Sample records for yellow fever infection

  1. [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

  2. 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

  3. 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 ...

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. [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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. [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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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

  8. [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.

  9. 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.

  10. 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

  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. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  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. 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

  19. [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.

  20. 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 ≥ ...

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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,

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  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: 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.).

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  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 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

  9. 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.

  10. 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.

  11. Alterations in the Aedes aegypti Transcriptome during Infection with West Nile, Dengue and Yellow Fever Viruses

    PubMed Central

    Colpitts, Tonya M.; Cox, Jonathan; Vanlandingham, Dana L.; Feitosa, Fabiana M.; Cheng, Gong; Kurscheid, Sebastian; Wang, Penghua; Krishnan, Manoj N.; Higgs, Stephen; Fikrig, Erol

    2011-01-01

    West Nile (WNV), dengue (DENV) and yellow fever (YFV) viruses are (re)emerging, mosquito-borne flaviviruses that cause human disease and mortality worldwide. Alterations in mosquito gene expression common and unique to individual flaviviral infections are poorly understood. Here, we present a microarray analysis of the Aedes aegypti transcriptome over time during infection with DENV, WNV or YFV. We identified 203 mosquito genes that were ≥5-fold differentially up-regulated (DUR) and 202 genes that were ≥10-fold differentially down-regulated (DDR) during infection with one of the three flaviviruses. Comparative analysis revealed that the expression profile of 20 DUR genes and 15 DDR genes was quite similar between the three flaviviruses on D1 of infection, indicating a potentially conserved transcriptomic signature of flaviviral infection. Bioinformatics analysis revealed changes in expression of genes from diverse cellular processes, including ion binding, transport, metabolic processes and peptidase activity. We also demonstrate that virally-regulated gene expression is tissue-specific. The overexpression of several virally down-regulated genes decreased WNV infection in mosquito cells and Aedes aegypti mosquitoes. Among these, a pupal cuticle protein was shown to bind WNV envelope protein, leading to inhibition of infection in vitro and the prevention of lethal WNV encephalitis in mice. This work provides an extensive list of targets for controlling flaviviral infection in mosquitoes that may also be used to develop broad preventative and therapeutic measures for multiple flaviviruses. PMID:21909258

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

    PubMed

    Colpitts, Tonya M; Cox, Jonathan; Vanlandingham, Dana L; Feitosa, Fabiana M; Cheng, Gong; Kurscheid, Sebastian; Wang, Penghua; Krishnan, Manoj N; Higgs, Stephen; Fikrig, Erol

    2011-09-01

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

  13. [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.

  14. 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.

  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. 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

  17. 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

  18. 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.

  19. [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.

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. [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.

  8. 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.

  9. Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti.

    PubMed

    van den Hurk, Andrew F; Hall-Mendelin, Sonja; Pyke, Alyssa T; Frentiu, Francesca D; McElroy, Kate; Day, Andrew; Higgs, Stephen; O'Neill, Scott L

    2012-01-01

    Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 10(4) times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.

  10. Impact of Wolbachia on Infection with Chikungunya and Yellow Fever Viruses in the Mosquito Vector Aedes aegypti

    PubMed Central

    van den Hurk, Andrew F.; Hall-Mendelin, Sonja; Pyke, Alyssa T.; Frentiu, Francesca D.; McElroy, Kate; Day, Andrew; Higgs, Stephen; O'Neill, Scott L.

    2012-01-01

    Incidence of disease due to dengue (DENV), chikungunya (CHIKV) and yellow fever (YFV) viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 104 times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression. PMID:23133693

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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.

  5. [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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. A mouse model for studying viscerotropic disease caused by yellow fever virus infection.

    PubMed

    Meier, Kathryn C; Gardner, Christina L; Khoretonenko, Mikhail V; Klimstra, William B; Ryman, Kate D

    2009-10-01

    Mosquito-borne yellow fever virus (YFV) causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta) in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129) or the STAT1 signaling molecule (STAT129) were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129-derived, but not WT

  20. 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.

  1. 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.

  2. 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.

  3. Live attenuated yellow fever 17D infects human DCs and allows for presentation of endogenous and recombinant T cell epitopes.

    PubMed

    Barba-Spaeth, Giovanna; Longman, Randy S; Albert, Matthew L; Rice, Charles M

    2005-11-07

    The yellow fever (YF) 17D vaccine is one of the most successful live attenuated vaccines available. A single immunization induces both long-lasting neutralizing antibody and YF-specific T cell responses. Surprisingly, the mechanism for this robust immunity has not been addressed. In light of several recent reports suggesting flavivirus interaction with dendritic cells (DCs), we investigated the mechanism of YF17D interaction with DCs and the importance of this interaction in generating T cell immunity. Our results show that YF17D can infect immature and mature human DCs. Viral entry is Ca(2+) dependent, but it is independent of DC-SIGN as well as multiple integrins expressed on the DC surface. Similar to infection of cell lines, YF infection of immature DCs is cytopathic. Although infection itself does not induce DC maturation in vitro, TNF-alpha-induced maturation protects DCs from YF-induced cytopathogenicity. Furthermore, we show that DCs infected with YF17D or YF17D carrying a recombinant epitope can process and present antigens for CD8(+) T cell stimulation. These findings offer insight into the immunologic mechanisms associated with the highly capable YF17D vaccine that may guide effective vaccine design.

  4. 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

  5. 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.

  6. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients.

    PubMed

    Avelino-Silva, Vivian I; Miyaji, Karina T; Hunt, Peter W; Huang, Yong; Simoes, Marisol; Lima, Sheila B; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Costa, Dayane Alves; Dias, Juliana Zanatta C; Cerqueira, Natalia B; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M; Kallas, Esper G

    2016-12-01

    HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation-characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity-may influence vaccine response in this population. We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV-infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio.

  7. CD4/CD8 Ratio and KT Ratio Predict Yellow Fever Vaccine Immunogenicity in HIV-Infected Patients

    PubMed Central

    Hunt, Peter W.; Huang, Yong; Simoes, Marisol; Lima, Sheila B.; Freire, Marcos S.; Caiaffa-Filho, Helio H.; Hong, Marisa A.; Costa, Dayane Alves; Dias, Juliana Zanatta C.; Cerqueira, Natalia B.; Nishiya, Anna Shoko; Sabino, Ester Cerdeira; Sartori, Ana M.; Kallas, Esper G.

    2016-01-01

    Background HIV-infected individuals have deficient responses to Yellow Fever vaccine (YFV) and may be at higher risk for adverse events (AE). Chronic immune activation–characterized by low CD4/CD8 ratio or high indoleamine 2,3-dioxygenase-1 (IDO) activity—may influence vaccine response in this population. Methods We prospectively assessed AE, viremia by the YFV virus and YF-specific neutralizing antibodies (NAb) in HIV-infected (CD4>350) and -uninfected adults through 1 year after vaccination. The effect of HIV status on initial antibody response to YFV was measured during the first 3 months following vaccination, while the effect on persistence of antibody response was measured one year following vaccination. We explored CD4/CD8 ratio, IDO activity (plasma kynurenine/tryptophan [KT] ratio) and viremia by Human Pegivirus as potential predictors of NAb response to YFV among HIV-infected participants with linear mixed models. Results 12 HIV-infected and 45-uninfected participants were included in the final analysis. HIV was not significantly associated with AE, YFV viremia or NAb titers through the first 3 months following vaccination. However, HIV–infected participants had 0.32 times the NAb titers observed for HIV-uninfected participants at 1 year following YFV (95% CI 0.13 to 0.83, p = 0.021), independent of sex, age and prior vaccination. In HIV-infected participants, each 10% increase in CD4/CD8 ratio predicted a mean 21% higher post-baseline YFV Nab titer (p = 0.024). Similarly, each 10% increase in KT ratio predicted a mean 21% lower post-baseline YFV Nab titer (p = 0.009). Viremia by Human Pegivirus was not significantly associated with NAb titers. Conclusions HIV infection appears to decrease the durability of NAb responses to YFV, an effect that may be predicted by lower CD4/CD8 ratio or higher KT ratio. PMID:27941965

  8. 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

  9. 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.

  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. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. [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

  3. Substitution of wild-type yellow fever Asibi sequences for 17D vaccine sequences in ChimeriVax-dengue 4 does not enhance infection of Aedes aegypti mosquitoes.

    PubMed

    McGee, Charles E; Tsetsarkin, Konstantin; Vanlandingham, Dana L; McElroy, Kate L; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen

    2008-03-01

    To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax-dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field-collected and laboratory-colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low-level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal.

  4. Substitution of Wild-Type Yellow Fever Asibi Sequences for 17D Vaccine Sequences in ChimeriVax–Dengue 4 Does Not Enhance Infection of Aedes aegypti Mosquitoes

    PubMed Central

    McGee, Charles E.; Tsetsarkin, Konstantin; Vanlandingham, Dana L.; McElroy, Kate L.; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen

    2008-01-01

    To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax– dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field-collected and laboratory-colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low-level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal. PMID:18266608

  5. 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

  6. 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

  7. CD4/CD8 Ratio Predicts Yellow Fever Vaccine-Induced Antibody Titers in Virologically Suppressed HIV-Infected Patients.

    PubMed

    Avelino-Silva, Vivian Iida; Miyaji, Karina Takesaki; Mathias, Augusto; Costa, Dayane Alves; de Carvalho Dias, Juliana Zanatta; Lima, Sheila Barbosa; Simoes, Marisol; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Lopes, Marta H; Sartori, Ana M; Kallas, Esper G

    2016-02-01

    Yellow fever vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Characterization of the antigen distribution and tissue tropisms of three phenotypically distinct yellow fever virus variants in orally infected Aedes aegypti mosquitoes.

    PubMed

    McElroy, Kate L; Girard, Yvette A; McGee, Charles E; Tsetsarkin, Konstantin A; Vanlandingham, Dana L; Higgs, Stephen

    2008-10-01

    Arbovirus dissemination from the midgut of a vector mosquito is a critical step in facilitating virus transmission to a susceptible host. We previously characterized the genetic determinants of yellow fever virus (YFV) dissemination from the Aedes aegypti mosquito midgut using 2 genetically and phenotypically distinct strains of YFV: the wild-type, disseminating YFV Asibi strain and the attenuated, midgut-restricted YFV 17D vaccine strain. We examined the process of viral dissemination in YFV-infected Ae. aegypti by characterizing the tissue tropisms of 3 YF viruses in Ae. aegypti: Asibi, 17D, and a chimeric virus (17D/Asibi M-E) containing the Asibi membrane (M) and envelope (E) structural protein genes and 17D nonstructural genes. Ae. aegypti were infected orally, and whole, sectioned mosquitoes were evaluated for antigen distribution at 3, 7, 10, 14, and 21 days postinfection by immunohistochemical staining. Virus antigen was consistently observed in the posterior and anterior midgut, cardial epithelium, salivary glands, fat body, and nervous tissues in Asibi- and 17D/Asibi M-E-infected Ae. aegypti following 10 or 14-day extrinsic incubation, respectively. Amplification of virus in the abdominal and thoracic fat body is hypothesized to facilitate YFV infection of the Ae. aegypti salivary glands. As expected, 17D infection was generally limited to the midgut following oral infection. However, there did not appear to be a direct correlation between distribution of infection in the midgut and dissemination to the secondary tissues.

  5. 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.

  6. 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

  7. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells

    PubMed Central

    Cong, Yu; McArthur, Monica A.; Cohen, Melanie; Jahrling, Peter B.; Janosko, Krisztina B.; Josleyn, Nicole; Kang, Kai; Zhang, Tengfei; Holbrook, Michael R.

