Sample records for valley fever activity

  1. Patterns of Rift Valley fever activity in Zambia.

    PubMed Central

    Davies, F. G.; Kilelu, E.; Linthicum, K. J.; Pegram, R. G.

    1992-01-01

    An hypothesis that there was an annual emergence of Rift Valley fever virus in Zambia, during or after the seasonal rains, was examined with the aid of sentinel cattle. Serum samples taken during 1974 and 1978 showed evidence of epizootic Rift Valley fever in Zambia, with more than 80% positive. A sentinel herd exposed from 1982 to 1986 showed that some Rift Valley fever occurred each year. This was usually at a low level, with 3-8% of the susceptible cattle seroconverting. In 1985-6 more than 20% of the animals seroconverted, and this greater activity was associated with vegetational changes--which could be detected by remote-sensing satellite imagery--which have also been associated with greater virus activity in Kenya. PMID:1547835

  2. Valley Fever (Coccidioidomycosis) Statistics

    MedlinePlus

    ... Valley fever may be under-recognized. 2 , 3 Public health surveillance for Valley fever Valley fever is reportable ... MMWR) . Check with your local, state, or territorial public health department for more information about disease reporting requirements ...

  3. Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) is a mosquito-transmitted virus or arbovirus that is endemic in sub-Saharan Africa. In the last decade, Rift Valley fever (RVF) outbreaks have resulted in loss of human and animal life, as well as had significant economic impact. The disease in livestock is primarily a...

  4. The First Prediction of a Rift Valley Fever Outbreak

    NASA Technical Reports Server (NTRS)

    Anyamba, Assaf; Chretien, Jean-Paul; Small, Jennifer; Tucker, Compton J.; Formenty, Pierre; Richardson, Jason H.; Britch, Seth C.; Schnabel, David C.; Erickson, Ralph L.; Linthicum, Kenneth J.

    2009-01-01

    El Nino/Southern Oscillation (ENSO) related anomalies were analyzed using a combination of satellite measurements of elevated sea surface temperatures, and subsequent elevated rainfall and satellite derived normalized difference vegetation index data. A Rift Valley fever risk mapping model using these climate data predicted areas where outbreaks of Rift Valley fever in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. This is the first prospective prediction of a Rift Valley fever outbreak.

  5. Rift Valley fever in Namibia, 2010.

    PubMed

    Monaco, Federica; Pinoni, Chiara; Cosseddu, Gian Mario; Khaiseb, Siegfried; Calistri, Paolo; Molini, Umberto; Bishi, Alec; Conte, Annamaria; Scacchia, Massimo; Lelli, Rossella

    2013-12-01

    During May-July 2010 in Namibia, outbreaks of Rift Valley fever were reported to the National Veterinary Service. Analysis of animal specimens confirmed virus circulation on 7 farms. Molecular characterization showed that all outbreaks were caused by a strain of Rift Valley fever virus closely related to virus strains responsible for outbreaks in South Africa during 2009-2010.

  6. Airborne Dust Models in Valley Fever Research

    NASA Astrophysics Data System (ADS)

    Sprigg, W. A.; Galgiani, J. N.; Vujadinovic, M.; Pejanovic, G.; Vukovic, A. J.; Prasad, A. K.; Djurdjevic, V.; Nickovic, S.

    2011-12-01

    Dust storms (haboobs) struck Phoenix, Arizona, in 2011 on July 5th and again on July 18th. One potential consequence: an estimated 3,600 new cases of Valley Fever in Maricopa County from the first storm alone. The fungi, Coccidioides immitis, the cause of the respiratory infection, Valley Fever, lives in the dry desert soils of the American southwest and southward through Mexico, Central America and South America. The fungi become part of the dust storm and, a few weeks after inhalation, symptoms of Valley Fever may appear, including pneumonia-like illness, rashes, and severe fatigue. Some fatalities occur. Our airborne dust forecast system predicted the timing and extent of the storm, as it has done with other, often different, dust events. Atmosphere/land surface models can be part of public health services to reduce risk of Valley Fever and exacerbation of other respiratory and cardiovascular illness.

  7. Rift Valley fever outbreak, southern Mauritania, 2012.

    PubMed

    Sow, Abdourahmane; Faye, Ousmane; Ba, Yamar; Ba, Hampathé; Diallo, Diawo; Faye, Oumar; Loucoubar, Cheikh; Boushab, Mohamed; Barry, Yahya; Diallo, Mawlouth; Sall, Amadou Alpha

    2014-02-01

    After a period of heavy rainfall, an outbreak of Rift Valley fever occurred in southern Mauritania during September-November 2012. A total of 41 human cases were confirmed, including 13 deaths, and 12 Rift Valley fever virus strains were isolated. Moudjeria and Temchecket Departments were the most affected areas.

  8. Detection and Response for Rift Valley fever

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever is a viral disease that impacts domestic livestock and humans in Africa and the Middle East, and poses a threat to military operations in these areas. We describe a Rift Valley fever Risk Monitoring website, and its ability to predict risk of disease temporally and spatially. We al...

  9. Rift Valley fever outbreak, Mauritania, 1998: seroepidemiologic, virologic, entomologic, and zoologic investigations.

    PubMed

    Nabeth, P; Kane, Y; Abdalahi, M O; Diallo, M; Ndiaye, K; Ba, K; Schneegans, F; Sall, A A; Mathiot, C

    2001-01-01

    A Rift Valley fever outbreak occurred in Mauritania in 1998. Seroepidemiologic and virologic investigation showed active circulation of the Rift Valley fever virus, with 13 strains isolated, and 16% (range 1.5%-38%) immunoglobulin (Ig) M-positivity in sera from 90 humans and 343 animals (sheep, goats, camels, cattle, and donkeys). One human case was fatal.

  10. Sociocultural and Economic Dimensions of Rift Valley Fever

    PubMed Central

    Muga, Geoffrey Otieno; Onyango-Ouma, Washington; Sang, Rosemary; Affognon, Hippolyte

    2015-01-01

    Health researchers have advocated for a cross-disciplinary approach to the study and prevention of infectious zoonotic diseases, such as Rift Valley Fever. It is believed that this approach can help bring out the social determinants and effects of the zoonotic diseases for the design of appropriate interventions and public health policy. A comprehensive literature review using a systematic search strategy was undertaken to explore the sociocultural and economic factors that influence the transmission and spread of Rift Valley Fever. Although the findings reveal a paucity of social research on Rift Valley Fever, they suggest that livestock sacrificial rituals, food preparation and consumption practices, gender roles, and inadequate resource base for public institutions are the key factors that influence the transmission. It is concluded that there is need for cross-disciplinary studies to increase the understanding of Rift Valley Fever and facilitate appropriate and timely response and mitigation measures. PMID:25688166

  11. Current status of rift valley fever vaccine development

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease that presents substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Pheuniviridae within the order Bunyavirales. The wide distribution of ...

  12. Sociocultural and economic dimensions of Rift Valley fever.

    PubMed

    Muga, Geoffrey Otieno; Onyango-Ouma, Washington; Sang, Rosemary; Affognon, Hippolyte

    2015-04-01

    Health researchers have advocated for a cross-disciplinary approach to the study and prevention of infectious zoonotic diseases, such as Rift Valley Fever. It is believed that this approach can help bring out the social determinants and effects of the zoonotic diseases for the design of appropriate interventions and public health policy. A comprehensive literature review using a systematic search strategy was undertaken to explore the sociocultural and economic factors that influence the transmission and spread of Rift Valley Fever. Although the findings reveal a paucity of social research on Rift Valley Fever, they suggest that livestock sacrificial rituals, food preparation and consumption practices, gender roles, and inadequate resource base for public institutions are the key factors that influence the transmission. It is concluded that there is need for cross-disciplinary studies to increase the understanding of Rift Valley Fever and facilitate appropriate and timely response and mitigation measures. © The American Society of Tropical Medicine and Hygiene.

  13. Rift Valley Fever.

    PubMed

    Hartman, Amy

    2017-06-01

    Rift Valley fever (RVF) is a severe veterinary disease of livestock that also causes moderate to severe illness in people. The life cycle of RVF is complex and involves mosquitoes, livestock, people, and the environment. RVF virus is transmitted from either mosquitoes or farm animals to humans, but is generally not transmitted from person to person. People can develop different diseases after infection, including febrile illness, ocular disease, hemorrhagic fever, or encephalitis. There is a significant risk for emergence of RVF into new locations, which would affect human health and livestock industries. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Rift Valley Fever Outbreak in Livestock, Mozambique, 2014.

    PubMed

    Fafetine, José M; Coetzee, Peter; Mubemba, Benjamin; Nhambirre, Ofélia; Neves, Luis; Coetzer, J A W; Venter, Estelle H

    2016-12-01

    In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa.

  15. The Pathogenesis of Rift Valley Fever

    PubMed Central

    Ikegami, Tetsuro; Makino, Shinji

    2011-01-01

    Rift Valley fever (RVF) is an emerging zoonotic disease distributed in sub-Saharan African countries and the Arabian Peninsula. The disease is caused by the Rift Valley fever virus (RVFV) of the family Bunyaviridae and the genus Phlebovirus. The virus is transmitted by mosquitoes, and virus replication in domestic ruminant results in high rates of mortality and abortion. RVFV infection in humans usually causes a self-limiting, acute and febrile illness; however, a small number of cases progress to neurological disorders, partial or complete blindness, hemorrhagic fever, or thrombosis. This review describes the pathology of RVF in human patients and several animal models, and summarizes the role of viral virulence factors and host factors that affect RVFV pathogenesis. PMID:21666766

  16. Rift Valley Fever Outbreak in Livestock, Mozambique, 2014

    PubMed Central

    Coetzee, Peter; Mubemba, Benjamin; Nhambirre, Ofélia; Neves, Luis; Coetzer, J.A.W.; Venter, Estelle H.

    2016-01-01

    In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa. PMID:27869589

  17. Climate controls on valley fever incidence in Kern County, California

    NASA Astrophysics Data System (ADS)

    Zender, Charles S.; Talamantes, Jorge

    2006-01-01

    Coccidiodomycosis (valley fever) is a systemic infection caused by inhalation of airborne spores from Coccidioides immitis, a soil-dwelling fungus found in the southwestern United States, parts of Mexico, and Central and South America. Dust storms help disperse C. immitis so risk factors for valley fever include conditions favorable for fungal growth (moist, warm soil) and for aeolian soil erosion (dry soil and strong winds). Here, we analyze and inter-compare the seasonal and inter-annual behavior of valley fever incidence and climate risk factors for the period 1980-2002 in Kern County, California, the US county with highest reported incidence. We find weak but statistically significant links between disease incidence and antecedent climate conditions. Precipitation anomalies 8 and 20 months antecedent explain only up to 4% of monthly variability in subsequent valley fever incidence during the 23 year period tested. This is consistent with previous studies suggesting that C. immitis tolerates hot, dry periods better than competing soil organisms and, as a result, thrives during wet periods following droughts. Furthermore, the relatively small correlation with climate suggests that the causes of valley fever in Kern County could be largely anthropogenic. Seasonal climate predictors of valley fever in Kern County are similar to, but much weaker than, those in Arizona, where previous studies find precipitation explains up to 75% of incidence. Causes for this discrepancy are not yet understood. Higher resolution temporal and spatial monitoring of soil conditions could improve our understanding of climatic antecedents of severe epidemics.

  18. Regional dust storm modeling for health services: The case of valley fever

    NASA Astrophysics Data System (ADS)

    Sprigg, William A.; Nickovic, Slobodan; Galgiani, John N.; Pejanovic, Goran; Petkovic, Slavko; Vujadinovic, Mirjam; Vukovic, Ana; Dacic, Milan; DiBiase, Scott; Prasad, Anup; El-Askary, Hesham

    2014-09-01

    On 5 July 2011, a massive dust storm struck Phoenix, Arizona (USA), raising concerns for increased cases of valley fever (coccidioidomycosis, or, cocci). A quasi-operational experimental airborne dust forecast system predicted the event and provides model output for continuing analysis in collaboration with public health and air quality communities. An objective of this collaboration was to see if a signal in cases of valley fever in the region could be detected and traced to the storm - an American haboob. To better understand the atmospheric life cycle of cocci spores, the DREAM dust model (also herein, NMME-DREAM) was modified to simulate spore emission, transport and deposition. Inexact knowledge of where cocci-causing fungus grows, the low resolution of cocci surveillance and an overall active period for significant dust events complicate analysis of the effect of the 5 July 2011 storm. In the larger context of monthly to annual disease surveillance, valley fever statistics, when compared against PM10 observation networks and modeled airborne dust concentrations, may reveal a likely cause and effect. Details provided by models and satellites fill time and space voids in conventional approaches to air quality and disease surveillance, leading to land-atmosphere modeling and remote sensing that clearly mark a path to advance valley fever epidemiology, surveillance and risk avoidance.

  19. Rift Valley fever virus infection induces activation of the NLRP3 inflammasome.

    PubMed

    Ermler, Megan E; Traylor, Zachary; Patel, Krupen; Schattgen, Stefan A; Vanaja, Sivapriya K; Fitzgerald, Katherine A; Hise, Amy G

    2014-01-20

    Inflammasome activation is gaining recognition as an important mechanism for protection during viral infection. Here, we investigate whether Rift Valley fever virus, a negative-strand RNA virus, can induce inflammasome responses and IL-1β processing in immune cells. We have determined that RVFV induces NLRP3 inflammasome activation in murine dendritic cells, and that this process is dependent upon ASC and caspase-1. Furthermore, absence of the cellular RNA helicase adaptor protein MAVS/IPS-1 significantly reduces extracellular IL-1β during infection. Finally, direct imaging using confocal microscopy shows that the MAVS protein co-localizes with NLRP3 in the cytoplasm of RVFV infected cells. © 2013 Published by Elsevier Inc.

  20. Observations on the epidemiology of Rift Valley fever in Kenya.

    PubMed

    Davies, F G

    1975-10-01

    The epizootic range of Rift Valley fever in Kenya is defined from the results of virus isolations during epizootics, and form an extensive serological survey of cattle which were exposed during an epizootic. A study of the sera from a wide range of wild bovidae sampled immediately after the epizootic, showed that they did not act as reservoir or amplifying hosts for RVF. Virus isolation attempts from a variety of rodents proved negative. Rift Valley fever did not persist between epizootics by producing symptomless abortions in cattle in areas within its epizootic range. A sentinel herd sampled annually after an epizootic in 1968 revealed not one single seroconversion from 1969 to 1974. Certain forest and forest edge situations were postulated as enzootic for Rift Valley fever, and a small percentage of seroconversions were detected in cattle in these areas, born four years after the last epizootic. This has been the only evidence for the persistence of the virus in Kenya since 1968, and may be a part of the interepizootic maintenance cycle for Rift Valley fever in Kenya, which otherwise remains unknown.

  1. Unexpected Rift Valley Fever Outbreak, Northern Mauritania

    PubMed Central

    El Mamy, Ahmed B. Ould; Baba, Mohamed Ould; Barry, Yahya; Isselmou, Katia; Dia, Mamadou L.; Hampate, Ba; Diallo, Mamadou Y.; El Kory, Mohamed Ould Brahim; Diop, Mariam; Lo, Modou Moustapha; Thiongane, Yaya; Bengoumi, Mohammed; Puech, Lilian; Plee, Ludovic; Claes, Filip; Doumbia, Baba

    2011-01-01

    During September–October 2010, an unprecedented outbreak of Rift Valley fever was reported in the northern Sahelian region of Mauritania after exceptionally heavy rainfall. Camels probably played a central role in the local amplification of the virus. We describe the main clinical signs (hemorrhagic fever, icterus, and nervous symptoms) observed during the outbreak. PMID:22000364

  2. Intensified dust storm activity and Valley fever infection in the southwestern United States

    NASA Astrophysics Data System (ADS)

    Tong, Daniel Q.; Wang, Julian X. L.; Gill, Thomas E.; Lei, Hang; Wang, Binyu

    2017-05-01

    Climate models have consistently projected a drying trend in the southwestern United States, aiding speculation of increasing dust storms in this region. Long-term climatology is essential to documenting the dust trend and its response to climate variability. We have reconstructed long-term dust climatology in the western United States, based on a comprehensive dust identification method and continuous aerosol observations from the Interagency Monitoring of Protected Visual Environments (IMPROVE) network. We report here direct evidence of rapid intensification of dust storm activity over American deserts in the past decades (1988-2011), in contrast to reported decreasing trends in Asia and Africa. The frequency of windblown dust storms has increased 240% from 1990s to 2000s. This dust trend is associated with large-scale variations of sea surface temperature in the Pacific Ocean, with the strongest correlation with the Pacific Decadal Oscillation. We further investigate the relationship between dust and Valley fever, a fast-rising infectious disease caused by inhaling soil-dwelling fungus (Coccidioides immitis and C. posadasii) in the southwestern United States. The frequency of dust storms is found to be correlated with Valley fever incidences, with a coefficient (r) comparable to or stronger than that with other factors believed to control the disease in two endemic centers (Maricopa and Pima County, Arizona).

  3. Valley Fever (Coccidioidomycosis) Risk and Prevention

    MedlinePlus

    ... 2012 Jun;14(3):300-4. Shubitz LF. Comparative aspects of coccidioidomycosis in animals and humans. Ann ... spherule vaccine in humans. The Valley Fever Vaccine Study Group. Am Rev Respir Dis. 1993 Sep;148( ...

  4. Detection of Rift Valley fever viral activity in Kenya by satellite remote sensing imagery

    NASA Technical Reports Server (NTRS)

    Linthicum, Kenneth J.; Bailey, Charles L.; Davies, F. Glyn; Tucker, Compton J.

    1987-01-01

    Data from the advanced very high resolution radiometer on board the National Oceanic and Atmospheric Administration's polar-orbiting meteorological satellites have been used to infer ecological parameters associated with Rift Valley fever (RVF) viral activity in Kenya. An indicator of potential viral activity was produced from satellite data for two different ecological regions in Kenya, where RVF is enzootic. The correlation between the satellite-derived green vegetation index and the ecological parameters associated with RVF virus suggested that satellite data may become a forecasting tool for RVF in Kenya and, perhaps, in other areas of sub-Saharan Africa.

  5. Diagnostic approaches for Rift Valley Fever

    USDA-ARS?s Scientific Manuscript database

    Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus (RVFV) is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in Sub-Saha...

  6. Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

    DTIC Science & Technology

    1990-01-01

    hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

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

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) has been expanding its geographical distribution with important implications for both human and animal health. The emergence of Rift Valley fever (RVF) in the Middle East, and its continuing presence in many areas of Africa, has negatively impacted both medical and vet...

  8. Novel approaches to develop Rift Valley fever vaccines

    PubMed Central

    Indran, Sabarish V.; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed. PMID:23112960

  9. Novel approaches to develop Rift Valley fever vaccines.

    PubMed

    Indran, Sabarish V; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever (RVF) is endemic to sub-Saharan Africa, and has spread into Madagascar, Egypt, Saudi Arabia, and Yemen. Rift Valley fever virus (RVFV) of the family Bunyaviridae, genus Phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. RVFV is classified as a Category A Priority pathogen and overlap select agent by CDC/USDA due to its potential impact on public health and agriculture. There is a gap in the safety and immunogenicity in traditional RVF vaccines; the formalin-inactivated RVFV vaccine TSI-GSD-200 requires three doses for protection, and the live-attenuated Smithburn vaccine has a risk to cause abortion and fetal malformation in pregnant ruminants. In this review, problems of traditional vaccines and the safety and efficacy of recently reported novel RVF candidate vaccines including subunit vaccines, virus vector, and replicons are discussed.

  10. Valley Fever: Earth Observations for Risk Reduction

    NASA Astrophysics Data System (ADS)

    Sprigg, W. A.

    2012-12-01

    Advances in satellite Earth observation systems, numerical weather prediction, and dust storm modeling yield new tools for public health warnings, advisories and epidemiology of illnesses associated with airborne desert dust. Valley Fever, endemic from California through the US/Mexico border region into Central and South America, is triggered by inhalation of soil-dwelling fungal spores. The path from fungal growth to airborne threat depends on environmental conditions observable from satellite. And space-based sensors provide initial conditions for dust storm forecasts and baselines for the epidemiology of Valley Fever and other dust-borne aggravation of respiratory and cardiovascular disease. A new Pan-American Center for the World Meteorological Organization Sand and Dust Storm Warning Advisory and Assessment System creates an opportunity to advance Earth science applications in public health.

  11. Mouse model for the Rift Valley fever virus MP12 strain infection

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), a Category A pathogen and select agent, is the causative agent of Rift Valley fever. To date, no fully licensed vaccine is available in the U.S. for human or animal use and effective antiviral drugs have not been identified. The RVFV MP12 strain is conditionally licen...

  12. Rift Valley fever.

    PubMed

    Paweska, J T

    2015-08-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease affecting domestic and wild ruminants, camels and humans. The causative agent of RVF, the RVF virus (RVFV), has the capacity to cause large and severe outbreaks in animal and human populations and to cross significant natural geographic barriers. Rift Valley fever is usually inapparent in non-pregnant adult animals, but pregnant animals and newborns can be severely affected; outbreaks are characterised by a sudden onset of abortions and high neonatal mortality. The majority of human infections are subclinical or associated with moderate to severe, non-fatal, febrile illness, but some patients may develop a haemorrhagic syndrome and/or ocular and neurological lesions. In both animals and humans, the primary site of RVFV replication and tissue pathology is the liver. Outbreaks of RVF are associated with persistent high rainfalls leading to massive flooding and the emergence of large numbers of competent mosquito vectors that transmit the virus to a wide range of susceptible vertebrate species. Outbreaks of RVF have devastating economic effects on countries for which animal trade constitutes the main source of national revenue. The propensity of the virus to spread into new territories and re-emerge in traditionally endemic regions, where it causes large outbreaks in human and animal populations, presents a formidable challenge for public and veterinary health authorities. The presence of competent mosquito vectors in RVF-free countries, the wide range of mammals susceptible to the virus, altering land use, the global changes in climate, and increased animal trade and travel are some of the factors which might contribute to international spread of RVF.

  13. Rift Valley fever: the Nigerian story.

    PubMed

    Adeyeye, Adewale A; Ekong, Pius S; Pilau, Nicholas N

    2011-01-01

    Rift Valley fever (RVF) is an arthropod-borne zoonotic disease of livestock. It is characterised by fever, salivation, abdominal pain, diarrhoea, mucopurulent to bloody nasal discharge, abortion, rapid decrease in milk production and death in animals. Infected humans experience an influenza-like illness that is characterised by fever, malaise, headaches, nausea and epigastric pain followed by recovery, although mortality can occur. RVF was thought to be a disease of sub-Saharan Africa but with the outbreaks in Egypt and the Arabian Peninsula, it may be extending its range further afield. Virological and serological evidence indicates that the virus exists in Nigeria and, with the warning signal sent by international organisations to countries in Africa about an impending outbreak, co-ordinated research between veterinarians and physicians in Nigeria is advocated.

  14. Potential for autoimmune pathogenesis of Rift Valley Fever virus retinitis.

    PubMed

    Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J; Morrill, John; Lucas, Alexander H; King, Charles H; Kazura, James; LaBeaud, Angelle Desiree

    2013-09-01

    Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication.

  15. Potential for Autoimmune Pathogenesis of Rift Valley Fever Virus Retinitis

    PubMed Central

    Newman-Gerhardt, Shoshana; Muiruri, Samuel; Muchiri, Eric; Peters, Clarence J.; Morrill, John; Lucas, Alexander H.; King, Charles H.; Kazura, James; LaBeaud, Angelle Desiree

    2013-01-01

    Rift Valley Fever (RVF) is a significant threat to human health because it can progress to retinitis, encephalitis, and hemorrhagic fever. The timing of onset of Rift Valley Fever virus (RVFV) retinitis suggests an autoimmune origin. To determine whether RVFV retinitis is associated with increased levels of IgG against retinal tissue, we measured and compared levels of IgG against healthy human eye tissue by immunohistochemical analysis. We found that serum samples from RVFV-exposed Kenyans with retinitis (n = 8) were slightly more likely to have antibodies against retinal tissue than control populations, but the correlation was not statistically significant. Further investigation into the possible immune pathogenesis of RVFV retinitis could lead to improved therapies to prevent or treat this severe complication. PMID:23918215

  16. Mosquitoes and the environment in Nile Delta villages with previous rift valley fever activity

    USDA-ARS?s Scientific Manuscript database

    Egypt is affected by serious human and animal mosquito-borne diseases such as Rift Valley fever (RVF). We investigated how potential RVF virus mosquito vector populations are affected by environmental conditions in the Nile Delta region of Egypt by collecting mosquitoes and environmental data from t...

  17. Statistical modeling of valley fever data in Kern County, California

    NASA Astrophysics Data System (ADS)

    Talamantes, Jorge; Behseta, Sam; Zender, Charles S.

    2007-03-01

    Coccidioidomycosis (valley fever) is a fungal infection found in the southwestern US, northern Mexico, and some places in Central and South America. The fungus that causes it ( Coccidioides immitis) is normally soil-dwelling but, if disturbed, becomes air-borne and infects the host when its spores are inhaled. It is thus natural to surmise that weather conditions that foster the growth and dispersal of the fungus must have an effect on the number of cases in the endemic areas. We present here an attempt at the modeling of valley fever incidence in Kern County, California, by the implementation of a generalized auto regressive moving average (GARMA) model. We show that the number of valley fever cases can be predicted mainly by considering only the previous history of incidence rates in the county. The inclusion of weather-related time sequences improves the model only to a relatively minor extent. This suggests that fluctuations of incidence rates (about a seasonally varying background value) are related to biological and/or anthropogenic reasons, and not so much to weather anomalies.

  18. Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean

    PubMed Central

    2013-01-01

    Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007–2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean. PMID:24016237

  19. Towards a better understanding of Rift Valley fever epidemiology in the south-west of the Indian Ocean.

    PubMed

    Balenghien, Thomas; Cardinale, Eric; Chevalier, Véronique; Elissa, Nohal; Failloux, Anna-Bella; Jean Jose Nipomichene, Thiery Nirina; Nicolas, Gaelle; Rakotoharinome, Vincent Michel; Roger, Matthieu; Zumbo, Betty

    2013-09-09

    Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in East Africa. Infection causes severe and often fatal illness in young sheep, goats and cattle. Domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. Rift Valley fever virus was historically restricted to sub-Saharan countries. The probability of Rift Valley fever emerging in virgin areas is likely to be increasing. Its geographical range has extended over the past years. As a recent example, autochthonous cases of Rift Valley fever were recorded in 2007-2008 in Mayotte in the Indian Ocean. It has been proposed that a single infected animal that enters a naive country is sufficient to initiate a major outbreak before Rift Valley fever virus would ever be detected. Unless vaccines are available and widely used to limit its expansion, Rift Valley fever will continue to be a critical issue for human and animal health in the region of the Indian Ocean.

  20. 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

  1. 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.

  2. A recombinant Rift Valley fever virus glycoprotein subunit vaccine confers full protection against Rift Valley fever challenge in sheep

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suita...

  3. Reemergence of Rift Valley fever, Mauritania, 2010.

    PubMed

    Faye, Ousmane; Ba, Hampathé; Ba, Yamar; Freire, Caio C M; Faye, Oumar; Ndiaye, Oumar; Elgady, Isselmou O; Zanotto, Paolo M A; Diallo, Mawlouth; Sall, Amadou A

    2014-02-01

    A Rift Valley fever (RVF) outbreak in humans and animals occurred in Mauritania in 2010. Thirty cases of RVF in humans and 3 deaths were identified. RVFV isolates were recovered from humans, camels, sheep, goats, and Culex antennatus mosquitoes. Phylogenetic analysis of isolates indicated a virus origin from western Africa.

  4. Rift Valley Fever, Mayotte, 2007–2008

    PubMed Central

    Giry, Claude; Gabrie, Philippe; Tarantola, Arnaud; Pettinelli, François; Collet, Louis; D’Ortenzio, Eric; Renault, Philippe; Pierre, Vincent

    2009-01-01

    After the 2006–2007 epidemic wave of Rift Valley fever (RVF) in East Africa and its circulation in the Comoros, laboratory case-finding of RVF was conducted in Mayotte from September 2007 through May 2008. Ten recent human RVF cases were detected, which confirms the indigenous transmission of RFV virus in Mayotte. PMID:19331733

  5. Rift Valley fever: a mosquito-borne emerging disease

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) (Bunyaviridae: Phlebovirus) is mosquito-borne zoonotic emerging infectious viral disease caused by RVF virus (RVFV) that presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant conce...

  6. Potency of a thermostabilised chimpanzee adenovirus Rift Valley Fever vaccine in cattle.

    PubMed

    Dulal, Pawan; Wright, Daniel; Ashfield, Rebecca; Hill, Adrian V S; Charleston, Bryan; Warimwe, George M

    2016-04-29

    Development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. Here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored Rift Valley Fever vaccine (ChAdOx1-GnGc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. Thermostabilised ChAdOx1-GnGc vaccine stored for 6 months at 25, 37 or 45 ° C elicited comparable Rift Valley Fever virus neutralising antibody titres to those elicited by the 'cold chain' vaccine (stored at -80 ° C throughout) at the same dose, and these were within the range associated with protection against Rift Valley Fever in cattle. The results support the use of sugar-membrane thermostabilised vaccines in target livestock species. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Phosphoproteomic analysis reveals Smad protein family activation following Rift Valley fever virus infection.

    PubMed

    de la Fuente, Cynthia; Pinkham, Chelsea; Dabbagh, Deemah; Beitzel, Brett; Garrison, Aura; Palacios, Gustavo; Hodge, Kimberley Alex; Petricoin, Emanuel F; Schmaljohn, Connie; Campbell, Catherine E; Narayanan, Aarthi; Kehn-Hall, Kylene

    2018-01-01

    Rift Valley fever virus (RVFV) infects both ruminants and humans leading to a wide variance of pathologies dependent on host background and age. Utilizing a targeted reverse phase protein array (RPPA) to define changes in signaling cascades after in vitro infection of human cells with virulent and attenuated RVFV strains, we observed high phosphorylation of Smad transcription factors. This evolutionarily conserved family is phosphorylated by and transduces the activation of TGF-β superfamily receptors. Moreover, we observed that phosphorylation of Smad proteins required active RVFV replication and loss of NSs impaired this activation, further corroborating the RPPA results. Gene promoter analysis of transcripts altered after RVFV infection identified 913 genes that contained a Smad-response element. Functional annotation of these potential Smad-regulated genes clustered in axonal guidance, hepatic fibrosis and cell signaling pathways involved in cellular adhesion/migration, calcium influx, and cytoskeletal reorganization. Furthermore, chromatin immunoprecipitation confirmed the presence of a Smad complex on the interleukin 1 receptor type 2 (IL1R2) promoter, which acts as a decoy receptor for IL-1 activation.

  8. Rift valley fever in the US: Commerce networks, climate, and susceptible vector and host populations

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a mosquito-borne hemorrhagic viral disease with substantial negative impacts on public and animal health in its endemic range of sub-Saharan Africa. Rift Valley fever virus (RVFV) could enter the United States and lead to widespread morbidity and mortality in humans, domes...

  9. A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease...

  10. Application of Immunosignatures for Diagnosis of Valley Fever

    PubMed Central

    Navalkar, Krupa Arun; Johnston, Stephen Albert; Woodbury, Neal; Galgiani, John N.; Magee, D. Mitchell; Chicacz, Zbigniew

    2014-01-01

    Valley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other community-acquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF false-negative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics. PMID:24964807

  11. Mapping the Risk of Rift Valley fever re-emergence in Southern Africa using remote sensing data

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever is a viral disease of animals and humans that occurs throughout sub-Saharan Africa, Egypt and the Arabian Peninsula. Outbreaks of the disease are episodic and closely linked to climate variability, especially widespread elevated rainfall that facilitates Rift Valley fever virus tra...

  12. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    DTIC Science & Technology

    2013-09-12

    Interests: The authors have declared that no competing interests exist. * E-mail: connie.schmaljohn@amedd.army.mil Introduction Rift Valley fever (RVF...against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR (S) 5d...MFLGWSFDFGSLWGNKPWF stem 450–468 RVFV-10sc WSSGLPFGNFGLSWFDMGFWS stem 447–467 doi:10.1371/journal.pntd.0002430.t001 Author Summary Entry into a cell is an essential

  13. Prediction of a Rift Valley fever outbreak

    PubMed Central

    Anyamba, Assaf; Chretien, Jean-Paul; Small, Jennifer; Tucker, Compton J.; Formenty, Pierre B.; Richardson, Jason H.; Britch, Seth C.; Schnabel, David C.; Erickson, Ralph L.; Linthicum, Kenneth J.

    2009-01-01

    El Niño/Southern Oscillation related climate anomalies were analyzed by using a combination of satellite measurements of elevated sea-surface temperatures and subsequent elevated rainfall and satellite-derived normalized difference vegetation index data. A Rift Valley fever (RVF) risk mapping model using these climate data predicted areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. To our knowledge, this is the first prospective prediction of a RVF outbreak. PMID:19144928

  14. Lay perceptions of risk factors for Rift Valley fever in a pastoral community in northeastern Kenya.

    PubMed

    Ng'ang'a, Caroline M; Bukachi, Salome A; Bett, Bernard K

    2016-01-13

    Human behavioral factors have been found to be central in the transmission of Rift Valley fever. Consumption of contaminated meat and milk in particular have been identified as one of the key risk factors for the transmission of Rift Valley fever in humans. In pastoral communities, livestock is the main source of livelihood from which many benefits such as food as well as economic and cultural services are derived. Zoonotic diseases therefore have a great impact on pastoral communities livelihoods. However, lay perceptions regarding the transmission of these diseases including Rift Valley fever hampers their effective control. This study investigated the lay perceptions of risks for Rift Valley fever transmission in a pastoral community in northeastern Kenya. A qualitative study was carried out in Ijara district, Kenya which was one of the hotspots of Rift Valley during the 2006/2007 outbreak. Data were collected using focus group discussions and narratives guided by checklists. Eight focus group discussions consisting of 83 participants and six narratives were conducted. Data was transcribed, coded and analysed according to Emergent themes. The participants reported that they had experienced Rift Valley fever in their livestock especially sheep and in humans both in 1997/1998 and 2006/2007. However, they believed that infections in humans occurred as a result of mosquito bites and had little to do with their consumption of meat, milk and blood from infected livestock. The participants in this study indicated that they had heard of the risks of acquiring the disease through consumption of livestock products but their experiences did not tally with the information they had received hence to them, Rift Valley fever was not transmissible through their dietary practices. Though the communities in this region were aware of Rift Valley fever, they did not have elaborate information regarding the disease transmission dynamics to humans. To avoid misconception about

  15. Drivers of Rift Valley fever epidemics in Madagascar.

    PubMed

    Lancelot, Renaud; Béral, Marina; Rakotoharinome, Vincent Michel; Andriamandimby, Soa-Fy; Héraud, Jean-Michel; Coste, Caroline; Apolloni, Andrea; Squarzoni-Diaw, Cécile; de La Rocque, Stéphane; Formenty, Pierre B H; Bouyer, Jérémy; Wint, G R William; Cardinale, Eric

    2017-01-31

    Rift Valley fever (RVF) is a vector-borne viral disease widespread in Africa. The primary cycle involves mosquitoes and wild and domestic ruminant hosts. Humans are usually contaminated after contact with infected ruminants. As many environmental, agricultural, epidemiological, and anthropogenic factors are implicated in RVF spread, the multidisciplinary One Health approach was needed to identify the drivers of RVF epidemics in Madagascar. We examined the environmental patterns associated with these epidemics, comparing human and ruminant serological data with environmental and cattle-trade data. In contrast to East Africa, environmental drivers did not trigger the epidemics: They only modulated local Rift Valley fever virus (RVFV) transmission in ruminants. Instead, RVFV was introduced through ruminant trade and subsequent movement of cattle between trade hubs caused its long-distance spread within the country. Contact with cattle brought in from infected districts was associated with higher infection risk in slaughterhouse workers. The finding that anthropogenic rather than environmental factors are the main drivers of RVF infection in humans can be used to design better prevention and early detection in the case of RVF resurgence in the region.

