for further genetic investigation, such as identification of new genes and positional cloning.

  20. Emergency Risk Communication: Lessons Learned from a Rapid Review of Recent Gray Literature on Ebola, Zika, and Yellow Fever.

    Science.gov (United States)

    Toppenberg-Pejcic, Deborah; Noyes, Jane; Allen, Tomas; Alexander, Nyka; Vanderford, Marsha; Gamhewage, Gaya

    2018-03-20

    A rapid review of gray literature from 2015 to 2016 was conducted to identify the lessons learned for emergency risk communication from recent outbreaks of Ebola, Zika, and yellow fever. Gray literature databases and key websites were searched and requests for documents were posted to expert networks. A total of 83 documents met inclusion criteria, 68 of which are cited in this report. This article focuses on the 3 questions, out of 12 posed by World Health Organization as part of a Guideline development process, dealing most directly with communicating risk during health emergencies: community engagement, trust building, and social media. Documents were evaluated for credibility using an Authority, Accuracy, Coverage, Objectivity, Date, Significance (AACODS) checklist? and if the document contained a study, a method-specific tool was applied. A rapid content analysis of included sources was undertaken with relevant text either extracted verbatim or summarized and mapped against the questions. A database subset was created for each question and citations were assigned to the subset(s) for which they contained relevant information. Multiple designations per document were common. Database subsets were used to synthesize the results into a coherent narrative. The gray literature strongly underlines the central importance of local communities. A one-size-fits-all approach does not work. For maximum effectiveness, local communities need to be involved with and own emergency risk communication processes, preferably well before an emergency occurs. Social media can open new avenues for communication, but is not a general panacea and should not be viewed as a replacement for traditional modes of communication. In general, the gray literature indicates movement toward greater recognition of emergency risk communication as a vitally important element of public health.

  1. Imidacloprid impairs the post-embryonic development of the midgut in the yellow fever mosquito Stegomyia aegypti (=Aedes aegypti).

    Science.gov (United States)

    Fernandes, K M; Gonzaga, W G; Pascini, T V; Miranda, F R; Tomé, H V V; Serrão, J E; Martins, G F

    2015-09-01

    The mosquito Stegomyia aegypti (=Aedes aegypti) (Diptera: Culicidae) is a vector for the dengue and yellow fever viruses. As blood digestion occurs in the midgut, this organ constitutes the route of entry of many pathogens. The effects of the insecticide imidacloprid on the survival of St. aegypti were investigated and the sub-lethal effects of the insecticide on midgut development were determined. Third instar larvae were exposed to different concentrations of imidacloprid (0.15, 1.5, 3.0, 6.0 and 15.0 p.p.m.) and survival was monitored every 24 h for 10 days. Midguts from imidacloprid-treated insects at different stages of development were dissected and processed for analyses by transmission electron microscopy, immunofluorescence microscopy and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assays. Imidacloprid concentrations of 3.0 and 15.0 p.p.m. were found to affect midgut development similarly. Digestive cells of the fourth instar larvae (L4) midgut exposed to imidacloprid had more multilamellar bodies, abundantly found in the cell apex, and more electron-lucent vacuoles in the basal region compared with those from untreated insects. Moreover, imidacloprid interfered with the differentiation of regenerative cells, dramatically reducing the number of digestive and endocrine cells and leading to malformation of the midgut epithelium in adults. The data demonstrate that imidacloprid can reduce the survival of mosquitoes and thus indicate its potentially high efficacy in the control of St. aegypti populations. © 2015 The Royal Entomological Society.

  2. Predicting Rift Valley Fever Inter-epidemic Activities and Outbreak Patterns: Insights from a Stochastic Host-Vector Model.

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    Sansao A Pedro

    2016-12-01

    Full Text Available Rift Valley fever (RVF outbreaks are recurrent, occurring at irregular intervals of up to 15 years at least in East Africa. Between outbreaks disease inter-epidemic activities exist and occur at low levels and are maintained by female Aedes mcintoshi mosquitoes which transmit the virus to their eggs leading to disease persistence during unfavourable seasons. Here we formulate and analyse a full stochastic host-vector model with two routes of transmission: vertical and horizontal. By applying branching process theory we establish novel relationships between the basic reproduction number, R0, vertical transmission and the invasion and extinction probabilities. Optimum climatic conditions and presence of mosquitoes have not fully explained the irregular oscillatory behaviour of RVF outbreaks. Using our model without seasonality and applying van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how outbreaks multi-year periodicity varies with the vertical transmission. Our theory predicts complex fluctuations with a dominant period of 1 to 10 years which essentially depends on the efficiency of vertical transmission. Our predictions are then compared to temporal patterns of disease outbreaks in Tanzania, Kenya and South Africa. Our analyses show that interaction between nonlinearity, stochasticity and vertical transmission provides a simple but plausible explanation for the irregular oscillatory nature of RVF outbreaks. Therefore, we argue that while rainfall might be the major determinant for the onset and switch-off of an outbreak, the occurrence of a particular outbreak is also a result of a build up phenomena that is correlated to vertical transmission efficiency.

  3. A dynamic case definition is warranted for adequate notification in an extended epidemic setting: the Dutch Q fever outbreak 2007-2009 as exemplar.

    Science.gov (United States)

    Jaramillo-Gutierrez, G; Wegdam-Blans, M C; ter Schegget, R; Korbeeck, J M; van Aken, R; Bijlmer, H A; Tjhie, J H; Koopmans, M P

    2013-10-10

    Q fever is a notifiable disease in the Netherlands:laboratories are obliged to notify possible cases to the Municipal Health Services. These services then try to reconfirm cases with additional clinical and epidemiological data and provide anonymised reports to the national case register of notifiable diseases. Since the start of the 2007–2009 Dutch Q fever outbreak,notification rules remained unchanged, despite new laboratory insights and altered epidemiology. In this study, we retrospectively analysed how these changes influenced the proportion of laboratory-defined acute Q fever cases (confirmed, probable and possible)that were included in the national case register, during(2009) and after the outbreak (2010 and 2011).The number of laboratory-defined cases notified to the Municipal Health Services was 377 in 2009, 96 in 2010 and 50 in 2011. Of these, 186 (49.3%) in 2009, 12(12.5%) in 2010 and 9 (18.0%) in 2011 were confirmed as acute infection by laboratory interpretation. The proportion of laboratory-defined acute Q fever cases that was reconfirmed by the Municipal Health Services and that were included in the national case register decreased from 90% in 2009, to 22% and 24% in 2010 and 2011, respectively. The decrease was observed in all categories of cases, including those considered to be confirmed by laboratory criteria. Continued use ofa pre-outbreak case definition led to over-reporting of cases to the Municipal Health Services in the post-epidemic years. Therefore we recommend dynamic laboratory notification rules, by reviewing case definitions periodically in an ongoing epidemic, as in the Dutch Q fever outbreak.

  4. Implementation and validation of an economic module in the Be-FAST model to predict costs generated by livestock disease epidemics: Application to classical swine fever epidemics in Spain.

    Science.gov (United States)

    Fernández-Carrión, E; Ivorra, B; Martínez-López, B; Ramos, A M; Sánchez-Vizcaíno, J M

    2016-04-01

    Be-FAST is a computer program based on a time-spatial stochastic spread mathematical model for studying the transmission of infectious livestock diseases within and between farms. The present work describes a new module integrated into Be-FAST to model the economic consequences of the spreading of classical swine fever (CSF) and other infectious livestock diseases within and between farms. CSF is financially one of the most damaging diseases in the swine industry worldwide. Specifically in Spain, the economic costs in the two last CSF epidemics (1997 and 2001) reached jointly more than 108 million euros. The present analysis suggests that severe CSF epidemics are associated with significant economic costs, approximately 80% of which are related to animal culling. Direct costs associated with control measures are strongly associated with the number of infected farms, while indirect costs are more strongly associated with epidemic duration. The economic model has been validated with economic information around the last outbreaks in Spain. These results suggest that our economic module may be useful for analysing and predicting economic consequences of livestock disease epidemics. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Fever versus Fever: the role of host and vector susceptibility and interspecific competition in shaping the current and future distributions of the sylvatic cycles of dengue virus and yellow fever virus

    Science.gov (United States)

    Hanley, Kathryn A.; Monath, Thomas P.; Weaver, Scott C.; Rossi, Shannan L.; Richman, Rebecca L.; Vasilakis, Nikos

    2013-01-01

    Two different species of flaviviruses, dengue virus (DENV) and yellow fever virus (YFV), that originated in sylvatic cycles maintained in non-human primates and forest-dwelling mosquitoes have emerged repeatedly into sustained human-to-human transmission by Aedes aegypti mosquitoes. Sylvatic cycles of both viruses remain active, and where the two viruses overlap in West Africa they utilize similar suites of monkeys and Aedes mosquitoes. These extensive similarities render the differences in the biogeography and epidemiology of the two viruses all the more striking. First, the sylvatic cycle of YFV originated in Africa and was introduced into the New World, probably as a result of the slave trade, but is absent in Asia; in contrast, sylvatic DENV likely originated in Asia and has spread to Africa but not to the New World. Second, while sylvatic YFV can emerge into extensive urban outbreaks in humans, these invariably die out, whereas four different types of DENV have established human transmission cycles that are ecologically and evolutionarily distinct from their sylvatic ancestors. Finally, transmission of YFV among humans has been documented only in Africa and the Americas, whereas DENV is transmitted among humans across most of the range of competent Aedes vectors, which in the last decade has included every continent save Antarctica. This review summarizes current understanding of sylvatic transmission cycles of YFV and DENV, considers possible explanations for their disjunct distributions, and speculates on the potential consequences of future establishment of a sylvatic cycle of DENV in the Americas. PMID:23523817

  6. Diphtheria, tetanus, poliomyelitis, yellow fever and hepatitis B seroprevalence among HIV1-infected migrants. Results from the ANRS VIHVO vaccine sub-study.

