Sample records for yellow fever wave

  1. Yellow Fever

    MedlinePlus

    ... 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 ...

  2. [Yellow fever].

    PubMed

    Sabbatani, Sergio; Fiorino, Sirio

    2007-06-01

    After the discovery of the New World, yellow fever proved to be an important risk factor of morbidity and mortality for Caribbean populations. In the following centuries epidemic risk, expanded by sea trade and travel, progressively reached the settlements in North America and Brazil as well as the Atlantic seaboard of tropical and equatorial Africa. In the eighteenth century and the first half of the nineteenth century epidemics of yellow fever were reported in some coastal towns in the Iberian peninsula, French coast, Great Britain and Italy, where, in 1804 at Leghorn, only one epidemic was documented. Prevention and control programs against yellow fever, developed at the beginning of the twentieth century in Cuba and in Panama, were a major breakthrough in understanding definitively its aetiology and pathogenesis. Subsequently, further advances in knowledge of yellow fever epidemiology were obtained when French scientists, working in West and Central Africa, showed that monkeys were major hosts of the yellow fever virus (the wild yellow fever virus), besides man. In addition, advances in research, contributing to the development of vaccines against the yellow fever virus in the first half of the nineteenth century, are reported in this paper.

  3. Yellow fever.

    PubMed

    Monath, Thomas P; Vasconcelos, Pedro F C

    2015-03-01

    Yellow fever, a mosquito-borne flavivirus disease occurs in tropical areas of South America and Africa. It is a disease of major historical importance, but remains a threat to travelers to and residents of endemic areas despite the availability of an effective vaccine for nearly 70 years. An important aspect is the receptivity of many non-endemic areas to introduction and spread of yellow fever. This paper reviews the clinical aspects, pathogenesis, and epidemiology of yellow fever, with an emphasis on recent changes in the distribution and incidence of the disease. Recent knowledge about yellow fever 17D vaccine mechanism of action and safety are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Yellow fever: epidemiology and prevention.

    PubMed

    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.

  5. Yellow fever: an update.

    PubMed

    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.

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

    PubMed

    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.

  7. Perinatal Yellow Fever: A Case Report.

    PubMed

    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. 17DD yellow fever vaccine

    PubMed Central

    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

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

    PubMed

    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.

  10. Yellow Fever Outbreak, Southern Sudan, 2003

    PubMed Central

    Onyango, Clayton O.; Grobbelaar, Antoinette A.; Gibson, Georgina V.F.; Sang, Rosemary C.; Sow, Abdourahmane; Swanepoel, Robert

    2004-01-01

    In May 2003, an outbreak of fatal hemorrhagic fever, caused by yellow fever virus, occurred in southern Sudan. Phylogenetic analysis showed that the virus belonged to the East African genotype, which supports the contention that yellow fever is endemic in East Africa with the potential to cause large outbreaks in humans. PMID:15498174

  11. Viscerotropic disease following yellow fever vaccination in Peru.

    PubMed

    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.

  12. Yellow fever: the recurring plague.

    PubMed

    Tomori, Oyewale

    2004-01-01

    Despite the availability of a safe and efficacious vaccine, yellow fever (YF) remains a disease of significant public health importance, with an estimated 200,000 cases and 30,000 deaths annually. The disease is endemic in tropical regions of Africa and South America; nearly 90% of YF cases and deaths occur in Africa. It is a significant hazard to unvaccinated travelers to these endemic areas. Virus transmission occurs between humans, mosquitoes, and monkeys. The mosquito, the true reservoir of YF, is infected throughout its life, and can transmit the virus transovarially through infected eggs. Man and monkeys, on the other hand, play the role of temporary amplifiers of the virus available 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, the Middle East, Asia, Australia, and Oceania. It is an acute infectious disease characterized by sudden onset with a two-phase development, separated by a short period of remission. The clinical spectrum of yellow fever varies from very mild, nonspecific, febrile illness to a fulminating, sometimes fatal disease with pathognomic features. In severe cases, jaundice, bleeding diathesis, with hepatorenal involvement are common. The case fatality rate of severe yellow fever is 50% or higher. The pathogenesis and pathophysiology of the disease are poorly understood and have not been the subject of modern clinical research. There is no specific treatment for YF, making the management of YF patients extremely problematic. YF is a zoonotic disease that cannot be eradicated, therefore instituting preventive vaccination through routine childhood vaccination in endemic countries, can significantly reduce the burden of the disease. The distinctive properties of lifelong immunity after a single dose of yellow fever vaccination are the

  13. [Present status of an arbovirus infection: yellow fever, its natural history of hemorrhagic fever, Rift Valley fever].

    PubMed

    Digoutte, J P

    1999-12-01

    In the early 20th century, when it was discovered that the yellow fever virus was transmitted in its urban cycle by Aedes aegypti, measures of control were introduced leading to its disappearance. Progressive neglect of the disease, however, led to a new outbreak in 1927 during which the etiological agent was isolated; some years later a vaccine was discovered and yellow fever disappeared again. In the 1960s, rare cases of encephalitis were observed in young children after vaccination and the administration of the vaccine was forbidden for children under 10 years. Five years later, a new outbreak of yellow fever in Diourbel, Senegal, was linked to the presence of Aedes aegypti. In the late 1970s, the idea of a selvatic cycle for yellow fever arose. Thanks to new investigative techniques in Senegal and Côte d'Ivoire, the yellow fever virus was isolated from the reservoir of virus and vectors. The isolated virus was identified in monkeys and several vectors: Aedes furcifer, Aedes taylori, Aedes luteocephalus. Most importantly, the virus was isolated in male mosquitoes. Until recently, the only known cycle had been that of Haddow in East Africa. The virus circulate in the canopea between monkeys and Aedes africanus. These monkeys infect Aedes bromeliae when they come to eat in banana plantations. This cycle does not occur in West Africa. Vertical transmission is the main method of maintenance of the virus through the dry season. "Reservoirs of virus" are often mentioned in medical literature, monkeys having a short viremia whereas mosquitoes remain infected throughout their life cycle. In such a selvatic cycle, circulation can reach very high levels and no child would be able to escape an infecting bite and yet no clinical cases of yellow fever have been reported. The virulence--as it affects man--of the yellow fever virus in its wild cycle is very low. In areas where the virus can circulate in epidemic form, two types of circulation can be distinguished

  14. THE TRANSMISSION OF YELLOW FEVER

    PubMed Central

    Davis, Nelson C.

    1930-01-01

    1. Saimiri sciureus has been infected with yellow fever virus, both by the inoculation of infectious blood and by the bites of infective mosquitoes. Some of the monkeys have died, showing lesions, including hepatic necrosis, suggesting yellow fever as seen in human beings and in rhesus monkeys. Virus has been transferred back to M. rhesus from infected Saimiri both by blood inoculation and by mosquito bites. The virus undoubtedly has been maintained through four direct passages in Saimiri. Reinoculations of infectious material into recovered monkeys have not given rise to invasion of the blood stream by virus. Sera from recovered animals have protected M. rhesus against the inoculation of virus. 2. It has been possible to pass the virus to and from Ateleus ater by the injection of blood or liver and by the bites of mosquitoes. The livers from two infected animals have shown no necrosis. The serum from one recovered monkey proved to be protective for M. rhesus. 3. Only three out of twelve Lagothrix lagotricha have reacted to yellow fever virus by a rise in temperature. Probably none have died as a result of the infection. In only one instance has the virus been transferred back to M. rhesus. The sera of recovered animals have had a protective action against yellow fever virus. PMID:19869721

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

    PubMed

    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.

  16. Yellow Fever Vaccine

    MedlinePlus

    ... way to prevent yellow fever is to avoid mosquito bites by:staying in well-screened or air-conditioned areas, wearing clothes that cover most of your body, using an effective insect repellent, such as those containing DEET.

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

    PubMed

    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.

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

    PubMed Central

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

    2018-01-01

    Abstract Objective To examine the potential for international travel to spread yellow fever virus to cities around the world. Methods 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. Findings 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. Conclusion 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. PMID:29875519

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

    PubMed

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

    2014-03-01

    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.

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

    PubMed

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

    2008-01-01

    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. 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 voluntary serum samples pre- and post-vaccination with YF vaccine. Dengue ELISA revealed IgM reactivity in 46,2 % of yellow fever patients and 42 % of vaccinees. Sixteen out of 20 dengue patients (80 %) had high YF virus neutralisation titres. Such very high cross-reactivity data challenged differential laboratory diagnosis of dengue and yellow fever in areas where both flaviviruses co-circulate. New laboratory strategies are thus needed for improving the tests and providing a specific laboratory diagnosis. Cross-reactivity between Flaviviruses represents a great difficulty for epidemiological surveillance and preventing dengue, both of which demand urgent attention.

  1. 42 CFR 71.3 - Designation of yellow fever vaccination centers; Validation stamps.

    Code of Federal Regulations, 2010 CFR

    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...

  2. Yellow fever in China is still an imported disease.

    PubMed

    Chen, Jun; Lu, Hongzhou

    2016-05-23

    Yellow fever is a vector-borne disease endemic to tropical regions of Africa and South America. A recent outbreak in Angola caused hundreds of deaths. Six cases of yellow fever imported from Angola were reported recently in China. This raised the question of whether it will spread in China and how it can be prevented. This article discusses the possibility of yellow fever transmission in China and the strategies to counter it.

  3. THE SUSCEPTIBILITY OF MARMOSETS TO YELLOW FEVER VIRUS

    PubMed Central

    Davis, Nelson C.

    1930-01-01

    1. It has been possible to introduce yellow fever virus into the small Brazilian monkeys, Callithrix albicollis and Leontocebus ursulus, by the bites of infected mosquitoes and to carry the virus through a series of four passages in each species and back to rhesus monkeys by the bites of Stegomyia mosquitoes fed on the last marmoset of each series. 2. Five specimens of L. ursulus were used. Four developed fever, and all died during the experiments. At least two showed liver necroses comparable to those found in human beings and rhesus monkeys that died of yellow fever. 3. Twenty specimens of C. albicollis were used. Very few showed a temperature reaction following the introduction of virus. Of those that died, none had lesions typical of yellow fever as seen in certain other species of monkeys and in humans. 4. The convalescent serum from each of five C. albicollis protected a rhesus monkey against yellow fever virus, but the serum from a normal marmoset of the same species was found to be non-protective. PMID:19869773

  4. Present status of yellow fever: memorandum from a PAHO meeting.

    PubMed

    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 fever and problems associated with case-finding and notification; features of yellow fever in individual countries of Latin America; health services and facilities for medical care as they relate to diagnosis and management of cases; prevention strategies for and current status of immunization programmes; clinical and pathological aspects of yellow fever in humans; pathogenesis and pathophysiology of yellow fever in experimental animal models; clinical and specific laboratory diagnosis; treatment of the disease and of complications in the functioning of individual organ systems; prognosis and prognostic indicators; and directions for future clinical and experimental research on pathophysiology and treatment.

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

    PubMed

    Machado, Vanessa Wolff; Vasconcelos, Pedro Fernando da Costa; Silva, Eliana Vieira Pinto; Santos, João Barberino

    2013-01-01

    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. 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. 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. 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.

  6. STUDIES ON SOUTH AMERICAN YELLOW FEVER

    PubMed Central

    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

  7. [Trends in yellow fever mortality in Colombia, 1998-2009].

    PubMed

    Segura, Ángela María; Cardona, Doris; Garzón, María Osley

    2013-09-01

    Yellow fever is a neglected tropical disease, thus, knowing the trends in mortality from this disease in Colombia is an important source of information for decision making and identifying public health interventions. To analyze trends in yellow fever mortality in Colombia during the 1998-2009 period and the differences in the morbidity and mortality information sources for the country, which affect indicators such as the lethality one. This is a descriptive study of deaths by yellow fever according to the Departamento Administrativo Nacional de Estadística and the incidence of the disease according to the Instituto Nacional de Salud . We used secondary sources of information in the calculation of proportions of socio-demographic characteristics of the deceased and epidemiological measures of lethality, incidence and mortality from yellow fever by department of residence of the deceased. Yellow fever deaths occur primarily in men of working age residing in scattered rural areas, who were members of the regimen vinculado, and who were living in the eastern, southeastern, northern and central zones in the country. We observed inconsistencies in the reports that affect the comparative analysis. The inhabitants of the departments located in national territories and Norte de Santander have an increased risk of illness and death from yellow fever, but this information could be underestimated, according to the source of information used for its calculation.

  8. Lost trust: a yellow fever patient response.

    PubMed

    Runge, John S

    2013-12-13

    In the 19th century, yellow fever thrived in the tropical, urban trade centers along the American Gulf Coast. Industrializing and populated, New Orleans and Memphis made excellent habitats for the yellow fever-carrying Aedes aegypti mosquitoes and the virulence they imparted on their victims. Known for its jaundice and black, blood-filled vomit, the malady terrorized the region for decades, sometimes claiming tens of thousands of lives during the near annual summertime outbreaks. In response to the failing medical community, a small, pronounced population of sick and healthy laypeople openly criticized the efforts to rid the Gulf region of yellow jack. Utilizing newspapers and cartoons to vocalize their opinions, these critics doubted and mocked the medical community, contributing to the regional and seasonal dilemma yellow fever posed for the American South. These sentient expressions prove to be an early example of patient distrust toward caregivers, a current problem in clinical heath care.

  9. Lost Trust: A Yellow Fever Patient Response

    PubMed Central

    Runge, John S.

    2013-01-01

    In the 19th century, yellow fever thrived in the tropical, urban trade centers along the American Gulf Coast. Industrializing and populated, New Orleans and Memphis made excellent habitats for the yellow fever-carrying Aedes aegypti mosquitoes and the virulence they imparted on their victims. Known for its jaundice and black, blood-filled vomit, the malady terrorized the region for decades, sometimes claiming tens of thousands of lives during the near annual summertime outbreaks. In response to the failing medical community, a small, pronounced population of sick and healthy laypeople openly criticized the efforts to rid the Gulf region of yellow jack. Utilizing newspapers and cartoons to vocalize their opinions, these critics doubted and mocked the medical community, contributing to the regional and seasonal dilemma yellow fever posed for the American South. These sentient expressions prove to be an early example of patient distrust toward caregivers, a current problem in clinical heath care. PMID:24348220

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

    PubMed

    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.

  11. THE USE OF MICE IN TESTS OF IMMUNITY AGAINST YELLOW FEVER

    PubMed Central

    Sawyer, W. A.; Lloyd, Wray

    1931-01-01

    1. A method of testing sera for protective power against yellow fever is described and designated as the intraperitoneal protection test in mice. 2. The test consists essentially of the inoculation of mice intra-peritoneally with yellow fever virus, fixed for mice, together with the serum to be tested, and the simultaneous injection of starch solution into the brain to localize the virus. If the serum lacks protective power the mice die of yellow fever encephalitis. 3. The test is highly sensitive. Consequently it is useful in epidemiological studies to determine whether individuals have ever had yellow fever and in tests to find whether vaccinated persons or animals have in reality been immunized. 4. When mice were given large intraperitoneal injections of yellow fever virus fixed for mice, the virus could be recovered from the blood for 4 days although encephalitis did not occur. If the brain was mildly injured at the time of the intraperitoneal injection, the symptoms of yellow fever encephalitis appeared 6 days later, but the virus was then absent from the blood. 5. Strains of white mice vary greatly in their susceptibility to yellow fever. PMID:19869938

  12. A Case of Yellow Fever Vaccine–Associated Viscerotropic Disease in Ecuador

    PubMed Central

    Douce, Richard W.; Freire, Diana; Tello, Betzabe; Vásquez, Gavino A.

    2010-01-01

    We report the first case of viscerotropic syndrome in Ecuador. Because of similarities between yellow fever and viscerotropic syndrome, the incidence of this recently described complication of vaccination with the 17D yellow fever vaccine is not known. There is a large population in South America that is considered at risk for possible reemergence of urban yellow fever. Knowledge of potentially fatal complications of yellow fever vaccine should temper decisions to vaccinate populations where the disease is not endemic. PMID:20348528

  13. Yellow fever.

    PubMed

    Litvoc, Marcelo Nóbrega; Novaes, Christina Terra Gallafrio; Lopes, Max Igor Banks Ferreira

    2018-02-01

    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.

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

    PubMed

    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.

  15. Travelers' Health: Yellow Fever

    MedlinePlus

    ... and local rate of virus transmission at the time of travel. Although reported cases of human disease are the ... be receiving yellow fever vaccine for the first time. If travel is unavoidable, the decision to vaccinate travelers aged ≥ ...

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  19. Yellow fever: a reemerging threat.

    PubMed

    Gardner, Christina L; Ryman, Kate D

    2010-03-01

    Yellow fever (YF) is a viral disease, endemic to tropical regions of Africa and the Americas, which principally affects humans and nonhuman primates and is transmitted via the bite of infected mosquitoes. Yellow fever virus (YFV) can cause devastating epidemics of potentially fatal, hemorrhagic disease. Despite mass vaccination campaigns to prevent and control these outbreaks, the risk of major YF epidemics, especially in densely populated, poor urban settings, both in Africa and South America, has greatly increased. Consequently, YF is considered an emerging, or reemerging disease of considerable importance. This article comprehensively reviews the history, microbiology, epidemiology, clinical presentation, diagnosis, and treatment of YFV, as well as the vaccines produced to combat YF. 2010 Elsevier Inc. All rights reserved.

  20. Serious adverse events associated with yellow fever vaccine.

    PubMed

    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.

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

    Cancer.gov

    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,

  2. Yellow Fever in an Unvaccinated Traveler to Peru.

    PubMed

    Winnicka, Lydia; Abdullah, Amirahwaty; Yang, Tsujung; Norville, Kim; Irizarry-Acosta, Melina

    2017-01-01

    We present a case of an unvaccinated traveler who traveled from New York to Peru and contracted yellow fever. He likely acquired the infection while visiting the Amazon River, with a point of exit of Lima, Peru. Our case illustrates the dramatic course that yellow fever may take, as well as the importance of pretravel vaccination.

  3. Current Assessment of Yellow Fever and Yellow Fever Vaccine.

    PubMed

    Lefeuvre, Anabelle; Marianneau, Philippe; Deubel, Vincent

    2004-04-01

    Yellow fever (YF) is a mosquito-borne viral illness that causes hemorrhagic fever in tropical Africa and South America. Although a very safe and efficient vaccine (17D) is available, it is underused. An estimated 200,000 people are still infected annually, and YF remains a major public health concern. This article reviews the recent data on YF epidemiology, virology, and immunity, and analyzes the rare postvaccination adverse effects that have been recently reported. YF vaccine should be included in the expanded program of immunization for children and sustained for people living in or traveling to endemic areas. A surveillance of vaccinated people also should be reinforced. New research programs should be developed to identify molecular markers of YF virus tropism and attenuation, and to understand mechanisms of host responses to virus infection.

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

    PubMed

    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.

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

    PubMed Central

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

    2001-01-01

    OBJECTIVES: 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. METHODS: 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. FINDINGS: 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. CONCLUSIONS: 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. PMID:11731813

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

    Cancer.gov

    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, including NCI at Frederick staff and scientists.

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

    PubMed

    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.

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

    PubMed

    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.

  9. Yellow fever virus vaccine-associated deaths in young women.

    PubMed

    Seligman, Stephen J

    2011-10-01

    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.

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

    PubMed

    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.

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

    PubMed

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

    PubMed

    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.

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

    PubMed

    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.

  14. Genomic and Phylogenetic Characterization of Brazilian Yellow Fever Virus Strains

    PubMed Central

    Palacios, Gustavo; Cardoso, Jedson F.; Martins, Livia C.; Sousa, Edivaldo C.; de Lima, Clayton P. S.; Medeiros, Daniele B. A.; Savji, Nazir; Desai, Aaloki; Rodrigues, Sueli G.; Carvalho, Valeria L.; Lipkin, W. Ian

    2012-01-01

    Globally, yellow fever virus infects nearly 200,000 people, leading to 30,000 deaths annually. Although the virus is endemic to Latin America, only a single genome from this region has been sequenced. Here, we report 12 Brazilian yellow fever virus complete genomes, their genetic traits, phylogenetic characterization, and phylogeographic dynamics. Variable 3′ noncoding region (3′NCR) patterns and specific mutations throughout the open reading frame altered predicted secondary structures. Our findings suggest that whereas the introduction of yellow fever virus in Brazil led to genotype I-predominant dispersal throughout South and Central Americas, genotype II remained confined to Bolivia, Peru, and the western Brazilian Amazon. PMID:23015713

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  18. [Completed sequences analysis on the Chinese attenuated yellow fever 17D vaccine strain and the WHO standard yellow fever 17D vaccine strain].

    PubMed

    Li, Jing; Yu, Yong-Xin; Dong, Guan-Mu

    2009-04-01

    To compare the molecular characteristics of the Chinese attenuated yellow fever 17D vaccine strain and the WHO reference yellow fever 17D vaccine strain. The primers were designed according to the published nucleotide sequences of YFV 17D strains in GenBank. Total RNA of was extracted by the Trizol and reverse transcripted. The each fragments of the YFV genome were amplified by PCR and sequenced subsequently. The fragments of the 5' and 3' end of the two strains were cloned into the pGEM T-easy vector and then sequenced. The nucleotide acid and amino acid sequences of the homology to both strains were 99% with each other. No obvious nulceotide changes were found in the sequences of the entire genome of each 17D strains. Moreover, there was no obvious changes in the E protein genes. But the E173 of YF17D Tiantan, associted with the virulence, had mutantions. And the two live attenuated yellow fever 17D vaccine strains fell to the same lineage by the phylogenetic analysis. The results indicated that the two attenuated yellow fever 17D vaccine viruses accumulates mutations at a very low frequency and the genomes were relative stable.

  19. Yellow Fever Virus Vaccine–associated Deaths in Young Women1

    PubMed Central

    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. PMID:22000363

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

    PubMed Central

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

    2017-01-01

    Background 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. Methodology/Principal findings 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%). Conclusions/Significance A clustered geographic pattern of yellow fever was identified mostly along the Andes eastern foothills. This risk map could support health policies in

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

    PubMed

    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

  2. Yellow Fever Outbreak, Imatong, Southern Sudan

    PubMed Central

    Ofula, Victor O.; Sang, Rosemary C.; Konongoi, Samson L.; Sow, Abdourahmane; De Cock, Kevin M.; Tukei, Peter M.; Okoth, Fredrick A.; Swanepoel, Robert; Burt, Felicity J.; Waters, Norman C.; Coldren, Rodney L.

    2004-01-01

    In May 2003, the World Health Organization received reports about a possible outbreak of a hemorrhagic disease of unknown cause in the Imatong Mountains of southern Sudan. Laboratory investigations were conducted on 28 serum samples collected from patients in the Imatong region. Serum samples from 13 patients were positive for immunoglobulin M antibody to flavivirus, and serum samples from 5 patients were positive by reverse transcription–polymerase chain reaction with both the genus Flavivirus–reactive primers and yellow fever virus–specific primers. Nucleotide sequencing of the amplicons obtained with the genus Flavivirus oligonucleotide primers confirmed yellow fever virus as the etiologic agent. Isolation attempts in newborn mice and Vero cells from the samples yielded virus isolates from five patients. Rapid and accurate laboratory diagnosis enabled an interagency emergency task force to initiate a targeted vaccination campaign to control the outbreak. PMID:15207058

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

    PubMed

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; Validation stamps. 71.3 Section 71.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... Designation of yellow fever vaccination centers; Validation stamps. (a) Designation of yellow fever... health department, may revoke designation. (b) Validation stamps. International Certificates of...

  5. 42 CFR 71.3 - Designation of yellow fever vaccination centers; Validation stamps.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...; Validation stamps. 71.3 Section 71.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... Designation of yellow fever vaccination centers; Validation stamps. (a) Designation of yellow fever... health department, may revoke designation. (b) Validation stamps. International Certificates of...

  6. 42 CFR 71.3 - Designation of yellow fever vaccination centers; Validation stamps.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; Validation stamps. 71.3 Section 71.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... Designation of yellow fever vaccination centers; Validation stamps. (a) Designation of yellow fever... health department, may revoke designation. (b) Validation stamps. International Certificates of...

  7. 42 CFR 71.3 - Designation of yellow fever vaccination centers; Validation stamps.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; Validation stamps. 71.3 Section 71.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN... Designation of yellow fever vaccination centers; Validation stamps. (a) Designation of yellow fever... health department, may revoke designation. (b) Validation stamps. International Certificates of...

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

    PubMed

    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.

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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.

  12. Advanced yellow fever virus genome detection in point-of-care facilities and reference laboratories.

    PubMed

    Domingo, Cristina; Patel, Pranav; Yillah, Jasmin; Weidmann, Manfred; Méndez, Jairo A; Nakouné, Emmanuel Rivalyn; Niedrig, Matthias

    2012-12-01

    Reported methods for the detection of the yellow fever viral genome are beset by limitations in sensitivity, specificity, strain detection spectra, and suitability to laboratories with simple infrastructure in areas of endemicity. We describe the development of two different approaches affording sensitive and specific detection of the yellow fever genome: a real-time reverse transcription-quantitative PCR (RT-qPCR) and an isothermal protocol employing the same primer-probe set but based on helicase-dependent amplification technology (RT-tHDA). Both assays were evaluated using yellow fever cell culture supernatants as well as spiked and clinical samples. We demonstrate reliable detection by both assays of different strains of yellow fever virus with improved sensitivity and specificity. The RT-qPCR assay is a powerful tool for reference or diagnostic laboratories with real-time PCR capability, while the isothermal RT-tHDA assay represents a useful alternative to earlier amplification techniques for the molecular diagnosis of yellow fever by field or point-of-care laboratories.

  13. STUDIES ON YELLOW FEVER IN SOUTH AMERICA

    PubMed Central

    Davis, Nelson C.; Shannon, Raymond C.

    1929-01-01

    1. Yellow fever virus has been transmitted from monkey to monkey both by the bites of Aëdes (Ochlerotatus) scapularis which had fed upon monkeys infected with yellow fever and by the injection of the ground up bodies of such mosquitoes. 2. A fatal infection has been obtained by the injection of the ground up bodies of Aëdes (Ochlerotatus) serratus, which had previously fed on an infected monkey, and a mild infection has been secured by the similar injection of Aëdes (Taeniorhynchus) taeniorhynchus. 3. No definite infection has been secured either by the bites or by the injection of Culex quinquefasciatus (C. fatigans). However, some of the experimental animals bitten by this species have been relatively immune following inoculations of blood or tissues containing virus. PMID:19869666

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

    PubMed

    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; P<0.001). Three adverse events occurred at a higher incidence in the two vaccine 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.).

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

    PubMed

    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

  16. VACCINATION AGAINST YELLOW FEVER WITH IMMUNE SERUM AND VIRUS FIXED FOR MICE

    PubMed Central

    Sawyer, W. A.; Kitchen, S. F.; Lloyd, Wray

    1932-01-01

    1. After preliminary experiments in monkeys, 15 persons were actively immunized by a single injection of a dried mixture of living yellow fever virus, fixed for mice, and human immune serum, with separate injections of enough additional serum to make up the amount required for protection. 2. One person was similarly immunized by injecting immune serum and dried virus separately. 3. By titration of the sera of vaccinated persons in mice, it was shown that the immunity rose in a few weeks to a height comparable to that reached after an attack of yellow fever, and remained there throughout an observation period of 6 months. 4. Yellow fever virus could not be recovered from the blood of vaccinated persons or monkeys, except when the latter had received less than the minimal effective amount of immune serum. 5. Neutralization of yellow fever virus by immune serum took place very slowly in vitro at room temperature in our experiments, and could not have been an appreciable factor in vaccination with the serum virus mixtures. 6. A mixture of fixed virus and immune serum retained its immunizing power for 8 months when dried in the frozen state and sealed in glass. 7. It appears that the immunizing reaction after yellow fever vaccination was a part of a true infectious process, as was also the observed leucopenia. PMID:19870044

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

    PubMed Central

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

    2008-01-01

    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, reactive SIAs were only

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

    PubMed

    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

  19. Development of a reverse transcription polymerase chain reaction method for yellow fever virus detection.

    PubMed

    Méndez, María C; Domingo, Cristina; Tenorio, Antonio; Pardo, Lissethe C; Rey, Gloria J; Méndez, Jairo A

    2013-09-01

    Yellow fever is considered a re-emerging disease and is endemic in tropical regions of Africa and South America. At present, there are no standardized or commercialized kits available for yellow fever virus detection. Therefore, diagnosis must be made by time-consuming routine techniques, and sometimes, the virus or its proteins are not detected. Furthermore, co-circulation with other flaviviruses, including dengue virus, increases the difficulty of diagnosis. To develop a specific reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR-based assay to improve the detection and diagnosis of yellow fever virus using both serum and fresh tissue samples. RT-PCR primers were designed to amplify a short fragment of all yellow fever virus genotypes reported. A second set of primers was used in a nested PCR to increase sensitivity. Thirty-three clinical samples were tested with the standardized reaction. The expected amplicon was obtained in 25 out of 33 samples analyzed using this approach, and 2 more samples tested positive after a subsequent nested PCR approach. This improved technique not only ensures the specific detection of a wide range of yellow fever virus genotypes but also may increase the sensitivity of detection by introducing a second round of amplification, allowing a rapid differential diagnosis between dengue and yellow fever infection, which is required for effective surveillance and opportune epidemiologic measures.

  20. Enzootic transmission of yellow fever virus, Venezuela.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:3501739

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

    PubMed

    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.

  4. THE TRANSMISSION OF NEUROTROPIC YELLOW FEVER VIRUS BY STEGOMYIA MOSQUITOES

    PubMed Central

    Davis, Nelson C.; Lloyd, Wray; Frobisher, Martin

    1932-01-01

    1. By the bites of stegomyia mosquitoes carrying neurotropic yellow fever virus, encephalitis has been produced both in white mice and in rhesus monkeys. 2. The fixed neurotropic strain of virus cannot be maintained in the mosquito host as well as can the viscerotropic strains. This is doubtless attributable in part to a smaller amount of virus ingested, because of paucity in the blood stream of the mammalian host. 3. These experiments furnish additional evidence that the long established neurotropic yellow fever virus has changed fundamentally from the parent French strain. PMID:19870108

  5. Enzootic Transmission of Yellow Fever Virus, Venezuela

    PubMed Central

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

    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. PMID:25531105

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

    PubMed

    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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

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

    PubMed Central

    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

    2017-01-01

    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 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. PMID:28333617

  9. Yellow fever in two unvaccinated French tourists to Brazil, January and March, 2018.

    PubMed

    Oliosi, Emma; Serero Corcos, Chantal; Barroso, Paulo Feijo; Bleibtreu, Alexandre; Grard, Gilda; De Filippis, Bispo Ana Maria; Caumes, Eric

    2018-05-01

    We report two yellow fever cases in unvaccinated French travellers in Brazil in January and March 2018, respectively; one exposed during an excursion in Minas Gerais and the other in Ilha Grande. Both presented with fever, hepatitis, thrombocytopenia and leucopenia. Yellow fever diagnosis was based on RT-PCR and serological tests. Both patients recovered within a few days. The increasing occurrence of cases in unvaccinated travellers highlights the need to reinforce vaccination recommendation for travellers at-risk.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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 < 0.01] compared with the price from agencies that did mention health risks. Almost all who acknowledged malaria (97%) and/or 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.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:29546100

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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.

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

    PubMed Central

    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. Experimental therapies for yellow fever

    PubMed Central

    Julander, Justin G.