  16. Assessing the Habitat of Coccidioides posadasii, the Valley Fever Pathogen: A Study of Environmental Variables and Human Incidence Data in Arizona

    NASA Astrophysics Data System (ADS)

    Mann, Sarina N.

    Coccidioidomycosis, or Valley Fever, is an infectious disease caused by inhalation of soil-dwelling fungus Coccidioides posadasii spores in the Lower Sonoran Life Zone (LSLZ) in Arizona. In the context of climate change, the habitat of environmentally-mediated infectious diseases, such as Valley Fever, are expected to change. Connections have been drawn between climate and Valley Fever infection. The operational scale of the organism is still unknown. Here, we use climatic variables, including precipitation, soil moisture, and temperature. We use PRISM precipitation and temperature data, and Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) as a measure of soil moisture for the entire state of Arizona, divided into 126 primary care areas (PCA). These data are analyzed and regressed with Valley Fever incidence to determine the effects of climatic variability on disease distribution and timing. This study confirms that Valley Fever occurrence is clustered in the LSLZ. Seasonal Valley Fever outbreak was found to be variable year-to-year based on climatic variability. The inconclusive regression analyses indicate that the operational scale of Coccidioides is smaller than the PCA region. All variables are related to Valley Fever infection, but one variable was not found to hold more predictive power than others.

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

    PubMed

    Digoutte, J P

    1999-12-01

    . Intermediate yellow fever--a term coined to define epidemia which do not correspond exactly to urban yellow fever. The cycle involves men and monkeys through wild vectors as Aedes furcifer but also through Aedes aegypti and the mortality rate is much lower than for urban epidemics. In urban yellow fever, man is the only vertebrate host involved in the circulation of the virus, the vector being generally Aedes aegypti. This vector maintains a selective pressure, increasing the transmission of virus capable of producing high viremia in man. In the selvatic cycles, two cycles can be distinguished: one of maintenance which does not increase the quantity of virus in circulation and one of amplification which does increase this quantity. As we shall see, it develops into an epizootic form but also in an epidemic form in man. When the decrease in yellow fevers across Africa is considered, it appears that all major epidemics occur in West Africa inspite of the presence of wild cycles of the yellow fever virus in Central and East Africa. For the rare epidemics that have occurred there, the vector has never been Aedes aegypti. In a recent outbreak in Kenya, the vector was Aedes bromeliae. The examination of part of the gene encoding for envelope protein showed the presence of two geographical types corresponding to West-Africa and Central East-Africa. Clinically speaking, yellow fever is an haemorrhagic fever with hepatitis similar to other haemorrhagic fevers such as Rift Valley fever. When, in 1987, an outbreak of haemorrhagic fever occurred in southern Mauritania, for several days it was thought to be yellow fever. Four days later, the diagnosis was corrected by isolating and identifying the virus as that of Rift Valley fever (RVFV). RVFV causes several pathogenic syndromes in human beings: acute febrile illness, haemorrhagic fever, haemorrhagic fever with hepatitis, nervous syndromes or ocular disease. Mortality rate was high for haemorrhagic fever with hepatitis, reaching 36

  18. The Example of Eastern Africa: the dynamic of Rift Valley fever and tools for monitoring virus activity

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever is a mosquito-borne viral zoonosis that primarily affects animals but also has the capacity to infect humans. Outbreaks of this disease in eastern Africa are closely associated with periods of heavy rainfall and forecasting models and early warning systems have been developed to en...

  19. Drivers of Rift Valley fever epidemics in Madagascar

    PubMed Central

    Lancelot, Renaud; Béral, Marina; Rakotoharinome, Vincent Michel; Andriamandimby, Soa-Fy; Héraud, Jean-Michel; Coste, Caroline; Apolloni, Andrea; Squarzoni-Diaw, Cécile; de La Rocque, Stéphane; Wint, G. R. William; Cardinale, Eric

    2017-01-01

    Rift Valley fever (RVF) is a vector-borne viral disease widespread in Africa. The primary cycle involves mosquitoes and wild and domestic ruminant hosts. Humans are usually contaminated after contact with infected ruminants. As many environmental, agricultural, epidemiological, and anthropogenic factors are implicated in RVF spread, the multidisciplinary One Health approach was needed to identify the drivers of RVF epidemics in Madagascar. We examined the environmental patterns associated with these epidemics, comparing human and ruminant serological data with environmental and cattle-trade data. In contrast to East Africa, environmental drivers did not trigger the epidemics: They only modulated local Rift Valley fever virus (RVFV) transmission in ruminants. Instead, RVFV was introduced through ruminant trade and subsequent movement of cattle between trade hubs caused its long-distance spread within the country. Contact with cattle brought in from infected districts was associated with higher infection risk in slaughterhouse workers. The finding that anthropogenic rather than environmental factors are the main drivers of RVF infection in humans can be used to design better prevention and early detection in the case of RVF resurgence in the region. PMID:28096420

  20. Relating coccidioidomycosis (Valley Fever) incidence via to soil moisture conditions

    USDA-ARS?s Scientific Manuscript database

    Coccidioidomycosis (also called Valley fever) is caused by a soil-borne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe ...

  1. Biologically Informed Individual-based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a zoonotic disease endemic in Sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is ...

  2. Development of a sheep challenge model for Rift Valley fever

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a zoonotic disease that causes severe epizootic disease in ruminants, characterized by mass abortion and high mortality rates in younger animals. The development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A stu...

  3. Rift Valley fever vaccines: current and future needs.

    PubMed

    Dungu, Baptiste; Lubisi, Baratang A; Ikegami, Tetsuro

    2018-04-01

    Rift Valley fever (RVF) is a zoonotic mosquito-borne bunyaviral disease associated with high abortion rates, neonatal deaths, and fetal malformations in ruminants, and mild to severe disease in humans. Outbreaks of RVF cause huge economic losses and public health impacts in endemic countries in Africa and the Arabian Peninsula. A proper vaccination strategy is important for preventing or minimizing outbreaks. Vaccination against RVF is not practiced in many countries, however, due to absence or irregular occurrences of outbreaks, despite serological evidence of RVF viral activity. Nonetheless, effective vaccination strategies, and functional national and international multi-disciplinary networks, remain crucial for ensuring availability of vaccines and supporting execution of vaccination in high risk areas for efficient response to RVF alerts and outbreaks. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Development of a sheep challenge model for Rift Valley fever

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever is a zoonotic disease responsible for severe outbreaks in ruminant livestock characterized by mass abortion and high mortality rates in younger animals. The lack of a fully licensed vaccine in the US has spurred increased demand for a protective vaccine. Thus, development of a reli...

  5. Current Status of Rift Valley Fever Vaccine Development

    PubMed Central

    Faburay, Bonto; LaBeaud, Angelle Desiree; McVey, D. Scott; Wilson, William C.; Richt, Juergen A.

    2017-01-01

    Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease. PMID:28925970

  6. Potential Effects of Rift Valley Fever in the United States

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) has been the cause of disease outbreaks throughout Africa and the Arabian Peninsula, and the infection often results in heavy economic costs through loss of livestock. If RVFV, which is common to select agent lists of the US Department of Health and Human Services and ...

  7. Impact of Global Climate on Rift Valley Fever Disease Outbreaks

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever is a viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. Since the virus was first isolated in Kenya in 1930 it has caused significant impact to animal and human health and national economies, and it is of concern to the internationa...

  8. Rift Valley fever virus NSs protein functions and the similarity to other bunyavirus NSs proteins.

    PubMed

    Ly, Hoai J; Ikegami, Tetsuro

    2016-07-02

    Rift Valley fever is a mosquito-borne zoonotic disease that affects both ruminants and humans. The nonstructural (NS) protein, which is a major virulence factor for Rift Valley fever virus (RVFV), is encoded on the S-segment. Through the cullin 1-Skp1-Fbox E3 ligase complex, the NSs protein promotes the degradation of at least two host proteins, the TFIIH p62 and the PKR proteins. NSs protein bridges the Fbox protein with subsequent substrates, and facilitates the transfer of ubiquitin. The SAP30-YY1 complex also bridges the NSs protein with chromatin DNA, affecting cohesion and segregation of chromatin DNA as well as the activation of interferon-β promoter. The presence of NSs filaments in the nucleus induces DNA damage responses and causes cell-cycle arrest, p53 activation, and apoptosis. Despite the fact that NSs proteins have poor amino acid similarity among bunyaviruses, the strategy utilized to hijack host cells are similar. This review will provide and summarize an update of recent findings pertaining to the biological functions of the NSs protein of RVFV as well as the differences from those of other bunyaviruses.

  9. A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection.

    PubMed

    Riblett, Amber M; Blomen, Vincent A; Jae, Lucas T; Altamura, Louis A; Doms, Robert W; Brummelkamp, Thijn R; Wojcechowskyj, Jason A

    2016-02-01

    Rift Valley fever virus (RVFV) causes recurrent insect-borne epizootics throughout the African continent, and infection of humans can lead to a lethal hemorrhagic fever syndrome. Deep mutagenesis of haploid human cells was used to identify host factors required for RVFV infection. This screen identified a suite of enzymes involved in glycosaminoglycan (GAG) biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex, one of the central components of Golgi complex trafficking. In addition, disruption of PTAR1 led to RVFV resistance as well as reduced heparan sulfate surface levels, consistent with recent observations that PTAR1-deficient cells exhibit altered Golgi complex morphology and glycosylation defects. A variety of biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection on some, but not all, cell types, with the block to infection being at the level of virion attachment. Examination of other members of the Bunyaviridae family for GAG-dependent infection suggested that the interaction with GAGs is not universal among bunyaviruses, indicating that these viruses, as well as RVFV on certain cell types, employ additional unidentified virion attachment factors and/or receptors. Rift Valley fever virus (RVFV) is an emerging pathogen that can cause severe disease in humans and animals. Epizootics among livestock populations lead to high mortality rates and can be economically devastating. Human epidemics of Rift Valley fever, often initiated by contact with infected animals, are characterized by a febrile disease that sometimes leads to encephalitis or hemorrhagic fever. The global burden of the pathogen is increasing because it has recently disseminated beyond Africa, which is of particular concern because the virus can be transmitted by widely distributed mosquito species. There are no FDA-licensed vaccines or antiviral agents with activity

  10. Pathology Review of Two New Rift Valley Fever Virus Ruminant Models

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neona...

  11. USDA, ARS, ABDRL Research on Countermeasures for Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    The United State Department of Agriculture, Agriculture Research Service has recently established research program to address countermeasures for of Rift Valley fever (RVF) virus (RVFV). The recent outbreak in Kenya, Tanzania and Somalia demonstrates the impact this virus can have on human and live...

  12. Potential for North American Mosquitoes to Transmit Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

  13. The impact of climate change on the epidemiology and control of Rift Valley fever.

    PubMed

    Martin, V; Chevalier, V; Ceccato, P; Anyamba, A; De Simone, L; Lubroth, J; de La Rocque, S; Domenech, J

    2008-08-01

    Climate change is likely to change the frequency of extreme weather events, such as tropical cyclones, floods, droughts and hurricanes, and may destabilise and weaken the ecosystem services upon which human society depends. Climate change is also expected to affect animal, human and plant health via indirect pathways: it is likely that the geography of infectious diseases and pests will be altered, including the distribution of vector-borne diseases, such as Rift Valley fever, yellow fever, malaria and dengue, which are highly sensitive to climatic conditions. Extreme weather events might then create the necessary conditions for Rift Valley fever to expand its geographical range northwards and cross the Mediterranean and Arabian seas, with an unexpected impact on the animal and human health of newly affected countries. Strengthening global, regional and national early warning systems is crucial, as are co-ordinated research programmes and subsequent prevention and intervention measures.

  14. Potential for North American mosquitoes to transmit Rift Valley fever virus

    USDA-ARS?s Scientific Manuscript database

    The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, possibly even North A...

  15. Correlative Gene Expression to Protective Seroconversion in Rift Valley Fever Vaccinates.

    PubMed

    Laughlin, Richard C; Drake, Kenneth L; Morrill, John C; Adams, L Garry

    2016-01-01

    Rift Valley fever Virus (RVFV), a negative-stranded RNA virus, is the etiological agent of the vector-borne zoonotic disease, Rift Valley fever (RVF). In both humans and livestock, protective immunity can be achieved through vaccination. Earlier and more recent vaccine trials in cattle and sheep demonstrated a strong neutralizing antibody and total IgG response induced by the RVF vaccine, authentic recombinant MP-12 (arMP-12). From previous work, protective immunity in sheep and cattle vaccinates normally occurs from 7 to 21 days after inoculation with arMP-12. While the serology and protective response induced by arMP-12 has been studied, little attention has been paid to the underlying molecular and genetic events occurring prior to the serologic immune response. To address this, we isolated RNA from whole blood of vaccinated calves over a time course of 21 days before and after vaccination with arMP-12. The time course RNAs were sequenced by RNASeq and bioinformatically analyzed. Our results revealed time-dependent activation or repression of numerous gene ontologies and pathways related to the vaccine induced immune response and its regulation. Additional bioinformatic analyses identified a correlative relationship between specific host immune response genes and protective immunity prior to the detection of protective serum neutralizing antibody responses. These results contribute an important proof of concept for identifying molecular and genetic components underlying the immune response to RVF vaccination and protection prior to serologic detection.

  16. Seroprevalence of Sheep and Goat Pox, Peste Des Petits Ruminants and Rift Valley Fever in Saudi Arabia.

    PubMed

    Boshra, Hani; Truong, Thang; Babiuk, Shawn; Hemida, Maged Gomaa

    2015-01-01

    Sheep and goat pox, peste des petits ruminants and Rift Valley fever are important diseases of small ruminant livestock. Sheep and goat pox, along with peste des petits ruminants, are endemic throughout most of Africa, Asia and the Middle East. Whereas Rift Valley fever is endemic in Africa, outbreaks in the Middle East have been reported over the past decade, including the Arabian Peninsula. Saudi Arabia is a major importer of livestock, and understanding the prevalence of these viral infections would be useful for disease control. In this study, sera from sheep and goats were collected from 3 regions in Saudi Arabia. They were evaluated for antibodies specific to sheep and goat pox, peste des petits ruminants and Rift Valley fever by virus neutralization assays. To the best of our knowledge, this is the first study to evaluate the seroprevalence of these viruses in sheep and goats.

  17. An epidemic of Rift Valley fever in Egypt

    PubMed Central

    Imam, Imam Z. E.; Karamany, R. El; Darwish, Medhat A.

    1979-01-01

    During the epidemic of Rift Valley fever (RVF) that occurred in Egypt and other areas of North Africa in 1977, the virus was isolated from various species of domestic animal and rats (Rattus rattus frugivorus) as well as man. The highest number of RVF virus isolates were obtained from sheep; only one isolate was recovered from each of the other species tested, viz. cow, camel, goat, horse, and rat. RVF virus was reisolated from both camel and horse sera, apparently for the first time. PMID:314355

  18. Modelling Rift Valley fever (RVF) disease vector habitats using active and passive remote sensing systems

    NASA Technical Reports Server (NTRS)

    Ambrosia, Vincent G.; Linthicum, K. G.; Bailey, C. L.; Sebesta, P.

    1989-01-01

    The NASA Ames Ecosystem Science and Technology Branch and the U.S. Army Medical Research Institute of Infectious Diseases are conducting research to detect Rift Valley fever (RVF) vector habitats in eastern Africa using active and passive remote-sensing. The normalized difference vegetation index (NDVI) calculated from Landsat TM and SPOT data is used to characterize the vegetation common to the Aedes mosquito. Relationships have been found between the highest NDVI and the 'dambo' habitat areas near Riuru, Kenya on both wet and dry data. High NDVI values, when combined with the vegetation classifications, are clearly related to the areas of vector habitats. SAR data have been proposed for use during the rainy season when optical systems are of minimal use and the short frequency and duration of the optimum RVF mosquito habitat conditions necessitate rapid evaluation of the vegetation/moisture conditions; only then can disease potential be stemmed and eradication efforts initiated.

  19. Prediction, Assessment of the Rift Valley fever Activity in East and Southern Africa 2006 - 2008 and Possible Vector Control Strategies

    USDA-ARS?s Scientific Manuscript database

    Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Nino/Southern Oscillation (ENSO) phenomenon which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and ...

  20. Aedes mosquito saliva modulates Rift Valley fever virus pathogenicity.

    PubMed

    Le Coupanec, Alain; Babin, Divya; Fiette, Laurence; Jouvion, Grégory; Ave, Patrick; Misse, Dorothee; Bouloy, Michèle; Choumet, Valerie

    2013-01-01

    Rift Valley fever (RVF) is a severe mosquito-borne disease affecting humans and domestic ruminants. Mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. Modulation of these defensive responses may facilitate virus infection. Indeed, Aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the Cache Valley and West Nile viruses. The role of mosquito saliva in the transmission of Rift Valley fever virus (RVFV) has not been investigated. Using a murine model, we explored the potential for mosquitoes to impact the course of RVF disease by determining whether differences in pathogenesis occurred in the presence or absence of mosquito saliva and salivary gland extract. C57BL/6NRJ male mice were infected with the ZH548 strain of RVFV via intraperitoneal or intradermal route, or via bites from RVFV-exposed mosquitoes. The virus titers in mosquitoes and mouse organs were determined by plaque assays. After intraperitoneal injection, RVFV infection primarily resulted in liver damage. In contrast, RVFV infection via intradermal injection caused both liver and neurological symptoms and this route best mimicked the natural infection by mosquitoes. Co-injections of RVFV with salivary gland extract or saliva via intradermal route increased the mortality rates of mice, as well as the virus titers measured in several organs and in the blood. Furthermore, the blood cell counts of infected mice were altered compared to those of uninfected mice. Different routes of infection determine the pattern in which the virus spreads and the organs it targets. Aedes saliva significantly increases the pathogenicity of RVFV.

  1. Blood Meal Analysis of Mosquitoes Involved in a Rift Valley fever Outbreak

    USDA-ARS?s Scientific Manuscript database

    Background: Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were sc...

  2. Multilevel Methodology for Simulation of Spatio-Temporal Systems with Heterogeneous Activity; Application to Spread of Valley Fever Fungus

    USGS Publications Warehouse

    Jammalamadaka, Rajanikanth

    2009-01-01

    This report consists of a dissertation submitted to the faculty of the Department of Electrical and Computer Engineering, in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Graduate College, The University of Arizona, 2008. Spatio-temporal systems with heterogeneity in their structure and behavior have two major problems associated with them. The first one is that such complex real world systems extend over very large spatial and temporal domains and consume so many computational resources to simulate that they are infeasible to study with current computational platforms. The second one is that the data available for understanding such systems is limited because they are spread over space and time making it hard to obtain micro and macro measurements. This also makes it difficult to get the data for validation of their constituent processes while simultaneously considering their global behavior. For example, the valley fever fungus considered in this dissertation is spread over a large spatial grid in the arid Southwest and typically needs to be simulated over several decades of time to obtain useful information. It is also hard to get the temperature and moisture data (which are two critical factors on which the survival of the valley fever fungus depends) at every grid point of the spatial domain over the region of study. In order to address the first problem, we develop a method based on the discrete event system specification which exploits the heterogeneity in the activity of the spatio-temporal system and which has been shown to be effective in solving relatively simple partial differential equation systems. The benefit of addressing the first problem is that it now makes it feasible to address the second problem. We address the second problem by making use of a multilevel methodology based on modeling and simulation and systems theory. This methodology helps us in the construction of models with different resolutions (base and

  3. Rift Valley Fever: Recent Insights into Pathogenesis and Prevention▿

    PubMed Central

    Boshra, Hani; Lorenzo, Gema; Busquets, Núria; Brun, Alejandro

    2011-01-01

    Rift Valley fever virus (RVFV) is a zoonotic pathogen that primarily affects ruminants but can also be lethal in humans. A negative-stranded RNA virus of the family Bunyaviridae, this pathogen is transmitted mainly via mosquito vectors. RVFV has shown the ability to inflict significant damage to livestock and is also a threat to public health. While outbreaks have traditionally occurred in sub-Saharan Africa, recent outbreaks in the Middle East have raised awareness of the potential of this virus to spread to Europe, Asia, and the Americas. Although the virus was initially characterized almost 80 years ago, the only vaccine approved for widespread veterinary use is an attenuated strain that has been associated with significant pathogenic side effects. However, increased understanding of the molecular biology of the virus over the last few years has led to recent advances in vaccine design and has enabled the development of more-potent prophylactic measures to combat infection. In this review, we discuss several aspects of RVFV, with particular emphasis on the molecular components of the virus and their respective roles in pathogenesis and an overview of current vaccine candidates. Progress in understanding the epidemiology of Rift Valley fever has also enabled prediction of potential outbreaks well in advance, thus providing another tool to combat the physical and economic impact of this disease. PMID:21450816

  4. A Hierarchical Network Approach for Modeling Rift Valley Fever Epidemics with Applications in North America

    PubMed Central

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

    2013-01-01

    Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread. PMID:23667453

  5. A hierarchical network approach for modeling Rift Valley fever epidemics with applications in North America.

    PubMed

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

    2013-01-01

    Rift Valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. In the event Rift Valley fever virus is introduced to the United States or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. Presented here is a general network-based mathematical model of Rift Valley fever. Given a lack of empirical data on disease vector species and their vector competence, this discrete time epidemic model uses stochastic parameters following several PERT distributions to model the dynamic interactions between hosts and likely North American mosquito vectors in dispersed geographic areas. Spatial effects and climate factors are also addressed in the model. The model is applied to a large directed asymmetric network of 3,621 nodes based on actual farms to examine a hypothetical introduction to some counties of Texas, an important ranching area in the United States of America. The nodes of the networks represent livestock farms, livestock markets, and feedlots, and the links represent cattle movements and mosquito diffusion between different nodes. Cattle and mosquito (Aedes and Culex) populations are treated with different contact networks to assess virus propagation. Rift Valley fever virus spread is assessed under various initial infection conditions (infected mosquito eggs, adults or cattle). A surprising trend is fewer initial infectious organisms result in a longer delay before a larger and more prolonged outbreak. The delay is likely caused by a lack of herd immunity while the infection expands geographically before becoming an epidemic involving many dispersed farms and animals almost simultaneously. Cattle movement between farms is a large driver of virus expansion, thus quarantines can be efficient mitigation strategy to prevent further geographic spread.

  6. Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006 - 2008 and Possible Vector Control Strategies

    USDA-ARS?s Scientific Manuscript database

    Historical episodic outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns (El Niño and La Niña) of El Niño Southern Oscillation (ENSO) phenomenon which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite ...

  7. Rift Valley Fever Virus Control: Integration of Virus, Host and Vector Studies

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a disease of animals and humans that occurs in Africa and the Arabian Peninsula. It is caused by a Phlebovirus in the family Bunyaviridae. Mosquito-borne epizootics occur during years of unusually heavy rainfall. Domestic cattle, sheep and goats are highly susceptible to i...

  8. Potential for North American Mosquitoes (Diptera: Culicidae) to Transmit Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    To determine which biting insects should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America, we evaluated Culex erraticus, Culex erythrothorax, Culex pipiens, Culex quinquefasciatus, Culex tarsalis, Aedes dorsalis, Aedes vexans, Anopheles quadrimaculatus, and ...

  9. Molecular and serological studies on the Rift Valley fever outbreak in Mauritania in 2010.

    PubMed

    Jäckel, S; Eiden, M; El Mamy, B O; Isselmou, K; Vina-Rodriguez, A; Doumbia, B; Groschup, M H

    2013-11-01

    Rift Valley fever virus (RVFV) is a vector-borne RNA virus affecting humans, livestock and wildlife. In October/November 2010, after a period of unusually heavy rainfall, a Rift Valley fever outbreak occurred in northern Mauritania causing clinical cases in cattle, sheep, goats and camels, 21 of which were of lethal outcome. The aim of this study was to obtain further information on the continuation of RVF virus activity and spread in animal species in Mauritania after this outbreak. We therefore tested sera from small ruminants, cattle and camels for the presence of viral RNA and antibodies against RVFV. These sera were collected in different parts of the country from December 2010 to February 2011 and tested with three different ELISAs and an indirect immunofluorescence assay. The results show a high seroprevalence of RVFV IgM and IgG antibodies of about 57% in all animals investigated. Moreover, in four camel sera, viral RNA was detected emphasizing the important role camels played during the latest RVF outbreak in Mauritania. The study demonstrates the continuous spread of RVFV in Mauritania after initial emergence and highlights the potential role of small ruminants and camels in virus dissemination. © 2013 Blackwell Verlag GmbH.

  10. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: implications from other RNA viruses

    PubMed Central

    Nishiyama, Shoko; Ikegami, Tetsuro

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae). Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the U.S. MP-12 displays a temperature-sensitive (ts) phenotype and does not replicate at 41°C. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF. PMID:26322023

  11. Rift Valley Fever Virus among Wild Ruminants, Etosha National Park, Namibia, 2011.

    PubMed

    Capobianco Dondona, Andrea; Aschenborn, Ortwin; Pinoni, Chiara; Di Gialleonardo, Luigina; Maseke, Adrianatus; Bortone, Grazia; Polci, Andrea; Scacchia, Massimo; Molini, Umberto; Monaco, Federica

    2016-01-01

    After a May 2011 outbreak of Rift Valley fever among livestock northeast of Etosha National Park, Namibia, wild ruminants in the park were tested for the virus. Antibodies were detected in springbok, wildebeest, and black-faced impala, and viral RNA was detected in springbok. Seroprevalence was high, and immune response was long lasting.

  12. Vertical transmission of fatal Rift Valley fever in a newborn.

    PubMed

    Arishi, Haider M; Aqeel, Ali Y; Al Hazmi, Mohamed M

    2006-09-01

    Rift Valley Fever (RVF) is a viral disease transmitted to humans by mosquito bite and contact with animals or their infected tissues. Other modes of transmission include aerosol inhalation and possibly ingestion of raw milk from infected animals. We present a 5-day-old neonate with fatal RVF. Onset of the infant's illness on the 2nd day of life combined with positive RVF-IgM and serological evidence of maternal disease supports vertical transmission.

  13. A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep.

    PubMed

    Faburay, Bonto; Wilson, William C; Gaudreault, Natasha N; Davis, A Sally; Shivanna, Vinay; Bawa, Bhupinder; Sunwoo, Sun Young; Ma, Wenjun; Drolet, Barbara S; Morozov, Igor; McVey, D Scott; Richt, Juergen A

    2016-06-14

    Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts.

  14. A Recombinant Rift Valley Fever Virus Glycoprotein Subunit Vaccine Confers Full Protection against Rift Valley Fever Challenge in Sheep

    PubMed Central

    Faburay, Bonto; Wilson, William C.; Gaudreault, Natasha N.; Davis, A. Sally; Shivanna, Vinay; Bawa, Bhupinder; Sunwoo, Sun Young; Ma, Wenjun; Drolet, Barbara S.; Morozov, Igor; McVey, D. Scott; Richt, Juergen A.

    2016-01-01

    Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing disease outbreaks in Africa and the Arabian Peninsula. The virus has great potential for transboundary spread due to the presence of competent vectors in non-endemic areas. There is currently no fully licensed vaccine suitable for use in livestock or humans outside endemic areas. Here we report the evaluation of the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins. In a previous study, the vaccine elicited strong virus neutralizing antibody responses in sheep and was DIVA (differentiating naturally infected from vaccinated animals) compatible. In the current efficacy study, a group of sheep (n = 5) was vaccinated subcutaneously with the glycoprotein-based subunit vaccine candidate and then subjected to heterologous challenge with the virulent Kenya-128B-15 RVFV strain. The vaccine elicited high virus neutralizing antibody titers and conferred complete protection in all vaccinated sheep, as evidenced by prevention of viremia, fever and absence of RVFV-associated histopathological lesions. We conclude that the subunit vaccine platform represents a promising strategy for the prevention and control of RVFV infections in susceptible hosts. PMID:27296136

  15. Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates

    PubMed Central

    Terasaki, Kaori; Tercero, Breanna R.; Makino, Shinji

    2015-01-01

    Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever, which was first recognized in the Great Rift Valley of Kenya in 1931. RVFV is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines’ residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. PMID:26022573

  16. Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates.

    PubMed

    Terasaki, Kaori; Tercero, Breanna R; Makino, Shinji

    2016-05-02

    Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever (RVF), which was first recognized in the Great Rift Valley of Kenya in 1931. RVF is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines' residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Mosquito host choices on livestock amplifiers of Rift Valley fever virus in Kenya

    USDA-ARS?s Scientific Manuscript database

    Animal hosts may vary in their attraction and acceptability as components of the host location process for assessing biting rates of vectors and risk of exposure to pathogens. However, these parameters remain poorly understood for mosquito vectors of the Rift Valley fever (RVF), an arboviral disease...

  18. Factors Affecting the Ability of American Mosquitoes to Transmit Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    The recent outbreaks of disease caused by Rift Valley fever virus (RVFV) in Kenya, Mauritania, Yemen, Tanzania, Somalia, and Madagascar indicate the potential for RVFV to cause severe disease in both humans and domestic animals and its potential to be introduced into new areas, including North Ameri...

  19. NSs protein of severe fever with thrombocytopenia syndrome virus suppresses interferon production through different mechanism than Rift Valley fever virus.

    PubMed

    Zhang, S; Zheng, B; Wang, T; Li, A; Wan, J; Qu, J; Li, C H; Li, D; Liang, M

    Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified Phlebovirus that causes severe fever with thrombocytopenia syndrome. Our study demonstrated that SFTSV NSs functioned as IFN antagonist mainly by suppressing TBK1/IKKε-IRF3 signaling pathway. NSs interacted with and relocalized TANK-binding kinase 1 (TBK1) into NSs-induced cytoplasmic structures and this interaction could effectively inhibit downstream phosphorylation and dimerization of interferon regulatory factor 3 (IRF3), resulting in the suppression of antiviral signaling and IFN induction. Functional sites of SFTSV NSs binding with TBK1 were then studied and results showed that NSs had lost their IFN-inhibiting activity after deleting the 25 amino acids in N-terminal. Furthermore, the mechanism of Rift Valley fever virus (RVFV) NSs blocking IFN-β response were also investigated. Preliminary results showed that RVFV NSs proteins could neither interact nor co-localize with TBK1 in cytoplasm, but suppressed its expression levels, phosphorylation and dimerization of IRF3 in the subsequent steps, resulting in inhibition of the IFN-β production. Altogether, our data demonstrated the probable mechanism used by SFTSV to inhibit IFN responses which was different from RVFV and pointed toward a novel mechanism for RVFV suppressing IFN responses.

  20. Evaluation of lamb and calf responses to Rift Valley fever MP-12 vaccination

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is an important viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. The disease is of concern to international agricultural and public health communities. The RVF MP-12 strain has been the most safety tested attenuated vaccine ...

  1. Rift Valley fever virus: A review of diagnosis and vaccination, and implications for emergence in Europe.

    PubMed

    Mansfield, Karen L; Banyard, Ashley C; McElhinney, Lorraine; Johnson, Nicholas; Horton, Daniel L; Hernández-Triana, Luis M; Fooks, Anthony R

    2015-10-13

    Rift Valley fever virus (RVFV) is a mosquito-borne virus, and is the causative agent of Rift Valley fever (RVF), a zoonotic disease characterised by an increased incidence of abortion or foetal malformation in ruminants. Infection in humans can also lead to clinical manifestations that in severe cases cause encephalitis or haemorrhagic fever. The virus is endemic throughout much of the African continent. However, the emergence of RVFV in the Middle East, northern Egypt and the Comoros Archipelago has highlighted that the geographical range of RVFV may be increasing, and has led to the concern that an incursion into Europe may occur. At present, there is a limited range of veterinary vaccines available for use in endemic areas, and there is no licensed human vaccine. In this review, the methods available for diagnosis of RVFV infection, the current status of vaccine development and possible implications for RVFV emergence in Europe, are discussed. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  2. Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

    PubMed Central

    Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  3. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

    PubMed

    Lihoradova, Olga A; Indran, Sabarish V; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  4. Experimental infection of calves by two genetically-distinct strains of rift valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously we developed a reliable challenge model for sheep that improves the evaluation of ...

  5. Single-particle cryo-electron microscopy of Rift Valley fever virus

    PubMed Central

    Sherman, Michael B.; Freiberg, Alexander N.; Holbrook, Michael R.; Watowich, Stanley J.

    2009-01-01

    Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human veterinary pathogen causing acute hepatitis in ruminants and has the potential to Single-particle cryo-EM reconstruction of RVFV MP-12 hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T=12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure provides a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit-vaccines. PMID:19304307

  6. Single-particle cryo-electron microscopy of Rift Valley fever virus

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

    Sherman, Michael B.; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555; Freiberg, Alexander N.

    2009-04-25

    Rift Valley fever virus (RVFV; Bunyaviridae; Phlebovirus) is an emerging human and veterinary pathogen causing acute hepatitis in ruminants and has the potential to cause hemorrhagic fever in humans. We report a three-dimensional reconstruction of RVFV vaccine strain MP-12 (RVFV MP-12) by cryo-electron microcopy using icosahedral symmetry of individual virions. Although the genomic core of RVFV MP-12 is apparently poorly ordered, the glycoproteins on the virus surface are highly symmetric and arranged on a T = 12 icosahedral lattice. Our RVFV MP-12 structure allowed clear identification of inter-capsomer contacts and definition of possible glycoprotein arrangements within capsomers. This structure providesmore » a detailed model for phleboviruses, opens new avenues for high-resolution structural studies of the bunyavirus family, and aids the design of antiviral diagnostics and effective subunit vaccines.« less

  7. Utility of Antibody Avidity for Rift Valley Fever Virus Vaccine Potency and Immunogenicity Studies

    USDA-ARS?s Scientific Manuscript database

    Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in sub-Saharan Afr...

  8. Potential for mosquitoes (Diptera: Culicidae) from Florida to transmit rift valley fever virus

    USDA-ARS?s Scientific Manuscript database

    We evaluated 8 species of mosquitoes collected in Florida to determine which of these should be targeted for control should Rift Valley fever virus (RVFV) be detected in North America. Female mosquitoes that had fed on adult hamsters inoculated with RVFV were incubated for 7-21 d at 26°C, allowed to...

  9. Rift Valley Fever vaccines: An overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate

    PubMed Central

    Ikegami, Tetsuro

    2017-01-01

    Introduction Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions. PMID:28425834

  10. Rift Valley fever vaccines: an overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate.

    PubMed

    Ikegami, Tetsuro

    2017-06-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered: This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary: The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions.

  11. The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection.

    PubMed

    Pinkham, Chelsea; An, Soyeon; Lundberg, Lindsay; Bansal, Neha; Benedict, Ashwini; Narayanan, Aarthi; Kehn-Hall, Kylene

    2016-09-01

    Rift Valley fever (RVF) is a zoonotic disease that can cause severe illness in humans and livestock, triggering spontaneous abortion in almost 100% of pregnant ruminants. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3) is phosphorylated on its conserved tyrosine residue (Y705) following RVFV infection. This phosphorylation was dependent on a major virulence factor, the viral nonstructural protein NSs. Loss of STAT3 had little effect on viral replication, but rather resulted in cells being more susceptible to RVFV-induced cell death. Phosphorylated STAT3 translocated to the nucleus, coinciding with inhibition of fos, jun, and nr4a2 gene expression, and the presence of STAT3 and NSs at the nr4a2 promoter. NSs was found predominantly in the cytoplasm of STAT3 null cells, indicating that STAT3 influences NSs nuclear localization. Collectively, these data demonstrate that STAT3 functions in a pro-survival capacity through modulation of NSs localization. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Rift Valley fever outbreak--Kenya, November 2006-January 2007.