    Science.gov (United States)

    Mullaert, Jimmy; Abgrall, Sophie; Lele, Nathalie; Batteux, Frederic; Slama, Lilia Ben; Meritet, Jean-Francois; Lebon, Pierre; Bouchaud, Olivier; Grabar, Sophie; Launay, Odile

    2015-09-11

    Few data are available on the seroprotection status of HIV1-infected patients with respect to vaccine-preventable diseases. To describe, in a population of HIV1-infected migrants on stable, effective ART therapy, the seroprevalence of diphtheria, poliomyelitis, tetanus, yellow fever antibodies and serostatus for hepatitis B, and to identify factors associated with seroprotection. Vaccine responses against diphtheria, tetanus, poliomyelitis and yellow fever were also studied. Sub-Saharan African patients participating in the ANRS-VIHVO cohort were enrolled prior to travel to their countries of origin. Serologic analyses were performed in a central laboratory before and after the trip. Univariate and multivariate logistic regression was used to identify factors associated with initial seroprotection. 250 patients (99 men and 151 women) were included in the seroprevalence study. Median age was 45 years (IQR 39-52), median CD4 cell count was 440/μL (IQR 336-571), and 237 patients (95%) had undetectable HIV1 viral load. The initial seroprevalence rates were 69.0% (95%CI 63.2-74.7) for diphtheria, 70.7% (95%CI 65.0-76.3) for tetanus, and 85.9% (95%CI 81.6-90.2) for yellow fever. Only 64.4% (95%CI 58.5-70.3) of patients had protective antibody titers against all three poliomyelitis vaccine strains before travel. No serological markers of hepatitis B were found in 18.6% of patients (95%CI 13.7-23.3). Patient declaration of prior vaccination was the only factor consistently associated with initial seroprotection. We found a low prevalence of seroprotection against diphtheria, poliomyelitis, tetanus and hepatitis B. HIV infected migrants living in France and traveling to their native countries need to have their vaccine schedule completed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Randomized, double-blind, multicenter study of the immunogenicity and reactogenicity of 17DD and WHO 17D-213/77 yellow fever vaccines in children: implications for the Brazilian National Immunization Program.

    Science.gov (United States)

    2007-04-20

    Vaccines against yellow fever currently recommended by the World Health Organization contain either virus sub-strains 17D or 17DD. In adults, the 17DD vaccine demonstrated high seroconversion and similar performance to vaccines manufactured with the WHO 17D-213/77 seed-lot. In another study, 17DD vaccine showed lower seroconversion rates in children younger than 2 years. Data also suggested lower seroconversion with simultaneous application of measles vaccine. This finding in very young children is not consistent with data from studies with 17D vaccines. A multicenter, randomized, double-blind clinical trial was designed (1) to compare the immunogenicity and reactogenicity of two yellow fever vaccines: 17DD (licensed product) and 17D-213/77 (investigational product) in children aged 9-23 months; (2) to assess the effect of simultaneous administration of yellow fever and the measles-mumps-rubella vaccines; and (3) to investigate the interference of maternal antibodies in the response to yellow fever vaccination. The anticipated implications of the results are changes in vaccine sub-strains used in manufacturing YF vaccine used in several countries and changes in the yellow fever vaccination schedule recommendations in national immunization programs.

  8. Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico border: results of a household-based seroepidemiologic survey, December 2005.

    Science.gov (United States)

    Ramos, Mary M; Mohammed, Hamish; Zielinski-Gutierrez, Emily; Hayden, Mary H; Lopez, Jose Luis Robles; Fournier, Marta; Trujillo, Alfredo Rodríguez; Burton, Roy; Brunkard, Joan M; Anaya-Lopez, Luis; Banicki, Allison Abell; Morales, Pablo Kuri; Smith, Brian; Muñoz, Jorge L; Waterman, Stephen H

    2008-03-01

    A dengue-2 epidemic causing dengue hemorrhagic fever (DHF) occurred in the contiguous border cities of Matamoros, Tamaulipas (Mexico), and Brownsville, TX, in 2005. In December, we conducted a household-based epidemiologic survey to determine the incidence and seroprevalence of dengue infection among Matamoros and Brownsville residents and to identify risk factors associated with infection. Antibodies to dengue were measured in 273 individuals. The estimated incidence of recent dengue infection was 32% and 4% among Matamoros and Brownsville participants, respectively. The estimated prevalence of past dengue infection was 77% and 39% among Matamoros and Brownsville participants, respectively. The Breteau index was 28 in Matamoros and 16 in Brownsville, reflecting an abundant winter population of Aedes mosquitoes. Discarded waste tires and buckets were the two largest categories of infested containers found in both cities. Our results underscore the risk for epidemic dengue and DHF in the Texas-Mexico border region.

  9. Modeling the Effects of Duration and Size of the Control Zones on the Consequences of a Hypothetical African Swine Fever Epidemic in Denmark

    DEFF Research Database (Denmark)

    Halasa, Tariq; Bøtner, Anette; Mortensen, Sten

    2018-01-01

    control an epidemic of ASF. A previously published and well documented simulation model for ASF virus spread between herds was used to examine the epidemiologic and economic impacts of the duration and size of the control zones around affected herds. In the current study, scenarios were run, where......African swine fever (ASF) is a notifiable infectious disease. The disease is endemic in certain regions in Eastern Europe constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning, it is important to continuously explore strategies that can effectively...... or clinical and serological surveillance of herds within the zones. Sensitivity analysis was conducted on influential input parameters in the model. The model predicts that reducing the duration of the protection and surveillance zones has no impact on the epidemiological consequences of the epidemics, while...

  10. Spatial and temporal abundance of three sylvatic yellow fever vectors in the influence area of the Manso hydroelectric power plant, Mato Grosso, Brazil.

    Science.gov (United States)

    Ribeiro, A L M; Miyazaki, R D; Silva, M; Zeilhofer, P

    2012-01-01

    Human biting catches of sylvatic yellow fever (SYF) vectors were conducted at eight stations in the influence area of the Manso hydroelectric power plant (Central Brazil) in sampling campaigns every 2 mo from July 2000 to November 2001. In total, 206 individuals were captured and classified as one of three species important for the transmission of SYF in Mato Grosso state: Haemagogus (Haemagogus) janthinomys (Dyar, 1921); Haemagogus (Conopostegus) leucocelaenus (Dyar & Shannon, 1924); and Sabethes (Sabethoides) chloropterus (Humboldt, 1819). The highest vector abundance was observed during the rainy season (November through March) and SYF vectors were present in all sampling points throughout the year, mainly in riparian and shadowed transitional forests at shadowed ramps.

  11. Feeding habits of mosquitoes (Diptera: Culicidae) in an area of sylvatic transmission of yellow fever in the state of São Paulo, Brazil.

    Science.gov (United States)

    Mucci, Luis Filipe; Júnior, Rubens Pinto Cardoso; de Paula, Marcia Bicudo; Scandar, Sirle Abdo Salloum; Pacchioni, Márcio Lunardeli; Fernandes, Aristides; Consales, Cleide Aschenbrenner

    2015-01-01

    The reintroduction of sylvatic yellow fever in the state of São Paulo after about six decades was confirmed in the Northwestern region in 2000, where in 2008 there also occurred an important epizootic. The purpose of this study was to investigate the feeding habits of culicids potentially involved in the sylvatic transmission of the virus in this region. Specimens were collected in 24 forested localities at ground level with hand nets and mouth aspirators. Collections were made quarterly between October 2006 and July 2008 during daylight hours. Blood-meal identification was carried out in mosquitoes of the tribes Aedini, Mansoniini and Sabethini. The biotin/avidin sandwich ELISA was employed to determine six source types: bird, bovine, equine, rat, human and monkey. A total of 24,879 females of the three tribes were obtained, 245 (0.98%) of which were engorged. The presence of three different blood sources per engorged female was the predominant situation, and included 35.10% of the total of samples processed. Samples with two or four different sources were represented by 25.31% and 25.71%, of the specimens, respectively, while just 9.39% had only one type and 1.22%, five different sources. Aedes scapularis, Ae. serratus (Group), Psorophora albigenu and Ps. ferox were the most abundant species and accounted for about 95% of the engorged specimens. Of the principal vector species, Haemagogus janthinomys/capricornii was found with bird, bovine and primate blood. These sources were predominant and alternated top ranking as the most frequent source according to the mosquito species and collection site. In general, primate blood was the most prevalent source. The human population of the region visits this ecotone frequently, which indicates the need for the periodical assessment of vaccination coverage against yellow fever. The frequency of non-human primate blood source in mosquito species that show minor vector importance in yellow fever virus transmission deserves

  12. Clustered lot quality assurance sampling: a tool to monitor immunization coverage rapidly during a national yellow fever and polio vaccination campaign in Cameroon, May 2009.

    Science.gov (United States)

    Pezzoli, L; Tchio, R; Dzossa, A D; Ndjomo, S; Takeu, A; Anya, B; Ticha, J; Ronveaux, O; Lewis, R F

    2012-01-01

    We used the clustered lot quality assurance sampling (clustered-LQAS) technique to identify districts with low immunization coverage and guide mop-up actions during the last 4 days of a combined oral polio vaccine (OPV) and yellow fever (YF) vaccination campaign conducted in Cameroon in May 2009. We monitored 17 pre-selected districts at risk for low coverage. We designed LQAS plans to reject districts with YF vaccination coverage LQAS proved to be useful in guiding the campaign vaccination strategy before the completion of the operations.