    2013-01-01

    A number of viruses in the family Flaviviridae are the focus of efforts to develop effective antiviral therapies. Success has been achieved with inhibitors for the treatment of hepatitis C, and there is interest in clinical trials of drugs against dengue fever. Antiviral therapies have also been evaluated in patients with Japanese encephalitis and West Nile encephalitis. However, no treatment has been developed against the prototype flavivirus, yellow fever virus (YFV). Despite the availability of the live, attenuated 17D vaccine, thousands of cases of YF continue to occur each year in Africa and South America, with a significant mortality rate. In addition, a small number of vaccinees develop severe systemic infections with the 17D virus. This paper reviews current efforts to develop antiviral therapies, either directly targeting the virus or blocking detrimental host responses to infection. PMID:23237991

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

    PubMed

    Vasconcelos, Pedro Fernando da Costa

    2010-12-01

    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.

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

    PubMed

    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.

  6. Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever.

    PubMed

    Quaresma, Juarez A S; Pagliari, Carla; Medeiros, Daniele B A; Duarte, Maria I S; Vasconcelos, Pedro F C

    2013-09-01

    Yellow fever is a viral hemorrhagic fever, which affects people living in Africa and South America and is caused by the yellow fever virus, the prototype species in the Flavivirus genus (Flaviviridae family). Yellow fever virus infection can produce a wide spectrum of symptoms, ranging from asymptomatic infection or oligosymptomatic illness to severe disease with a high fatality rate. In this review, we focus in the mechanisms associated with the physiopathology of yellow fever in humans and animal models. It has been demonstrated that several factors play a role in the pathological outcome of the severe form of the disease including direct viral cytopathic effect, necrosis and apoptosis of hepatocyte cells in the midzone, and a minimal inflammatory response as well as low-flow hypoxia and cytokine overproduction. New information has filled several gaps in the understanding of yellow fever pathogenesis and helped comprehend the course of illness. Finally, we discuss prospects for an immune therapy in the light of new immunologic, viral, and pathologic tools. Copyright © 2013 John Wiley & Sons, Ltd.

  7. Enzootic Transmission of Yellow Fever Virus in Peru

    PubMed Central

    Bryant, Juliet; Wang, Heiman; Cabezas, Cesar; Ramirez, Gladys; Watts, Douglas; Russell, Kevin

    2003-01-01

    The prevailing paradigm of yellow fever virus (YFV) ecology in South America is that of wandering epizootics. The virus is believed to move from place to place in epizootic waves involving monkeys and mosquitoes, rather than persistently circulating within particular locales. After a large outbreak of YFV illness in Peru in 1995, we used phylogenetic analyses of virus isolates to reexamine the hypothesis of virus movement. We sequenced a 670-nucleotide fragment of the prM/E gene region of from 25 Peruvian YFV samples collected from 1977 to 1999, and delineated six clades representing the states (Departments) of Puno, Pasco, Junin, Ayacucho, San Martin/Huanuco, and Cusco. The concurrent appearance of at least four variants during the 1995 epidemic and the genetic stability of separate virus lineages over time, indicate that Peruvian YFV is locally maintained and circulates continuously in discrete foci of enzootic transmission. PMID:12967489

  8. Construction of yellow fever-influenza A chimeric virus particles.

    PubMed

    Oliveira, B C E P D; Liberto, M I M; Barth, O M; Cabral, M C

    2002-12-01

    In order to obtain a better understanding of the functional mechanisms involved in the fusogenesis of enveloped viruses, the influenza A (X31) and the yellow fever (17DD) virus particles were used to construct a chimeric structure based on their distinct pH requirements for fusion, and the distinct malleability of their nucleocapsids. The malleable nucleocapsid of the influenza A virus particle is characterized by a pleomorphic configuration when observed by electron microscopy. A heat inactivated preparation of X31 virus was used as a lectin to interact with the sialic acid domains present in the 17DD virus envelope. The E spikes of 17DD virus were induced to promote fusion of both envelopes, creating a double genome enveloped structure, the chimeric yellow fever-influenza A virus particle. These chimeric viral particles, originally denominated 'partículas virais quiméricas' (PVQ), were characterized by their infectious capacity for different biological systems. Cell inoculation with PVQ resulted in viral products that showed similar characteristics to those obtained after 17DD virus infections. Our findings open new opportunities towards the understanding of both virus particles and aspects of cellular physiologic quality control. The yellow fever-influenza A chimeric particles, by means of their hybrid composition, should be a valuable tool in the study of cell biology and the function of viral components. Copyright 2002 Elsevier Science B.V.

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

    PubMed

    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

  10. NON-FATAL INFECTION OF MICE FOLLOWING INTRACEREBRAL INOCULATION OF YELLOW FEVER VIRUS

    PubMed Central

    Fox, John P.

    1943-01-01

    Observations have been reported which indicate that mice inoculated intracerebrally with active yellow fever virus may develop an infection which is not only non-fatal but may also be completely inapparent. The most extensive observations were made on mice which showed signs of infection but were still alive 22 days after inoculation with virus of one or another of several 17D substrains. In such cases, the infection usually progressed no further and partial or complete recovery often ensued. Agents other than yellow fever virus were excluded as a significant cause of such nonfatal infections by the failure of repeated attempts to isolate other infective agents, by the demonstration of antibodies against yellow fever virus in the sera of the mice, and by the demonstration of a high degree of resistance on the part of such surviving mice to reinoculation with large doses of neurotropic yellow fever virus. Completely inapparent infections with 17D virus were also shown to occur. Studies of apparently normal survivors of 17D virus titrations revealed a small but significant number of animals resistant to intracerebral challenge with neurotropic yellow fever virus. Further, pooled sera from such mice were shown to contain specific protective antibodies. The occurrence of non-fatal infections with 17D virus was found related to virus dose and substrain. Small doses of virus provoked a significantly higher proportion of non-fatal infections than large doses; while different 17D substrains, tested over equivalent ranges of virus dose, varied greatly with respect to the proportion of infections which did not terminate with death. In the case of two substrains (17DD low and 17D3), non-fatal infections (as demonstrated by resistance to intracerebral challenge with neurotropic virus) were sufficiently frequent to cause an increase, when included in the computation of the infective titers, of 25 per cent above the figures based on deaths alone. The demonstration of non

  11. Japanese encephalitis virus/yellow fever virus chimera is safe and confers full protection against yellow fever virus in intracerebrally challenged mice.

    PubMed

    Yang, Huiqiang; Yang, Huan; Li, Zhushi; Liu, Lina; Wang, Wei; He, Ting; Fan, Fengming; Sun, Yan; Liu, Jie; Li, Yuhua; Zeng, Xianwu

    2018-04-25

    Yellow fever (YF) is an acute viral haemorrhagic disease caused by the yellow fever virus (YFV), which remains a potential threat to public health. The live-attenuated YF vaccine (17D strain) is a safe and highly effective measure against YF. However, increasing adverse events have been associated with YF vaccinations in recent years; thus, safer, alternative vaccines are needed. In this study, using the Japanese encephalitis live vaccine strain SA14-14-2 as a backbone, a novel chimeric virus was constructed by replacing the pre-membrane (prM) and envelope (E) genes with their YFV 17D counterparts.The chimeric virus exhibited a reduced growth rate and a much smaller plaque morphology than did either parental virus. Furthermore, the chimera was much less neurovirulent than was YF17D and protected mice that were challenged with a lethal dose of the YF virus. These results suggest that this chimera has potential as a novel attenuated YF vaccine. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  13. Yellow Fever Vaccination of a Primary Vaccinee During Adalimumab Therapy.

    PubMed

    Nash, Esther R; Brand, Myron; Chalkias, Spyridon

    2015-01-01

    In this case report, we describe a 63-year-old female with Crohn's disease since age 16 years, and on adalimumab therapy, who inadvertently received a yellow fever vaccine (YFV) 4 days before her next dose of adalimumab. She had never received YFV. Her next dose of tumor necrosis factor (TNF) antagonist was held. She did not report any adverse effects referable to the vaccine. Reverse transcriptase-polymerase chain reaction (RT-PCR) for yellow fever (YF) viral RNA on days 12 and 18 postvaccination was negative. Neutralizing antibody to YF virus vaccine was immunoprotective on day 18 following vaccination, which further increased by day 26. A neutralizing antibody obtained 2 years following vaccination also remained immunoprotective. © 2015 International Society of Travel Medicine.

  14. Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Preliminary Report.

    PubMed

    Ahuka-Mundeke, Steve; Casey, Rebecca M; Harris, Jennifer B; Dixon, Meredith G; Nsele, Pierre M; Kizito, Gabriel M; Umutesi, Grace; Laven, Janeen; Paluku, Gilson; Gueye, Abdou S; Hyde, Terri B; Sheria, Guylain K M; Muyembe-Tanfum, Jean-Jacques; Staples, J Erin

    2018-02-14

    Background In 2016, the response to a yellow fever outbreak in Angola and the Democratic Republic of Congo led to a global shortage of yellow fever vaccine. As a result, a fractional dose of the 17DD yellow fever vaccine (containing one fifth [0.1 ml] of the standard dose) was offered to 7.6 million children 2 years of age or older and nonpregnant adults in a preemptive campaign in Kinshasa. The goal of this study was to assess the immune response to the fractional dose in a large-scale campaign. Methods We recruited participants in four age strata at six vaccination sites. We assessed neutralizing antibody titers against yellow fever virus in blood samples obtained before vaccination and 28 to 35 days after vaccination, using a plaque reduction neutralization test with a 50% cutoff (PRNT 50 ). Participants with a PRNT 50 titer of 10 or higher at baseline were considered to be seropositive. Those with a baseline titer of less than 10 who became seropositive at follow-up were classified as having undergone seroconversion. Participants who were seropositive at baseline and who had an increase in the titer by a factor of 4 or more at follow-up were classified as having an immune response. Results Among 716 participants who completed follow-up, 705 (98%; 95% confidence interval [CI], 97 to 99) were seropositive after vaccination. Among 493 participants who were seronegative at baseline, 482 (98%; 95% CI, 96 to 99) underwent seroconversion. Among 223 participants who were seropositive at baseline, 148 (66%; 95% CI, 60 to 72) had an immune response. Lower baseline titers were associated with a higher probability of having an immune response (P<0.001). Conclusions A fractional dose of the 17DD yellow fever vaccine was effective at inducing seroconversion in most of the participants who were seronegative at baseline. These findings support the use of fractional-dose vaccination for outbreak control. (Funded by the U.S. Agency for International Development and the Centers

  15. Crotoxin and phospholipases A₂ from Crotalus durissus terrificus showed antiviral activity against dengue and yellow fever viruses.

    PubMed

    Muller, Vanessa Danielle Menjon; Russo, Raquel Rinaldi; Cintra, Adelia Cristina Oliveira; Sartim, Marco Aurélio; Alves-Paiva, Raquel De Melo; Figueiredo, Luiz Tadeu Moraes; Sampaio, Suely Vilela; Aquino, Victor Hugo

    2012-03-15

    Dengue is the most important arbovirus in the world with an estimated of 50 million dengue infections occurring annually and approximately 2.5 billion people living in dengue endemic countries. Yellow fever is a viral hemorrhagic fever with high mortality that is transmitted by mosquitoes. Effective vaccines against yellow fever have been available for almost 70 years and are responsible for a significant reduction of occurrences of the disease worldwide; however, approximately 200,000 cases of yellow fever still occur annually, principally in Africa. Therefore, it is a public health priority to develop antiviral agents for treatment of these virus infections. Crotalus durissus terrificus snake, a South American rattlesnake, presents venom with several biologically actives molecules. In this study, we evaluated the antiviral activity of crude venom and isolated toxins from Crotalus durissus terrificus and found that phospholipases A₂ showed a high inhibition of Yellow fever and dengue viruses in VERO E6 cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  17. Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters.

    PubMed

    Mateo, Rosa I; Xiao, Shu-Yuan; Travassos da Rosa, Amelia P A; Lei, Hao; Guzman, Hilda; Lu, Liang; Tesh, Robert B

    2007-11-01

    Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.

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

    PubMed

    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.

  19. STUDIES ON YELLOW FEVER IN SOUTH AMERICA

    PubMed Central

    Davis, Nelson C.; Shannon, Raymond C.

    1929-01-01

    1. Batches of Aëdes (Stegomyia) aegypti which had fed on monkeys in the early febrile stage of yellow fever and which has subsequently passed the usually accepted extrinsic incubation period for the virus, failed to transmit the disease to normal monkeys in approximately fifty per cent of the experiments. During the same time over eighty per cent of blood transfers were successful. 2. The monkeys which failed to show fever following mosquito bites later proved resistant to the inoculation of blood or tissues containing virus. 3. The incubation, or afebrile, period in monkeys following the bites of infected mosquitoes varied from less than twenty-four hours to fifteen days. It averaged somewhat longer in non-fatal than in fatal infections. PMID:19869665

  20. Isolation of yellow fever virus from mosquitoes in Misiones province, Argentina.

    PubMed

    Goenaga, Silvina; Fabbri, Cintia; Dueñas, Juan Climaco Rondan; Gardenal, Cristina Noemí; Rossi, Gustavo Carlos; Calderon, Gladys; Morales, Maria Alejandra; Garcia, Jorge Braulio; Enria, Delia Alcira; Levis, Silvana

    2012-11-01

    Yellow fever (YF) is a viral hemorrhagic fever endemic to tropical regions of South America and Africa. From 2007 to 2009 an important epidemic/epizootic of YF was detected in different populations of howler monkeys (Alouatta species) in Misiones, a northeastern Argentinian province. Yellow fever virus (YFV) infection was researched and documented by laboratory tests in humans and in dead Alouatta carayá. The objective of that research was to investigate the circulation of YFV in mosquitoes, which could be implicated in the sylvatic transmission of YF in Argentina. The above-mentioned mosquitoes were captured in the same geographical region where the epizootic took place. A YFV strain was isolated in cell culture from pools of Sabethes albiprivus. This study is not only the first isolation of YFV from mosquitoes in Argentina, but it is also the first YFV isolation reported in the species Sabethes albiprivus, suggesting that this species might be playing a key role in sylvatic YF in Argentina.

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

    PubMed

    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.

  2. Zika virus infection, associated microcephaly, and low yellow fever vaccination coverage in Brazil: is there any causal link?

    PubMed

    De Góes Cavalcanti, Luciano Pamplona; Tauil, Pedro Luiz; Alencar, Carlos Henrique; Oliveira, Wanderson; Teixeira, Mauro Martins; Heukelbach, Jorg

    2016-06-30

    Since the end of 2014, Zika virus (ZIKV) infection has been rapidly spreading in Brazil. To analyze the possible association of yellow fever vaccine with a protective effect against ZIKV-related microcephaly, the following spatial analyses were performed, using Brazilian municipalities as units: i) yellow fever vaccination coverage in Brazilian municipalities in individuals aged 15-49; ii) reported cases of microcephaly by municipality; and iii) confirmed cases of microcephaly related to ZIKV, by municipality. SaTScan software was used to identify clusters of municipalities for high risk of microcephaly. There were seven significant high risk clusters of confirmed microcephaly cases, with four of them located in the Northeast where yellow fever vaccination rates were the lowest. The clusters harbored only 2.9% of the total population of Brazil, but 15.2% of confirmed cases of microcephaly. We hypothesize that pregnant women in regions with high yellow fever vaccination coverage may pose their offspring to lower risk for development of microcephaly. There is an urgent need for systematic studies to confirm the possible link between low yellow fever vaccination coverage, Zika virus infection and microcephaly.

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

    PubMed

    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.

  4. The enigma of yellow fever in East Africa.

    PubMed

    Ellis, Brett R; Barrett, Alan D T

    2008-01-01

    Despite a safe and effective vaccine, there are approximately 200,000 cases, including 30,000 deaths, due to yellow fever virus (YFV) each year, of which 90% are in Africa. The natural history of YFV has been well described, especially in West Africa, but in East Africa yellow fever (YF) remains characterised by unpredictable focal periodicity and a precarious potential for large epidemics. Recent outbreaks of YF in Kenya (1992-1993) and Sudan (2003 and 2005) are important because each of these outbreaks have involved the re-emergence of a YFV genotype (East Africa) that remained undetected for nearly 40 years and was previously unconfirmed in a clinically apparent outbreak. In addition, unlike West Africa and South America, YF has yet to emerge in urban areas of East Africa and be vectored by Aedes (Stegomyia) aegypti. This is a significant public health concern in a region where the majority of the population remains unvaccinated. This review describes historical findings, highlights a number of disease indicators, and provides clarification regarding the natural history, recent emergence and future risk of YF in East Africa. Copyright (c) 2008 John Wiley & Sons, Ltd.

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

    PubMed

    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.

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

    PubMed

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

    PubMed

    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.

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

    PubMed

    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.

  9. Insights into human CD8(+) T-cell memory using the yellow fever and smallpox vaccines.

    PubMed

    Ahmed, Rafi; Akondy, Rama S

    2011-03-01

    Live virus vaccines provide a unique opportunity to study human CD8(+) T-cell memory in the context of a controlled, primary acute viral infection. Yellow fever virus-17D and Dryvax are two such live-virus vaccines that are highly efficacious, used worldwide and provide long-term immunity against yellow fever and smallpox respectively. In this review, we describe the properties of virus-specific memory CD8(+) T cells generated in smallpox and yellow fever vaccinees. We address fundamental questions regarding magnitude, functional quality and longevity of the CD8(+) T-cell response, which are otherwise challenging to address in humans. These findings provide insights into the attributes of the human immune system as well as provide a benchmark for the optimal quality of a CD8(+) T-cell response that can be used to evaluate novel candidate vaccines.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  14. Gestational exposure to yellow fever vaccine at different developmental stages induces behavioral alterations in the progeny.

    PubMed

    Marianno, P; Salles, M J S; Sonego, A B; Costa, G A; Galvão, T C; Lima, G Z; Moreira, E G

    2013-01-01

    The most effective method to prevent yellow fever and control the disease is a vaccine made with attenuated live virus. Due to the neurological tropism of the virus, preventive vaccination is not recommended for infants under 6 months and for pregnant women. However there is a paucity of data regarding the safety for pregnant women and there are no experimental studies investigating adverse effects to the offspring after maternal exposure to the vaccine. This study aimed to investigate, in mice, the effects of maternal exposure to the yellow fever vaccine at three different gestational ages on the physical and behavioral development of the offspring. Pregnant Swiss mice received a single subcutaneous injection of water for injection (control groups) or 2 log Plaque Forming Units (vaccine-treated groups) of the yellow fever vaccine on gestational days (GD) 5, 10 or 15. Neither maternal signs of toxicity nor alterations in physical development and reflex ontogeny of the offspring were observed in any of the groups. Data from behavioral evaluation indicated that yellow fever vaccine exposure induced motor hypoactivity in 22-day-old females independent of the day of exposure; and in 60-day-old male and female pups exposed at GD 10. Moreover, 22-day-old females also presented with a deficit in habituation memory. Altogether, these results indicate that in utero exposure to the yellow fever vaccine may induce behavioral alterations in the pups that may persist to adulthood in the absence of observed maternal toxicity or disruption of physical development milestones or reflex ontogeny. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Proved and potential vectors of yellow fever in South Africa

    PubMed Central

    De Meillon, Botha

    1954-01-01

    This paper, based on records obtained from the Entomology Department of the South African Institute for Medical Research, Johannesburg, gives a summary of the distribution, adult habits, and breeding-places of the proved and potential vectors of yellow fever in South Africa. PMID:13209304

  16. [Serological diagnosis of dengue and yellow fever infections in suspected cases from Pará State, Brazil, 1999].

    PubMed

    de Araújo, Tais Pinheiro; Rodrigues, Sueli Guerreiro; Costa, Maria Irene Weyl de A; Vasconcelos, Pedro Fernando da Costa; da Rosa, Amélia P A Travassos

    2002-01-01

    From June to December 1999, 785 serum samples were obtained from patients clinically suspected of having dengue or yellow fever. The patients were referred by public health centers distributed within the six mesoregions of Par State, Brazil. Serum samples were tested for Flavivirus antibodies by hemagglutination inhibition test and for dengue and yellow fever viruses by enzyme-linked immunosorbent assay for IgM detection. Of the sera collected, 563 (71.7%) were positive by HI test and out of these 150 (26.6%) were positive by ELISA-IgM. Dengue virus was responsible for most of the recent infections in all regions; yellow fever cases detected in the current study were restricted to the Maraj and Southeast regions.

  17. 58. Photographic copy of historic medal, The Yellow Fever Medal, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    58. Photographic copy of historic medal, The Yellow Fever Medal, presented to the Portsmouth Naval Hospital by the Town Council of Portsmouth, 1856. (Portsmouth Naval Shipyard Museum, Portsmouth, VA) - Portsmouth Naval Hospital, Hospital Building, Rixey Place, bounded by Williamson Drive, Holcomb Road, & The Circle, Portsmouth, Portsmouth, VA

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

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24245856

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

    PubMed

    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.

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

    PubMed

    Mercier-Delarue, Séverine; Durier, Christine; Colin de Verdière, Nathalie; Poveda, Jean-Dominique; Meiffrédy, Vincent; Fernandez Garcia, Maria Dolores; Lastère, Stéphane; Césaire, Raymond; Manuggera, Jean-Claude; Molina, Jean-Michel; Amara, Ali; Simon, François

    2017-01-01

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  3. Yellow fever vaccination: some thoughts on how much is enough [Vaccine 23 (2005) 3908-3914].

    PubMed

    Martins, Reinaldo M; Galler, Ricardo; Freire, Marcos Silva; Camacho, Luiz Antonio B; de Lourdes S Maia, Maria; Homma, Akira

    2007-01-02

    In a recently published article in this journal, Massad et al. contraindicates yellow fever vaccination to persons 60 years or older, considering that the risk of serious adverse events is higher for this age class. The conclusion was based on the input of available data on age-related probabilities of developing serious adverse events in the United States, as well on other data not firmly established. We consider such contraindication inadequate, because the data input has limitations, higher letality of wild-type yellow fever infection in older adults, risk of introduction of yellow fever by travelers into new countries, lower risk of vaccine adverse events in revaccinated or immune people in endemic countries, and the experience of Brazil, with only one suspect case of associated viscerotropic disease in an individual older than 60 years. The model proposed by Massad et al. is useful but can lead to different conclusions, depending on the epidemiological context and individual risk profile.

  4. Longitudinal myelitis associated with yellow fever vaccination.

    PubMed

    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.

  5. The Yellow Fever Vaccine: A History

    PubMed Central

    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 Professor of Epidemiology and Public Health at Yale from 1964-67, and whose work on virus attenuation created the modern vaccine and earned him the Nobel Prize. PMID:20589188

  6. How many published cases of serious adverse events after yellow fever vaccination meet Brighton Collaboration diagnostic criteria?

    PubMed

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

    2013-12-16

    To perform a systematic review of all serious adverse events (SAEs) after yellow fever vaccination and to assess them according to Brighton Collaboration criteria. Nine electronic databases were searched with the terms "yellow fever vaccine" and "adverse events" to 10 July 2013 (no language/date limits). Two reviewers independently assessed studies, entered data, and assessed cases with Brighton Collaboration criteria. One hundred and thirty-one cases met Brighton Collaboration criteria: 32 anaphylaxis, 41 neurologic (one death), 56 viscerotropic (24 deaths), and 2 both neurologic and viscerotropic criteria. All SAEs occurred following first yellow fever (YF) vaccination. Two additional cases which met Brighton Collaboration criteria were proven due to wild virus. An additional 345 cases were presented with insufficient detail to meet Brighton Collaboration criteria:173 neurological, 68 viscerotropic (24 deaths), 67 anaphylaxis, and 34 cases from a UK database and 3 from a Swiss database described as "serious adverse events" but not further classified into neurologic or viscerotropic. A further 253 cases were excluded as presenting insufficient data to be regarded as yellow fever vaccine (YFV) related SAEs. One hundred and thirty-one cases met Brighton Collaboration criteria for serious adverse events after yellow fever vaccination. Another 345 cases did not meet Brighton criteria and 253 were excluded as presenting insufficient data to be regarded as serious adverse events after YFV. There are likely to be cases in areas that are remote or with insufficient diagnostic resources that are neither correctly assessed nor not published. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

    PubMed

    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

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

    PubMed Central

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

    2016-01-01

    ABSTRACT Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 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 BDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the 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 virus 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. IMPORTANCE Yellow fever is an acute viral hemorrhagic disease which threatens approximately 1 billion people living in tropical areas of Africa and Latin America. Although a highly effective yellow fever vaccine has been available for more than 7 decades, the low vaccination

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

    PubMed

    Bagonza, James; Rutebemberwa, Elizeus; Mugaga, Malimbo; Tumuhamye, Nathan; Makumbi, Issa

    2013-03-07

    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. 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. 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%). Our results show that actual yellow fever vaccination coverage was high and satisfactory in Pader district since it was above the desired minimum threshold coverage of 80% according

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

    PubMed Central

    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

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

    PubMed

    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.

  12. New developments in flavivirus vaccines with special attention to yellow fever.

    PubMed

    Pugachev, Konstantin V; Guirakhoo, Farshad; Monath, Thomas P

    2005-10-01

    Here we review recent epidemiological trends in flavivirus diseases, findings related to existing vaccines, and new directions in flavivirus vaccine research. We emphasize the need for stepped-up efforts to stop further spread and intensification of these infections worldwide. Although the incidence and geographic distribution of flavivirus diseases have increased in recent years, human vaccines are available only for yellow fever, Japanese encephalitis, tick-borne encephalitis and Kyasanur forest disease. Factors contributing to resurgence include insufficient supplies of available vaccines, incomplete vaccination coverage and relaxation in vector control. Research has been underway for 60 years to develop effective vaccines against dengue, and recent progress is encouraging. The development of vaccines against West Nile, virus recently introduced to North America, has been initiated. In addition, there is considerable interest in improving existing vaccines with respect to increasing safety (e.g. eliminating the newly recognized syndrome of yellow fever vaccine-associated viscerotropic adverse disease), and to reducing the cost and number of doses required for effective immunization. Traditional approaches to flavivirus vaccines are still employed, while recent advancements in biotechnology produced new approaches to vaccine design, such as recombinant live virus, subunit and DNA vaccines. Live chimeric vaccines against dengue, Japanese encephalitis and West Nile based on yellow fever 17D virus (ChimeriVax) are in phase I/II trials, with encouraging results. Other chimeric dengue, tick-borne encephalitis and West Nile virus candidates were developed based on attenuated dengue backbones. To further reduce the impact of flavivirus diseases, vaccination policies and vector control programs in affected countries require revision.

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

    PubMed

    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.

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

    PubMed

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

    PubMed

    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.

  16. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    PubMed

    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.

  17. THE SURVIVAL OF YELLOW FEVER VIRUS IN CULTURES

    PubMed Central

    Lewis, Paul A.

    1930-01-01

    1. The virus of yellow fever has been found to survive in artificial culture media for at least 12 days at a temperature of 35°C. No visible growth has been present and no reproduction of the virus has been demonstrated. 2. Infections have been obtained in rhesus monkeys with two strains of virus in quantities as small as 0.00001 cc. of infectious blood, and with one strain in an amount probably as minute as 0.000001 cc. PMID:19869744

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  1. Functional Characterization of the Octenol Receptor Neuron on the Maxillary Palps of the Yellow Fever Mosquito, Aedes aegypti

    DTIC Science & Technology

    2011-06-30

    Functional Characterization of the Octenol Receptor Neuron on the Maxillary Palps of the Yellow Fever Mosquito, Aedes aegypti Alan J. Grant, Joseph C...Dickens JC (2011) Functional Characterization of the Octenol Receptor Neuron on the Maxillary Palps of the Yellow Fever Mosquito, Aedes aegypti . PLoS...palps. Both sexes of mosquitoes possess basiconic sensilla that contain three neurons; in Aedes aegypti these sensilla number about 35 in females and 21

  2. Impact of yellow fever on the developing world.

    PubMed

    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.

  3. [Yellow fever vaccination in non-immunocompetent patients].

    PubMed

    Bruyand, M; Receveur, M C; Pistone, T; Verdière, C H; Thiebaut, R; Malvy, D

    2008-10-01

    Any person travelling in countries where yellow fever (YF) is endemic and without presenting contra-indication for the vaccination against YF may be vaccinated. This vaccination can very rarely induce a potentially lethal neurotropic or viscerotropic disease. In severely immunodeficient patients, the vaccination is contra-indicated because postvaccinal encephalitis may occur after the vaccination, due to vaccine strain pathogenecity. It is important to evaluate the general health status in elderly individuals before vaccinating because of the increased risk of viscerotropic disease in people of 60 years of age and over. Pregnant women should not be vaccinated, except if departure to an endemic zone is unavoidable. YF vaccinatio is contra-indicated for newborns under six months of age. Solid organ grafts, congenital immunodeficiency, leukemia, lymphoma, cancer, and immunosuppressive treatments are contra-indications for this vaccination. Nevertheless, YF immunization is possible after a bone marrow graft and a two-year period without graft-versus-host disease or immunosuppressive treatment. There is no data to support that immunization of the dono prior to the graft could confer protection against yellow fever to the recipient. Low doses, short courses of corticosteroids either as systemic treatment or intra-articular injections are not contra-indications for YF vaccination. Patients infected with HIV with stable clinical status and T CD4-cel count above 200 cells per millimetre cube may be vaccinated. Thymic diseases, including thymoma and thymectomy, are contra-indications for YF vaccination. Finally, a substantial residual level of antibodies beyond 10 years after the latest vaccination could confer protection, thus avoiding a new vaccination when it is an issue.

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

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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.

  7. [Antibody responses in Japanese volunteers after immunization with yellow fever vaccine].

    PubMed

    Taga, Kenichiro; Imura, Shunro; Hayashi, Akihiro; Kamakura, Kazumasa; Hashimoto, Satoru; Takasaki, Tomohiko; Kurane, Ichiro; Uchida, Yukinori

    2002-09-01

    To monitor the development of specific and cross-reactive antibody response in twenty Japanese volunteers after vaccination with live yellow fever vaccine. Serum samples were collected on various days after vaccination and examined for hemagglutination inhibition (HI) antibodies against yellow fever virus (YFV), Japanese encephalitis virus (JEV) and dengue virus (DV), neutralizing antibodies against YFV and JEV, and IgM antibodies against YFV. None of the volunteers had been previously immunized with this vaccine. Fifteen of 20 had pre-vaccinated with JEV 7 to 40 years before. Ten of the 20 had neutralizing antibodies against JEV before immunization. None of the 20 had detectable antibodies against YFV or DV before vaccination. On day 10th after the vaccination, neutralizing antibodies to YFV were detected in 6 of 19 volunteers and IgM antibodies against YFV were detected in 7 of 19. On day 14th, HI, neutralizing, and IgM antibodies against YFV were detected in all the tested sera. Neutralizing antibodies against JEV were developed in 2 volunteers and HI antibodies against JEV were increased in 3 of 6 volunteers respectively. On day 29th, cross-reactive HI antibodies for JEV and DV were detected in all the tested sera. The results indicate that YF vaccine induces YFV-specific antibodies in all the tested volunteers and that it also induces HI antibodies cross-reactive for JEV and DV. The YF vaccine has a strong immunogenicity because it is a live vaccine, and induces antibody against YFV predominantly. The international certificate of yellow fever vaccination becomes valid 10 days after vaccination. On day 14th after vaccination, we detected neutralizing antibodies against YFV from all tested volunteers, however, only 6 of 19 volunteers had detectable neutralizing antibody on the 10th day after vaccination. Therefore, the vaccine may not be perfectly effective on day 10th after the vaccination.