    PubMed

    2007-02-02

    In mid-December 2006, several unexplained fatalities associated with fever and generalized bleeding were reported to the Kenya Ministry of Health (KMOH) from Garissa District in North Eastern Province (NEP). By December 20, a total of 11 deaths had been reported. Of serum samples collected from the first 19 patients, Rift Valley fever (RVF) virus RNA or immunoglobulin M (IgM) antibodies against RVF virus were found in samples from 10 patients; all serum specimens were negative for yellow fever, Ebola, Crimean-Congo hemorrhagic fever, and dengue viruses. The outbreak was confirmed by isolation of RVF virus from six of the specimens. Humans can be infected with RVF virus from bites of mosquitoes or other arthropod vectors that have fed on animals infected with RVF virus, or through contact with viremic animals, particularly livestock. Reports of livestock deaths and unexplained animal abortions in NEP provided further evidence of an RVF outbreak. On December 20, an investigation was launched by KMOH, the Kenya Field Epidemiology and Laboratory Training Program (FELTP), the Kenya Medical Research Institute (KEMRI), the Walter Reed Project of the U.S. Army Medical Research Unit, CDC-Kenya's Global Disease Detection Center, and other partners, including the World Health Organization (WHO) and Médecins Sans Frontières (MSF). This report describes the findings from that initial investigation and the control measures taken in response to the RVF outbreak, which spread to multiple additional provinces and districts, resulting in 404 cases with 118 deaths as of January 25, 2007.

  13. Development of Enzyme-Linked Immunosorbent Assays Using Expressed Proteins of Rift Valley Fever Virus

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) is a member of the genus Phlebovirus, family Bunyaviridae that can cause severe disease in both humans and animals. The disease is enzootic in sub-Saharan Africa and RVFV epidemics/epizootics occur periodically, primarily in eastern and southern Africa. Since the virus...

  14. Immunohistochemical Detection of Rift Valley Fever Virus with Non-Infectious, Recombinant Viral Protein Antibodies

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) causes re-emerging disease outbreaks and abortion storms in mature cattle, sheep, and goats, and can cause 100% mortality in young animals. The spread of this exotic, insect transmitted virus is of particular concern because of its widely recognized potential for being...

  15. Development of a Rift Valley fever virus viremia challenge model in sheep and goats

    USDA-ARS?s Scientific Manuscript database

    Rift valley fever virus (RVFV), a member of the family Bunyaviridae, causes severe to fatal disease in newborn ruminants, as well as abortions in pregnant animals; both preventable by vaccination. Availability of a challenge model is a pre-requisite for vaccine efficacy trials. Several modes of ino...

  16. Serological surveillance studies confirm the Rift Valley fever virus free status in South Korea.

    PubMed

    Kim, Hyun Joo; Park, Jee-Yong; Jeoung, Hye-Young; Yeh, Jung-Yong; Cho, Yun-Sang; Choi, Jeong-Soo; Lee, Ji-Youn; Cho, In-Soo; Yoo, Han-Sang

    2015-10-01

    Rift Valley fever is a mosquito-borne zoonotic disease of domestic ruminants. This disease causes abortions in pregnant animals, and it has a high mortality rate in newborn animals. Recently, a Rift Valley fever virus (RVFV) outbreak in the Arabian Peninsula increased its potential spread to new regions worldwide. In non-endemic or disease-free countries, early detection and surveillance are important for preventing the introduction of RVFV. In this study, a serological surveillance was conducted to detect antibodies against RVFV. A total of 2382 serum samples from goats and cattle were randomly collected from nine areas in South Korea from 2011 to 2013. These samples were tested for antibodies against RVFV, using commercial ELISA kits. None of the goats and cattle were positive for antibodies against RVFV. This finding suggests that this disease is not present in South Korea, and furthermore presents the evidence of the RVFV-free status of this country.

  17. Rift Valley fever virus-infected mosquito ova and associated pathology: possible implications for endemic maintenance

    USDA-ARS?s Scientific Manuscript database

    Background: Endemic/enzootic maintenance mechanisms like vertical transmission, pathogen passage from infected adults to their offspring, are central in the epidemiology of zoonotic pathogens. In Kenya, Rift Valley fever virus (RVFV) may be maintained by vertical transmission in ground-pool mosquit...

  18. Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015.

    PubMed

    Boushab, Boushab Mohamed; Fall-Malick, Fatima Zahra; Ould Baba, Sidi El Wafi; Ould Salem, Mohamed Lemine; Belizaire, Marie Roseline Darnycka; Ledib, Hamade; Ould Baba Ahmed, Mohamed Mahmoud; Basco, Leonardo Kishi; Ba, Hampaté

    2016-10-01

    Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania. Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae. The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance.

  19. Impact of Global Climate on Rift Valley Fever and other Vector-borne Disease Outbreaks

    NASA Astrophysics Data System (ADS)

    Linthicum, K. J.

    2017-12-01

    Rift Valley fever is a viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. Since the virus was first isolated in Kenya in 1930 it has caused significant impact to animal and human health and national economies, and it is of concern to the international agricultural and public health community. In this presentation we will describe the (1) ecology of disease transmission as it relates to climate, (2) the impact of climate and other environmental conditions on outbreaks, (3) the ability to use global climate information to predict outbreaks, (4) effective response activities, and (4) the potential to mitigate globalization.

  20. Studies of Infection and Dissemination of Rift Valley Fever Virus in Mosquitoes.

    DTIC Science & Technology

    1991-10-15

    have carried out the following studies:(l) Ultrastructural study of Rift Valley fever ( RVF ) virions in the cardia. (2) Immunocytochemical studies of...tissues for RVF virus in hemocoelically-infected Cx. pipiens. (5) Development of an immunogold procedure for in situ labelling of RVF viri-ons in electron...microscopic preps. (6) Worked toward the idetiTifTcation and isolation of the mosquito cell surface receptor molecule for RVF virus. (7) Developed and

  1. Studies of Infection and Dissemination of Rift Valley Fever Virus in Mosquitoes

    DTIC Science & Technology

    1990-05-01

    study of Rift Valley fever ( RVF ) virus in mosquitoes. During this year, we~havelcarrled out: (1) Immuno- cytochemical and ultrastructurai studies of...the proventriculus of adult, fkmale CuIex o infected with RVF virus. (2) irlmunocytochomical studies of the salivary glands and other tissues in...3) work on the development of an Immunogold procedure for InL.si labelling of RVF virlons In -_ + 20. DISTRIBUTION /AVAILABILITY OF ABSTRACT 21

  2. Comparison of Rift Valley fever virus replication in North American livestock and wildlife cell lines

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) causes outbreaks of endemic disease across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spr...

  3. 77 FR 68783 - Prospective Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... Grant of Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for Disease... territories other than Africa, in the field of use of veterinary vaccines, to practice the inventions listed... precisely defined attenuated vaccine constructs that contain complete deletions of critical virulence...

  4. Seroprevalence of Rift Valley fever, Q fever, and brucellosis in ruminants on the southeastern shore of Lake Chad.

    PubMed

    Abakar, Mahamat Fayiz; Naré, Ngandolo B; Schelling, Esther; Hattendorf, Jan; Alfaroukh, Idriss O; Zinsstag, Jakob

    2014-10-01

    The seroprevalence of Rift Valley fever (RVF), brucellosis, and Q fever among domestic ruminants on the southeastern shore of Lake Chad was studied. The study area consisted of two parts, including mainland and islands. On the mainland, the study was conducted in nine randomly selected villages and camps. On the islands, samples were collected from all four available sites. A total of 985 serum samples were collected and 924 were analyzed using enzyme-linked immunosorbent assay (ELISA) for RVF. A total of 561 samples collected from islands were analyzed using ELISA for Q fever and both ELISA and Rose Bengal tests (RBT) for brucellosis. The apparent RVF seroprevalence by species was 37.8% (95% confidence interval [CI] 34.2-41.3) in cattle, 18.8% (95% CI 12.3-25.2) in goats, and 10.8% (95% CI 3.0-18.5) in sheep. For brucellosis and Q fever, only cattle samples from islands were analyzed. For Q fever, the apparent seroprevalence was 7.8% (95% CI 5.6-10.1). For brucellosis, the RBT showed a prevalence of 5.7% (95% CI 3.8-7.6), and ELISA showed 11.9% (95% CI 9.3-14.6) with a kappa value of 0.53 showing a moderate agreement between the two tests. This study confirms the presence of the three diseases in the study area. More research is required to assess the importance for public health and conservation of the Kouri cattle breed.

  5. Phylogeography of Rift Valley Fever Virus in Africa and the Arabian Peninsula

    PubMed Central

    Peterson, A. Townsend; Hall, Matthew

    2017-01-01

    Rift Valley Fever is an acute zoonotic viral disease caused by Rift Valley Fever virus (RVFV) that affects ruminants and humans in Sub-Saharan Africa and the Arabian Peninsula. We used phylogenetic analyses to understand the demographic history of RVFV populations, using sequence data from the three minigenomic segments of the virus. We used phylogeographic approaches to infer RVFV historical movement patterns across its geographic range, and to reconstruct transitions among host species. Results revealed broad circulation of the virus in East Africa, with many lineages originating in Kenya. Arrival of RVFV in Madagascar resulted from three major waves of virus introduction: the first from Zimbabwe, and the second and third from Kenya. The two major outbreaks in Egypt since 1977 possibly resulted from a long-distance introduction from Zimbabwe during the 1970s, and a single introduction took RVFV from Kenya to Saudi Arabia. Movement of the virus between Kenya and Sudan, and CAR and Zimbabwe, was in both directions. Viral populations in West Africa appear to have resulted from a single introduction from Central African Republic. The overall picture of RVFV history is thus one of considerable mobility, and dynamic evolution and biogeography, emphasizing its invasive potential, potentially more broadly than its current distributional limits. PMID:28068340

  6. Phylogeography of Rift Valley Fever Virus in Africa and the Arabian Peninsula.

    PubMed

    Samy, Abdallah M; Peterson, A Townsend; Hall, Matthew

    2017-01-01

    Rift Valley Fever is an acute zoonotic viral disease caused by Rift Valley Fever virus (RVFV) that affects ruminants and humans in Sub-Saharan Africa and the Arabian Peninsula. We used phylogenetic analyses to understand the demographic history of RVFV populations, using sequence data from the three minigenomic segments of the virus. We used phylogeographic approaches to infer RVFV historical movement patterns across its geographic range, and to reconstruct transitions among host species. Results revealed broad circulation of the virus in East Africa, with many lineages originating in Kenya. Arrival of RVFV in Madagascar resulted from three major waves of virus introduction: the first from Zimbabwe, and the second and third from Kenya. The two major outbreaks in Egypt since 1977 possibly resulted from a long-distance introduction from Zimbabwe during the 1970s, and a single introduction took RVFV from Kenya to Saudi Arabia. Movement of the virus between Kenya and Sudan, and CAR and Zimbabwe, was in both directions. Viral populations in West Africa appear to have resulted from a single introduction from Central African Republic. The overall picture of RVFV history is thus one of considerable mobility, and dynamic evolution and biogeography, emphasizing its invasive potential, potentially more broadly than its current distributional limits.

  7. Rift Valley fever virus and European mosquitoes: vector competence of Culex pipiens and Stegomyia albopicta (= Aedes albopictus).

    PubMed

    Brustolin, M; Talavera, S; Nuñez, A; Santamaría, C; Rivas, R; Pujol, N; Valle, M; Verdún, M; Brun, A; Pagès, N; Busquets, N

    2017-12-01

    Rift Valley fever (RVF) is a mosquito-borne disease caused by the Rift Valley fever virus (RVFV). Rift Valley fever affects a large number of species, including human, and has severe impact on public health and the economy, especially in African countries. The present study examined the vector competence of three different European mosquito species, Culex pipiens (Linnaeus, 1758) form molestus (Diptera: Culicidae), Culex pipiens hybrid form and Stegomyia albopicta (= Aedes albopictus) (Skuse, 1894) (Diptera: Culicidae). Mosquitoes were artificially fed with blood containing RVFV. Infection, disseminated infection and transmission efficiency were evaluated. This is the first study to assess the transmission efficiency of European mosquito species using a virulent RVFV strain. The virus disseminated in Cx. pipiens hybrid form and in S. albopicta. Moreover, infectious viral particles were isolated from saliva of both species, showing their RVFV transmission capacity. The presence of competent Cx. pipiens and S. albopicta in Spain indicates that an autochthonous outbreak of RVF may occur if the virus is introduced. These findings provide information that will help health authorities to set up efficient entomological surveillance and RVFV vector control programmes. © 2017 The Authors. Medical and Veterinary Entomology published by John Wiley & Sons Ltd on behalf of Royal Entomological Society.

  8. Effect of environmental temperature on the vector competence of mosquitoes for Rift Valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Environmental temperature has been shown to affect the ability of mosquitoes to transmit numerous arboviruses and for Rift Valley fever virus (RVFV) in particular. We evaluated the effect of incubation temperatures ranging from 14-26ºC on infection, dissemination, and transmission rates for Culex ta...

  9. Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006-2008 and Possible Vector Control Strategies

    DTIC Science & Technology

    2010-01-01

    and Hygiene INTRODUCTION Rift Valley fever ( RVF ) is a mosquito-borne viral disease with pronounced health and economic impacts on domestic...animals and humans in much of sub-Saharan Africa. 1 The eco- nomic loss from RVF in East Africa is estimated to exceed $60 million because of disruption in...morbidity and mortality in humans. The RVF epizootics and epidemics are closely linked to the occurrence of the warm phase of the El Niño/Southern

  10. RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems.

    PubMed

    Dietrich, Isabelle; Jansen, Stephanie; Fall, Gamou; Lorenzen, Stephan; Rudolf, Martin; Huber, Katrin; Heitmann, Anna; Schicht, Sabine; Ndiaye, El Hadji; Watson, Mick; Castelli, Ilaria; Brennan, Benjamin; Elliott, Richard M; Diallo, Mawlouth; Sall, Amadou A; Failloux, Anna-Bella; Schnettler, Esther; Kohl, Alain; Becker, Stefanie C

    2017-01-01

    The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes. By addressing the production of small RNAs in adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C. quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C. quinquefasciatus mosquitoes is similar to the described activities of RNAi in Aedes sp. mosquitoes. We also show that these have antiviral activity, since silencing of RNAi pathway effectors enhances viral replication. Moreover, our data suggest that RVFV does not encode a suppressor of RNAi. These findings point toward a significant role of RNAi in the control of RVFV in mosquitoes. IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus , Bunyaviridae ) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect Drosophila

  11. RNA Interference Restricts Rift Valley Fever Virus in Multiple Insect Systems

    PubMed Central

    Jansen, Stephanie; Fall, Gamou; Lorenzen, Stephan; Rudolf, Martin; Huber, Katrin; Heitmann, Anna; Schicht, Sabine; Ndiaye, El Hadji; Watson, Mick; Castelli, Ilaria; Elliott, Richard M.; Diallo, Mawlouth; Sall, Amadou A.; Failloux, Anna-Bella; Schnettler, Esther

    2017-01-01

    ABSTRACT The emerging bunyavirus Rift Valley fever virus (RVFV) is transmitted to humans and livestock by a large number of mosquito species. RNA interference (RNAi) has been characterized as an important innate immune defense mechanism used by mosquitoes to limit replication of positive-sense RNA flaviviruses and togaviruses; however, little is known about its role against negative-strand RNA viruses such as RVFV. We show that virus-specific small RNAs are produced in infected mosquito cells, in Drosophila melanogaster cells, and, most importantly, also in RVFV vector mosquitoes. By addressing the production of small RNAs in adult Aedes sp. and Culex quinquefasciatus mosquitoes, we showed the presence of virus-derived Piwi-interacting RNAs (piRNAs) not only in Aedes sp. but also in C. quinquefasciatus mosquitoes, indicating that antiviral RNA interference in C. quinquefasciatus mosquitoes is similar to the described activities of RNAi in Aedes sp. mosquitoes. We also show that these have antiviral activity, since silencing of RNAi pathway effectors enhances viral replication. Moreover, our data suggest that RVFV does not encode a suppressor of RNAi. These findings point toward a significant role of RNAi in the control of RVFV in mosquitoes. IMPORTANCE Rift Valley fever virus (RVFV; Phlebovirus, Bunyaviridae) is an emerging zoonotic mosquito-borne pathogen of high relevance for human and animal health. Successful strategies of intervention in RVFV transmission by its mosquito vectors and the prevention of human and veterinary disease rely on a better understanding of the mechanisms that govern RVFV-vector interactions. Despite its medical importance, little is known about the factors that govern RVFV replication, dissemination, and transmission in the invertebrate host. Here we studied the role of the antiviral RNA interference immune pathways in the defense against RVFV in natural vector mosquitoes and mosquito cells and draw comparisons to the model insect

  12. 77 FR 68783 - Prospective Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-16

    ... Grant of Co-Exclusive License: Veterinary Vaccines for Rift Valley Fever Virus AGENCY: Centers for... veterinary vaccines, to practice the inventions listed in the patent applications referred to below to... generation of precisely defined attenuated vaccine constructs that contain complete deletions of critical...

  13. Potential for stable flies and house flies (Diptera: Muscidae) to transmit Rift Valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in hundreds of thousands of human infections and major economic disruption due to loss of livestock and to trade restrictions. As indicated by the rapid spread of West N...

  14. Interventions against West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus: where are we?

    PubMed

    Kortekaas, Jeroen; Ergönül, Onder; Moormann, Rob J M

    2010-10-01

    ARBO-ZOONET is an international network financed by the European Commission's seventh framework program. The major goal of this initiative is capacity building for the control of emerging viral vector-borne zoonotic diseases, with a clear focus on West Nile virus, Rift Valley fever virus, and Crimean-Congo hemorrhagic fever virus. To evaluate the status quo of control measures against these viruses, an ARBO-ZOONET meeting was held in Istanbul, Turkey, from 19 to 20 November 2009. The symposium consisted of three themes: (1) vaccines: new and existing ones; (2) antivirals: existing and new developments; and (3) antivector vaccines. In addition, a satellite workshop was held on epidemiology and diagnosis. The meeting brought together foremost international experts on the subjects from both within and without the ARBO-ZOONET consortium. This report highlights selected results from these presentations and major conclusions that emanated from the discussions held.

  15. Rift Valley Fever Virus Growth Curve Kinetics in Cattle and Sheep Peripheral Blood Monocyte Derived Macrophages

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), is a mosquito-borne, zoonotic pathogen within genus Phlebovirus, family Bunyaviridae that typically causes outbreaks in sub-Saharan Africa and recently spread to the Arabian Peninsula. In ruminants, RVFV infections cause mass abortion and high mortality rates in neona...

  16. Epidemiologic and environmental risk factors of rift valley fever in southern Africa from 2008 to 2011

    USDA-ARS?s Scientific Manuscript database

    BACKGROUND: Rift Valley fever outbreaks have been associated with periods of widespread and above average rainfall over several months which allows for the virus infected mosquito vector populations to emerge and propagate. This has provided basis to develop complex models based on environmental fa...

  17. Rift Valley Fever, Sudan, 2007 and 2010

    PubMed Central

    Aradaib, Imadeldin E.; Erickson, Bobbie R.; Elageb, Rehab M.; Khristova, Marina L.; Carroll, Serena A.; Elkhidir, Isam M.; Karsany, Mubarak E.; Karrar, AbdelRahim E.; Elbashir, Mustafa I.

    2013-01-01

    To elucidate whether Rift Valley fever virus (RVFV) diversity in Sudan resulted from multiple introductions or from acquired changes over time from 1 introduction event, we generated complete genome sequences from RVFV strains detected during the 2007 and 2010 outbreaks. Phylogenetic analyses of small, medium, and large RNA segment sequences indicated several genetic RVFV variants were circulating in Sudan, which all grouped into Kenya-1 or Kenya-2 sublineages from the 2006–2008 eastern Africa epizootic. Bayesian analysis of sequence differences estimated that diversity among the 2007 and 2010 Sudan RVFV variants shared a most recent common ancestor circa 1996. The data suggest multiple introductions of RVFV into Sudan as part of sweeping epizootics from eastern Africa. The sequences indicate recent movement of RVFV and support the need for surveillance to recognize when and where RVFV circulates between epidemics, which can make data from prediction tools easier to interpret and preventive measures easier to direct toward high-risk areas. PMID:23347790

  18. Rift Valley Fever Seroprevalence in Coastal Kenya.

    PubMed

    Grossi-Soyster, Elysse N; Banda, Tamara; Teng, Crystal Y; Muchiri, Eric M; Mungai, Peter L; Mutuku, Francis M; Gildengorin, Ginny; Kitron, Uriel; King, Charles H; Desiree Labeaud, A

    2017-07-01

    Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI 95 ] 1.3-2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI 95 3.6-9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children ( P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle ( P < 0.01), suggesting exposure is associated with lower socioeconomic standing ( P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

  19. DoD-GEIS Rift Valley Fever Monitoring and Prediction System as a Tool for Defense and US Diplomacy

    NASA Technical Reports Server (NTRS)

    Anyamba, Assaf; Tucker, Compton J.; Linthicum, Kenneth J.; Witt, Clara J.; Gaydos, Joel C.; Russell, Kevin L.

    2011-01-01

    Over the last 10 years the Armed Forces Health Surveillance Center's Global Emerging Infections Surveillance and Response System (GEIS) partnering with NASA'S Goddard Space Flight Center and USDA's USDA-Center for Medical, Agricultural & Veterinary Entomology established and have operated the Rift Valley fever Monitoring and Prediction System to monitor, predict and assess the risk of Rift Valley fever outbreaks and other vector-borne diseases over Africa and the Middle East. This system is built on legacy DoD basic research conducted by Walter Reed Army Institute of Research overseas laboratory (US Army Medical Research Unit-Kenya) and the operational satellite environmental monitoring by NASA GSFC. Over the last 10 years of operation the system has predicted outbreaks of Rift Valley fever in the Horn of Africa, Sudan, South Africa and Mauritania. The ability to predict an outbreak several months before it occurs provides early warning to protect deployed forces, enhance public health in concerned countries and is a valuable tool use.d by the State Department in US Diplomacy. At the international level the system has been used by the Food and Agricultural Organization (FAD) and the World Health Organization (WHO) to support their monitoring, surveillance and response programs in the livestock sector and human health. This project is a successful testament of leveraging resources of different federal agencies to achieve objectives of force health protection, health and diplomacy.

  20. A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the...

  1. Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice.

    PubMed

    Indran, Sabarish V; Lihoradova, Olga A; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A; Tigabu, Bersabeh; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

    2013-07-01

    Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV.

  2. Rift Valley fever virus MP-12 vaccine encoding Toscana virus NSs retains neuroinvasiveness in mice

    PubMed Central

    Indran, Sabarish V.; Lihoradova, Olga A.; Phoenix, Inaia; Lokugamage, Nandadeva; Kalveram, Birte; Head, Jennifer A.; Tigabu, Bersabeh; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Freiberg, Alexander N.

    2013-01-01

    Rift Valley fever is a mosquito-borne zoonotic disease endemic to sub-Saharan Africa. Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. The MP-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. However, MP-12 lacks a marker to differentiate infected from vaccinated animals. In this study, we originally aimed to characterize the efficacy of a recombinant RVFV MP-12 strain encoding Toscana virus (TOSV) NSs gene in place of MP-12 NSs (rMP12-TOSNSs). TOSV NSs promotes the degradation of dsRNA-dependent protein kinase (PKR) and inhibits interferon-β gene up-regulation without suppressing host general transcription. Unexpectedly, rMP12-TOSNSs increased death in vaccinated outbred mice and inbred BALB/c or C57BL/6 mice. Immunohistochemistry showed diffusely positive viral antigens in the thalamus, hypothalamus and brainstem, including the medulla. No viral antigens were detected in spleen or liver, which is similar to the antigen distribution of moribund mice infected with MP-12. These results suggest that rMP12-TOSNSs retains neuroinvasiveness in mice. Our findings demonstrate that rMP12-TOSNSs causes neuroinvasion without any hepatic disease and will be useful for studying the neuroinvasion mechanism of RVFV and TOSV. PMID:23515022

  3. Rift Valley fever risk map model and seroprevalence in selected wild ungulates and camels from Kenya

    USDA-ARS?s Scientific Manuscript database

    Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based...

  4. Potential for Psorophora columbiae and Psorophora ciliata mosquitoes (Diptera: Culicidae) to transmit Rift Valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) continues to pose a threat to much of the world. Unlike many arboviruses, numerous mosquito species have been associated with RVFV in nature, and many species have been demonstrated as competent vectors in the laboratory. In this study, we evaluated two field-collect...

  5. Arabidopsis thaliana plants expressing Rift Valley fever virus antigens: Mice exhibit systemic immune responses as the result of oral administration of the transgenic plants.

    PubMed

    Kalbina, Irina; Lagerqvist, Nina; Moiane, Bélisario; Ahlm, Clas; Andersson, Sören; Strid, Åke; Falk, Kerstin I

    2016-11-01

    The zoonotic Rift Valley fever virus affects livestock and humans in Africa and on the Arabian Peninsula. The economic impact of this pathogen due to livestock losses, as well as its relevance to public health, underscores the importance of developing effective and easily distributed vaccines. Vaccines that can be delivered orally are of particular interest. Here, we report the expression in transformed plants (Arabidopsis thaliana) of Rift Valley fever virus antigens. The antigens used in this study were the N protein and a deletion mutant of the Gn glycoprotein. Transformed lines were analysed for specific mRNA and protein content by RT-PCR and Western blotting, respectively. Furthermore, the plant-expressed antigens were evaluated for their immunogenicity in mice fed the transgenic plants. After oral intake of fresh transgenic plant material, a proportion of the mice elicited specific IgG antibody responses, as compared to the control animals that were fed wild-type plants and of which none sero-converted. Thus, we show that transgenic plants can be readily used to express and produce Rift Valley Fever virus proteins, and that the plants are immunogenic when given orally to mice. These are promising findings and provide a basis for further studies on edible plant vaccines against the Rift Valley fever virus. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs.

    PubMed

    Lihoradova, Olga; Ikegami, Tetsuro

    2014-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae . RVFV encodes a major virulence factor, NSs , which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the virology and pathology of RVF, and countermeasure development for RVF, with emphasis on NSs function and applications.

  7. Countermeasure development for Rift Valley fever: deletion, modification or targeting of major virulence factor NSs

    PubMed Central

    Lihoradova, Olga; Ikegami, Tetsuro

    2014-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease characterized by a high rate of abortion in ruminants, and febrile illness, hemorrhagic fever, retinitis and encephalitis in humans. RVF is caused by the RVF virus (RVFV), belonging to the genus Phlebovirus of the family Bunyaviridae. RVFV encodes a major virulence factor, NSs, which is dispensable for viral replication, yet required for evasion of host innate immune responses. RVFV NSs inhibits host gene upregulation at the transcriptional level, while promoting viral translation in the cytoplasm. In this article, we summarize the virology and pathology of RVF, and countermeasure development for RVF, with emphasis on NSs function and applications. PMID:24910709

  8. A Replication-incompetent Rift Valley Fever Vaccine: Chimeric Virus-like Particles Protect Mice and Rats Against Lethal Challenge

    PubMed Central

    Mandell, Robert B.; Koukuntla, Ramesh; Mogler, Laura J. K.; Carzoli, Andrea K.; Freiberg, Alexander N.; Holbrook, Michael R.; Martin, Brian K.; Staplin, William R.; Vahanian, Nicholas N.; Link, Charles J.; Flick, Ramon

    2009-01-01

    Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins GN and GC, nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate. PMID:19932911

  9. Molecular biology and genetic diversity of Rift Valley fever virus

    PubMed Central

    Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever (RVF), a mosquito-borne disease of ruminant animals and humans. The generation of a large sequence database has facilitated studies of the evolution and spread of the virus. Bayesian analyses indicate that currently circulating strains of RVFV are descended from an ancestral species that emerged from a natural reservoir in Africa when large-scale cattle and sheep farming were introduced during the 19th century. Viruses descended from multiple lineages persist in that region, through infection of reservoir animals and vertical transmission in mosquitoes, emerging in years of heavy rainfall to cause epizootics and epidemics. On a number of occasions, viruses from these lineages have been transported outside the enzootic region through the movement of infected animals or mosquitoes, triggering outbreaks in countries such as Egypt, Saudi Arabia, Mauritania and Madagascar, where RVF had not previously been seen. Such viruses could potentially become established in their new environments through infection of wild and domestic ruminants and other animals and vertical transmission in local mosquito species. Despite their extensive geographic dispersion, all strains of RVFV remain closely related at the nucleotide and amino acid level. The high degree of conservation of genes encoding the virion surface glycoproteins suggests that a single vaccine should protect against all currently circulating RVFV strains. Similarly, preservation of the sequence of the RNA-dependent RNA polymerase across viral lineages implies that antiviral drugs targeting the enzyme should be effective against all strains. Researchers should be encouraged to collect additional RVFV isolates and perform whole-genome sequencing and phylogenetic analysis, so as to enhance our understanding of the continuing evolution of this important virus. This review forms part of a series

  10. Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR

    PubMed Central

    Nishiyama, Shoko; Slack, Olga A. L.; Lokugamage, Nandadeva; Hill, Terence E.; Juelich, Terry L.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Gong, Bin; Freiberg, Alexander N.; Ikegami, Tetsuro

    2016-01-01

    ABSTRACT Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker. PMID:27248570

  11. Attenuation of pathogenic Rift Valley fever virus strain through the chimeric S-segment encoding sandfly fever phlebovirus NSs or a dominant-negative PKR.

    PubMed

    Nishiyama, Shoko; Slack, Olga A L; Lokugamage, Nandadeva; Hill, Terence E; Juelich, Terry L; Zhang, Lihong; Smith, Jennifer K; Perez, David; Gong, Bin; Freiberg, Alexander N; Ikegami, Tetsuro

    2016-11-16

    Rift Valley fever is a mosquito-borne zoonotic disease affecting ruminants and humans. Rift Valley fever virus (RVFV: family Bunyaviridae, genus Phlebovirus) causes abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or retinitis in humans. The live-attenuated MP-12 vaccine is conditionally licensed for veterinary use in the US. However, this vaccine lacks a marker for the differentiation of vaccinated from infected animals (DIVA). NSs gene is dispensable for RVFV replication, and thus, rMP-12 strains lacking NSs gene is applicable to monitor vaccinated animals. However, the immunogenicity of MP-12 lacking NSs was not as high as parental MP-12. Thus, chimeric MP-12 strains encoding NSs from either Toscana virus (TOSV), sandfly fever Sicilian virus (SFSV) or Punta Toro virus Adames strain (PTA) were characterized previously. Although chimeric MP-12 strains are highly immunogenic, the attenuation through the S-segment remains unknown. Using pathogenic ZH501 strain, we aimed to demonstrate the attenuation of ZH501 strain through chimeric S-segment encoding either the NSs of TOSV, SFSV, PTA, or Punta Toro virus Balliet strain (PTB). In addition, we characterized rZH501 encoding a human dominant-negative PKR (PKRΔE7), which also enhances the immunogenicity of MP-12. Study done on mice revealed that attenuation of rZH501 occurred through the S-segment encoding either PKRΔE7 or SFSV NSs. However, rZH501 encoding either TOSV, PTA, or PTB NSs in the S-segment uniformly caused lethal encephalitis. Our results indicated that the S-segments encoding PKRΔE7 or SFSV NSs are attenuated and thus applicable toward next generation MP-12 vaccine candidates that encode a DIVA marker.

  12. Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus.

    PubMed

    Spik, Kristin; Shurtleff, Amy; McElroy, Anita K; Guttieri, Mary C; Hooper, Jay W; SchmalJohn, Connie

    2006-05-22

    DNA vaccines for Rift Valley fever virus (RVFV), Crimean Congo hemorrhagic fever virus (CCHFV), tick-borne encephalitis virus (TBEV), and Hantaan virus (HTNV), were tested in mice alone or in various combinations. The bunyavirus vaccines (RVFV, CCHFV, and HTNV) expressed Gn and Gc genes, and the flavivirus vaccine (TBEV) expressed the preM and E genes. All vaccines were delivered by gene gun. The TBEV DNA vaccine and the RVFV DNA vaccine elicited similar levels of antibodies and protected mice from challenge when delivered alone or in combination with other DNAs. Although in general, the HTNV and CCHFV DNA vaccines were not very immunogenic in mice, there were no major differences in performance when given alone or in combination with the other vaccines.

  13. The Rift Valley fever: could re-emerge in Egypt again?

    PubMed

    El-Bahnasawy, Mamdouh; Megahed, Laila Abdel-Mawla; Abdalla Saleh, Hala Ahmed; Morsy, Tosson A

    2013-04-01

    The Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus of the family of Bunyaviridae, genus Phlebovirus. RVF is an acute, febrile disease affecting humans and a wide range of animals. The virus is trans-mitted through the bites from mosquitoes and exposure to viremic blood, body fluids, or contact with tissues of infected animals or by inhaling natural virus aerosols, also possibly by consumption of infected unpasteurized milk. The RVF-virus replicate at the site introduction and in local lymphatic followed by viremia and spread to other organs as the liver and central nervous system, causing the hepatic necrosis and eosinophilia cytoplasmic degeneration. The main signs and symptoms are fever, headache, myalgia, arthralgia, photophobia, bradycardia, conjunctivitis and flushing face. Main complications include jaundice, hemorrhagic, meningoencephalitis and retinal lesions. Generally speaking, in the 21st Century, the vector-borne infectious diseases, was accepted as the disaster issues with the considerable significant morbidity and mortality. These facts should be considered by the public health, veterinary and agricultural authorities

  14. Serological Evidence for the Circulation of Rift Valley Fever Virus in Domestic Small Ruminants in Southern Gabon.

    PubMed

    Maganga, Gael Darren; Abessolo Ndong, Andre Lea; Mikala Okouyi, Clency Sylde; Makiala Mandanda, Sheila; N'Dilimabaka, Nadine; Pinto, Anais; Agossou, Ernest; Cossic, Brieuc; Akue, Jean-Paul; Leroy, Eric Maurice

    2017-06-01

    Rift Valley fever (RVF) is a zoonotic disease, which caused several epidemics in humans in many countries of Africa. Using an inhibition enzyme-linked immunosorbent assay (ELISA), real-time reverse transcription PCR, and nested one-step reverse transcription PCR, we conducted a cross-sectional study in populations of sheep and goats from the Mongo County in 2014 to determine the circulation of the Rift Valley fever virus (RVFV) in small ruminants from this area. From a total of 201 small ruminants (95 sheep and 106 goats), the overall IgG seroprevalence against the RVFV was 6.47% (13/201). No RVFV RNA was detected in the animal plasmas. Logistic regression analysis showed that age, species, sex, and locality were not the significant risk factors. The findings of this study highlight the risk of RVF for domestic ruminants bred in this region and for the human rural population living in contact with these animals and they emphasize the need to develop adequate control measures to limit this threat.

  15. Evaluation of Fluorescence Microsphere Immunoassay for the Detection of Antibodies to Rift Valley Fever Nucleocapsid Protein and Glycoproteins

    USDA-ARS?s Scientific Manuscript database

    Rift Valley Fever virus (RVFV) is a zoonotic virus that infects ruminants including cattle, sheep, goats, camels and buffalo. Multiplexing diagnostic assays that can simultaneously detect antibodies against multiple RVFV antigens offer a high throughput test for disease surveillance and vaccine eva...