  13. 17DD and 17D-213/77 yellow fever substrains trigger a balanced cytokine profile in primary vaccinated children.

    Directory of Open Access Journals (Sweden)

    Ana Carolina Campi-Azevedo

    Full Text Available BACKGROUND: This study aimed to compare the cytokine-mediated immune response in children submitted to primary vaccination with the YF-17D-213/77 or YF-17DD yellow fever (YF substrains. METHODS: A non-probabilistic sample of eighty healthy primary vaccinated (PV children was selected on the basis of their previously known humoral immune response to the YF vaccines. The selected children were categorized according to their YF-neutralizing antibody titers (PRNT and referred to as seroconverters (PV-PRNT(+ or nonseroconverters (PV-PRNT(-. Following revaccination with the YF-17DD, the PV-PRNT(- children (YF-17D-213/77 and YF-17DD groups seroconverted and were referred as RV-PRNT(+. The cytokine-mediated immune response was investigated after short-term in vitro cultures of whole blood samples. The results are expressed as frequency of high cytokine producers, taking the global median of the cytokine index (YF-Ag/control as the cut-off. RESULTS: The YF-17D-213/77 and the YF-17DD substrains triggered a balanced overall inflammatory/regulatory cytokine pattern in PV-PRNT(+, with a slight predominance of IL-12 in YF-17DD vaccinees and a modest prevalence of IL-10 in YF-17D-213/77. Prominent frequency of neutrophil-derived TNF-α and neutrophils and monocyte-producing IL-12 were the major features of PV-PRNT(+ in the YF-17DD, whereas relevant inflammatory response, mediated by IL-12(+CD8(+ T cells, was the hallmark of the YF-17D-213/77 vaccinees. Both substrains were able to elicit particular but relevant inflammatory events, regardless of the anti-YF PRNT antibody levels. PV-PRNT(- children belonging to the YF-17DD arm presented gaps in the inflammatory cytokine signature, especially in terms of the innate immunity, whereas in the YF-17D-213/77 arm the most relevant gap was the deficiency of IL-12-producing CD8(+T cells. Revaccination with YF-17DD prompted a balanced cytokine profile in YF-17DD nonresponders and a robust inflammatory profile in YF-17D

  14. Identification and characterization of avian retroviruses in chicken embryo-derived yellow fever vaccines: investigation of transmission to vaccine recipients.

    Science.gov (United States)

    Hussain, Althaf I; Johnson, Jeffrey A; Da Silva Freire, Marcos; Heneine, Walid

    2003-01-01

    All currently licensed yellow fever (YF) vaccines are propagated in chicken embryos. Recent studies of chick cell-derived measles and mumps vaccines show evidence of two types of retrovirus particles, the endogenous avian retrovirus (EAV) and the endogenous avian leukosis virus (ALV-E), which originate from the chicken embryonic fibroblast substrates. In this study, we investigated substrate-derived avian retrovirus contamination in YF vaccines currently produced by three manufacturers (YF-vax [Connaught Laboratories], Stamaril [Aventis], and YF-FIOCRUZ [FIOCRUZ-Bio-Manguinhos]). Testing for reverse transcriptase (RT) activity was not possible because of assay inhibition. However, Western blot analysis of virus pellets with anti-ALV RT antiserum detected three distinct RT proteins in all vaccines, indicating that more than one source is responsible for the RTs present in the vaccines. PCR analysis of both chicken substrate DNA and particle-associated RNA from the YF vaccines showed no evidence of the long terminal repeat sequences of exogenous ALV subgroups A to D in any of the vaccines. In contrast, both ALV-E and EAV particle-associated RNA were detected at equivalent titers in each vaccine by RT-PCR. Quantitative real-time RT-PCR revealed 61,600, 348,000, and 1,665,000 ALV-E RNA copies per dose of Stamaril, YF-FIOCRUZ, and YF-vax vaccines, respectively. ev locus-specific PCR testing of the vaccine-associated chicken substrate DNA was positive both for the nondefective ev-12 locus in two vaccines and for the defective ev-1 locus in all three vaccines. Both intact and ev-1 pol sequences were also identified in the particle-associated RNA. To investigate the risks of transmission, serum samples from 43 YF vaccine recipients were studied. None of the samples were seropositive by an ALV-E-based Western blot assay or had detectable EAV or ALV-E RNA sequences by RT-PCR. YF vaccines produced by the three manufacturers all have particles containing EAV genomes and

  15. The first detected airline introductions of yellow fever mosquitoes (Aedes aegypti) to Europe, at Schiphol International airport, the Netherlands.

    Science.gov (United States)

    Ibañez-Justicia, A; Gloria-Soria, A; den Hartog, W; Dik, M; Jacobs, F; Stroo, A

    2017-12-08

    Air-borne introduction of exotic mosquitoes to Schiphol airport in the Netherlands has been considered plausible based upon findings of mosquitoes in aircraft cabins during 2008, 2010 and 2011. Beginning in 2013, surveillance efforts at Schiphol had focused on promptly detecting accidental introductions at the airport facilities in order to quickly react and avoid temporary proliferation or establishment of mosquito populations, identify the origin of the introductions, and avoid potential transmission of vector-borne diseases. BG-Mosquitaire mosquito traps were set at the most likely locations for arrival of the invasive Aedes mosquitoes as part of the mosquito monitoring program at Schiphol airport. Samples were collected bi-weekly. Upon detection of exotic specimens, information about the origin of the flights arriving to the particular location at the airport where specimens were captured was requested from airport authorities. The GIS tool Intersect was then used to identify airports of origin common to positive trapping locations during the specific trapping period. Captured Aedes aegypti mosquitoes were subsequently genotyped at 12 highly polymorphic microsatellite markers and compared to a reference database of 79 populations around the world to further narrow down their location of origin. In 2016, six adult yellow fever mosquitoes were captured indoors and outdoors at the airport of Schiphol in the Netherlands confirming, for the first time, air-borne transport of this mosquito vector species into Europe. Mosquitoes were captured during three time periods: June, September and October. Containers carried by aircrafts are considered the most likely pathway for this introduction. GIS analysis and genetic assignment tests on these mosquitoes point to North America or the Middle East as possible origins, but the small sample size prevents us from reliably identifying the geographic origin of this introduction. The arrival of Ae. aegypti mosquitoes to Schiphol

  16. Travelers' Health: Yellow Fever

    Science.gov (United States)

    ... Paraguay Peru 2 Suriname Trinidad and Tobago 2 Venezuela 2 1 Countries or areas where “a risk ... Vision Using this Site Legal Link to Us Policies FOIA Accessibility Privacy No FEAR Act Inspector General ...

  17. Blood Meal Analysis of and Virus Detection in Mosquitoes Collected during a Rift Valley fever Epizootic/Epidemic: Implications for epidemic disease transmission dynamics

    Science.gov (United States)

    Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were screened for v...

  18. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    Directory of Open Access Journals (Sweden)

    Marco A B Almeida

    2014-03-01

    Full Text Available In Brazil, epizootics among New World monkey species may indicate circulation of yellow fever (YF virus and provide early warning of risk to humans. Between 1999 and 2001, the southern Brazilian state of Rio Grande do Sul initiated surveillance for epizootics of YF in non-human primates to inform vaccination of human populations. Following a YF outbreak, we analyzed epizootic surveillance data and assessed YF vaccine coverage, timeliness of implementation of vaccination in unvaccinated human populations. From October 2008 through June 2009, circulation of YF virus was confirmed in 67 municipalities in Rio Grande do Sul State; vaccination was recommended in 23 (34% prior to the outbreak and in 16 (24% within two weeks of first epizootic report. In 28 (42% municipalities, vaccination began more than two weeks after first epizootic report. Eleven (52% of 21 laboratory-confirmed human YF cases occurred in two municipalities with delayed vaccination. By 2010, municipalities with confirmed YF epizootics reported higher vaccine coverage than other municipalities that began vaccination. In unvaccinated human populations timely response to epizootic events is critical to prevent human yellow fever cases.

  19. The synergistic effect of combined immunization with a DNA vaccine and chimeric yellow fever/dengue virus leads to strong protection against dengue.

    Directory of Open Access Journals (Sweden)

    Adriana S Azevedo

    Full Text Available The dengue envelope glycoprotein (E is the major component of virion surface and its ectodomain is composed of domains I, II and III. This protein is the main target for the development of a dengue vaccine with induction of neutralizing antibodies. In the present work, we tested two different vaccination strategies, with combined immunizations in a prime/booster regimen or simultaneous inoculation with a DNA vaccine (pE1D2 and a chimeric yellow fever/dengue 2 virus (YF17D-D2. The pE1D2 DNA vaccine encodes the ectodomain of the envelope DENV2 protein fused to t-PA signal peptide, while the YF17D-D2 was constructed by replacing the prM and E genes from the 17D yellow fever vaccine virus by those from DENV2. Balb/c mice were inoculated with these two vaccines by different prime/booster or simultaneous immunization protocols and most of them induced a synergistic effect on the elicited immune response, mainly in neutralizing antibody production. Furthermore, combined immunization remarkably increased protection against a lethal dose of DENV2, when compared to each vaccine administered alone. Results also revealed that immunization with the DNA vaccine, regardless of the combination with the chimeric virus, induced a robust cell immune response, with production of IFN-γ by CD8+ T lymphocytes.