  8. ELECTROPHORESIS EXPERIMENTS WITH THE VIRUS AND PROTECTIVE BODIES OF YELLOW FEVER

    PubMed Central

    Frobisher, Martin

    1931-01-01

    1. When suspended in slightly alkaline (pH 7.4 to 7.8) saline dilutions of clear, hemoglobin-free normal monkey serum, the virus of yellow fever from infected monkeys and from infected, but blood-free, mosquitoes, usually acts as if it were possessed of a positive electrical charge. 2. The virus tends to assume a negative charge in fluids having a slightly acid reaction. 3. The isoelectric point of the virus seems to be in the neighborhood of pH 7.0, possibly ranging from pH 7.3 to pH 6.9. 4. Exposure to fluid having a reaction of pH 5.0 for 3 hours appeared to inactivate the virus. 5. In experiments in which the suspending fluid was prepared with normal serum diluted with distilled water and containing a good quantity of partly hemolyzed erythrocytes, the virus tended to migrate to the anode. 6. The protective bodies in yellow fever immune serum appear to carry a negative charge in slightly alkaline saline dilutions of serum. PMID:19869954

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

    PubMed

    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.

  10. Midzonal lesions in yellow fever: a specific pattern of liver injury caused by direct virus action and in situ inflammatory response.

    PubMed

    Quaresma, Juarez A S; Duarte, Maria I S; Vasconcelos, Pedro F C

    2006-01-01

    Yellow fever is an acute infectious, non-contagious disease characterized by intense vasculopathy and lesions in different organs. In the liver, one of the main targets of the virus, the infection induces a characteristic midzonal injury characterized by hepatocyte necrosis, apoptosis and steatosis. This characteristics pattern of liver injury in yellow fever is also observed in conditions of low-flow hypoxia and other infections such as dengue and Rift Valley fever. There are no reports in the literature explaining the genesis of this peculiar histopathological pattern in yellow fever. Some hypotheses have been proposed to explain the mechanism of this midzonal distribution pattern observed in the liver such as low-flow hypoxia and tropism of the virus toward hepatocytes in this area. These hypotheses are discussed in view of more recent findings regarding the pathogenesis of yellow fever and regarding hepatic physiopathology, and a new hypothesis is proposed: the midzonal necrosis is consequence of action of combined factors mainly the direct cytopathic effect of YFV associated with a potent immune response in which CD4+ and CD8+ lymphocytes and the cytokines, especially TGF-beta, but also TNF-alpha and IFN-gamma play an important role.

  11. RNA interference inhibits yellow fever virus replication in vitro and in vivo.

    PubMed

    Pacca, Carolina C; Severino, Adriana A; Mondini, Adriano; Rahal, Paula; D'avila, Solange G P; Cordeiro, José Antonio; Nogueira, Mara Correa Lelles; Bronzoni, Roberta V M; Nogueira, Maurício L

    2009-04-01

    RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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.

  16. Yellow fever virus in Haemagogus leucocelaenus and Aedes serratus mosquitoes, southern Brazil, 2008.

    PubMed

    Cardoso, Jader da C; de Almeida, Marco A B; dos Santos, Edmilson; da Fonseca, Daltro F; Sallum, Maria A M; Noll, Carlos A; Monteiro, Hamilton A de O; Cruz, Ana C R; Carvalho, Valeria L; Pinto, Eliana V; Castro, Francisco C; Nunes Neto, Joaquim P; Segura, Maria N O; Vasconcelos, Pedro F C

    2010-12-01

    Yellow fever virus (YFV) was isolated from Haemagogus leucocelaenus mosquitoes during an epizootic in 2001 in the Rio Grande do Sul State in southern Brazil. In October 2008, a yellow fever outbreak was reported there, with nonhuman primate deaths and human cases. This latter outbreak led to intensification of surveillance measures for early detection of YFV and support for vaccination programs. We report entomologic surveillance in 2 municipalities that recorded nonhuman primate deaths. Mosquitoes were collected at ground level, identified, and processed for virus isolation and molecular analyses. Eight YFV strains were isolated (7 from pools of Hg. leucocelaenus mosquitoes and another from Aedes serratus mosquitoes); 6 were sequenced, and they grouped in the YFV South American genotype I. The results confirmed the role of Hg. leucocelaenus mosquitoes as the main YFV vector in southern Brazil and suggest that Ae. serratus mosquitoes may have a potential role as a secondary vector.

  17. A real-time reverse transcription loop-mediated isothermal amplification assay for the rapid detection of yellow fever virus.

    PubMed

    Kwallah, Allan ole; Inoue, Shingo; Muigai, Anne W T; Kubo, Toru; Sang, Rosemary; Morita, Kouichi; Mwau, Matilu

    2013-10-01

    Yellow fever, a mosquito-borne disease, is an important viral hemorrhagic fever in Africa and South America where it is endemic. Detection of yellow fever virus (YFV) in Africa remains a challenge due to a lack of highly specific tests. The aim of this study was to develop and optimize a rapid detection reverse transcription loop-mediated isothermal amplification (RT-LAMP) for YFV. The RT-LAMP was done isothermally at 62 °C using a real-time turbidimeter that allowed detection within 1h. Specificity of the RT-LAMP was determined using RNA from flaviviruses and other related viruses where only YFV RNA was detected: West Nile virus, dengue viruses, Japanese encephalitis virus, Rift Valley fever virus, and chikungunya virus. In addition, equal sensitivity was also observed when the RT-LAMP and the real-time RT-PCR were compared using YFV-spiked human serum samples with a detection limit of 0.29 PFU/ml. Two Kenyan YFV wild strains showed an equal detection limit as the vaccine strain 17D in this study. The RT-LAMP reduced the time of reaction from 3h to 1h and increased sensitivity tenfold compared to RT-PCR. Therefore, this test offers a simple, rapid and reliable diagnostic tool for yellow fever when there are outbreaks of acute hemorrhagic fever in Kenya and other African countries. Copyright © 2013 Elsevier B.V. All rights reserved.

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

    PubMed

    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.

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

    PubMed Central

    Le Gal, Frédéric; Ngwaka-Matsung, Nadine; Ahuka-Mundeke, Steve; Onanga, Richard; Pukuta-Simbu, Elisabeth; Gerber, Athenaïs; Abbate, Jessica L.; Mwamba, Dieudonné; Berthet, Nicolas; Leroy, Eric Maurice; Muyembe-Tamfum, Jean-Jacques

    2017-01-01

    ABSTRACT 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 × 105 IU/ml for HBV (range, 769 to 9.82 × 109 IU/ml) and 1.4 × 106 IU/ml for HDV (range, 3.1 × 102 to 2.9 × 108 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. PMID:28202798

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

    PubMed

    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.

  1. [The "plague" of Barcelona. Yellow fever epidemic of 1821].

    PubMed

    Chastel, C

    1999-12-01

    The outbreak of yellow fever that struck Barcelona in 1821 followed a typical pattern for the times: a brick from Cuba introduced the disease in the port docks; the epidemic first reached the poor suburbs, and finally the center of the city. It was assumed that at least 20,000 inhabitants died from the scourge, that is a sixth of the total population of the city estimated 120,000. French authorities promptly took emergency measures at land and maritime borders by locking French ports to Catalan vessels and defining a quarantine line along the Pyrenean border controlled by an army 15,000 strong. French medical team including six physicians and two nuns was sent to Barcelona to provide assistance. Long after the epidemic had receded, the Pyrenean quarantine line was maintained by the French authorities for a hidden political purpose: Paris wished to contain Spanish Liberalism, a "revolutionary pest". French troops engaged in the so-called quarantine line were used in 1823 for invading the Spanish kingdom, while French physicians returning to Paris were celebrated as heroes and benefactors of the mankind although they had not provided any serious contribution to the therapeutics or the epidemiology of yellow fever. They were glorified in publications of the time without reserve. This unexpected manifestation of nationalism was welcomed and encouraged by the government of Louis XVIII who felt himself threatened by the liberal opposition.

  2. Human genetic variation and yellow fever mortality during 19th century U.S. epidemics.

    PubMed

    Blake, Lauren E; Garcia-Blanco, Mariano A

    2014-06-03

    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. Different degrees of severity of yellow fever have been observed across diverse populations, but this study is the first to demonstrate a statistically significant association between ancestry and the outcome of yellow fever (YF). With the global burden of mosquito-borne flaviviral infections, such as YF and dengue, on the rise, identifying and characterizing host factors could prove pivotal in the prevention of epidemics and the development of effective treatments. Copyright © 2014 Blake and Garcia-Blanco.

  3. The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review.

    PubMed

    Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

    2012-02-01

    Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.

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

    PubMed

    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.

  5. Yellow Fever Virus in Haemagogus leucocelaenus and Aedes serratus Mosquitoes, Southern Brazil, 2008

    PubMed Central

    Cardoso, Jáder da C.; de Almeida, Marco A.B.; dos Santos, Edmilson; da Fonseca, Daltro F.; Sallum, Maria A.M.; Noll, Carlos A.; Monteiro, Hamilton A. de O.; Cruz, Ana C.R.; Carvalho, Valéria L.; Pinto, Eliana V.; Castro, Francisco C.; Neto, Joaquim P. Nunes; Segura, Maria N.O.

    2010-01-01

    Yellow fever virus (YFV) was isolated from Haemagogus leucocelaenus mosquitoes during an epizootic in 2001 in the Rio Grande do Sul State in southern Brazil. In October 2008, a yellow fever outbreak was reported there, with nonhuman primate deaths and human cases. This latter outbreak led to intensification of surveillance measures for early detection of YFV and support for vaccination programs. We report entomologic surveillance in 2 municipalities that recorded nonhuman primate deaths. Mosquitoes were collected at ground level, identified, and processed for virus isolation and molecular analyses. Eight YFV strains were isolated (7 from pools of Hg. leucocelaenus mosquitoes and another from Aedes serratus mosquitoes); 6 were sequenced, and they grouped in the YFV South American genotype I. The results confirmed the role of Hg. leucocelaenus mosquitoes as the main YFV vector in southern Brazil and suggest that Ae. serratus mosquitoes may have a potential role as a secondary vector. PMID:21122222

  6. Yellow fever and Max Theiler: the only Nobel Prize for a virus vaccine

    PubMed Central

    Norrby, Erling

    2007-01-01

    In 1951, Max Theiler of the Rockefeller Foundation received the Nobel Prize in Physiology or Medicine for his discovery of an effective vaccine against yellow fever—a discovery first reported in the JEM 70 years ago. This was the first, and so far the only, Nobel Prize given for the development of a virus vaccine. Recently released Nobel archives now reveal how the advances in the yellow fever vaccine field were evaluated more than 50 years ago, and how this led to a prize for Max Theiler. PMID:18039952

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

    PubMed

    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.

  8. Yellow fever vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Staples, J Erin; Gershman, Mark; Fischer, Marc

    2010-07-30

    This report updates CDC's recommendations for using yellow fever (YF) vaccine (CDC. Yellow fever vaccine: recommendations of the Advisory Committee on Immunizations Practices: MMWR 2002;51[No. RR-17]). Since the previous YF vaccine recommendations were published in 2002, new or additional information has become available on the epidemiology of YF, safety profile of the vaccine, and health regulations related to the vaccine. This report summarizes the current epidemiology of YF, describes immunogenicity and safety data for the YF vaccine, and provides recommendations for the use of YF vaccine among travelers and laboratory workers. YF is a vectorborne disease resulting from the transmission of yellow fever virus (YFV) to a human from the bite of an infected mosquito. It is endemic to sub-Saharan Africa and tropical South America and is estimated to cause 200,000 cases of clinical disease and 30,000 deaths annually. Infection in humans is capable of producing hemorrhagic fever and is fatal in 20%-50% of persons with severe disease. Because no treatment exists for YF disease, prevention is critical to lower disease risk and mortality. A traveler's risk for acquiring YFV is determined by multiple factors, including immunization status, location of travel, season, duration of exposure, occupational and recreational activities while traveling, and local rate of virus transmission at the time of travel. All travelers to countries in which YF is endemic should be advised of the risks for contracting the disease and available methods to prevent it, including use of personal protective measures and receipt of vaccine. Administration of YF vaccine is recommended for persons aged >or=9 months who are traveling to or living in areas of South America and Africa in which a risk exists for YFV transmission. Because serious adverse events can occur following YF vaccine administration, health-care providers should vaccinate only persons who are at risk for exposure to YFV or who

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

    PubMed

    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.

  10. WHO position on the use of fractional doses - June 2017, addendum to vaccines and vaccination against yellow fever WHO: Position paper - June 2013.

    PubMed

    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.

  11. Broadening the horizons for yellow fever: new uses for an old vaccine.

    PubMed

    Van Epps, Heather L

    2005-01-17

    The vaccine against yellow fever is one of the safest and most effective ever developed. With an outstanding record in humans, has this live attenuated vaccine been overlooked as a promising vector for the development of vaccines against pathogens outside its own genus? Recent studies, including a report by Tao et al. on page 201 of this issue, have sparked renewed interest.

  12. Ocular manifestations of emerging arboviruses: Dengue fever, Chikungunya, Zika virus, West Nile virus, and yellow fever.

    PubMed

    Merle, H; Donnio, A; Jean-Charles, A; Guyomarch, J; Hage, R; Najioullah, F; Césaire, R; Cabié, A

    2018-06-18

    Arboviruses are viral diseases transmitted by mosquitoes and tick bites. They are a major cause of morbidity and sometimes mortality. Their expansion is constant and due in part to climate change and globalization. Mostly found in tropical regions, arboviruses are sometimes the source of epidemics in Europe. Recently, the Chikungunya virus and the Zika virus were responsible for very large epidemics impacting populations that had never been in contact with those viruses. There are currently no effective antiviral treatments or vaccines. Ocular manifestations due to those infections are thus more frequent and increasingly better described. They are sometimes, as with Zika, complicated by a congenital ocular syndrome. The goal of this review is to describe the ophthalmological manifestations of Dengue fever, Chikungunya virus, Zika virus, West Nile virus, and yellow fever. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

    PubMed

    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.

  14. Using Local History To Understand National Themes: The Yellow Fever Epidemic in Philadelphia in 1793.

    ERIC Educational Resources Information Center

    Westbury, Susan

    2003-01-01

    Provides background information for a local history project about the 1793 Philadelphia (Pennsylvania) yellow fever outbreak. Offers potential project topics to help students learn about local history and understand life in the eighteenth century United States. (CMK)

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

    PubMed

    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.

  16. Increased risk of yellow fever infections among unvaccinated European travellers due to ongoing outbreak in Brazil, July 2017 to March 2018.

    PubMed

    Gossner, Céline M; Haussig, Joana M; de Bellegarde de Saint Lary, Chiara; Kaasik Aaslav, Kaja; Schlagenhauf, Patricia; Sudre, Bertrand

    2018-03-01

    Since December 2016, Brazil has faced a large outbreak of yellow fever with ca 1,500 confirmed human cases. In the first 2 months of 2018, Brazil reported almost as many cases as in 2017 as a whole. In these 2 months, five imported cases were reported among unvaccinated European travellers. Three had travelled to Ilha Grande, a popular destination among European tourists. Physicians and European travellers visiting Brazil should follow yellow fever vaccination recommendations.

  17. A Flow Cytometry-Based Assay for Quantifying Non-Plaque Forming Strains of Yellow Fever Virus

    PubMed Central

    Hammarlund, Erika; Amanna, Ian J.; Dubois, Melissa E.; Barron, Alex; Engelmann, Flora; Messaoudi, Ilhem; Slifka, Mark K.

    2012-01-01

    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. PMID:23028428

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

    PubMed

    Hammarlund, Erika; Amanna, Ian J; Dubois, Melissa E; Barron, Alex; Engelmann, Flora; Messaoudi, Ilhem; Slifka, Mark K

    2012-01-01

    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.

  19. POSSIBILITY OF HEREDITARY TRANSMISSION OF YELLOW FEVER VIRUS BY AEDES AEGYPTI (LINN.)

    PubMed Central

    Philip, Cornelius B.

    1929-01-01

    Attempts to obtain passage of yellow fever virus from one generation to the next in A. aegypti were unsuccessful. Subcutaneous injections at varying intervals of a saline emulsion of 200 eggs laid by an infective lot of mosquitoes produced no reaction in six normal M. rhesus monkeys. Negative results were also obtained in five biting and two injection experiments with progeny of the same infective lot of mosquitoes in which seven normal monkeys were used. The eggs consisted of batches laid after the first, second and fourth blood-meals of the original lot; the latter feeding occurred 41 days after the initial infecting meal. The imaginal offspring represented rearings following the first, second and fifth blood-meals of the parent lot. The last feeding occurred 54 days after the first. It is concluded that under the conditions of the experiments here reported hereditary transmission of yellow fever by A. aegypti is improbable. Variations in age and in number of blood-meals of parent and offspring mosquitoes had no effect in achieving passage of the virus from one stage of the insect to another. PMID:19869656

  20. Yellow Fever Virus Exhibits Slower Evolutionary Dynamics than Dengue Virus ▿ †

    PubMed Central

    Sall, Amadou A.; Faye, Ousmane; Diallo, Mawlouth; Firth, Cadhla; Kitchen, Andrew; Holmes, Edward C.

    2010-01-01

    Although yellow fever has historically been one of the most important viral infections of humans, relatively little is known about the evolutionary processes that shape its genetic diversity. Similarly, there is limited information on the molecular epidemiology of yellow fever virus (YFV) in Africa even though it most likely first emerged on this continent. Through an analysis of complete E gene sequences, including a newly acquired viral collection from Central and West Africa (Senegal, Cameroon, Central African Republic, Côte d'Ivoire, Mali, and Mauritania), we show that YFV exhibits markedly lower rates of evolutionary change than dengue virus, despite numerous biological similarities between these two viruses. From this observation, along with a lack of clock-like evolutionary behavior in YFV, we suggest that vertical transmission, itself characterized by lower replication rates, may play an important role in the evolution of YFV in its enzootic setting. Despite a reduced rate of nucleotide substitution, phylogenetic patterns and estimates of times to common ancestry in YFV still accord well with the dual histories of colonialism and the slave trade, with areas of sylvatic transmission (such as Kedougou, Senegal) acting as enzootic/epidemic foci. PMID:19889759

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

    PubMed

    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.

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

    PubMed

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

    PubMed

    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

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

    PubMed

    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

  5. Revisiting the liver in human yellow fever: virus-induced apoptosis in hepatocytes associated with TGF-beta, TNF-alpha and NK cells activity.

    PubMed

    Quaresma, Juarez A S; Barros, Vera L R S; Pagliari, Carla; Fernandes, Elaine R; Guedes, Fernanda; Takakura, Cleusa F H; Andrade, Heitor F; Vasconcelos, Pedro F C; Duarte, Maria I S

    2006-02-05

    Flavivirus infection as dengue and yellow fever persists as a terrible menace to pandemics, due to Aedes prevalence in the Americas. Yellow fever is characterized by hepatocyte damage, with steatosis, apoptosis and necrosis, mainly in the midzonal region of the liver, but the injury mechanism has not been studied at the light of recent knowledge, such as the advances in cell death mechanisms, inflammatory response and cytokine cell expression tools. We studied 53 human liver paraffin embedded blocks from patients who died with yellow fever, all with histological demonstration of higher prevalence of apoptosis over necrosis and mild disproportionate inflammatory response. Viral antigens were found most frequently in hepatocytes from the midzonal area than other lobule areas, as detected by specific immunohistochemistry. Infiltrating cell subpopulations showed mainly CD4+ T lymphocytes, with small numbers of CD8+ cytotoxic lymphocytes, CD20+ B lymphocytes, NKT+ cells and S100+ dendritic cells in the sites of inflammation, as compared to normal and leptospirosis liver blocks. Some cells expressed TNF-alpha and IFN-gamma, but a much more intense proportion of TGF-beta expressing cells were found, suggesting both a Th1 and Th3 patterns of immune response in yellow fever. Most affected hepatocyte presented apoptosis markers that appear at the cell death main pathway in this infection. Viral antigens, which production could interfere in hepatocyte biology, could induce the activation of apoptosis cascade, but TGF-beta was also an apoptosis promoter. Our finding supports the key effect of the yellow fever virus in hepatocyte injury, resulting in prevalence of apoptosis over necrosis, aside from a TGF-beta action induced by the inflammatory response.

  6. EXPERIMENTAL STUDIES ON YELLOW FEVER IN NORTHERN PERU.

    PubMed

    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. Prevention of yellow fever in persons traveling to the tropics.

    PubMed

    Monath, Thomas P; Cetron, Martin S

    2002-05-15

    Yellow fever (YF) is a potentially lethal mosquito-borne viral hemorrhagic fever endemic in Africa and South America. Nine million tourists annually arrive in countries where YF is endemic, and fatal cases of YF have occurred recently in travelers. In this article, we review the risk factors for YF during travel and the use of YF 17D vaccine to prevent the disease. Although the vaccine is highly effective and has a long history of safe use, the occurrence of rare, fatal adverse events has raised new concerns. These events should not deter travelers to areas where YF is endemic from being immunized, because the risk of YF infection and illness may be high in rural areas and cannot be easily defined by existing surveillance. To avoid unnecessary vaccination, physicians should vaccinate persons at risk on the basis of knowledge of the epidemiology of the disease, reports of epidemic activity, season, and the likelihood of exposure to vector mosquitoes.

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

    PubMed

    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

  9. Severe post-vaccination reaction to 17D yellow fever vaccine in Nigeria.

    PubMed

    Oyelami, S A; Olaleye, O D; Oyejide, C O; Omilabu, S A; Fatunla, B A

    1994-01-01

    An unusual outbreak of post-vaccination reactions to 17D yellow fever vaccine occurred at Shaki, Nigeria, in May 1987. Twenty-five of the affected people were treated at the Baptist Hospital Shaki. The patients presented with rapidly progressing swelling of the left arm with associated fever and other constitutional symptoms few hours after inoculation with the vaccine. Some of the patients developed gangrene of the affected limb, five of them went into coma and died. Poor hygiene and improper handling of vaccine as well as contamination of vaccine from the source are possible causes. A review of vaccine delivery strategies especially at local community levels; sound training, supervision of vaccinators and health education are strongly recommended to prevent reoccurrence of similar reactions.

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

    PubMed

    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.

    PubMed

    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. 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.

    PubMed

    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

  13. IMMUNITY TO YELLOW FEVER ENCEPHALITIS OF MONKEYS AND MICE IMMUNIZED BY NEURAL AND EXTRANEURAL ROUTES

    PubMed Central

    Fox, John P.

    1943-01-01

    Monkeys and mice surviving cerebral infection with yellow fever virus of relatively avirulent strains have been found to resist maximal intracerebral doses of yellow fever virus of a highly neurotropic strain. Such animals, however, do not resist more than very small doses of intracerebrally inoculated virus of Eastern equine encephalomyelitis. Animals immunized by extraneural routes, on the other hand, are not uniformly resistant to neural infection with neurotropic yellow fever virus. Monkeys which have undergone systemic infection with virus of the avirulent 17D strain or of several jungle strains resist only small intracerebral doses of neurotropic virus; while mice, even when possessed of very high serum-antibody levels as the result of intraperitoneal hyperimmunization, manifest only an irregular resistance to intracerebral challenge inocula. The difference in the resistance of neurally and extraneurally immunized animals is not related to similar differences in the levels of protective antibody in the sera. Indeed, the average of the serum-antibody titers of the hyperimmune mice is several times that of the intracerebral immunes. A possibly significant relation does exist, however, between the resistance of mice to neural infection and the content of protective antibody in the brain. The protective activity of suspensions of brains from mice surviving cerebral infection was found to be several times that of brain suspensions from the hyperimmunized animals. It is concluded that the superior resistance to neural infection of animals whose immunity results from a previous non-fatal infection of the nervous system is effected by a specific local mechanism which is based at least in part upon an increased concentration of antibody in the cerebral tissue. PMID:19871299

  14. Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology.

    PubMed

    Pulendran, Bali

    2009-10-01

    Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. Here I review how these developments are yielding insights into the mechanism of action of the yellow fever vaccine, one of the most successful vaccines ever developed, and the broader implications for vaccinology.

  15. Yellow fever vector live-virus vaccines: West Nile virus vaccine development.

    PubMed

    Arroyo, J; Miller, C A; Catalan, J; Monath, T P

    2001-08-01

    By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World afflicting humans, horses and birds, the success of this recombinant technology has prompted the rapid development of a live-virus attenuated candidate vaccine against West Nile virus.

  16. Administration of yellow fever vaccine in patients with egg allergy.

    PubMed

    Rutkowski, K; Ewan, P W; Nasser, S M

    2013-01-01

    The population of large parts of Africa, South America and travellers to these areas are at risk of yellow fever (YF) with a 50% mortality risk. Yellow fever vaccine (YFV) propagated in hens' eggs confers protection in 95% of the vaccinated. The rate of anaphylaxis for YFV ranges from 0.42 to 1.8/100,000 doses with most cases considered to be due to egg allergy. Egg allergy is a contraindication for the YFV. Nevertheless, the potential fatal sequelae from YF give the incentive to protect everyone at risk irrespective of their allergic status. Six subjects who had had a recent reaction to egg and who were travelling to endemic areas (3 adults and 3 children) underwent skin prick tests (SPT) with undiluted YFV and egg extract. Intradermal tests for YFV were undertaken at a 1:10 dilution. In 4 egg-allergic patients with a positive SPT to YFV, a 7-step desensitization protocol was used. A 2-step (10 + 90%) protocol was used in the 2 subjects with a negative YFV SPT. Premedication was not administered. All 6 patients were successfully vaccinated. Four patients completed desensitization: 1 developed mild local erythema at the injection site, 1 had fleeting generalized urticaria with local erythema/angioedema and 2 did not experience any adverse reactions. Patients who received YFV in 2 steps developed no adverse reactions. We describe the successful administration of YFV in 6 egg-allergic patients. The Cambridge Allergy 7-step protocol allows for its safe administration in patients with positive SPT to YFV. A 2-step protocol can be used in patients with negative YFV SPT. Copyright © 2013 S. Karger AG, Basel.

  17. Demographic profile of sylvatic yellow fever in Brazil from 1973 to 2008.

    PubMed

    Câmara, Fernando Portela; de Carvalho, Luiz Max; Gomes, Ana Luisa Bacellar

    2013-05-01

    Yellow fever is an acute, frequently fatal, febrile arbovirosis that in Brazil occurs only in the sylvatic form. Sylvatic yellow fever (SYF) appears in sporadic outbreaks over a large area of Brazil. In this paper, we analyze the demographic profile of 831 SYF cases that occurred between 1973 and 2008, to determine which segments of the exposed population are at greater risk. Data were statistically analyzed and were also geo-referenced in order to observe their spatial pattern. The basic reproductive number of infections, R0, was estimated by the ratio between average life expectancy and the average age of the cases. SYF cases showed a modal profile of young male adults, approximately 30 years of age, living in rural areas of the states of Pará, Goiás, Maranhão and Minas Gerais, who were unvaccinated or whose vaccination was out of date. The disease showed a high mortality rate (51%, 421/831) among the notified cases, with death occurring on around the seventh day of illness for most patients. The R0 for SYF was estimated at approximately 2.4. The results of this study suggest that lack of vaccination coverage is a major risk factor for SYF, and that the groups most at risk are migrant laborers, farm workers and tourists.

  18. Late or Lack of Vaccination Linked to Importation of Yellow Fever from Angola to China.

    PubMed

    Song, Rui; Guan, Shengcan; Lee, Shui Shan; Chen, Zhihai; Chen, Chen; Han, Lifen; Xu, Yanli; Li, Ang; Zeng, Hui; Ye, Hanhui; Zhang, Fujie

    2018-07-17

    During March and April 2016, 11 yellow fever cases were identified in China. We report epidemic and viral information for 10 of these patients, 6 of whom had been vaccinated before travel. Phylogenetic analyses suggest these viruses nested within the diversity of strains endemic to Angola, where an outbreak began in 2015.

  19. Hemorrhagic Fevers - Multiple Languages

    MedlinePlus

    ... 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 ( ...

  20. [City-laboratory: Campinas and yellow fever at the dawn of the Republican era].

    PubMed

    Martins, Valter

    2015-01-01

    In the late nineteenth century, there were yellow fever epidemics in Campinas. Considered a seaside disease, the fever startled lay people and physicians. The scientific debate about the etiology of the disease left the domain of magazines and medical correspondence to orient political and sanitary actions. In order to combat the disease, the city began to resemble a laboratory and experienced its "era of sanitation and demolition," with victories over the ailment and inconvenience to the public. The State Sanitary Commission led by Emilio Ribas, aware of Finlay's Culicidae theory, rehearsed in Campinas what would happen with Oswaldo Cruz and Pereira Passos in Rio de Janeiro. The novelty of combating mosquitoes coexisted with age-old practices dear to miasmatic theory, such as disinfection.

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

    PubMed

    Kassar, Telissa C; Magalhães, Tereza; S, José V J; Carvalho, Amanda G O; Silva, Andréa N M R DA; Queiroz, Sabrina R A; Bertani, Giovani R; Gil, Laura H V G

    2017-01-01

    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.

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

    PubMed Central

    Oliveira, Ana Cristina Vanderley; Maria Henrique da Mota, Licia; dos Santos-Neto, Leopoldo Luiz; De Carvalho, Jozélio Freire; Caldas, Iramaya Rodrigues; Martins Filho, Olindo Assis; Tauil, Pedro Luis

    2014-01-01

    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. PMID:25405025

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

    PubMed

    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.

  4. Haemagogus leucocelaenus and Other Mosquitoes Potentially Associated With Sylvatic Yellow Fever In Cantareira State Park In the São Paulo Metropolitan Area, Brazil.

    PubMed

    Mucci, Luis Filipe; Medeiros-Sousa, Antônio Ralph; Ceretti-Júnior, Walter; Fernandes, Aristides; Camargo, Amanda Alves; Evangelista, Eduardo; de Oliveira Christe, Rafael; Montes, Joyce; Teixeira, Renildo Souza; Marrelli, Mauro Toledo

    2016-12-01

    The aim of this work was to investigate whether Haemagogus leucocelaenus and other mosquito species associated with sylvatic transmission of yellow fever virus are present in Cantareira State Park (CSP) in the São Paulo Metropolitan Area (SPMA). From October 2015 to March 2016, adult mosquitoes were captured with the Centers for Disease Control and Prevention traps, manual battery-powered aspirators, and Shannon traps; larvae and pupae were collected in natural and artificial breeding sites. A total of 109 adult mosquito specimens and 30 immature forms belonging to 11 taxonomic categories in 4 genera (Aedes, Psorophora, Sabethes, and Haemagogus) were collected, including Hg. leucocelaenus, the main vector of yellow fever. The entomological findings of the present study indicate that the area is of strategic importance for yellow fever surveillance not only because of the significant numbers of humans and nonhuman primates circulating in CSP and its vicinity but also because it represents a potential route for the disease to be introduced to the SPMA.

  5. Yellow fever: ecology, epidemiology, and role in the collapse of the Classic lowland Maya civilization.

    PubMed

    Wilkinson, R L

    1995-07-01

    Mystery has long surrounded the collapse of the Classic lowland Mayan civilization of the Peten region in Guatemala. Recent population reconstructions derived from archaeological evidence from the central lowlands show population declines from urban levels of between 2.5 and 3.5 million to around 536,000 in the two hundred year interval between 800 A.D. and 1000 A.D., the period known as the Classic Maya Collapse. A steady, but lesser rate of population decline continued until the time of European contact. When knowledge of the ecology and epidemiology of yellow fever and its known mosquito vectors are compared with what is known of the ecological conditions of lowland Guatemala as modified by the Classic Maya, provocative similarities are observed. When infection and mortality patterns of more recent urban yellow fever epidemics are used as models for a possible series of Classic Maya epidemics, a correlation is noted between the modeled rate of population decline for a series of epidemics, and population decline figures reconstructed from archaeological evidence.