  16. Serologic evidence of exposure to Rift Valley fever virus detected in Tunisia

    PubMed Central

    Bosworth, A.; Ghabbari, T.; Dowall, S.; Varghese, A.; Fares, W.; Hewson, R.; Zhioua, E.; Chakroun, M.; Tiouiri, H.; Ben Jemaa, M.; Znazen, A.; Letaief, A.

    2015-01-01

    Rift Valley fever virus (RVFv) is capable of causing dramatic outbreaks amongst economically important animal species and is capable of causing severe symptoms and mortality in humans. RVFv is known to circulate widely throughout East Africa; serologic evidence of exposure has also been found in some northern African countries, including Mauritania. This study aimed to ascertain whether RVFv is circulating in regions beyond its known geographic range. Samples from febrile patients (n = 181) and nonfebrile healthy agricultural and slaughterhouse workers (n = 38) were collected during the summer of 2014 and surveyed for exposure to RVFv by both serologic tests and PCR. Of the 219 samples tested, 7.8% of nonfebrile participants showed immunoglobulin G reactivity to RVFv nucleoprotein and 8.3% of febrile patients showed immunoglobulin M reactivity, with the latter samples indicating recent exposure to the virus. Our results suggest an active circulation of RVFv and evidence of human exposure in the population of Tunisia. PMID:26740887

  17. Rift Valley Fever Risk Map Model and Seroprevalence in Selected Wild Ungulates and Camels from Kenya

    PubMed Central

    Ruder, Mark G.; Linthicum, Kenneth J.; Anyamba, Assaf; Small, Jennifer L.; Tucker, Compton J.; Ateya, Leonard O.; Oriko, Abuu A.; Gacheru, Stephen; Wilson, William C.

    2013-01-01

    Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based on key environmental indicators that precede Rift Valley fever (RVF) epizootics and epidemics. Although the timing and locations of human case data from the 2006–2007 RVF outbreak in Kenya have been compared to risk zones flagged by the model, seroprevalence of RVF antibodies in wildlife has not yet been analyzed in light of temporal and spatial predictions of RVF activity. Primarily wild ungulate serum samples from periods before, during, and after the 2006–2007 RVF epizootic were analyzed for the presence of RVFV IgM and/or IgG antibody. Results show an increase in RVF seropositivity from samples collected in 2007 (31.8%), compared to antibody prevalence observed from 2000–2006 (3.3%). After the epizootic, average RVF seropositivity diminished to 5% in samples collected from 2008–2009. Overlaying maps of modeled RVF risk assessments with sampling locations indicated positive RVF serology in several species of wild ungulate in or near areas flagged as being at risk for RVF. Our results establish the need to continue and expand sero-surveillance of wildlife species Kenya and elsewhere in the Horn of Africa to further calibrate and improve the RVF risk model, and better understand the dynamics of RVFV transmission. PMID:23840512

  18. Rift Valley Fever Risk Map Model and Seroprevalence in Selected Wild Ungulates and Camels from Kenya

    NASA Technical Reports Server (NTRS)

    Britch, Seth C.; Binepal, Yatinder S.; Ruder, Mark G.; Kariithi, Henry M.; Linthicum, Kenneth J.; Anyamba, Assaf; Small, Jennifer L.; Tucker, Compton J.; Ateya, Leonard O.; Oriko, Abuu A.; hide

    2013-01-01

    Since the first isolation of Rift Valley fever virus (RVFV) in the 1930s, there have been multiple epizootics and epidemics in animals and humans in sub-Saharan Africa. Prospective climate-based models have recently been developed that flag areas at risk of RVFV transmission in endemic regions based on key environmental indicators that precede Rift Valley fever (RVF) epizootics and epidemics. Although the timing and locations of human case data from the 2006-2007 RVF outbreak in Kenya have been compared to risk zones flagged by the model, seroprevalence of RVF antibodies in wildlife has not yet been analyzed in light of temporal and spatial predictions of RVF activity. Primarily wild ungulate serum samples from periods before, during, and after the 2006-2007 RVF epizootic were analyzed for the presence of RVFV IgM and/or IgG antibody. Results show an increase in RVF seropositivity from samples collected in 2007 (31.8%), compared to antibody prevalence observed from 2000-2006 (3.3%). After the epizootic, average RVF seropositivity diminished to 5% in samples collected from 2008-2009. Overlaying maps of modeled RVF risk assessments with sampling locations indicated positive RVF serology in several species of wild ungulate in or near areas flagged as being at risk for RVF. Our results establish the need to continue and expand sero-surveillance of wildlife species Kenya and elsewhere in the Horn of Africa to further calibrate and improve the RVF risk model, and better understand the dynamics of RVFV transmission.

  19. Rift Valley Fever Outbreak in Livestock in Kenya, 2006–2007

    PubMed Central

    Munyua, Peninah; Murithi, Rees M.; Wainwright, Sherrilyn; Githinji, Jane; Hightower, Allen; Mutonga, David; Macharia, Joseph; Ithondeka, Peter M.; Musaa, Joseph; Breiman, Robert F.; Bloland, Peter; Njenga, M. Kariuki

    2010-01-01

    We analyzed the extent of livestock involvement in the latest Rift Valley fever (RVF) outbreak in Kenya that started in December 2006 and continued until June 2007. When compared with previous RVF outbreaks in the country, the 2006–07 outbreak was the most extensive in cattle, sheep, goats, and camels affecting thousands of animals in 29 of 69 administrative districts across six of the eight provinces. This contrasted with the distribution of approximately 700 human RVF cases in the country, where over 85% of these cases were located in four districts; Garissa and Ijara districts in Northeastern Province, Baringo district in Rift Valley Province, and Kilifi district in Coast Province. Analysis of livestock and human data suggests that livestock infections occur before virus detection in humans, as supported by clustering of human RVF cases around livestock cases in Baringo district. The highest livestock morbidity and mortality rates were recorded in Garissa and Baringo districts, the same districts that recorded a high number of human cases. The districts that reported RVF in livestock for the first time in 2006/07 included Kitui, Tharaka, Meru South, Meru central, Mwingi, Embu, and Mbeere in Eastern Province, Malindi and Taita taveta in Coast Province, Kirinyaga and Murang'a in Central Province, and Baringo and Samburu in Rift Valley Province, indicating that the disease was occurring in new regions in the country. PMID:20682907

  20. Rift Valley Fever: An Emerging Mosquito-Borne Disease.

    PubMed

    Linthicum, Kenneth J; Britch, Seth C; Anyamba, Assaf

    2016-01-01

    Rift Valley fever (RVF), an emerging mosquito-borne zoonotic infectious viral disease caused by the RVF virus (RVFV) (Bunyaviridae: Phlebovirus), presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant potential for international spread and use in bioterrorism. RVFV has caused large, devastating periodic epizootics and epidemics in Africa over the past ∼60 years, with severe economic and nutritional impacts on humans from illness and livestock loss. In the past 15 years alone, RVFV caused tens of thousands of human cases, hundreds of human deaths, and more than 100,000 domestic animal deaths. Cattle, sheep, goats, and camels are particularly susceptible to RVF and serve as amplifying hosts for the virus. This review highlights recent research on RVF, focusing on vectors and their ecology, transmission dynamics, and use of environmental and climate data to predict disease outbreaks. Important directions for future research are also discussed.

  1. Prediction, Assessment of the Rift Valley Fever Activity in East and Southern Africa 2006–2008 and Possible Vector Control Strategies

    PubMed Central

    Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer; Britch, Seth C.; Pak, Edwin; de La Rocque, Stephane; Formenty, Pierre; Hightower, Allen W.; Breiman, Robert F.; Chretien, Jean-Paul; Tucker, Compton J.; Schnabel, David; Sang, Rosemary; Haagsma, Karl; Latham, Mark; Lewandowski, Henry B.; Magdi, Salih Osman; Mohamed, Mohamed Ally; Nguku, Patrick M.; Reynes, Jean-Marc; Swanepoel, Robert

    2010-01-01

    Historical outbreaks of Rift Valley fever (RVF) since the early 1950s have been associated with cyclical patterns of the El Niño/Southern Oscillation (ENSO) phenomenon, which results in elevated and widespread rainfall over the RVF endemic areas of Africa. Using satellite measurements of global and regional elevated sea surface temperatures, elevated rainfall, and satellite derived-normalized difference vegetation index data, we predicted with lead times of 2–4 months areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa, Sudan, and Southern Africa at different time periods from September 2006 to March 2008. Predictions were confirmed by entomological field investigations of virus activity and by reported cases of RVF in human and livestock populations. This represents the first series of prospective predictions of RVF outbreaks and provides a baseline for improved early warning, control, response planning, and mitigation into the future. PMID:20682905

  2. Seroepidemiological Survey of Rift Valley Fever Virus in Ruminants in Garissa, Kenya.

    PubMed

    Nanyingi, Mark O; Muchemi, Gerald M; Thumbi, Samuel M; Ade, Fredrick; Onyango, Clayton O; Kiama, Stephen G; Bett, Bernard

    2017-02-01

    Rift Valley fever (RVF) is a vector-borne zoonotic disease caused by phlebovirus in the family Bunyaviridae. In Kenya, major outbreaks occurred in 1997-1998 and 2006-2007 leading to human deaths, huge economic losses because of livestock morbidity, mortality, and restrictions on livestock trade. This study was conducted to determine RVF seroprevalence in cattle, sheep, and goats during an interepidemic period in Garissa County in Kenya. In July 2013, we performed a cross-sectional survey and sampled 370 ruminants from eight RVF-prone areas of Garissa County. Rift Valley fever virus (RVFV) antibodies were detected using a multispecies competitive enzyme-linked immunosorbent assay. Mixed effect logistic regression models were used to determine the association between RVF seropositivity and species, sex, age, and location of the animals. A total of 271 goats, 87 sheep, and 12 cattle were sampled and the overall immunoglobulin G seroprevalence was 27.6% (95% CI [23-32.1]). Sheep, cattle, and goats had seroprevalences of 32.2% (95% CI [20.6-31]), 33.3% (95% CI [6.7-60]), and 25.8% (95% CI [22.4-42]), respectively. Seropositivity in males was 31.8% (95% CI [22.2-31.8]), whereas that of females was 27% (95% CI [18.1-45.6]). The high seroprevalence suggests RVFV circulation in domestic ruminants in Garissa and may be indicative of a subclinal infection. These findings provide evidence of RVF disease status that will assist decision-makers to flag areas of high risk of RVF outbreaks and prioritize the implementation of timely and cost-effective vaccination programs.

  3. Mouse model for the Rift Valley fever virus MP12 strain infection.

    PubMed

    Lang, Yuekun; Henningson, Jamie; Jasperson, Dane; Li, Yonghai; Lee, Jinhwa; Ma, Jingjiao; Li, Yuhao; Cao, Nan; Liu, Haixia; Wilson, William; Richt, Juergen; Ruder, Mark; McVey, Scott; Ma, Wenjun

    2016-11-15

    Rift Valley fever virus (RVFV), a Category A pathogen and select agent, is the causative agent of Rift Valley fever. To date, no fully licensed vaccine is available in the U.S. for human or animal use and effective antiviral drugs have not been identified. The RVFV MP12 strain is conditionally licensed for use for veterinary purposes in the U.S. which was excluded from the select agent rule of Health and Human Services and the U.S. Department of Agriculture. The MP12 vaccine strain is commonly used in BSL-2 laboratories that is generally not virulent in mice. To establish a small animal model that can be used in a BSL-2 facility for antiviral drug development, we investigated susceptibility of six mouse strains (129S6/SvEv, STAT-1 KO, 129S1/SvlmJ, C57BL/6J, NZW/LacJ, BALB/c) to the MP12 virus infection via an intranasal inoculation route. Severe weight loss, obvious clinical and neurologic signs, and 50% mortality was observed in the STAT-1 KO mice, whereas the other 5 mouse strains did not display obvious and/or severe disease. Virus replication and histopathological lesions were detected in brain and liver of MP12-infected STAT-1 KO mice that developed the acute-onset hepatitis and delayed-onset encephalitis. In conclusion, the STAT-1 KO mouse strain is susceptible to MP12 virus infection, indicating that it can be used to investigate RVFV antivirals in a BSL-2 environment. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Development of a Rift Valley fever real-time RT-PCR assay that can detect all three genome segments

    USDA-ARS?s Scientific Manuscript database

    Outbreaks of Rift Valley fever in Kenya, Madagascar, Mauritania, and South Africa had devastating effects on livestock and human health. In addition, this disease is a food security issue for endemic countries. There is growing concern for the potential introduction of RVF into non-endemic countries...

  5. Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies

    PubMed Central

    Scoglio, Caterina M.

    2016-01-01

    Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States. PMID:27662585

  6. Biologically Informed Individual-Based Network Model for Rift Valley Fever in the US and Evaluation of Mitigation Strategies.

    PubMed

    Scoglio, Caterina M; Bosca, Claudio; Riad, Mahbubul H; Sahneh, Faryad D; Britch, Seth C; Cohnstaedt, Lee W; Linthicum, Kenneth J

    Rift Valley fever (RVF) is a zoonotic disease endemic in sub-Saharan Africa with periodic outbreaks in human and animal populations. Mosquitoes are the primary disease vectors; however, Rift Valley fever virus (RVFV) can also spread by direct contact with infected tissues. The transmission cycle is complex, involving humans, livestock, and multiple species of mosquitoes. The epidemiology of RVFV in endemic areas is strongly affected by climatic conditions and environmental variables. In this research, we adapt and use a network-based modeling framework to simulate the transmission of RVFV among hypothetical cattle operations in Kansas, US. Our model considers geo-located livestock populations at the individual level while incorporating the role of mosquito populations and the environment at a coarse resolution. Extensive simulations show the flexibility of our modeling framework when applied to specific scenarios to quantitatively evaluate the efficacy of mosquito control and livestock movement regulations in reducing the extent and intensity of RVF outbreaks in the United States.

  7. The first imported case of Rift Valley fever in China reveals a genetic reassortment of different viral lineages.

    PubMed

    Liu, Jingyuan; Sun, Yulan; Shi, Weifeng; Tan, Shuguang; Pan, Yang; Cui, Shujuan; Zhang, Qingchao; Dou, Xiangfeng; Lv, Yanning; Li, Xinyu; Li, Xitai; Chen, Lijuan; Quan, Chuansong; Wang, Qianli; Zhao, Yingze; Lv, Qiang; Hua, Wenhao; Zeng, Hui; Chen, Zhihai; Xiong, Haofeng; Jiang, Chengyu; Pang, Xinghuo; Zhang, Fujie; Liang, Mifang; Wu, Guizhen; Gao, George F; Liu, William J; Li, Ang; Wang, Quanyi

    2017-01-18

    We report the first imported case of Rift Valley fever (RVF) in China. The patient returned from Angola, a non-epidemic country, with an infection of a new reassortant from different lineages of Rift Valley fever viruses (RVFVs). The patient developed multiorgan dysfunction and gradually recovered with continuous renal replacement therapy and a short regimen of methylprednisolone treatment. The disordered cytokines and chemokines in the plasma of the patient revealed hypercytokinemia, but the levels of protective cytokines were low upon admission and fluctuated as the disease improved. Whole-genome sequencing and phylogenetic analysis revealed that the imported strain was a reassortant comprising the L and M genes from lineage E and the S gene from lineage A. This case highlights that RVFV had undergone genetic reassortment, which could potentially alter its biological properties, cause large outbreaks and pose a serious threat to global public health as well as the livestock breeding industry.

  8. Rift Valley fever virus NS{sub S} gene expression correlates with a defect in nuclear mRNA export

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

    Copeland, Anna Maria; Van Deusen, Nicole M.; Schmaljohn, Connie S., E-mail: Connie.s.schmaljohn.civ@mail.mil

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NS{sub S} gene, but not the N, G{sub N} or NS{sub M} genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NS{sub S}, confirming that expression of NS{sub S} is likely responsible for this phenomenon. - Highlights: • Riftmore » Valley fever virus (RVFV) infection alters the localization of host mRNA. • mRNA accumulates in the nuclei of RVFV-infected but not mock-infected cells. • NS{sub S} is likely responsible for mRNA relocalization to the nucleus.« less

  9. Potential for Stable Flies and House Flies (Diptera: Muscidae) to Transmit Rift Valley Fever Virus

    DTIC Science & Technology

    2010-01-01

    14. ABSTRACT Rift Valley fever ( RVF ), a disease of ruminants and humans, has been responsible for large outbreaks in Africa that have resulted in...regions. Although RVF virus (RVFV) is normally transmitted by mosquitoes, we wanted to determine the potential for this virus to replicate in 2 of...of a RVF outbreak. Other Stomoxys species present in Africa and elsewhere may also play similar roles. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION

  10. Rift Valley fever virus structural and non-structural proteins: Recombinant protein expression and immunoreactivity against antisera from sheep

    USDA-ARS?s Scientific Manuscript database

    The Rift Valley fever virus (RVFV) encodes structural proteins, nucleoprotein (N), N-terminus glycoprotein (Gn), C-terminus glycoprotein (Gc) and L protein, 78-kDa and non-structural proteins NSm and NSs. Using the baculovirus system we expressed the full-length coding sequence of N, NSs, NSm, Gc an...

  11. Remote Sensing Contributions to Prediction and Risk Assessment of Natural Disasters Caused by Large Scale Rift Valley Fever Outbreaks

    NASA Technical Reports Server (NTRS)

    Anyamba, Assaf; Linthicum, Kenneth J.; Small, Jennifer; Britch, S. C.; Tucker, C. J.

    2012-01-01

    Remotely sensed vegetation measurements for the last 30 years combined with other climate data sets such as rainfall and sea surface temperatures have come to play an important role in the study of the ecology of arthropod-borne diseases. We show that epidemics and epizootics of previously unpredictable Rift Valley fever are directly influenced by large scale flooding associated with the El Ni o/Southern Oscillation. This flooding affects the ecology of disease transmitting arthropod vectors through vegetation development and other bioclimatic factors. This information is now utilized to monitor, model, and map areas of potential Rift Valley fever outbreaks and is used as an early warning system for risk reduction of outbreaks to human and animal health, trade, and associated economic impacts. The continuation of such satellite measurements is critical to anticipating, preventing, and managing disease epidemics and epizootics and other climate-related disasters.

  12. Innate Immune Response to Rift Valley Fever Virus in Goats

    PubMed Central

    Nfon, Charles K.; Marszal, Peter; Zhang, Shunzhen; Weingartl, Hana M.

    2012-01-01

    Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings. PMID:22545170

  13. Innate immune response to Rift Valley fever virus in goats.

    PubMed

    Nfon, Charles K; Marszal, Peter; Zhang, Shunzhen; Weingartl, Hana M

    2012-01-01

    Rift Valley fever (RVF), a re-emerging mosquito-borne disease of ruminants and man, was endemic in Africa but spread to Saudi Arabia and Yemen, meaning it could spread even further. Little is known about innate and cell-mediated immunity to RVF virus (RVFV) in ruminants, which is knowledge required for adequate vaccine trials. We therefore studied these aspects in experimentally infected goats. We also compared RVFV grown in an insect cell-line and that grown in a mammalian cell-line for differences in the course of infection. Goats developed viremia one day post infection (DPI), which lasted three to four days and some goats had transient fever coinciding with peak viremia. Up to 4% of peripheral blood mononuclear cells (PBMCs) were positive for RVFV. Monocytes and dendritic cells in PBMCs declined possibly from being directly infected with virus as suggested by in vitro exposure. Infected goats produced serum IFN-γ, IL-12 and other proinflammatory cytokines but not IFN-α. Despite the lack of IFN-α, innate immunity via the IL-12 to IFN-γ circuit possibly contributed to early protection against RVFV since neutralising antibodies were detected after viremia had cleared. The course of infection with insect cell-derived RVFV (IN-RVFV) appeared to be different from mammalian cell-derived RVFV (MAM-RVFV), with the former attaining peak viremia faster, inducing fever and profoundly affecting specific immune cell subpopulations. This indicated possible differences in infections of ruminants acquired from mosquito bites relative to those due to contact with infectious material from other animals. These differences need to be considered when testing RVF vaccines in laboratory settings.

  14. Molecular biology and genetic diversity of Rift Valley fever virus.

    PubMed

    Ikegami, Tetsuro

    2012-09-01

    Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever (RVF), a mosquito-borne disease of ruminant animals and humans. The generation of a large sequence database has facilitated studies of the evolution and spread of the virus. Bayesian analyses indicate that currently circulating strains of RVFV are descended from an ancestral species that emerged from a natural reservoir in Africa when large-scale cattle and sheep farming were introduced during the 19th century. Viruses descended from multiple lineages persist in that region, through infection of reservoir animals and vertical transmission in mosquitoes, emerging in years of heavy rainfall to cause epizootics and epidemics. On a number of occasions, viruses from these lineages have been transported outside the enzootic region through the movement of infected animals or mosquitoes, triggering outbreaks in countries such as Egypt, Saudi Arabia, Mauritania and Madagascar, where RVF had not previously been seen. Such viruses could potentially become established in their new environments through infection of wild and domestic ruminants and other animals and vertical transmission in local mosquito species. Despite their extensive geographic dispersion, all strains of RVFV remain closely related at the nucleotide and amino acid level. The high degree of conservation of genes encoding the virion surface glycoproteins suggests that a single vaccine should protect against all currently circulating RVFV strains. Similarly, preservation of the sequence of the RNA-dependent RNA polymerase across viral lineages implies that antiviral drugs targeting the enzyme should be effective against all strains. Researchers should be encouraged to collect additional RVFV isolates and perform whole-genome sequencing and phylogenetic analysis, so as to enhance our understanding of the continuing evolution of this important virus. This review forms part of a series

  15. Protein Phosphatase-1 regulates Rift Valley fever virus replication.

    PubMed

    Baer, Alan; Shafagati, Nazly; Benedict, Ashwini; Ammosova, Tatiana; Ivanov, Andrey; Hakami, Ramin M; Terasaki, Kaori; Makino, Shinji; Nekhai, Sergei; Kehn-Hall, Kylene

    2016-03-01

    Rift Valley fever virus (RVFV), genus Phlebovirus family Bunyaviridae, is an arthropod-borne virus endemic throughout sub-Saharan Africa. Recent outbreaks have resulted in cyclic epidemics with an increasing geographic footprint, devastating both livestock and human populations. Despite being recognized as an emerging threat, relatively little is known about the virulence mechanisms and host interactions of RVFV. To date there are no FDA approved therapeutics or vaccines for RVF and there is an urgent need for their development. The Ser/Thr protein phosphatase 1 (PP1) has previously been shown to play a significant role in the replication of several viruses. Here we demonstrate for the first time that PP1 plays a prominent role in RVFV replication early on during the viral life cycle. Both siRNA knockdown of PP1α and a novel PP1-targeting small molecule compound 1E7-03, resulted in decreased viral titers across several cell lines. Deregulation of PP1 was found to inhibit viral RNA production, potentially through the disruption of viral RNA transcript/protein interactions, and indicates a potential link between PP1α and the viral L polymerase and nucleoprotein. These results indicate that PP1 activity is important for RVFV replication early on during the viral life cycle and may prove an attractive therapeutic target. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Rift Valley fever virus infection in golden Syrian hamsters.

    PubMed

    Scharton, Dionna; Van Wettere, Arnaud J; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Siddharthan, Venkatraman; Gowen, Brian B

    2015-01-01

    Rift Valley fever virus (RVFV) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

  17. Interim Report on SNP analysis and forensic microarray probe design for South American hemorrhagic fever viruses, tick-borne encephalitis virus, henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever viruses, Rift Valley fever

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

    Jaing, C; Gardner, S

    The goal of this project is to develop forensic genotyping assays for select agent viruses, enhancing the current capabilities for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the whole genomemore » wide SNP analysis and microarray probe design for forensics characterization of South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.« less

  18. The role of signal transducer and activator of transcription 3 in Rift Valley fever virus infection

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

    Pinkham, Chelsea; An, Soyeon; Lundberg, Lindsay

    Rift Valley fever (RVF) is a zoonotic disease that can cause severe illness in humans and livestock, triggering spontaneous abortion in almost 100% of pregnant ruminants. In this study, we demonstrate that signal transducer and activator of transcription 3 (STAT3) is phosphorylated on its conserved tyrosine residue (Y705) following RVFV infection. This phosphorylation was dependent on a major virulence factor, the viral nonstructural protein NSs. Loss of STAT3 had little effect on viral replication, but rather resulted in cells being more susceptible to RVFV-induced cell death. Phosphorylated STAT3 translocated to the nucleus, coinciding with inhibition of fos, jun, and nr4a2more » gene expression, and the presence of STAT3 and NSs at the nr4a2 promoter. NSs was found predominantly in the cytoplasm of STAT3 null cells, indicating that STAT3 influences NSs nuclear localization. Collectively, these data demonstrate that STAT3 functions in a pro-survival capacity through modulation of NSs localization. - Highlights: • STAT3 is phosphorylated on tyrosine residue 705 following RVFV infection. • Phosphorylation of STAT3 was dependent on the viral protein NSs. • STAT3 -/- MEFs were more susceptible to RVFV-induced cell death. • Loss of STAT3 led to an increase in pro-apoptotic gene expression. • STAT3 functions in a pro-survival capacity by modulation of NSs localization.« less

  19. Efficacy of a recombinant Rift Valley fever virus MP-12 with NSm deletion as a vaccine candidate in sheep

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family and Phlebovirus genus, causes RVF, a disease of ruminants and man, endemic in Sub-Saharan African countries. However, outbreaks in Yemen and Saudi Arabia demonstrate the ability for RVFV to spread into virgin territory...

  20. A dynamic, climate-driven model of Rift Valley fever.

    PubMed

    Leedale, Joseph; Jones, Anne E; Caminade, Cyril; Morse, Andrew P

    2016-03-31

    Outbreaks of Rift Valley fever (RVF) in eastern Africa have previously occurred following specific rainfall dynamics and flooding events that appear to support the emergence of large numbers of mosquito vectors. As such, transmission of the virus is considered to be sensitive to environmental conditions and therefore changes in climate can impact the spatiotemporal dynamics of epizootic vulnerability. Epidemiological information describing the methods and parameters of RVF transmission and its dependence on climatic factors are used to develop a new spatio-temporal mathematical model that simulates these dynamics and can predict the impact of changes in climate. The Liverpool RVF (LRVF) model is a new dynamic, process-based model driven by climate data that provides a predictive output of geographical changes in RVF outbreak susceptibility as a result of the climate and local livestock immunity. This description of the multi-disciplinary process of model development is accessible to mathematicians, epidemiological modellers and climate scientists, uniting dynamic mathematical modelling, empirical parameterisation and state-of-the-art climate information.

  1. Rift Valley fever on the east coast of Madagascar.

    PubMed

    Morvan, J; Saluzzo, J F; Fontenille, D; Rollin, P E; Coulanges, P

    1991-01-01

    In March 1990, a Rift Valley fever virus (RVFV) outbreak was suspected in the district of Fenerive on the east coast of Madagascar after an abnormally high incidence of abortions and disease in livestock. Sera from humans and cattle were tested for RVFV antibodies by immunofluorescence assay (IFA) and ELISA-IgM capture. Sera and mosquitoes collected in the same area were tested for virus isolation by tissue culture and suckling mouse intracerebral inoculation, and for antigen detection by an ELISA antigen capture assay. Among cattle from the area, RVFV antibody prevalence was 58.6% by IFA and 29.6% by ELISA-IgM. In contrast, human populations in the same area had a lower RVFV antibody prevalence, with 8.01% IFA and 5.4% IgM-positive sera. No RVFV antigen was detected and virus isolation was unsuccessful from the sera and mosquito pools tested. Different hypotheses concerning the emergence and diffusion of RVFV in this area and the occurrence of the outbreak are discussed.

  2. Rift Valley fever trasmission dynamics described by compartmental models.

    PubMed

    Danzetta, Maria Luisa; Bruno, Rossana; Sauro, Francesca; Savini, Lara; Calistri, Paolo

    2016-11-01

    Rift Valley fever (RVF) is one of the most important zoonotic Transboundary Animal Diseases able to cross international borders and cause devastating effect on animal health and food security. Climate changes and the presence of competent vectors in the most of the current RVF-free temperate countries strongly support the inclusion of RVF virus (RVFV) among the most significant emerging viral threats for public and animal health. The transmission of RVFV is driven by complex eco-climatic factors making the epidemiology of RVF infection difficult to study and to understand. Mathematical, statistical and spatial models are often used to explain the mechanisms underlying these biological processes, providing new and effective tools to plan measures for public health protection. In this paper we performed a systematic literature review on RVF published papers with the aim of identifying and describing the most recent papers developing compartmental models for the study of RVFV transmission dynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Comparison of Rift Valley fever virus and MP-12 replication in domestic livestock and North American wildlife cell lines.

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) is a mosquito-transmitted pathogen that primarily affects livestock, but can also cause mild to fatal disease in humans. Currently, there is no approved vaccine for use in the United States if it were introduced. Domestic goats, sheep and cattle are susceptible hosts ...

  4. Rift Valley Fever Outbreaks in Mauritania and Related Environmental Conditions

    PubMed Central

    Caminade, Cyril; Ndione, Jacques A.; Diallo, Mawlouth; MacLeod, Dave A.; Faye, Ousmane; Ba, Yamar; Dia, Ibrahima; Morse, Andrew P.

    2014-01-01

    Four large outbreaks of Rift Valley Fever (RVF) occurred in Mauritania in 1998, 2003, 2010 and 2012 which caused lots of animal and several human deaths. We investigated rainfall and vegetation conditions that might have impacted on RVF transmission over the affected regions. Our results corroborate that RVF transmission generally occurs during the months of September and October in Mauritania, similarly to Senegal. The four outbreaks were preceded by a rainless period lasting at least a week followed by heavy precipitation that took place during the second half of the rainy season. First human infections were generally reported three to five weeks later. By bridging the gap between meteorological forecasting centers and veterinary services, an early warning system might be developed in Senegal and Mauritania to warn decision makers and health services about the upcoming RVF risk. PMID:24413703

  5. Rift Valley fever virus incorporates the 78kDa glycoprotein into virions matured in C6/36 2 mosquito cells

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV), genus Phlebovirus, family Bunyaviridae is a zoonotic arthropod-borne virus able to transition between distant host species, causing potentially severe disease in humans and ruminants. Viral proteins are encoded by three genomic segments, with the medium M segment codi...

  6. Remote Sensing Contributions to Prediction and Risk Assessment of Natural Diasters Caused by Large Scale Rift Valley fever Outbreaks

    USDA-ARS?s Scientific Manuscript database

    Remotely sensed vegetation measurements for the last 30 years combined with other climate data sets such as rainfall and sea surface temperatures have come to play an important role in the study of the ecology of vector-borne diseases. We show that episodic outbreaks of Rift Valley fever are influen...

  7. Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

    PubMed

    Rissmann, M; Ulrich, R; Schröder, C; Hammerschmidt, B; Hanke, D; Mroz, C; Groschup, M H; Eiden, M

    2017-01-23

    Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Development and validation of serological assays for viral hemorrhagic fevers and determination of the prevalence of Rift Valley fever in Borno State, Nigeria.

    PubMed

    Bukbuk, David Nadeba; Fukushi, Shuetsu; Tani, Hideki; Yoshikawa, Tomoki; Taniguchi, Satoshi; Iha, Koichiro; Fukuma, Aiko; Shimojima, Masayuki; Morikawa, Shigeru; Saijo, Masayuki; Kasolo, Francis; Baba, Saka Saheed

    2014-12-01

    Rift Valley fever (RVF) is endemic to the tropical regions of eastern and southern Africa. The seroprevalence of RVF was investigated among the human population in Borno State, Nigeria to determine the occurrence of the disease in the study area in comparison with that of Lassa fever and Crimean-Congo Hemorrhagic fever. Recombinant nucleoprotein (rNP)-based IgG-ELISAs for the detection of serum antibodies against RVF virus (RVFV), Lassa fever virus (LASV), and Crimean-Congo hemorrhagic fever virus (CCHFV) were used to test human sera in Borno State, Nigeria. The presence of neutralizing antibody against the RVFV-glycoprotein-bearing vesicular stomatitis virus pseudotype (RVFVpv) was also determined in the human sera. Of the 297 serum samples tested, 42 (14.1%) were positive for the presence of RVFV-IgG and 22 (7.4%) and 7 (2.4%) of the serum samples were positive for antibodies against LASV and CCHFV, respectively. There was a positive correlation between the titers of neutralizing antibodies obtained using RVFVpv and those obtained using the conventional neutralization assay with the attenuated RVFV-MP12 strain. The seroprevalence of RVF was significantly higher than that of LASV and CCHF in Borno State, Nigeria. The RVFVpv-based neutralization assay developed in this study has the potential to replace the traditional assays based on live viruses for the diagnosis and seroepidemiological studies of RVF. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Spectrum of Rift Valley Fever Virus Transmission in Kenya: Insights from three Distinct Regions

    PubMed Central

    Labeaud, A. Desiree; Ochiai, Yoshitsugu; Peters, C.J.; Muchiri, Eric M.; King, Charles H.

    2008-01-01

    Rift Valley fever virus (RVFV) is an emerging pathogen that maintains high biodefense priority based on its threat to livestock, its ability to cause human hemorrhagic fever, and its potential for aerosol spread. To define the range of human transmission during inter-epidemic and epidemic periods in Kenya, we tested archived sera from defined populations (N = 1,263) for anti-RVFV IgG by ELISA and plaque reduction neutralization testing. RVFV seroprevalence was 10.8% overall and varied significantly by location, sex, and age. In NW Kenya, high seroprevalence among those born before 1980 indicates that an undetected epidemic may have occurred then. Seroconversion documented in highland areas suggests previously unsuspected inter-epidemic transmission. RVFV seroprevalence is strikingly high in certain Kenyan areas, suggesting endemic transmission patterns that may preclude accurate estimation of regional acute outbreak incidence. The extent of both epidemic and inter-epidemic RVFV transmission in Kenya is greater than previously documented. PMID:17488893

  10. Curcumin Inhibits Rift Valley Fever Virus Replication in Human Cells*

    PubMed Central

    Narayanan, Aarthi; Kehn-Hall, Kylene; Senina, Svetlana; Lundberg, Lindsay; Van Duyne, Rachel; Guendel, Irene; Das, Ravi; Baer, Alan; Bethel, Laura; Turell, Michael; Hartman, Amy Lynn; Das, Bhaskar; Bailey, Charles; Kashanchi, Fatah

    2012-01-01

    Rift Valley fever virus (RVFV) is an arbovirus that is classified as a select agent, an emerging infectious virus, and an agricultural pathogen. Understanding RVFV-host interactions is imperative to the design of novel therapeutics. Here, we report that an infection by the MP-12 strain of RVFV induces phosphorylation of the p65 component of the NFκB cascade. We demonstrate that phosphorylation of p65 (serine 536) involves phosphorylation of IκBα and occurs through the classical NFκB cascade. A unique, low molecular weight complex of the IKK-β subunit can be observed in MP-12-infected cells, which we have labeled IKK-β2. The IKK-β2 complex retains kinase activity and phosphorylates an IκBα substrate. Inhibition of the IKK complex using inhibitors impairs viral replication, thus alluding to the requirement of an active IKK complex to the viral life cycle. Curcumin strongly down-regulates levels of extracellular infectious virus. Our data demonstrated that curcumin binds to and inhibits kinase activity of the IKK-β2 complex in infected cells. Curcumin partially exerts its inhibitory influence on RVFV replication by interfering with IKK-β2-mediated phosphorylation of the viral protein NSs and by altering the cell cycle of treated cells. Curcumin also demonstrated efficacy against ZH501, the fully virulent version of RVFV. Curcumin treatment down-regulated viral replication in the liver of infected animals. Our data point to the possibility that RVFV infection may result in the generation of novel versions of host components (such as IKK-β2) that, by virtue of altered protein interaction and function, qualify as unique therapeutic targets. PMID:22847000

  11. Climate-disease connections: Rift Valley Fever in Kenya

    NASA Technical Reports Server (NTRS)

    Anyamba, A.; Linthicum, K. J.; Tucker, C. J.