  20. Enrollment in YFV Vaccine Trial: An Evaluation of Recruitment Outcomes Associated with a Randomized Controlled Double-Blind Trial of a Live Attenuated Yellow Fever Vaccine.

    Science.gov (United States)

    Frew, Paula M; Shapiro, Eve T; Lu, Lu; Edupuganti, Srilatha; Keyserling, Harry L; Mulligan, Mark J

    2013-04-15

    This investigation evaluated several factors associated with diverse participant enrollment of a clinical trial assessing safety, immunogenicity, and comparative viremia associated with administration of 17-D live, attenuated yellow fever vaccine given alone or in combination with human immune globulin. We obtained baseline participant information (e.g., sociodemographic, medical) and followed recruitment outcomes from 2005 to 2007. Of 355 potential Yellow Fever vaccine study participants, 231 cases were analyzed. Strong interest in study participation was observed among racial and ethnically diverse persons with 36.34% eligible following initial study screening, resulting in 18.75% enrollment. The percentage of white participants increased from 63.66% (prescreened sample) to 81.25% (enrollment group). The regression model was significant with white race as a predictor of enrollment (OR=2.744, 95% CI=1.415-5.320, p=0.003).In addition, persons were more likely to enroll via direct outreach and referral mechanisms compared to mass advertising (OR=2.433, 95% CI=1.102-5.369). The findings indicate that racially diverse populations can be recruited to vaccine clinical trials, yet actual enrollment may not reflect that diversity.

  1. Modeling the Effects of Duration and Size of the Control Zones on the Consequences of a Hypothetical African Swine Fever Epidemic in Denmark

    Science.gov (United States)

    Halasa, Tariq; Bøtner, Anette; Mortensen, Sten; Christensen, Hanne; Wulff, Sisse Birk; Boklund, Anette

    2018-01-01

    African swine fever (ASF) is a notifiable infectious disease. The disease is endemic in certain regions in Eastern Europe constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning, it is important to continuously explore strategies that can effectively control an epidemic of ASF. A previously published and well documented simulation model for ASF virus spread between herds was used to examine the epidemiologic and economic impacts of the duration and size of the control zones around affected herds. In the current study, scenarios were run, where the duration of the protection and surveillance zones were reduced from 50 and 45 days to 35 and 25 days or to 35 and 25 days, respectively. These scenarios were run with or without enlargement of the surveillance zone around detected herds from 10 to 15 km. The scenarios were also run with only clinical or clinical and serological surveillance of herds within the zones. Sensitivity analysis was conducted on influential input parameters in the model. The model predicts that reducing the duration of the protection and surveillance zones has no impact on the epidemiological consequences of the epidemics, while it may result in a substantial reduction in the total economic losses. In addition, the model predicts that increasing the size of the surveillance zone from 10 to 15 km may reduce both the epidemic duration and the total economic losses, in case of large epidemics. The ranking of the control strategies by the total costs of the epidemics was not influenced by changes of input parameters in the sensitivity analyses. PMID:29616228

  2. Inter-epidemic transmission of Rift Valley fever in livestock in the Kilombero River Valley, Tanzania: a cross-sectional survey.

    Directory of Open Access Journals (Sweden)

    Robert D Sumaye

    Full Text Available BACKGROUND: In recent years, evidence of Rift Valley fever (RVF transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. METHODOLOGY: A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. FINDINGS: An overall seroprevalence of 11.3% (n = 1680 was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158 whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p15 km from the flood plain were more likely to have antibodies than those living <5 km (OR 1.92; 95% CI 1.04-3.56. Species, breed, herd composition, grazing practices and altitude were not associated with seropositivity. CONCLUSION: These findings indicate post-epidemic transmission of RVFV in the study area. The linear increase in seroprevalence in the post-epidemic annual cohorts

  3. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

    2011-02-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    Science.gov (United States)

    Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

    2010-01-01

    Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

  5. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa

    Directory of Open Access Journals (Sweden)

    Clement Nyamunura Mweya

    2013-10-01

    Full Text Available Background: The East African region has experienced several Rift Valley fever (RVF outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. Methods: Diverse ecological niche modelling techniques have been developed for this purpose: we present a maximum entropy (Maxent approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Results: Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Conclusion: Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  6. Predicting distribution of Aedes aegypti and Culex pipiens complex, potential vectors of Rift Valley fever virus in relation to disease epidemics in East Africa.

    Science.gov (United States)

    Mweya, Clement Nyamunura; Kimera, Sharadhuli Iddi; Kija, John Bukombe; Mboera, Leonard E G

    2013-01-01

    The East African region has experienced several Rift Valley fever (RVF) outbreaks since the 1930s. The objective of this study was to identify distributions of potential disease vectors in relation to disease epidemics. Understanding disease vector potential distributions is a major concern for disease transmission dynamics. DIVERSE ECOLOGICAL NICHE MODELLING TECHNIQUES HAVE BEEN DEVELOPED FOR THIS PURPOSE: we present a maximum entropy (Maxent) approach for estimating distributions of potential RVF vectors in un-sampled areas in East Africa. We modelled the distribution of two species of mosquitoes (Aedes aegypti and Culex pipiens complex) responsible for potential maintenance and amplification of the virus, respectively. Predicted distributions of environmentally suitable areas in East Africa were based on the presence-only occurrence data derived from our entomological study in Ngorongoro District in northern Tanzania. Our model predicted potential suitable areas with high success rates of 90.9% for A. aegypti and 91.6% for C. pipiens complex. Model performance was statistically significantly better than random for both species. Most suitable sites for the two vectors were predicted in central and northwestern Tanzania with previous disease epidemics. Other important risk areas include western Lake Victoria, northern parts of Lake Malawi, and the Rift Valley region of Kenya. Findings from this study show distributions of vectors had biological and epidemiological significance in relation to disease outbreak hotspots, and hence provide guidance for the selection of sampling areas for RVF vectors during inter-epidemic periods.

  7. [Investigation of dengue virus and yellow fever virus seropositivities in blood donors from Central/Northern Anatolia, Turkey].

    Science.gov (United States)

    Ergünay, Koray; Saygan, Mehmet B; Aydoğan, Sibel; Litzba, Nadine; Niedrig, Matthias; Pınar, Ahmet; Us, Dürdal

    2010-07-01

    Dengue virus (DENV) and yellow fever virus (YFV) are two of the globally prevalent vector-borne flaviviruses. Data on these viruses from Turkey is limited to a single study originating from the western, Aegean region of Turkey, where evidence for DENV exposure had been confirmed in residents and presence of hemagglutination inhibiting antibodies against YFV had been revealed. The aim of this study was to investigate the rates of seropositivity of DENV and YFV in blood donors from Central/Northern Anatolia, Turkey, for the demonstration of possible human exposure. Serum samples were collected by the Turkish Red Crescent Middle Anatolia Regional Blood Center from donation sites at Ankara, Konya, Eskişehir and Zonguldak provinces and included in the study after informed consent. Ankara is the capital and second most-populated city in Turkey. All samples were previously evaluated for West Nile and tick-borne encephalitis virus antibodies and found to be negative. A total of 2435 and 1502 sera have been evaluated for IgG antibodies against DENV and YFV, respectively. Commercial enzymelinked immunosorbent assays (ELISAs) and indirect immunofluorescence tests (IIFTs) were applied (Euroimmun, Germany) for DENV/YFV IgG surveillance. DENV IgG reactive sera were further evaluated for IgM by ELISA and a commercial mosaic IIFT to determine DENV subtypes. IgM positive samples were also analyzed by a commercial NS1 antigen detection assay (Bio-Rad Laboratories, France). YFV IgG reactive samples were evaluated by IIFT for IgM and via mosaic IIFT and antibody specificity were confirmed by plaque reduction neutralization test (PRNT). Anti-DENV IgGs were demonstrated in repeated assays in 0.9% (21/2435) of the sera. In two samples with borderline IgG results, presence of DENV IgM was detected, one of which was also borderline positive for DENV NS1 antigen. In 14.3% (3/21) of the IgG reactive sera, mosaic IIFT was evaluated as positive and displayed prominent reactivity for DENV-2 in

  8. Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

    Science.gov (United States)

    Hacker, U T; Erhardt, S; Tschöp, K; Jelinek, T; Endres, S

    2001-09-01

    The inflammatory response in infectious and autoimmune diseases is regulated by the balance between pro- and anti-inflammatory cytokines. The IL-1 complex contains polymorphic genes coding for IL-1alpha, IL-1beta and IL-1Ra. The IL-1Ra (variable number of tanden repeat) VNTR polymorphism has been shown to influence the capacity to produce IL-1beta and IL-1Ra after in vitro stimulation. Allele 2 of this polymorphism is associated with a number of inflammatory diseases. To determine the impact of the IL-1Ra polymorphism on in vivo human cytokine synthesis, we used a yellow fever vaccination model for the induction of cytokine synthesis in healthy volunteers. Two different yellow fever vaccines were used. After administration of the RKI vaccine (34 volunteers), plasma TNF-alpha concentration increased from 13.4 +/- 0.9 pg/ml to 23.3 +/- 1.1 pg/ml (P < 0.001), and plasma IL-1Ra concentration increased from 308 +/- 25 pg/ml to 1019 +/- 111 pg/ml (P < 0.001), on day 2. Using Stamaril vaccine, no increase in the plasma concentrations of either TNF-alpha or IL-1Ra could be detected (n = 17). Only the RKI vaccine induced TNF-alpha synthesis after in vitro stimulation of MNC. Carriers of allele 2 of the IL-1Ra polymorphism had increased baseline concentrations of IL-1Ra (350 +/- 32 pg/ml) compared with non-carriers (222 +/- 18 pg/ml, P < 0.001), and decreased concentrations of IL-1beta (0.9 +/- 0.2 pg/ml for carriers versus 2.8 +/- 0.7 pg/ml for non-carriers, P = 0.017). After yellow fever vaccination (RKI vaccine), no significant differences in the increase of IL-1Ra plasma levels were detected between carriers and non-carriers of allele 2 of the IL-1Ra gene polymorphism. This is the first study to examine the influence of this genetic polymorphism on in vivo-induced human IL-1beta and IL-1Ra synthesis. Baseline concentrations of IL-1Ra and IL-1beta were significantly influenced by the IL-1Ra polymorphism. No influence of the IL-1Ra polymorphism on the in vivo

  9. Hemorrhagic Fevers - Multiple Languages

    Science.gov (United States)

    ... dialect) (繁體中文) Expand Section Vaccine Information Statement (VIS) -- Yellow Fever Vaccine: What You Need to Know - English PDF Vaccine Information Statement (VIS) -- Yellow Fever Vaccine: What You Need to Know - 繁體中文 (Chinese, Traditional ( ...