    2016-01-01

    Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease. PMID:27191161

  8. Characterization of Yellow Fever Virus Infection of Human and Non-human Primate Antigen Presenting Cells and Their Interaction with CD4+ T Cells.

    PubMed

    Cong, Yu; McArthur, Monica A; Cohen, Melanie; Jahrling, Peter B; Janosko, Krisztina B; Josleyn, Nicole; Kang, Kai; Zhang, Tengfei; Holbrook, Michael R

    2016-05-01

    Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. DNA-immunisation with dengue virus E protein domains I/II, but not domain III, enhances Zika, West Nile and Yellow Fever virus infection.

    PubMed

    Slon Campos, Jose L; Poggianella, Monica; Marchese, Sara; Mossenta, Monica; Rana, Jyoti; Arnoldi, Francesca; Bestagno, Marco; Burrone, Oscar R

    2017-01-01

    Dengue virus (DENV), the causative agent of dengue disease, is among the most important mosquito-borne pathogens worldwide. DENV is composed of four closely related serotypes and belongs to the Flaviviridae family alongside other important arthropod-borne viral pathogens such as Zika virus (ZIKV), West Nile virus (WNV) and Yellow Fever virus (YFV). After infection, the antibody response is mostly directed to the viral E glycoprotein which is composed of three structural domains named DI, DII and DIII that share variable degrees of homology among different viruses. Recent evidence supports a close serological interaction between ZIKV and DENV. The possibility of worse clinical outcomes as a consequence of antibody-dependent enhancement of infection (ADE) due to cross-reactive antibodies with poor neutralisation activity is a matter of concern. We tested polyclonal sera from groups of female Balb/C mice vaccinated with DNA constructs expressing DI/DII, DIII or the whole sE from different DENV serotypes and compared their activity in terms of cross-reactivity, neutralisation of virus infection and ADE. Our results indicate that the polyclonal antibody responses against the whole sE protein are highly cross-reactive with strong ADE and poor neutralisation activities due to DI/DII immunodominance. Conversely, anti-DIII polyclonal antibodies are type-specific, with no ADE towards ZIKV, WNV and YFV, and strong neutralisation activity restricted only to DENV.

  18. Host-cell interaction of attenuated and wild-type strains of yellow fever virus can be differentiated at early stages of hepatocyte infection.

    PubMed

    Lefeuvre, Anabelle; Contamin, Hugues; Decelle, Thierry; Fournier, Christophe; Lang, Jean; Deubel, Vincent; Marianneau, Philippe

    2006-05-01

    Yellow fever (YF) virus is currently found in tropical Africa and South America, and is responsible for a febrile to severe illness characterized by organ failure and shock. The attenuated YF 17D strain, used in YF vaccine, was derived from the wild-type strain Asibi. Although studies have been done on genetic markers of YF virulence, differentiation of the two strains in terms of host-cell interaction during infection remains elusive. As YF wild-type strains are hepatotropic, we chose a hepatic cell line (HepG2) to study YF virus-host cell interaction. HepG2 cells rapidly produced high titres of infectious viral particles for 17D and Asibi YF strains. However, HepG2 cells were more susceptible to the attenuated 17D virus infection, and only this virus strain induced early apoptosis in these cells. Molecular markers specific for the 17D virus were identified by microarray analysis and confirmed by quantitative RT-PCR analysis. As early as 1h postinfection, three genes, (IEX-1, IRF-1, DEC-1) all implicated in apoptosis pathways, were upregulated. Later in infection (48 h) two other genes (HSP70-1A and 1B), expressed in cases of cellular stress, were highly upregulated in 17D-infected HepG2 cells. The early specific upregulation of these cellular genes in HepG2 cells may be considered markers of the 17D virus. This study on the YF attenuated strain gives a new approach to the analysis of the factors involved in virus attenuation.

  19. 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.

  20. 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.

  1. 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)

  2. 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.

  3. [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.

  4. [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.

  5. 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.

  6. 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

  7. 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.

  8. The threat of emerging infections.

    PubMed

    1996-11-01

    A variety of newly discovered pathogens and new forms of older infectious agents threaten to reemerge. Typical symptoms of acute infection are fever, headache, malaise, vomiting, and diarrhea. Some of the better-known emerging viral infections include dengue, filoviruses (Ebola, Marburg), hantaviruses, hepatitis B, hepatitis C, HIV, influenza, lassa fever, measles, rift valley fever, rotavirus, and yellow fever. Emerging bacterial infections include cholera, Escherichia coli 0157:H7, legionnaires disease (Legionella), lyme disease, streptococcus infections (group A), tuberculosis, and typhoid. Emerging parasitic infections include cryptosporidium and other waterborne pathogens and malaria. The causes of many diseases are still shrouded in mystery; thus, treatments and cures for them are as yet unknown.

  9. 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.

  10. Rotavirus infection as a frequent cause of neonatal fever.

    PubMed

    Kang, Ha-Na; Park, Hyun Kyung; Lee, Hyun-Ju; Moon, Jin-Hwa; Oh, Jae Won; Kim, Chang-Ryul

    2018-04-01

    Fever rather than diarrhea or vomiting was the most common symptom of neonatal rotavirus (RV) infection in our previous study. We investigated whether RV infection is a major cause of neonatal fever and compared the clinical characteristics of bacterial infection, viral infection and unknown causes of neonatal fever. We reviewed the electronic medical records of 48 newborns aged ≤28 days who were admitted to the Special Care Nursery of Hanyang University Guri Hospital for fever (≥38°C) from 2005 to 2009. All the newborns underwent complete blood count, urinalysis, C-reactive protein, cultures of blood, urine, and cerebrospinal fluid as well as stool RV enzyme-linked immunosorbent assay. Respiratory virus polymerase chain reaction for cough or rhinorrhea, and stool culture for diarrhea were also done. All the babies were term, with mean age 13 ± 8 days and peak body temperature 38.5 ± 0.5°C. The causes of neonatal fever were viral (44%), bacterial (10%) and unknown (46%). The viral infections included RV (n = 12), enterovirus (n = 6), respiratory syncytial virus (n = 2), and rhinovirus (n = 1). All the rotavirus genotypes were G4P[6]. Only three of 12 RV-infected febrile newborns had diarrhea. The bacterial infections included three cases of urinary tract infection (Escherichia coli, n = 2; Klebsiella pneumoniae, n = 1), and two cases of sepsis complicated with meningitis (all Streptococcus agalactiae). RV infection is the most common single cause of neonatal fever. It may be necessary to include stool RV tests for febrile newborns. © 2017 Japan Pediatric Society.

  11. Development of a SYBR green I based RT-PCR assay for yellow fever virus: application in assessment of YFV infection in Aedes aegypti.

    PubMed

    Dash, Paban Kumar; Boutonnier, Alain; Prina, Eric; Sharma, Shashi; Reiter, Paul

    2012-01-22

    Yellow Fever virus (YFV) is an important arboviral pathogen in much of sub-Saharan Africa and the tropical Americas. It is the prototype member of the genus Flavivirus and is transmitted primarily by Aedes (Stegomyia) mosquitoes. The incidence of human infections in endemic areas has risen in recent years. Prompt and dependable identification of YFV is a critical component of response to suspect cases. We developed a one-step SYBR Green I-based real-time quantitative RT-PCR (qRT-PCR) assay targeting the 5'NTR and capsid-gene junction--for rapid detection and quantification of YFV. The detection limit was 1 PFU/mL, 10-fold more sensitive than conventional RT-PCR, and there was no cross-reactivity with closely related flaviviruses or with alphaviruses. Viral load in samples was determined by standard curve plotted from cycle threshold (Ct) values and virus concentration. The efficacy of the assay in mosquitoes was assessed with spiked samples. The utility of the assay for screening of pooled mosquitoes was also confirmed. Replication of a Cameroon isolate of YFV in Ae. aegypti revealed a marked variation in susceptibility among different colonies at different days post infection (pi). The SYBR Green-1 based qRT-PCR assay is a faster, simpler, more sensitive and less expensive procedure for detection and quantification of YFV than other currently used methods.

  12. Development of a SYBR green I based RT-PCR assay for yellow fever virus: application in assessment of YFV infection in Aedes aegypti

    PubMed Central

    2012-01-01

    Background Yellow Fever virus (YFV) is an important arboviral pathogen in much of sub-Saharan Africa and the tropical Americas. It is the prototype member of the genus Flavivirus and is transmitted primarily by Aedes (Stegomyia) mosquitoes. The incidence of human infections in endemic areas has risen in recent years. Prompt and dependable identification of YFV is a critical component of response to suspect cases. Results We developed a one-step SYBR Green I-based real-time quantitative RT-PCR (qRT-PCR) assay targeting the 5'NTR and capsid-gene junction--for rapid detection and quantification of YFV. The detection limit was 1 PFU/mL, 10-fold more sensitive than conventional RT-PCR, and there was no cross-reactivity with closely related flaviviruses or with alphaviruses. Viral load in samples was determined by standard curve plotted from cycle threshold (Ct) values and virus concentration. The efficacy of the assay in mosquitoes was assessed with spiked samples. The utility of the assay for screening of pooled mosquitoes was also confirmed. Replication of a Cameroon isolate of YFV in Ae. aegypti revealed a marked variation in susceptibility among different colonies at different days post infection (pi). Conclusions The SYBR Green-1 based qRT-PCR assay is a faster, simpler, more sensitive and less expensive procedure for detection and quantification of YFV than other currently used methods. PMID:22264275

  13. 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.

  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. 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

  16. 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.

  17. Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model.

    PubMed

    Engelmann, Flora; Josset, Laurence; Girke, Thomas; Park, Byung; Barron, Alex; Dewane, Jesse; Hammarlund, Erika; Lewis, Anne; Axthelm, Michael K; Slifka, Mark K; Messaoudi, Ilhem

    2014-01-01

    Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection

  18. Pathophysiologic and Transcriptomic Analyses of Viscerotropic Yellow Fever in a Rhesus Macaque Model

    PubMed Central

    Engelmann, Flora; Josset, Laurence; Girke, Thomas; Park, Byung; Barron, Alex; Dewane, Jesse; Hammarlund, Erika; Lewis, Anne; Axthelm, Michael K.; Slifka, Mark K.; Messaoudi, Ilhem

    2014-01-01

    Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection

  19. 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.

  20. 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.

  1. 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 ( ...

  2. [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.

  3. 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

  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. 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.

  6. Inactivation of Dengue and Yellow Fever viruses by heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX.

    PubMed

    Assunção-Miranda, I; Cruz-Oliveira, C; Neris, R L S; Figueiredo, C M; Pereira, L P S; Rodrigues, D; Araujo, D F F; Da Poian, A T; Bozza, M T

    2016-03-01

    To investigate the effect of heme, cobalt-protoporphyrin IX and tin-protoporphyrin IX (CoPPIX and SnPPIX), macrocyclic structures composed by a tetrapyrrole ring with a central metallic ion, on Dengue Virus (DENV) and Yellow Fever Virus (YFV) infection. Treatment of HepG2 cells with heme, CoPPIX and SnPPIX after DENV infection reduced infectious particles without affecting viral RNA contents in infected cells. The reduction of viral load occurs only with the direct contact of DENV with porphyrins, suggesting a direct effect on viral particles. Previously incubation of DENV and YFV with heme, CoPPIX and SnPPIX resulted in viral particles inactivation in a dose-dependent manner. Biliverdin, a noncyclical porphyrin, was unable to inactivate the viruses tested. Infection of HepG2 cells with porphyrin-pretreated DENV2 results in a reduced or abolished viral protein synthesis, RNA replication and cell death. Treatment of HepG2 or THP-1 cell lineage with heme or CoPPIX after DENV infection with a very low MOI resulted in a decreased DENV replication and protection from death. Heme, CoPPIX and SnPPIX possess a marked ability to inactivate DENV and YFV, impairing its ability to infect and induce cytopathic effects on target cells. These results open the possibility of therapeutic application of porphyrins or their use as models to design new antiviral drugs against DENV and YFV. © 2016 The Society for Applied Microbiology.