    2001-01-01

    All known Rift Valley fever(RVF) outbreaks in Kenya from 1950 to 1998 followed periods of abnormally high rainfall. On an interannual scale, periods of above normal rainfall in East Africa are associated with the warm phase of the El Nino/Southern Oscillation (ENSO) phenomenon. Anomalous rainfall floods mosquito-breeding habitats called dambos, which contain transovarially infected mosquito eggs. The eggs hatch Aedes mosquitoes that transmit the RVF virus preferentially to livestock and to humans as well. Analysis of historical data on RVF outbreaks and indicators of ENSO (including Pacific and Indian Ocean sea surface temperatures and the Southern Oscillation Index) indicates that more than three quarters of the RVF outbreaks have occurred during warm ENSO event periods. Mapping of ecological conditions using satellite normalized difference vegetation index (NDVI) data show that areas where outbreaks have occurred during the satellite recording period (1981-1998) show anomalous positive departures in vegetation greenness, an indicator of above-normal precipitation. This is particularly observed in arid areas of East Africa, which are predominantly impacted by this disease. These results indicate a close association between interannual climate variability and RVF outbreaks in Kenya.

  12. Climate-disease connections: Rift Valley Fever in Kenya.

    PubMed

    Anyamba, A; Linthicum, K J; Tucker, C J

    2001-01-01

    All known Rift Valley fever(RVF) outbreaks in Kenya from 1950 to 1998 followed periods of abnormally high rainfall. On an interannual scale, periods of above normal rainfall in East Africa are associated with the warm phase of the El Niño/Southern Oscillation (ENSO) phenomenon. Anomalous rainfall floods mosquito-breeding habitats called dambos, which contain transovarially infected mosquito eggs. The eggs hatch Aedes mosquitoes that transmit the RVF virus preferentially to livestock and to humans as well. Analysis of historical data on RVF outbreaks and indicators of ENSO (including Pacific and Indian Ocean sea surface temperatures and the Southern Oscillation Index) indicates that more than three quarters of the RVF outbreaks have occurred during warm ENSO event periods. Mapping of ecological conditions using satellite normalized difference vegetation index (NDVI) data show that areas where outbreaks have occurred during the satellite recording period (1981-1998) show anomalous positive departures in vegetation greenness, an indicator of above-normal precipitation. This is particularly observed in arid areas of East Africa, which are predominantly impacted by this disease. These results indicate a close association between interannual climate variability and RVF outbreaks in Kenya.

  13. Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus.

    PubMed

    Wilson, William C; Davis, A Sally; Gaudreault, Natasha N; Faburay, Bonto; Trujillo, Jessie D; Shivanna, Vinay; Sunwoo, Sun Young; Balogh, Aaron; Endalew, Abaineh; Ma, Wenjun; Drolet, Barbara S; Ruder, Mark G; Morozov, Igor; McVey, D Scott; Richt, Juergen A

    2016-05-23

    Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves.

  14. Factors Associated with Severe Human Rift Valley Fever in Sangailu, Garissa County, Kenya

    PubMed Central

    LaBeaud, A. Desirée; Pfeil, Sarah; Muiruri, Samuel; Dahir, Saidi; Sutherland, Laura J.; Traylor, Zachary; Gildengorin, Ginny; Muchiri, Eric M.; Morrill, John; Peters, C. J.; Hise, Amy G.; Kazura, James W; King, Charles H.

    2015-01-01

    Background Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya. Methodology/Principal Findings: A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13–17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ≤15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93–13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63–26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype. Conclusions/Significance Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision

  15. Development of real-time RT-PCR for the detection of low concentrations of Rift Valley fever virus.

    PubMed

    Maquart, Marianne; Temmam, Sarah; Héraud, Jean-Michel; Leparc-Goffart, Isabelle; Cêtre-Sossah, Catherine; Dellagi, Koussay; Cardinale, Eric; Pascalis, Hervé

    2014-01-01

    In recent years, Madagascar and the Comoros archipelago have been affected by epidemics of Rift Valley fever (RVF), however detection of Rift Valley fever virus (RVFV) in zebu, sheep and goats during the post epidemic periods was frequently unsuccessful. Thus, a highly sensitive real-time RT-PCR assay was developed for the detection of RVFV at low viral loads. A new RVF SYBR Green RT-PCR targeting the M segment was tested on serum from different RVF seronegative ruminant species collected from May 2010 to August 2011 in Madagascar and the Comoros archipelago and compared with a RVF specific quantitative real time RT-PCR technique, which is considered as the reference technique. The specificity was tested on a wide range of arboviruses or other viruses giving RVF similar clinical signs. A total of 38 out of 2756 serum samples tested positive with the new RT-PCR, whereas the reference technique only detected 5 out of the 2756. The described RT-PCR is an efficient diagnostic tool for the investigation of enzootic circulation of the RVF virus. It allows the detection of low viral RNA loads adapted for the investigations of reservoirs or specific epidemiological situations such as inter-epizootic periods. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Risk analysis of inter-species reassortment through a Rift Valley fever phlebovirus MP-12 vaccine strain.

    PubMed

    Ly, Hoai J; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

    2017-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula. The causative agent, Rift Valley fever phlebovirus (RVFV), belongs to the genus Phlebovirus in the family Phenuiviridae and causes high rates of abortions in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral maintenance by mosquito vectors has led to sporadic RVF outbreaks in ruminants and humans in endemic countries, and effective vaccination of animals and humans may minimize the impact of this disease. A live-attenuated MP-12 vaccine strain is one of the best characterized RVFV strains, and was conditionally approved as a veterinary vaccine in the U.S. Live-attenuated RVF vaccines including MP-12 strain may form reassortant strains with other bunyavirus species. This study thus aimed to characterize the occurrence of genetic reassortment between the MP-12 strain and bunyavirus species closely related to RVFV. The Arumowot virus (AMTV) and Gouleako goukovirus (GOLV), are transmitted by mosquitoes in Africa. The results of this study showed that GOLV does not form detectable reassortant strains with the MP-12 strain in co-infected C6/36 cells. The AMTV also did not form any reassortant strains with MP-12 strain in co-infected C6/36 cells, due to the incompatibility among N, L, and Gn/Gc proteins. A lack of reassortant formation could be due to a functional incompatibility of N and L proteins derived from heterologous species, and due to a lack of packaging via heterologous Gn/Gc proteins. The MP-12 strain did, however, randomly exchange L-, M-, and S-segments with a genetic variant strain, rMP12-GM50, in culture cells. The MP-12 strain is thus unlikely to form any reassortant strains with AMTV or GOLV in nature.

  17. Advances in Rift Valley Fever Research: Insights for Disease Prevention

    PubMed Central

    LaBeaud, A. Desiree; Kazura, James W.; King, Charles H.

    2011-01-01

    Purpose of review The purpose of the study was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates. Recent findings RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines. Summary RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority. PMID:20613512

  18. Application of Droplet Digital PCR to Validate Rift Valley Fever Vaccines.

    PubMed

    Ly, Hoai J; Lokugamage, Nandadeva; Ikegami, Tetsuro

    2016-01-01

    Droplet Digital™ polymerase chain reaction (ddPCR™) is a promising technique that quantitates the absolute concentration of nucleic acids in a given sample. This technique utilizes water-in-oil emulsion technology, a system developed by Bio-Rad Laboratories that partitions a single sample into thousands of nanoliter-sized droplets and counts nucleic acid molecules encapsulated in each individual particle as one PCR reaction. This chapter discusses the applications and methodologies of ddPCR for development of Rift Valley fever (RVF) vaccine, using an example that measures RNA copy numbers of a live-attenuated MP-12 vaccine from virus stocks, infected cells, or animal blood. We also discuss how ddPCR detects a reversion mutant of MP-12 from virus stocks accurately. The use of ddPCR improves the quality control of live-attenuated vaccines in the seed lot systems.

  19. Culex pipiens, an Experimental Efficient Vector of West Nile and Rift Valley Fever Viruses in the Maghreb Region

    PubMed Central

    Amraoui, Fadila; Krida, Ghazi; Bouattour, Ali; Rhim, Adel; Daaboub, Jabeur; Harrat, Zoubir; Boubidi, Said-Chawki; Tijane, Mhamed; Sarih, Mhammed; Failloux, Anna-Bella

    2012-01-01

    West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 107.8 and 108.5 plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14–21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology. PMID:22693557

  20. Epidemiologic and clinical aspects of a Rift Valley fever outbreak in humans in Tanzania, 2007.

    PubMed

    Mohamed, Mohamed; Mosha, Fausta; Mghamba, Janeth; Zaki, Sherif R; Shieh, Wun-Ju; Paweska, Janusz; Omulo, Sylvia; Gikundi, Solomon; Mmbuji, Peter; Bloland, Peter; Zeidner, Nordin; Kalinga, Raphael; Breiman, Robert F; Njenga, M Kariuki

    2010-08-01

    In January 2007, an outbreak of Rift Valley fever (RVF) was detected among humans in northern Tanzania districts. By the end of the outbreak in June, 2007, 511 suspect RVF cases had been recorded from 10 of the 21 regions of Tanzania, with laboratory confirmation of 186 cases and another 123 probable cases. All confirmed RVF cases were located in the north-central and southern regions of the country, with an eventual fatality rate of 28.2% (N = 144). All suspected cases had fever; 89% had encephalopathy, 10% hemorrhage, and 3% retinopathy. A total of 169 (55%) of the 309 confirmed or probable cases were also positive for malaria as detected by peripheral blood smear. In a cohort of 20 RVF cases with known outcome that were also positive for human immunodeficiency virus, 15 (75%) died. Contact with sick animals and animal products, including blood, meat, and milk, were identified as major risk factors of acquiring RVF.

  1. Epidemiologic and Clinical Aspects of a Rift Valley Fever Outbreak in Humans in Tanzania, 2007

    PubMed Central

    Mohamed, Mohamed; Mosha, Fausta; Mghamba, Janeth; Zaki, Sherif R.; Shieh, Wun-Ju; Paweska, Janusz; Omulo, Sylvia; Gikundi, Solomon; Mmbuji, Peter; Bloland, Peter; Zeidner, Nordin; Kalinga, Raphael; Breiman, Robert F.; Njenga, M. Kariuki

    2010-01-01

    In January 2007, an outbreak of Rift Valley fever (RVF) was detected among humans in northern Tanzania districts. By the end of the outbreak in June, 2007, 511 suspect RVF cases had been recorded from 10 of the 21 regions of Tanzania, with laboratory confirmation of 186 cases and another 123 probable cases. All confirmed RVF cases were located in the north-central and southern regions of the country, with an eventual fatality rate of 28.2% (N = 144). All suspected cases had fever; 89% had encephalopathy, 10% hemorrhage, and 3% retinopathy. A total of 169 (55%) of the 309 confirmed or probable cases were also positive for malaria as detected by peripheral blood smear. In a cohort of 20 RVF cases with known outcome that were also positive for human immunodeficiency virus, 15 (75%) died. Contact with sick animals and animal products, including blood, meat, and milk, were identified as major risk factors of acquiring RVF. PMID:20682902

  2. Predicting Rift Valley Fever Inter-epidemic Activities and Outbreak Patterns: Insights from a Stochastic Host-Vector Model.

    PubMed

    Pedro, Sansao A; Abelman, Shirley; Tonnang, Henri E Z

    2016-12-01

    Rift Valley fever (RVF) outbreaks are recurrent, occurring at irregular intervals of up to 15 years at least in East Africa. Between outbreaks disease inter-epidemic activities exist and occur at low levels and are maintained by female Aedes mcintoshi mosquitoes which transmit the virus to their eggs leading to disease persistence during unfavourable seasons. Here we formulate and analyse a full stochastic host-vector model with two routes of transmission: vertical and horizontal. By applying branching process theory we establish novel relationships between the basic reproduction number, R0, vertical transmission and the invasion and extinction probabilities. Optimum climatic conditions and presence of mosquitoes have not fully explained the irregular oscillatory behaviour of RVF outbreaks. Using our model without seasonality and applying van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how outbreaks multi-year periodicity varies with the vertical transmission. Our theory predicts complex fluctuations with a dominant period of 1 to 10 years which essentially depends on the efficiency of vertical transmission. Our predictions are then compared to temporal patterns of disease outbreaks in Tanzania, Kenya and South Africa. Our analyses show that interaction between nonlinearity, stochasticity and vertical transmission provides a simple but plausible explanation for the irregular oscillatory nature of RVF outbreaks. Therefore, we argue that while rainfall might be the major determinant for the onset and switch-off of an outbreak, the occurrence of a particular outbreak is also a result of a build up phenomena that is correlated to vertical transmission efficiency.

  3. Predicting Rift Valley Fever Inter-epidemic Activities and Outbreak Patterns: Insights from a Stochastic Host-Vector Model

    PubMed Central

    Pedro, Sansao A.; Abelman, Shirley; Tonnang, Henri E. Z.

    2016-01-01

    Rift Valley fever (RVF) outbreaks are recurrent, occurring at irregular intervals of up to 15 years at least in East Africa. Between outbreaks disease inter-epidemic activities exist and occur at low levels and are maintained by female Aedes mcintoshi mosquitoes which transmit the virus to their eggs leading to disease persistence during unfavourable seasons. Here we formulate and analyse a full stochastic host-vector model with two routes of transmission: vertical and horizontal. By applying branching process theory we establish novel relationships between the basic reproduction number, R0, vertical transmission and the invasion and extinction probabilities. Optimum climatic conditions and presence of mosquitoes have not fully explained the irregular oscillatory behaviour of RVF outbreaks. Using our model without seasonality and applying van Kampen system-size expansion techniques, we provide an analytical expression for the spectrum of stochastic fluctuations, revealing how outbreaks multi-year periodicity varies with the vertical transmission. Our theory predicts complex fluctuations with a dominant period of 1 to 10 years which essentially depends on the efficiency of vertical transmission. Our predictions are then compared to temporal patterns of disease outbreaks in Tanzania, Kenya and South Africa. Our analyses show that interaction between nonlinearity, stochasticity and vertical transmission provides a simple but plausible explanation for the irregular oscillatory nature of RVF outbreaks. Therefore, we argue that while rainfall might be the major determinant for the onset and switch-off of an outbreak, the occurrence of a particular outbreak is also a result of a build up phenomena that is correlated to vertical transmission efficiency. PMID:28002417

  4. A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania

    PubMed Central

    Sindato, Calvin; Pfeiffer, Dirk U.; Karimuribo, Esron D.; Mboera, Leonard E. G.; Rweyemamu, Mark M.; Paweska, Janusz T.

    2015-01-01

    Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and speciesspecific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1–2 years, those aged 3 and 4–5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem. PMID:26162089

  5. A Spatial Analysis of Rift Valley Fever Virus Seropositivity in Domestic Ruminants in Tanzania.

    PubMed

    Sindato, Calvin; Pfeiffer, Dirk U; Karimuribo, Esron D; Mboera, Leonard E G; Rweyemamu, Mark M; Paweska, Janusz T

    2015-01-01

    Rift Valley fever (RVF) is an acute arthropod-borne viral zoonotic disease primarily occurring in Africa. Since RVF-like disease was reported in Tanzania in 1930, outbreaks of the disease have been reported mainly from the eastern ecosystem of the Great Rift Valley. This cross-sectional study was carried out to describe the variation in RVF virus (RVFV) seropositivity in domestic ruminants between selected villages in the eastern and western Rift Valley ecosystems in Tanzania, and identify potential risk factors. Three study villages were purposively selected from each of the two Rift Valley ecosystems. Serum samples from randomly selected domestic ruminants (n = 1,435) were tested for the presence of specific immunoglobulin G (IgG) and M (IgM), using RVF enzyme-linked immunosorbent assay methods. Mixed effects logistic regression modelling was used to investigate the association between potential risk factors and RVFV seropositivity. The overall RVFV seroprevalence (n = 1,435) in domestic ruminants was 25.8% and species specific seroprevalence was 29.7%, 27.7% and 22.0% in sheep (n = 148), cattle (n = 756) and goats (n = 531), respectively. The odds of seropositivity were significantly higher in animals sampled from the villages in the eastern than those in the western Rift Valley ecosystem (OR = 1.88, CI: 1.41, 2.51; p<0.001), in animals sampled from villages with soils of good than those with soils of poor water holding capacity (OR = 1.97; 95% CI: 1.58, 3.02; p< 0.001), and in animals which had been introduced than in animals born within the herd (OR = 5.08, CI: 2.74, 9.44; p< 0.001). Compared with animals aged 1-2 years, those aged 3 and 4-5 years had 3.40 (CI: 2.49, 4.64; p< 0.001) and 3.31 (CI: 2.27, 4.82, p< 0.001) times the odds of seropositivity. The findings confirm exposure to RVFV in all the study villages, but with a higher prevalence in the study villages from the eastern Rift Valley ecosystem.

  6. Experimental Infection of Calves by Two Genetically-Distinct Strains of Rift Valley Fever Virus

    PubMed Central

    Wilson, William C.; Davis, A. Sally; Gaudreault, Natasha N.; Faburay, Bonto; Trujillo, Jessie D.; Shivanna, Vinay; Sunwoo, Sun Young; Balogh, Aaron; Endalew, Abaineh; Ma, Wenjun; Drolet, Barbara S.; Ruder, Mark G.; Morozov, Igor; McVey, D. Scott; Richt, Juergen A.

    2016-01-01

    Recent outbreaks of Rift Valley fever in ruminant livestock, characterized by mass abortion and high mortality rates in neonates, have raised international interest in improving vaccine control strategies. Previously, we developed a reliable challenge model for sheep that improves the evaluation of existing and novel vaccines in sheep. This sheep model demonstrated differences in the pathogenesis of Rift Valley fever virus (RVFV) infection between two genetically-distinct wild-type strains of the virus, Saudi Arabia 2001 (SA01) and Kenya 2006 (Ken06). Here, we evaluated the pathogenicity of these two RVFV strains in mixed breed beef calves. There was a transient increase in rectal temperatures with both virus strains, but this clinical sign was less consistent than previously reported with sheep. Three of the five Ken06-infected animals had an early-onset viremia, one day post-infection (dpi), with viremia lasting at least three days. The same number of SA01-infected animals developed viremia at 2 dpi, but it only persisted through 3 dpi in one animal. The average virus titer for the SA01-infected calves was 1.6 logs less than for the Ken06-infected calves. Calves, inoculated with either strain, seroconverted by 5 dpi and showed time-dependent increases in their virus-neutralizing antibody titers. Consistent with the results obtained in the previous sheep study, elevated liver enzyme levels, more severe liver pathology and higher virus titers occurred with the Ken06 strain as compared to the SA01 strain. These results demonstrate the establishment of a virulent challenge model for vaccine evaluation in calves. PMID:27223298

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

    PubMed

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

    2012-08-07

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

  8. Modelling Vaccination Strategies against Rift Valley Fever in Livestock in Kenya.

    PubMed

    Gachohi, John M; Njenga, M Kariuki; Kitala, Philip; Bett, Bernard

    2016-12-01

    The impacts of vaccination on the transmission of Rift Valley fever virus (RVFV) have not been evaluated. We have developed a RVFV transmission model comprising two hosts-cattle as a separate host and sheep and goats as one combined host (herein after referred to as sheep)-and two vectors-Aedes species (spp) and Culex spp-and used it to predict the impacts of: (1) reactive vaccination implemented at various levels of coverage at pre-determined time points, (2) targeted vaccination involving either of the two host species, and (3) a periodic vaccination implemented biannually or annually before an outbreak. The model comprises coupled vector and host modules where the dynamics of vectors and hosts are described using a system of difference equations. Vector populations are structured into egg, larva, pupa and adult stages and the latter stage is further categorized into three infection categories: susceptible, exposed and infectious mosquitoes. The survival rates of the immature stages (egg, larva and pupa) are dependent on rainfall densities extracted from the Tropical Rainfall Measuring Mission (TRMM) for a Rift Valley fever (RVF) endemic site in Kenya over a period of 1827 days. The host populations are structured into four age classes comprising young, weaners, yearlings and adults and four infection categories including susceptible, exposed, infectious, and immune categories. The model reproduces the 2006/2007 RVF outbreak reported in empirical surveys in the target area and other seasonal transmission events that are perceived to occur during the wet seasons. Mass reactive vaccination strategies greatly reduce the potential for a major outbreak. The results also suggest that the effectiveness of vaccination can be enhanced by increasing the vaccination coverage, targeting vaccination on cattle given that this species plays a major role in the transmission of the virus, and using both periodic and reactive vaccination strategies. Reactive vaccination can be

  9. Multiplex detection of IgG and IgM to Rift Valley fever virus nucleoprotein, nonstructural proteins, and glycoprotein in ovine and bovine

    USDA-ARS?s Scientific Manuscript database

    A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were...

  10. Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis.

    PubMed

    Wonderlich, Elizabeth R; Caroline, Amy L; McMillen, Cynthia M; Walters, Aaron W; Reed, Douglas S; Barratt-Boyes, Simon M; Hartman, Amy L

    2018-02-01

    Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8 + T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4 + and CD8 + T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model. IMPORTANCE Rift Valley Fever (RVF) is an important emerging viral disease for which

  11. Common host-derived chemicals increase catches of disease-transmitting mosquitoes and can improve early warning systems for rift valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health problem in sub-Saharan Africa. The emergence and re-emergence of the disease in the last 20 years especially in East Africa, poses a looming health threat which is likely to spread to beyond Africa. This threat is exacerbat...

  12. Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley and Congo-Crimean Hemorrhagic Fever in Kenya.

    DTIC Science & Technology

    1994-01-27

    VALLEY AND CONGO-CRIMEAN HEMORRHAGIC FEVER IN KENYA PRINCIPAL INVESTIGATOR: J. K. Omuse CONTRACTING ORGANIZATION : Kenya Trypanosomiasis Research...J. K. Omuse 7. PERFORMING ORGANIZATION NAME(S) AND ADORESS(ES) 8. PERFORMING ORGANIZATION Kenya Trypanosomiasis Research Institute REPORT NUMBER P.O...these flagellated protozoan parasites "homes" to the microvasculature of the brain and skeletal muscles, and the frequent paucity of organisms in the

  13. A Rift Valley Fever Vaccine Trial. 1. Side Effects and Serologic Response Over a Six-Month Follow-Up

    DTIC Science & Technology

    1982-01-01

    strep - injection. One volunteer was excluded tomycin and 10 per cent fetal calf serum. from the trial following detection of se- The cells were...ml swelling, induration) were recorded. Each of lot 1. Three additional individuals who symptom was individually scored on a received the 1 ml dose...plaque-forming units of the tivities, nasal discharge, sore throat , ZH501 strain of Rift Valley fever virus cough, nausea or anorexia, vomiting, and and

  14. Valley Fever: Finding New Places for an Old Disease: Coccidioides immitis Found in Washington State Soil Associated With Recent Human Infection

    PubMed Central

    Litvintseva, Anastasia P.; Marsden-Haug, Nicola; Hurst, Steven; Hill, Heather; Gade, Lalitha; Driebe, Elizabeth M.; Ralston, Cindy; Roe, Chandler; Barker, Bridget M.; Goldoft, Marcia; Keim, Paul; Wohrle, Ron; Thompson, George R.; Engelthaler, David M.; Brandt, Mary E.; Chiller, Tom

    2015-01-01

    We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients. PMID:25165087

  15. Favipiravir (T-705) protects against peracute Rift Valley fever virus infection and reduces delayed-onset neurologic disease observed with ribavirin treatment.

    PubMed

    Scharton, Dionna; Bailey, Kevin W; Vest, Zachary; Westover, Jonna B; Kumaki, Yohichi; Van Wettere, Arnaud; Furuta, Yousuke; Gowen, Brian B

    2014-04-01

    Rift Valley fever is a zoonotic, arthropod-borne disease that affects livestock and humans. The etiologic agent, Rift Valley fever virus (RVFV; Bunyaviridae, Phlebovirus) is primarily transmitted through mosquito bites, but can also be transmitted by exposure to infectious aerosols. There are presently no licensed vaccines or therapeutics to prevent or treat severe RVFV infection in humans. We have previously reported on the activity of favipiravir (T-705) against the MP-12 vaccine strain of RVFV and other bunyaviruses in cell culture. In addition, efficacy has also been documented in mouse and hamster models of infection with the related Punta Toro virus. Here, hamsters challenged with the highly pathogenic ZH501 strain of RVFV were used to evaluate the activity of favipiravir against lethal infection. Subcutaneous RVFV challenge resulted in substantial serum and tissue viral loads and caused severe disease and mortality within 2-3 days of infection. Oral favipiravir (200 mg/kg/day) prevented mortality in 60% or greater of hamsters challenged with RVFV when administered within 1 or 6h post-exposure and reduced RVFV titers in serum and tissues relative to the time of treatment initiation. In contrast, although ribavirin (75 mg/kg/day) was effective at protecting animals from the peracute RVFV disease, most ultimately succumbed from a delayed-onset neurologic disease associated with high RVFV burden observed in the brain in moribund animals. When combined, T-705 and ribavirin treatment started 24 h post-infection significantly improved survival outcome and reduced serum and tissue virus titers compared to monotherapy. Our findings demonstrate significant post-RVFV exposure efficacy with favipiravir against both peracute disease and delayed-onset neuroinvasion, and suggest added benefit when combined with ribavirin. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Dual functions of Rift Valley fever virus NSs protein: inhibition of host mRNA transcription and post-transcriptional downregulation of protein kinase PKR.

    PubMed

    Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

    2009-09-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis, or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-beta mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase (PKR), to prevent phosphorylation of eIF2alpha and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts.

  17. Dual Functions of Rift Valley Fever Virus NSs Protein: Inhibition of Host mRNA Transcription and Post-transcriptional Downregulation of Protein Kinase PKR

    PubMed Central

    Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C. J.; Makino, Shinji

    2011-01-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, is a negative-stranded RNA virus carrying a single-stranded, tripartite RNA genome. RVFV is an important zoonotic pathogen transmitted by mosquitoes and causes large outbreaks among ruminants and humans in Africa and the Arabian Peninsula. Human patients develop an acute febrile illness, followed by a fatal hemorrhagic fever, encephalitis or ocular diseases. A viral nonstructural protein, NSs, is a major viral virulence factor. Past studies showed that NSs suppresses the transcription of host mRNAs, including interferon-β mRNAs. Here we demonstrated that the NSs protein induced post-transcriptional downregulation of dsRNA-dependent protein kinase, PKR, to prevent phosphorylation of eIF2α and promoted viral translation in infected cells. These two biological activities of the NSs most probably have a synergistic effect in suppressing host innate immune functions and facilitate efficient viral replication in infected mammalian hosts. PMID:19751406

  18. Observations on rift valley fever virus and vaccines in Egypt

    PubMed Central

    2011-01-01

    Rift Valley Fever virus (RVFV, genus: Phlebovirus, family: Bunyaviridae), is an arbovirus which causes significant morbidity and mortality in animals and humans. RVFV was introduced for the first time in Egypt in 1977. In endemic areas, the insect vector control and vaccination is considering appropriate measures if applied properly and the used vaccine is completely safe and the vaccination programs cover all the susceptible animals. Egypt is importing livestock and camels from the African Horn & the Sudan for human consumption. The imported livestock and camels were usually not vaccinated against RVFV. But in rare occasions, the imported livestock were vaccinated but with unknown date of vaccination and the unvaccinated control contacts were unavailable for laboratory investigations. Also, large number of the imported livestock and camels are often escaped slaughtering for breeding which led to the spread of new strains of FMD and the introduction of RVFV from the enzootic African countries. This article provide general picture about the present situation of RVFV in Egypt to help in controlling this important disease. PMID:22152149

  19. Development of a sheep challenge model for Rift Valley fever.

    PubMed

    Faburay, Bonto; Gaudreault, Natasha N; Liu, Qinfang; Davis, A Sally; Shivanna, Vinay; Sunwoo, Sun Young; Lang, Yuekun; Morozov, Igor; Ruder, Mark; Drolet, Barbara; Scott McVey, D; Ma, Wenjun; Wilson, William; Richt, Juergen A

    2016-02-01

    Rift Valley fever (RVF) is a zoonotic disease that causes severe epizootics in ruminants, characterized by mass abortion and high mortality rates in younger animals. The development of a reliable challenge model is an important prerequisite for evaluation of existing and novel vaccines. A study aimed at comparing the pathogenesis of RVF virus infection in US sheep using two genetically different wild type strains of the virus (SA01-1322 and Kenya-128B-15) was performed. A group of sheep was inoculated with both strains and all infected sheep manifested early-onset viremia accompanied by a transient increase in temperatures. The Kenya-128B-15 strain manifested higher virulence compared to SA01-1322 by inducing more severe liver damage, and longer and higher viremia. Genome sequence analysis revealed sequence variations between the two isolates, which potentially could account for the observed phenotypic differences. We conclude that Kenya-128B-15 sheep infection represents a good and virulent challenge model for RVF. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Generation and characterization of monoclonal antibodies against Rift Valley fever virus nucleoprotein.

    PubMed

    Fafetine, J M; Domingos, A; Antunes, S; Esteves, A; Paweska, J T; Coetzer, J A W; Rutten, V P M G; Neves, L

    2013-11-01

    Due to the unpredictable and explosive nature of Rift Valley fever (RVF) outbreaks, rapid and accurate diagnostic assays for low-resource settings are urgently needed. To improve existing diagnostic assays, monoclonal antibodies (MAbs) specific for the nucleocapsid protein of RVF virus (RVFV) were produced and characterized. Four IgG2a MAbs showed specific binding to denatured nucleocapsid protein, both from a recombinant source and from inactivated RVFV, in Western blot analysis and in an enzyme-linked immunosorbent assay (ELISA). Cross-reactivity with genetically related and non-related arboviruses including Bunyamwera and Calovo viruses (Bunyaviridae family), West Nile and Dengue-2 viruses (Flaviviridae family), and Sindbis and Chikungunya viruses (Togaviridae family) was not detected. These MAbs represent a useful tool for the development of rapid diagnostic assays for early recognition of RVF. © 2013 Blackwell Verlag GmbH.

  1. Blood Meal Analysis of and Virus Detection in Mosquitoes Collected during a Rift Valley fever Epizootic/Epidemic: Implications for epidemic disease transmission dynamics

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever (RVF) is a zoonosis of domestic ruminants in Africa. Bloodfed mosquitoes collected during the 2006-2007 RVF outbreak in Kenya were analyzed to determine the virus infection status and animal source of the bloodmeals. Bloodmeals from individual mosquito abdomens were screened for v...

  2. Ultrastructural study of Rift Valley fever virus in the mouse model

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

    Reed, Christopher; Steele, Keith E.; Honko, Anna

    Detailed ultrastructural studies of Rift Valley fever virus (RVFV) in the mouse model are needed to develop and characterize a small animal model of RVF for the evaluation of potential vaccines and therapeutics. In this study, the ultrastructural features of RVFV infection in the mouse model were analyzed. The main changes in the liver included the presence of viral particles in hepatocytes and hepatic stem cells accompanied by hepatocyte apoptosis. However, viral particles were observed rarely in the liver; in contrast, particles were extremely abundant in the CNS. Despite extensive lymphocytolysis, direct evidence of viral replication was not observed inmore » the lymphoid tissue. These results correlate with the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF, but suggest that host immune-mediated mechanisms contribute significantly to pathology. The results of this study expand our knowledge of RVFV-host interactions and further characterize the mouse model of RVF.« less

  3. Rapamycin modulation of p70 S6 kinase signaling inhibits Rift Valley fever virus pathogenesis.

    PubMed

    Bell, Todd M; Espina, Virginia; Senina, Svetlana; Woodson, Caitlin; Brahms, Ashwini; Carey, Brian; Lin, Shih-Chao; Lundberg, Lindsay; Pinkham, Chelsea; Baer, Alan; Mueller, Claudius; Chlipala, Elizabeth A; Sharman, Faye; de la Fuente, Cynthia; Liotta, Lance; Kehn-Hall, Kylene

    2017-07-01

    Despite over 60 years of research on antiviral drugs, very few are FDA approved to treat acute viral infections. Rift Valley fever virus (RVFV), an arthropod borne virus that causes hemorrhagic fever in severe cases, currently lacks effective treatments. Existing as obligate intracellular parasites, viruses have evolved to manipulate host cell signaling pathways to meet their replication needs. Specifically, translation modulation is often necessary for viruses to establish infection in their host. Here we demonstrated phosphorylation of p70 S6 kinase, S6 ribosomal protein, and eIF4G following RVFV infection in vitro through western blot analysis and in a mouse model of infection through reverse phase protein microarrays (RPPA). Inhibition of p70 S6 kinase through rapamycin treatment reduced viral titers in vitro and increased survival and mitigated clinical disease in RVFV challenged mice. Additionally, the phosphorylation of p70 S6 kinase was decreased following rapamycin treatment in vivo. Collectively these data demonstrate modulating p70 S6 kinase can be an effective antiviral strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Integrative Medicine Preferences Among Coccidioidomycosis (Valley Fever) Patients.

    PubMed

    Short, Jack H; Bradley, Constance; Blair, Janis E; Stewart, Terry D; Burns, Mark W; Patron, Roberto L; Millstine, Denise M

    2017-02-01

    To understand the extent and modalities of integrative medicine strategies that patients with coccidioidomycosis (valley fever) have incorporated into their treatment regimens. A direct patient survey was distributed, with 100 unique responses, at a single infectious diseases clinic at an academic medical center in Arizona. Eligible patients, defined as those with confirmed coccidioidomycosis or currently under evaluation, were polled on their personal use of 36 integrative medicine modalities. Patients were also asked to indicate their level of fatigue on a 10-point scale in an attempt to correlate levels of fatigue to use of specific integrative medicine modalities. Of the patients surveyed, 64% had used at least one integrative medicine modality, and 53% used two or more, along with conventional medical therapy. The top three modalities were nutrition (39%), massage (27%), and breathing exercises (26%). The mean reported fatigue level was 4.7 on a 10-point scale, with a standard deviation of 3.0. There was no statistically significant association between use of a specific modality and reported level of fatigue. Nearly two thirds of patients (64%) surveyed had used at least one integrative medicine modality throughout the course of their therapy. Clinicians are probably unaware of the extent to which many patients, including this population, have embraced integrative medicine. Awareness of patients' goal and preferences is valuable in shared clinical decision making.

  5. A public health issue related to collateral seismic hazards: The valley fever outbreak triggered by the 1994 Northridge, California earthquake

    USGS Publications Warehouse

    Jibson, R.W.

    2002-01-01

    Following the 17 January 1994 Northridge. California earthquake (M = 6.7), Ventura County, California, experienced a major outbreak of coccidioidomycosis (CM), commonly known as valley fever, a respiratory disease contracted by inhaling airborne fungal spores. In the 8 weeks following the earthquake (24 January through 15 March), 203 outbreak-associated cases were reported, which is about an order of magnitude more than the expected number of cases, and three of these cases were fatal. Simi Valley, in easternmost Ventura County, had the highest attack rate in the county, and the attack rate decreased westward across the county. The temporal and spatial distribution of CM cases indicates that the outbreak resulted from inhalation of spore-contaminated dust generated by earthquake-triggered landslides. Canyons North East of Simi Valley produced many highly disrupted, dust-generating landslides during the earthquake and its aftershocks. Winds after the earthquake were from the North East, which transported dust into Simi Valley and beyond to communities to the West. The three fatalities from the CM epidemic accounted for 4 percent of the total earthquake-related fatalities.