  10. A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil.

    Science.gov (United States)

    Ribeiro, Ana Freitas; Tengan, Ciléa; Sato, Helena Keico; Spinola, Roberta; Mascheretti, Melissa; França, Ana Cecilia Costa; Port-Carvalho, Marcio; Pereira, Mariza; Souza, Renato Pereira de; Amaku, Marcos; Burattini, Marcelo Nascimento; Coutinho, Francisco Antonio Bezerra; Lopez, Luis Fernandez; Massad, Eduardo

    2015-04-01

    We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

  11. Contrasting female-male mortality ratios after routine vaccinations with pentavalent vaccine versus measles and yellow fever vaccine. A cohort study from urban Guinea-Bissau

    DEFF Research Database (Denmark)

    Fisker, Ane B; Biering-Sørensen, Sofie; Lund, Najaaraq

    2016-01-01

    , DTP vaccine is associated with increased female mortality relative to male mortality. In 2008, Guinea-Bissau replaced DTP with the DTP-containing pentavalent vaccine (Penta; DTP-H. influenza type B-Hepatitis B) at 6, 10 and 14weeks and yellow fever vaccine (YF) was to be given with MV. We investigated......BACKGROUND: In addition to protection against the target diseases, vaccines may have non-specific effects (NSEs). Measles vaccine (MV) has beneficial NSEs, providing protection against non-measles deaths, most so for girls. By contrast, though protecting against diphtheria, tetanus and pertussis...... possible sex-differential mortality rates following Penta and MV+YF vaccination. METHODS: Bandim Health Project (BHP) registers vaccines given by the three government health centres in the study area and vital status through demographic surveillance. We assessed the association between sex and mortality...

  12. A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Ana Freitas Ribeiro

    2015-04-01

    Full Text Available We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP, Brazil, when 28 yellow fever (YF cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

  13. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice

    DEFF Research Database (Denmark)

    Bassi, Maria R; Larsen, Mads Andreas Bay; Kongsgaard, Michael

    2016-01-01

    The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should...... be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using......, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both...

  14. WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13-14 May 2009.

    Science.gov (United States)

    Ferguson, Morag; Shin, Jinho; Knezevic, Ivana; Minor, Philip; Barrett, Alan

    2010-12-06

    In May 2009, WHO convened a meeting of Working Group on Technical Specifications for Manufacturing and Evaluating Yellow Fever (YF) Vaccines, Geneva, Switzerland to initiate revision of the WHO Recommendations (formerly, Requirements) for YF vaccine published in WHO Technical Report Series number 872 (1998). The Working Group, consisting of experts from academia, industry, national regulatory authorities and national control laboratories, reviewed the latest issues of safety, efficacy and quality of YF vaccines and agreed that (i) the revision should focus on live attenuated YF vaccine virus 17D lineage; and that (ii) nonclinical and clinical guidelines for new vaccines prepared from 17D lineage be developed. Copyright © 2010. Published by Elsevier Ltd.. All rights reserved.

  15. Reference gene selection for quantitative real-time PCR analysis in virus infected cells: SARS corona virus, Yellow fever virus, Human Herpesvirus-6, Camelpox virus and Cytomegalovirus infections

    Directory of Open Access Journals (Sweden)

    Müller Marcel A

    2005-02-01

    Full Text Available Abstract Ten potential reference genes were compared for their use in experiments investigating cellular mRNA expression of virus infected cells. Human cell lines were infected with Cytomegalovirus, Human Herpesvirus-6, Camelpox virus, SARS coronavirus or Yellow fever virus. The expression levels of these genes and the viral replication were determined by real-time PCR. Genes were ranked by the BestKeeper tool, the GeNorm tool and by criteria we reported previously. Ranking lists of the genes tested were tool dependent. However, over all, β-actin is an unsuitable as reference gene, whereas TATA-Box binding protein and peptidyl-prolyl-isomerase A are stable reference genes for expression studies in virus infected cells.

  16. Molecular phylogeny of edge hill virus supports its position in the yellow Fever virus group and identifies a new genetic variant.

    Science.gov (United States)

    Macdonald, Joanne; Poidinger, Michael; Mackenzie, John S; Russell, Richard C; Doggett, Stephen; Broom, Annette K; Phillips, Debra; Potamski, Joseph; Gard, Geoff; Whelan, Peter; Weir, Richard; Young, Paul R; Gendle, Debra; Maher, Sheryl; Barnard, Ross T; Hall, Roy A

    2010-06-15

    Edge Hill virus (EHV) is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV) sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence), indicating a distinct subtype or variant within the EHV subgroup.

  17. Molecular Phylogeny of Edge Hill Virus Supports its Position in the Yellow Fever Virus Group and Identifies a New Genetic Variant

    Directory of Open Access Journals (Sweden)

    Joanne Macdonald

    2010-06-01

    Full Text Available Edge Hill virus (EHV is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence, indicating a distinct subtype or variant within the EHV subgroup.

  18. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

    Directory of Open Access Journals (Sweden)

    Andréa Barbosa de Melo

    Full Text Available The yellow fever vaccines (YF-17D-204 and 17DD are considered to be among the safest vaccines and the presence of neutralizing antibodies is correlated with protection, although other immune effector mechanisms are known to be involved. T-cell responses are known to play an important role modulating antibody production and the killing of infected cells. However, little is known about the repertoire of T-cell responses elicited by the YF-17DD vaccine in humans. In this report, a library of 653 partially overlapping 15-mer peptides covering the envelope (Env and nonstructural (NS proteins 1 to 5 of the vaccine was utilized to perform a comprehensive analysis of the virus-specific CD4(+ and CD8(+ T-cell responses. The T-cell responses were screened ex-vivo by IFN-γ ELISPOT assays using blood samples from 220 YF-17DD vaccinees collected two months to four years after immunization. Each peptide was tested in 75 to 208 separate individuals of the cohort. The screening identified sixteen immunodominant antigens that elicited activation of circulating memory T-cells in 10% to 33% of the individuals. Biochemical in-vitro binding assays and immunogenetic and immunogenicity studies indicated that each of the sixteen immunogenic 15-mer peptides contained two or more partially overlapping epitopes that could bind with high affinity to molecules of different HLAs. The prevalence of the immunogenicity of a peptide in the cohort was correlated with the diversity of HLA-II alleles that they could bind. These findings suggest that overlapping of HLA binding motifs within a peptide enhances its T-cell immunogenicity and the prevalence of the response in the population. In summary, the results suggests that in addition to factors of the innate immunity, "promiscuous" T-cell antigens might contribute to the high efficacy of the yellow fever vaccines.

  19. Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

    Science.gov (United States)

    Martins, M A; Silva, M L; Marciano, A P V; Peruhype-Magalhães, V; Eloi-Santos, S M; Ribeiro, j G L; Correa-Oliveira, R; Homma, A; Kroon, E G; Teixeira-Carvalho, A; Martins-Filho, O A

    2007-04-01

    Over past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature.

  20. De miasmas a mosquitos: el pensamiento médico sobre la fiebre amarilla en Yucatán, 1890-1920 From miasmas to mosquitoes: medical thought on yellow fever in Yucatan, 1890-1920

    Directory of Open Access Journals (Sweden)

    Carlos Alcalá Ferráez

    2012-03-01

    Full Text Available La fiebre amarilla fue un problema de salud pública desde la época colonial debido a la frecuencia con que se presentaba en forma epidémica y a su alta letalidad. El objetivo de este trabajo es analizar el pensamiento médico y su evolución con respecto al vómito prieto entre 1890 y 1921 en Yucatán. Dos aspectos serán abordados: algunos antecedentes con respecto a la enfermedad y las ideas predominantes hasta 1881; y la propuesta de Carlos Finlay para vencer el escepticismo ante su teoría por parte de la comunidad médica. En segundo lugar se analizará la mezcla de las ideas miasmáticas y bacterianas. En tercer lugar, se mostrará cómo, a partir de la demostración de sus postulados, la mirada médica se dirigió al exterminio del mosquito transmisor de este padecimiento.Yellow fever has been a public health concern since colonial days because of its frequent epidemics and high mortality rate. This analysis of medical thought about "the black vomit" in the Yucatan and the evolution of this thinking from 1890 through 1921 first addresses some of the disease's antecedents and preponderant ideas prior to 1881 as well as Carlos Finlay's efforts to convince the medical community that his theory was right. The article goes on to analyze the co-existence of miasmatic and bacterial ideas and to show how medical initiatives began focusing on eradication of the mosquito transmitter once Finlay's postulates had been demonstrated.