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

    PubMed

    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.

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  8. 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.

    PubMed

    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.

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

    PubMed

    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.

  10. Theories about the propagation of yellow fever: the scientific debate in the São Paulo press between 1895 and 1903.

    PubMed

    Lódola, Soraya; Góis Junior, Edivaldo

    2015-01-01

    This article describes the debate over theories about the propagation of yellow fever in the São Paulo press. Our time span was defined as the period between 1895 and 1903, a time that saw high indices of the disease in Brazil. Documentary research involved mass circulation newspapers in São Paulo and medical journals of the period. The empirical data was collected from the Public Archives of the State of São Paulo and from the library of the Faculdade de Saúde Pública at Universidade de São Paulo. It was observed a clash between theories as to the propagation of yellow fever that revealed a symbolic dispute for influence in the formation of the scientific field.

  11. The Global Distribution of Yellow Fever and Dengue

    PubMed Central

    Rogers, D.J.; Wilson, A.J.; Hay, S.I.; Graham, A.J.

    2011-01-01

    Yellow fever has been subjected to partial control for decades, but there are signs that case numbers are now increasing globally, with the risk of local epidemic outbreaks. Dengue case numbers have also increased dramatically during the past 40 years and different serotypes have invaded new geographical areas. Despite the temporal changes in these closely related diseases, and their enormous public health impact, few attempts have been made to collect a comprehensive dataset of their spatial and temporal distributions. For this review, records of the occurrence of both diseases during the 20th century have been collected together and are used to define their climatic limits using remotely sensed satellite data within a discriminant analytical model framework. The resulting risk maps for these two diseases identify their different environmental requirements, and throw some light on their potential for co-occurrence in Africa and South East Asia. PMID:16647971

  12. Standards of yellow fever vaccination and travel medicine practice in the Republic of Ireland: A questionnaire-based evaluation.

    PubMed

    Noone, Peter; Hamza, Mohammed; Tang, John; Flaherty, Gerard

    2015-01-01

    The Department of Health regulates the designation of yellow fever vaccination centres (YFVCs) in the Republic of Ireland to ensure appropriate standards in the safe, effective use of yellow fever vaccine for overseas travellers. The process of designation of YFVCs is delegated to Directors of Public Health who direct Principal Medical Officers. Variation in implementation of specific criteria for designation exists and no formal follow up inspection is carried out. This survey of all designated YFVCs in the Republic of Ireland aimed to assess compliance with standards to ensure the objectives of the national yellow fever vaccination programme were met. A piloted questionnaire devised from a United Kingdom (UK) YFVC survey was developed and tested in five YFVCs. The questionnaire was adapted for the postal survey and captured data on professional training, reference sources, services provided, physical facilities and supplies, and was distributed to 655 YFVCs in a stamped addressed envelope. During the period 2010-2011, there were 655 designated YFVCs in the Republic of Ireland. Responses were received from 246 centres (38% response rate), 91% of which were in general practice. Deficiencies were identified in respect of vaccine refrigeration protocols, record keeping, attendance at YFVC training sessions, and clinical protocols for adverse events. Specific deficiencies in relation to training, vaccine storage, administration and documentation should be addressed to ensure standardised YFVC practices and thus align them with best international practice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Neutralizing Antibody Response to Booster Vaccination with the 17d Yellow Fever Vaccine

    DTIC Science & Technology

    2006-01-18

    FY03-28, approved 18 December 2003). 2.2. PRNT Patient sera were tested for neutralizing antibody to yellow fever virus ( YFV ) using a PRNT80 as...described by Man- giafico et al. [16], but modified for use with the Asibi strain of YFV . Briefly, test sera and controls were initially diluted 1:10 in...the 1:10 dilution, in HBSS containing human serum albumin, HEPES, peni- cillin and streptomycin. An equal volume of YFV , calculated to yield

  14. Immunogenicity and tolerability of yellow fever vaccination in 23 French HIV-infected patients.

    PubMed

    Pistone, Thierry; Verdière, Claire-Hélène; Receveur, Marie-Catherine; Ezzedine, Khaled; Lafon, Marie-Edith; Malvy, Denis

    2010-09-01

    Vaccination of asymptomatic human immunodeficiency virus (HIV)-infected patients with a CD4 cell count ≥ 200/mm³ is strongly suggested prior to travel to a region where yellow fever (YF) is endemic. However, few data describing YF vaccination in such patients are available. In this retrospective observational study of 23 HIV-infected patients, YF antibody titers, CD4 cell counts, and viral loads were measured before and after vaccination. Serologies were performed retrospectively on samples that had been stored as part of routine hospital procedures. Ninety-three percent of patients (13/14) with no baseline immunity, seroconverted after vaccination. Immunogenicity appeared slowly; only 2 of the 5 patients tested within 5 weeks of vaccination had seroconverted. A booster effect was noted in 3 of the 9 patients with baseline immunogenicity. Finally, due to unawareness of his HIV status, one patient was vaccinated and was found later to have a CD4 cell count < 200/mm³.The YF vaccine was well tolerated and no serious adverse events were reported. The impact of vaccination on immunologic and viral parameters was variable. Both decreases (n = 7) and increases (n = 5) in CD4 cell counts were recorded. Viral loads became undetectable in 2 patients and doubled or became positive in 3 patients. Yellow fever vaccination was safe and effective in a large majority of this cohort of stable, HIV-infected patients.

  15. Isolation and characterization of a Brazilian strain of yellow fever virus from an epizootic outbreak in 2009.

    PubMed

    Jorge, Taissa Ricciardi; Mosimann, Ana Luiza Pamplona; Noronha, Lucia de; Maron, Angela; Duarte Dos Santos, Claudia Nunes

    2017-02-01

    During a series of epizootics caused by Yellow fever virus in Brazil between 2007 and 2009, a monkey was found dead (May 2009) in a sylvatic area in the State of Paraná. Brain samples from this animal were used for immunohistochemical analysis and isolation of a wild-type strain of YFV. This viral strain was characterized, and sequence analyzes demonstrated that it is closely related with YFV strains of the recently identified subclade 1E of the South American genotype I. Further characterization included indirect-immunofluorescence of different infected cell lines and analysis of the kinetics of virus replication and infectivity inhibition by type I IFN. The generated data contributes to the knowledge of YFV evolution and phylogeny. Additionally, the reagents generated and characterized during this study, such as a panel of monoclonal antibodies, are useful tools for further studies on YFV. Lastly, this case stresses the importance of yellow fever surveillance through sentinel monkeys. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed

    Moreno, Eduardo Stramandinoli; Rocco, Iray Maria; Bergo, Eduardo Sterlino; Brasil, Roosecelis Araujo; Siciliano, Melissa Mascheratti; Suzuki, Akemi; Silveira, Vivian Regina; Bisordi, Ivani; Souza, Renato Pereira de

    2011-01-01

    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. 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. 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 Alouatta caraya. 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 Psorophora ferox, 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. 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.

  17. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  18. Genetic Divergence and Dispersal of Yellow Fever Virus, Brazil

    PubMed Central

    Bryant, Juliet E.; Travassos da Rosa, Amelia P.A.; Tesh, Robert B.; Rodrigues, Sueli G.; Barrett, Alan D.T.

    2004-01-01

    An analysis of 79 yellow fever virus (YFV) isolates collected from 1935 to 2001 in Brazil showed a single genotype (South America I) circulating in the country, with the exception of a single strain from Rondônia, which represented South America genotype II. Brazilian YFV strains have diverged into two clades; an older clade appears to have become extinct and another has become the dominant lineage in recent years. Pairwise nucleotide diversity between strains ranged from 0% to 7.4%, while amino acid divergence ranged from 0% to 4.6%. Phylogenetic analysis indicated traffic of virus variants through large geographic areas and suggested that migration of infected people may be an important mechanism of virus dispersal. Isolation of vaccine virus from a patient with a fatal case suggests that vaccine-related illness may have been misdiagnosed in the past. PMID:15498159

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

    USDA-ARS?s Scientific Manuscript database

    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...

  20. Surface expression of an immunodominant malaria protein B cell epitope by yellow fever virus.

    PubMed

    Bonaldo, Myrna C; Garratt, Richard C; Caufour, Philippe S; Freire, Marcos S; Rodrigues, Mauricio M; Nussenzweig, Ruth S; Galler, Ricardo

    2002-01-25

    The yellow fever 17D virus (YF17D) has several characteristics that are desirable for the development of new, live attenuated vaccines. We approached its development as a vector for heterologous antigens by studying the expression of a humoral epitope at the surface of the E protein based on the results of modelling its three-dimensional structure. This model indicated that the most promising insertion site is between beta-strands f and g, a site that is exposed at the external surface of the virus. The large deletion of six residues from the fg loop of the E protein from yellow fever virus, compared to tick-born encephalitis virus, leaves space at the dimer interface for a large insertion without creating steric hindrance. We have tested this hypothesis by inserting a model humoral epitope from the circumsporozoite protein of Plasmodium falciparum consisting of triple NANP repeats. Recombinant virus (17D/8) expressing this insertion flanked by two glycine residues at each end, is specifically neutralized by a monoclonal antibody to the model epitope. Furthermore, mouse antibodies raised to the recombinant virus recognize the parasite protein in an ELISA assay. Serial passage analysis confirmed the genetic stability of the insertion made in the viral genome and the resulting 17D/8 virus is significantly more attenuated in mouse neurovirulence tests than the 17DD vaccine. The fg loop belongs to the dimerization domain of the E protein and lies at the interface between monomers. This domain undergoes a low pH transition, which is related to the fusion of the viral envelope to the endosome membrane. It is conceivable that a slower rate of fusion, resulting from the insertion close to the dimer interface, may delay the onset of virus production and thereby lead to a milder infection of the host. This would account for the more attenuated phenotype of the recombinant virus in the mouse model and lower extent of replication in cultured cells. The vectorial capacity of

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

    PubMed

    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.

  2. Genetic stability of a dengue vaccine based on chimeric yellow fever/dengue viruses.

    PubMed

    Mantel, N; Girerd, Y; Geny, C; Bernard, I; Pontvianne, J; Lang, J; Barban, V

    2011-09-02

    A tetravalent dengue vaccine based on four live, attenuated, chimeric viruses (CYD1-4), constructed by replacing the genes coding for premembrane (prM) and envelope (E) proteins of the yellow fever (YF)-17D vaccine strain with those of the four serotypes of dengue virus, is in clinical phase III evaluation. We assessed the vaccine's genetic stability by fully sequencing each vaccine virus throughout the development and manufacturing process. The four viruses displayed complete genetic stability, with no change from premaster seed lots to bulk lots. When pursuing the virus growth beyond bulk lots, a few genetic variations were observed. Usually both the initial nucleotide and the new one persisted, and mutations appeared after a relatively high number of virus duplication cycles (65-200, depending on position). Variations were concentrated in the prM-E and non-structural (NS)4B regions. PrM-E variations had no impact on lysis-plaque size or neurovirulence in mice. None of the variations located in the YF-17D-derived genes corresponded with reversion to the wild-type Yellow Fever sequence. Variations in NS4B likely reflect virus adaptation to Vero cells growth. A low to undetectable viremia has been reported previously [1-3] in vaccinated non-human and human primates. Combined with the data reported here about the genetic stability of the vaccine strains, the probability of in vivo emergence of mutant viruses appears very low. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Early molecular correlates of adverse events following yellow fever vaccination

    PubMed Central

    Chan, Candice Y.Y.; Chan, Kuan Rong; Chua, Camillus J.H.; nur Hazirah, Sharifah; Ghosh, Sujoy; Ooi, Eng Eong; Low, Jenny G.

    2017-01-01

    The innate immune response shapes the development of adaptive immunity following infections and vaccination. However, it can also induce symptoms such as fever and myalgia, leading to the possibility that the molecular basis of immunogenicity and reactogenicity of vaccination are inseparably linked. To test this possibility, we used the yellow fever live-attenuated vaccine (YFLAV) as a model to study the molecular correlates of reactogenicity or adverse events (AEs). We analyzed the outcome of 68 adults who completed a YFLAV clinical trial, of which 43 (63.2%) reported systemic AEs. Through whole-genome profiling of blood collected before and after YFLAV dosing, we observed that activation of innate immune genes at day 1, but not day 3 after vaccination, was directly correlated with AEs. These findings contrast with the gene expression profile at day 3 that we and others have previously shown to be correlated with immunogenicity. We conclude that although the innate immune response is a double-edged sword, its expression that induces AEs is temporally distinct from that which engenders robust immunity. The use of genomic profiling thus provides molecular insights into the biology of AEs that potentially forms a basis for the development of safer vaccines. PMID:28978802

  4. A Possible Connection between the 1878 Yellow Fever Epidemic in the Southern United States and the 1877-78 El Niño Episode.

    NASA Astrophysics Data System (ADS)

    Diaz, Henry F.; McCabe, Gregory J.

    1999-01-01

    One of the most severe outbreaks of yellow fever, a viral disease transmitted by the Aedes aegypti mosquito, affected the southern United States in the summer of 1878. The economic and human toll was enormous, and the city of Memphis, Tennessee, was one of the most affected. The authors suggest that as a consequence of one of the strongest El Niño episodes on record-that which occurred in 1877-78-exceptional climate anomalies occurred in the United States (as well as in many other parts of the world), which may have been partly responsible for the widespread nature and severity of the 1878 yellow fever outbreak.This study documents some of the extreme climate anomalies that were recorded in 1877 and 1878 in parts of the eastern United States, with particular emphasis on highlighting the evolution of these anomalies, as they might have contributed to the epidemic. Other years with major outbreaks of yellow fever in the eighteenth and nineteenth centuries also occurred during the course of El Niño episodes, a fact that appears not to have been noted before in the literature.

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

    PubMed

    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.

  6. IMMUNOLOGICAL STUDIES WITH A STRAIN OF LEPTOSPIRA ISOLATED FROM A CASE OF YELLOW FEVER IN MERIDA, YUCATAN

    PubMed Central

    Noguchi, Hideyo; Kligler, I. J.

    1920-01-01

    Identification of the leptospira isolated from a case of yellow fever in Merida was accomplished by means of an anti-icteroides immune serum prepared in a horse with several Guayaquil strains of Leptospira icteroides. The immune serum showed a protective action of high titer against the Merida strain, thus establishing its efficacy as a therapeutic agent against this strain. Polyvalent anti-icteroides immune serum prepared in the horse or monovalent anti-icteroides immune serums prepared in the rabbit had a definite devitalizing action upon the Merida strain, while immune serums similarly prepared with strains of icterohœmorrhagiœ had no perceptible effect upon the Merida strain. Serums from yellow fever convalescents in Merida gave a positive Pfeiffer reaction with the Merida strain of Leptospira icteroides. The reactions between the Guayaquil strains (Nos. 1 and 5) and two of these serums from convalescents varied from definitely positive to doubtful, owing probably to the diminution of active immune principles in the serums during the prolonged and unfavorable conditions of their transportation. PMID:19868465

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

    PubMed

    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.

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

    PubMed

    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.

  9. Adaptive Diversification Between Yellow Fever Virus West African and South American Lineages: A Genome-Wide Study.

    PubMed

    Li, Yan; Yang, Zexiao

    2017-03-01

    AbstractYellow fever virus (YFV) has emerged as the causative agent of a vector-borne disease with devastating mortality in the tropics of Africa and the Americas. YFV phylogenies indicate that the isolates collected from West Africa, East and Central Africa, and South America cluster into different lineages and the virus spread into the Americas from Africa. To determine the nature of genetic variation accompanying the intercontinental epidemic, we performed a genome-wide evolutionary study on the West African and South American lineages of YFV. Our results reveal that adaptive genetic diversification has occurred on viral nonstructural protein 5 (NS5), which is crucially required for viral genome replication, in the early epidemic phase of these currently circulating lineages. Furthermore, major amino acid changes relevant to the adaptive diversification generally cluster in different structural regions of NS5 in a lineage-specific manner. These results suggest that YFV has experienced adaptive diversification in the epidemic spread between the continents and shed insights into the genetic determinants of such diversification, which might be beneficial for understanding the emergence and re-emergence of yellow fever as an important global public health issue.

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

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

    PubMed

    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.

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

    PubMed

    Briand, Sylvie; Beresniak, Ariel; Nguyen, Tim; Yonli, Tajoua; Duru, Gerard; Kambire, Chantal; Perea, William

    2009-07-14

    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. 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. 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.

  15. Frog skin cultures secrete anti-yellow fever compounds.

    PubMed

    Muñoz-Camargo, Carolina; Méndez, Margarita Correa; Salazar, Vivian; Moscoso, Johanna; Narváez, Diana; Torres, Maria Mercedes; Florez, Franz Kaston; Groot, Helena; Mitrani, Eduardo

    2016-11-01

    There is an urgent need to develop novel antimicrobial substances. Antimicrobial peptides (AMPs) are considered as promising candidates for future therapeutic use. Because of the re-emergence of the Flavivirus infection, and particularly the yellow fever virus (YFV), we have compared the antiviral activities from skin secretions of seven different frog species against YFV (strain 17D). Secretions from Sphaenorhynchus lacteus, Cryptobatrachus boulongeri and Leptodactylus fuscus displayed the more powerful activities. S. lacteus was found to inhibit viral lysis of Vero E6 cells even at the highest viral concentration evaluated of 10 LD 50 . We also report the identification of a novel frenatin-related peptide from S. lacteus and found that this peptide-on its own-can lead to 35% protection against YVF, while displaying no cytotoxicity against somatic cells even at fivefold higher concentrations. These results are attractive and support the need for continued exploration of new sources of AMPs from frog skin secretions such as those described here in the development of new compounds for the treatment of infectious diseases in general and specific viral infections in particular.

  16. Haemorrhagic Fevers, Viral

    MedlinePlus

    ... Filoviridae (Ebola and Marburg) and Flaviviridae (yellow fever, dengue, Omsk haemorrhagic fever, Kyasanur forest disease). General information ... the Ebola vaccine trials in Guinea What is dengue and how is it treated? Fact sheets Crimean- ...

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

    PubMed

    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.

  18. Current Status and Future Prospects of Yellow Fever Vaccines

    PubMed Central

    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

  19. Vector competence of Australian mosquitoes for yellow fever virus.

    PubMed

    van den Hurk, Andrew F; McElroy, Kate; Pyke, Alyssa T; McGee, Charles E; Hall-Mendelin, Sonja; Day, Andrew; Ryan, Peter A; Ritchie, Scott A; Vanlandingham, Dana L; Higgs, Stephen

    2011-09-01

    The vector competence of Australian mosquitoes for yellow fever virus (YFV) was evaluated. Infection and transmission rates in Cairns and Townsville populations of Aedes aegypti and a Brisbane strain of Ae. notoscriptus were not significantly different from a well-characterized YFV-susceptible strain of Ae. aegypti. After exposure to 10⁷·² tissue culture infectious dose (TCID₅₀)/mL of an African strain of YFV, > 70% of Ae. aegypti and Ae. notoscriptus became infected, and > 50% transmitted the virus. When exposed to 10⁶·⁷) TCID₅₀/mL of a South American strain of YFV, the highest infection (64%) and transmission (56%) rates were observed in Ae. notoscriptus. The infection and transmission rates in the Cairns Ae. aegypti were both 24%, and they were 36% and 28%, respectively, for the Townsville population. Because competent vectors are present, the limited number of travelers from endemic areas and strict vaccination requirements will influence whether YFV transmission occurs in Australia.

  20. Serological Evidence of Dengue Fever Among Refugees, Hargeysa, Somalia

    DTIC Science & Technology

    1989-01-01

    fever, Sindbis, Chikungunya, yellow HISTORY OF THE DISEASE IN THE fever, and Zika viruses . However, antibody reac- DAM CAMP tive to dengue 2 virus was...fever, Crimean-Congo hemorrhagic fever, Sindbis, Chikungunya, yellow fever, and Zika viruses . However, antibody reactive to dengue 2 virus was detected... ZIKA ) viruses . Further testing of sera for evidence of dengue S Barbera S , MOGAISCIO . viral infection was done by the enzyme immunoassay " (EIA

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Analysis of two imported cases of yellow fever infection from Ivory Coast and The Gambia to Germany and Belgium.

    PubMed

    Bae, Hi-Gung; Drosten, Christian; Emmerich, Petra; Colebunders, Robert; Hantson, Philippe; Pest, Stefan; Parent, Muriel; Schmitz, Herbert; Warnat, Marc-Aurel; Niedrig, Matthias

    2005-08-01

    Yellow fever remains one of the great burdens for public health in the endemic regions in Africa and South America. The under reporting of yellow fever cases in the respective regions and lack of international interest leads to an underestimation of the constant danger in these areas. Non-vaccinated travelers take a high risk without the effective protection of YFV 17D vaccination. Two YF cases were imported to Europe in the last 4 years. We characterized two yellow fever virus (YFV) isolates from severely infected patients coming back from Africa, Ivory Coast and The Gambia, by genome sequencing and phylogenetic analysis. The virus infections in different organs were analyzed with pathological, immunohistological, electronmicroscopical and quantitative real-time PCR methods. High virus loads in spleen and liver (2.4 x 10 (6) to 3 x 10 (7)GE/mL) demonstrated by real time PCR show massive virus replication leading to extraordinary progression of the disease in these patients. Immunohistological and electronmicroscopical analysis confirms virus particles in liver tissue. In all other organs no virus could be detected. A fast, specific and sensitive virus PCR detection is recommended for diagnostic of acute infections. The further sequence alignments show that the new isolates belong to the type II West African strain with great homology to over 40-year old YF isolates from Senegal and Ghana. The divergence observed was on average 3.3%, ranging from 0.0% to 5.0% in the coding region of Gambia 2001 strain and 2.9 %, ranging from 0.0% to 4.3% in the coding region of the Ivory C 1999 strain. Most mutations (5.0%/4.3%, respectively) occurred in the envelope protein.

  3. Genomic and structural features of the yellow fever virus from the 2016-2017 Brazilian outbreak.

    PubMed

    Gómez, Mariela Martínez; Abreu, Filipe Vieira Santos de; Santos, Alexandre Araujo Cunha Dos; Mello, Iasmim Silva de; Santos, Marta Pereira; Ribeiro, Ieda Pereira; Ferreira-de-Brito, Anielly; Miranda, Rafaella Moraes de; Castro, Marcia Gonçalves de; Ribeiro, Mario Sergio; Laterrière Junior, Roberto da Costa; Aguiar, Shirlei Ferreira; Meira, Guilherme Louzada Silva; Antunes, Deborah; Torres, Pedro Henrique Monteiro; Mir, Daiana; Vicente, Ana Carolina Paulo; Guimarães, Ana Carolina Ramos; Caffarena, Ernesto Raul; Bello, Gonzalo; Lourenço-de-Oliveira, Ricardo; Bonaldo, Myrna Cristina

    2018-04-01

    Southeastern Brazil has been suffering a rapid expansion of a severe sylvatic yellow fever virus (YFV) outbreak since late 2016, which has reached one of the most populated zones in Brazil and South America, heretofore a yellow fever-free zone for more than 70 years. In the current study, we describe the complete genome of 12 YFV samples from mosquitoes, humans and non-human primates from the Brazilian 2017 epidemic. All of the YFV sequences belong to the modern lineage (sub-lineage 1E) of South American genotype I, having been circulating for several months prior to the December 2016 detection. Our data confirm that viral strains associated with the most severe YF epidemic in South America in the last 70 years display unique amino acid substitutions that are mainly located in highly conserved positions in non-structural proteins. Our data also corroborate that YFV has spread southward into Rio de Janeiro state following two main sylvatic dispersion routes that converged at the border of the great metropolitan area comprising nearly 12 million unvaccinated inhabitants. Our original results can help public health authorities to guide the surveillance, prophylaxis and control measures required to face such a severe epidemiological problem. Finally, it will also inspire other workers to further investigate the epidemiological and biological significance of the amino acid polymorphisms detected in the Brazilian 2017 YFV strains.

  4. Assessment of Yellow Fever Epidemic Risk: An Original Multi-criteria Modeling Approach

    PubMed Central

    Briand, Sylvie; Beresniak, Ariel; Nguyen, Tim; Yonli, Tajoua; Duru, Gerard; Kambire, Chantal; Perea, William

    2009-01-01

    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. PMID:19597548

  5. Innate immunity phenotypic features point toward simultaneous raise of activation and modulation events following 17DD live attenuated yellow fever first-time vaccination.

    PubMed

    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.

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

    PubMed

    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.

  7. 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

    PubMed Central

    2011-01-01

    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. PMID:21619598

  8. 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.

    PubMed

    Barros, Maria C E S; Galasso, Tatiane G C M; Chaib, Antônio J M; Degallier, Nicolas; Nagata, Tatsuya; Ribeiro, Bergmann M

    2011-05-27

    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. 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. 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.

  9. Entomological profile of yellow fever epidemics in the Central African Republic, 2006-2010.

    PubMed

    Ngoagouni, Carine; Kamgang, Basile; Manirakiza, Alexandre; Nangouma, Auguste; Paupy, Christophe; Nakoune, Emmanuel; Kazanji, Mirdad

    2012-08-16

    The causative agent of yellow fever is an arbovirus of the Flaviviridae family transmitted by infected Aedes mosquitoes, particularly in Africa. In the Central African Republic since 2006, cases have been notified in the provinces of Ombella-Mpoko, Ouham-Pende, Basse-Kotto, Haute-Kotto and in Bangui the capital. As the presence of a vector of yellow fever virus (YFV) represents a risk for spread of the disease, we undertook entomological investigations at these sites to identify potential vectors of YFV and their abundance. Between 2006 and 2010, 5066 mosquitoes belonging to six genera and 43 species were identified. The 20 species of the Aedes genus identified included Ae. aegypti, the main vector of YFV in urban settings, and species found in tropical forests, such as Ae. africanus, Ae. simpsoni, Ae. luteocephalus, Ae. vittatus and Ae. opok. These species were not distributed uniformly in the various sites studied. Thus, the predominant Aedes species was Ae. aegypti in Bangui (90.7 %) and Basse-Kotto (42.2 %), Ae. africanus in Ombella-Mpoko (67.4 %) and Haute-Kotto (77.8 %) and Ae. vittatus in Ouham-Pende (62.2 %). Ae. albopictus was also found in Bangui. The distribution of these dominant species differed significantly according to study site (P < 0.0001). None of the pooled homogenates of Aedes mosquitoes analysed by polymerase chain reaction contained the YFV genome. The results indicate a wide diversity of vector species for YFV in the Central African Republic. The establishment of surveillance and vector control programs should take into account the ecological specificity of each species.

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

    PubMed

    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.

  11. Strong alkalinization in the anterior midgut of larval yellow fever mosquitoes (Aedes aegypti): involvement of luminal Na+/K+-ATPase.

    PubMed

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

    PubMed

    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.

  13. Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization

    PubMed Central

    Co, Mary Dawn T; Kilpatrick, Elizabeth D; Rothman, Alan L

    2009-01-01

    Management of yellow fever is focused on the prevention of illness by the use of the yellow fever virus (YFV) 17D vaccine. The role of neutralizing antibodies in protection is generally accepted with YFV-specific T cells likely contributing to the control of viral replication. We studied CD8+ T-cell responses to four defined human leucocyte antigen-B35-restricted epitopes in YFV vaccine recipients as a model of the kinetics of cytotoxic T-lymphocyte responses to an acute human viral infection. Multiple features of these epitope-specific responses were analysed after vaccination including magnitude, cytokine production, phenotype and T-cell receptor repertoire. Peak peptide-specific interferon-γ (IFN-γ) responses of almost 1% of CD8+ T cells were seen as early as 2 weeks post-vaccination; however, dominant responses varied between donors. Peptide-specific responses were still detectable at 54 months post-vaccination. Tetramer-positive cells, at high frequencies, were detected as early as 7–9 days, before detectable IFN-γ-producing cells, suggesting a defect in the functional capacity of some antigen-specific cells early post-vaccination. The predominant memory phenotype of the tetramer-positive population was a differentiated effector (CD45RA+ CCR7− CD62L−) phenotype. The T-cell receptor Vβ analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell populations in two individuals. These characteristics of the YFV-specific T-cell response could contribute to vaccine effectiveness. PMID:19740333

  14. Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization.

    PubMed

    Co, Mary Dawn T; Kilpatrick, Elizabeth D; Rothman, Alan L

    2009-09-01

    Management of yellow fever is focused on the prevention of illness by the use of the yellow fever virus (YFV) 17D vaccine. The role of neutralizing antibodies in protection is generally accepted with YFV-specific T cells likely contributing to the control of viral replication. We studied CD8(+) T-cell responses to four defined human leucocyte antigen-B35-restricted epitopes in YFV vaccine recipients as a model of the kinetics of cytotoxic T-lymphocyte responses to an acute human viral infection. Multiple features of these epitope-specific responses were analysed after vaccination including magnitude, cytokine production, phenotype and T-cell receptor repertoire. Peak peptide-specific interferon-gamma (IFN-gamma) responses of almost 1% of CD8(+) T cells were seen as early as 2 weeks post-vaccination; however, dominant responses varied between donors. Peptide-specific responses were still detectable at 54 months post-vaccination. Tetramer-positive cells, at high frequencies, were detected as early as 7-9 days, before detectable IFN-gamma-producing cells, suggesting a defect in the functional capacity of some antigen-specific cells early post-vaccination. The predominant memory phenotype of the tetramer-positive population was a differentiated effector (CD45RA(+) CCR7(-) CD62L(-)) phenotype. The T-cell receptor Vbeta analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell populations in two individuals. These characteristics of the YFV-specific T-cell response could contribute to vaccine effectiveness.

  15. Synthetic strategy and antiviral evaluation of diamide containing heterocycles targeting dengue and yellow fever virus.