  6. Neutralizing antibodies against flaviviruses, Babanki virus, and Rift Valley fever virus in Ugandan bats.

    PubMed

    Kading, Rebekah C; Kityo, Robert M; Mossel, Eric C; Borland, Erin M; Nakayiki, Teddie; Nalikka, Betty; Nyakarahuka, Luke; Ledermann, Jeremy P; Panella, Nicholas A; Gilbert, Amy T; Crabtree, Mary B; Peterhans, Julian Kerbis; Towner, Jonathan S; Amman, Brian R; Sealy, Tara K; Nichol, Stuart T; Powers, Ann M; Lutwama, Julius J; Miller, Barry R

    2018-01-01

    Introduction: A number of arboviruses have previously been isolated from naturally-infected East African bats, however the role of bats in arbovirus maintenance is poorly understood. The aim of this study was to investigate the exposure history of Ugandan bats to a panel of arboviruses. Materials and methods: Insectivorous and fruit bats were captured from multiple locations throughout Uganda during 2009 and 2011-2013. All serum samples were tested for neutralizing antibodies against West Nile virus (WNV), yellow fever virus (YFV), dengue 2 virus (DENV-2), Zika virus (ZIKV), Babanki virus (BBKV), and Rift Valley fever virus (RVFV) by plaque reduction neutralization test (PRNT). Sera from up to 626 bats were screened for antibodies against each virus. Results and Discussion:  Key findings include the presence of neutralizing antibodies against RVFV in 5/52 (9.6%) of little epauletted fruit bats ( Epomophorus labiatus ) captured from Kawuku and 3/54 (5.6%) Egyptian rousette bats from Kasokero cave. Antibodies reactive to flaviviruses were widespread across bat taxa and sampling locations. Conclusion: The data presented demonstrate the widespread exposure of bats in Uganda to arboviruses, and highlight particular virus-bat associations that warrant further investigation.

  7. Phylogeography of Rift Valley Fever Virus in Africa Reveals Multiple Introductions in Senegal and Mauritania

    PubMed Central

    Faye, Ousmane; Diallo, Mawlouth; de Oliveira, Juliana Velasco C.; Zanotto, Paolo M. A.; Sall, Amadou Alpha

    2012-01-01

    Rift Valley Fever (RVF) virus (Family Bunyaviridae) is an arthropod-borne RNA virus that infects primarily domestic ruminants and occasionally humans. RVF epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications. RVF virus is widespread and endemic in many regions of Africa. In Western Africa, several outbreaks have been reported since 1987 when the first major one occurred at the frontier of Senegal and Mauritania. Aiming to evaluate the spreading and molecular epidemiology in these countries, RVFV isolates from 1944 to 2008 obtained from 18 localities in Senegal and Mauritania and 15 other countries were investigated. Our results suggest that a more intense viral activity possibly took place during the last century compared to the recent past and that at least 5 introductions of RVFV took place in Senegal and Mauritania from distant African regions. Moreover, Barkedji in Senegal was possibly a hub associated with the three distinct entries of RVFV in West Africa. PMID:22539961

  8. Reduced Rift Valley fever virus infection rates in mosquitoes associated with pledget feedings.

    PubMed

    Turell, M J

    1988-12-01

    Infection rates were compared in Culex pipiens and Aedes taeniorhynchus after they fed on Rift Valley fever (RVF) viremic hamsters or ingested similar doses of RVF virus from blood-soaked pledgets. Infection rates were significantly lower for mosquitoes that ingested virus from a pledget than for those that ingested similar doses from viremic hamsters. The method used to prevent normal clot formation for the pledget feedings (i.e., defibrination by shaking with glass beads or addition of heparin) did not affect subsequent infection rates. Both inhibition of normal clot formation and freezing of virus after it had last been propagated were associated with significantly reduced infection rates with the pledget feedings. Laboratory studies using artificial feeding techniques may not give reliable estimates of the vector competence of mosquitoes for arboviruses.

  9. A novel highly sensitive, rapid and safe Rift Valley fever virus neutralization test.

    PubMed

    Wichgers Schreur, Paul J; Paweska, Janusz T; Kant, Jet; Kortekaas, Jeroen

    2017-10-01

    Antibodies specific for Rift Valley fever virus (RVFV) can be detected by diverse methods, including ezyme-linked immunosortbent assay (ELISA) and virus neutralization test (VNT). The VNT is superior in sensitivity and specificity and is therefore considered the gold standard serological assay. Classical VNTs make use of virulent RVFV and therefore have to be performed in biosafety level 3 laboratories. Here, we report the development of a novel VNT that is based on an avirulent RVFV expressing the enhanced green fluorescent protein (eGFP), which can be performed safely outside level 3 biocontainment facilities. Evaluation with a broad panel of experimental sera and field sera demonstrated that this novel VNT is faster and more sensitive than the classical VNT. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export.

    PubMed

    Copeland, Anna Maria; Van Deusen, Nicole M; Schmaljohn, Connie S

    2015-12-01

    We investigated the localization of host mRNA during Rift Valley fever virus (RVFV) infection. Fluorescence in situ hybridization revealed that infection with RVFV altered the localization of host mRNA. mRNA accumulated in the nuclei of RVFV-infected but not mock-infected cells. Further, overexpression of the NSS gene, but not the N, GN or NSM genes correlated with mRNA nuclear accumulation. Nuclear accumulation of host mRNA was not observed in cells infected with a strain of RVFV lacking the gene encoding NSS, confirming that expression of NSS is likely responsible for this phenomenon. Published by Elsevier Inc.

  11. Functional analysis of Rift Valley fever virus NSs encoding a partial truncation.

    PubMed

    Head, Jennifer A; Kalveram, Birte; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210-230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6-30, 31-55, 56-80, 81-105, 106-130, 131-155, 156-180, 181-205, 206-230, 231-248 or 249-265 lack functions of IFN-β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81-105, 106-130, 131-155, 156-180, 181-205, 206-230 or 231-248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant-negative phenotype.

  12. Potential application of silver nanoparticles to control the infectivity of Rift Valley fever virus in vitro and in vivo.

    PubMed

    Borrego, Belén; Lorenzo, Gema; Mota-Morales, Josué D; Almanza-Reyes, Horacio; Mateos, Francisco; López-Gil, Elena; de la Losa, Nuria; Burmistrov, Vasily A; Pestryakov, Alexey N; Brun, Alejandro; Bogdanchikova, Nina

    2016-07-01

    In this work we have tested the potential antiviral activity of silver nanoparticles formulated as Argovit™ against Rift Valley fever virus (RVFV). The antiviral activity of Argovit was tested on Vero cell cultures and in type-I interferon receptor deficient mice (IFNAR (-/-) mice) by two different approaches: (i) different dilutions of Argovit were added to previously infected cells or administrated to animals infected with a lethal dose of virus; (ii) virus was pre-incubated with different dilutions of Argovit before inoculation in mice or cells. Though the ability of silver nanoparticles to control an ongoing RVFV infection in the conditions tested was limited, the incubation of virus with Argovit before the infection led to a reduction of the infectivity titers both in vitro and in vivo. These results reveal the potential application of silver nanoparticles to control the infectivity of RVFV, which is an important zoonotic pathogen. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A Review of Mosquitoes Associated with Rift Valley Fever Virus in Madagascar

    PubMed Central

    Tantely, Luciano M.; Boyer, Sébastien; Fontenille, Didier

    2015-01-01

    Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar. PMID:25732680

  14. Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions.

    PubMed

    Coopersmith, E J; Bell, J E; Benedict, K; Shriber, J; McCotter, O; Cosh, M H

    2017-04-17

    Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp. , in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location.

  15. NSs protein of rift valley fever virus induces the specific degradation of the double-stranded RNA-dependent protein kinase.

    PubMed

    Habjan, Matthias; Pichlmair, Andreas; Elliott, Richard M; Overby, Anna K; Glatter, Timo; Gstaiger, Matthias; Superti-Furga, Giulio; Unger, Hermann; Weber, Friedemann

    2009-05-01

    Rift Valley fever virus (RVFV) continues to cause large outbreaks of acute febrile and often fatal illness among humans and domesticated animals in Africa, Saudi Arabia, and Yemen. The high pathogenicity of this bunyavirus is mainly due to the viral protein NSs, which was shown to prevent transcriptional induction of the antivirally active type I interferons (alpha/beta interferon [IFN-alpha/beta]). Viruses lacking the NSs gene induce synthesis of IFNs and are therefore attenuated, whereas the noninducing wild-type RVFV strains can only be inhibited by pretreatment with IFN. We demonstrate here in vitro and in vivo that a substantial part of the antiviral activity of IFN against RVFV is due to a double-stranded RNA-dependent protein kinase (PKR). PKR-mediated virus inhibition, however, was much more pronounced for the strain Clone 13 with NSs deleted than for the NSs-expressing strain ZH548. In vivo, Clone 13 was nonpathogenic for wild-type (wt) mice but could regain pathogenicity if mice lacked the PKR gene. ZH548, in contrast, killed both wt and PKR knockout mice indiscriminately. ZH548 was largely resistant to the antiviral properties of PKR because RVFV NSs triggered the specific degradation of PKR via the proteasome. The NSs proteins of the related but less virulent sandfly fever Sicilian virus and La Crosse virus, in contrast, had no such anti-PKR activity despite being efficient suppressors of IFN induction. Our data suggest that RVFV NSs has gained an additional anti-IFN function that may explain the extraordinary pathogenicity of this virus.

  16. Inter-epidemic Transmission of Rift Valley Fever in Livestock in the Kilombero River Valley, Tanzania: A Cross-Sectional Survey

    PubMed Central

    Sumaye, Robert D.; Geubbels, Eveline; Mbeyela, Edgar; Berkvens, Dirk

    2013-01-01

    Background In recent years, evidence of Rift Valley fever (RVF) transmission during inter-epidemic periods in parts of Africa has increasingly been reported. The inter-epidemic transmissions generally pass undetected where there is no surveillance in the livestock or human populations. We studied the presence of and the determinants for inter-epidemic RVF transmission in an area experiencing annual flooding in southern Tanzania. Methodology A cross-sectional sero-survey was conducted in randomly selected cattle, sheep and goats in the Kilombero river valley from May to August 2011, approximately four years after the 2006/07 RVF outbreak in Tanzania. The exposure status to RVF virus (RVFV) was determined using two commercial ELISA kits, detecting IgM and IgG antibodies in serum. Information about determinants was obtained through structured interviews with herd owners. Findings An overall seroprevalence of 11.3% (n = 1680) was recorded; 5.5% in animals born after the 2006/07 RVF outbreak and 22.7% in animals present during the outbreak. There was a linear increase in prevalence in the post-epidemic annual cohorts. Nine inhibition-ELISA positive samples were also positive for RVFV IgM antibodies indicating a recent infection. The spatial distribution of seroprevalence exhibited a few hotspots. The sex difference in seroprevalence in animals born after the previous epidemic was not significant (6.1% vs. 4.6% for females and males respectively, p = 0.158) whereas it was significant in animals present during the outbreak (26.0% vs. 7.8% for females and males respectively, p<0.001). Animals living >15 km from the flood plain were more likely to have antibodies than those living <5 km (OR 1.92; 95% CI 1.04–3.56). Species, breed, herd composition, grazing practices and altitude were not associated with seropositivity. Conclusion These findings indicate post-epidemic transmission of RVFV in the study area. The linear increase in seroprevalence in the post

  17. Seroprevalence of Rift Valley fever virus in livestock during inter-epidemic period in Egypt, 2014/15.

    PubMed

    Mroz, Claudia; Gwida, Mayada; El-Ashker, Maged; El-Diasty, Mohamed; El-Beskawy, Mohamed; Ziegler, Ute; Eiden, Martin; Groschup, Martin H

    2017-04-05

    Rift Valley fever virus (RVFV) caused several outbreaks throughout the African continent and the Arabian Peninsula posing significant threat to human and animal health. In Egypt the first and most important Rift Valley fever epidemic occurred during 1977/78 with a multitude of infected humans and huge economic losses in livestock. After this major outbreak, RVF epidemics re-occurred in irregular intervals between 1993 and 2003. Seroprevalence of anti-RVFV antibodies in livestock during inter-epidemic periods can be used for supporting the evaluation of the present risk exposure for animal and public health. A serosurvey was conducted during 2014/2015 in non-vaccinated livestock including camels, sheep, goats and buffalos in different areas of the Nile River Delta as well as the furthermost southeast of Egypt to investigate the presence of anti-RVFV antibodies for further evaluating of the risk exposure for animal and human health. All animals integrated in this study were born after the last Egyptian RVF epidemic in 2003 and sampled buffalos and small ruminants were not imported from other endemic countries. A total of 873 serum samples from apparently healthy animals from different host species (camels: n = 221; sheep: n = 438; goats: n = 26; buffalo: n = 188) were tested serologically using RVFV competition ELISA, virus neutralization test and/or an indirect immunofluorescence assay, depending on available serum volume. Sera were assessed positive when virus neutralization test alone or least two assays produced consistent positive results. The overall seroprevalence was 2.29% (95%CI: 1.51-3.07) ranging from 0% in goats, 0.46% in sheep (95%CI: 0.41-0.5), and 3.17% in camels (95%CI: 0.86-5.48) up to 5.85% in buffalos (95%CI: 2.75-8.95). Our findings assume currently low level of circulating virus in the investigated areas and suggest minor indication for a new RVF epidemic. Further the results may indicate that during long inter-epidemic periods

  18. Molecular detection of Rift Valley fever virus in serum samples from selected areas of Tanzania.

    PubMed

    Chengula, Augustino Alfred; Kasanga, Christopher Jacob; Mdegela, Robinson Hammerthon; Sallu, Raphael; Yongolo, Mmeta

    2014-04-01

    Rift Valley fever (RVF) is an acute mosquito-borne viral zoonotic disease affecting domestic animals and humans caused by the Rift Valley fever virus (RVFV). The virus belongs to the genus Phlebovirus of the family Bunyaviridae. The main aim of this study was to detect the presence of antibodies to RVFV as well as the virus in the serum samples that were collected from livestock during the 2006/2007 RVF outbreaks in different locations in Tanzania. Analysis of selected samples was done using a RVF-specific inhibition enzyme-linked immunosorbent assay (I-ELISA) and reverse transcription polymerase chain reaction (RT-PCR). Genomic viral RNA was extracted directly from serum samples using a QIAamp Viral RNA Mini Kit (QIAGEN), and a one-step RT-PCR protocol was used to amplify the S segment of RVFV. Positive results were obtained in 39.5% (n = 200) samples using the RVF I-ELISA, and 17.6% (n = 108) of samples were positive by RT-PCR. I-ELISA detected 41 (38.7%), 32 (39.0%), and 6 (50.0%) positive results in cattle, goats, and sheep sera, respectively, whereas the RT-PCR detected 11 (0.2%), 7 (0.2%), and 1 (0.1%) positive results in cattle, goats, and sheep sera, respectively. These findings have demonstrated the presence of RVFV in Tanzania during the 2006/2007 RVF outbreaks. To our knowledge, this is the first report to detect RVFV in serum samples from domestic animals in Tanzania using PCR technique. Therefore, a detailed molecular study to characterize the virus from different geographical locations in order to establish the profile of strains circulating in the country and develop more effective and efficient control strategies should be done.

  19. Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

    PubMed

    Warimwe, George M; Gesharisha, Joseph; Carr, B Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K; Al-dubaib, Musaad A; Brun, Alejandro; Gilbert, Sarah C; Nene, Vishvanath; Hill, Adrian V S

    2016-02-05

    Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

  20. Serological tests for detecting Rift Valley fever viral antibodies in sheep from the Nile Delta.

    PubMed Central

    Scott, R M; Feinsod, F M; Allam, I H; Ksiazek, T G; Peters, C J; Botros, B A; Darwish, M A

    1986-01-01

    To determine the accuracy of serological methods in detecting Rift Valley fever (RVF) viral antibodies, we examined serum samples obtained from 418 sheep in the Nile Delta by using five tests. The plaque reduction neutralization test (PRNT) was considered the standard serological method against which the four other tests were compared. Twenty-four serum samples had RVF viral antibodies detected by PRNT. Hemagglutination inhibition and enzyme-linked immunosorbent assay antibodies to RVF virus were also present in the same 24 serum samples. Indirect immunofluorescence was less sensitive in comparison with PRNT, and complement fixation was the least sensitive. These results extend observations made with laboratory animals to a large field-collected group of Egyptian sheep. PMID:3533977

  1. Inflammatory Biomarkers Associated with Lethal Rift Valley Fever Encephalitis in the Lewis Rat Model

    PubMed Central

    Caroline, Amy L.; Kujawa, Michael R.; Oury, Tim D.; Reed, Douglas S.; Hartman, Amy L.

    2016-01-01

    Rift Valley fever (RVF) is an emerging viral disease that causes significant human and veterinary illness in Africa and the Arabian Peninsula. Encephalitis is one of the severe complications arising from RVF virus (RVFV) infection of people, and the pathogenesis of this form of RVF is completely unknown. We use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection. Lewis rats were infected with RVFV strain ZH501 by aerosol exposure, then sacrificed daily to determine the course of infection and evaluation of clinical, virological, and immunological parameters. Weight loss, fever, and clinical signs occurred during the last 1–2 days prior to death. Prior to onset of clinical indications of disease, rats displayed marked granulocytosis and thrombocytopenia. In addition, high levels of inflammatory chemokines (MCP-1, MCS-F, Gro/KC, RANTES, and IL-1β) were detected first in serum (3–5 dpi) followed by brain (5–7 dpi). The results of this study are consistent with clinical data from human RVF patients and validate Lewis rats as an appropriate small animal model for RVF encephalitis. The biomarkers we identified here will be useful in future studies evaluating the efficacy of novel vaccines and therapeutics. PMID:26779164

  2. Rift Valley Fever Virus Epidemic in Kenya, 2006/2007: The Entomologic Investigations

    PubMed Central

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

    2010-01-01

    In December 2006, Rift Valley fever (RVF) was diagnosed in humans in Garissa Hospital, Kenya and an outbreak reported affecting 11 districts. Entomologic surveillance was performed in four districts to determine the epidemic/epizootic vectors of RVF virus (RVFV). Approximately 297,000 mosquitoes were collected, 164,626 identified to species, 72,058 sorted into 3,003 pools and tested for RVFV by reverse transcription-polymerase chain reaction. Seventy-seven pools representing 10 species tested positive for RVFV, including Aedes mcintoshi/circumluteolus (26 pools), Aedes ochraceus (23 pools), Mansonia uniformis (15 pools); Culex poicilipes, Culex bitaeniorhynchus (3 pools each); Anopheles squamosus, Mansonia africana (2 pools each); Culex quinquefasciatus, Culex univittatus, Aedes pembaensis (1 pool each). Positive Ae. pembaensis, Cx. univittatus, and Cx. bitaeniorhynchus was a first time observation. Species composition, densities, and infection varied among districts supporting hypothesis that different mosquito species serve as epizootic/epidemic vectors of RVFV in diverse ecologies, creating a complex epidemiologic pattern in East Africa. PMID:20682903

  3. A review of mosquitoes associated with Rift Valley fever virus in Madagascar.

    PubMed

    Tantely, Luciano M; Boyer, Sébastien; Fontenille, Didier

    2015-04-01

    Rift Valley fever (RVF) is a viral zoonotic disease occurring throughout Africa, the Arabian Peninsula, and Madagascar. The disease is caused by a Phlebovirus (RVF virus [RVFV]) transmitted to vertebrate hosts through the bite of infected mosquitoes. In Madagascar, the first RVFV circulation was reported in 1979 based on detection in mosquitoes but without epidemic episode. Subsequently, two outbreaks occurred: the first along the east coast and in the central highlands in 1990 and 1991 and the most recent along the northern and eastern coasts and in the central highlands in 2008 and 2009. Despite the presence of 24 mosquitoes species potentially associated with RVFV transmission in Madagascar, little associated entomological information is available. In this review, we list the RVFV vector, Culex antennatus, as well as other taxa as candidate vector species. We discuss risk factors from an entomological perspective for the re-emergence of RVF in Madagascar. © The American Society of Tropical Medicine and Hygiene.

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

    PubMed

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

    2010-08-01

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

  5. Benefits of a one health approach: An example using Rift Valley fever.

    PubMed

    Rostal, Melinda K; Ross, Noam; Machalaba, Catherine; Cordel, Claudia; Paweska, Janusz T; Karesh, William B

    2018-06-01

    One Health has been promoted by international institutions as a framework to improve public health outcomes. Despite strong overall interest in One Health, country-, local- and project-level implementation remains limited, likely due to the lack of pragmatic and tested operational methods for implementation and metrics for evaluation. Here we use Rift Valley fever virus as an example to demonstrate the value of using a One Health approach for both scientific and resources advantages. We demonstrate that coordinated, a priori investigations between One Health sectors can yield higher statistical power to elucidate important public health relationships as compared to siloed investigations and post-hoc analyses. Likewise, we demonstrate that across a project or multi-ministry health study a One Health approach can result in improved resource efficiency, with resultant cost-savings (35% in the presented case). The results of these analyses demonstrate that One Health approaches can be directly and tangibly applied to health investigations.

  6. The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype

    PubMed Central

    Nishiyama, Shoko; Lokugamage, Nandadeva

    2016-01-01

    ABSTRACT Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by “abortion storms” in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. IMPORTANCE Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature

  7. The L, M, and S Segments of Rift Valley Fever Virus MP-12 Vaccine Independently Contribute to a Temperature-Sensitive Phenotype.

    PubMed

    Nishiyama, Shoko; Lokugamage, Nandadeva; Ikegami, Tetsuro

    2016-01-27

    Rift Valley fever (RVF) is endemic to Africa, and the mosquito-borne disease is characterized by "abortion storms" in ruminants and by hemorrhagic fever, encephalitis, and blindness in humans. Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) has a tripartite negative-stranded RNA genome (L, M, and S segments). A live-attenuated vaccine for RVF, the MP-12 vaccine, is conditionally licensed for veterinary use in the United States. MP-12 is fully attenuated by the combination of the partially attenuated L, M, and S segments. Temperature sensitivity (ts) limits viral replication at a restrictive temperature and may be involved with viral attenuation. In this study, we aimed to characterize the ts mutations for MP-12. The MP-12 vaccine showed restricted replication at 38°C and replication shutoff (100-fold or greater reduction in virus titer compared to that at 37°C) at 39°C in Vero and MRC-5 cells. Using rZH501 reassortants with either the MP-12 L, M, or S segment, we found that all three segments encode a temperature-sensitive phenotype. However, the ts phenotype of the S segment was weaker than that of the M or L segment. We identified Gn-Y259H, Gc-R1182G, L-V172A, and L-M1244I as major ts mutations for MP-12. The ts mutations in the L segment decreased viral RNA synthesis, while those in the M segment delayed progeny production from infected cells. We also found that a lack of NSs and/or 78kD/NSm protein expression minimally affected the ts phenotype. Our study revealed that MP-12 is a unique vaccine carrying ts mutations in the L, M, and S segments. Rift Valley fever (RVF) is a mosquito-borne viral disease endemic to Africa, characterized by high rates of abortion in ruminants and severe diseases in humans. Vaccination is important to prevent the spread of disease, and a live-attenuated MP-12 vaccine is currently the only vaccine with a conditional license in the United States. This study determined the temperature sensitivity (ts) of MP-12

  8. Prevalence of antibodies against Rift Valley fever virus in Kenyan wildlife

    PubMed Central

    EVANS, A.; GAKUYA, F.; PAWESKA, J. T.; ROSTAL, M.; AKOOLO, L.; VAN VUREN, P. J.; MANYIBE, T.; MACHARIA, J. M.; KSIAZEK, T. G.; FEIKIN, D. R.; BREIMAN, R. F.; KARIUKI NJENGA, M.

    2008-01-01

    SUMMARY Rift Valley fever virus (RVFV) is an arbovirus associated with periodic outbreaks, mostly on the African continent, of febrile disease accompanied by abortion in livestock, and a severe, fatal haemorrhagic syndrome in humans. However, the maintenance of the virus during the inter-epidemic period (IEP) when there is low or no disease activity detected in livestock or humans has not been determined. This study report prevalence of RVFV-neutralizing antibodies in sera (n=896) collected from 16 Kenyan wildlife species including at least 35% that were born during the 1999–2006 IEP. Specimens from seven species had detectable neutralizing antibodies against RVFV, including African buffalo, black rhino, lesser kudu, impala, African elephant, kongoni, and waterbuck. High RVFV antibody prevalence (>15%) was observed in black rhinos and ruminants (kudu, impala, buffalo, and waterbuck) with the highest titres (up to 1:1280) observed mostly in buffalo, including animals born during the IEP. All lions, giraffes, plains zebras, and warthogs tested were either negative or less than two animals in each species had low (⩽1:16) titres of RVFV antibodies. Of 249 sera collected from five wildlife species during the 2006–2007 outbreak, 16 out of 19 (84%) of the ruminant (gerenuk, waterbuck, and eland) specimens had RVFV-neutralizing titres ⩾1:80. These data provide evidence that wild ruminants are infected by RVFV but further studies are required to determine whether these animals play a role in the virus maintenance between outbreaks and virus amplification prior to a noticeable outbreak. PMID:17988425

  9. Development and evaluation of one-step rRT-PCR and immunohistochemical methods for detection of Rift Valley fever virus in biosafety level 2 diagnostic laboratories

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) is a zoonotic insect transmitted virus endemic to Africa and the Arabian Peninsula. Infection causes abortions and high mortality in newborn ruminants with an overall human infection rate of <1%. The potential of RVFV as a bioterrorism agent and/or being accidentally i...

  10. Inter-epidemic Acquisition of Rift Valley Fever Virus in Humans in Tanzania

    PubMed Central

    Sumaye, Robert David; Abatih, Emmanuel Nji; Thiry, Etienne; Amuri, Mbaraka; Berkvens, Dirk; Geubbels, Eveline

    2015-01-01

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

  11. Relating coccidioidomycosis (valley fever) incidence to soil moisture conditions

    PubMed Central

    Coopersmith, E. J.; Bell, J. E.; Benedict, K.; Shriber, J.; McCotter, O.; Cosh, M. H.

    2017-01-01

    Coccidioidomycosis (also called Valley fever) is caused by a soilborne fungus, Coccidioides spp., in arid regions of the southwestern United States. Though some who develop infections from this fungus remain asymptomatic, others develop respiratory disease as a consequence. Less commonly, severe illness and death can occur when the infection spreads to other regions of the body. Previous analyses have attempted to connect the incidence of coccidioidomycosis to broadly available climatic measurements, such as precipitation or temperature. However, with the limited availability of long-term, in situ soil moisture data sets, it has not been feasible to perform a direct analysis of the relationships between soil moisture levels and coccidioidomycosis incidence on a larger temporal and spatial scale. Utilizing in situ soil moisture gauges throughout the southwest from the U.S. Climate Reference Network and a model with which to extend those estimates, this work connects periods of higher and lower soil moisture in Arizona and California between 2002 and 2014 to the reported incidence of coccidioidomycosis. The results indicate that in both states, coccidioidomycosis incidence is related to soil moisture levels from previous summers and falls. Stated differently, a higher number of coccidioidomycosis cases are likely to be reported if previous bands of months have been atypically wet or dry, depending on the location. PMID:29124249

  12. Spatial and Temporal Pattern of Rift Valley Fever Outbreaks in Tanzania; 1930 to 2007

    PubMed Central

    Sindato, Calvin; Karimuribo, Esron D.; Pfeiffer, Dirk U.; Mboera, Leonard E. G.; Kivaria, Fredrick; Dautu, George; Bernard, Bett; Paweska, Janusz T.

    2014-01-01

    Background Rift Valley fever (RVF)-like disease was first reported in Tanzania more than eight decades ago and the last large outbreak of the disease occurred in 2006–07. This study investigates the spatial and temporal pattern of RVF outbreaks in Tanzania over the past 80 years in order to guide prevention and control strategies. Materials and Methods A retrospective study was carried out based on disease reporting data from Tanzania at district or village level. The data were sourced from the Ministries responsible for livestock and human health, Tanzania Meteorological Agency and research institutions involved in RVF surveillance and diagnosis. The spatial distribution of outbreaks was mapped using ArcGIS 10. The space-time permutation model was applied to identify clusters of cases, and a multivariable logistic regression model was used to identify risk factors associated with the occurrence of outbreaks in the district. Principal Findings RVF outbreaks were reported between December and June in 1930, 1947, 1957, 1960, 1963, 1968, 1977–79, 1989, 1997–98 and 2006–07 in 39.2% of the districts in Tanzania. There was statistically significant spatio-temporal clustering of outbreaks. RVF occurrence was associated with the eastern Rift Valley ecosystem (OR = 6.14, CI: 1.96, 19.28), total amount of rainfall of >405.4 mm (OR = 12.36, CI: 3.06, 49.88), soil texture (clay [OR = 8.76, CI: 2.52, 30.50], and loam [OR = 8.79, CI: 2.04, 37.82]). Conclusion/Significance RVF outbreaks were found to be distributed heterogeneously and transmission dynamics appeared to vary between areas. The sequence of outbreak waves, continuously cover more parts of the country. Whenever infection has been introduced into an area, it is likely to be involved in future outbreaks. The cases were more likely to be reported from the eastern Rift Valley than from the western Rift Valley ecosystem and from areas with clay and loam rather than sandy soil texture. PMID:24586433

  13. The 2007 Rift Valley Fever Outbreak in Sudan

    PubMed Central

    Hassan, Osama Ahmed; Ahlm, Clas; Sang, Rosemary; Evander, Magnus

    2011-01-01

    Rift Valley fever (RVF) is a neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health and economy. RVF is caused by RVF virus (RVFV) affecting humans and a wide range of animals. The virus is transmitted through bites from mosquitoes and exposure to viremic blood, body fluids, or tissues of infected animals. During 2007 a large RVF outbreak occurred in Sudan with a total of 747 confirmed human cases including 230 deaths (case fatality 30.8%); although it has been estimated 75,000 were infected. It was most severe in White Nile, El Gezira, and Sennar states near to the White Nile and the Blue Nile Rivers. Notably, RVF was not demonstrated in livestock until after the human cases appeared and unfortunately, there are no records or reports of the number of affected animals or deaths. Ideally, animals should serve as sentinels to prevent loss of human life, but the situation here was reversed. Animal contact seemed to be the most dominant risk factor followed by animal products and mosquito bites. The Sudan outbreak followed an unusually heavy rainfall in the country with severe flooding and previous studies on RVF in Sudan suggest that RVFV is endemic in parts of Sudan. An RVF outbreak results in human disease, but also large economic loss with an impact beyond the immediate influence on the directly affected agricultural producers. The outbreak emphasizes the need for collaboration between veterinary and health authorities, entomologists, environmental specialists, and biologists, as the best strategy towards the prevention and control of RVF. PMID:21980543

  14. A Public Health Issue Related To Collateral Seismic Hazards: The Valley Fever Outbreak Triggered By The 1994 Northridge, California Earthquake

    NASA Astrophysics Data System (ADS)

    Jibson, Randall W.

    Following the 17 January 1994 Northridge, California earthquake (M = 6.7), Ventura County, California, experienced a major outbreak ofcoccidioidomycosis (CM), commonly known as valley fever, a respiratory disease contracted byinhaling airborne fungal spores. In the 8 weeks following the earthquake (24 Januarythrough 15 March), 203 outbreak-associated cases were reported, which is about an order of magnitude more than the expected number of cases, and three of these cases were fatal.Simi Valley, in easternmost Ventura County, had the highest attack rate in the county,and the attack rate decreased westward across the county. The temporal and spatial distribution of CM cases indicates that the outbreak resulted from inhalation of spore-contaminated dust generated by earthquake-triggered landslides. Canyons North East of Simi Valleyproduced many highly disrupted, dust-generating landslides during the earthquake andits aftershocks. Winds after the earthquake were from the North East, which transporteddust into Simi Valley and beyond to communities to the West. The three fatalities from the CM epidemic accounted for 4 percent of the total earthquake-related fatalities.

  15. Evidence for enzootic circulation of Rift Valley fever virus among livestock in Cameroon.

    PubMed

    Rissmann, M; Eiden, M; Wade, A; Poueme, R; Abdoulkadiri, S; Unger, H; Ziegler, U; Homeier, T; Groschup, M H

    2017-08-01

    Rift Valley fever virus (RVFV) is an arthropod-borne pathogen, causing serious epidemics in Africa and the Arabian Peninsula. In Cameroon serological data indicate the presence of RVFV, but active circulation of RVFV, causing clinical infections has not been proven yet. For this purpose we carried out a serological and molecular study on a total of 1953 randomly selected serum samples of small ruminants and cattle, which were collected in years 2013 and 2014 in Cameroon. In a first step, sera were screened serologically using a variety of assay formats to reveal RVFV specific antibodies. At the second stage, seropositive specimen were assessed for acute RVFV infections via IgM-specific ELISA and quantitative real-time RT-PCR. Our data show a significant difference in the antibody prevalence in cattle (13.5% [95% confidence interval: 11.4-15.7]) and small ruminants (3.4% [95% confidence interval: 2.3-4.7]), with indications for annual fluctuations and significant regional differences of seropositivity. One small ruminant and three bovines were eventually found to be positive in IgM ELISA and indications for viremia were found in one bovine by RVFV genome detection using quantitative real-time RT-PCR. The results of this study therefore corroborate the presence of acute RVFV-infection and its circulation in Cameroon. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells.

    PubMed

    Lokugamage, Nandadeva; Ikegami, Tetsuro

    2017-01-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa which affects both ruminants and humans. RVF causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-, Medium (M)-, and Small (S)-segments. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the U.S. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-, M-, and S-segments. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L- and M-segments. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive (ts) phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital PCR analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A ts mutation after excessive viral passages in culture cells.

  17. Functional Analysis of Rift Valley Fever Virus NSs Encoding a Partial Truncation

    PubMed Central

    Head, Jennifer A.; Kalveram, Birte; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV), belongs to genus Phlebovirus of the family Bunyaviridae, causes high rates of abortion and fetal malformation in infected ruminants as well as causing neurological disorders, blindness, or lethal hemorrhagic fever in humans. RVFV is classified as a category A priority pathogen and a select agent in the U.S., and currently there are no therapeutics available for RVF patients. NSs protein, a major virulence factor of RVFV, inhibits host transcription including interferon (IFN)-β mRNA synthesis and promotes degradation of dsRNA-dependent protein kinase (PKR). NSs self-associates at the C-terminus 17 aa., while NSs at aa.210–230 binds to Sin3A-associated protein (SAP30) to inhibit the activation of IFN-β promoter. Thus, we hypothesize that NSs function(s) can be abolished by truncation of specific domains, and co-expression of nonfunctional NSs with intact NSs will result in the attenuation of NSs function by dominant-negative effect. Unexpectedly, we found that RVFV NSs truncated at aa. 6–30, 31–55, 56–80, 81–105, 106–130, 131–155, 156–180, 181–205, 206–230, 231–248 or 249–265 lack functions of IFN–β mRNA synthesis inhibition and degradation of PKR. Truncated NSs were less stable in infected cells, while nuclear localization was inhibited in NSs lacking either of aa.81–105, 106–130, 131–155, 156–180, 181–205, 206–230 or 231–248. Furthermore, none of truncated NSs had exhibited significant dominant-negative functions for NSs-mediated IFN-β suppression or PKR degradation upon co-expression in cells infected with RVFV. We also found that any of truncated NSs except for intact NSs does not interact with RVFV NSs even in the presence of intact C-terminus self-association domain. Our results suggest that conformational integrity of NSs is important for the stability, cellular localization and biological functions of RVFV NSs, and the co-expression of truncated NSs does not exhibit dominant

  18. Evaluation of efficacy, potential for vector transmission and duration of immunity testing of MP-12, an attenuated Rift Valley fever virus vaccine candidate, in sheep

    USDA-ARS?s Scientific Manuscript database

    Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. There are currently no fully licensed vaccines for this arthropod-borne virus in the US. Studies in sheep and cattle have found an attenuated strain of RVFV, MP-12, to be both safe and efficacious, and a conditi...