  1. Epidemic O'Nyong-Nyong fever in southcentral Uganda, 1996-1997: entomologic studies in Bbaale village, Rakai District.

    Science.gov (United States)

    Lutwama, J J; Kayondo, J; Savage, H M; Burkot, T R; Miller, B R

    1999-07-01

    Entomologic studies were conducted between January 27 and February 2, 1997, in Bbaale village in southcentral Uganda during an o'nyong-nyong (ONN) virus epidemic, which began in mid 1996 and continued into 1997. The objectives were to confirm the role of anophelines in ONN virus transmission and to examine other mosquito species as epidemic vectors of ONN virus. Of 10,050 mosquitoes collected using light traps and pyrethrum knockdown sprays, Anopheles (Cellia) funestus Giles was presumed to be the principal vector because it was the most abundant mosquito species from which a strain of ONN virus was isolated. This virus was isolated for the first time from a culicine species, Mansonia (Mansonioides) uniformis Theobald. Bwamba virus and Nyando virus were also isolated from An. funestus.

  2. Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study.

    Directory of Open Access Journals (Sweden)

    Junxiong Pang

    Full Text Available BACKGROUND: Dengue hemorrhagic fever (DHF is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1 and in year 2007-2008 (predominantly serotype 2. METHODS: A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007-2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007-2008, respectively. RESULTS: Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01-3.56 was independently associated with DHF in year 2006. In contrast, age groups of 30-39 years (AOR = 1.41; 95% CI:1.09-1.81, 40-49 years (AOR = 1.34; 95% CI:1.09-1.81, female (AOR = 1.57; 95% CI:1.28-1.94, Chinese (AOR = 1.67; 95% CI:1.24-2.24, diabetes (AOR = 1.78; 95% CI:1.06-2.97, and diabetes with hypertension (AOR = 2.16; 95%CI:1.18-3.96 were independently associated with DHF in year 2007-2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07-4.12 times higher risk of DHF compared with Chinese who had no diabetes and no hypertension. CONCLUSIONS: Adult dengue patients in Singapore who were 30-49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors

  3. Imaginal Discs ? A New Source of Chromosomes for Genome Mapping of the Yellow Fever Mosquito Aedes aegypti

    OpenAIRE

    Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Yang, Fan; Demin, Sergei Iu.; Severson, David W.; Sharakhov, Igor V.

    2011-01-01

    Author Summary Dengue fever is an emerging health threat to as much as half of the human population around the world. No vaccines or drug treatments are currently available. Thus, disease prevention is largely based on efforts to control its major mosquito vector Ae. aegypti. Novel vector control strategies, such as population replacement with pathogen-incompetent transgenic mosquitoes, rely on detailed knowledge of the genome organization for the mosquito. However, the current genome assembl...

  4. The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

    Science.gov (United States)

    Morais, Ana Ts; Terzian, Ana Cb; Duarte, Danilo Vb; Bronzoni, Roberta Vm; Madrid, Maria Cfs; Gavioli, Arieli F; Gil, Laura Hvg; Oliveira, Amanda G; Zanelli, Cleslei F; Valentini, Sandro R; Rahal, Paula; Nogueira, Mauricio L

    2013-06-22

    Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and the expansion of YFV-endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains methyltransferase and RNA-dependent RNA polymerase (RdRp) domains, which are essential for viral replication, and the interactions between NS5 and cellular proteins have been studied to better understand viral replication. The aim of this study was to characterize the interaction of the NS5 protein with eukaryotic translation initiation factor 3 subunit L (eIF3L) and to evaluate the role of eIF3L in yellow fever replication. To identify interactions of YFV NS5 with cellular proteins, we performed a two-hybrid screen using the YFV NS5 RdRp domain as bait with a human cDNA library, and RNApol deletion mutants were generated and analyzed using the two-hybrid system for mapping the interactions. The RNApol region involved was segmented into three fragments and analyzed using an eIF3L-expressing yeast strain. To map the NS5 residues that are critical for the interactions, we performed site-direct mutagenesis in segment 3 of the interaction domain (ID) and confirmed the interaction using in vitro assays and in vivo coimmunoprecipitation. The significance of eIF3L for YFV replication was investigated using eIF3L overexpression and RNA interference. In this work, we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed using in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs at a region (the interaction domain of the RNApol domain) that is conserved in several flaviviruses and that is, therefore, likely to be relevant to the genus. eIF3L overexpression and plaque reduction assays showed a slight effect on YFV replication, indicating that the interaction of eIF3L with YFV NS5 may play a role

  5. Comparative study of adverse events after yellow fever vaccination between elderly and non-elderly travellers: questionnaire survey in Japan over a 1-year period.

    Science.gov (United States)

    Tanizaki, Ryutaro; Ujiie, Mugen; Hori, Narumi; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Hayakawa, Kayoko; Kato, Yasuyuki; Ohmagari, Norio

    2016-03-01

    A live attenuated yellow fever (YF) vaccination is required of all travellers visiting countries where YF virus is endemic. Although the risk of serious adverse events (AEs) after YF vaccination is known to be greater in elderly people than in younger people, information about other AEs among elderly travellers is lacking. A prospective observational questionnaire study was conducted to investigate the occurrence of AEs after YF vaccination in travellers who attended a designated YF vaccination centre in Tokyo, Japan, from 1 November 2011 to 31 October 2012. A questionnaire enquiring about any AEs experienced in the 2 weeks following YF vaccination was distributed to all vaccinees enrolled in this study, and responses were collected subsequently by mail or phone. For child vaccinees, their parents were allowed to respond in their stead. Of the 1298 vaccinees who received the YF vaccine, 1044 (80.4%) were enrolled in the present study and 666 (63.8%) responded to the questionnaire. Of these 666 respondents, 370 (55.6%) reported AEs, of which 258 (38.7%) were systemic and 230 (34.5%) were local. No severe AEs associated with YF vaccination were reported. Elderly vaccinees (aged ≥60 years) reported fewer total AEs than those aged yellow vaccination reported among elderly vaccinees than among non-elderly vaccinees. These results could provide supplementary information for judging the adaptation of vaccination in elderly travellers. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

  6. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Science.gov (United States)

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-07

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. The centennial of the Yellow Fever Commission and the use of informed consent in medical research El centenario de la Comisión de la Fiebre Amarilla y el uso del consentimiento informado en la investigación médica

    Directory of Open Access Journals (Sweden)

    Fernando Güereña-Burgueño

    2002-04-01

    Full Text Available The year 2000 marked the centennial of the discovery of the mode of transmission of yellow fever. Informed consent was systematically used for the first time in research. This process was the result of a complex social phenomenon involving the American Public Health Association, the US and Spanish Governments, American and Cuban scientists, the media, and civilian and military volunteers. The public health and medical communities face the AIDS pandemic at the beginning of the 21st Century, as they faced the yellow fever epidemic at the beginning of the 20th Century. Current medical research dilemmas have fueled the debate about the ethical conduct of research in human subjects. The AIDS pandemic is imposing enormous new ethical challenges on the conduct of medical research, especially in the developing world. Reflecting on the yellow fever experiments of 1900, lessons can be learned and applied to the current ethical challenges faced by the international public health research community.En el año 2000 se cumplió el primer centenario del descubrimiento del modo de transmisión de la fiebre amarilla. El consentimiento informado fue utilizado por primera vez de manera sistemática en una investigación médica. Este proceso fue el resultado de un fenómeno social complejo que involucró a la Asociación Americana de Salud Pública, a los gobiernos de los Estados Unidos de América y España, a científicos norteamericanos y cubanos, a la prensa y a voluntarios civiles y militares. Al inicio del siglo XXI las comunidades de salud pública y médicas en el ámbito internacional enfrentan la pandemia de SIDA al igual que enfrentaron a la fiebre amarilla al iniciarse el siglo XX. A la vez, también debaten los retos éticos que la investigación médica contemporánea les ofrece, especialmente en los países en desarrollo. La reflexión sobre los experimentos de 1900 podría ofrecer enseñanzas aplicables a los retos éticos enfrentados por las

  8. Spatio-temporal variation in prevalence of Rift Valley fever: a post-epidemic serum survey in cattle and wildlife in Kenya.