    PubMed

    Saudi, Milind; Zmurko, Joanna; Kaptein, Suzanne; Rozenski, Jef; Gadakh, Bharat; Chaltin, Patrick; Marchand, Arnaud; Neyts, Johan; Van Aerschot, Arthur

    2016-10-04

    High-throughput screening of a subset of the CD3 chemical library (Centre for Drug Design and Discovery; KU Leuven) provided us with a lead compound 1, displaying low micromolar potency against dengue virus and yellow fever virus. Within a project aimed at discovering new inhibitors of flaviviruses, substitution of its central imidazole ring led to synthesis of variably substituted pyrazine dicarboxylamides and phthalic diamides, which were evaluated in cell-based assays for cytotoxicity and antiviral activity against the dengue virus (DENV) and yellow fever virus (YFV). Fourteen compounds inhibited DENV replication (EC50 ranging between 0.5 and 3.4 μM), with compounds 6b and 6d being the most potent inhibitors (EC50 0.5 μM) with selectivity indices (SI) > 235. Compound 7a likewise exhibited anti-DENV activity with an EC50 of 0.5 μM and an SI of >235. In addition, good antiviral activity of seven compounds in the series was also noted against the YFV with EC50 values ranging between 0.4 and 3.3 μM, with compound 6n being the most potent for this series with an EC50 0.4 μM and a selectivity index of >34. Finally, reversal of one of the central amide bonds as in series 13 proved deleterious to the inhibitory activity. Copyright © 2016 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26435066

  18. An unusual case of influenza-like illness after yellow fever vaccination.

    PubMed

    Lamson, Daryl M; Ramani, Rama; Kleabonas, Matthew; Metcalfe, Maureen; Humphrey, Charles; St George, Kirsten

    2014-05-01

    Yellow fever (YF) is an important public health concern in areas where the disease is endemic. For more than 60 years a highly effective live attenuated vaccine has been available, its widespread use resulting in a dramatic decrease in the number of cases. On rare occasions, YF vaccine can cause mild to severe disease and rare adverse vaccine-associated events have been reported. Additionally, an average viremia of 3-5 days after administration of the YF vaccine has been published. Here we present a case where YF vaccine was isolated in cell culture from a respiratory swab collected from a patient presenting with influenza-like illness. To the best of our knowledge, this is the first report finding replicating YF vaccine in the respiratory sample of a post inoculated individual. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed

    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

  20. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tretyakova, Irina; Nickols, Brian; Hidajat, Rachmat

    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 deficientmore » 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.« less

  1. Survival and swimming behavior of insecticide-exposed larvae and pupae of the yellow fever mosquito Aedes aegypti.

    PubMed

    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

  2. Survival and swimming behavior of insecticide-exposed larvae and pupae of the yellow fever mosquito Aedes aegypti

    PubMed Central

    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

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

    PubMed

    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.

  4. Contribution of wave-induced liquefaction in triggering hyperpycnal flows in Yellow River Estuary

    NASA Astrophysics Data System (ADS)

    Liu, X.; Jia, Y.

    2017-12-01

    Hyperpycnal flows, driven mainly by the gravity of near-bed negatively buoyant layers, are one of the most important processes for moving marine sediment across the earth. The issue of hyperpycnal flows existing in marine environment has drawn increasing scholars' attention since that was observed in situ off the Yellow River estuary in the 1980s. Most researches maintain that hyperpycnal flows in the Yellow River estuary are caused by the high-concentration sediments discharged from the Yellow River into sea, however, other mechanisms have been discounted since the sediment input from the river has been significantly changed due to climate and anthropogenic change. Here we demonstrate that wave-seabed interactions can generate hyperpycnal flows, without river input, by sediment flux convergence above an originally consolidated seabed. Using physical model experiments and multi-sensor field measurements, we characterize the composition-dependent liquefaction properties of the sediment due to wave-induced pore water pressure accumulation. This allows quantification of attenuation of sediment threshold velocity and critical shear stress (predominant variables in transport mechanics) during the liquefaction under waves. Parameterising the wave-seabed interactions in a new concept model shows that high waves propagating over the seabed sediment can act as a scarifier plough remoulding the seabed sediment. This contributes to marine hyperpycnal flows as the sediment is quickly resuspended under accumulating attenuation in strength. Therefore, the development of more integrative numerical models could supply realistic predictions of marine record in response to rising magnitude and frequency of storms.

  5. [Poison and the mosquito: epistemological aspects of the etiology and prophylactics of yellow fever].

    PubMed

    Caponi, S

    2000-01-01

    The strategies against yellow fever developed by Argentina and Brazil were discussed at the Second Medical Congress of Latin America which was held in Buenos Aires in 1904. The study of the controversy between physicians from Argentina and Brazil around the existing explanatory models of this illness and the international prophylactic strategies in use at the time enables an epistemological understanding of the breakthrough brought about by the emergence of medicine of vectors. This chapter of Latin American medicine history constitutes a unique opportunity to analyze that reorganization of knowledge, which permitted the inclusion of intermediary living beings into the medical and epidemiological discourse.

  6. [Yellow fever: nurse counseling on travelers' health at basic health clinics].

    PubMed

    Mallet, Anna Paula; Dall'Agnol, Clarice Maria; Souza, Dirciara Barañano

    2010-06-01

    The objective of this qualitative, exploratory and descriptive study is to investigate the nursing practices related to travelers' health counseling. Data were collected from nursing professionals who work in the immunization sector of three Basic Health Units in Porto Alegre, Rio Grande do Sul, Brazil, using the technique of semi-structured interview. Five categories emerged from content analysis: care profile, health orientation, referrals to exchange the National Immunization Card for the International Certificate of Vaccination, information source and information material. The results signal the beginning of an organization of nursing practices focused on travelers' health, going beyond the focus on yellow fever. Failures in guidelines for acquisition of International Certificate of Vaccination still occur and information materials are missing. It points out to the need of broadening the discussion on travelers' health for a review of strategies for care organization and referrals for the construction of a specific policy.

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

    PubMed

    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

  8. Phylodynamics of Yellow Fever Virus in the Americas: new insights into the origin of the 2017 Brazilian outbreak.

    PubMed

    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.

  9. 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.

    PubMed

    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.

  10. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    PubMed

    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

    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. 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. 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.

  11. Frequency of histopathological changes in Howler monkeys ( Alouatta sp.) naturally infected with yellow fever virus in Brazil.

    PubMed

    Leal, Silvana Gomes; Romano, Alessandro Pecego Martins; Monteiro, Rafael Veríssimo; Melo, Cristiano Barros de; Vasconcelos, Pedro Fernando da Costa; Castro, Márcio Botelho de

    2016-02-01

    Due to the importance that Howler monkeys have on the yellow fever (YF) epidemiological sylvatic cycle in Brazil, more accurate morphological diagnostic criteria needs to be established, especially considering the differences that may exist between the genera of Brazilian non-human primates (NHPs) involved in yellow fever virus (YFV) epizootics. Records of YF epizootics in NHPs in Brazil between 2007 and 2009 were obtained from the Brazilian Ministry of Health database to select YF positive (n=98) Howler monkeys (Alouatta sp.) for this study. The changes described in the histopathological reports were categorized by organ and their frequencies calculated. The most frequent lesions observed in the animals with YF were hepatocyte apoptosis (Councilman body formation), midzonal hepatocyte necrosis, steatosis, liver hemorrhage, inflammatory mononuclear cell infiltration of the liver, renal acute tubular necrosis and interstitial nephritis. Midzonal hepatocyte necrosis, steatosis and hemorrhage presented positive correlations with apoptosis of hepatocytes, suggesting strong YFV pathogenic effect association; they were also the main histopathological changes in the Alouatta sp. A pronounced negative correlation between apoptosis of hepatocytes and hepatic mononuclear cell infiltration pointed to significant histopathological differences between YFV infection in Howler monkeys and humans. The results warn that NHPs may exhibit different response patterns following YFV infection and require a more careful diagnosis. Presumptive diagnosis based on primate histopathological lesions may contribute to public health service control.

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

    PubMed

    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.

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

    PubMed Central

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

    2017-01-01

    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. PMID:28749337

  14. BCX4430, a novel nucleoside analog, effectively treats yellow fever in a Hamster model.

    PubMed

    Julander, Justin G; Bantia, Shanta; Taubenheim, Brian R; Minning, Dena M; Kotian, Pravin; Morrey, John D; Smee, Donald F; Sheridan, William P; Babu, Yarlagadda S

    2014-11-01

    No effective antiviral therapies are currently available to treat disease after infection with yellow fever virus (YFV). A Syrian golden hamster model of yellow fever (YF) was used to characterize the effect of treatment with BCX4430, a novel adenosine nucleoside analog. Significant improvement in survival was observed after treatment with BCX4430 at 4 mg/kg of body weight per day dosed intraperitoneally (i.p.) twice daily (BID). Treatment with BCX4430 at 12.5 mg/kg/day administered i.p. BID for 7 days offered complete protection from mortality and also resulted in significant improvement of other YF disease parameters, including weight loss, serum alanine aminotransferase levels (6 days postinfection [dpi]), and viremia (4 dpi). In uninfected hamsters, BCX4430 at 200 mg/kg/day administered i.p. BID for 7 days was well tolerated and did not result in mortality or weight loss, suggesting a potentially wide therapeutic index. Treatment with BCX4430 at 12 mg/kg/day i.p. remained effective when administered once daily and for only 4 days. Moreover, BCX4430 dosed at 200 mg/kg/day i.p. BID for 7 days effectively treated YF, even when treatment was delayed up to 4 days after virus challenge, corresponding with peak viral titers in the liver and serum. BCX4430 treatment did not preclude a protective antibody response, as higher neutralizing antibody (nAb) concentrations corresponded with increasing delays of treatment initiation, and greater nAb responses resulted in the protection of animals from a secondary challenge with YFV. In summary, BCX4430 is highly active in a hamster model of YF, even when treatment is initiated at the peak of viral replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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

    PubMed

    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.

  16. Rapid Molecular Assays for the Detection of Yellow Fever Virus in Low-Resource Settings

    PubMed Central

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

    2014-01-01

    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 YFV detection in

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

    PubMed

    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.

  18. TLR expression and NK cell activation after human yellow fever vaccination.

    PubMed

    Neves, Patrícia Cristina da Costa; Matos, Denise Cristina de Souza; Marcovistz, Rugimar; Galler, Ricardo

    2009-09-18

    The yellow fever vaccine is very effective with a single injection conferring protection for at least 10 years. Recent evidence suggests that the innate immune cells activated through Toll-like receptors (TLRs), are critical determinants of the robustness of the adaptive response. Therefore, we investigated the NK cell status in eight healthy volunteers after vaccination with YF 17DD virus. Shortly after vaccination, we observed increased expression of TLR-3 and TLR-9 in NK cells and markers such as CD69, HLA-DP-DQ-DR, CD38 and CD16. The up-regulation of CD69 was positively correlated with the presence of TLRs throughout the post-vaccination period and the circulating IFN-gamma was significantly augmented. These results suggest that TLRs may play an important role in NK cell activation during the immune response to vaccination, indicating a potential role for NK cells in helping the development of long-lasting protective memory.

  19. Construction and applications of yellow fever virus replicons.

    PubMed

    Jones, Christopher T; Patkar, Chinmay G; Kuhn, Richard J

    2005-01-20

    Subgenomic replicons of yellow fever virus (YFV) were constructed to allow expression of heterologous reporter genes in a replication-dependent manner. Expression of the antibiotic resistance gene neomycin phosphotransferase II (Neo) from one of these YFV replicons allowed selection of a stable population of cells (BHK-REP cells) in which the YFV replicon persistently replicated. BHK-REP cells were successfully used to trans-complement replication-defective YFV replicons harboring large internal deletions within either the NS1 or NS3 proteins. Although replicons with large deletions in either NS1 or NS3 were trans-complemented in BHK-REP, replicons that contained deletions of NS3 were trans-complemented at lower levels. In addition, replicons that retained the N-terminal protease domain of NS3 in cis were trans-complemented with higher efficiency than replicons in which both the protease and helicase domains of NS3 were deleted. To study packaging of YFV replicons, Sindbis replicons were constructed that expressed the YFV structural proteins in trans. Using these Sindbis replicons, both replication-competent and trans-complemented, replication-defective YFV replicons could be packaged into pseudo-infectious particles (PIPs). Although these results eliminate a potential role of either NS1 or full-length NS3 in cis for packaging and assembly of the flavivirus virion, they do not preclude the possibility that these proteins may act in trans during these processes.

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

    PubMed

    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.

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

    PubMed

    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.

  2. Distinct gene expression profiles in peripheral blood mononuclear cells from patients infected with vaccinia virus, yellow fever 17D virus, or upper respiratory infections.

    PubMed

    Scherer, Christina A; Magness, Charles L; Steiger, Kathryn V; Poitinger, Nicholas D; Caputo, Christine M; Miner, Douglas G; Winokur, Patricia L; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A; Gillham, Martha H; Haulman, N Jean; Stapleton, Jack T; Iadonato, Shawn P

    2007-08-29

    Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents.

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

    PubMed Central

    Hamlet, Arran; Perea, William; Yactayo, Sergio; Biey, Joseph; Van Kerkhove, Maria; Ferguson, Neil

    2018-01-01

    Background 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. Methodology/Principal findings 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. Conclusions/Significance 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

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

    PubMed

    Kongsgaard, Michael; Bassi, Maria R; Rasmussen, Michael; Skjødt, Karsten; Thybo, Søren; Gabriel, Mette; Hansen, Morten Bagge; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup; Buus, Soren; Stryhn, Anette

    2017-04-06

    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. Although most vaccinees responded to a booster vaccination, both the humoral and cellular immune responses observed following booster vaccination were strikingly reduced compared to primary responses. This suggests that pre-existing immunity efficiently controls booster inoculums of YF-17D. In a situation with epidemic outbreaks, one could argue that a more efficient use of a limited supply of the vaccine would be to focus on primary vaccinations.

  5. Development of a quantitative NS1-capture enzyme-linked immunosorbent assay for early detection of yellow fever virus infection.

    PubMed

    Ricciardi-Jorge, Taissa; Bordignon, Juliano; Koishi, Andrea; Zanluca, Camila; Mosimann, Ana Luiza; Duarte Dos Santos, Claudia Nunes

    2017-11-24

    Yellow fever is an arboviral disease that causes thousands of deaths every year in Africa and the Americas. However, few commercial diagnostic kits are available. Non-structural protein 1 (NS1) is an early marker of several flavivirus infections and is widely used to diagnose dengue virus (DENV) infection. Nonetheless, little is known about the dynamics of Yellow fever virus (YFV) NS1 expression and secretion, to encourage its use in diagnosis. To tackle this issue, we developed a quantitative NS1-capture ELISA specific for YFV using a monoclonal antibody and recombinant NS1 protein. This test was used to quantify NS1 in mosquito and human cell line cultures infected with vaccine and wild YFV strains. Our results showed that NS1 was detectable in the culture supernatants of both cell lines; however, a higher concentration was maintained as cell-associated rather than secreted into the extracellular milieu. A panel of 73 human samples was used to demonstrate the suitability of YFV NS1 as a diagnostic tool, resulting in 80% sensitivity, 100% specificity, a 100% positive predictive value and a 95.5% negative predictive value compared with RT-PCR. Overall, the developed NS1-capture ELISA showed potential as a promising assay for the detection of early YF infection.

  6. Genetic structure and phylogeography of Aedes aegypti, the dengue and yellow-fever mosquito vector in Bolivia.

    PubMed

    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, P<0.0001) in relation with the recent re-expansion of Ae. aegypti in Bolivia. 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.

  7. Vaccination against yellow fever in French Guiana: The impact of educational level, negative beliefs and attitude towards vaccination.

    PubMed

    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.

  8. Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model.

    PubMed

    Julander, Justin G; Trent, Dennis W; Monath, Thomas P

    2011-08-11

    Live, attenuated yellow fever (YF) 17D vaccine is highly efficacious but causes rare, serious adverse events resulting from active replication in the host and direct viral injury to vital organs. We recently reported development of a potentially safer β-propiolactone-inactivated whole virion YF vaccine (XRX-001), which was highly immunogenic in mice, hamsters, monkeys, and humans [10,11]. To characterize the protective efficacy of neutralizing antibodies stimulated by the inactivated vaccine, graded doses of serum from hamsters immunized with inactivated XRX-001 or live 17D vaccine were transferred to hamsters by the intraperitoneal (IP) route 24h prior to virulent, viscerotropic YF virus challenge. Neutralizing antibody (PRNT(50)) titers were determined in the sera of treated animals 4h before challenge and 4 and 21 days after challenge. Neutralizing antibodies were shown to mediate protection. Animals having 50% plaque reduction neutralization test (PRNT(50)) titers of ≥40 4h before challenge were completely protected from disease as evidenced by viremia, liver enzyme elevation, and protection against illness (weight change) and death. Passive titers of 10-20 were partially protective. Immunization with the XRX-001 vaccine stimulated YF neutralizing antibodies that were equally effective (based on dose response) as antibodies stimulated by live 17D vaccine. The results will be useful in defining the level of seroprotection in clinical studies of new yellow fever vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

    PubMed Central

    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

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

    PubMed Central

    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

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

    PubMed

    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

    2016-07-13

    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.

  12. Diphtheria, tetanus, poliomyelitis, yellow fever and hepatitis B seroprevalence among HIV1-infected migrants. Results from the ANRS VIHVO vaccine sub-study.

    PubMed

    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.

  13. Yellow fever risk assessment in the Central African Republic

    PubMed Central

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

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24947520

  14. Surveillance for yellow Fever virus in non-human primates in southern Brazil, 2001-2011: a tool for prioritizing human populations for vaccination.

    PubMed

    Almeida, Marco A B; Cardoso, Jader da C; Dos Santos, Edmilson; da Fonseca, Daltro F; Cruz, Laura L; Faraco, Fernando J C; Bercini, Marilina A; Vettorello, Kátia C; Porto, Mariana A; Mohrdieck, Renate; Ranieri, Tani M S; Schermann, Maria T; Sperb, Alethéa F; Paz, Francisco Z; Nunes, Zenaida M A; Romano, Alessandro P M; Costa, Zouraide G; Gomes, Silvana L; Flannery, Brendan

    2014-03-01

    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.

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

    PubMed Central

    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

  16. Emergence of traveling waves in the spreading of dengue fever

    NASA Astrophysics Data System (ADS)

    Bianco, Simone; Faatz, Andrea; Cummings, Derek; Shaw, Leah

    2010-03-01

    Dengue fever is a multistrain mosquito-borne subtropical disease that exhibits complex oscillatory outbreaks. Epidemiological data from Thailand displays traveling waves of infection originating in Bangkok, the largest population center (Cummings et al., Nature 427: 344, 2004). We present a multistrain metapopulation model in which traveling wave like behavior results from migration coupling between heterogeneous regions. The region with the highest effective person-to-person contact rate leads the dynamics. A stochastic version of the model will also be presented.

  17. 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

    USDA-ARS?s Scientific Manuscript database

    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...

  18. Large genetic differentiation and low variation in vector competence for dengue and yellow fever viruses of Aedes albopictus from Brazil, the United States, and the Cayman Islands.

    PubMed

    Lourenço de Oliveira, Ricardo; Vazeille, Marie; de Filippis, Ana Maria Bispo; Failloux, Anna-Bella

    2003-07-01

    We conducted a population genetic analysis of Aedes albopictus collected from 20 sites in Brazil, the United States (Florida, Georgia, and Illinois), and the Cayman Islands. Using isoenzyme analysis, we examined genetic diversity and patterns of gene flow. High genetic differentiation was found among Brazilian samples, and between them and North American samples. Regression analysis of genetic differentiation according to geographic distances indicated that Ae. albopictus samples from Florida were genetically isolated by distance. Infection rates with dengue and yellow fever viruses showed greater differences between two Brazilian samples than between the two North American samples or between a Brazilian sample and a North American sample. Introductions and establishments of new Ae. albopictus populations in the Americas are still in progress, shaping population genetic composition and potentially modifying both dengue and yellow fever transmission patterns.

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

    PubMed

    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.

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

    PubMed Central

    Curtis, Andrew J

    2008-01-01

    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 turn might mean traditional

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

    PubMed

    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

  2. [Detection and management of the yellow fever epidemic in the Ivory Coast, 2001].

    PubMed

    Akoua-Koffi, C; Ekra, K D; Kone, A B; Dagnan, N S; Akran, V; Kouadio, K L; Loukou, Y G; Odehouri, K; Tagliante-Saracino, J; Ehouman, A

    2002-01-01

    From March to December 2001, an outbreak of yellow fever was observed in Cote d'Ivoire. Sentinel surveillance for hemorrhagic fever allowed detection of the first case in the Duekoue health district in the heavily wooded western part of the country. A weekly reporting system was established. For each suspected case recorded and reported to the Epidemiological Surveillance Department at the National Institute of Public Hygiene, a sample was collected and sent for confirmation at the Pasteur Institute of the Cote d'Ivoire. The outbreak progressed from West to East reaching Abidjan, the economic capital of the country located in the southeast. The epidemic emergency plan consisted of setting up a crisis committee to implement epidemiological, entomological and virological surveillance, mass vaccination campaigns in areas around confirmed cases, and vector control. A total of 280 cases were reported including 32 confirmed cases and 6 deaths. Eleven out of 62 districts were affected with most cases occurring in cities with more than 10000 inhabitants. Over 3.7 million persons were vaccinated for an overall coverage of 92.2% in the areas where campaigns were carried out. As a result of this outbreak, surveillance for potentially epidemic diseases has been reinforced and surveillance of viral transmission is now being considered. A vaccination program for adults has also been established.

  3. A Meta-Analysis of Serological Response Associated with Yellow Fever Vaccination.

    PubMed

    Jean, Kévin; Donnelly, Christl A; Ferguson, Neil M; Garske, Tini

    2016-12-07

    Despite previous evidence of high level of efficacy, no synthetic metric of yellow fever (YF) vaccine efficacy is currently available. Based on the studies identified in a recent systematic review, we conducted a random-effects meta-analysis of the serological response associated with YF vaccination. Eleven studies conducted between 1965 and 2011 representing 4,868 individual observations were included in the meta-analysis. The pooled estimate of serological response was 97.5% (95% confidence interval [CI] = 82.9-99.7%). There was evidence of between-study heterogeneity (I 2 = 89.1%), but this heterogeneity did not appear to be related to study size, study design, or seroconversion measurement or definition. Pooled estimates were significantly higher (P < 0.0001) among studies conducted in nonendemic settings (98.9%, 95% CI = 98.2-99.4%) than among those conducted in endemic settings (94.2%, 95% CI = 83.8-98.1%). These results provide background information against which to evaluate the efficacy of fractional doses of YF vaccine that may be used in outbreak situations. © The American Society of Tropical Medicine and Hygiene.

  4. Development of a Real-Time Reverse Transcription-PCR Assay for Global Differentiation of Yellow Fever Virus Vaccine-Related Adverse Events from Natural Infections.

    PubMed

    Hughes, Holly R; Russell, Brandy J; Mossel, Eric C; Kayiwa, John; Lutwama, Julius; Lambert, Amy J

    2018-06-01

    Yellow fever (YF) is a reemerging public health threat, with frequent outbreaks prompting large vaccination campaigns in regions of endemicity in Africa and South America. Specific detection of vaccine-related adverse events is resource-intensive, time-consuming, and difficult to achieve during an outbreak. To address this, we have developed a highly transferable rapid yellow fever virus (YFV) vaccine-specific real-time reverse transcription-PCR (RT-PCR) assay that distinguishes vaccine from wild-type lineages. The assay utilizes a specific hydrolysis probe that includes locked nucleic acids to enhance specific discrimination of the YFV17D vaccine strain genome. Promisingly, sensitivity and specificity analyses reveal this assay to be highly specific to vaccine strain(s) when tested on clinical samples and YFV cell culture isolates of global origin. Taken together, our data suggest the utility of this assay for use in laboratories of varied capacity for the identification and differentiation of vaccine-related adverse events from wild-type infections of both African and South American origin. Copyright © 2018 American Society for Microbiology.

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

    NASA Astrophysics Data System (ADS)

    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.

  6. 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.

    PubMed

    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.

  7. 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

    PubMed Central

    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

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

    PubMed

    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.

  9. [Microeconomic evaluation of a mass preventive immunisation campaign against meningococcal meningitis and yellow fever in Senegal in 1997].

    PubMed

    da Silva, Alfred; Parent du Châtelet, Isabelle; Beckr Gaye, Abou; Dompnier, Jean-Pierre; Seck, Ibrahima

    2003-01-01

    Large epidemics of group A meningococcal meningitis occurred in 1995 and 1996 in several countries of the Sub-Saharan Africa zone known as the "meningitis belt", and more particularly in West Africa. Most of these countries affected by the epidemics met difficulties to set up the strategy recommended by the World Health Organization and which includes: Epidemiological surveillance and epidemic incidence threshold calculation to detect early meningitis epidemics and emergency vaccination campaigns with meningococcal A + C polysaccharide vaccine, if possible within the 4-to-6 weeks following the moment the threshold is reached. In this context of epidemics, notably in Mali, and in front of the risk of resurgence of yellow fever, the Ministry of Health of Senegal decided to conduct mass preventive immunization campaigns in 1997 against meningo- coccal meningitis and yellow fever in the districts located in the eastern part of the country and where emergency vaccination would have been difficult in case of epidemic because these area are difficult to reach. A short-term microeconomic evaluation of additional costs that are necessary to organize one of these mass preventive immunization campaigns was conducted in 1997 in the Matam District, in the Northeast part of Senegal. The method rested on value attribution and accounting procedure. The cost was defined as the monetary value of all mobilized resources to product the campaign corresponding to a plurality of charges and representing all of the effective expenses and donations. During this campaign, 85,925 people were vaccinated and a total number of 163,981 doses of both polysaccharide A + C meningococcal and yellow fever vaccines were administered within 3 weeks. Four intervention strategies were involved: Three for vaccination (mobile, fixed and outreach strategy) and one for coordination, information and training. The total cost of the campaign was 55,322.75 euros. Vaccines and solvents represented 60% of the

  10. 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.

    PubMed

    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

  11. What Controls the Acute Viral Infection Following Yellow Fever Vaccination?

    PubMed

    Moore, James; Ahmed, Hasan; Jia, Jonathan; Akondy, Rama; Ahmed, Rafi; Antia, Rustom

    2018-01-01

    Does target cell depletion, innate immunity, or adaptive immunity play the dominant role in controlling primary acute viral infections? Why do some individuals have higher peak virus titers than others? Answering these questions is a basic problem in immunology and can be particularly difficult in humans due to limited data, heterogeneity in responses in different individuals, and limited ability for experimental manipulation. We address these questions for infections following vaccination with the live attenuated yellow fever virus (YFV-17D) by analyzing viral load data from 80 volunteers. Using a mixed effects modeling approach, we find that target cell depletion models do not fit the data as well as innate or adaptive immunity models. Examination of the fits of the innate and adaptive immunity models to the data allows us to select a minimal model that gives improved fits by widely used model selection criteria (AICc and BIC) and explains why it is hard to distinguish between the innate and adaptive immunity models. We then ask why some individuals have over 1000-fold higher virus titers than others and find that most of the variation arises from differences in the initial/maximum growth rate of the virus in different individuals.

  12. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo

    PubMed Central

    Douam, Florian; Soto Albrecht, Yentli E.; Hrebikova, Gabriela; Sadimin, Evita; Davidson, Christian; Kotenko, Sergei V.

    2017-01-01

    ABSTRACT 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. PMID:28811340

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

    PubMed

    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.

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

    PubMed

    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.

  15. Yellow fever in the Americas: the growing concern about new epidemics.

    PubMed

    Ortiz-Martínez, Yeimer; Patiño-Barbosa, Andrés Mauricio; Rodriguez-Morales, Alfonso J

    2017-01-01

    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.

  16. Molecular epidemiology of yellow fever in Bolivia from 1999 to 2008.

    PubMed

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

    2011-03-01

    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.

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

    PubMed

    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.

  18. Surveillance for Yellow Fever Virus in Non-Human Primates in Southern Brazil, 2001–2011: A Tool for Prioritizing Human Populations for Vaccination

    PubMed Central

    Almeida, Marco A. B.; Cardoso, Jader da C.; dos Santos, Edmilson; da Fonseca, Daltro F.; Cruz, Laura L.; Faraco, Fernando J. C.; Bercini, Marilina A.; Vettorello, Kátia C.; Porto, Mariana A.; Mohrdieck, Renate; Ranieri, Tani M. S.; Schermann, Maria T.; Sperb, Alethéa F.; Paz, Francisco Z.; Nunes, Zenaida M. A.; Romano, Alessandro P. M.; Costa, Zouraide G.; Gomes, Silvana L.; Flannery, Brendan

    2014-01-01

    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. PMID:24625681

  19. Increasing Vero viable cell densities for yellow fever virus production in stirred-tank bioreactors using serum-free medium.

    PubMed

    Mattos, Diogo A; Silva, Marlon V; Gaspar, Luciane P; Castilho, Leda R

    2015-08-20

    In this work, changes in Vero cell cultivation methods have been employed in order to improve cell growth conditions to obtain higher viable cell densities and to increase viral titers. The propagation of the 17DD yellow fever virus (YFV) in Vero cells grown on Cytodex I microcarriers was evaluated in 3-L bioreactor vessels. Prior to the current changes, Vero cells were repeatedly displaying insufficient microcarrier colonization. A modified cultivation process with four changes has resulted in higher cell densities and higher virus titers than previously observed for 17DD YFV. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shustov, Alexandr V.; Frolov, Ilya, E-mail: ivfrolov@UAB.ed

    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 ofmore » 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.« less

  1. Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review.

    PubMed

    Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

    2011-07-01

    To assess the reporting rates of serious adverse events attributable to yellow fever vaccination with 17D and 17DD strains as reported in pharmacovigilance databases, and assess reasons for differences in reporting rates. We searched 9 electronic databases for peer reviewed and grey literature (government reports, conferences), in all languages. Reference lists of key studies were also reviewed to identify additional studies. We identified 2,415 abstracts, of which 472 were selected for full text review. We identified 15 pharmacovigilance databases which reported adverse events attributed to yellow fever vaccination, of which 10 contributed data to this review with about 107,600,000 patients (allowing for overlapping time periods for the studies of the US VAERS database), and the data are very heavily weighted (94%) by the Brazilian database. The estimates of serious adverse events form three groups. 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 provide an estimate of 3.6/cases per million YEL-AND in one analysis and 7.8 in another, and 3.1 YEL-AVD in one analysis and 3.9 in another. The estimates for the UK used only the inclusive term of "serious adverse events" not further classified into YEL-And or YEL-AND and reported 34 "serious adverse events." The Swiss database used the term "serious adverse events" and reported 7 such events (including 4 "neurologic reactions") for a reporting rate of 25 "serious adverse events"/million doses. Reporting rates for serious adverse events following yellow fever vaccination are low. Differences in reporting rates may be due to differences in definitions, surveillance system organisation, methods of reporting cases

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

    PubMed

    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.

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed Central

    Zhao, Shi; Stone, Lewi; Gao, Daozhou

    2018-01-01

    Background 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. Model 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 (R0), 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). Findings 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 R0≈2.6-3.4 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 R0 are in line with previous studies. Unusually, R0 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 R0, and vice-versa. The time

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

    PubMed

    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.

  7. Improved genetic stability of recombinant yellow fever 17D virus expressing a lentiviral Gag gene fragment.

    PubMed

    de Santana, Marlon G Veloso; Neves, Patrícia C C; dos Santos, Juliana Ribeiro; Lima, Noemia S; dos Santos, Alexandre A C; Watkins, David I; Galler, Ricardo; Bonaldo, Myrna C

    2014-03-01

    We have previously designed a method to construct viable recombinant Yellow Fever (YF) 17D viruses expressing heterologous polypeptides including part of the Simian Immunodeficiency Virus (SIV) Gag protein. However, the expressed region, encompassing amino acid residues from 45 to 269, was genetically unstable. In this study, we improved the genetic stability of this recombinant YF 17D virus by introducing mutations in the IRES element localized at the 5' end of the SIV gag gene. The new stable recombinant virus elicited adaptive immune responses similar to those induced by the original recombinant virus. It is, therefore, possible to increase recombinant stability by removing functional motifs from the insert that may have deleterious effects on recombinant YF viral fitness. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Development and characterization of a packaging cell line for pseudo-infectious yellow fever virus particle generation.