  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. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Arthropod-borne viral infections associated with a fever outbreak in the northern province of Sudan.

    PubMed

    Watts, D M; el-Tigani, A; Botros, B A; Salib, A W; Olson, J G; McCarthy, M; Ksiazek, T G

    1994-08-01

    An outbreak of acute febrile illness occurred during August and September 1989 in the Northern Province of Sudan coinciding with a high population density of phlebotomine sandflies. An investigation was conducted to determine whether arboviruses were associated with human illness during this outbreak. Sera were obtained from 185 febrile individuals and tested for IgG and IgM antibody to selected arboviruses by enzyme immunoassay (EIA). The prevalence of IgG antibody was 59% for West Nile (WN), 53% for Sandfly Fever Sicilian (SFS), 32% for Sandfly Fever Naples (SFN), 39% for Yellow Fever (YF), 24% for dengue-2 (DEN-2), 23% for Rift Valley Fever (RVF), 12% for Chikungunya (CHIK) and 5% for Crimean-Congo haemorrhagic Fever (CCHF) viruses. Antibody prevalences tended to increase with age for WN and YF viruses. Antibody rates were about the same for males and females for most of the viruses tested. The prevalence of IgM antibody to SFN was 24% and reciprocal IgM titre exceeded 12,800 for some individuals suggesting that this virus was the cause of recent infection. The prevalence of IgM antibody for the other viruses did not exceed 5%. The study indicated that several arboviruses were endemic and some of them may have caused human disease in the Northern Province of Sudan.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Predictors of serious bacterial infections in pediatric burn patients with fever.

    PubMed

    Vyles, David; Sinha, Madhumita; Rosenberg, David I; Foster, Kevin N; Tran, Melissa; Drachman, David

    2014-01-01

    To determine predictors of serious bacterial infections in pediatric burn patients with fever (core temp ≥38.5°C), the authors conducted a retrospective review of medical records of pediatric (0-18 years) patients admitted to the Arizona Burn Center between 2008 and 2011 with greater than 5% TBSA and inpatient hospitalization for ≥72 hours. The study group comprised patients with a febrile episode during their inpatient stay. Serious bacterial infection (the primary outcome variable) was defined as: bacteremia, urinary tract infection, meningitis (blood, urine, or cerebrospinal fluid culture positive for a pathogen respectively), pneumonia, line, and wound infection. A generalized estimating equation analysis was done to predict the presence or absence of serious bacterial infection. Of 1082 pediatric burn patients hospitalized during the study period, 353 met the study eligibility criteria. A total of 108 patients (30.6%) had at least one fever episode (fever group). No difference in demographic characteristics was noted between the fever and no-fever groups; significant differences were observed for: third-degree TBSA, second-degree TBSA, total operating room visits, length of stay, Injury Severity Score, and death. A total of 47.2% of the patients had one or more episodes of fever with serious bacterial infection. In a generalized estimating equation predictive model, presence of a central line, second-, and third-degree TBSA were predictive of serious bacterial infection in burn patients with fever. In this study, individual clinical variables such as tachypnea and tachycardia were not predictive of serious bacterial infections, but the presence of a central line, and larger TBSA were significant predictors of serious bacterial infections. Younger age (P =.08) and ventilator support (P =.057) also approached significance as predictors of serious bacterial infections.

  4. 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 ...

  5. 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...

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Association between infection and fever in terminations of pregnancy using misoprostol: a retrospective cohort study.

    PubMed

    Nijman, Tobias A J; Voogdt, Kevin G J A; Teunissen, Pim W; van der Voorn, Patrick J Jp; de Groot, Christianne J M; Bakker, Petra C A M

    2017-01-05

    Fever is a well-known side effect of misoprostol, but clinically difficult to distinguish from an intra uterine infection. The aim of this study was to determine the incidence of fever in terminations of pregnancy (TOP) using misoprostol and to evaluate fever as indication of intra uterine infection. A retrospective cohort study was performed. Consecutive second trimester TOP with misoprostol between January 2008 and October 2012 were selected. We included 403 cases and determined the incidence of fever. To examine intra uterine infection as plausible cause of fever, pathological examination reports of placentas were reviewed for signs of infections. The incidence of fever was 42%. Logistic regression showed a dose dependent association between dosage misoprostol and degree of fever (OR 1.86; 95% CI: 1.3-2.7). There was no association between fever and epidural analgesia. Fever has a sensitivity of 55% and a specificity of 58% as a marker of intra uterine infection. The positive predictive value of fever for an intra uterine infection is 4% and the negative predictive value is 98%. Administration of misoprostol for the indication TOP is strongly associated with fever during labor. Fever is a poor predictor of intra uterine infection in the context of TOP.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. [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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Infection, fever, and exogenous and endogenous pyrogens: some concepts have changed.

    PubMed

    Dinarello, Charles A

    2004-01-01

    For many years, it was thought that bacterial products caused fever via the intermediate production of a host-derived, fever-producing molecule, called endogenous pyrogen (EP). Bacterial products and other fever-producing substances were termed exogenous pyrogens. It was considered highly unlikely that exogenous pyrogens caused fever by acting directly on the hypothalamic thermoregulatory center since there were countless fever-producing microbial products, mostly large molecules, with no common physical structure. In vivo and in vitro, lipopolysaccharides (LPSs) and other microbial products induced EP, subsequently shown to be interleukin-1 (IL-1). The concept of the 'endogenous pyrogen' cause of fever gained considerable support when pure, recombinant IL-1 produced fever in humans and in animals at subnanomolar concentrations. Subsequently, recombinant tumor necrosis factor-alpha (TNF-alpha), IL-6 and other cytokines were also shown to cause fever and EPs are now termed pyrogenic cytokines. However, the concept was challenged when specific blockade of either IL-1 or TNF activity did not diminish the febrile response to LPS, to other microbial products or to natural infections in animals and in humans. During infection, fever could occur independently of IL-1 or TNF activity. The cytokine-like property of Toll-like receptor (TLR) signal transduction provides an explanation by which any microbial product can cause fever by engaging its specific TLR on the vascular network supplying the thermoregulatory center in the anterior hypothalamus. Since fever induced by IL-1, TNF-alpha, IL-6 or TLR ligands requires cyclooxygenase-2, production of prostaglandin E2 (PGE2) and activation of hypothalamic PGE2 receptors provides a unifying mechanism for fever by endogenous and exogenous pyrogens. Thus, fever is the result of either cytokine receptor or TLR triggering; in autoimmune diseases, fever is mostly cytokine mediated whereas both cytokine and TLR account for fever during

  5. 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- ...

  6. From Q Fever to Coxiella burnetii Infection: a Paradigm Change

    PubMed Central

    Eldin, Carole; Mélenotte, Cléa; Mediannikov, Oleg; Ghigo, Eric; Million, Matthieu; Edouard, Sophie; Mege, Jean-Louis; Maurin, Max

    2016-01-01

    SUMMARY Coxiella burnetii is the agent of Q fever, or “query fever,” a zoonosis first described in Australia in 1937. Since this first description, knowledge about this pathogen and its associated infections has increased dramatically. We review here all the progress made over the last 20 years on this topic. C. burnetii is classically a strict intracellular, Gram-negative bacterium. However, a major step in the characterization of this pathogen was achieved by the establishment of its axenic culture. C. burnetii infects a wide range of animals, from arthropods to humans. The genetic determinants of virulence are now better known, thanks to the achievement of determining the genome sequences of several strains of this species and comparative genomic analyses. Q fever can be found worldwide, but the epidemiological features of this disease vary according to the geographic area considered, including situations where it is endemic or hyperendemic, and the occurrence of large epidemic outbreaks. In recent years, a major breakthrough in the understanding of the natural history of human infection with C. burnetii was the breaking of the old dichotomy between “acute” and “chronic” Q fever. The clinical presentation of C. burnetii infection depends on both the virulence of the infecting C. burnetii strain and specific risks factors in the infected patient. Moreover, no persistent infection can exist without a focus of infection. This paradigm change should allow better diagnosis and management of primary infection and long-term complications in patients with C. burnetii infection. PMID:27856520

  7. Rickettsial Infections and Fever, Vientiane, Laos

    PubMed Central

    Phongmany, Simaly; Rolain, Jean-Marc; Phetsouvanh, Rattanaphone; Blacksell, Stuart D.; Soukkhaseum, Vimone; Rasachack, Bouachanh; Phiasakha, Khamphong; Soukkhaseum, Surn; Frichithavong, Khamthavi; Chu, Vang; Keolouangkhot, Valy; Martinez-Aussel, Bertrand; Chang, Ko; Darasavath, Chirapha; Rattanavong, Oudayvone; Sisouphone, Siho; Mayxay, Mayfong; Vidamaly, Sisouphane; Parola, Philippe; Thammavong, Chanpheng; Heuangvongsy, Mayboun; Syhavong, Bounkong; Raoult, Didier; White, Nicholas J.

    2006-01-01

    Rickettsial diseases have not been described previously from Laos, but in a prospective study, acute rickettsial infection was identified as the cause of fever in 115 (27%) of 427 adults with negative blood cultures admitted to Mahosot Hospital in Vientiane, Laos. The organisms identified by serologic analysis were Orientia tsutsugamushi (14.8%), Rickettsia typhi (9.6%), and spotted fever group rickettsia (2.6% [8 R. helvetica, 1 R. felis, 1 R. conorii subsp. indica, and 1 Rickettsia "AT1"]). Patients with murine typhus had a lower frequency of peripheral lymphadenopathy than those with scrub typhus (3% vs. 46%, p<0.001). Rickettsioses are an underrecognized cause of undifferentiated febrile illnesses among adults in Laos. This finding has implications for the local empiric treatment of fever. PMID:16494751

  8. 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.

  9. 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

  10. Treatment of yellow fever virus with an adenovirus-vectored interferon, DEF201, in a hamster model.

    PubMed

    Julander, Justin G; Ennis, Jane; Turner, Jeffrey; Morrey, John D

    2011-05-01

    Interferon (IFN) is an innate immune response protein that is involved in the antiviral response during viral infection. Treatment of acute viral infections with exogenous interferon may be effective but is generally not feasible for clinical use due to many factors, including cost, stability, and availability. To overcome these limitations, an adenovirus type 5-vectored consensus alpha IFN, termed DEF201, was constructed as a potential way to deliver sustained therapeutic levels of systemic IFN. To demonstrate the efficacy of DEF201 against acute flaviviral disease, various concentrations of the construct were administered as a single intranasal dose prior to virus infection, which resulted in a dose-responsive, protective effect in a hamster model of yellow fever virus (YFV) disease. A DEF201 dose of 5×10(7) PFU/animal administered intranasally just prior to YFV challenge protected 100% of the animals, while a 10-fold lower DEF201 dose exhibited lower, although significant, levels of protection. Virus titers in the liver and serum and levels of serum alanine aminotransferase were all significantly reduced as a result of DEF201 administration at all doses tested. No toxicity, as indicated by weight loss or gross morbidity, was observed in non-YFV-infected animals treated with DEF201. Protection of YFV-infected animals was observed when DEF201 was delivered as early as 7 days prior to virus challenge and as late as 2 days after virus challenge, demonstrating effective prophylaxis and therapy in a hamster model of disease. Overall, it appears that DEF201 is effective in the treatment of YFV in a hamster model.