    Science.gov (United States)

    Lwande, Olivia Wesula; Paul, George Omondi; Chiyo, Patrick I; Ng'ang'a, Eliud; Otieno, Viola; Obanda, Vincent; Evander, Magnus

    2015-01-01

    Rift Valley fever (RVF) is a fatal arthropod-borne zoonotic disease of livestock and humans. Since the identification of RVF in Kenya in the 1930s, repeated epizootics and epidemics coinciding with El Niño events have occurred in several locations in Africa and Saudi Arabia, causing mass deaths of livestock and humans. RVF is of great interest worldwide because of its negative effect on international livestock trade and its potential to spread globally. The latter is due to the increasing incidence of extreme climatic phenomena caused by global warming, as well as to the increase in global trade and international travel. How RVF is maintained and sustained between epidemics and epizootics is not clearly understood, but it has been speculated that wildlife reservoirs and trans-ovarian transmission in the vector may be important. Several studies have examined the role of wildlife and livestock in isolation or in a limited geographical location within the one country over a short time (usually less than a year). In this study, we examined the seroprevalence of anti-RVF antibodies in cattle and several wildlife species from several locations in Kenya over an inter-epidemic period spanning up to 7 years. A serological survey of immunoglobulin G (IgG) antibodies to RVF using competitive ELISA was undertaken on 297 serum samples from different wildlife species at various locations in Kenya. The samples were collected between 2008 and 2015. Serum was also collected in 2014 from 177 cattle from Ol Pejeta Conservancy; 113 of the cattle were in close contact with wildlife and the other 64 were kept separate from buffalo and large game by an electric fence. The seroprevalence of RVF virus (RVFV) antibody was 11.6% in wildlife species during the study period. Cattle that could come in contact with wildlife and large game were all negative for RVFV. The seroprevalence was relatively high in elephants, rhinoceros, and buffalo, but there were no antibodies in zebras, baboons

  9. Spatio-temporal variation in prevalence of Rift Valley fever: a post-epidemic serum survey in cattle and wildlife in Kenya

    Directory of Open Access Journals (Sweden)

    Olivia Wesula Lwande

    2015-12-01

    Full Text Available Background: Rift Valley fever (RVF is a fatal arthropod-borne zoonotic disease of livestock and humans. Since the identification of RVF in Kenya in the 1930s, repeated epizootics and epidemics coinciding with El Niño events have occurred in several locations in Africa and Saudi Arabia, causing mass deaths of livestock and humans. RVF is of great interest worldwide because of its negative effect on international livestock trade and its potential to spread globally. The latter is due to the increasing incidence of extreme climatic phenomena caused by global warming, as well as to the increase in global trade and international travel. How RVF is maintained and sustained between epidemics and epizootics is not clearly understood, but it has been speculated that wildlife reservoirs and trans-ovarian transmission in the vector may be important. Several studies have examined the role of wildlife and livestock in isolation or in a limited geographical location within the one country over a short time (usually less than a year. In this study, we examined the seroprevalence of anti-RVF antibodies in cattle and several wildlife species from several locations in Kenya over an inter-epidemic period spanning up to 7 years. Methods: A serological survey of immunoglobulin G (IgG antibodies to RVF using competitive ELISA was undertaken on 297 serum samples from different wildlife species at various locations in Kenya. The samples were collected between 2008 and 2015. Serum was also collected in 2014 from 177 cattle from Ol Pejeta Conservancy; 113 of the cattle were in close contact with wildlife and the other 64 were kept separate from buffalo and large game by an electric fence. Results: The seroprevalence of RVF virus (RVFV antibody was 11.6% in wildlife species during the study period. Cattle that could come in contact with wildlife and large game were all negative for RVFV. The seroprevalence was relatively high in elephants, rhinoceros, and buffalo, but

  10. The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.

    Science.gov (United States)

    Watson, Alan M; Lam, L K Metthew; Klimstra, William B; Ryman, Kate D

    2016-07-01

    A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.

  11. Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.

    Science.gov (United States)

    Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T

    2014-02-01

    The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.

  12. The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.

    Directory of Open Access Journals (Sweden)

    Alan M Watson

    2016-07-01

    Full Text Available A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.

  13. Innovative in cellulo method as an alternative to in vivo neurovirulence test for the characterization and quality control of human live Yellow Fever virus vaccines: A pilot study.

    Science.gov (United States)

    da Costa, Anaelle; Prehaud, Christophe; Khou, Cecile; Pardigon, Nathalie; Saulnier, Aure; Nougarede, Nolwenn; Lafon, Monique

    2018-05-01

    Live attenuated vaccines have proved to be mostly valuable in the prevention of infectious diseases in humans, especially in developing countries. The safety and potency of vaccine, and the consistency of vaccine batch-to-batch manufacturing, must be proven before being administrated to humans. For now, the tests used to control vaccine safety largely involve animal testing. For live viral vaccines, regulations require suppliers to demonstrate the absence of neurovirulence in animals, principally in non-human primates and mice. In a search to reduce the use of animals and embracing the 3Rs principles (Replacement, Reduction, Refinement in the use of laboratory animals), we developed a new Blood-Brain Barrier Minibrain (BBB-Minibrain) in cellulo device to evaluate the neuroinvasiveness/neurovirulence of live Yellow Fever virus (YFV) vaccines. A pilot study was performed using the features of two distinct YFV strains, with the ultimate goal of proposing a companion test to characterize YFV neurovirulence. Here, we demonstrate that the BBB-Minibrain model is a promising alternative to consider for future replacement of YFV vaccine in vivo neurovirulence testing (see graphical abstract). Copyright © 2018. Published by Elsevier Ltd.

  14. Genome-wide RNA profiling of long-lasting stem cell-like memory CD8 T cells induced by Yellow Fever vaccination in humans

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    Silvia A. Fuertes Marraco

    2015-09-01

    Full Text Available The live-attenuated Yellow Fever (YF vaccine YF-17D induces a broad and polyfunctional CD8 T cell response in humans. Recently, we identified a population of stem cell-like memory CD8 T cells induced by YF-17D that persists at stable frequency for at least 25 years after vaccination. The YF-17D is thus a model system of human CD8 T cell biology that furthermore allows to track and study long-lasting and antigen-specific human memory CD8 T cells. Here, we describe in detail the sample characteristics and preparation of a microarray dataset acquired for genome-wide gene expression profiling of long-lasting YF-specific stem cell-like memory CD8 T cells, compared to the reference CD8 T cell differentiation subsets from total CD8 T cells. We also describe the quality controls, annotations and exploratory analyses of the dataset. The microarray data is available from the Gene Expression Omnibus (GEO public repository with accession number GSE65804.

  15. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity.

    Science.gov (United States)

    Querec, Troy; Bennouna, Soumaya; Alkan, Sefik; Laouar, Yasmina; Gorden, Keith; Flavell, Richard; Akira, Shizuo; Ahmed, Rafi; Pulendran, Bali

    2006-02-20

    The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

  16. Substitution of wild-type yellow fever Asibi sequences for 17D vaccine sequences in ChimeriVax-dengue 4 does not enhance infection of Aedes aegypti mosquitoes.

    Science.gov (United States)

    McGee, Charles E; Tsetsarkin, Konstantin; Vanlandingham, Dana L; McElroy, Kate L; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen

    2008-03-01

    To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax-dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field-collected and laboratory-colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low-level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal.

  17. Formation and loss of large, unstable tandem arrays of the piggyBac transposable element in the yellow fever mosquito, Aedes aegypti.

    Science.gov (United States)

    Adelman, Zach N; Jasinskiene, Nijole; Vally, K J M; Peek, Corrie; Travanty, Emily A; Olson, Ken E; Brown, Susan E; Stephens, Janice L; Knudson, Dennis L; Coates, Craig J; James, Anthony A

    2004-10-01

    The Class II transposable element, piggyBac, was used to transform the yellow fever mosquito, Aedes aegypti. In two transformed lines only 15-30% of progeny inherited the transgene, with these individuals displaying mosaic expression of the EGFP marker gene. Southern analyses, gene amplification of genomic DNA, and plasmid rescue experiments provided evidence that these lines contained a high copy number of piggyBac transformation constructs and that much of this DNA consisted of both donor and helper plasmids. A detailed analysis of one line showed that the majority of piggyBac sequences were unit-length donor or helper plasmids arranged in a large tandem array that could be lost en masse in a single generation. Despite the presence of a transposase source and many intact donor elements, no conservative (cut and paste) transposition of piggyBac was observed in these lines. These results reveal one possible outcome of uncontrolled and/or unexpected recombination in this mosquito, and support the conclusion that further investigation is necessary before transposable elements such as piggyBac can be used as genetic drive mechanisms to move pathogen-resistance genes into mosquito populations.

  18. Yellow fever virus isolated from a fatal post vaccination event: an experimental comparative study with the 17DD vaccine strain in the Syrian hamster (Mesocricetus auratus

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    Sueli Guerreiro Rodrigues

    2004-01-01

    Full Text Available In order to investigate the pathogenicity of the virus strain GOI 4191 that was isolated from a fatal adverse event after yellow fever virus (YFV vaccination, an experimental assay using hamsters (Mesocricetus auratus as animal model and YFV 17DD vaccine strain as virus reference was accomplished. The two virus strains were inoculated by intracerebral, intrahepatic and subcutaneous routes. The levels of viremia, antibody response, and aminotransferases were determined in sera; while virus, antigen and histopathological changes were determined in the viscera. No viremia was detected for either strain following infection; the immune response was demonstrated to be more effective to strain GOI 4191; and no significant aminotransferase levels alterations were detected. Strain GOI 4191 was recovered only from the brain of animals inoculated by the IC route. Viral antigens were detected in liver and brain by immunohistochemical assay. Histothological changes in the viscera were characterized by inflammatory infiltrate, hepatocellular necrosis, and viral encephalitis. Histological alterations and detection of viral antigen were observed in the liver of animals inoculated by the intrahepatic route. These findings were similar for both strains used in the experiment; however, significant differences were observed from those results previously reported for wild type YFV strains.

  19. Differences in Mortality and Clinical Manifestations of Dengue Hemorrhagic Fever in Taiwan in Different Years: A Comparison for Cases in 2014 and 2015 Epidemics.