    PubMed

    Queiroz, Sabrina Ribeiro de Almeida; Silva Júnior, José Valter Joaquim; Silva, Andréa Nazaré Monteiro Rangel da; Carvalho, Amanda Gomes de Oliveira; Santos, Jefferson José da Silva; Gil, Laura Helena Vega Gonzales

    2018-01-01

    Pseudo-infectious yellow fever viral particles (YFV-PIVs) have been used to study vaccines and viral packaging. Here, we report the development of a packaging cell line, which expresses the YFV prM/E proteins. HEK293 cells were transfected with YFV prM/E and C (84 nt) genes to generate HEK293-YFV-PrM/E-opt. The cells were evaluated for their ability to express the heterologous proteins and to package the replicon repYFV-17D-LucIRES, generating YFV-PIVs. The expression of prM/E proteins was confirmed, and the cell line trans-packaged the replicon for recovery of a reporter for the YFV-PIVs. HEK293-YFV-prM/E-opt trans-packaging capacity demonstrates its possible biotechnology application.

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

    PubMed

    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.

  10. Yellow fever vaccination elicits broad functional CD4+ T cell responses that recognize structural and nonstructural proteins.

    PubMed

    James, Eddie A; LaFond, Rebecca E; Gates, Theresa J; Mai, Duy T; Malhotra, Uma; Kwok, William W

    2013-12-01

    Yellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8(+) T cell responses, less is known about YFV-specific CD4(+) T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4(+) T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4(+) T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4(+) T cell responses that contract, forming a detectable memory population.

  11. Yellow Fever Vaccination Elicits Broad Functional CD4+ T Cell Responses That Recognize Structural and Nonstructural Proteins

    PubMed Central

    James, Eddie A.; LaFond, Rebecca E.; Gates, Theresa J.; Mai, Duy T.; Malhotra, Uma

    2013-01-01

    Yellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8+ T cell responses, less is known about YFV-specific CD4+ T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4+ T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4+ T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4+ T cell responses that contract, forming a detectable memory population. PMID:24049183

  12. Equilibrium analysis of a yellow Fever dynamical model with vaccination.

    PubMed

    Martorano Raimundo, Silvia; Amaku, Marcos; Massad, Eduardo

    2015-01-01

    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.

  13. Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients after a preventive immunisation campaign in Mali.

    PubMed

    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.

  14. Plasmid DNA initiates replication of yellow fever vaccine in vitro and elicits virus-specific immune response in mice.

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  17. Characterization of recombinant yellow fever-dengue vaccine viruses with human monoclonal antibodies targeting key conformational epitopes.

    PubMed

    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

  18. Evaluation of travel medicine practice by yellow fever vaccination centers in England, Wales, and Northern Ireland.

    PubMed

    Boddington, Nicola L; Simons, Hilary; Launders, Naomi; Gawthrop, Mary; Stillwell, Alexandra; Wong, Claire; Mathewson, John; Hill, David R

    2012-01-01

    The National Travel Health Network and Centre (NaTHNaC) introduced a program of registration, training, standards, and audit for yellow fever vaccination centers (YFVCs) in England, Wales, and Northern Ireland (EWNI) in 2005. Prior to rolling out the program, NaTHNaC surveyed YFVCs in England. To reassess the practice of YFVCs in 2009, 4 years after the institution of the NaTHNaC program, to identify areas for ongoing support, and to assess the impact of the program. In 2009, all YFVCs in EWNI were asked to complete a questionnaire on type of practice, administration of travel vaccines, staff training, vaccine storage and patient record keeping, use of travel health information, evaluation of NaTHNaC yellow fever (YF) training, and resource and training needs. Data were analyzed using Microsoft Excel® and STATA 9®. The questionnaire was completed by 1,438 YFVCs (41.5% of 3,465 YFVCs). Most YFVCs were based in General Practice (87.4%). In nearly all YFVCs (97.0%), nurses advised travelers and administered YF vaccine. An annual median of 50 doses of YF vaccine was given by each YFVC. A total of 96.7% of nurses had received training in travel medicine, often through study days run by vaccine manufacturers. The internet was frequently used for information during travel consultations (84.8%) and NaTHNaC's on-line and telephone advice resources were highly rated. Following YF training, 95.8% of attendees expressed improved confidence regarding YF vaccination issues. There was excellent adherence to vaccination standards: ≥ 94% correctly stored vaccines, recorded refrigerator temperatures, and maintained YF vaccination records. In the 4 years since institution of the NaTHNaC program for YFVCs, there has been improved adherence to basic standards of immunization practice and increased confidence of health professionals in YF vaccination. The NaTHNaC program could be a model for other national public health bodies, as they establish a program for YF centers. © 2012

  19. Molecular pathogenesis of viral hemorrhagic fever.

    PubMed

    Basler, Christopher F

    2017-07-01

    The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

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

    PubMed Central

    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

  1. Lessons Learned from Emergency Response Vaccination Efforts for Cholera, Typhoid, Yellow Fever, and Ebola

    PubMed Central

    Date, Kashmira A.; Sreenivasan, Nandini; Harris, Jennifer B.; Hyde, Terri B.

    2017-01-01

    Countries must be prepared to respond to public health threats associated with emergencies, such as natural disasters, sociopolitical conflicts, or uncontrolled disease outbreaks. Rapid vaccination of populations vulnerable to epidemic-prone vaccine-preventable diseases is a major component of emergency response. Emergency vaccination planning presents challenges, including how to predict resource needs, expand vaccine availability during global shortages, and address regulatory barriers to deliver new products. The US Centers for Disease Control and Prevention supports countries to plan, implement, and evaluate emergency vaccination response. We describe work of the Centers for Disease Control and Prevention in collaboration with global partners to support emergency vaccination against cholera, typhoid, yellow fever, and Ebola, diseases for which a new vaccine or vaccine formulation has played a major role in response. Lessons learned will help countries prepare for future emergencies. Integration of vaccination with emergency response augments global health security through reducing disease burden, saving lives, and preventing spread across international borders. PMID:29155670

  2. Yellow Fever prevention strategies awareness among HIV-infected patients in São Paulo, Brazil.

    PubMed

    Avelino-Silva, Vivian Iida; Francelino, Hilario Sousa; Kallás, Esper Georges

    2014-01-01

    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. 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. 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. YF is an important and preventable public health concern, and these results demonstrate that more information is necessary for the HIV-infected population.

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

    PubMed Central

    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. PMID:24553128

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

    PubMed

    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.

  5. Biological and Phylogenetic Characteristics of Yellow Fever Virus Lineages from West Africa

    PubMed Central

    Laraway, Hewád; Faye, Ousmane; Diallo, Mawlouth; Niedrig, Matthias

    2013-01-01

    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. PMID:23269797

  6. Patterns of a sylvatic yellow fever virus amplification in southeastern Senegal, 2010.

    PubMed

    Diallo, Diawo; Sall, Amadou A; Diagne, Cheikh T; Faye, Oumar; Hanley, Kathryn A; Buenemann, Michaela; Ba, Yamar; Faye, Ousmane; Weaver, Scott C; Diallo, Mawlouth

    2014-06-01

    During the wet season of 2010, yellow fever virus (YFV) was detected in field-collected mosquitoes in the Kédougou region in southeastern Senegal. During this outbreak, we studied the association of the abundance of YFV-infected mosquitoes and land cover features to try and understand the dynamics of YFV transmission within the region. In total, 41,234 mosquito females were collected and tested for virus infection in 5,152 pools. YFV was detected in 67 pools; species including Aedes furcifer (52.2% of the infected pools), Ae. luteocephalus (31.3% of the infected pools), Ae. taylori (6.0% of the infected pools) and six other species (10.4% of the infected pools) captured in September (13.4%), October (70.1%), and November (16.4%). Spatially, YFV was detected from mosquitoes collected in all land cover classes but mainly, forest canopies (49.2%). Human infection is likely mediated by Ae. furcifer, the only species found infected with YFV within villages. Villages containing YFV-infected mosquitoes were significantly closer to large forests (> 2 ha) than villages in which no infected mosquitoes were detected. © The American Society of Tropical Medicine and Hygiene.

  7. The synergistic effect of combined immunization with a DNA vaccine and chimeric yellow fever/dengue virus leads to strong protection against dengue.

    PubMed

    Azevedo, Adriana S; Gonçalves, Antônio J S; Archer, Marcia; Freire, Marcos S; Galler, Ricardo; Alves, Ada M B

    2013-01-01

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  10. Description of a Prospective 17DD Yellow Fever Vaccine Cohort in Recife, Brazil

    PubMed Central

    de Melo, Andréa Barbosa; da Silva, Maria da Paz C.; Magalhães, Maria Cecília F.; Gonzales Gil, Laura Helena Vega; Freese de Carvalho, Eduardo M.; Braga-Neto, Ulisses M.; Bertani, Giovani Rota; Marques, Ernesto T. A.; Cordeiro, Marli Tenório

    2011-01-01

    From September 2005 to March 2007, 238 individuals being vaccinated for the first time with the yellow fever (YF) -17DD vaccine were enrolled in a cohort established in Recife, Brazil. A prospective study indicated that, after immunization, anti-YF immunoglobulin M (IgM) and anti-YF IgG were present in 70.6% (IgM) and 98.3% (IgG) of the vaccinated subjects. All vaccinees developed protective immunity, which was detected by the plaque reduction neutralization test (PRNT) with a geometric mean titer of 892. Of the 238 individuals, 86.6% had IgG antibodies to dengue virus; however, the presence of anti-dengue IgG did not interfere significantly with the development of anti-YF neutralizing antibodies. In a separate retrospective study of individuals immunized with the 17DD vaccine, the PRNT values at 5 and 10 years post-vaccination remained positive but showed a significant decrease in neutralization titer (25% with PRNT titers < 100 after 5 years and 35% after 10 years). PMID:21976581

  11. 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.

    PubMed

    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.

  12. Inhibitory effect of essential oils obtained from plants grown in Colombia on yellow fever virus replication in vitro.

    PubMed

    Meneses, Rocío; Ocazionez, Raquel E; Martínez, Jairo R; Stashenko, Elena E

    2009-03-06

    An antiviral drug is needed for the treatment of patients suffering from yellow fever. Several compounds present in plants can inactive in vitro a wide spectrum of animal viruses. In the present study the inhibitory effect of essential oils of Lippia alba, Lippia origanoides, Oreganum vulgare and Artemisia vulgaris on yellow fever virus (YFV) replication was investigated. The cytotoxicity (CC(50)) on Vero cells was evaluated by the MTT reduction method. The minimum concentration of the essential oil that inhibited virus titer by more than 50% (MIC) was determined by virus yield reduction assay. YFV was incubated 24 h at 4 degrees C with essential oil before adsorption on Vero cell, and viral replication was carried out in the absence or presence of essential oil. Vero cells were exposed to essential oil 24 h at 37 degrees C before the adsorption of untreated-virus. The CC(50) values were less than 100 microg/mL and the MIC values were 3.7 and 11.1 microg/mL. The CC(50)/MIC ratio was of 22.9, 26.4, 26.5 and 8.8 for L. alba, L origanoides, O. vulgare and A. vulgaris, respectively. The presence of essential oil in the culture medium enhances the antiviral effect: L. origanoides oil at 11.1 microg/mL produced a 100% reduction of virus yield, and the same result was observed with L. alba, O. vulgare and A. vulgaris oils at 100 microg/mL. No reduction of virus yield was observed when Vero cells were treated with essential oil before the adsorption of untreated-virus. The essential oils evaluated in the study showed antiviral activities against YFV. The mode of action seems to be direct virus inactivation.

  13. Inhibitory effect of essential oils obtained from plants grown in Colombia on yellow fever virus replication in vitro

    PubMed Central

    Meneses, Rocío; Ocazionez, Raquel E; Martínez, Jairo R; Stashenko, Elena E

    2009-01-01

    Background An antiviral drug is needed for the treatment of patients suffering from yellow fever. Several compounds present in plants can inactive in vitro a wide spectrum of animal viruses. Aim In the present study the inhibitory effect of essential oils of Lippia alba, Lippia origanoides, Oreganum vulgare and Artemisia vulgaris on yellow fever virus (YFV) replication was investigated. Methods The cytotoxicity (CC50) on Vero cells was evaluated by the MTT reduction method. The minimum concentration of the essential oil that inhibited virus titer by more than 50% (MIC) was determined by virus yield reduction assay. YFV was incubated 24 h at 4°C with essential oil before adsorption on Vero cell, and viral replication was carried out in the absence or presence of essential oil. Vero cells were exposed to essential oil 24 h at 37°C before the adsorption of untreated-virus. Results The CC50 values were less than 100 μg/mL and the MIC values were 3.7 and 11.1 μg/mL. The CC50/MIC ratio was of 22.9, 26.4, 26.5 and 8.8 for L. alba, L origanoides, O. vulgare and A. vulgaris, respectively. The presence of essential oil in the culture medium enhances the antiviral effect: L. origanoides oil at 11.1 μg/mLproduced a 100% reduction of virus yield, and the same result was observed with L. alba, O. vulgare and A. vulgaris oils at100 μg/mL. No reduction of virus yield was observed when Vero cells were treated with essential oil before the adsorption of untreated-virus. Conclusion The essential oils evaluated in the study showed antiviral activities against YFV. The mode of action seems to be direct virus inactivation. PMID:19267922

  14. Intriguing olfactory proteins from the yellow fever mosquito, Aedes aegypti

    NASA Astrophysics Data System (ADS)

    Ishida, Yuko; Chen, Angela M.; Tsuruda, Jennifer M.; Cornel, Anthon J.; Debboun, Mustapha; Leal, Walter S.

    2004-09-01

    Four antennae-specific proteins (AaegOBP1, AaegOBP2, AaegOBP3, and AaegASP1) were isolated from the yellow fever mosquito, Aedes aegypti and their full-length cDNAs were cloned. RT-PCR indicated that they are expressed in female and, to a lesser extent, in male antennae, but not in control tissues (legs). AaegOBP1 and AaegOBP3 showed significant similarity to previously identified mosquito odorant-binding proteins (OBPs) in cysteine spacing pattern and sequence. Two of the isolated proteins have a total of eight cysteine residues. The similarity of the spacing pattern of the cysteine residues and amino acid sequence to those of previously identified olfactory proteins suggests that one of the cysteine-rich proteins (AaegOBP2) is an OBP. The other (AaegASP1) did not belong to any group of known OBPs. Structural analyses indicate that six of the cysteine residues in AaegOBP2 are linked in a similar pattern to the previously known cysteine pairing in OBPs, i.e., Cys-24 Cys-55, Cys-51 Cys-104, Cys-95 Cys-113. The additional disulfide bridge, Cys-38 Cys-125, knits the extended C-terminal segment of the protein to a predicted α2-helix. As indicated by circular dichroism (CD) spectra, the extra rigidity seems to prevent the predicted formation of a C-terminal α-helix at low pH.

  15. Vaccine administration decision making: the case of yellow fever vaccine.

    PubMed

    Lown, Beth A; Chen, Lin H; Wilson, Mary E; Sisson, Emily; Gershman, Mark; Yanni, Emad; Jentes, Emily S; Hochberg, Natasha S; Hamer, Davidson H; Barnett, Elizabeth D

    2012-09-01

    Providers must counsel travelers to yellow fever (YF)-endemic areas, although risk estimates of disease and vaccine serious adverse events (SAEs) may be imprecise. The impact of risk information and patients' requests for participation in vaccine decisions on providers' recommendations is unknown. Vaccine providers were surveyed regarding decisions for 4 patient scenarios before and after being presented information about risk of YF disease vs vaccine SAEs. Participants' theoretical attitudes were compared with actual responses to scenarios in which patients wanted to share vaccine decisions. Analyses were done by using χ(2) tests with significance level of .05. Forty-six percent of respondents made appropriate initial YF vaccine administration decisions for a pregnant woman, 73% for an immunosuppressed man, and 49% for an 8-month-old infant. After receiving scenario-specific information, 20%, 54%, and 23% of respondents respectively who initially responded incorrectly changed to a more appropriate decision. Thirty-one percent of participants made consistently appropriate decisions. Among participants who made ≥1 incorrect decision, 35.7% made no decision changes after receiving information. In the scenario in which either a decision to withhold or to administer vaccine was acceptable, 19% of respondents refused a patient's request for vaccine. Targeted information is necessary but insufficient to change the process of vaccine administration decision making. Providers need additional education to enable them to apply evidence, overcome cognitive decision-making errors, and involve patients in vaccine decisions.

  16. Germ line transformation of the yellow fever mosquito, Aedes aegypti, mediated by transpositional insertion of a piggyBac vector.

    PubMed

    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.

  17. A Possible connection between the 1878 yellow fever epidemic in the southern United States and the 1877-78 El Niño episode

    USGS Publications Warehouse

    Diaz, Henry F.; McCabe, Gregory J.

    1999-01-01

    This study documents some of the extreme climate anomalies that were recorded in 1877 and 1878 in parts of the eastern United States, with particular emphasis on highlighting the evolution of these anomalies, as they might have contributed to the epidemic. Other years with major outbreaks of yellow fever in the eighteenth and nineteenth centuries also occurred during the course of El Niño episodes, a fact that appears not to have been noted before in the literature.

  18. Yellow fever from Angola and Congo: a storm gathers.

    PubMed

    Ahmed, Qanta A; Memish, Ziad A

    2017-04-01

    In common with Zika, Chikungunya and Dengue, Yellow Fever (YF) is an arthropod-borne flavivirus. It is transmitted between humans and from monkeys by mosquitoes of the Aedes aegypti (its principal vector), haemogogus and albopictus varieties. Three cycles of transmission may occur: urban; sylvatic; and intermediate. Recently, sub-Saharan Africa has seen the resurgence of this neglected disease. The current YF outbreak in Angola began in December 2015 in the capital Luanda and by October 2016 there had been > 4300 suspected cases, with 376 deaths (case fatality rate = 8.8%). A total of 884 were laboratory confirmed but it is likely that case numbers may be seriously underestimated. YF has subsequently quickly spread to neighbouring Congo and further afield to Kenya and also China, this being of grave concern as this was a first introduction of YF to Asia. YF has recently hit Brazil, with 555 suspected cases and 107 deaths reported by the end of January 2017. Extremely rapid unplanned urban migration in Africa by non-immune rural populations to already densely populated cities, where high densities of mosquitoes co-exist with city dwellers in makeshift flimsy accommodation, poses a ready recipe for an epidemic of massive proportion. In such conditions, with enormously strained public services existing among the most needy and vulnerable populations, mosquito control programmes are nearly impossible. YF in Congo is a tempest barely restrained. However, it is one that can be controlled by focused and committed international collaboration, by intense and united political will and by the marriage of old and trusted techniques: a vaccine almost a century old and some of the most modern technologies available to man.

  19. End-pumped continuous-wave intracavity yellow Raman laser at 590 nm with SrWO4 Raman crystal

    NASA Astrophysics Data System (ADS)

    Yang, F. G.; You, Z. Y.; Zhu, Z. J.; Wang, Y.; Li, J. F.; Tu, C. Y.

    2010-01-01

    We present an end-pumped continuous-wave intra-cavity yellow Raman laser at 590 nm with a 60 mm long pure crystal SrWO4 and an intra-cavity LiB3O5 frequency doubling crystal. The highest output power of yellow laser at 590 nm was 230 mW and the output power and threshold were found to be correlative with the polarized directions of pure single crystal SrWO4 deeply. Along different directions, the minimum and maximum thresholds of yellow Raman laser at 590 nm were measured to be 2.8 W and 14.3 W with respect to 808 nm LD pump power, respectively.

  20. Active and passive surveillance of yellow fever vaccine 17D or 17DD-associated serious adverse events: systematic review.

    PubMed

    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

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

    PubMed

    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.

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

    PubMed

    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

  3. Wave processes and geologic responses on the floor of the Yellow Sea

    USGS Publications Warehouse

    Booth, James S.; Winters, William J.

    1991-01-01

    The floor of the Yellow Sea is a geologically mundane surface: it is nearly horizontal, lacks relief, and, with few exceptions, is devoid of conspicuous geomorphologic features. However, it is the principal repository for the prodigious sediment load of the Huanghe (Yellow River); and, due to its inherent shallowness (average depth is 40 m), it is frequently stressed by waves generated by winter storms and typhoons. Analyses of mass physical properties of cores representing the upper few meters of sediment in the central and north-central Yellow Sea (near the Shandong Peninsula), in conjunction with analyses of slope stability, failure modes, and erodibility, permit an assessment of the likelihood and effect of dynamic, transient geologic events on the seabed.Vane shear-strength profiles along with consolidation test data indicate that the present surface of the seabed is in a depositional mode and is compacting normally. in addition, liquid-limit profiles imply that in the study area these neritic sediments have been accumulating in an environment that probably has not been modified significantly since sea level reached its current level. There is no geotechnical evidence in the nine cores recovered that slope failures have occurred, and clasts, sand lenses or other manifestations of mass movements, including flows, also are absent. These observations support previous interpretations of seismic records. Moreover, slope stability analysis for static conditions shows that the sea floor is quite stable.Regardless, shear-stress levels generated by cyclic loading during major storms may approach the sediment shear strengths, and, when coupled with concomitant excess pore pressures, could cause slope failure. Unless the failed beds collapsed or flowed, however, there probably would be little conspicuous evidence of such a failure. in fact, evaluation of the potential of these sediments for disintegrative behavior suggests that they are not prone to either collapse or

  4. [Estimated operational costs of vaccination campaign to combat yellow fever in Abidjan].

    PubMed

    Zengbe-Acray, Pétronille; Douba, Alfred; Traore, Youssouf; Dagnan, Simplice; Attoh-Toure, Harvey; Ekra, Daniel

    2009-01-01

    A cost effectiveness study was conducted with the main objective to assess the operational costs of a vaccination campaign against yellow fever organised and implemented in Abidjan from September 21st to October 2nd, 2001. The study was carried out from the perspective of the health authorities. Data was collected retrospectively on all information related to resources needed and required activities. The justification of the monetary value of resources was provided with written proof and receipts as well as other supporting documents. The coverage achieved was 91.33% with 2 584 360 doses of vaccine having been administered. Spending on vaccines and vaccine supplies amounted to 1 123 177 128 FCFA; the average cost per dose was 539.40 FCFA. Human resource costs amounted to 2590 people who were mobilized for a total cost of 125 678 400 FCFA. The total operational cost of the vaccination campaign was 1 394 010 829 FCFA. Vaccines and supplies were the largest item of expenditure, or 80.57% of the total spent. The results of this study could serve as a tool for decision-making related to funding a vaccination campaign. Taking account of these results could contribute to the development of strategies to effectively reduce the operational cost of a vaccination campaign.

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

    PubMed

    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.

  6. Gamma-interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204.

    PubMed

    Lam, L K Metthew; Watson, Alan M; Ryman, Kate D; Klimstra, William B

    2018-01-01

    Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation. Using subcutaneous infection of interferon-deficient mouse models of wild type yellow fever virus (WT YFV) pathogenesis and 17D-mediated immunity, we found that, in the absence of type I IFN (IFN-α/β), type II interferon (IFN-γ) restricted 17D replication, but not that of WT YFV, by 1-2 days post-infection. In this context, IFN-γ responses protected 17D-infected animals from mortality, largely restricted the virus to lymphoid organs, and eliminated viscerotropic disease signs such as steatosis in the liver and inflammatory cell infiltration into the spleen. However, WT YFV caused a disseminated infection, gross liver pathology, and rapid death of the animals. In vitro, IFN-γ treatment of myeloid cells suppressed the replication of 17D significantly more than that of WT YFV, suggesting a direct differential effect on 17D virus replication. Together these data indicate that an important mechanism of 17D attenuation in vivo is increased sensitivity to IFN-γ stimulated responses elicited early after infection.

  7. Distinct Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Patients Infected with Vaccinia Virus, Yellow Fever 17D Virus, or Upper Respiratory Infections Running Title: PBMC Expression Response to Viral Agents

    PubMed Central

    Scherer, Christina A.; Magness, Charles L.; Steiger, Kathryn V.; Poitinger, Nicholas D.; Caputo, Christine M.; Miner, Douglas G.; Winokur, Patricia L.; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A.; Gillham, Martha H.; Haulman, N. Jean; Stapleton, Jack T.; Iadonato, Shawn P.

    2007-01-01

    Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents. PMID:17651872

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed Central

    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

  11. Dynamic Viral Dissemination in Mice Infected with Yellow Fever Virus Strain 17D

    PubMed Central

    Erickson, Andrea K.

    2013-01-01

    Arboviruses such as yellow fever virus (YFV) are transmitted between arthropod vectors and vertebrate hosts. While barriers limiting arbovirus population diversity have been observed in mosquitoes, whether barriers exist in vertebrate hosts is unclear. To investigate whether arboviruses encounter bottlenecks during dissemination in the vertebrate host, we infected immunocompetent mice and immune-deficient mice lacking alpha/beta interferon (IFN-α/β) receptors (IFNAR−/− mice) with a pool of genetically marked viruses to evaluate dissemination and host barriers. We used the live attenuated vaccine strain YFV-17D, which contains many mutations compared with virulent YFV. We found that intramuscularly injected immunocompetent mice did not develop disease and that viral dissemination was restricted. Conversely, 32% of intramuscularly injected IFNAR−/− mice developed disease. By following the genetically marked viruses over time, we found broad dissemination in IFNAR−/− mice followed by clearance. The patterns of viral dissemination were similar in mice that developed disease and mice that did not develop disease. Unlike our previous results with poliovirus, these results suggest that YFV-17D encounters no major barriers during dissemination within a vertebrate host in the absence of the type I IFN response. PMID:24027319

  12. Places, attitudes and moments during the epidemics: representations of yellow fever and cholera in the city of Buenos Aires, 1867-1871.

    PubMed

    Fiquepron, Maximiliano Ricardo

    2018-01-01

    The goal of this article is to analyze the different representations of health and disease associated with the epidemics of yellow fever and cholera that took place from 1867-1871 in the city of Buenos Aires. It argues that there was a very broad and heterogeneous repertoire of representations that resulted in a variety of attitudes on the part of individuals dealing with the crisis, and led to the transformation of space and social time. In order to handle this traumatic experience, people chose very different methods for maintaining social contact, which was also a way of maintaining their health.

  13. Dissection of Antibody Specificities Induced by Yellow Fever Vaccination

    PubMed Central

    Vratskikh, Oksana; Stiasny, Karin; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Jarmer, Johanna; Karrer, Urs; Roggendorf, Michael; Roggendorf, Hedwig; Allwinn, Regina; Heinz, Franz X.

    2013-01-01

    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-specific factors

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

    PubMed

    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.

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

    PubMed

    Vratskikh, Oksana; Stiasny, Karin; Zlatkovic, Jürgen; Tsouchnikas, Georgios; Jarmer, Johanna; Karrer, Urs; Roggendorf, Michael; Roggendorf, Hedwig; Allwinn, Regina; Heinz, Franz X

    2013-01-01

    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-specific factors

  16. Immunogenicity and Safety of Yellow Fever Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients After Withdrawal of Immunosuppressive Therapy.

    PubMed

    Sicre de Fontbrune, Flore; Arnaud, Cécile; Cheminant, Morgane; Boulay, Aude; Konopacki, Johana; Lapusan, Simona; Robin, Christine; Bernaudin, Françoise; Suarez, Felipe; Simon, François; Socié, Gérard; Colin de Verdière, Nathalie; Consigny, Paul-Henri

    2018-01-17

    As a live attenuated vaccine, yellow fever vaccine (YFV) is not routinely performed after allogeneic hematopoietic stem cell transplant (HSCT) despite it being the only efficient preventive therapy. We retrospectively identified 21 HSCT recipients immunized with YFV at a median of 39 months after HSCT and a median of 33 months after withdrawal of immunosuppression without any side effects. Eighteen evaluable patients had protective immunity after YFV. We also observed that a third of the recipients vaccinated with YFV before HSCT had persistent protective immunity after HSCT. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  17. Yellow Fever Virus Modulates the Expression of Key Proteins Related to the microRNA Pathway in the Human Hepatocarcinoma Cell Line HepG2.

    PubMed

    Holanda, Gustavo Moraes; Casseb, Samir Mansour Moraes; Mello, Karla Fabiane Lopes; Vasconcelos, Pedro Fernando Costa; Cruz, Ana Cecília Ribeiro

    2017-06-01

    Yellow fever is a zoonotic disease caused by the yellow fever virus (YFV) and transmitted by mosquitoes of the family Culicidae. It is well known that cellular and viral microRNAs (miRNAs) are involved in modulation of viral and cellular gene expression, as well as immune response, and are considered by the scientific community as possible targets for an effective therapy against viral infections. This regulation may be involved in different levels of infection and clinical symptomatology. We used viral titration techniques, viral kinetics from 24 to 96 hours postinfection (hpi), and analyzed the expression of key proteins related to the miRNA pathway by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The expression of Dicer was different when compared over the course of infection by the distinct YFV genotypes. Drosha expression was similar during infection by YFV genotype 1 or 2, with a decrease in their expression over time and a slight increase in 96 hpi. Ago1, Ago2, and Ago4 showed different levels of expression between the viral genotypes: for YFV genotype 1 infection, Ago1 presented a positive expression, while for YFV genotype 2, it showed a negative expression, when compared with negative controls. We conclude that YFV infection modulates the proteins involved in miRNA biogenesis, which can regulate both viral replication and cellular immune response.

  18. Out of Africa: a molecular perspective on the introduction of yellow fever virus into the Americas.

    PubMed

    Bryant, Juliet E; Holmes, Edward C; Barrett, Alan D T

    2007-05-18

    Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300-400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease.

  19. Out of Africa: A Molecular Perspective on the Introduction of Yellow Fever Virus into the Americas

    PubMed Central

    Bryant, Juliet E; Holmes, Edward C; Barrett, Alan D. T

    2007-01-01

    Yellow fever virus (YFV) remains the cause of severe morbidity and mortality in South America and Africa. To determine the evolutionary history of this important reemerging pathogen, we performed a phylogenetic analysis of the largest YFV data set compiled to date, representing the prM/E gene region from 133 viral isolates sampled from 22 countries over a period of 76 years. We estimate that the currently circulating strains of YFV arose in Africa within the last 1,500 years and emerged in the Americas following the slave trade approximately 300–400 years ago. These viruses then spread westwards across the continent and persist there to this day in the jungles of South America. We therefore illustrate how gene sequence data can be used to test hypotheses of viral dispersal and demographics, and document the role of human migration in the spread of infectious disease. PMID:17511518

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

    PubMed

    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.

  1. Yellow fever in Pará State, Amazon region of Brazil, 1998-1999: entomologic and epidemiologic findings.

    PubMed

    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.

  2. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

    PubMed

    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.

  3. Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

    PubMed Central

    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

  4. Dengue hemorrhagic fever and acute hepatitis: a case report.

    PubMed

    Mourão, Maria Paula Gomes; Lacerda, Marcus Vinícius Guimarães de; Bastos, Michele de Souza; Albuquerque, Bernardino Cláudio de; Alecrim, Wilson Duarte

    2004-12-01

    Dengue fever is the world's most important viral hemorrhagic fever disease, the most geographically wide-spread of the arthropod-born viruses, and it causes a wide clinical spectrum of disease. We report a case of dengue hemorrhagic fever complicated by acute hepatitis. The initial picture of classical dengue fever was followed by painful liver enlargement, vomiting, hematemesis, epistaxis and diarrhea. Severe liver injury was detected by laboratory investigation, according to a syndromic surveillance protocol, expressed in a self-limiting pattern and the patient had a complete recovery. The serological tests for hepatitis and yellow fever viruses were negative. MAC-ELISA for dengue was positive.