  11. 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...

  12. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    PubMed

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-05-12

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

  13. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B

    PubMed Central

    2014-01-01

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy. PMID:24884719

  14. African swine fever virus infection in Classical swine fever subclinically infected wild boars.

    PubMed

    Cabezón, Oscar; Muñoz-González, Sara; Colom-Cadena, Andreu; Pérez-Simó, Marta; Rosell, Rosa; Lavín, Santiago; Marco, Ignasi; Fraile, Lorenzo; de la Riva, Paloma Martínez; Rodríguez, Fernando; Domínguez, Javier; Ganges, Llilianne

    2017-08-01

    Recently moderate-virulence classical swine fever virus (CSFV) strains have been proven capable of generating postnatal persistent infection (PI), defined by the maintenance of viremia and the inability to generate CSFV-specific immune responses in animals. These animals also showed a type I interferon blockade in the absence of clinical signs. In this study, we assessed the infection generated in 7-week-old CSFV PI wild boars after infection with the African swine fever virus (ASFV). The wild boars were divided in two groups and were infected with ASFV. Group A comprised boars who were CSFV PI in a subclinical form and Group B comprised pestivirus-free wild boars. Some relevant parameters related to CSFV replication and the immune response of CSFV PI animals were studied. Additionally, serum soluble factors such as IFN-α, TNF-α, IL-6, IL-10, IFN-γ and sCD163 were analysed before and after ASFV infection to assess their role in disease progression. After ASFV infection, only the CSFV PI wild boars showed progressive acute haemorrhagic disease; however, the survival rates following ASFV infection was similar in both experimental groups. Notwithstanding, the CSFV RNA load of CSFV PI animals remained unaltered over the study; likewise, the ASFV DNA load detected after infection was similar between groups. Interestingly, systemic type I FN-α and IL-10 levels in sera were almost undetectable in CSFV PI animals, yet detectable in Group B, while detectable levels of IFN-γ were found in both groups. Finally, the flow cytometry analysis showed an increase in myelomonocytic cells (CD172a + ) and a decrease in CD4 + T cells in the PBMCs from CSFV PI animals after ASFV infection. Our results showed that the immune response plays a role in the progression of disease in CSFV subclinically infected wild boars after ASFV infection, and the immune response comprised the systemic type I interferon blockade. ASFV does not produce any interference with CSFV replication, or vice

  15. The presence of fever in adults with influenza and other viral respiratory infections.

    PubMed

    Chughtai, A A; Wang, Q; Dung, T C; Macintyre, C R

    2017-01-01

    We compared the rates of fever in adult subjects with laboratory-confirmed influenza and other respiratory viruses and examined the factors that predict fever in adults. Symptom data on 158 healthcare workers (HCWs) with a laboratory-confirmed respiratory virus infection were collected using standardized data collection forms from three separate studies. Overall, the rate of fever in confirmed viral respiratory infections in adult HCWs was 23·4% (37/158). Rates varied by virus: human rhinovirus (25·3%, 19/75), influenza A virus (30%, 3/10), coronavirus (28·6%, 2/7), human metapneumovirus (28·6%, 2/7), respiratory syncytial virus (14·3%, 4/28) and parainfluenza virus (8·3%, 1/12). Smoking [relative risk (RR) 4·65, 95% confidence interval (CI) 1·33-16·25] and co-infection with two or more viruses (RR 4·19, 95% CI 1·21-14·52) were significant predictors of fever. Fever is less common in adults with confirmed viral respiratory infections, including influenza, than described in children. More than 75% of adults with a viral respiratory infection do not have fever, which is an important finding for clinical triage of adult patients with respiratory infections. The accepted definition of 'influenza-like illness' includes fever and may be insensitive for surveillance when high case-finding is required. A more sensitive case definition could be used to identify adult cases, particularly in event of an emerging viral infection.

  16. 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.

  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. 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.

  19. 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

  20. 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.

  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. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Association between Helicobacter pylori infection and increased risk of typhoid fever.

    PubMed

    Bhan, Maharaj K; Bahl, Rajiv; Sazawal, Sunil; Sinha, Anju; Kumar, Ramesh; Mahalanabis, Dilip; Clemens, John D

    2002-12-15

    Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

  8. 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.

  9. 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.

  10. Timing and Predictors of Fever and Infection after Craniotomy for Epilepsy in Children

    PubMed Central

    Phung, Jennifer; Mathern, Gary W.; Krogstad, Paul

    2013-01-01

    Background Fevers and leukocytosis after pediatric craniotomy trigger diagnostic evaluation and antimicrobial therapy for possible brain infection. This study determined the incidence and predictors of infection in infants and children undergoing epilepsy neurosurgery. Methods We reviewed the postoperative course of 100 consecutive surgeries for pediatric epilepsy, comparing those with and without infections for clinical variables and daily maximum temperatures, blood WBC and differential, and cerebrospinal fluid (CSF) studies. Results Infections were the most common adverse events following these surgeries. Four patients (4%) had CSF infections and 12 had non-CSF infections (including one with distinct CSF and bloodstream infections). Most (88%) infections occurred before postoperative day 12 and were associated with larger resections involving ventriculostomies. Fevers (T ≥38.5°C) were observed in the first 12-days postsurgery in 43 % of cases, and were associated with patients undergoing hemispherectomy and multilobar resections. Fevers in the first three days postsurgery identified infections with 73% sensitivity, 69% specificity, and 70% accuracy; two (13%) patients with infections never developed fevers. Peripheral blood WBC >15,000 was found in 49% of patients and 5 cases of infections never had elevated WBC counts. WBC differential, CSF protein, RBC, WBC, and RBC/WBC ratios were poor predictors of infections. Longer hospital stays were associated with infections and hemispherectomy and multilobar resections. Patients with and without infections were equally likely to be seizure free after surgery. Conclusions Fevers and elevated blood WBC counts were common after pediatric epilepsy surgery, but CSF infections were uncommon. Positive cultures and other confirmatory microbiologic tests should drive changes in antimicrobial therapy after surgery. PMID:23348815

  11. Zika, dengue and yellow fever viruses induce differential anti-viral immune responses in human monocytic and first trimester trophoblast cells.

    PubMed

    Luo, Huanle; Winkelmann, Evandro R; Fernandez-Salas, Ildefonso; Li, Li; Mayer, Sandra V; Danis-Lozano, Rogelio; Sanchez-Casas, Rosa Ma; Vasilakis, Nikos; Tesh, Robert; Barrett, Alan D; Weaver, Scott C; Wang, Tian

    2018-03-01

    Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal birth defects, but the causative mechanism is incompletely understood. ZIKV shares sequence homology and early clinical manifestations with yellow fever virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by the same species of mosquitoes. However, YFV and DENV have been rarely reported to cause congenital diseases. Here, we compared infection with a contemporary ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and first-trimester trophoblasts (HTR-8). Our results suggest that all three viruses have similar tropisms for both cells. Nevertheless, ZIKV induced strong type 1 IFN and inflammatory cytokine and chemokine production in monocytes and peripheral blood mononuclear cells. Furthermore, ZIKV infection in trophoblasts induced lower IFN and higher inflammatory immune responses. Placental inflammation is known to contribute to the risk of brain damage in preterm newborns. Inhibition of toll-like receptor (TLR)3 and TLR8 each abrogated the inflammatory cytokine responses in ZIKV-infected trophoblasts. Our findings identify a potential link between maternal immune activation and ZIKV-induced congenital diseases, and a potential therapeutic strategy that targets TLR-mediated inflammatory responses in the placenta. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. 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.

  13. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice.

    PubMed

    Bassi, Maria R; Larsen, Mads A B; Kongsgaard, Michael; Rasmussen, Michael; Buus, Søren; Stryhn, Anette; Thomsen, Allan R; Christensen, Jan P

    2016-02-01

    The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. Studies on the pathogenesis of fever. V. The relation of circulating endogenous pyrogen to the fever of acute bacterial infections.

    PubMed

    KING, M K; WOOD, W B

    1958-02-01

    An endogenous pyrogen, which is indistinguishable from leucocytic pyrogen, has been demonstrated in the blood streams of rabbits with fevers caused by experimental pneumococcal and streptococcal infections. Like the endogenous pyrogen previously detected in the serum of animals with fever produced by the intravenous injection of typhoid vaccine, the newly discovered circulating factor acts directly upon the thermoregulatory centers of the brain. Its origin from polymorphonuclear leucocytes at the site of infection appears to have been established. The possible relationship of this circulating endogenous pyrogen to the pathogenesis of other forms of fever is discussed.

  20. Recent advances in the development of antiviral therapeutics for Rift Valley fever virus infection.

    PubMed

    Atkins, Colm; Freiberg, Alexander N

    2017-11-01

    Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus endemic to sub-Saharan Africa and the Arabian Peninsula and the etiological agent of Rift Valley fever. Rift Valley fever is a disease of major public health and economic concern, affecting livestock and humans. In ruminants, RVFV infection is characterized by high mortality rates in newborns and near 100% abortion rates in pregnant animals. Infection in humans is typically manifested as a self-limiting febrile illness, but can lead to severe and fatal hepatitis, encephalitis, hemorrhagic fever or retinitis with partial or complete blindness. Currently, there are no specific treatment options available for RVFV infection. This review presents a summary of the therapeutic approaches that have been explored on the treatment of RVFV infection.

  1. 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

  2. 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

  3. 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

  4. [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.

  5. 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.

  6. 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

  7. [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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. A humanized IgG but not IgM antibody is effective in prophylaxis and therapy of yellow fever infection in an AG129/17D-204 peripheral challenge mouse model.

    PubMed

    Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Schlesinger, Jacob J; Blair, Carol D; Roehrig, John T

    2012-04-01

    Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne virus found in tropical regions of Africa and South America that causes severe hepatic disease and death in humans. Despite the availability of effective vaccines, YFV is responsible for an estimated 200,000 cases and 30,000 deaths annually. There are currently no prophylactic or therapeutic strategies approved for use in human YFV infections. Furthermore, implementation of YFV 17D-204 vaccination campaigns has become problematic due to an increase in reported post-vaccinal adverse events. We have created human/murine chimeric MAbs of a YFV-reactive murine monoclonal antibody (mMAb), 2C9, that was previously shown to protect mice from lethal YFV infection and to have therapeutic activity. The new chimeric (cMAbs) were constructed by fusion of the m2C9 IgG gene variable regions with the constant regions of human IgG and IgM and expressed in Sp2 murine myelomas. The 2C9 cMAbs (2C9-cIgG and 2C9-cIgM) reacted with 17D-204 vaccine strain in an enzyme-linked immunosorbent assay and neutralized virus in vitro similarly to the parent m2C9. Both m2C9 and 2C9-cIgG when administered prophylactically 24h prior to infection protected AG129 mice from peripheral 17D-204 challenge at antibody concentrations ≥1.27 μg/mouse; however, the 2C9-cIgM did not protect even at a dose of 127 μg/mouse. The 17D-204 infection of AG129 mice is otherwise uniformly lethal. While the m2C9 was shown previously to be therapeutically effective in YFV-infected BALB/c mice at day 4 post-infection, the m2C9 and 2C9-cIgG demonstrated therapeutic activity only when administered 1 day post-infection in 17D-204-infected AG129 mice. Published by Elsevier B.V.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Acute arboviral infections in Guinea, West Africa, 2006.