  19. Postepidemic analysis of Rift Valley fever virus transmission in northeastern kenya: a village cohort study.

    PubMed

    LaBeaud, A Desirée; Muiruri, Samuel; Sutherland, Laura J; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M; Peters, Clarence J; King, Charles H

    2011-08-01

    In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an

  20. Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study

    PubMed Central

    LaBeaud, A. Desirée; Muiruri, Samuel; Sutherland, Laura J.; Dahir, Saidi; Gildengorin, Ginny; Morrill, John; Muchiri, Eric M.; Peters, Clarence J.; King, Charles H.

    2011-01-01

    Background In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006–2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies. Methodology/Findings We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006–2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI95%:17%–29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI95%: 20%–39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT80)) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤20/80) was much more likely in the RVFV-seropositive group (P<0.0001). Conclusions Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at >1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with

  1. High-throughput label-free microcontact printing graphene-based biosensor for valley fever.

    PubMed

    Tsai, Shih-Ming; Goshia, Tyler; Chen, Yen-Chang; Kagiri, Agnes; Sibal, Angelo; Chiu, Meng-Hsuen; Gadre, Anand; Tung, Vincent; Chin, Wei-Chun

    2018-06-18

    The highly prevalent and virulent disease in the Western Hemisphere Coccidioidomycosis, also known as Valley Fever, can cause serious illness such as severe pneumonia with respiratory failure. It can also take on a disseminated form where the infection spreads throughout the body. Thus, a serious impetus exists to develop effective detection of the disease that can also operate in a rapid and high-throughput fashion. Here, we report the assembly of a highly sensitive biosensor using reduced graphene oxide (rGO) with Coccidioides(cocci) antibodies as the target analytes. The facile design made possible by the scalable microcontact printing (μCP) surface patterning technique which enables rapid, ultrasensitive detection. It provides a wide linear range and sub picomolar (2.5 pg/ml) detection, while also delivering high selectivity and reproducibility. This work demonstrates an important advancement in the development of a sensitive label-free rGO biosensor for Coccidioidomycosis detection. This result also provides the potential application of direct pathogen diagnosis for the future biosensor development. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Multiplex Detection of IgG and IgM to Rift Valley Fever Virus Nucleoprotein, Nonstructural Proteins, and Glycoprotein in Ovine and Bovine.

    PubMed

    Hossain, Mohammad M; Wilson, William C; Faburay, Bonto; Richt, Jürgen; McVey, David S; Rowland, Raymond R

    2016-08-01

    A multiplex fluorescence microsphere immunoassay (FMIA) was used to detect bovine and ovine IgM and IgG antibodies to several Rift Valley fever virus (RVFV) proteins, including the major surface glycoprotein, Gn; the nonstructural proteins, NSs and NSm; and the nucleoprotein, N. Target antigens were assembled into a multiplex and tested in serum samples from infected wild-type RVFV or MP12, a modified live virus vaccine. As expected, the N protein was immunodominant and the best target for early detection of infection. Antibody activity against the other targets was also detected. The experimental results demonstrate the capabilities of FMIA for the detection of antibodies to RVFV structural and nonstructural proteins, which can be applied to future development and validation of diagnostic tests that can be used to differentiate vaccinated from infected animals.

  3. Persistence of Rift Valley fever virus in East Africa

    NASA Astrophysics Data System (ADS)

    Gachohi, J.; Hansen, F.; Bett, B.; Kitala, P.

    2012-04-01

    Rift Valley fever virus (RVFv) is a mosquito-borne pathogen of livestock, wildlife and humans that causes severe outbreaks in intervals of several years. One of the open questions is how the virus persists between outbreaks. We developed a spatially-explicit, individual-based simulation model of the RVFv transmission dynamics to investigate this question. The model, is based on livestock and mosquito population dynamics. Spatial aspects are explicitly represented by a set of grid cells that represent mosquito breeding sites. A grid cell measures 500 by 500m and the model considers a grid of 100 by 100 grid cells; the model thus operates on the regional scale of 2500km2. Livestock herds move between grid cells, and provide connectivity between the cells. The model is used to explore the spatio-temporal dynamics of RVFv persistence in absence of a wildlife reservoir in an east African semi-arid context. Specifically, the model assesses the importance of local virus persistence in mosquito breeding sites relative to global virus persistence mitigated by movement of hosts. Local persistence is determined by the length of time the virus remains in a mosquito breeding site once introduced. In the model, this is a function of the number of mosquitoes that emerge infected and their lifespan. Global persistence is determined by the level of connectivity between isolated grid cells. Our work gives insights into the ecological and epidemiological conditions under which RVFv persists. The implication for disease surveillance and management are discussed.

  4. Nonspreading Rift Valley Fever Virus Infection of Human Dendritic Cells Results in Downregulation of CD83 and Full Maturation of Bystander Cells.

    PubMed

    Oreshkova, Nadia; Wichgers Schreur, Paul J; Spel, Lotte; Vloet, Rianka P M; Moormann, Rob J M; Boes, Marianne; Kortekaas, Jeroen

    2015-01-01

    Vaccines based on nonspreading Rift Valley fever virus (NSR) induce strong humoral and robust cellular immune responses with pronounced Th1 polarisation. The present work was aimed to gain insight into the molecular basis of NSR-mediated immunity. Recent studies have demonstrated that wild-type Rift Valley fever virus efficiently targets and replicates in dendritic cells (DCs). We found that NSR infection of cultured human DCs results in maturation of DCs, characterized by surface upregulation of CD40, CD80, CD86, MHC-I and MHC-II and secretion of the proinflammatory cytokines IFN-β, IL-6 and TNF. Interestingly, expression of the most prominent marker of DC maturation, CD83, was consistently downregulated at 24 hours post infection. Remarkably, NSR infection also completely abrogated CD83 upregulation by LPS. Downregulation of CD83 was not associated with reduced mRNA levels or impaired CD83 mRNA transport from the nucleus and could not be prevented by inhibition of the proteasome or endocytic degradation pathways, suggesting that suppression occurs at the translational level. In contrast to infected cells, bystander DCs displayed full maturation as evidenced by upregulation of CD83. Our results indicate that bystander DCs play an important role in NSR-mediated immunity.

  5. Pathogenic effects of Rift Valley fever virus NSs gene are alleviated in cultured cells by expressed antiviral short hairpin RNAs.

    PubMed

    Scott, Tristan; Paweska, Janusz T; Arbuthnot, Patrick; Weinberg, Marc S

    2012-01-01

    Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, may cause severe hepatitis, encephalitis and haemorrhagic fever in humans. There are currently no available licensed vaccines or therapies to treat the viral infection in humans. RNA interference (RNAi)-based viral gene silencing offers a promising approach to inhibiting replication of this highly pathogenic virus. The small (S) segment of the RVFV tripartite genome carries the genetic determinates for pathogenicity during infection. This segment encodes the non-structural S (NSs) and essential nucleocapsid (N) genes. To advance RNAi-based inhibition of RVFV replication, we designed several Pol III short hairpin RNA (shRNA) expression cassettes against the NSs and N genes, including a multimerized plasmid vector that included four shRNA expression cassettes. Effective target silencing was demonstrated using full- and partial-length target reporter assays, and confirmed by western blot analysis of exogenous N and NSs expression. Small RNA northern blots showed detectable RNAi guide strand formation from single and multimerized shRNA constructs. Using a cell culture model of RVFV replication, shRNAs targeting the N gene decreased intracellular nucleocapsid protein concentration and viral replication. The shRNAs directed against the NSs gene reduced NSs protein concentrations and alleviated NSs-mediated cytotoxicity, which may be caused by host transcription suppression. These data are the first demonstration that RNAi activators have a potential therapeutic benefit for countering RVFV infection.

  6. Epidemiology of brucellosis, Q Fever and Rift Valley Fever at the human and livestock interface in northern Côte d'Ivoire.

    PubMed

    Kanouté, Youssouf B; Gragnon, Biégo G; Schindler, Christian; Bonfoh, Bassirou; Schelling, Esther

    2017-01-01

    Northern Côte d'Ivoire is the main livestock breeding zone and has the highest livestock cross-border movements in Côte d'Ivoire. The aim of this study was to provide updated epidemiological data on three neglected zoonotic diseases, namely brucellosis, Q Fever and Rift Valley Fever (RVF). We conducted three-stage cross-sectional cluster surveys in livestock and humans between 2012 and 2014 in a random selection of 63 villages and a sample of 633 cattle, 622 small ruminants and 88 people. We administered questionnaires to capture risk factors and performed serological tests including the Rose Bengal Plate Test (RBPT), Brucella spp. indirect and competitive ELISAs, Coxiella burnetii indirect ELISA and RVF competitive ELISA. The human seroprevalence for Brucella spp. was 5.3%. RBPT-positive small ruminants tested negative by the indirect ELISA. The seroprevalence of Brucella spp. in cattle adjusted for clustering was 4.6%. Cattle aged 5-8 years had higher odds of seropositivity (OR=3.5) than those aged ≤4years. The seropositivity in cattle was associated with having joint hygromas (OR=9), sharing the pastures with small ruminants (OR=5.8) and contact with pastoralist herds (OR=11.3). The seroprevalence of Q Fever was 13.9% in cattle, 9.4% in sheep and 12.4% in goats. The seroprevalence of RVF was 3.9% in cattle, 2.4% in sheep and 0% in goats. Seropositive ewes had greater odds (OR=4.7) of abortion than seronegative ones. In cattle, a shorter distance between the night pens and nearest permanent water bodies was a protective factor (OR=0.1). The study showed that the exposure to the three zoonoses is rather low in northern Côte d'Ivoire. Within a One Health approach, cost-benefit and cost-effectiveness of control measures should be assessed for an integrated control. Copyright © 2016. Published by Elsevier B.V.

  7. Incorporation of antigens from whole cell lysates and purified virions from MP12 into fluorescence microsphere immunoassays for the detection of antibodies against Rift Valley fever virus

    USDA-ARS?s Scientific Manuscript database

    Background: The purpose of this study was the development of multiplex fluorescence microsphere immunoassay (FMIA) for the detection of Rift Valley fever virus (RVFV) IgG and IgM antibodies by incorporation of antigens from whole cell lysates and purified virions from MP12. Methods and Findings: Vir...

  8. N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN.

    PubMed

    Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E; Huante, Matthew B; Slack, Olga A L; Carpio, Victor H; Freiberg, Alexander N; Ikegami, Tetsuro

    2016-05-23

    Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)-any amino acid (X)-serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: "Gc-large" and "Gc-small", and N1077 was responsible for "Gc-large" band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN.

  9. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    PubMed Central

    Koehler, Jeffrey W.; Smith, Jeffrey M.; Ripoll, Daniel R.; Spik, Kristin W.; Taylor, Shannon L.; Badger, Catherine V.; Grant, Rebecca J.; Ogg, Monica M.; Wallqvist, Anders; Guttieri, Mary C.; Garry, Robert F.; Schmaljohn, Connie S.

    2013-01-01

    For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors. PMID:24069485

  10. Nuclear relocalization of polyadenylate binding protein during rift valley fever virus infection involves expression of the NSs gene.

    PubMed

    Copeland, Anna Maria; Altamura, Louis A; Van Deusen, Nicole M; Schmaljohn, Connie S

    2013-11-01

    Rift Valley fever virus (RVFV), an ambisense member of the family Bunyaviridae, genus Phlebovirus, is the causative agent of Rift Valley fever, an important zoonotic infection in Africa and the Middle East. Phlebovirus proteins are translated from virally transcribed mRNAs that, like host mRNA, are capped but, unlike host mRNAs, are not polyadenylated. Here, we investigated the role of PABP1 during RVFV infection of HeLa cells. Immunofluorescence studies of infected cells demonstrated a gross relocalization of PABP1 to the nucleus late in infection. Immunofluorescence microscopy studies of nuclear proteins revealed costaining between PABP1 and markers of nuclear speckles. PABP1 relocalization was sharply decreased in cells infected with a strain of RVFV lacking the gene encoding the RVFV nonstructural protein S (NSs). To determine whether PABP1 was required for RVFV infection, we measured the production of nucleocapsid protein (N) in cells transfected with small interfering RNAs (siRNAs) targeting PABP1. We found that the overall percentage of RVFV N-positive cells was not changed by siRNA treatment, indicating that PABP1 was not required for RVFV infection. However, when we analyzed populations of cells producing high versus low levels of PABP1, we found that the percentage of RVFV N-positive cells was decreased in cell populations producing physiologic levels of PABP1 and increased in cells with reduced levels of PABP1. Together, these results suggest that production of the NSs protein during RVFV infection leads to sequestration of PABP1 in the nuclear speckles, creating a state within the cell that favors viral protein production.

  11. Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice

    PubMed Central

    Papin, James F.; Verardi, Paulo H.; Jones, Leslie A.; Monge-Navarro, Francisco; Brault, Aaron C.; Holbrook, Michael R.; Worthy, Melissa N.; Freiberg, Alexander N.; Yilma, Tilahun D.

    2011-01-01

    Rift Valley fever (RVF) is a zoonotic disease endemic in Africa and the Arabian Peninsula caused by the highly infectious Rift Valley fever virus (RVFV) that can be lethal to humans and animals and results in major losses in the livestock industry. RVF is exotic to the United States; however, mosquito species native to this region can serve as biological vectors for the virus. Thus, accidental or malicious introduction of this virus could result in RVFV becoming endemic in North America. Such an event would likely lead to significant morbidity and mortality in humans, and devastating economic effects on the livestock industry. Currently, there are no licensed vaccines for RVF that are both safe and efficacious. To address this issue, we developed two recombinant RVFV vaccines using vaccinia virus (VACV) as a vector for use in livestock. The first vaccine, vCOGnGc, was attenuated by the deletion of a VACV gene encoding an IFN-γ binding protein, insertional inactivation of the thymidine kinase gene, and expression of RVFV glycoproteins, Gn and Gc. The second vaccine, vCOGnGcγ, is identical to the first and also expresses the human IFN-γ gene to enhance safety. Both vaccines are extremely safe; neither resulted in weight loss nor death in severe combined immunodeficient mice, and pock lesions were smaller in baboons compared with the controls. Furthermore, both vaccines induced protective levels of antibody titers in vaccinated mice and baboons. Mice were protected from lethal RVFV challenge. Thus, we have developed two safe and efficacious recombinant vaccines for RVF. PMID:21873194

  12. Operational guidelines (version 1.0) for geological fieldwork in areas endemic for Coccidioidomycosis (Valley Fever)

    USGS Publications Warehouse

    Fisher, Frederick S.; Bultman, Mark W.; Pappagianis, Demosthenes

    2000-01-01

    Coccidioidomycosis (Valley Fever) is a disease caused by the inhalation of the arthroconidia (spores) of Coccidioides immitis, a fungus that lives in the soils of southwestern United States. Although large numbers of people are exposed to the arthroconidia and are consequently infected, very few individuals contract the more serious forms of the disease. Earth scientists working in field areas where Coccidioides immitis is endemic have an increased risk of becoming infected. Because field operations often disturb the upper surface of the ground, they may inhale large numbers of arthroconidia. This also increases their risk of developing more severe forms of the disease. Any other occupations or activities that create dusty conditions in endemic areas also have increased risk of infection. Risk management strategies can lower the incidence of infection and also reduce the numbers of arthroconidia inhaled thereby decreasing the chances of developing more serious disease. Dust control, by utilizing dust masks, and dust prevention, by limiting ground disturbing activities, are the primary weapons against infection. However, infection risk can also be lowered by conducting fields studies in the winter months; avoiding sites favorable for Coccidioides immitis growth; seeking prompt medical treatment if flu-like or respiratory illness occur during, or within a few weeks following, fieldwork; getting a coccidioidin skin test to determine susceptibility to the disease; and by educating all members of the field party about the possibilities and consequences of infection.

  13. Rift valley fever virus infection of human cells and insect hosts is promoted by protein kinase C epsilon.

    PubMed

    Filone, Claire Marie; Hanna, Sheri L; Caino, M Cecilia; Bambina, Shelly; Doms, Robert W; Cherry, Sara

    2010-11-24

    As an arthropod-borne human pathogen, Rift Valley fever virus (RVFV) cycles between an insect vector and mammalian hosts. Little is known about the cellular requirements for infection in either host. Here we developed a tissue culture model for RVFV infection of human and insect cells that is amenable to high-throughput screening. Using this approach we screened a library of 1280 small molecules with pharmacologically defined activities and identified 59 drugs that inhibited RVFV infection with 15 inhibiting RVFV replication in both human and insect cells. Amongst the 15 inhibitors that blocked infection in both hosts was a subset that inhibits protein kinase C. Further studies found that infection is dependent upon the novel protein kinase C isozyme epsilon (PKCε) in both human and insect cells as well as in adult flies. Altogether, these data show that inhibition of cellular factors required for early steps in the infection cycle including PKCε can block RVFV infection, and may represent a starting point for the development of anti-RVFV therapeutics.

  14. Identification of central Kenyan Rift Valley Fever virus vector habitats with Landsat TM and evaluation of their flooding status with airborne imaging radar

    NASA Technical Reports Server (NTRS)

    Pope, K. O.; Sheffner, E. J.; Linthicum, K. J.; Bailey, C. L.; Logan, T. M.; Kasischke, E. S.; Birney, K.; Njogu, A. R.; Roberts, C. R.

    1992-01-01

    Rift Valley Fever (RVF) is a mosquito-borne virus that affects livestock and humans in Africa. Landsat TM data are shown to be effective in identifying dambos, intermittently flooded areas that are potential mosquite breeding sites, in an area north of Nairobi, Kenya. Positive results were obtained from a limited test of flood detection in dambos with airborne high resolution L, C, and X band multipolarization SAR imagery. L and C bands were effective in detecting flooded dambos, but LHH was by far the best channel for discrimination between flooded and nonflooded sites in both sedge and short-grass environments. This study demonstrates the feasibility of a combined passive and active remote sensing program for monitoring the location and condition of RVF vector habitats, thus making future control of the disease more promising.

  15. Rift Valley fever virus (Bunyaviridae: Phlebovirus): an update on pathogenesis, molecular epidemiology, vectors, diagnostics and prevention

    PubMed Central

    Pepin, Michel; Bouloy, Michèle; Bird, Brian H.; Kemp, Alan; Paweska, Janusz

    2010-01-01

    Rift Valley fever (RVF) virus is an arbovirus in the Bunyaviridae family that, from phylogenetic analysis, appears to have first emerged in the mid-19th century and was only identified at the begininning of the 1930s in the Rift Valley region of Kenya. Despite being an arbovirus with a relatively simple but temporally and geographically stable genome, this zoonotic virus has already demonstrated a real capacity for emerging in new territories, as exemplified by the outbreaks in Egypt (1977), Western Africa (1988) and the Arabian Peninsula (2000), or for re-emerging after long periods of silence as observed very recently in Kenya and South Africa. The presence of competent vectors in countries previously free of RVF, the high viral titres in viraemic animals and the global changes in climate, travel and trade all contribute to make this virus a threat that must not be neglected as the consequences of RVF are dramatic, both for human and animal health. In this review, we present the latest advances in RVF virus research. In spite of this renewed interest, aspects of the epidemiology of RVF virus are still not fully understood and safe, effective vaccines are still not freely available for protecting humans and livestock against the dramatic consequences of this virus. PMID:21188836

  16. Valley fever: finding new places for an old disease: Coccidioides immitis found in Washington State soil associated with recent human infection.

    PubMed

    Litvintseva, Anastasia P; Marsden-Haug, Nicola; Hurst, Steven; Hill, Heather; Gade, Lalitha; Driebe, Elizabeth M; Ralston, Cindy; Roe, Chandler; Barker, Bridget M; Goldoft, Marcia; Keim, Paul; Wohrle, Ron; Thompson, George R; Engelthaler, David M; Brandt, Mary E; Chiller, Tom

    2015-01-01

    We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. Evaluation of lamb and calf responses to Rift Valley fever MP-12 vaccination.

    PubMed

    Wilson, William C; Bawa, Bhupinder; Drolet, Barbara S; Lehiy, Chris; Faburay, Bonto; Jasperson, Dane C; Reister, Lindsey; Gaudreault, Natasha N; Carlson, Jolene; Ma, Wenjun; Morozov, Igor; McVey, D Scott; Richt, Jürgen A

    2014-08-06

    Rift Valley fever (RVF) is an important viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. The disease is of concern to international agricultural and public health communities. The RVFV MP-12 strain has been the most safety tested attenuated vaccine strain; thus it is being considered as a potential vaccine for the US national veterinary stockpile. This study was designed to establish safety protocols for large animal research with virulent RVF viruses, establish a target host immune response baseline using RVF MP-12 strain, and independently evaluate this strain as a potential US emergency response vaccine. Ten, approximately four month-old lambs and calves were vaccinated with RVF MP-12 strain; two additional animals per species provided negative control specimens. The animals were monitored for clinical and immune response, fever, and viremia. Two animals per species were sacrificed on 2, 3, 4, 10 and 28 days post infection and full necropsies were performed for histopathological examination. No clinical or febrile responses were observed in this study. The onset and titer of the immune response is discussed. There was no significant histopathology in the lambs; however, 6 out of 10 vaccinated calves had multifocal, random areas of hepatocellular degeneration and necrosis. RVF MP12 antigen was detected in these areas of necrosis by immunohistochemistry in one calf. This study provides independent and baseline information on the RVF MP-12 attenuated vaccination in vaccine relevant age target species and indicates the importance of performing safety testing on vaccine relevant aged target animals. Published by Elsevier B.V.

  18. The Nonstructural Protein NSs Induces a Variable Antibody Response in Domestic Ruminants Naturally Infected with Rift Valley Fever Virus

    PubMed Central

    Fernandez, José-Carlos; Billecocq, Agnès; Durand, Jean Paul; Cêtre-Sossah, Catherine; Cardinale, Eric; Marianneau, Philippe; Pépin, Michel; Tordo, Noël

    2012-01-01

    Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines. PMID:22072723

  19. The nonstructural protein NSs induces a variable antibody response in domestic ruminants naturally infected with Rift Valley fever virus.

    PubMed

    Fernandez, José-Carlos; Billecocq, Agnès; Durand, Jean Paul; Cêtre-Sossah, Catherine; Cardinale, Eric; Marianneau, Philippe; Pépin, Michel; Tordo, Noël; Bouloy, Michèle

    2012-01-01

    Rift Valley fever (RVF) is an emerging zoonosis in Africa which has spread to Egypt, the Arabian Peninsula, Madagascar, and Comoros. RVF virus (RVFV) (Bunyaviridae family, Phlebovirus genus) causes a wide range of symptoms in humans, from benign fever to fatal hemorrhagic fever. Ruminants are severely affected by the disease, which leads to a high rate of mortality in young animals and to abortions and teratogenesis in pregnant females. Diagnostic tests include virus isolation and genome or antibody detection. During RVFV infection, the nucleoprotein encapsidating the tripartite RNA genome is expressed in large amounts and raises a robust antibody response, while the envelope glycoproteins elicit neutralizing antibodies which play a major role in protection. Much less is known about the antigenicity/immunogenicity of the nonstructural protein NSs, which is a major virulence factor. Here we have developed a competitive enzyme-linked immunosorbent assay (ELISA) enabling detection of low levels of NSs-specific antibodies in naturally infected or vaccinated ruminants. Detection of the NSs antibodies was validated by Western blotting. Altogether, our data showed that the NSs antibodies were detected in only 55% of animals naturally infected by RVFV, indicating that NSs does not induce a consistently high immune response. These results are discussed in light of differentiation between infected and vaccinated animals (DIVA) tests distinguishing naturally infected animals and those vaccinated with NSs-defective vaccines.

  20. N-Glycans on the Rift Valley Fever Virus Envelope Glycoproteins Gn and Gc Redundantly Support Viral Infection via DC-SIGN

    PubMed Central

    Phoenix, Inaia; Nishiyama, Shoko; Lokugamage, Nandadeva; Hill, Terence E.; Huante, Matthew B.; Slack, Olga A.L.; Carpio, Victor H.; Freiberg, Alexander N.; Ikegami, Tetsuro

    2016-01-01

    Rift Valley fever is a mosquito-transmitted, zoonotic disease that infects humans and ruminants. Dendritic cell specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) acts as a receptor for members of the phlebovirus genus. The Rift Valley fever virus (RVFV) glycoproteins (Gn/Gc) encode five putative N-glycan sequons (asparagine (N)–any amino acid (X)–serine (S)/threonine (T)) at positions: N438 (Gn), and N794, N829, N1035, and N1077 (Gc). The N-glycosylation profile and significance in viral infection via DC-SIGN have not been elucidated. Gc N-glycosylation was first evaluated by using Gc asparagine (N) to glutamine (Q) mutants. Subsequently, we generated a series of recombinant RVFV MP-12 strain mutants, which encode N-to-Q mutations, and the infectivity of each mutant in Jurkat cells stably expressing DC-SIGN was evaluated. Results showed that Gc N794, N1035, and N1077 were N-glycosylated but N829 was not. Gc N1077 was heterogeneously N-glycosylated. RVFV Gc made two distinct N-glycoforms: “Gc-large” and “Gc-small”, and N1077 was responsible for “Gc-large” band. RVFV showed increased infection of cells expressing DC-SIGN compared to cells lacking DC-SIGN. Infection via DC-SIGN was increased in the presence of either Gn N438 or Gc N1077. Our study showed that N-glycans on the Gc and Gn surface glycoproteins redundantly support RVFV infection via DC-SIGN. PMID:27223297

  1. Laboratory Validation of the Sand Fly Fever Virus Antigen Assay

    DTIC Science & Technology

    2015-12-01

    several commercially available assays from VecTOR Test Systems Inc. for malaria, West Nile virus, Rift Valley fever virus, dengue , chikungunya, and...Sabin AB. 1955. Recent advances in our knowledge of dengue and sandfly fever. Am J Trop Med Hyg 4:198–207. Sather GE. 1970. Catalogue of arthropod

  2. Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication.

    PubMed

    Bell, Todd M; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Carey, Brian D; Lin, Shih-Chao; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A; Bailey, Charles L; Kehn-Hall, Kylene

    2018-04-13

    Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.

  3. Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

    PubMed Central

    Bell, Todd M.; Espina, Virginia; Lundberg, Lindsay; Pinkham, Chelsea; Brahms, Ashwini; Dahal, Bibha; Woodson, Caitlin; de la Fuente, Cynthia; Liotta, Lance A.; Bailey, Charles L.

    2018-01-01

    Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection. PMID:29652799

  4. Using remote sensing, ecological niche modeling, and Geographic Information Systems for Rift Valley fever risk assessment in the United States

    NASA Astrophysics Data System (ADS)

    Tedrow, Christine Atkins

    The primary goal in this study was to explore remote sensing, ecological niche modeling, and Geographic Information Systems (GIS) as aids in predicting candidate Rift Valley fever (RVF) competent vector abundance and distribution in Virginia, and as means of estimating where risk of establishment in mosquitoes and risk of transmission to human populations would be greatest in Virginia. A second goal in this study was to determine whether the remotely-sensed Normalized Difference Vegetation Index (NDVI) can be used as a proxy variable of local conditions for the development of mosquitoes to predict mosquito species distribution and abundance in Virginia. As part of this study, a mosquito surveillance database was compiled to archive the historical patterns of mosquito species abundance in Virginia. In addition, linkages between mosquito density and local environmental and climatic patterns were spatially and temporally examined. The present study affirms the potential role of remote sensing imagery for species distribution prediction, and it demonstrates that ecological niche modeling is a valuable predictive tool to analyze the distributions of populations. The MaxEnt ecological niche modeling program was used to model predicted ranges for potential RVF competent vectors in Virginia. The MaxEnt model was shown to be robust, and the candidate RVF competent vector predicted distribution map is presented. The Normalized Difference Vegetation Index (NDVI) was found to be the most useful environmental-climatic variable to predict mosquito species distribution and abundance in Virginia. However, these results indicate that a more robust prediction is obtained by including other environmental-climatic factors correlated to mosquito densities (e.g., temperature, precipitation, elevation) with NDVI. The present study demonstrates that remote sensing and GIS can be used with ecological niche and risk modeling methods to estimate risk of virus establishment in mosquitoes and

  5. Serological evidence of rift valley fever virus among acute febrile patients in Southern Mozambique during and after the 2013 heavy rainfall and flooding: implication for the management of febrile illness.

    PubMed

    Gudo, Eduardo Samo; Pinto, Gabriela; Weyer, Jacqueline; le Roux, Chantel; Mandlaze, Arcildo; José, Américo Feriano; Muianga, Argentina; Paweska, Janusz Tadeusz

    2016-06-08

    Rift Valley fever virus (RVFV) remains heavily neglected in humans in Mozambique, even though recent outbreaks were reported in neighboring countries in humans and several cases of RVFV in cattle were reported in several districts in Mozambique. We conducted a cross sectional study during and after severe flooding that occurred in 2013 in Mozambique. Paired acute and convalescent serum samples were tested from febrile patients attending a primary health care unit in a suburban area of Maputo city for the presence of IgG and IgM antibodies against Rift Valley fever virus (RVFV) using enzyme-linked immunosorbent assay (ELISA). Seroconversion of IgG anti-RVFV was observed in 5 % (10/200) of convalescent patients and specific IgM anti-RVFV was detected in one acute patient (0.5 %; 1/200). All sera from acute patient tested negative by real time PCR. In conclusion, our results suggest that RVF represent an important but neglected cause of febrile illness following periods of flooding in southern Mozambique.

  6. Reprint of "Epidemiology of brucellosis, Q Fever and Rift Valley Fever at the human and livestock interface in northern Côte d'Ivoire".

    PubMed

    Kanouté, Youssouf B; Gragnon, Biégo G; Schindler, Christian; Bonfoh, Bassirou; Schelling, Esther

    2017-11-01

    Northern Côte d'Ivoire is the main livestock breeding zone and has the highest livestock cross-border movements in Côte d'Ivoire. The aim of this study was to provide updated epidemiological data on three neglected zoonotic diseases, namely brucellosis, Q Fever and Rift Valley Fever (RVF). We conducted three-stage cross-sectional cluster surveys in livestock and humans between 2012 and 2014 in a random selection of 63 villages and a sample of 633 cattle, 622 small ruminants and 88 people. We administered questionnaires to capture risk factors and performed serological tests including the Rose Bengal Plate Test (RBPT), Brucella spp. indirect and competitive ELISAs, Coxiella burnetii indirect ELISA and RVF competitive ELISA. The human seroprevalence for Brucella spp. was 5.3%. RBPT-positive small ruminants tested negative by the indirect ELISA. The seroprevalence of Brucella spp. in cattle adjusted for clustering was 4.6%. Cattle aged 5-8 years had higher odds of seropositivity (OR=3.5) than those aged ≤4years. The seropositivity in cattle was associated with having joint hygromas (OR=9), sharing the pastures with small ruminants (OR=5.8) and contact with pastoralist herds (OR=11.3). The seroprevalence of Q Fever was 13.9% in cattle, 9.4% in sheep and 12.4% in goats. The seroprevalence of RVF was 3.9% in cattle, 2.4% in sheep and 0% in goats. Seropositive ewes had greater odds (OR=4.7) of abortion than seronegative ones. In cattle, a shorter distance between the night pens and nearest permanent water bodies was a protective factor (OR=0.1). The study showed that the exposure to the three zoonoses is rather low in northern Côte d'Ivoire. Within a One Health approach, cost-benefit and cost-effectiveness of control measures should be assessed for an integrated control. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments

    PubMed Central

    Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M

    2017-01-01

    Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83–248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence. PMID:28915104

  8. Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments.

    PubMed

    Barski, Michal; Brennan, Benjamin; Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M; Schwarz-Linek, Ulrich

    2017-09-15

    Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

  9. A Genome-Wide RNA Interference Screen Identifies a Role for Wnt/β-Catenin Signaling during Rift Valley Fever Virus Infection.

    PubMed

    Harmon, Brooke; Bird, Sara W; Schudel, Benjamin R; Hatch, Anson V; Rasley, Amy; Negrete, Oscar A

    2016-08-15

    Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. These studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses. Copyright © 2016 Harmon et al.

  10. A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

    DOE PAGES

    Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.; ...

    2016-05-25

    Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

  11. A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

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

    Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.

    Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

  12. Risk factors associated with human Rift Valley fever infection: systematic review and meta-analysis.

    PubMed

    Nicholas, Dennis E; Jacobsen, Kathryn H; Waters, Nigel M

    2014-12-01

    To identify risk factors for human Rift Valley fever virus (RVFV) infection. A systematic review identified 17 articles reporting on 16 studies examining risk factors for RVFV. Pooled odds ratios (pOR) were calculated for exposures examined in four or more studies. Being male [pOR = 1.4 (1.0, 1.8)], contact with aborted animal tissue [pOR = 3.4 (1.6, 7.3)], birthing an animal [pOR = 3.2 (2.4, 4.2)], skinning an animal [pOR = 2.5 (1.9, 3.2)], slaughtering an animal [pOR = 2.4 (1.4, 4.1)] and drinking raw milk [pOR = 1.8 (1.2, 2.6)] were significantly associated with RVF infection after meta-analysis. Other potential risk factors include sheltering animals in the home and milking an animal, which may both involve contact with animal body fluids. Based on the identified risk factors, use of personal protective equipment and disinfectants by animal handlers may help reduce RVFV transmission during outbreaks. Milk pasteurisation and other possible preventive methods require further investigation. © 2014 John Wiley & Sons Ltd.

  13. Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments

    PubMed Central

    Hill, Terence E.; Smith, Jennifer K.; Zhang, Lihong; Juelich, Terry L.; Gong, Bin; Slack, Olga A. L.; Ly, Hoai J.; Lokugamage, Nandadeva; Freiberg, Alexander N.

    2015-01-01

    ABSTRACT Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. IMPORTANCE Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to

  14. Rift Valley Fever Virus MP-12 Vaccine Is Fully Attenuated by a Combination of Partial Attenuations in the S, M, and L Segments.

    PubMed

    Ikegami, Tetsuro; Hill, Terence E; Smith, Jennifer K; Zhang, Lihong; Juelich, Terry L; Gong, Bin; Slack, Olga A L; Ly, Hoai J; Lokugamage, Nandadeva; Freiberg, Alexander N

    2015-07-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and characterized by a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. RVF is caused by Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), which has a tripartite negative-stranded RNA genome (consisting of the S, M, and L segments). Further spread of RVF into countries where the disease is not endemic may affect the economy and public health, and vaccination is an effective approach to prevent the spread of RVFV. A live-attenuated MP-12 vaccine is one of the best-characterized RVF vaccines for safety and efficacy and is currently conditionally licensed for use for veterinary purposes in the United States. Meanwhile, as of 2015, no other RVF vaccine has been conditionally or fully licensed for use in the United States. The MP-12 strain is derived from wild-type pathogenic strain ZH548, and its genome encodes 23 mutations in the three genome segments. However, the mechanism of MP-12 attenuation remains unknown. We characterized the attenuation of wild-type pathogenic strain ZH501 carrying a mutation(s) of the MP-12 S, M, or L segment in a mouse model. Our results indicated that MP-12 is attenuated by the mutations in the S, M, and L segments, while the mutations in the M and L segments confer stronger attenuation than those in the S segment. We identified a combination of 3 amino acid changes, Y259H (Gn), R1182G (Gc), and R1029K (L), that was sufficient to attenuate ZH501. However, strain MP-12 with reversion mutations at those 3 sites was still highly attenuated. Our results indicate that MP-12 attenuation is supported by a combination of multiple partial attenuation mutations and a single reversion mutation is less likely to cause a reversion to virulence of the MP-12 vaccine. Rift Valley fever (RVF) is a mosquito-transmitted viral disease that is endemic to Africa and that has the potential to spread into other

  15. NSs protein of rift valley fever virus promotes posttranslational downregulation of the TFIIH subunit p62.

    PubMed

    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-07-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.