  5. Production of pseudoinfectious yellow fever virus with a two-component genome.

    PubMed

    Shustov, Alexandr V; Mason, Peter W; Frolov, Ilya

    2007-11-01

    Application of genetically modified, deficient-in-replication flaviviruses that are incapable of developing productive, spreading infection is a promising means of designing safe and effective vaccines. Here we describe a two-component genome yellow fever virus (YFV) replication system in which each of the genomes encodes complete sets of nonstructural proteins that form the replication complex but expresses either only capsid or prM/E instead of the entire structural polyprotein. Upon delivery to the same cell, these genomes produce together all of the viral structural proteins, and cells release a combination of virions with both types of genomes packaged into separate particles. In tissue culture, this modified YFV can be further passaged at an escalating scale by using a high multiplicity of infection (MOI). However, at a low MOI, only one of the genomes is delivered into the cells, and infection cannot spread. The replicating prM/E-encoding genome produces extracellular E protein in the form of secreted subviral particles that are known to be an effective immunogen. The presented strategy of developing viruses defective in replication might be applied to other flaviviruses, and these two-component genome viruses can be useful for diagnostic or vaccine applications, including the delivery and expression of heterologous genes. In addition, the achieved separation of the capsid-coding sequence and the cyclization signal in the YFV genome provides a new means for studying the mechanism of the flavivirus packaging process.

  6. Yellow Fever Vaccine: What You Need to Know

    MedlinePlus

    ... to any component of the vaccine, including eggs, chicken proteins, or gelatin, or who has had a ... allergic reaction, very high fever, behavior changes, or flu-like symptoms that occur 1-30 days after ...

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

    PubMed

    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.

  8. AaCAT1 of the Yellow Fever Mosquito, Aedes aegypti

    PubMed Central

    Hansen, Immo A.; Boudko, Dmitri Y.; Shiao, Shin-Hong; Voronov, Dmitri A.; Meleshkevitch, Ella A.; Drake, Lisa L.; Aguirre, Sarah E.; Fox, Jeffrey M.; Attardo, Geoffrey M.; Raikhel, Alexander S.

    2011-01-01

    Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to l-histidine at neutral pH (K0.5l-His = 0.34 ± 0.07 mm, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His+-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues. PMID:21262963

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

    PubMed Central

    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

  10. Comparative study on in vitro activities of citral, limonene and essential oils from Lippia citriodora and L. alba on yellow fever virus.

    PubMed

    Gómez, Luz Angela; Stashenko, Elena; Ocazionez, Raquel Elvira

    2013-02-01

    The aim of this study was to compare the antiviral activities in vitro of citral, limonene and essential oils (EOs) from Lippia citriodora and L. alba on the replication of yellow fever virus (YFV). Citral and EOs were active before and after virus adsorption on cells; IC50 values were between 4.3 and 25 microg/mL and SI ranged from 1.1 to 10.8. Results indicate that citral could contribute to the antiviral activity of the L. citriodora EO. Limonene was not active and seemed to play an insignificant role in the antiviral activity of the examined EOs.

  11. Defining Risk Groups to Yellow Fever Vaccine-Associated Viscerotropic Disease in the Absence of Denominator Data

    PubMed Central

    Seligman, Stephen J.; Cohen, Joel E.; Itan, Yuval; Casanova, Jean-Laurent; Pezzullo, John C.

    2014-01-01

    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. PMID:24394480

  12. Defining risk groups to yellow fever vaccine-associated viscerotropic disease in the absence of denominator data.

    PubMed

    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.

  13. WHO Working Group on Technical Specifications for Manufacture and Evaluation of Yellow Fever Vaccines, Geneva, Switzerland, 13-14 May 2009.

    PubMed

    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.

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

    PubMed

    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.

  15. Development and characterization of polyclonal peptide antibodies for the detection of Yellow fever virus proteins.

    PubMed

    Stock, N K; Escadafal, C; Achazi, K; Cissé, M; Niedrig, M

    2015-09-15

    There is still a considerable need for development of new tools and methods detecting specific viral proteins for the diagnosis and pathogenesis study of the Yellow fever virus (YFV). This study aimed to develop and characterize polyclonal peptide antisera for detection of YFV-C and -NS1 proteins. The antisera were used further to investigate NS1 protein expression during YFV infection in mammalian cells. YFV target proteins were detected by all antisera in western blot and immunofluorescence assays. No cross-reactivity was observed with Dengue virus, West Nile virus, Tick-borne encephalitis virus and Japanese encephalitis virus. Nuclear localization of the YFV-C protein was demonstrated for the first time. Experiments investigating NS1 expression suggested a potential use of the YFV-NS1 antisera for development of diagnostic approaches targeting the secreted form of the NS1 protein. The antisera described in this study offer new possibilities for use in YFV research and for the development of novel diagnostic tests. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    PubMed Central

    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

  17. Oropouche Fever: A Review.

    PubMed

    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.

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

    PubMed

    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.

  19. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis

    PubMed Central

    Slifka, Mark K.; Leung, Donald Y. M.; Hammarlund, Erika; Raué, Hans-Peter; Simpson, Eric L.; Tofte, Susan; Baig-Lewis, Shahana; David, Gloria; Lynn, Henry; Woolson, Rob; Hata, Tissa; Milgrom, Henry; Hanifin, Jon

    2013-01-01

    Background Atopic dermatitis (AD) is a common inflammatory skin disease with global prevalence ranging from 3% to 20%. AD patients have an increased risk for complications following viral infection (e.g., herpes simplex virus), and vaccination of AD patients with live vaccinia virus is contraindicated due to a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination. Objective To develop a better understanding of immunity to cutaneous viral infection in AD patients. Methods In a double-blind, randomized study, we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of non-atopic (NA) subjects and AD patients following standard subcutaneous (SC) inoculation or transcutaneous (TC) vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T cell responses were analyzed for up to 30 days post-vaccination. Results YFV vaccination by either route was well tolerated. SC vaccination resulted in higher seroconversion rates than TC vaccination but elicited similar antiviral antibody levels and T cell responses in both NA and AD groups. Following TC vaccination, both groups mounted similar neutralizing antibody responses, but AD patients demonstrated lower antiviral T cell responses by 30 days after vaccination. Among TC-vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4+ T cell responses was observed. Conclusions YFV vaccination of AD patients by the TC route revealed that high baseline IgE levels provides a potential biomarker for predicting reduced virus-specific immune memory following TC infection with a live virus. PMID:24331381

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

    PubMed

    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

  1. Identification of pathogens for differential diagnosis of fever with jaundice in the Central African Republic: a retrospective assessment, 2008-2010.

    PubMed

    Gadia, Christelle Luce Bobossi; Manirakiza, Alexandre; Tekpa, Gaspard; Konamna, Xavier; Vickos, Ulrich; Nakoune, Emmanuel

    2017-11-29

    Febrile jaundice results clinically in generalized yellow coloration of the teguments and mucous membranes due to excess plasma bilirubin, accompanied by fever. Two types are found: conjugated and unconjugated bilirubin jaundice. Jaundice is a sign in several diseases due to viruses (viral hepatitis and arbovirus), parasites (malaria) and bacteria (leptospirosis). In the Central African Republic (CAR), only yellow fever is included on the list of diseases for surveillance. The aim of this study was to identify the other pathogens that can cause febrile jaundice, for better management of patients. Between 2008 and 2010, 198 sera negative for yellow fever IgM were randomly selected from 2177 samples collected during yellow fever surveillance. Laboratory analyses targeted four groups of pathogens: hepatitis B, C, delta and E viruses; dengue, chikungunya, Zika, Crimean-Congo haemorrhagic fever, West Nile and Rift Valley arboviruses; malaria parasites; and bacteria (leptospirosis). Overall, 30.9% sera were positive for hepatitis B, 20.2% for hepatitis E, 12.3% for hepatitis C and 8.2% for malaria. The majority of positive sera (40.4%) were from people aged 16-30 years. Co-infection with at least two of these pathogens was also found. These findings suggest that a systematic investigation should be undertaken of infectious agents that cause febrile jaundice in the CAR.

  2. Influence of the IL-1Ra gene polymorphism on in vivo synthesis of IL-1Ra and IL-1beta after live yellow fever vaccination.

    PubMed

    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

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

    PubMed

    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.

  4. Immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite Plasmodium yoelii.

    PubMed

    Stoyanov, Cristina T; Boscardin, Silvia B; Deroubaix, Stephanie; Barba-Spaeth, Giovanna; Franco, David; Nussenzweig, Ruth S; Nussenzweig, Michel; Rice, Charles M

    2010-06-23

    The live-attenuated yellow fever vaccine (YF17D) is one of the safest and most effective vaccines available today. Here, YF17D was genetically altered to express the circumsporozoite protein (CSP) from the murine malarial parasite Plasmodium yoelii. Reconstituted recombinant virus was viable and exhibited robust CSP expression. Immunization of naïve mice resulted in extensive proliferation of adoptively transferred CSP-specific transgenic CD8(+) T-cells. A single immunization of naïve mice with recombinant YF17D resulted in robust production of IFN-gamma by CD8(+) T-cells and IFN-gamma and IL-2 by CD4(+) T-cells. A prime-boost regimen consisting of recombinant virus followed by a low-dose of irradiated sporozoites conferred protection against challenge with P. yoelii. Taken together, these results show that recombinant YF17D can efficiently express CSP in culture, and prime a protective immune response in vivo. (c) 2010 Elsevier Ltd. All rights reserved.

  5. CD8+ gamma-delta TCR+ and CD4+ T cells produce IFN-γ at 5-7 days after yellow fever vaccination in Indian rhesus macaques, before the induction of classical antigen-specific T cell responses.

    PubMed

    Neves, Patrícia C C; Rudersdorf, Richard A; Galler, Ricardo; Bonaldo, Myrna C; de Santana, Marlon Gilsepp Veloso; Mudd, Philip A; Martins, Maurício A; Rakasz, Eva G; Wilson, Nancy A; Watkins, David I

    2010-11-29

    The yellow fever 17D (YF-17D) vaccine is one of the most efficacious vaccines developed to date. Interestingly, vaccination with YF-17D induces IFN-γ production early after vaccination (days 5-7) before the development of classical antigen-specific CD8(+) and CD4(+) T cell responses. Here we investigated the cellular source of this early IFN-γ production. At days 5 and 7 post-vaccination activated CD8(+) gamma-delta TCR T cells produced IFN-γ and TNF-α. Activated CD4(+) T cells produced IFN-γ and TNF-α at day 7 post-vaccination. This early IFN-γ production was also induced after vaccination with recombinant YF-17D (rYF-17D), but was not observed after recombinant Adenovirus type 5 (rAd5) vaccination. Early IFN-γ production, therefore, might be an important aspect of yellow fever vaccination. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    PubMed

    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.

  7. Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

    PubMed

    Michel, R; Berger, F; Ravelonarivo, J; Dussart, P; Dia, M; Nacher, M; Rogier, S; Moua, D; Sarr, F D; Diop, O M; Sall, A A; Baril, L

    2015-05-11

    The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Current status, challenges and perspectives in the development of vaccines against yellow fever, dengue, Zika and chikungunya viruses.

    PubMed

    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.

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

    PubMed

    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.

  10. Internally Controlled, Multiplex Real-Time Reverse Transcription PCR for Dengue Virus and Yellow Fever Virus Detection.

    PubMed

    Rojas, Alejandra; Diagne, Cheikh T; Stittleburg, Victoria D; Mohamed-Hadley, Alisha; de Guillén, Yvalena Arévalo; Balmaseda, Angel; Faye, Oumar; Faye, Ousmane; Sall, Amadou A; Harris, Eva; Pinsky, Benjamin A; Waggoner, Jesse J

    2018-04-02

    The differential diagnosis of dengue virus (DENV) and yellow fever virus (YFV) infections in endemic areas is complicated by nonspecific early clinical manifestations. In this study, we describe an internally controlled, multiplex real-time reverse transcription PCR (rRT-PCR) for the detection of DENV and YFV. The DENV-YFV assay demonstrated specific detection and had a dynamic range of 2.0-8.0 log 10 copies/μL of eluate for each DENV serotype and YFV. Clinical performance was similar to a published pan-DENV assay: 48/48 acute-phase samples from dengue cases were detected in both assays. For YFV detection, mock samples were prepared with nine geographically diverse YFV isolates over a range of concentrations. The DENV-YFV assay detected 62/65 replicates, whereas 54/65 were detected using a reference YFV rRT-PCR. Given the reemergence of DENV and YFV in areas around the world, the DENV-YFV assay should be a useful tool to narrow the differential diagnosis and provide early case detection.

  11. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis.

    PubMed

    Slifka, Mark K; Leung, Donald Y M; Hammarlund, Erika; Raué, Hans-Peter; Simpson, Eric L; Tofte, Susan; Baig-Lewis, Shahana; David, Gloria; Lynn, Henry; Woolson, Rob; Hata, Tissa; Milgrom, Henry; Hanifin, Jon

    2014-02-01

    Atopic dermatitis (AD) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. Patients with AD have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with AD with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination. We sought to develop a better understanding of immunity to cutaneous viral infection in patients with AD. In a double-blind randomized study we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of nonatopic subjects and patients with AD after standard subcutaneous inoculation or transcutaneous vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for up to 30 days after vaccination. YFV vaccination administered through either route was well tolerated. Subcutaneous vaccination resulted in higher seroconversion rates than transcutaneous vaccination but elicited similar antiviral antibody levels and T-cell responses in both the nonatopic and AD groups. After transcutaneous vaccination, both groups mounted similar neutralizing antibody responses, but patients with AD demonstrated lower antiviral T-cell responses by 30 days after vaccination. Among transcutaneously vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was observed. YFV vaccination of patients with AD through the transcutaneous route revealed that high baseline IgE levels provide a potential biomarker for predicting reduced virus-specific immune memory after transcutaneous infection with a live virus. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  12. Analysis of a Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) for yellow fever diagnostic.

    PubMed

    Nunes, Marcio R T; Vianez, João Lídio; Nunes, Keley N B; da Silva, Sandro Patroca; Lima, Clayton P S; Guzman, Hilda; Martins, Lívia C; Carvalho, Valéria L; Tesh, Robert B; Vasconcelos, Pedro F C

    2015-12-15

    Yellow Fever virus (YFV) is an important human pathogen in tropical areas of Africa and South America. Although an efficient vaccine is available and has been used since the early 1940s, sylvatic YFV transmission still occurs in forested areas where anthropogenic actions are present, such as mineral extraction, rearing livestock and agriculture, and ecological tourism. In this context, two distinct techniques based on the RT-PCR derived method have been previously developed, however both methods are expensive due to the use of thermo cyclers and labeled probes. We developed isothermal genome amplification, which is a rapid, sensitive, specific and low cost molecular approach for YFV genome detection. This assay used a set of degenerate primers designed for the NS1 gene and was able to amplify, within 30 min in isothermal conditions, the YFV 17D vaccine strain derived from an African wild prototype strain (Asibi), as well as field strains from Brazil, other endemic countries from South and Central America, and the Caribbean. The generic RT-LAMP assay could be helpful for YFV surveillance in field and rapid response during outbreaks in endemic areas. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. T-cell memory responses elicited by yellow fever vaccine are targeted to overlapping epitopes containing multiple HLA-I and -II binding motifs.

    PubMed

    de Melo, Andréa Barbosa; Nascimento, Eduardo J M; Braga-Neto, Ulisses; Dhalia, Rafael; Silva, Ana Maria; Oelke, Mathias; Schneck, Jonathan P; Sidney, John; Sette, Alessandro; Montenegro, Silvia M L; Marques, Ernesto T A

    2013-01-01

    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.

  14. T-Cell Memory Responses Elicited by Yellow Fever Vaccine are Targeted to Overlapping Epitopes Containing Multiple HLA-I and -II Binding Motifs

    PubMed Central

    de Melo, Andréa Barbosa; Nascimento, Eduardo J. M.; Braga-Neto, Ulisses; Dhalia, Rafael; Silva, Ana Maria; Oelke, Mathias; Schneck, Jonathan P.; Sidney, John; Sette, Alessandro; Montenegro, Silvia M. L.; Marques, Ernesto T. A.

    2013-01-01

    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. PMID:23383350

  15. The whole iceberg: estimating the incidence of yellow fever virus infection from the number of severe cases.

    PubMed

    Johansson, Michael A; Vasconcelos, Pedro F C; Staples, J Erin

    2014-08-01

    Like many infectious agents, yellow fever (YF) virus only causes disease in a proportion of individuals it infects and severe illness only represents the tip of the iceberg relative to the total number of infections, the more critical factor for virus transmission. We compiled data on asymptomatic infections, mild disease, severe disease (fever with jaundice or hemorrhagic symptoms) and fatalities from 11 studies in Africa and South America between 1969 and 2011. We used a Bayesian model to estimate the probability of each infection outcome. For YF virus infections, the probability of being asymptomatic was 0.55 (95% credible interval [CI] 0.37-0.74), mild disease 0.33 (95% CI 0.13-0.52) and severe disease 0.12 (95% CI 0.05-0.26). The probability of death for people experiencing severe disease was 0.47 (95% CI 0.31-0.62). In outbreak situations where only severe cases may initially be detected, we estimated that there may be between one and seventy infections that are either asymptomatic or cause mild disease for every severe case identified. As it is generally only the most severe cases that are recognized and reported, these estimates will help improve the understanding of the burden of disease and the estimation of the potential risk of spread during YF outbreaks. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  16. Adaptation of yellow fever virus 17D to Vero cells is associated with mutations in structural and non-structural protein genes.

    PubMed

    Beasley, David W C; Morin, Merribeth; Lamb, Ashley R; Hayman, Edward; Watts, Douglas M; Lee, Cynthia K; Trent, Dennis W; Monath, Thomas P

    2013-09-01

    Serial passaging of yellow fever virus 17D in Vero cells was employed to derive seed material for a novel inactivated vaccine, XRX-001. Two independent passaging series identified a novel lysine to arginine mutation at amino acid 160 of the envelope protein, a surface-exposed residue in structural domain I. A third passage series resulted in an isoleucine to methionine mutation at residue 113 of the NS4B protein, a central membrane spanning region of the protein which has previously been associated with Vero cell adaptation of other mosquito-borne flaviviruses. These studies confirm that flavivirus adaptation to growth in Vero cells can be mediated by structural or non-structural protein mutations. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

    PubMed

    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

  18. Evaluation of chimeric yellow fever 17D/dengue viral replication in ticks.

    PubMed

    Kazimírová, Mária; Mantel, Nathalie; Raynaud, Sandrine; Slovák, Mirko; Ustaniková, Katarína; Lang, Jean; Guy, Bruno; Barban, Veronique; Labuda, Milan

    2012-11-01

    Chimeric yellow fever 17D/DENV-1-4 viruses (CYD-1-4) have been developed as a tetravalent dengue vaccine candidate which is currently being evaluated in efficacy trials in Asia and America. While YF 17D and DENV are mosquito-borne flaviviruses, it has been shown that CYD-1-4 do not replicate after oral infection in mosquitoes and are not transmitted to new hosts. To further document the risk of environmental dissemination of these viruses, we evaluated the replication of CYD-1-4 in ticks, the vector of tick-borne encephalitis virus (TBEV), another member of the flavivirus family. Females of two hard tick species, Ixodes ricinus and Rhipicephalus appendiculatus, were inoculated intracoelomically with CYD-1-4 viruses and parent viruses (DENV-1-4 and YF 17D). Virus persistence and replication was assessed 2, 16, and 44 days post-inoculation by plaque titration and qRT-PCR. CYD-1-4 viruses were detected in I. ricinus ticks at early time points post-inoculation, but with infectious titers at least 100-fold lower than those observed in TBEV-infected ticks. Unlike TBEV, complete viral clearance occurred by day 44 in most ticks except for CYD-2, which had a tendency to decline. In addition, while about 70% of TBEV-infected I. ricinus nymphs acquired infection by co-feeding with infected tick females on non-viremic hosts, no co-feeding transmission of CYD-2 virus was detected. Based on these results, we conclude that the risk of dissemination of the candidate vaccine viruses by tick bite is highly unlikely.

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

    PubMed

    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

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

    PubMed

    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.

  1. Distinctive TLR7 signaling, type I IFN production, and attenuated innate and adaptive immune responses to yellow fever virus in a primate reservoir host.

    PubMed

    Mandl, Judith N; Akondy, Rama; Lawson, Benton; Kozyr, Natalia; Staprans, Silvija I; Ahmed, Rafi; Feinberg, Mark B

    2011-06-01

    Why cross-species transmissions of zoonotic viral infections to humans are frequently associated with severe disease when viruses responsible for many zoonotic diseases appear to cause only benign infections in their reservoir hosts is unclear. Sooty mangabeys (SMs), a reservoir host for SIV, do not develop disease following SIV infection, unlike nonnatural HIV-infected human or SIV-infected rhesus macaque (RM) hosts. SIV infections of SMs are characterized by an absence of chronic immune activation, in association with significantly reduced IFN-α production by plasmacytoid dendritic cells (pDCs) following exposure to SIV or other defined TLR7 or TLR9 ligands. In this study, we demonstrate that SM pDCs produce significantly less IFN-α following ex vivo exposure to the live attenuated yellow fever virus 17D strain vaccine, a virus that we show is also recognized by TLR7, than do RM or human pDCs. Furthermore, in contrast to RMs, SMs mount limited activation of innate immune responses and adaptive T cell proliferative responses, along with only transient antiviral Ab responses, following infection with yellow fever vaccine 17D strain. However, SMs do raise significant and durable cellular and humoral immune responses comparable to those seen in RMs when infected with modified vaccinia Ankara, a virus whose immunogenicity does not require TLR7/9 recognition. Hence, differences in the pattern of TLR7 signaling and type I IFN production by pDCs between primate species play an important role in determining their ability to mount and maintain innate and adaptive immune responses to specific viruses, and they may also contribute to determining whether disease follows infection.

  2. Assessment of atrial electromechanical delay in children with acute rheumatic fever.

    PubMed

    Ciftel, Murat; Turan, Ozlem; Simşek, Ayşe; Kardelen, Fırat; Akçurin, Gayaz; Ertuğ, Halil

    2014-02-01

    There may be an increase in the risk of atrial arrhythmia due to left atrial enlargement and the influence on conduction system in acute rheumatic fever. The aim of this study is to investigate atrial electromechanical delay and P-wave dispersion in patients with acute rheumatic fever. A total of 48 patients diagnosed with acute rheumatic fever and 40 volunteers of similar age, sex, and body mass index were included in the study. The study groups were compared for M-mode echocardiographic parameters, interatrial electromechanical delay, intra-atrial electromechanical delay, and P-wave dispersion. Maximum P-wave duration, P-wave dispersion, and interatrial electromechanical delay were significantly higher in patients with acute rheumatic fever compared with the control group (p < 0.001). However, there was no difference in terms of intra-atrial electromechanical delay (p > 0.05). For patients with acute rheumatic fever, a positive correlation was identified between the left atrium diameter and the P-wave dispersion and interatrial electromechanical delay (r = 0.524 and p < 0.001, and r = 0.351 and p = 0.014, respectively). Furthermore, an important correlation was also identified between the P-wave dispersion and the interatrial electromechanical delay (r = 0.494 and p < 0.001). This study shows the prolongation of P-wave dispersion and interatrial electromechanical delay in acute rheumatic fever. Left atrial enlargement can be one of the underlying reasons for the increase in P-wave dispersion and interatrial electromechanical delay.

  3. IMOJEV(®): a Yellow fever virus-based novel Japanese encephalitis vaccine.

    PubMed

    Appaiahgari, Mohan Babu; Vrati, Sudhanshu

    2010-12-01

    Japanese encephalitis (JE) is a disease of the CNS caused by Japanese encephalitis virus (JEV). The disease appears in the form of frequent outbreaks in most south- and southeast Asian countries and the virus has become endemic in several areas. There is no licensed therapy available and disease control by vaccination is considered to be most effective. Mouse brain-derived inactivated JE vaccines, although immunogenic, have several limitations in terms of safety, availability and requirement for multiple doses. Owing to these drawbacks, the WHO called for the development of novel, safe and more efficacious JE vaccines. Several candidate vaccines have been developed and at least three of them that demonstrated strong immunogenicity after one or two doses of the vaccine in animal models were subsequently tested in various clinical trials. One of these vaccines, IMOJEV(®) (JE-CV and previously known as ChimeriVax™-JE), is a novel recombinant chimeric virus vaccine, developed using the Yellow fever virus (YFV) vaccine vector YFV17D, by replacing the cDNA encoding the envelope proteins of YFV with that of an attenuated JEV strain SA14-14-2. IMOJEV was found to be safe, highly immunogenic and capable of inducing long-lasting immunity in both preclinical and clinical trials. Moreover, a single dose of IMOJEV was sufficient to induce protective immunity, which was similar to that induced in adults by three doses of JE-VAX(®), a mouse brain-derived inactivated JE vaccine. Recently, Phase III trials evaluating the immunogenicity and safety of the chimeric virus vaccine have been successfully completed in some JE-endemic countries and the vaccine manufacturers have filed an application for vaccine registration. IMOJEV may thus be licensed for use in humans as an improved alternative to the currently licensed JE vaccines.

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

    PubMed

    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.

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

    PubMed

    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.

  6. Immunological features underlying viral hemorrhagic fevers.

    PubMed

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Yellow fever virus capsid protein is a potent suppressor of RNA silencing that binds double-stranded RNA.

    PubMed

    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.

  8. Thiosemicarbazones and Phthalyl-Thiazoles compounds exert antiviral activity against yellow fever virus and Saint Louis encephalitis virus.

    PubMed

    Pacca, Carolina Colombelli; Marques, Rafael Elias; Espindola, José Wanderlan P; Filho, Gevânio B O Oliveira; Leite, Ana Cristina Lima; Teixeira, Mauro Martins; Nogueira, Mauricio L

    2017-03-01

    Arboviruses, arthropod-borneviruses, are frequency associated to human outbreak and represent a serious health problem. The genus Flavivirus, such as Yellow Fever Virus (YFV) and Saint Louis Encephalitis Virus (SLEV), are important pathogens with high morbidity and mortality worldwide. In Brazil, YFV is maintained in sylvatic cycle, but many cases are notified annually, despite the efficiency of vaccine. SLEV causes an acute encephalitis and is widely distributed in the Americas. There is no specific antiviral drugs for these viruses, only supporting treatment that can alleviate symptoms and prevent complications. Here, we evaluated the potential anti-YFV and SLEV activity of a series of thiosemicarbazones and phthalyl-thiazoles. Plaque reduction assay, flow cytometry, immunofluorescence and cellular viability were used to test the compounds in vitro. Treated cells showed efficient inhibition of the viral replication at concentrations that presented minimal toxicity to cells. The assays showed that phthalyl-thiazole and phenoxymethyl-thiosemicarbazone reduced 60% of YFV replication and 75% of SLEV replication. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Spatial and temporal abundance of three sylvatic yellow fever vectors in the influence area of the Manso hydroelectric power plant, Mato Grosso, Brazil.

    PubMed

    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.

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

    PubMed

    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 <9 months and >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 (P<0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine 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.

  11. The elderly, the young and the pregnant traveler -- A retrospective data analysis from a large Swiss Travel Center with a special focus on malaria prophylaxis and yellow fever vaccination.

    PubMed

    Jaeger, Veronika K; Tschudi, Nadine; Rüegg, Rolanda; Hatz, Christoph; Bühler, Silja

    2015-01-01

    Vulnerable individuals such as elderly, children/adolescents and pregnant/breastfeeding women increasingly travel overseas. We describe the travel and vaccination patterns of these groups at the largest Travel Clinic in Switzerland especially focusing on travel to yellow fever and malaria-endemic countries, and yellow fever vaccination (YFV) and malaria medications. An analysis of pre-travel visits between 2010 and 2012 at the Travel Clinic of the University of Zurich, was performed assessing differences between the elderly, young and middle-aged travelers as well as between pregnant/breastfeeding and other female travelers. Overall, the vulnerable groups did not differ from other travelers regarding their travel patterns. YFV was the most often administered vaccine to elderly travelers; half of them received it for the first time. More than 30% of children/adolescents received YFV, but no child below six months was vaccinated. 80% of young travelers and a similar percentage of pregnant women went to malaria-endemic regions. Twenty-five pregnant/breastfeeding women traveled to YF endemic areas. Travel patterns of vulnerable travelers are comparable to those of other travelers. In view of the limited data on malaria medications and precautions against YFV during pregnancy and at the extreme ages of life, giving travel advice to these groups is challenging. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. New approaches for the standardization and validation of a real-time qPCR assay using TaqMan probes for quantification of yellow fever virus on clinical samples with high quality parameters.

    PubMed

    Fernandes-Monteiro, Alice G; Trindade, Gisela F; Yamamura, Anna M Y; Moreira, Otacilio C; de Paula, Vanessa S; Duarte, Ana Cláudia M; Britto, Constança; Lima, Sheila Maria B

    2015-01-01

    The development and production of viral vaccines, in general, involve several steps that need the monitoring of viral load throughout the entire process. Applying a 2-step quantitative reverse transcription real time PCR assay (RT-qPCR), viral load can be measured and monitored in a few hours. In this context, the development, standardization and validation of a RT-qPCR test to quickly and efficiently quantify yellow fever virus (YFV) in all stages of vaccine production are extremely important. To serve this purpose we used a plasmid construction containing the NS5 region from 17DD YFV to generate the standard curve and to evaluate parameters such as linearity, precision and specificity against other flavivirus. Furthermore, we defined the limits of detection as 25 copies/reaction, and quantification as 100 copies/reaction for the test. To ensure the quality of the method, reference controls were established in order to avoid false negative results. The qRT-PCR technique based on the use of TaqMan probes herein standardized proved to be effective for determining yellow fever viral load both in vivo and in vitro, thus becoming a very important tool to assure the quality control for vaccine production and evaluation of viremia after vaccination or YF disease.

  13. New approaches for the standardization and validation of a real-time qPCR assay using TaqMan probes for quantification of yellow fever virus on clinical samples with high quality parameters

    PubMed Central

    Fernandes-Monteiro, Alice G; Trindade, Gisela F; Yamamura, Anna MY; Moreira, Otacilio C; de Paula, Vanessa S; Duarte, Ana Cláudia M; Britto, Constança; Lima, Sheila Maria B

    2015-01-01

    The development and production of viral vaccines, in general, involve several steps that need the monitoring of viral load throughout the entire process. Applying a 2-step quantitative reverse transcription real time PCR assay (RT-qPCR), viral load can be measured and monitored in a few hours. In this context, the development, standardization and validation of a RT-qPCR test to quickly and efficiently quantify yellow fever virus (YFV) in all stages of vaccine production are extremely important. To serve this purpose we used a plasmid construction containing the NS5 region from 17DD YFV to generate the standard curve and to evaluate parameters such as linearity, precision and specificity against other flavivirus. Furthermore, we defined the limits of detection as 25 copies/reaction, and quantification as 100 copies/reaction for the test. To ensure the quality of the method, reference controls were established in order to avoid false negative results. The qRT-PCR technique based on the use of TaqMan probes herein standardized proved to be effective for determining yellow fever viral load both in vivo and in vitro, thus becoming a very important tool to assure the quality control for vaccine production and evaluation of viremia after vaccination or YF disease. PMID:26011746

  14. Protein structure shapes immunodominance in the CD4 T cell response to yellow fever vaccination.

    PubMed

    Koblischke, Maximilian; Mackroth, Maria S; Schwaiger, Julia; Fae, Ingrid; Fischer, Gottfried; Stiasny, Karin; Heinz, Franz X; Aberle, Judith H

    2017-08-21

    The live attenuated yellow fever (YF) vaccine is a highly effective human vaccine and induces long-term protective neutralizing antibodies directed against the viral envelope protein E. The generation of such antibodies requires the help of CD4 T cells which recognize peptides derived from proteins in virus particles internalized and processed by E-specific B cells. The CD4 T helper cell response is restricted to few immunodominant epitopes, but the mechanisms of their selection are largely unknown. Here, we report that CD4 T cell responses elicited by the YF-17D vaccine are focused to hotspots of two helices of the viral capsid protein and to exposed strands and loops of E. We found that the locations of immunodominant epitopes within three-dimensional protein structures exhibit a high degree of overlap between YF virus and the structurally homologous flavivirus tick-borne encephalitis virus, although amino acid sequence identity of the epitope regions is only 15-45%. The restriction of epitopes to exposed E protein surfaces and their strikingly similar positioning within proteins of distantly related flaviviruses are consistent with a strong influence of protein structure that shapes CD4 T cell responses and provide leads for a rational design of immunogens for vaccination.