    PubMed

    Jentes, Emily S; Robinson, Jaimie; Johnson, Barbara W; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G; Bryan, Juliet

    2010-08-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

  19. Acute Arboviral Infections in Guinea, West Africa, 2006

    PubMed Central

    Jentes, Emily S.; Robinson, Jaimie; Johnson, Barbara W.; Conde, Ibrahima; Sakouvougui, Yosse; Iverson, Jennifer; Beecher, Shanna; Bah, M. Alpha; Diakite, Fousseny; Coulibaly, Mamadi; Bausch, Daniel G.

    2010-01-01

    Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region. PMID:20682888

  20. Human Immune Response to Dengue Infections

    DTIC Science & Technology

    1991-06-30

    had been immunized with yellow fever vaccine and later became infected with dengue 3 virus, responded best to dengue 3 antigen but also responded to...effective dengue virus subunit vaccines . We found evidence of marked T cell activation in patients with DHF. T cell activation in patients with DF was similar...Treatment and Control of Dengue Hemorrhagic Fever. World Health Organization, Geneva, Switzerland 7. Sabin AB (1952) Research on dengue during World

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Predicting serious bacterial infection in young children with fever without apparent source.

    PubMed

    Bleeker, S E; Moons, K G; Derksen-Lubsen, G; Grobbee, D E; Moll, H A

    2001-11-01

    The aim of this study was to design a clinical rule to predict the presence of a serious bacterial infection in children with fever without apparent source. Information was collected from the records of children aged 1-36 mo who attended the paediatric emergency department because of fever without source (temperature > or = 38 degrees C and no apparent source found after evaluation by a general practitioner or history by a paediatrician). Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis and ethmoiditis. Using multivariate logistic regression and the area under the receiver operating characteristic curve (ROC area), the diagnostic value of predictors for serious bacterial infection was judged, resulting in a risk stratification. Twenty-five percent of the 231 patients enrolled in the study (mean age 1.1 y) had a serious bacterial infection. Independent predictors from history and examination included duration of fever, poor micturition, vomiting, age, temperature < 36.7 degrees C or > or = 40 degrees C at examination, chest-wall retractions and poor peripheral circulation (ROC area: 0.75). Independent predictors from laboratory tests were white blood cell count, serum C-reactive protein and the presence of >70 white blood cells in urinalysis (ROC area: 0.83). The risk stratification for serious bacterial infection ranged from 6% to 92%. The probability of a serious bacterial infection in the individual patient with fever without source can be estimated more precisely by using a limited number of symptoms, signs and laboratory tests.

  8. 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.

  9. 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

  10. 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.

  11. Dengue fever with hepatitis E and hepatitis A infection.

    PubMed

    Yakoob, Javed; Jafri, Wasim; Siddiqui, Shaheer; Riaz, Mehmood

    2009-03-01

    Infection with dengue viruses produces a spectrum of clinical illness ranging from a nonspecific viral syndrome to severe and fatal haemorrhagic disease. Important risk factors include the strain and serotype of the infecting virus, as well as the age, immune status, and genetic predisposition of the patient. The teaching point in this case study was Dengue fever which occurred concomitantly with Hepatitis A and Hepatitis E virus infection.

  12. 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.

  13. Review of the risks and benefits of yellow fever vaccination including some new analyses.

    PubMed

    Monath, Thomas P

    2012-04-01

    The live, attenuated yellow fever (YF) 17D vaccine provides highly effective and durable immunity and is widely used for travelers to and residents of endemic areas of South America and Africa. Neurotropic and viscerotropic serious adverse events associated with these vaccines occur rarely, but YF 17D vaccine-associated viscerotropic disease (YEL-AVD) is notable for its lethality. There appear to be two distinct patterns of risk for YEL-AVD: the first in younger persons, particularly women, with defects in innate immunity, in whom the case-fatality rate is higher; and the second in elderly persons, particularly men with age-related immune senescence and a lower case-fatality rate. From 1990 to the present, the number of cases (n = 31) and deaths (n = 12) from YEL-AVD in travelers has exceeded the reports of YF (n = 6) acquired by natural infection, raising the question whether the risk of vaccination exceeds the benefit in travelers. To provide some guidance on this point, the rate of vaccine-related injury is compared with the rate of naturally acquired disease in a new analysis that estimates the immunologically susceptible denominator population in YF endemic and epidemic areas. For many years, the risk of vaccine-related illness and death was similar to the risk of illness and death from natural infection with YF in South America. Africa posed a substantially higher estimated risk of wild-type YF than vaccine-related injury. Multiple factors should be considered in making decisions about YF vaccination, including specific destination, season of the year, local evidence for YF transmission, likelihood of exposure to vector mosquitoes and individual risk factors for YEL-AVD, with the goal of increasing vaccine coverage for travel to high-risk areas and reducing unnecessary vaccination. Prospects for future, safer vaccines are also described.

  14. 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.

  15. 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.

  16. 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

  17. Association of Rift Valley fever virus infection with miscarriage in Sudanese women: a cross-sectional study.

    PubMed

    Baudin, Maria; Jumaa, Ammar M; Jomma, Huda J E; Karsany, Mubarak S; Bucht, Göran; Näslund, Jonas; Ahlm, Clas; Evander, Magnus; Mohamed, Nahla

    2016-11-01

    Rift Valley fever virus is an emerging mosquito-borne virus that causes infections in animals and human beings in Africa and the Arabian Peninsula. Outbreaks of Rift Valley fever lead to mass abortions in livestock, but such abortions have not been identified in human beings. Our aim was to investigate the cause of miscarriages in febrile pregnant women in an area endemic for Rift Valley fever. Pregnant women with fever of unknown origin who attended the governmental hospital of Port Sudan, Sudan, between June 30, 2011, and Nov 17, 2012, were sampled at admission and included in this cross-sectional study. Medical records were retrieved and haematological tests were done on patient samples. Presence of viral RNA as well as antibodies against a variety of viruses were analysed. Any association of viral infections, symptoms, and laboratory parameters to pregnancy outcome was investigated using Pearson's χ 2 test. Of 130 pregnant women with febrile disease, 28 were infected with Rift Valley fever virus and 31 with chikungunya virus, with typical clinical and laboratory findings for the infection in question. 15 (54%) of 28 women with an acute Rift Valley fever virus infection had miscarriages compared with 12 (12%) of 102 women negative for Rift Valley fever virus (p<0·0001). In a multiple logistic regression analysis, adjusting for age, haemorrhagic disease, and chikungunya virus infection, an acute Rift Valley fever virus infection was an independent predictor of having a miscarriage (odds ratio 7·4, 95% CI 2·7-20·1; p<0·0001). This study is the first to show an association between infection with Rift Valley fever virus and miscarriage in pregnant women. Further studies are warranted to investigate the possible mechanisms. Our findings have implications for implementation of preventive measures, and evidence-based information to the public in endemic countries should be strongly recommended during Rift Valley fever outbreaks. Schlumberger Faculty for the

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands1

    PubMed Central

    Krijger, Elmer; Delsing, Corine E.; Sprong, Tom; Nabuurs-Franssen, Marrigje H.; Bleeker-Rovers, Chantal P.

    2015-01-01

    Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case–control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised. PMID:26196955

  4. 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...

  5. 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

  6. UDDER INFECTION WITH STREPTOCOCCI OF THE SCARLET FEVER TYPE

    PubMed Central

    Jones, F. S.; Little, Ralph B.

    1928-01-01

    The clinical and bacteriological findings in two cows the udders of which became infected under natural conditions with hemolytic streptococci of the scarlet fever type are discussed. One of the cows was found in a herd supplying raw milk to a small town where a milkborne outbreak of scarlet fever had occurred a short time before. When small numbers of the streptococcus obtained from this case were injected into the udder of a normal cow severe mastitis accompanied by a well marked general reaction resulted. Evidence leads to the conclusion that a severe attack of mastitis due to this organism in one quarter does not sufficiently immunize the other quarters to protect them completely since the streptococcus can be readily implanted in them. The secondary infections were much milder than the original process. PMID:19869456

  7. The immune strategies of mosquito Aedes aegypti against microbial infection.

    PubMed

    Wang, Yan-Hong; Chang, Meng-Meng; Wang, Xue-Li; Zheng, Ai-Hua; Zou, Zhen

    2018-06-01

    Yellow fever mosquito Aedes aegypti transmits many devastating arthropod-borne viruses (arboviruses), such as dengue virus, yellow fever virus, Chikungunya virus, and Zika virus, which cause great concern to human health. Mosquito control is an effective method to block the spread of infectious diseases. Ae. aegypti uses its innate immune system to fight against arboviruses, parasites, and fungi. In this review, we briefly summarize the recent findings in the immune response of Ae. aegypti against arboviral and entomopathogenic infections. This review enriches our understanding of the mosquito immune system and provides evidence to support the development of novel mosquito control strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. 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

  9. 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

  10. [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.

  11. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

    PubMed Central

    Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

    2014-01-01

    Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

  12. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

    PubMed

    Vatter, Heather A; Donaldson, Eric F; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F; Lewis, Anne D; Colgin, Lois M A; Axthelm, Michael K; Pecotte, Jerilyn K; Baric, Ralph S; Wong, Scott W; Brinton, Margo A

    2015-01-01

    Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. 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.

  14. A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.

    PubMed

    Thibodeaux, Brett A; Garbino, Nina C; Liss, Nathan M; Piper, Joseph; Blair, Carol D; Roehrig, John T

    2012-05-02

    Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually. Besides vaccination, there are no other prophylactic or therapeutic strategies approved for use in human YF. Current small animal models of YF require either intra-cranial inoculation of YF vaccine to establish infection, or use of wt strains (e.g., Asibi) in order to achieve pathology. We have developed and characterized a BSL2, adult mouse peripheral challenge model for YFV infection in mice lacking receptors for interferons α, β, and γ (strain AG129). Intraperitoneal challenge of AG129 mice with 17D-204 is a uniformly lethal in a dose-dependent manner, and 17D-204-infected AG129 mice exhibit high viral titers in both brain and liver suggesting this infection is both neurotropic and viscerotropic. Furthermore the use of a mouse model permitted the construction of a 59-biomarker multi-analyte profile (MAP) using samples of brain, liver, and serum taken at multiple time points over the course of infection. This MAP serves as a baseline for evaluating novel therapeutics and their effect on disease progression. Changes (4-fold or greater) in serum and tissue levels of pro- and anti-inflammatory mediators as well as other factors associated with tissue damage were noted in AG129 mice infected with 17D-204 as compared to mock-infected control animals. Published by Elsevier Ltd.

  15. Mosquito Bites

    MedlinePlus

    ... humans. Other mosquito-borne infections include yellow fever, malaria and some types of brain infection (encephalitis). Symptoms ... carry certain diseases, such as West Nile virus, malaria, yellow fever and dengue fever. The mosquito obtains ...

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Vaccination against mosquito borne viral infections: current status.

    PubMed

    Wiwanitkit, Viroj

    2007-12-01

    Mosquito borne infectious diseases are among important group of diseases worldwide. Vaccination is available for some tropical mosquito-borne diseases, especially for Japanese encephalitis virus infection and yellow fever. There are also several attempts to develop new vaccines for the other mosquito-borne diseases such as malaria, dengue infection and West Nile virus infection. In this article, the author reviews the issues on vaccination of some important tropical mosquito borne infectious diseases.