    Science.gov (United States)

    Chang, Ko; Huang, Chung-Hao; Lee, Ing-Kit; Lu, Po-Liang; Lin, Chun-Yu; Chen, Tun-Chieh; Lai, Ping-Chang; Hsieh, Hsiao-Cheng; Yu, Hsin-Liang; Hung, Chih-Hsing; Wu, Meng-Chieh; Chin, Yi-Ying; Huang, Chun-Chi; Wu, Deng-Chyang; Chen, Yen-Hsu

    2017-08-01

    People in southern Taiwan experienced two major dengue outbreaks in 2014 and 2015. The mortality and clinical features were very different between these 2 years. Dengue virus serotype 1 (DENV-1) caused epidemic outbreak in 2014 and DENV-2 was predominant in 2015. The characteristics of dengue hemorrhagic fever (DHF) cases in the 2 years was analyzed. We conducted a retrospective chart review to analyze the clinical and laboratory features of 206 adult patients with DHF in southern Taiwan in 2014 and 2015. The mortality rate of DHF cases in 2015 was higher than that of cases in 2014 (38.7% versus 12.4%, P mortality cases, diabetes, chronic renal failure, proton-pump inhibitors using, platelet transfusion, and Charlson comorbidity index score (Charlson score) were also higher in 2015. Multivariate analysis for the mortality cases revealed that the risk factors were Charlson score ≥ 5 ( P = 0.02, odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.244-13.307), severe hepatitis ( P mortality and more complications, such as gastrointestinal bleeding, severe hepatitis, and myocarditis, than in 2014 in southern Taiwan. In the 2-year DHF case series, Charlson score ≥ 5, severe hepatitis, and acute renal failure were independent significant variables for mortality.

  20. Dobrava virus carried by the yellow-necked field mouse Apodemus flavicollis, causing hemorrhagic fever with renal syndrome in Romania.

    Science.gov (United States)

    Panculescu-Gatej, Raluca Ioana; Sirbu, Anca; Dinu, Sorin; Waldstrom, Maria; Heyman, Paul; Murariu, Dimitru; Petrescu, Angela; Szmal, Camelia; Oprisan, Gabriela; Lundkvist, Ake; Ceianu, Cornelia S

    2014-05-01

    Hemorrhagic fever with renal syndrome (HFRS) has been confirmed by serological methods during recent years in Romania. In the present study, focus-reduction neutralization tests (FRNT) confirmed Dobrava hantavirus (DOBV) as the causative agent in some HFRS cases, but could not distinguish between DOBV and Saaremaa virus (SAAV) infections in other cases. DOBV was detected by a DOBV-specific TaqMan assay in sera of nine patients out of 22 tested. Partial sequences of the M genomic segment of DOBV were obtained from sera of three patients and revealed the circulation of two DOBV lineages in Romania. Investigation of rodents trapped in Romania found three DOBV-positive Apodemus flavicollis out of 83 rodents tested. Two different DOBV lineages were also detected in A. flavicollis as determined from partial sequences of the M and S genomic segments. Sequences of DOBV in A. flavicollis were either identical or closely related to the sequences obtained from the HFRS patients. The DOBV strains circulating in Romania clustered in two monophyletic groups, together with strains from Slovenia and the north of Greece. This is the first evidence for the circulation of DOBV in wild rodents and for a DOBV etiology of HFRS in Romania.

  1. Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.

    Science.gov (United States)

    Clarke, Ed; Saidu, Yauba; Adetifa, Jane U; Adigweme, Ikechukwu; Hydara, Mariama Badjie; Bashorun, Adedapo O; Moneke-Anyanwoke, Ngozi; Umesi, Ama; Roberts, Elishia; Cham, Pa Modou; Okoye, Michael E; Brown, Kevin E; Niedrig, Matthias; Chowdhury, Panchali Roy; Clemens, Ralf; Bandyopadhyay, Ananda S; Mueller, Jenny; Jeffries, David J; Kampmann, Beate

    2016-08-01

    The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7

  2. Entomologic and avian investigations of an epidemic of West Nile fever in Romania in 1996, with serologic and molecular characterization of a virus isolate from mosquitoes.

    Science.gov (United States)

    Savage, H M; Ceianu, C; Nicolescu, G; Karabatsos, N; Lanciotti, R; Vladimirescu, A; Laiv, L; Ungureanu, A; Romanca, C; Tsai, T F

    1999-10-01

    Between July and October 1996, a West Nile (WN) fever epidemic occurred in the southern plain and Danube Valley of Romania and in the capital city of Bucharest, resulting in hundreds of neurologic cases and 17 fatalities. In early October 1996, entomologic and avian investigations of the epidemic were conducted in the city of Bucharest and nearby rural areas. Thirty (41%) of 73 domestic fowl sampled had neutralizing antibody to WN virus, including 5 of 13 ducks (38%), 1 of 1 goose, 19 of 52 chickens (37%), 1 of 1 peahen, and 4 of 6 turkeys (67%). Seroprevalence in domestic fowl (27%, or 7 of 26) from the urban Bucharest site was not significantly different (P = 0.08, by Fisher's exact test) than rates at three rural sites (50%, or 23 of 46). Serum collected from one of 12 Passeriformes, an Erithacus rubecula, was positive for neutralizing antibody to WN virus. A total of 5,577 mosquitoes representing seven taxa were collected. Culex pipiens pipiens accounted for 96% of the mosquitoes collected. A single virus isolate, RO97-50, was obtained from a pool of 30 Cx. p. pipiens females aspirated from the walls and ceiling of a blockhouse located near the center of Bucharest, resulting in a minimum infection rate of 0.19 per 1,000. Antisera prepared against RO97-50 failed to distinguish among RO97-50, WN virus strain Eg101, and Kunjin (KUN) virus strain MRM16. A 2,323-basepair DNA fragment of the envelope (E) glycoprotein gene from RO97-50 and a Romanian WN virus strain obtained from a human cerebrospinal fluid sample, RO96-1030, were sequenced. Phylogenetic analyses of 23 WN virus strains and one KUN virus strain using the amino acid and nucleotide sequences for a small portion of the E gene suggest the existence of two large lineages of viruses. Bootstrap analysis of the nucleotide alignment indicated strong support (95%) for a lineage composed of WN virus strains from northern Africa, including isolates from Egypt and Algeria, and west, central, and east Africa, all of

  3. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

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    Yu Cong

    2016-05-01

    Full Text Available Humans infected with yellow fever virus (YFV, a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM and dendritic cells (MoDC from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

  4. Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

    Science.gov (United States)

    Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  5. Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

    Science.gov (United States)

    Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

    2015-01-01

    The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

  6. Heparin removal by ecteola-cellulose pre-treatment enables the use of plasma samples for accurate measurement of anti-Yellow fever virus neutralizing antibodies.

    Science.gov (United States)

    Campi-Azevedo, Ana Carolina; Peruhype-Magalhães, Vanessa; Coelho-Dos-Reis, Jordana Grazziela; Costa-Pereira, Christiane; Yamamura, Anna Yoshida; Lima, Sheila Maria Barbosa de; Simões, Marisol; Campos, Fernanda Magalhães Freire; de Castro Zacche Tonini, Aline; Lemos, Elenice Moreira; Brum, Ricardo Cristiano; de Noronha, Tatiana Guimarães; Freire, Marcos Silva; Maia, Maria de Lourdes Sousa; Camacho, Luiz Antônio Bastos; Rios, Maria; Chancey, Caren; Romano, Alessandro; Domingues, Carla Magda; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2017-09-01

    Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice.

    Science.gov (United States)

    Bassi, Maria R; Larsen, Mads A B; Kongsgaard, Michael; Rasmussen, Michael; Buus, Søren; Stryhn, Anette; Thomsen, Allan R; Christensen, Jan P

    2016-02-01

    The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested.

  8. Evaluation of a Booster Dose of Pentavalent Rotavirus Vaccine Co-Administered with Measles, Yellow Fever and Meningitis A Vaccines in 9-month-old Malian Infants.

    Science.gov (United States)

    Haidara, Fadima C; Tapia, Milagritos D; Sow, Samba O; Doumbia, Moussa; Coulibaly, Flanon; Diallo, Fatoumata; Traoré, Awa; Kodio, Mamoudou; Kelly, Corey L; Fitzpatrick, Meagan; Kotloff, Karen; Victor, John C; Neuzil, Kathleen

    2018-04-12

    Rotavirus vaccines given to infants are safe and efficacious. A booster dose of rotavirus vaccine could extend protection into the second year of life in low resource countries. We conducted an open-label, individual-randomized trial in Bamako, Mali. We assigned 600 9- to 11-month old infants to measles (MV), yellow fever (YFV), and meningococcal A conjugate vaccines with or without pentavalent rotavirus vaccine (PRV). We assessed non-inferiority of seroconversion and seroresponse rates (<10% difference) to MV, YFV and MenAV. We compared the seroresponse to PRV. Seroconversion to measles occurred in 255/261 (97.7%) and 246/252 (97.6%) of the PRV and control group; difference, 0.1% (95% CI, - 4.0 to 4.2). Seroresponse to YFV occurred in 48.1% (141/293) of the PRV group compared to 52.2% (153/293) of the control group; difference - 4.1% (95% CI, -12.2 to 4.0). A 4-fold rise in meningococcal A bactericidal titer was observed in 273/292 (93.5%) PRV recipients and 276/293 (94.2%) controls; difference, -0.7% (95% CI, - 5.2 to 3.8). Rises in anti-rotavirus IgA and IgG geometric mean concentrations were higher among PRV recipients (118 [95% CI, 91 to 154] and 364 [95% CI, 294 to 450]) compared to controls (68 [95% CI, 50 to 92] and 153 [95% CI, 114 to 207]. PRV did not interfere with MV and MenAV; this study could not rule out interference with YFV. PRV increased serum rotavirus antibody levels. NCT02286895.