  15. Yellow fever vaccine for patients with HIV infection.

    PubMed

    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

  16. Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours.

    PubMed

    Dekker, Teun; Geier, Martin; Cardé, Ring T

    2005-08-01

    Female mosquitoes are noted for their ability to use odours to locate a host for a blood meal. Two sensory organs contribute to their sense of smell: the maxillary palps, which measure the level of CO2, and the antennae, which detect other host-released odours. To establish the relative importance and interactions of CO2 and other body emissions in freely flying mosquitoes, we presented female yellow fever mosquitoes Aedes aegypti L. with broad plumes of human skin odour and CO2 at natural concentrations and dilutions thereof in a wind tunnel. 3-D video-recorded flight tracks were reconstructed. Activation, flight velocity, upwind turning and source finding waned quickly as skin odours were diluted, whereas in the presence of CO2 these parameters remained unchanged over more than a 100-fold dilution from exhaled concentrations. Although mosquitoes were behaviourally less sensitive to skin odours than to CO2, their sensitivity to skin odours increased transiently by at least fivefold immediately following a brief encounter with a filament of CO2. This sensitization was reflected in flight velocity, track angle, turning rate upon entering and exiting the broad odour plume and, ultimately, in the source-finding rate. In Ae. aegypti, CO2 thus functions as a ;releaser' for a higher sensitivity and responsiveness to skin odours. The initially low responsiveness of mosquitoes to skin odours, their high sensitivity to CO2, and the sensitization of the olfactory circuitry by CO2 are ecologically relevant, because rapidly fluctuating CO2 levels reliably signal a potential host. Possible mechanisms of the instantaneous sensitization are considered.

  17. Yellow fever virus maintenance in Trinidad and its dispersal throughout the Americas.

    PubMed

    Auguste, Albert J; Lemey, Philippe; Pybus, Oliver G; Suchard, Marc A; Salas, Rosa Alba; Adesiyun, Abiodun A; Barrett, Alan D; Tesh, Robert B; Weaver, Scott C; Carrington, Christine V F

    2010-10-01

    Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate.

  18. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo.

    PubMed

    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

  19. Potential risk of re-emergence of urban transmission of Yellow Fever virus in Brazil facilitated by competent Aedes populations.

    PubMed

    Couto-Lima, Dinair; Madec, Yoann; Bersot, Maria Ignez; Campos, Stephanie Silva; Motta, Monique de Albuquerque; Santos, Flávia Barreto Dos; Vazeille, Marie; Vasconcelos, Pedro Fernando da Costa; Lourenço-de-Oliveira, Ricardo; Failloux, Anna-Bella

    2017-07-07

    Yellow fever virus (YFV) causing a deadly viral disease is transmitted by the bite of infected mosquitoes. In Brazil, YFV is restricted to a forest cycle maintained between non-human primates and forest-canopy mosquitoes, where humans can be tangentially infected. Since late 2016, a growing number of human cases have been reported in Southeastern Brazil at the gates of the most populated areas of South America, the Atlantic coast, with Rio de Janeiro state hosting nearly 16 million people. We showed that the anthropophilic mosquitoes Aedes aegypti and Aedes albopictus as well as the YFV-enzootic mosquitoes Haemagogus leucocelaenus and Sabethes albiprivus from the YFV-free region of the Atlantic coast were highly susceptible to American and African YFV strains. Therefore, the risk of reemergence of urban YFV epidemics in South America is major with a virus introduced either from a forest cycle or by a traveler returning from the YFV-endemic region of Africa.

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

    PubMed

    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

  1. Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques.

    PubMed

    Bonaldo, Myrna C; Martins, Mauricio A; Rudersdorf, Richard; Mudd, Philip A; Sacha, Jonah B; Piaskowski, Shari M; Costa Neves, Patrícia C; Veloso de Santana, Marlon G; Vojnov, Lara; Capuano, Saverio; Rakasz, Eva G; Wilson, Nancy A; Fulkerson, John; Sadoff, Jerald C; Watkins, David I; Galler, Ricardo

    2010-04-01

    Here we describe a novel vaccine vector for expressing human immunodeficiency virus (HIV) antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8(+) T-cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8(+) T-cell responses after recombinant YF17D boosting. These recombinant YF17D-induced SIV-specific CD8(+) T cells secreted several cytokines, were largely effector memory T cells, and suppressed viral replication in CD4(+) T cells.

  2. Efficacy and Duration of Immunity after Yellow Fever Vaccination: Systematic Review on the Need for a Booster Every 10 Years

    PubMed Central

    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

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

    PubMed

    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.

  4. Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

    PubMed Central

    McGee, Charles E.; Tsetsarkin, Konstantin A.; Guy, Bruno; Lang, Jean; Plante, Kenneth; Vanlandingham, Dana L.; Higgs, Stephen

    2011-01-01

    Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely. PMID:21826243

  5. Stability of yellow fever virus under recombinatory pressure as compared with chikungunya virus.

    PubMed

    McGee, Charles E; Tsetsarkin, Konstantin A; Guy, Bruno; Lang, Jean; Plante, Kenneth; Vanlandingham, Dana L; Higgs, Stephen

    2011-01-01

    Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4 x 10⁶ in BHK-21 (vertebrate) cells and ∼1.05 x 10⁵ in C₇10 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely.

  6. Activity of T-1106 in a hamster model of yellow Fever virus infection.

    PubMed

    Julander, Justin G; Furuta, Yousuke; Shafer, Kristiina; Sidwell, Robert W

    2007-06-01

    Yellow fever virus (YFV) causes 30,000 deaths worldwide, despite the availability of a vaccine. There are no approved antiviral therapies for the treatment of YFV disease in humans, and, therefore, these studies were designed to investigate the anti-YFV properties of T-1106, a substituted pyrazine, in a hamster model of YFV disease. Intraperitoneal (i.p.) treatment with 100 mg/kg of body weight/day of T-1106 starting 4 h prior to virus inoculation and continuing twice daily through 7 days post-virus inoculation (dpi) resulted in significantly improved survival, alanine aminotransferase levels in the serum, weight gain, and mean day to death. Virus titer in the liver at 4 dpi was significantly reduced in treated animals, as determined by both quantitative real-time PCR and infectious cell culture assay. No toxicity (weight loss or mortality) was observed at a dose of 100 mg/kg/day in sham-infected control animals. The observed minimal effective dose of T-1106 was 32 mg/kg/day administered either by oral or i.p. treatment. Therapeutic treatment was effective in significantly improving survival when T-1106 was administered beginning as late as 4 days after virus challenge with twice-daily treatment for 8 days at a dose of 100 mg/kg/day. With favorable safety, bioavailability, and postviral challenge treatment efficacy, T-1106 was effective in the treatment of disease in hamsters infected with YFV and should be further studied for potential use as a therapy for human YFV disease.

  7. Molecular phylogeny of edge hill virus supports its position in the yellow Fever virus group and identifies a new genetic variant.

    PubMed

    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.

  8. The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by type I interferon.

    PubMed

    Laurent-Rolle, Maudry; Morrison, Juliet; Rajsbaum, Ricardo; Macleod, Jesica M Levingston; Pisanelli, Giuseppe; Pham, Alissa; Ayllon, Juan; Miorin, Lisa; Martinez, Carles; tenOever, Benjamin R; García-Sastre, Adolfo

    2014-09-10

    To successfully establish infection, flaviviruses have to overcome the antiviral state induced by type I interferon (IFN-I). The nonstructural NS5 proteins of several flaviviruses antagonize IFN-I signaling. Here we show that yellow fever virus (YFV) inhibits IFN-I signaling through a unique mechanism that involves binding of YFV NS5 to the IFN-activated transcription factor STAT2 only in cells that have been stimulated with IFN-I. This NS5-STAT2 interaction requires IFN-I-induced tyrosine phosphorylation of STAT1 and the K63-linked polyubiquitination at a lysine in the N-terminal region of YFV NS5. We identified TRIM23 as the E3 ligase that interacts with and polyubiquitinates YFV NS5 to promote its binding to STAT2 and trigger IFN-I signaling inhibition. Our results demonstrate the importance of YFV NS5 in overcoming the antiviral action of IFN-I and offer a unique example of a viral protein that is activated by the same host pathway that it inhibits. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. High stability of yellow fever 17D-204 vaccine: a 12-year restrospective analysis of large-scale production.

    PubMed

    Barban, V; Girerd, Y; Aguirre, M; Gulia, S; Pétiard, F; Riou, P; Barrere, B; Lang, J

    2007-04-12

    We have retrospectively analyzed 12 bulk lots of yellow fever vaccine Stamaril, produced between 1990 and 2002 and prepared from the same seed lot that has been in continuous use since 1990. All vaccine batches displayed identical genome sequence. Only four nucleotide substitutions were observed, compared to previously published sequence, with no incidence at amino-acid level. Fine analysis of viral plaque size distribution was used as an additional marker for genetic stability and demonstrated a remarkable homogeneity of the viral population. The total virus load, measured by qRT-PCR, was also homogeneous pointing out reproducibility of the vaccine production process. Mice inoculated intracerebrally with the different bulks exhibited a similar average survival time, and ratio between in vitro potency and mouse LD(50) titers remained constant from batch-to-batch. Taken together, these data demonstrate the genetic stability of the strain at mass production level over a period of 12 years and reinforce the generally admitted idea of the safety of YF17D-based vaccines.

  10. The interferon signaling antagonist function of yellow fever virus NS5 protein is activated by Type I interferon

    PubMed Central

    Rajsbaum, Ricardo; Macleod, Jesica M. Levingston; Pisanelli, Giuseppe; Pham, Alissa; Ayllon, Juan; Miorin, Lisa; Martinez, Carles; tenOever, Benjamin R; García-Sastre, Adolfo

    2014-01-01

    Summary To successfully establish infection Flaviviruses have to overcome the antiviral state induced by type I interferon (IFN-I). The nonstructural NS5 proteins of several flaviviruses antagonize IFN-I signaling. Here we show that yellow fever virus (YFV) inhibits IFN-I signaling through a unique mechanism that involves binding of YFV NS5 to the IFN-activated transcription factor STAT2 only in cells that have been stimulated with IFN-I. This NS5-STAT2 interaction requires IFN-I-induced tyrosine phosphorylation of STAT1 and the K63-linked polyubiquitination at a lysine in the N-terminal region of YFV NS5. We identified TRIM23 as the E3 ligase that interacts with and polyubiquitinates YFV NS5 to promote its binding to STAT2 and trigger IFN-I signaling inhibition. Our results demonstrate the importance of YFV NS5 in overcoming the antiviral action of IFN-I and offer a unique example of a viral protein that is activated by the same host pathway that it inhibits. PMID:25211074

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

    PubMed

    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 a proxy for potentially longer lasting immunity. PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07-3.1%). On day 180, these cells were still present (median 0.06%, range 0.02-0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells. The presence of a functionally competent YF

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

    PubMed Central

    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

    Introduction 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 a proxy for potentially longer lasting immunity. Methods and Findings PBMCs and serum were collected in six individuals on days 0, 3, 5, 12, 28 and 180, and in 99 individuals >10 years after YF-vaccination. Phenotypic characteristics of YF- tetramer+ CD8+ T-cells were determined using class I tetramers. Antibody responses were measured using a standardized plaque reduction neutralization test (PRNT). Also, characteristics of YF-tetramer positive CD8+ T-cells were compared between individuals who had received a primary- and a booster vaccination. YF-tetramer+ CD8+ T-cells were detectable on day 12 (median tetramer+ cells as percentage of CD8+ T-cells 0.2%, range 0.07–3.1%). On day 180, these cells were still present (median 0.06%, range 0.02–0.78%). The phenotype of YF-tetramer positive CD8+ T-cells shifted from acute phase effector cells on day 12, to late differentiated or effector memory phenotype (CD45RA-/+CD27-) on day 28. Two subsets of YF-tetramer positive T-cells (CD45RA+CD27- and CD45RA+CD27+) persisted until day 180. Within all phenotypic subsets, the T-bet: Eomes ratio tended to be high on day 28 after vaccination and shifted towards predominant Eomes expression on day 180 (median 6.0 (day 28) vs. 2.2 (day 180) p = 0.0625), suggestive of imprinting compatible with long-lived memory properties. YF-tetramer positive CD8+ T-cells were detectable up to 18 years post vaccination, YF-specific antibodies were detectable up to 40 years after single vaccination. Booster vaccination did not increase titers of YF-specific antibodies (mean 12.5 vs. 13.1, p = 0.583), nor induce frequencies or alter phenotypes of YF-tetramer+ CD8+ T-cells. Conclusion The

  13. The risk of urban yellow fever resurgence in Aedes-infested American cities.

    PubMed

    Massad, Eduardo; Amaku, Marcos; Coutinho, Francisco Antonio Bezerra; Struchiner, Claudio José; Lopez, Luis Fernandez; Coelho, Giovanini; Wilder-Smith, Annelies; Burattini, Marcelo Nascimento

    2018-05-30

    Aedes aegypti, historically known as yellow fever (YF) mosquito, transmits a great number of other viruses such as Dengue, West Nile, Chikungunya, Zika, Mayaro and perhaps Oropouche, among others. Well established in Africa and Asia, Aedes mosquitoes are now increasingly invading large parts of the American continent, and hence the risk of urban YF resurgence in the American cities should because of great concern to public health authorities. Although no new urban cycle of YF was reported in the Americas since the end of an Aedes eradication programme in the late 1950s, the high number of non-vaccinated individuals that visit endemic areas, that is, South American jungles where the sylvatic cycle of YF is transmitted by canopy mosquitoes, and return to Aedes-infested urban areas, increases the risk of resurgence of the urban cycle of YF. We present a method to estimate the risk of urban YF resurgence in dengue-endemic cities. This method consists in (1) to estimate the number of Aedes mosquitoes that explains a given dengue outbreak in a given region; (2) calculate the force of infection caused by the introduction of one infective individual per unit area in the endemic area under study; (3) using the above estimates, calculate the probability of at least one autochthonous YF case per unit area produced by one single viraemic traveller per unit area arriving from a YF endemic or epidemic sylvatic region at the city studied. We demonstrate that, provided the relative vector competence, here defined as the capacity to being infected and disseminate the virus, of Ae. aegypti is greater than 0.7 (with respect to dengue), one infected traveller can introduce urban YF in a dengue endemic area.

  14. [Countermeasure against viral hemorrhagic fever at the border in Japan].

    PubMed

    Iwasaki, Emiko

    2005-12-01

    Human have struggled against many infectious diseases such as cholera, plague, dysentery and yellow fever for a long time. And we have spent a lot of energy to control these infectious diseases and developed various tool for them. One of these efforts was Quarantine system that was established in 14th century in Europe. But during recent days, we are suffering from newly emerged diseases. These new infectious diseases are zoonosis and most of them are serious and highly infectious. Viral hemorrhagic fever such as Ebola hemorrhagic fever, Marburg hemorrhagic fever and Lassa fever are typical these emerging serious diseases, and these outbreak always have occurred in Africa and neighboring countries. Fortunately we have never experienced any case, but as these diseases are so serious, we are so nervous diseases entering in Japan. Against these serious diseases, in Japan, Quarantine Station are doing screening examination at airport and port by questionnaire and measuring body temperature, because these viral hemorrhagic fever patients show high fever. If people were suspected viral hemorrhagic fever at Quarantine Station at the border, they will be leaded to hospital for further examination and treatment as soon as possible.

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

    PubMed Central

    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

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

    PubMed

    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

  17. Long-term Immune Response to Yellow Fever Vaccination in Human Immunodeficiency Virus (HIV)-Infected Individuals Depends on HIV RNA Suppression Status: Implications for Vaccination Schedule.

    PubMed

    Veit, Olivia; Domingo, Cristina; Niedrig, Matthias; Staehelin, Cornelia; Sonderegger, Beat; Héquet, Delphine; Stoeckle, Marcel; Calmy, Alexandra; Schiffer, Veronique; Bernasconi, Enos; Flury, Domenica; Hatz, Christoph; Zwahlen, Marcel; Furrer, Hansjakob

    2018-03-19

    In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood. We studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression. At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/μL. PRNT was reactive in 46% (95% confidence interval [CI], 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years. HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.

  18. Assessing the risk of international spread of yellow fever virus: a mathematical analysis of an urban outbreak in Asuncion, 2008.

    PubMed

    Johansson, Michael A; Arana-Vizcarrondo, Neysarí; Biggerstaff, Brad J; Gallagher, Nancy; Marano, Nina; Staples, J Erin

    2012-02-01

    Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission.

  19. Update: Temporary Total Depletion of U.S. Licensed Yellow Fever Vaccine for Civilian Travelers Addressed by Investigational New Drug Use of Imported Stamaril Vaccine.

    PubMed

    Gershman, Mark D; Sotir, Mark J

    2017-07-28

    Sanofi Pasteur, the manufacturer of the only yellow fever vaccine (YF-VAX) licensed in the United States, has announced that their stock of YF-VAX is totally depleted as of July 24, 2017. YF-VAX for civilian use will be unavailable for ordering from Sanofi Pasteur until mid-2018, when their new manufacturing facility is expected to be completed. However, YF-VAX might be available at some clinics for several months, until remaining supplies at those sites are exhausted. In anticipation of this temporary total depletion, in 2016, Sanofi Pasteur submitted an expanded access investigational new drug application to the Food and Drug Administration to allow for importation and use of Stamaril. The Food and Drug Administration accepted Sanofi Pasteur's application in October 2016.

  20. Yellow fever vaccination in organ transplanted patients: is it safe? A multicenter study.

    PubMed

    Azevedo, L S; Lasmar, E P; Contieri, F L C; Boin, I; Percegona, L; Saber, L T S; Selistre, L S; Netto, M V P; Moreira, M C V; Carvalho, R M; Bruno, R M; Ferreira, T C A; David-Neto, E

    2012-06-01

    Yellow fever (YF) may be very serious, with mortality reaching 50%. Live attenuated virus YF vaccine (YFV) is effective, but may present, although rare, life-threatening side effects and is contraindicated in immunocompromised patients. However, some transplant patients may inadvertently receive the vaccine. A questionnaire was sent to all associated doctors to the Brazilian Organ Transplantation Association through its website, calling for reports of organ transplanted patients who have been vaccinated against YF. Twelve doctors reported 19 cases. None had important side effects. Only one had slight reaction at the site of YFV injection. Eleven patients were male. Organs received were 14 kidneys, 3 hearts, and 2 livers. Twelve patients received organs from deceased donors. Mean age at YFV was 45.6 ± 13.6 years old (range 11-69); creatinine: 1.46 ± 0.62 mg/dL (range 0.8-3.4); post-transplant time: 65 ± 83.9 months (range 3-340); and time from YFV at the time of survey: 45 ± 51 months (range 3-241). Immunosuppression varied widely with different drug combinations: azathioprine (7 patients), cyclosporine (8), deflazacort (1), mycophenolate (10), prednisone (11), sirolimus (3), and tacrolimus (4). YFV showed no important side effects in this cohort of solid organ transplanted patients. However, owing to the small number of studied patients, it is not possible to extend these findings to the rest of the transplanted population, assuring safety. Therefore, these data are not strong enough to safely recommend YFV in organ transplanted recipients, as severe, even life-threatening side effects may occur. © 2011 John Wiley & Sons A/S.

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

    PubMed

    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.

  2. Yellow Fever Virus Maintenance in Trinidad and Its Dispersal throughout the Americas▿ †

    PubMed Central

    Auguste, Albert J.; Lemey, Philippe; Pybus, Oliver G.; Suchard, Marc A.; Salas, Rosa Alba; Adesiyun, Abiodun A.; Barrett, Alan D.; Tesh, Robert B.; Weaver, Scott C.; Carrington, Christine V. F.

    2010-01-01

    Trinidad, like many other American regions, experiences repeated epizootics of yellow fever virus (YFV). However, it is unclear whether these result from in situ evolution (enzootic maintenance) or regular reintroduction of YFV from the South American mainland. To discriminate between these hypotheses, we carried out a Bayesian phylogeographic analysis of over 100 prM/E gene sequences sampled from 8 South American countries. These included newly sequenced isolates from the recent 2008-2009 Trinidad epizootic and isolates derived from mainland countries within the last decade. The results indicate that the most recent common ancestor of the 2008-2009 epizootic existed in Trinidad 4.2 years prior to 2009 (95% highest probability density [HPD], 0.5 to 9.0 years). Our data also suggest a Trinidad origin for the progenitor of the 1995 Trinidad epizootic and support in situ evolution of YFV between the 1979 and 1988-1989 Trinidad epizootics. Using the same phylogeographic approach, we also inferred the historical spread of YFV in the Americas. The results suggest a Brazilian origin for YFV in the Americas and an overall dispersal rate of 182 km/year (95% HPD, 52 to 462 km/year), with Brazil as the major source population for surrounding countries. There is also strong statistical support for epidemiological links between four Brazilian regions and other countries. In contrast, while there were well-supported epidemiological links within Peru, the only statistically supported external link was a relatively weak link with neighboring Bolivia. Lastly, we performed a complete analysis of the genome of a newly sequenced Trinidad 2009 isolate, the first complete genome for a genotype I YFV isolate. PMID:20631128

  3. A public health risk assessment for yellow fever vaccination: a model exemplified by an outbreak in the state of São Paulo, Brazil.

    PubMed

    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.

  4. 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?

    PubMed

    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.

  5. Priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans.

    PubMed

    Qiao, Ming; Shaw, David; Forrat, Remi; Wartel-Tram, Anh; Lang, Jean

    2011-10-01

    A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.

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

    PubMed

    Souza, Renato Pereira de; Petrella, Selma; Coimbra, Terezinha Lisieux Moraes; Maeda, Adriana Yurika; Rocco, Iray Maria; Bisordi, Ivani; Silveira, Vivian Regina; Pereira, Luiz Eloy; Suzuki, Akemi; Silva, Sarai Joaquim Dos Santos; Silva, Fernanda Gisele; Salvador, Felipe Scassi; Tubaki, Rosa Maria; Menezes, Regiane Tironi; Pereira, Mariza; Bergo, Eduardo Sterlino; Hoffmann, Roberto Colozza; Spinola, Roberta Maria Fernandes; Tengan, Cílea Hatsumi; Siciliano, Melissa Mascheratti

    2011-01-01

    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.

  7. Spatiotemporal distribution of diurnal yellow fever vectors (Diptera: Culicidae) at two sylvan interfaces in Kenya, East Africa.

    PubMed

    Ellis, Brett Richard; Wesson, Dawn M; Sang, Rosemary C

    2007-01-01

    Yellow fever virus (YFV) remains a significant public health threat in sub-Saharan Africa in which 90% of the estimated 200,000 cases occur annually. In East Africa, human cases of YFV are characterized by unpredictable focal periodicity, lengthy inter-epidemic periods, and a precarious potential for large epidemics. YFV had remained undetected in this region for nearly 40 years until emerging in Kenya in 1992-93 and more recently in Sudan during 2003 and 2005. From an ecological perspective the emergence and epidemiological outcomes associated with YFV, and related vector-borne diseases, are critically dependent upon the underlying vector ecology at a local scale. The study here was aimed at defining the dynamics of important vector interactions at two important sites in Kenya with previous YFV or related arbovirus activity. The temporal abundance, spatial distribution, and human host seeking behavior of diurnal man-landing mosquito species along sylvan interfaces were investigated. A number of YFV vectors were identified including their abundances for the duration of the main rainy season. Spatially, results indicated that the greatest human-mosquito interactions occurred within the forest and decreased across more domesticated biotopes. A discussion of significant differences, ecological associations, and epidemiological implications is included.

  8. Efficacy of 2'-C-methylcytidine against yellow fever virus in cell culture and in a hamster model.

    PubMed

    Julander, Justin G; Jha, Ashok K; Choi, Jung-Ae; Jung, Kie-Hoon; Smee, Donald F; Morrey, John D; Chu, Chung K

    2010-06-01

    Yellow fever virus (YFV) continues to cause outbreaks of disease in endemic areas where vaccine is underutilized. Due to the effectiveness of the vaccine, antiviral development solely for the treatment of YFV is not feasible, but antivirals that are effective in the treatment of related viral diseases may be characterized for potential use against YFV as a secondary indication disease. 2'-C-methylcytidine (2'-C-MeC), a compound active against hepatitis C virus, was found to have activity against the 17D vaccine strain of YFV in cell culture (EC(90)=0.32 microg/ml, SI=141). This compound was effective when added as late as 16 h after virus challenge of Vero cells. When administered to YFV-infected hamsters 4 h prior to virus challenge at a dose as low as 80 mg/kg/d, 2'-C-MeC was effective in significantly improving survival and other disease parameters (weight change, serum ALT, and liver virus titers). Disease was improved when compound was administered beginning as late as 3 d post-virus infection. Broadly active antiviral compounds, such as 2'-C-MeC, represent potential for the development of compounds active against related viruses for the treatment of YFV. Copyright 2010 Elsevier B.V. All rights reserved.

  9. T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.

    PubMed

    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

    2018-02-01

    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 + T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8 + T cells are highly biased for the TCR α chain TRAV12-2. This bias is already present in A2/LLW-specific naïve T cells before vaccination with YF-17D. Using CD8 + T cell clones, we show that TRAV12-2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline-encoded complementarity determining region (CDR) 1α loop of TRAV12-2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T-cell responses specific for the A2/LLW epitope. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.

    PubMed

    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

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

    PubMed

    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.

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

    PubMed Central

    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

  13. Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in an induction of activation markers, cytokines and chemokines and secretion of different TNF-α and IFN-α profiles.

    PubMed

    Gandini, Mariana; Reis, Sonia Regina Nogueira Ignacio; Torrentes-Carvalho, Amanda; Azeredo, Elzinandes Leal; Freire, Marcos da Silva; Galler, Ricardo; Kubelka, Claire Fernandes

    2011-08-01

    Flaviviruses cause severe acute febrile and haemorrhagic infections, including dengue and yellow fever and the pathogenesis of these infections is caused by an exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus (DENV) and yellow fever virus (YF) replication and are the first cell population to interact with these viruses during a natural infection, which leads to an induction of protective immunity in humans. We studied the infectivity of DENV2 (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in monocyte-derived DCs in vitro with regard to cell maturation, activation and cytokine production. Higher viral antigen positive cell frequencies were observed for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures exhibited dendritic cell activation and maturation molecules. CD38 expression on DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was decreased as compared to mock-stimulated cells, suggesting that a T helper 1 profile is favoured. Tumor necrosis factor (TNF)-α production in cell cultures was significantly higher in DENV2-infected cultures than in cultures infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN-α levels than DENV2. The differential cytokine production indicates that DENV2 results in TNF induction, which discriminates it from vaccine viruses that preferentially stimulate interferon expression. These differential response profiles may influence the pathogenic infection outcome.

  14. The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication

    PubMed Central

    2013-01-01

    Background 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. Methods 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. Results 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

  15. The eukaryotic translation initiation factor 3 subunit L protein interacts with Flavivirus NS5 and may modulate yellow fever virus replication.

    PubMed

    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

  16. In situ observations of wave pumping of sediments in the Yellow River Delta with a newly developed benthic chamber

    NASA Astrophysics Data System (ADS)

    Zhang, Shaotong; Jia, Yonggang; Zhang, Yaqi; Liu, Xiaolei; Shan, Hongxian

    2018-03-01

    A specially designed benthic chamber for the field observation of sediment resuspension that is caused by the wave-induced oscillatory seepage effect (i.e., the wave pumping of sediments) is newly developed. Observational results from the first sea trial prove that the geometry design and skillful instrumentation of the chamber well realize the goal of monitoring the wave pumping of sediments (WPS) continuously. Based on this field dataset, the quantitative contribution of the WPS to the total sediment resuspension is estimated to be 20-60% merely under the continuous action of normal waves (Hs ≤ 1.5 m) in the subaqueous Yellow River Delta (YRD). Such a large contribution invalidates a commonly held opinion that sediments are purely eroded from the seabed surface by the horizontal "shearing effect" from the wave orbital or current velocities. In fact, a considerable amount of sediments could originate from the shallow subsurface of seabed driven by the vertical "pumping effect" of the wave-generated seepage flows during wavy periods. According to the new findings, an improved conceptual model for the resuspension mechanisms of silty sediments under various hydrodynamics is proposed for the first time.

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

    PubMed

    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.

  18. Assessing the Risk of International Spread of Yellow Fever Virus: A Mathematical Analysis of an Urban Outbreak in Asunción, 2008

    PubMed Central

    Johansson, Michael A.; Arana-Vizcarrondo, Neysarí; Biggerstaff, Brad J.; Gallagher, Nancy; Marano, Nina; Staples, J. Erin

    2012-01-01

    Yellow fever virus (YFV), a mosquito-borne virus endemic to tropical Africa and South America, is capable of causing large urban outbreaks of human disease. With the ease of international travel, urban outbreaks could lead to the rapid spread and subsequent transmission of YFV in distant locations. We designed a stochastic metapopulation model with spatiotemporally explicit transmissibility scenarios to simulate the global spread of YFV from a single urban outbreak by infected airline travelers. In simulations of a 2008 outbreak in Asunción, Paraguay, local outbreaks occurred in 12.8% of simulations and international spread in 2.0%. Using simple probabilistic models, we found that local incidence, travel rates, and basic transmission parameters are sufficient to assess the probability of introduction and autochthonous transmission events. These models could be used to assess the risk of YFV spread during an urban outbreak and identify locations at risk for YFV introduction and subsequent autochthonous transmission. PMID:22302873

  19. Development of a non-destructive method for determining protein nitrogen in a yellow fever vaccine by near infrared spectroscopy and multivariate calibration.

    PubMed

    Dabkiewicz, Vanessa Emídio; de Mello Pereira Abrantes, Shirley; Cassella, Ricardo Jorgensen

    2018-08-05

    Near infrared spectroscopy (NIR) with diffuse reflectance associated to multivariate calibration has as main advantage the replacement of the physical separation of interferents by the mathematical separation of their signals, rapidly with no need for reagent consumption, chemical waste production or sample manipulation. Seeking to optimize quality control analyses, this spectroscopic analytical method was shown to be a viable alternative to the classical Kjeldahl method for the determination of protein nitrogen in yellow fever vaccine. The most suitable multivariate calibration was achieved by the partial least squares method (PLS) with multiplicative signal correction (MSC) treatment and data mean centering (MC), using a minimum number of latent variables (LV) equal to 1, with the lower value of the square root of the mean squared prediction error (0.00330) associated with the highest percentage value (91%) of samples. Accuracy ranged 95 to 105% recovery in the 4000-5184 cm -1 region. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    PubMed

    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.