  1. [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

  2. 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

  3. [Chikungunya fever - A new global threat].

    PubMed

    Montero, Antonio

    2015-08-07

    The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  4. 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

  5. Self-reported infections during international travel and notifiable infections among returning international travellers, Sweden, 2009-2013.

    PubMed

    Dahl, Viktor; Wallensten, Anders

    2017-01-01

    We studied food and water-borne diseases (FWDs), sexually transmitted diseases (STDs), vector-borne diseases (VBDs) and diseases vaccinated against in the Swedish childhood vaccination programme among Swedish international travellers, in order to identify countries associated with a high number of infections. We used the national database for notifiable infections to estimate the number of FWDs (campylobacteriosis, salmonellosis, giardiasis, shigellosis, EHEC, Entamoeba histolytica, yersinosis, hepatitis A, paratyphoid fever, typhoid fever, hepatitis E, listeriosis, cholera), STIs (chlamydia, gonorrhoea and acute hepatitis B), VBDs (dengue fever, malaria, West Nile fever, Japanese encephalitis and yellow fever) and diseases vaccinated against in the Swedish childhood vaccination programme (pertussis, measles, mumps, rubella, diphtheria) acquired abroad 2009-2013. We obtained number and duration of trips to each country from a database that monthly collects travel data from a randomly selected proportion of the Swedish population. We calculated number of infections per country 2009-2013 and incidence/million travel days for the five countries with the highest number of infections. Thailand had the highest number of FWDs (7,697, incidence 191/million travel days), STIs (1,388, incidence 34/million travel days) and VBDs (358, incidence 9/million travel days). France had the highest number of cases of diseases vaccinated against in the Swedish childhood vaccination programme (8, 0.4/million travel days). Swedish travellers contracted most infections in Thailand. Special focus should be placed on giving advice to travellers to this destination.

  6. Self-reported infections during international travel and notifiable infections among returning international travellers, Sweden, 2009-2013

    PubMed Central

    Wallensten, Anders

    2017-01-01

    We studied food and water-borne diseases (FWDs), sexually transmitted diseases (STDs), vector-borne diseases (VBDs) and diseases vaccinated against in the Swedish childhood vaccination programme among Swedish international travellers, in order to identify countries associated with a high number of infections. We used the national database for notifiable infections to estimate the number of FWDs (campylobacteriosis, salmonellosis, giardiasis, shigellosis, EHEC, Entamoeba histolytica, yersinosis, hepatitis A, paratyphoid fever, typhoid fever, hepatitis E, listeriosis, cholera), STIs (chlamydia, gonorrhoea and acute hepatitis B), VBDs (dengue fever, malaria, West Nile fever, Japanese encephalitis and yellow fever) and diseases vaccinated against in the Swedish childhood vaccination programme (pertussis, measles, mumps, rubella, diphtheria) acquired abroad 2009–2013. We obtained number and duration of trips to each country from a database that monthly collects travel data from a randomly selected proportion of the Swedish population. We calculated number of infections per country 2009–2013 and incidence/million travel days for the five countries with the highest number of infections. Thailand had the highest number of FWDs (7,697, incidence 191/million travel days), STIs (1,388, incidence 34/million travel days) and VBDs (358, incidence 9/million travel days). France had the highest number of cases of diseases vaccinated against in the Swedish childhood vaccination programme (8, 0.4/million travel days). Swedish travellers contracted most infections in Thailand. Special focus should be placed on giving advice to travellers to this destination. PMID:28753671

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Alkhumra virus infection, a new viral hemorrhagic fever in Saudi Arabia.

    PubMed

    Madani, Tariq A

    2005-08-01

    Four patients with typical acute viral hemorrhagic fever were identified in the holy city of Makkah, Saudi Arabia, between 8 and 23 February 2001, the Hajj (pilgrimage) period of that year. Tests for Rift Valley fever (RVF), Crimean-Congo hemorrhagic fever (CCHF), and dengue were negative. Blood specimens were sent to the Centres for Disease Control and Prevention (CDC), Atlanta for viral culture and testing for other hemorrhagic fever viruses. A new flavivirus closely related to the tick-borne Kyasanur forest disease virus was isolated. This new flavivirus was originally isolated in 1995 from 6 patients with dengue-like hemorrhagic fever from Alkhumra district, south of Jeddah, Saudi Arabia. A case definition was formulated for surveillance of this new disease in Saudi Arabia. Blood specimens were collected from all patients with suspect 'Alkhumra' virus (ALKV) infection and tested for ALKV, RVF, CCHF, dengue, and West Nile encephalitis. Patients data were prospectively collected on standardized data collection forms. From 8 February 2001 through 9 February 2003, a total of 37 cases were identified in Makkah, 20 of them were laboratory confirmed. Acute febrile flu-like illness with hepatitis (100%), hemorrhagic manifestations (55%), and encephalitis (20%) were the main clinical features. The case fatality was 25%. The disease seemed to be transmitted from sheep or goat to humans by the mosquito bites or direct contact with these animals. ALKV infection is a novel serious zoonotic hemorrhagic fever virus discovered in Saudi Arabia. The role of arthropods such as ticks and mosquitoes, and animals such as sheep, goat, and rodents in the transmission and maintenance of the virus remains to be elucidated.

  12. Co-Infection of Rickettsia rickettsii and Streptococcus pyogenes: Is Fatal Rocky Mountain Spotted Fever Underdiagnosed?

    PubMed Central

    Raczniak, Gregory A.; Kato, Cecilia; Chung, Ida H.; Austin, Amy; McQuiston, Jennifer H.; Weis, Erica; Levy, Craig; Carvalho, Maria da Gloria S.; Mitchell, Audrey; Bjork, Adam; Regan, Joanna J.

    2014-01-01

    Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections. PMID:25331804

  13. [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.

  14. 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

  15. 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.

  16. Does Zika virus infection affect mosquito response to repellents?

    PubMed Central

    Leal, Walter S.; Barbosa, Rosângela M. R.; Zeng, Fangfang; Faierstein, Gabriel B.; Tan, Kaiming; Paiva, Marcelo H. S.; Guedes, Duschinka R. D.; Crespo, Mônica M.; Ayres, Constância F. J.

    2017-01-01

    The World Health Organization (WHO) recommends that people travelling to or living in areas with Zika virus (ZIKV) outbreaks or epidemics adopt prophylactic measures to reduce or eliminate mosquito bites, including the use of insect repellents. It is, however, unknown whether repellents are effective against ZIKV-infected mosquitoes, in part because of the ethical concerns related to exposing a human subject’s arm to infected mosquitoes in the standard arm-in-cage assay. We used a previously developed, human subject-free behavioural assay, which mimics a human subject to evaluate the top two recommended insect repellents. Our measurements showed that DEET provided significantly higher protection than picaridin provided against noninfected, host-seeking females of the southern house mosquito, Culex quinquefasciatus, and the yellow fever mosquito, Aedes aegypti. When tested at lower doses, we observed a significant reduction in DEET-elicited protection against ZIKV-infected yellow fever mosquitoes from old and recent laboratory colonies. The reduction in protection is more likely associated with aging than the virus infection and could be compensated by applying a 5x higher dose of DEET. A substantial protection against ZIKV-infected and old noninfected mosquitoes was achieved with 5% DEET, which corresponds approximately to a 30% dose in the conventional arm-in-cage assays. PMID:28205633

  17. 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

  18. Duration of fever and markers of serious bacterial infection in young febrile children.

    PubMed

    Pratt, Amanda; Attia, Magdy W

    2007-02-01

    Despite the drastic change in the evaluation of the febrile young child due to the decreased incidence of serious bacterial infections (SBI) effected by Haemophilus influenza type B and pneumococcal vaccine, there remains a small role for blood work in the evaluation of these patients. Bacterial markers including white blood cell (WBC) count, absolute neutrophil count (ANC) and C-reactive protein (CRP) have been studied and are widely used as predictors of SBI in febrile children. It has been suggested that CRP values should be interpreted cautiously when fever has been present <12 h based on the kinetics of this biological marker. This limitation has not been previously addressed with CRP, nor was it described with other markers, specifically WBC and ANC, therefore the purpose of the present paper was to assess WBC, ANC and CRP values as predictors of SBI in relation to duration of fever. Patients who presented to a pediatric emergency department between the ages of 1 and 36 months, with fever > or =39 degrees C and no source of infection had a complete blood count (CBC) blood culture, and CRP level drawn. A urinalysis and/or urine culture was obtained when age and gender appropriate. A chest X-ray was performed at the discretion of the treating physician. The study subjects were enrolled prospectively and then divided into two groups based on duration of fever of < or = or >12 h, and compared. One hundred and twenty-eight patients were originally enrolled. Nine patients were excluded. Seventeen patients (14%) had SBI. One patient (<1%) had bacteremia, three (3%) had pneumonia, and 13 (10%) had urinary tract infections. Forty-five patients presented with fever < or =12 h and 74 patients presented with fever >12 h. Area under the curve (AUC) for WBC, ANC and CRP was significantly larger in patients with SBI presenting with fever >12 h (0.85, 0.83, 0.92 respectively) compared to patients with SBI who presented with fever for <12 h (0.37, 0.42, 0.68 respectively

  19. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)

    PubMed Central

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-01-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50, were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals’ lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. PMID:23441639

  20. 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

  1. 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.

  2. 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

  3. Rapid Diagnosis of Arbovirus and Arenavirus Infections by Immunofluorescence.

    DTIC Science & Technology

    1981-01-01

    in the indirect imunofluorescence test, have been prepared. The viruses in the slide were: lanai, Japanese encephalitis, Langat , Rocio and yellow fever... Langat , Rocio and yellow fever. The slides gave positive reactions when tested with hyperimmune mouse sera including 6 of 7 sera for viruses not...Nakayama; Langat , TP21; Pongola, MP 781; Rocio, San Paulo ; Sicilian phlebotomus fever, Sabin; West Nile, EgIO; yellow fever, Asibi. the viruses are

  4. Urinary tract infections and post-operative fever in percutaneous nephrolithotomy.

    PubMed

    Gutierrez, Jorge; Smith, Arthur; Geavlete, Petrisor; Shah, Hemendra; Kural, Ali Riza; de Sio, Marco; Amón Sesmero, José H; Hoznek, András; de la Rosette, Jean

    2013-10-01

    To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre-operative urine samples and who received antibiotic prophylaxis were included. Pre-operative bladder urine culture and post-operative fever (>38.5°C) were assessed. Relationship between various patient and operative factors and occurrence of post-operative fever was assessed using logistic regression analyses. Eight hundred and sixty-five (16.2%) patients had a positive urine culture; Escherichia coli was the most common micro-organism found in urine of the 350 patients (6.5%). Of the patients with negative pre-operative urine cultures, 8.8% developed a fever post-PCNL, in contrast to 18.2% of patients with positive urine cultures. Fever developed more often among the patients whose urine cultures consisted of Gram-negative micro-organisms (19.4-23.8%) versus those with Gram-positive micro-organisms (9.7-14.5%). Multivariate analysis indicated that a positive urine culture (odds ratio [OR] = 2.12, CI [1.69-2.65]), staghorn calculus (OR = 1.59, CI [1.28-1.96]), pre-operative nephrostomy (OR = 1.61, CI [1.19-2.17]), lower patient age (OR for each year of 0.99, CI [0.99-1.00]), and diabetes (OR = 1.38, CI [1.05-1.81]) all increased the risk of post-operative fever. Limitations include the use of fever as a predictor of systemic infection. Approximately 10% of PCNL-treated patients developed fever in the post-operative period despite receiving antibiotic prophylaxis. Risk of post-operative fever increased in the presence of a positive urine bacterial culture, diabetes, staghorn calculi, and a pre-operative nephrostomy.

  5. Validating and updating a prediction rule for serious bacterial infection in patients with fever without source.

    PubMed

    Bleeker, S E; Derksen-Lubsen, G; Grobbee, D E; Donders, A R T; Moons, K G M; Moll, H A

    2007-01-01

    To externally validate and update a previously developed rule for predicting the presence of serious bacterial infections in children with fever without apparent source. Patients, 1-36 mo, presenting with fever without source, were prospectively enrolled. Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis/ethmoiditis. The generalizability of the original rule was determined. Subsequently, the prediction rule was updated using all available data of the patients with fever without source (1996-1998 and 2000-2001, n = 381) using multivariable logistic regression. the generalizability of the rule appeared insufficient in the new patients (n = 150). In the updated rule, independent predictors from history and examination were duration of fever, vomiting, ill clinical appearance, chest-wall retractions and poor peripheral circulation (ROC area (95%CI): 0.69 (0.63-0.75)). Additional independent predictors from laboratory were serum white blood cell count and C-reactive protein, and in urinalysis > or = 70 white bloods (ROC area (95%CI): 0.83 (0.78-0.88). A previously developed prediction rule for predicting the presence of serious bacterial infection in children with fever without apparent source was updated. Its clinical score can be used as a first screening tool. Additional laboratory testing may specify the individual risk estimate (range: 4-54%) further.

  6. Lymphocytic choriomeningitis virus (LCMV) infection of macaques: a model for Lassa fever

    PubMed Central

    Zapata, Juan C.; Pauza, C. David; Djavani, Mahmoud M.; Rodas, Juan D.; Moshkoff, Dmitry; Bryant, Joseph; Ateh, Eugene; Garcia, Cybele; Lukashevich, Igor S.; Salvato, Maria S.

    2011-01-01

    Arenaviruses such as Lassa fever virus (LASV) and lymphocytic choriomeningitis virus (LCMV) are benign in their natural reservoir hosts, and can occasionally cause severe viral hemorrhagic fever (VHF) in non-human primates and in human beings. LCMV is considerably more benign for human beings than Lassa virus, however certain strains, like the LCMV-WE strain, can cause severe disease when the virus is delivered as a high-dose inoculum. Here we describe a rhesus macaque model for Lassa fever that employs a virulent strain of LCMV. Since LASV must be studied within Biosafety Level-4 (BSL-4) facilities, the LCMV-infected macaque model has the advantage that it can be used at BSL-3. LCMV-induced disease is rarely as severe as other VHF, but it is similar in cases where vascular leakage leads to lethal systemic failure. The LCMV-infected macaque has been valuable for describing the course of disease with differing viral strains, doses and routes of infection. By monitoring system-wide changes in physiology and gene expression in a controlled experimental setting, it is possible to identify events that are pathognomonic for developing VHF and potential treatment targets. PMID:21820469

  7. Protocols to Assess Coagulation Following In Vitro Infection with Hemorrhagic Fever Viruses

    DTIC Science & Technology

    2016-05-25

    Likewise, patients infected with the flavivirus Dengue virus who develop Dengue hemorrhagic fever (DHF) have increased levels of TF in their sera/plasma...cells, coagulation and fibrinolysis in children with Dengue virus infection. Thrombosis and haemostasis 97:627-634. 5. Geisbert TW, Hensley LE

  8. Broad neutralization of wild-type dengue virus isolates following immunization in monkeys with a tetravalent dengue vaccine based on chimeric yellow fever 17D/dengue viruses.

    PubMed

    Barban, Veronique; Munoz-Jordan, Jorge L; Santiago, Gilberto A; Mantel, Nathalie; Girerd, Yves; Gulia, Sandrine; Claude, Jean-Baptiste; Lang, Jean

    2012-08-01

    The objective of the study was to evaluate if the antibodies elicited after immunization with a tetravalent dengue vaccine, based on chimeric yellow fever 17D/dengue viruses, can neutralize a large range of dengue viruses (DENV). A panel of 82 DENVs was developed from viruses collected primarily during the last decade in 30 countries and included the four serotypes and the majority of existing genotypes. Viruses were isolated and minimally amplified before evaluation against a tetravalent polyclonal serum generated during vaccine preclinical evaluation in monkey, a model in which protection efficacy of this vaccine has been previously demonstrated (Guirakhoo et al., 2004). Neutralization was observed across all the DENV serotypes, genotypes, geographical origins and isolation years. These data indicate that antibodies elicited after immunization with this dengue vaccine candidate should widely protect against infection with contemporary DENV lineages circulating in endemic countries. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. 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.

  10. Enhancing the antiviral potency of ER α-glucosidase inhibitor IHVR-19029 against hemorrhagic fever viruses in vitro and in vivo.

    PubMed

    Ma, Julia; Zhang, Xuexiang; Soloveva, Veronica; Warren, Travis; Guo, Fang; Wu, Shuo; Lu, Huagang; Guo, Jia; Su, Qing; Shen, Helen; Solon, Eric; Comunale, Mary Ann; Mehta, Anand; Guo, Ju-Tao; Bavari, Sina; Du, Yanming; Block, Timothy M; Chang, Jinhong

    2018-02-01

    Targeting host functions essential for viral replication has been considered as a broad spectrum and resistance-refractory antiviral approach. However, only a few host functions have, thus far, been validated as broad-spectrum antiviral targets in vivo. ER α-glucosidases I and II have been demonstrated to be essential for the morphogenesis of many enveloped viruses, including members from four families of viruses causing hemorrhagic fever. In vivo antiviral efficacy of various iminosugar-based ER α-glucosidase inhibitors has been reported in animals infected with Dengue, Japanese encephalitis, Ebola, Marburg and influenza viruses. Herein, we established Huh7.5-derived cell lines with ER α-glucosidase I or II knockout using CRISPR/Cas9 and demonstrated that the replication of Dengue, Yellow fever and Zika viruses was reduced by only 1-2 logs in the knockout cell lines. The results clearly indicate that only a partial suppression of viral replication can possibly be achieved with a complete inhibition of ER-α-glucosidases I or II by their inhibitors. We therefore explore to improve the antiviral efficacy of a lead iminosugar IHVR-19029 through combination with another broad-spectrum antiviral agent, favipiravir (T-705). Indeed, combination of IHVR-19029 and T-705 synergistically inhibited the replication of Yellow fever and Ebola viruses in cultured cells. Moreover, in a mouse model of Ebola virus infection, combination of sub-optimal doses of IHVR-19029 and T-705 significantly increased the survival rate of infected animals. We have thus proved the concept of combinational therapeutic strategy for the treatment of viral hemorrhagic fevers with broad spectrum host- and viral- targeting antiviral agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25516543

  13. Fever--an update.

    PubMed

    Becker, John H; Wu, Stephanie C

    2010-01-01

    Fever is an active yet nonspecific response of the body to infections and other insults that cause immune cells to release cytokines, resulting in a brain prostanoid-mediated rise in body temperature. The causes, types, clinical management, and postoperative consequences of fever are reviewed in this article. Physicians use fever as a clinical sign for diagnoses and prognoses, but "fevers of unknown origin" continue to be problematic. Fevers that arise 1 or 2 days after surgery are usually due to stress and trauma, but later postoperative fevers often have more serious causes and consequences, such as wound infection. Fever is commonly encountered by podiatric physicians and surgeons, and certain procedures with the lower extremity are more likely to eventuate in fever.

  14. Predictors of post-stroke fever and infections: a systematic review and meta-analysis.

    PubMed

    Wästfelt, Maja; Cao, Yang; Ström, Jakob O

    2018-04-23

    Fever after stroke is common, and often caused by infections. In the current study, we aimed to test the hypothesis that pneumonia, urinary tract infection and all-cause fever (thought to include at least some proportion of endogenous fever) have different predicting factors, since they differ regarding etiology. PubMed was searched systematically for articles describing predictors for post-stroke pneumonia, urinary tract infection and all-cause fever. A total of 5294 articles were manually assessed; first by title, then by abstract and finally by full text. Data was extracted from each study, and for variables reported in 3 or more articles, a meta-analysis was performed using a random effects model. Fifty-nine articles met the inclusion criteria. It was found that post-stroke pneumonia is predicted by age OR 1.07 (1.04-1.11), male sex OR 1.42 (1.17-1.74), National Institutes of Health Stroke Scale (NIHSS) OR 1.07 (1.05-1.09), dysphagia OR 3.53 (2.69-4.64), nasogastric tube OR 5.29 (3.01-9.32), diabetes OR 1.15 (1.08-1.23), mechanical ventilation OR 4.65 (2.50-8.65), smoking OR 1.16 (1.08-1.26), Chronic Obstructive Pulmonary Disease (COPD) OR 4.48 (1.82-11.00) and atrial fibrillation OR 1.37 (1.22-1.55). An opposite relation to sex may exist for UTI, which seems to be more common in women. The lack of studies simultaneously studying a wide range of predictors for UTI or all-cause fever calls for future research in this area. The importance of new research would be to improve our understanding of fever complications to facilitate greater vigilance, monitoring, prevention, diagnosis and treatment.

  15. 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.

  16. 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.

  17. 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.

  18. Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.

    PubMed

    Tilak, Rina; Ray, Sougat; Tilak, V W; Mukherji, Sandip

    2016-04-01

    Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever.

  19. 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.

  20. 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

  1. Fever

    MedlinePlus

    ... infections , sinus infections , mononucleosis , bronchitis , pneumonia , and tuberculosis Urinary tract infections Viral gastroenteritis and bacterial gastroenteritis Children may have a low-grade fever for 1 ...

  2. Yellow Fever Virus, but Not Zika Virus or Dengue Virus, Inhibits T-Cell Receptor-Mediated T-Cell Function by an RNA-Based Mechanism.

    PubMed

    McLinden, James H; Bhattarai, Nirjal; Stapleton, Jack T; Chang, Qing; Kaufman, Thomas M; Cassel, Suzanne L; Sutterwala, Fayyaz S; Haim, Hillel; Houtman, Jon C; Xiang, Jinhua

    2017-11-27

    The Flavivirus genus within the Flaviviridae family is comprised of many important human pathogens including yellow fever virus (YFV), dengue virus (DENV), and Zika virus (ZKV), all of which are global public health concerns. Although the related flaviviruses hepatitis C virus and human pegivirus (formerly named GBV-C) interfere with T-cell receptor (TCR) signaling by novel RNA and protein-based mechanisms, the effect of other flaviviruses on TCR signaling is unknown. Here, we studied the effect of YFV, DENV, and ZKV on TCR signaling. Both YFV and ZKV replicated in human T cells in vitro; however, only YFV inhibited TCR signaling. This effect was mediated at least in part by the YFV envelope (env) protein coding RNA. Deletion mutagenesis studies demonstrated that expression of a short, YFV env RNA motif (vsRNA) was required and sufficient to inhibit TCR signaling. Expression of this vsRNA and YFV infection of T cells reduced the expression of a Src-kinase regulatory phosphatase (PTPRE), while ZKV infection did not. YFV infection in mice resulted in impaired TCR signaling and PTPRE expression, with associated reduction in murine response to experimental ovalbumin vaccination. Together, these data suggest that viruses within the flavivirus genus inhibit TCR signaling in a species-dependent manner. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses

    PubMed Central

    Fernandez-Garcia, Maria Dolores; Meertens, Laurent; Chazal, Maxime; Hafirassou, Mohamed Lamine; Dejarnac, Ophélie; Zamborlini, Alessia; Despres, Philippe; Sauvonnet, Nathalie; Arenzana-Seisdedos, Fernando

    2016-01-01

    ABSTRACT 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. PMID:26861019

  4. 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.

  5. Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus).

    PubMed

    Smither, Sophie J; Nelson, Michelle; Eastaugh, Lin; Laws, Thomas R; Taylor, Christopher; Smith, Simon A; Salguero, Francisco J; Lever, Mark S

    2013-04-01

    Marburg virus causes a highly infectious and lethal haemorrhagic fever in primates and may be exploited as a potential biothreat pathogen. To combat the infection and threat of Marburg haemorrhagic fever, there is a need to develop and license appropriate medical countermeasures. To determine whether the common marmoset (Callithrix jacchus) would be an appropriate model to assess therapies against Marburg haemorrhagic fever, initial susceptibility, lethality and pathogenesis studies were performed. Low doses of virus, between 4 and 28 TCID50 , were sufficient to cause a lethal, reproducible infection. Animals became febrile between days 5 and 6, maintaining a high fever before succumbing to disease between 8 and 11 days postchallenge. Typical signs of Marburg virus infection were observed including haemorrhaging and a transient rash. In pathogenesis studies, virus was isolated from the animals' lungs from day 3 postchallenge and from the liver, spleen and blood from day 5 postchallenge. Early signs of histopathology were apparent in the kidney and liver from day 3. The most striking features were observed in animals exhibiting severe clinical signs, which included high viral titres in all organs, with the highest levels in the blood, increased levels in liver function enzymes and blood clotting times, decreased levels in platelets, multifocal moderate-to-severe hepatitis and perivascular oedema. © 2013 Crown copyright. International Journal of Experimental Pathology © 2013 International Journal of Experimental Pathology.

  6. An RNA pseudoknot is required for production of yellow fever virus subgenomic RNA by the host nuclease XRN1.

    PubMed

    Silva, Patrícia A G C; Pereira, Carina F; Dalebout, Tim J; Spaan, Willy J M; Bredenbeek, Peter J

    2010-11-01

    Cells and mice infected with arthropod-borne flaviviruses produce a small subgenomic RNA that is colinear with the distal part of the viral 3'-untranslated region (UTR). This small subgenomic flavivirus RNA (sfRNA) results from the incomplete degradation of the viral genome by the host 5'-3' exonuclease XRN1. Production of the sfRNA is important for the pathogenicity of the virus. This study not only presents a detailed description of the yellow fever virus (YFV) sfRNA but, more importantly, describes for the first time the molecular characteristics of the stalling site for XRN1 in the flavivirus genome. Similar to the case for West Nile virus, the YFV sfRNA was produced by XRN1. However, in contrast to the case for other arthropod-borne flaviviruses, not one but two sfRNAs were detected in YFV-infected mammalian cells. The smaller of these two sfRNAs was not observed in infected mosquito cells. The larger sfRNA could also be produced in vitro by incubation with purified XRN1. These two YFV sfRNAs formed a 5'-nested set. The 5' ends of the YFV sfRNAs were found to be just upstream of the previously predicted RNA pseudoknot PSK3. RNA structure probing and mutagenesis studies provided strong evidence that this pseudoknot structure was formed and served as the molecular signal to stall XRN1. The sequence involved in PSK3 formation was cloned into the Sinrep5 expression vector and shown to direct the production of an sfRNA-like RNA. These results underscore the importance of the RNA pseudoknot in stalling XRN1 and also demonstrate that it is the sole viral requirement for sfRNA production.

  7. Changes in Body Fluid Compartments, Tissue Water and Electrolyte Distribution, and Lipid Concentrations in Rhesus Macaques with Yellow Fever

    DTIC Science & Technology

    1982-11-01

    When these techniques were used for the changes are reported to be caused by the invasion of virus study of pathogenesis of Rocky Mountain spotted fever in...37. Beisel WR: Zinc metabolism in infection, in Brewer AJ, Prasad monkeys with Rocky Mountain spotted fever . JInfect Dis 138-42-48,1978. VTISGR13oI K1TA just’ ’ jnd/Or 2018AmJetRVo4ion/1

  8. 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

  9. Monitoring Procalcitonin in Febrile Neutropenia: What Is Its Utility for Initial Diagnosis of Infection and Reassessment in Persistent Fever?

    PubMed Central

    Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

    2011-01-01

    Background Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever. Methods PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%). Results At fever onset median PCT was 190 pg/mL (range 30–26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80–86350) vs. FUO (205, 33–771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570–771). A PCT peak >500 pg/mL (1196, 524–11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1–23) vs. 10 (3–22; p = 0.026), respectively. Conclusion While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses. PMID:21541027

  10. Monitoring procalcitonin in febrile neutropenia: what is its utility for initial diagnosis of infection and reassessment in persistent fever?

    PubMed

    Robinson, James Owen; Lamoth, Frédéric; Bally, Frank; Knaup, Marlies; Calandra, Thierry; Marchetti, Oscar

    2011-04-25

    Management of febrile neutropenic episodes (FE) is challenged by lacking microbiological and clinical documentation of infection. We aimed at evaluating the utility of monitoring blood procalcitonin (PCT) in FE for initial diagnosis of infection and reassessment in persistent fever. PCT kinetics was prospectively monitored in 194 consecutive FE (1771 blood samples): 65 microbiologically documented infections (MDI, 33.5%; 49 due to non-coagulase-negative staphylococci, non-CNS), 68 clinically documented infections (CDI, 35%; 39 deep-seated), and 61 fever of unexplained origin (FUO, 31.5%). At fever onset median PCT was 190 pg/mL (range 30-26'800), without significant difference among MDI, CDI and FUO. PCT peak occurred on day 2 after onset of fever: non-CNS-MDI/deep-seated-CDI (656, 80-86350) vs. FUO (205, 33-771; p<0.001). PCT >500 pg/mL distinguished non-CNS-MDI/deep-seated-CDI from FUO with 56% sensitivity and 90% specificity. PCT was >500 pg/ml in only 10% of FUO (688, 570-771). A PCT peak >500 pg/mL (1196, 524-11950) occurred beyond 3 days of persistent fever in 17/21 (81%) invasive fungal diseases (IFD). This late PCT peak identified IFD with 81% sensitivity and 57% specificity and preceded diagnosis according to EORTC-MSG criteria in 41% of cases. In IFD responding to therapy, median days to PCT <500 pg/mL and defervescence were 5 (1-23) vs. 10 (3-22; p = 0.026), respectively. While procalcitonin is not useful for diagnosis of infection at onset of neutropenic fever, it may help to distinguish a minority of potentially severe infections among FUOs on day 2 after onset of fever. In persistent fever monitoring procalcitonin contributes to early diagnosis and follow-up of invasive mycoses.

  11. The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response.

    PubMed

    Akondy, Rama S; Monson, Nathan D; Miller, Joseph D; Edupuganti, Srilatha; Teuwen, Dirk; Wu, Hong; Quyyumi, Farah; Garg, Seema; Altman, John D; Del Rio, Carlos; Keyserling, Harry L; Ploss, Alexander; Rice, Charles M; Orenstein, Walter A; Mulligan, Mark J; Ahmed, Rafi

    2009-12-15

    The live yellow fever vaccine (YF-17D) offers a unique opportunity to study memory CD8(+) T cell differentiation in humans following an acute viral infection. We have performed a comprehensive analysis of the virus-specific CD8(+) T cell response using overlapping peptides spanning the entire viral genome. Our results showed that the YF-17D vaccine induces a broad CD8(+) T cell response targeting several epitopes within each viral protein. We identified a dominant HLA-A2-restricted epitope in the NS4B protein and used tetramers specific for this epitope to track the CD8(+) T cell response over a 2 year period. This longitudinal analysis showed the following. 1) Memory CD8(+) T cells appear to pass through an effector phase and then gradually down-regulate expression of activation markers and effector molecules. 2) This effector phase was characterized by down-regulation of CD127, Bcl-2, CCR7, and CD45RA and was followed by a substantial contraction resulting in a pool of memory T cells that re-expressed CD127, Bcl-2, and CD45RA. 3) These memory cells were polyfunctional in terms of degranulation and production of the cytokines IFN-gamma, TNF-alpha, IL-2, and MIP-1beta. 4) The YF-17D-specific memory CD8(+) T cells had a phenotype (CCR7(-)CD45RA(+)) that is typically associated with terminally differentiated cells with limited proliferative capacity (T(EMRA)). However, these cells exhibited robust proliferative potential showing that expression of CD45RA may not always associate with terminal differentiation and, in fact, may be an indicator of highly functional memory CD8(+) T cells generated after acute viral infections.

  12. Role of neutrophil to lymphocyte and monocyte to lymphocyte ratios in the diagnosis of bacterial infection in patients with fever.

    PubMed

    Naess, Are; Nilssen, Siri Saervold; Mo, Reidun; Eide, Geir Egil; Sjursen, Haakon

    2017-06-01

    To study the role of the neutrophil:lymphocyte ratio (NLR) and monocyte:lymphocyte ratio (MLR) in discriminating between different patient groups hospitalized for fever due to infection and those without infection. For 299 patients admitted to hospital for fever with unknown cause, a number of characteristics including NLR and MLR were recorded. These characteristics were used in a multiple multinomial regression analysis to estimate the probability of a final diagnostic group of bacterial, viral, clinically confirmed, or no infection. Both NLR and MLR significantly predicted final diagnostic group. Being highly correlated, however, both variables could not be retained in the same model. Both variables also interacted significantly with duration of fever. Generally, higher values of NLR and MLR indicated larger probabilities for bacterial infection and low probabilities for viral infection. Patients with septicemia had significantly higher NLR compared to patients with other bacterial infections with fever for less than one week. White blood cell counts, neutrophil counts, and C-reactive proteins did not differ significantly between septicemia and the other bacterial infection groups. NLR is a more useful diagnostic tool to identify patients with septicemia than other more commonly used diagnostic blood tests. NLR and MLR may be useful in the diagnosis of bacterial infection among patients hospitalized for fever.

  13. Urinary tract infections in pediatric oncology patients with fever and neutropenia.

    PubMed

    Sandoval, Claudio; Sinaki, Banafsheh; Weiss, Robert; Munoz, Jose; Ozkaynak, M Fevzi; Tugal, Oya; Jayabose, Somasundaram

    2012-02-01

    The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

  14. 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

  15. 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

  16. Circulating Inflammatory Mediators in Patients with Fever: Predicting Bloodstream Infection

    PubMed Central

    Groeneveld, A. B. Johan; Bossink, Ailko W. J.; van Mierlo, Gerard J.; Hack, C. Erik

    2001-01-01

    The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A2 (sPLA2). To compare the value of the latter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0°C rectally or >38.3°C axillary). Microbiological culture results for 7 days after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with positive blood cultures, including one patient with malaria parasitemia. The area under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA2. The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AUC for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA2 was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry

  17. Human Spotted Fever Rickettsial Infections

    DTIC Science & Technology

    2005-04-01

    Ecological study of Rocky Mountain spotted fever in Costa Rica. Am J Trop Med Hyg. 1986;35:192–6. 6. Calero MC, Munez JM, Silva R. Rocky Mountain spotted fever in...J Jr, McKechnie DB, Treadwell TA, et al. Hidden mortality attributable to Rocky Mountain spotted fever : immunohistochemical detection of fatal

  18. 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

  19. 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

  20. 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