  16. Knowledge, attitudes and practices on Rift Valley fever among agro pastoral communities in Kongwa and Kilombero districts, Tanzania.

    PubMed

    Shabani, Sasita S; Ezekiel, Mangi J; Mohamed, Mohamed; Moshiro, Candida S

    2015-08-21

    Rift valley fever (RVF) is a re-emerging viral vector-borne disease with rapid global socio-economic impact. A large RVF outbreak occurred in Tanzania in 2007 and affected more than half of the regions with high (47 %) case fatality rate. Little is known about RVF and its dynamics. A cross sectional study was conducted to assess the knowledge, attitudes and practices regarding RVF in Kongwa and Kilombero districts, Tanzania. We conducted a cross sectional survey among a randomly selected sample of individuals in 2011. We administered questionnaires to collect data on demographic characteristics, knowledge on symptoms, mode of transmission, prevention, attitudes and health seeking practices. A total of 463 community members participated in this study. The mean (±SD) age was 39.8 ± 14.4 years and 238 (51.4 %) were female. Majority of respondents had heard of RVF. However, only 8.8 % knew that mosquitoes were transmitting vectors. Male respondents were more likely to have greater knowledge about RVF. A small proportion mentioned clinical signs and symptoms of RVF in animals while 73.7 % mentioned unhealthy practices related to handling and consumption of dead animals. Thorough boiling of milk and cooking of meat were commonly mentioned as preventive measures for RVF. Majority (74.6 %) sought care for febrile illness at health facilities. Few (24.3 %) reported the use of protective gears to handle dead/sick animal while 15.5 % were consuming dead animals. Our study highlights the need to address the limited knowledge about RVF and promoting appropriate and timely health seeking practices. Rift valley fever outbreaks can be effectively managed with collaborative efforts of lay and professional communities with a shared perception that it poses a serious threat to public and animal health. The fact that this study was conducted in "high risk transmission areas" warrants further inquiry in other geographic regions with relatively low risk of RVF.

  17. Understanding the legal trade of cattle and camels and the derived risk of Rift Valley Fever introduction into and transmission within Egypt

    PubMed Central

    Chevalier, Veronique; Busquets, Núria; Calistri, Paolo; Casal, Jordi; Attia, Mohamed; Elbassal, Rehab; Hosni, Heba; Farrag, Hatem; Hassan, Noura; Tawfik, Rasha; Abd Elkader, Sohair; Bayomy, Shahin

    2018-01-01

    Rift Valley Fever (RVF) is a mosquito-borne zoonosis, which may cause significant losses for the livestock sector and have serious public health implications. Egypt has been repeatedly affected by RVF epidemics, mainly associated to the importation of animals from sub-Saharan countries, where the disease is endemic. The objective of our study was the improvement of the surveillance and control strategies implemented in Egypt. In order to do that, first we evaluated the legal trade of live animals into and within Egypt. Then, we assessed the risk of Rift Valley Fever virus (RVFV) transmission within the country using a multi-criteria evaluation approach. Finally, we combined the animal trade and the risk of RVFV transmission data to identify those areas and periods in which the introduction of RVFV is more likely. Our results indicate that the main risk of RVFV introduction is posed by the continuous flow of large number of camels coming from Sudan. The risk of RVFV transmission by vectors is restricted to the areas surrounding the Nile river, and does not vary significantly throughout the year. Imported camels are taken to quarantines, where the risk of RVFV transmission by vectors is generally low. Then, they are taken to animal markets or slaughterhouses, many located in populated areas, where the risk of RVFV transmission to animals or humans is much higher. The measures currently implemented (quarantines, vaccination or testing) seem to have a limited effect in reducing the risk of RVFV introduction, and therefore other (risk-based) surveillance strategies are proposed. PMID:29351273

  18. Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent Protein Kinase PKR

    PubMed Central

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Lokugamage, Nandadeva; Head, Jennifer A.; Ikegami, Tetsuro

    2012-01-01

    Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. PMID:23063407

  19. Rift Valley fever virus NSs inhibits host transcription independently of the degradation of dsRNA-dependent protein kinase PKR.

    PubMed

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Lokugamage, Nandadeva; Head, Jennifer A; Ikegami, Tetsuro

    2013-01-20

    Rift Valley fever virus (RVFV) encodes one major virulence factor, the NSs protein. NSs suppresses host general transcription, including interferon (IFN)-β mRNA synthesis, and promotes degradation of the dsRNA-dependent protein kinase (PKR). We generated a novel RVFV mutant (rMP12-NSsR173A) specifically lacking the function to promote PKR degradation. rMP12-NSsR173A infection induces early phosphorylation of eIF2α through PKR activation, while retaining the function to inhibit host general transcription including IFN-β gene inhibition. MP-12 NSs but not R173A NSs binds to wt PKR. R173A NSs formed filamentous structure in nucleus in a mosaic pattern, which was distinct from MP-12 NSs filament pattern. Due to early phosphorylation of eIF2α, rMP12-NSsR173A could not efficiently accumulate viral proteins. Our results suggest that NSs-mediated host general transcription suppression occurs independently of PKR degradation, while the PKR degradation is important to inhibit the phosphorylation of eIF2α in infected cells undergoing host general transcription suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Epidemiological Assessment of the Rift Valley Fever Outbreak in Kenya and Tanzania in 2006 and 2007

    PubMed Central

    Jost, Christine C.; Nzietchueng, Serge; Kihu, Simon; Bett, Bernard; Njogu, George; Swai, Emmanuel S.; Mariner, Jeffrey C.

    2010-01-01

    To capture lessons from the 2007 Rift Valley fever (RVF) outbreak, epidemiological studies were carried out in Kenya and Tanzania. Somali pastoralists proved to be adept at recognizing symptoms of RVF and risk factors such as heavy rainfall and mosquito swarms. Sandik, which means “bloody nose,” was used by Somalis to denote disease consistent with RVF. Somalis reported that sandik was previously seen in 1997/98, the period of the last RVF epidemic. Pastoralists communicated valuable epidemiological information for surveillance and early warning systems that was observed before international warnings. The results indicate that an all or none approach to decision making contributed to the delay in response. In the future, a phased approach balancing actions against increasing risk of an outbreak would be more effective. Given the time required to mobilize large vaccine stocks, emergency vaccination did not contribute to the mitigation of explosive outbreaks of RVF. PMID:20682908

  1. Seroprevalence of Antibodies against Chikungunya, Dengue, and Rift Valley Fever Viruses after Febrile Illness Outbreak, Madagascar

    PubMed Central

    Girmann, Mirko; Randriamampionona, Njary; Bialonski, Alexandra; Maus, Deborah; Krefis, Anne Caroline; Njarasoa, Christine; Rajanalison, Jeanne Fleury; Ramandrisoa, Herly Daniel; Randriarison, Maurice Lucien; May, Jürgen; Schmidt-Chanasit, Jonas; Rakotozandrindrainy, Raphael

    2012-01-01

    In October 2009, two–3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450–1,300 m high, IgG seroprevalence against CHIKV was 0%–3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission. PMID:23092548

  2. Recent Outbreaks of Rift Valley Fever in East Africa and the Middle East

    PubMed Central

    Himeidan, Yousif E.; Kweka, Eliningaya J.; Mahgoub, Mostafa M.; El Rayah, El Amin; Ouma, Johnson O.

    2014-01-01

    Rift Valley fever (RVF) is an important neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health. Mosquitoes in the Aedes genus have been considered as the reservoir, as well as vectors, since their transovarially infected eggs withstand desiccation and larvae hatch when in contact with water. However, different mosquito species serve as epizootic/epidemic vectors of RVF, creating a complex epidemiologic pattern in East Africa. The recent RVF outbreaks in Somalia (2006–2007), Kenya (2006–2007), Tanzania (2007), and Sudan (2007–2008) showed extension to districts, which were not involved before. These outbreaks also demonstrated the changing epidemiology of the disease from being originally associated with livestock, to a seemingly highly virulent form infecting humans and causing considerably high-fatality rates. The amount of rainfall is considered to be the main factor initiating RVF outbreaks. The interaction between rainfall and local environment, i.e., type of soil, livestock, and human determine the space-time clustering of RVF outbreaks. Contact with animals or their products was the most dominant risk factor to transfer the infection to humans. Uncontrolled movement of livestock during an outbreak is responsible for introducing RVF to new areas. For example, the virus that caused the Saudi Arabia outbreak in 2000 was found to be the same strain that caused the 1997–98 outbreaks in East Africa. A strategy that involves active surveillance with effective case management and diagnosis for humans and identifying target areas for animal vaccination, restriction on animal movements outside the affected areas, identifying breeding sites, and targeted intensive mosquito control programs has been shown to succeed in limiting the effect of RVF outbreak and curb the spread of the disease from the onset. PMID:25340047

  3. Ethnic groups' knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya.

    PubMed

    Affognon, Hippolyte; Mburu, Peter; Hassan, Osama Ahmed; Kingori, Sarah; Ahlm, Clas; Sang, Rosemary; Evander, Magnus

    2017-03-01

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities.

  4. Ethnic groups’ knowledge, attitude and practices and Rift Valley fever exposure in Isiolo County of Kenya

    PubMed Central

    Affognon, Hippolyte; Mburu, Peter; Hassan, Osama Ahmed; Kingori, Sarah; Ahlm, Clas; Sang, Rosemary; Evander, Magnus

    2017-01-01

    Rift Valley fever (RVF) is an emerging mosquito-borne viral hemorrhagic fever in Africa and the Arabian Peninsula, affecting humans and livestock. For spread of infectious diseases, including RVF, knowledge, attitude and practices play an important role, and the understanding of the influence of behavior is crucial to improve prevention and control efforts. The objective of the study was to assess RVF exposure, in a multiethnic region in Kenya known to experience RVF outbreaks, from the behavior perspective. We investigated how communities in Isiolo County, Kenya were affected, in relation to their knowledge, attitude and practices, by the RVF outbreak of 2006/2007. A cross-sectional study was conducted involving 698 households selected randomly from three different ethnic communities. Data were collected using a structured questionnaire regarding knowledge, attitudes and practices that could affect the spread of RVF. In addition, information was collected from the communities regarding the number of humans and livestock affected during the RVF outbreak. This study found that better knowledge about a specific disease does not always translate to better practices to avoid exposure to the disease. However, the high knowledge, attitude and practice score measured as a single index of the Maasai community may explain why they were less affected, compared to other investigated communities (Borana and Turkana), by RVF during the 2006/2007 outbreak. We conclude that RVF exposure in Isiolo County, Kenya during the outbreak was likely determined by the behavioral differences of different resident community groups. We then recommend that strategies to combat RVF should take into consideration behavioral differences among communities. PMID:28273071

  5. Rift valley Fever in Kruger national park: do buffalo play a role in the inter-epidemic circulation of virus?

    PubMed

    Beechler, B R; Bengis, R; Swanepoel, R; Paweska, J T; Kemp, A; van Vuren, P Jansen; Joubert, J; Ezenwa, V O; Jolles, A E

    2015-02-01

    Rift Valley fever (RVF) is a zoonotic mosquito-borne virus disease of livestock and wild ruminants that has been identified as a risk for international spread. Typically, the disease occurs in geographically limited outbreaks associated with high rainfall events and can cause massive losses of livestock. It is unclear how RVF virus persists during inter-epidemic periods but cryptic cycling of the virus in wildlife populations may play a role. We investigated the role that free-living African buffalo (Syncerus caffer caffer) might play in inter-epidemic circulation of the virus and looked for geographic, age and sex patterns of Rift Valley fever virus (RVFV) infection in African buffalo. Buffalo serum samples were collected (n = 1615) in Kruger National Park (KNP), South Africa, during a period of 1996-2007 and tested for antibodies to RVF. We found that older animals were more likely to be seropositive for anti-RVFV antibody than younger animals, but sex was not correlated with the likelihood of being anti-RVFV antibody positive. We also found geographic variation within KNP; herds in the south were more likely to have acquired anti-RVFV antibody than herds farther north - which could be driven by host or vector ecology. In all years of the study between 1996 and 2007, we found young buffalo (under 2 years of age) that were seropositive for anti-RVFV antibody, with prevalence ranging between 0 and 27% each year, indicating probable circulation. In addition, we also conducted a 4-year longitudinal study on 227 initially RVFV seronegative buffalo to look for evidence of seroconversion outside known RVF outbreaks within our study period (2008-2012). In the longitudinal study, we found five individuals that seroconverted from anti-RVFV antibody negative to anti-RVFV antibody positive, outside of any detected outbreak. Overall, our results provide evidence of long-term undetected circulation of RVFV in the buffalo population. © 2013 Blackwell Verlag GmbH.

  6. High content image-based screening of a protease inhibitor library reveals compounds broadly active against Rift Valley fever virus and other highly pathogenic RNA viruses.

    PubMed

    Mudhasani, Rajini; Kota, Krishna P; Retterer, Cary; Tran, Julie P; Whitehouse, Chris A; Bavari, Sina

    2014-08-01

    High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and

  7. High Content Image-Based Screening of a Protease Inhibitor Library Reveals Compounds Broadly Active against Rift Valley Fever Virus and Other Highly Pathogenic RNA Viruses

    PubMed Central

    Mudhasani, Rajini; Kota, Krishna P.; Retterer, Cary; Tran, Julie P.; Whitehouse, Chris A.; Bavari, Sina

    2014-01-01

    High content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against Rift Valley fever virus (RVFV) and to determine their mechanism of action. RVFV is the causative agent of severe disease of humans and animals throughout Africa and the Arabian Peninsula. Of the 849 compounds screened, 34 compounds exhibited ≥50% inhibition against RVFV. All of the hit compounds could be classified into 4 distinct groups based on their unique chemical backbone. Some of the compounds also showed broad antiviral activity against several highly pathogenic RNA viruses including Ebola, Marburg, Venezuela equine encephalitis, and Lassa viruses. Four hit compounds (C795-0925, D011-2120, F694-1532 and G202-0362), which were most active against RVFV and showed broad-spectrum antiviral activity, were selected for further evaluation for their cytotoxicity, dose response profile, and mode of action using classical virological methods and high-content imaging analysis. Time-of-addition assays in RVFV infections suggested that D011-2120 and G202-0362 targeted virus egress, while C795-0925 and F694-1532 inhibited virus replication. We showed that D011-2120 exhibited its antiviral effects by blocking microtubule polymerization, thereby disrupting the Golgi complex and inhibiting viral trafficking to the plasma membrane during virus egress. While G202-0362 also affected virus egress, it appears to do so by a different mechanism, namely by blocking virus budding from the trans Golgi. F694-1532 inhibited viral replication, but also appeared to inhibit overall cellular gene expression. However, G202-0362 and C795-0925 did not alter any of the morphological features that we examined and thus may prove to be good candidates for antiviral drug development. Overall this work demonstrates that high-content image analysis can be used to screen chemical libraries for new antivirals and to determine their mechanism of action and

  8. Dengue Hemorrhagic Fever Virus in Saudi Arabia: A Review.

    PubMed

    Al-Tawfiq, Jaffar A; Memish, Ziad A

    2018-02-01

    Dengue fever is a global disease with a spectrum of clinical manifestation ranging from mild febrile disease to a severe disease in the form of dengue hemorrhagic fever and dengue shock syndrome. Dengue virus is one viral hemorrhagic fever that exists in the Kingdom of Saudi Arabia in addition to Alkhurma (Alkhurma) Hemorrhagic Fever, Chikungunya virus, Crimean-Congo Hemorrhagic Fever, and Rift Valley Fever. The disease is limited to the Western and South-western regions of Saudi Arabia, where Aedes aegypti exists. The majority of the cases in Saudi Arabia had mild disease and is related to serotypes 1-3 but not 4. The prospect for Dengue virus control relies on vector control, health education, and possibly vaccine use. Despite extensive collaborative efforts between multiple governmental sectors, including Ministry of Health, Ministry of Municipalities and Rural Affairs, and Ministry of Water, dengue remains a major public health concern in the regions affected.

  9. Rift Valley fever in kidney transplant recipient returning from Mali with viral RNA detected in semen up to four months from symptom onset, France, autumn 2015.

    PubMed

    Haneche, Fatiha; Leparc-Goffart, Isabelle; Simon, Fabrice; Hentzien, Maxime; Martinez-Pourcher, Valérie; Caumes, Eric; Maquart, Marianne

    2016-05-05

    A 29-year-old kidney transplant recipient returning from Mali was diagnosed with Rift Valley fever (RVF) in France in autumn 2015. The patient was immunosuppressed due to his renal transplant. IgM and IgG specific to RVF virus (RVFV) were detected in cerebrospinal fluid and blood up to two months after symptom onset, whereas in urine, RVFV genomic RNA was detected by RT-PCR up to three months, and in semen up to four months post symptom onset.

  10. Association of Symptoms and Severity of Rift Valley Fever with Genetic Polymorphisms in Human Innate Immune Pathways

    PubMed Central

    Hise, Amy G.; Traylor, Zachary; Hall, Noémi B.; Sutherland, Laura J.; Dahir, Saidi; Ermler, Megan E.; Muiruri, Samuel; Muchiri, Eric M.; Kazura, James W.; LaBeaud, A. Desirée; King, Charles H.; Stein, Catherine M.

    2015-01-01

    Background Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya. Methodology/Principal Findings We conducted a cross-sectional survey among residents (N = 1,080; 1–85 yrs) in 6 villages in the Sangailu Division of Ijara District. Participants completed questionnaires on past symptoms and exposures, physical exam, vision testing, and blood collection. Single nucleotide polymorphism (SNP) genotyping was performed on a subset of individuals who reported past clinical symptoms consistent with RVF and unrelated subjects. Four symptom clusters were defined: meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise specified. SNPs in 46 viral sensing and response genes were investigated. Association was analyzed between SNP genotype, serology and RVF symptom clusters. The meningoencephalitis symptom phenotype cluster among seropositive patients was associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF-related symptoms was significantly associated with polymorphisms in TICAM1/TRIF, MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease included three different polymorphisms TLR8 and hemorrhagic fever symptoms associated with TLR3, TLR7, TLR8 and MyD88. Conclusions/Significance Of the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical

  11. Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination.

    PubMed

    Wichgers Schreur, Paul J; Kant, Jet; van Keulen, Lucien; Moormann, Rob J M; Kortekaas, Jeroen

    2015-03-17

    Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family, causes recurrent outbreaks with severe disease in ruminants and occasionally humans. The virus comprises a segmented genome consisting of a small (S), medium (M) and large (L) RNA segment of negative polarity. The M-segment encodes a glycoprotein precursor (GPC) protein that is co-translationally cleaved into Gn and Gc, which are required for virus entry and fusion. Recently we developed a four-segmented RVFV (RVFV-4s) by splitting the M-genome segment, and used this virus to study RVFV genome packaging. Here we evaluated the potential of a RVFV-4s variant lacking the NSs gene (4s-ΔNSs) to induce protective immunity in sheep. Groups of seven lambs were either mock-vaccinated or vaccinated with 10(5) or 10(6) tissue culture infective dose (TCID50) of 4s-ΔNSs via the intramuscular (IM) or subcutaneous (SC) route. Three weeks post-vaccination all lambs were challenged with wild-type RVFV. Mock-vaccinated lambs developed high fever and high viremia within 2 days post-challenge and three animals eventually succumbed to the infection. In contrast, none of the 4s-ΔNSs vaccinated animals developed clinical signs during the course of the experiment. Vaccination with 10(5) TCID50 via the IM route provided sterile immunity, whereas a 10(6) dose was required to induce sterile immunity via SC vaccination. Protection was strongly correlated with the presence of RVFV neutralizing antibodies. This study shows that 4s-ΔNSs is able to induce sterile immunity in the natural target species after a single vaccination, preferably administrated via the IM route. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Transmission potential of Rift Valley fever virus over the course of the 2010 epidemic in South Africa.

    PubMed

    Métras, Raphaëlle; Baguelin, Marc; Edmunds, W John; Thompson, Peter N; Kemp, Alan; Pfeiffer, Dirk U; Collins, Lisa M; White, Richard G

    2013-06-01

    A Rift Valley fever (RVF) epidemic affecting animals on domestic livestock farms was reported in South Africa during January-August 2010. The first cases occurred after heavy rainfall, and the virus subsequently spread countrywide. To determine the possible effect of environmental conditions and vaccination on RVF virus transmissibility, we estimated the effective reproduction number (Re) for the virus over the course of the epidemic by extending the Wallinga and Teunis algorithm with spatial information. Re reached its highest value in mid-February and fell below unity around mid-March, when vaccination coverage was 7.5%-45.7% and vector-suitable environmental conditions were maintained. The epidemic fade-out likely resulted first from the immunization of animals following natural infection or vaccination. The decline in vector-suitable environmental conditions from April onwards and further vaccination helped maintain Re below unity. Increased availability of vaccine use data would enable evaluation of the effect of RVF vaccination campaigns.

  13. Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.

    PubMed

    Engelthaler, David M; Roe, Chandler C; Hepp, Crystal M; Teixeira, Marcus; Driebe, Elizabeth M; Schupp, James M; Gade, Lalitha; Waddell, Victor; Komatsu, Kenneth; Arathoon, Eduardo; Logemann, Heidi; Thompson, George R; Chiller, Tom; Barker, Bridget; Keim, Paul; Litvintseva, Anastasia P

    2016-04-26

    Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. Coccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a

  14. Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model.

    PubMed

    Ikegami, Tetsuro; Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B; Morrill, John C; Shivanna, Vinay; Indran, Sabarish V; Zhang, Lihong; Smith, Jennifer K; Perez, David; Juelich, Terry L; Morozov, Igor; Wilson, William C; Freiberg, Alexander N; Richt, Juergen A

    2017-01-01

    Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2-3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies.

  15. Distinct virulence of Rift Valley fever phlebovirus strains from different genetic lineages in a mouse model

    PubMed Central

    Balogh, Aaron; Nishiyama, Shoko; Lokugamage, Nandadeva; Saito, Tais B.; Morrill, John C.; Shivanna, Vinay; Indran, Sabarish V.; Zhang, Lihong; Smith, Jennifer K.; Perez, David; Juelich, Terry L.; Morozov, Igor; Wilson, William C.; Freiberg, Alexander N.; Richt, Juergen A.

    2017-01-01

    Rift Valley fever phlebovirus (RVFV) causes high rates of abortions and fetal malformations in ruminants, and hemorrhagic fever, encephalitis, or blindness in humans. Viral transmission occurs via mosquito vectors in endemic areas, which necessitates regular vaccination of susceptible livestock animals to prevent the RVF outbreaks. Although ZH501 strain has been used as a challenge strain for past vaccine efficacy studies, further characterization of other RVFV strains is important to optimize ruminant and nonhuman primate RVFV challenge models. This study aimed to characterize the virulence of wild-type RVFV strains belonging to different genetic lineages in outbred CD1 mice. Mice were intraperitoneally infected with 1x103 PFU of wild-type ZH501, Kenya 9800523, Kenya 90058, Saudi Arabia 200010911, OS1, OS7, SA75, Entebbe, or SA51 strains. Among them, mice infected with SA51, Entebbe, or OS7 strain showed rapid dissemination of virus in livers and peracute necrotic hepatitis at 2–3 dpi. Recombinant SA51 (rSA51) and Zinga (rZinga) strains were recovered by reverse genetics, and their virulence was also tested in CD1 mice. The rSA51 strain reproduced peracute RVF disease in mice, whereas the rZinga strain showed a similar virulence with that of rZH501 strain. This study showed that RVFV strains in different genetic lineages display distinct virulence in outbred mice. Importantly, since wild-type RVFV strains contain defective-interfering RNA or various genetic subpopulations during passage from original viral isolations, recombinant RVFV strains generated by reverse genetics will be better suitable for reproducible challenge studies for vaccine development as well as pathological studies. PMID:29267298

  16. Spatial, seasonal and climatic predictive models of Rift Valley fever disease across Africa.

    PubMed

    Redding, David W; Tiedt, Sonia; Lo Iacono, Gianni; Bett, Bernard; Jones, Kate E

    2017-07-19

    Understanding the emergence and subsequent spread of human infectious diseases is a critical global challenge, especially for high-impact zoonotic and vector-borne diseases. Global climate and land-use change are likely to alter host and vector distributions, but understanding the impact of these changes on the burden of infectious diseases is difficult. Here, we use a Bayesian spatial model to investigate environmental drivers of one of the most important diseases in Africa, Rift Valley fever (RVF). The model uses a hierarchical approach to determine how environmental drivers vary both spatially and seasonally, and incorporates the effects of key climatic oscillations, to produce a continental risk map of RVF in livestock (as a proxy for human RVF risk). We find RVF risk has a distinct seasonal spatial pattern influenced by climatic variation, with the majority of cases occurring in South Africa and Kenya in the first half of an El Niño year. Irrigation, rainfall and human population density were the main drivers of RVF cases, independent of seasonal, climatic or spatial variation. By accounting more subtly for the patterns in RVF data, we better determine the importance of underlying environmental drivers, and also make space- and time-sensitive predictions to better direct future surveillance resources.This article is part of the themed issue 'One Health for a changing world: zoonoses, ecosystems and human well-being'. © 2017 The Authors.

  17. Spatial, seasonal and climatic predictive models of Rift Valley fever disease across Africa

    PubMed Central

    2017-01-01

    Understanding the emergence and subsequent spread of human infectious diseases is a critical global challenge, especially for high-impact zoonotic and vector-borne diseases. Global climate and land-use change are likely to alter host and vector distributions, but understanding the impact of these changes on the burden of infectious diseases is difficult. Here, we use a Bayesian spatial model to investigate environmental drivers of one of the most important diseases in Africa, Rift Valley fever (RVF). The model uses a hierarchical approach to determine how environmental drivers vary both spatially and seasonally, and incorporates the effects of key climatic oscillations, to produce a continental risk map of RVF in livestock (as a proxy for human RVF risk). We find RVF risk has a distinct seasonal spatial pattern influenced by climatic variation, with the majority of cases occurring in South Africa and Kenya in the first half of an El Niño year. Irrigation, rainfall and human population density were the main drivers of RVF cases, independent of seasonal, climatic or spatial variation. By accounting more subtly for the patterns in RVF data, we better determine the importance of underlying environmental drivers, and also make space- and time-sensitive predictions to better direct future surveillance resources. This article is part of the themed issue ‘One Health for a changing world: zoonoses, ecosystems and human well-being’. PMID:28584173

  18. Pyrogen fever and prostaglandin-like activity in cerebrospinal fluid

    PubMed Central

    Feldberg, W.; Gupta, K. P.

    1973-01-01

    1. In the unanaesthetized cat, rectal temperature was recorded and c.s.f. was collected from a Collison cannula implanted into the third ventricle with its opening lying in close proximity to the anterior hypothalamus. Samples of c.s.f. were collected from the same cat, during normal temperature, during fever produced by Shigella dysenteriae injected into the third ventricle and during the fall in temperature which occurred when the antipyretic paracetamol was injected intraperitoneally during the pyrogen fever. 2. The samples of c.s.f., when tested on the rat stomach fundus preparation, caused contractions which were not due, or at most to a small degree only, to 5-hydroxytryptamine, as they were resistant to BOL. They were therefore probably due to a prostaglandin-like substance. 3. When assayed against PGE1, the activity of c.s.f. collected from cats when their body temperature was normal corresponded to between 1·3 and 10 ng/ml. The values, whether low or high, rose over 2·5-4 times to between 4 and 35 ng/ml. in c.s.f. collected during pyrogen fever; they were again low, between 1·5 and 6 ng/ml., in samples collected when the fever had been brought down by paracetamol, but rose again with the return of fever. 4. The results provide direct evidence for the theory that fever produced by pyrogens results from their ability to increase synthesis and release of prostaglandins, and that antipyretics bring down the fever because they inhibit the increased synthesis. PMID:4568386

  19. Rift Valley fever virus infections in Egyptian cattle and their prevention.

    PubMed

    Mroz, C; Gwida, M; El-Ashker, M; Ziegler, U; Homeier-Bachmann, T; Eiden, M; Groschup, M H

    2017-12-01

    Rift Valley fever virus (RVFV) causes consistently severe outbreaks with high public health impacts and economic losses in livestock in many African countries and has also been introduced to Saudi Arabia and Yemen. Egypt with its four large outbreaks in the last 40 years represents the northernmost endemic area of RVFV. The purpose of this study was to provide an insight into the current anti-RVFV antibody status in immunized as well as non-immunized dairy cattle from the Nile Delta of Egypt. During 2013-2015, a total of 4,167 dairy cattle from four governorates including Dakahlia, Damietta, Gharbia and Port Said were investigated. All cattle were born after 2007 and therewith after the last reported Egyptian RVFV outbreak in 2003. The samples derived from vaccinated animals from 26 different dairy farms as well as non-immunized cattle from 27 different smallholding flocks. All samples were examined following a three-part analysis including a commercially available competition ELISA, an in-house immunofluorescence assay and a virus neutralization test. Additionally, a subset of samples was analysed for acute infections using IgM ELISA and real-time reverse transcriptase PCR. The results indicated that the RVFV is still circulating in Egypt as about 10% of the non-immunized animals exhibited RVFV-specific antibodies. Surprisingly, the antibody prevalence in immunized animals was not significantly higher than that in non-vaccinated animals which points out the need for further evaluation of the vaccination programme. Due to the substantial role of livestock in the amplification and transmission of RVFV, further recurrent monitoring of the antibody prevalence in susceptible species is highly warranted. © 2017 Blackwell Verlag GmbH.

  20. Serological and genomic evidence of Rift Valley fever virus during inter-epidemic periods in Mauritania.

    PubMed

    Rissmann, M; Eiden, M; El Mamy, B O; Isselmou, K; Doumbia, B; Ziegler, U; Homeier-Bachmann, T; Yahya, B; Groschup, M H

    2017-04-01

    Rift Valley fever virus (RVFV) is an emerging pathogen of major concern throughout Africa and the Arabian Peninsula, affecting both livestock and humans. In the past recurrent epidemics were reported in Mauritania and studies focused on the analysis of samples from affected populations during acute outbreaks. To verify characteristics and presence of RVFV during non-epidemic periods we implemented a multi-stage serological and molecular analysis. Serum samples of small ruminants, cattle and camels were obtained from Mauritania during an inter-epidemic period in 2012-2013. This paper presents a comparative analysis of potential variations and shifts of antibody presence and the capability of inter-epidemic infections in Mauritanian livestock. We observed distinct serological differences between tested species (seroprevalence: small ruminants 3·8%, cattle 15·4%, camels 32·0%). In one single bovine from Nouakchott, a recent RVF infection could be identified by the simultaneous detection of IgM antibodies and viral RNA. This study indicates the occurrence of a low-level enzootic RVFV circulation in livestock in Mauritania. Moreover, results indicate that small ruminants can preferably act as sentinels for RVF surveillance.

  1. NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62▿

    PubMed Central

    Kalveram, Birte; Lihoradova, Olga; Ikegami, Tetsuro

    2011-01-01

    Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus. PMID:21543505

  2. Relationship of climate, geography, and geology to the incidence of Rift Valley fever in Kenya during the 2006-2007 outbreak.

    PubMed

    Hightower, Allen; Kinkade, Carl; Nguku, Patrick M; Anyangu, Amwayi; Mutonga, David; Omolo, Jared; Njenga, M Kariuki; Feikin, Daniel R; Schnabel, David; Ombok, Maurice; Breiman, Robert F

    2012-02-01

    We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006-2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage.

  3. Medical Surveillance Monthly Report (MSMR). Volume 9, Number 3, April 2003

    DTIC Science & Technology

    2003-04-01

    Rocky Mountain spotted fever , dengue, typhus, yellow fever, Rift Valley fever, or other hemorrhagic fevers among active duty servicemembers. During...Valley fever . . . . . E. coli O157:H7 3 3 9 3 1 Rocky Mountain spotted fever 2 . 12 2 . Ehrlichiosis 2 1 2 3 1 Rubella . . . . . Encephalitis...Dengue fever . . . 1 . Rheumatic fever, acute . . 1 . . Diphtheria . . . . . Rift Valley fever . . . . . E. coli O157:H7 . 1 1 1 . Rocky Mountain spotted

  4. Creation of Rift Valley Fever Viruses with Four-Segmented Genomes Reveals Flexibility in Bunyavirus Genome Packaging

    PubMed Central

    Oreshkova, Nadia; Moormann, Rob J. M.; Kortekaas, Jeroen

    2014-01-01

    ABSTRACT Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. IMPORTANCE Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for

  5. Creation of Rift Valley fever viruses with four-segmented genomes reveals flexibility in bunyavirus genome packaging.

    PubMed

    Wichgers Schreur, Paul J; Oreshkova, Nadia; Moormann, Rob J M; Kortekaas, Jeroen

    2014-09-01

    Bunyavirus genomes comprise a small (S), a medium (M), and a large (L) RNA segment of negative polarity. Although the untranslated regions have been shown to comprise signals required for transcription, replication, and encapsidation, the mechanisms that drive the packaging of at least one S, M, and L segment into a single virion to generate infectious virus are largely unknown. One of the most important members of the Bunyaviridae family that causes devastating disease in ruminants and occasionally humans is the Rift Valley fever virus (RVFV). We studied the flexibility of RVFV genome packaging by splitting the glycoprotein precursor gene, encoding the (NSm)GnGc polyprotein, into two individual genes encoding either (NSm)Gn or Gc. Using reverse genetics, six viruses with a segmented glycoprotein precursor gene were rescued, varying from a virus comprising two S-type segments in the absence of an M-type segment to a virus consisting of four segments (RVFV-4s), of which three are M-type. Despite that all virus variants were able to grow in mammalian cell lines, they were unable to spread efficiently in cells of mosquito origin. Moreover, in vivo studies demonstrated that RVFV-4s is unable to cause disseminated infection and disease in mice, even in the presence of the main virulence factor NSs, but induced a protective immune response against a lethal challenge with wild-type virus. In summary, splitting bunyavirus glycoprotein precursor genes provides new opportunities to study bunyavirus genome packaging and offers new methods to develop next-generation live-attenuated bunyavirus vaccines. Rift Valley fever virus (RVFV) causes devastating disease in ruminants and occasionally humans. Virions capable of productive infection comprise at least one copy of the small (S), medium (M), and large (L) RNA genome segments. The M segment encodes a glycoprotein precursor (GPC) protein that is cotranslationally cleaved into Gn and Gc, which are required for virus entry and

  6. High seroprevalence of Rift Valley fever phlebovirus in domestic ruminants and African Buffaloes in Mozambique shows need for intensified surveillance

    PubMed Central

    Moiane, Belisário; Mapaco, Lourenço; Thompson, Peter; Berg, Mikael; Albihn, Ann; Fafetine, José

    2017-01-01

    ABSTRACT Introduction: Rift Valley fever (RVF) is an arthropod-borne disease that affects both animals and humans. RVF phlebovirus (RVFPV) is widespread in Africa and Arabian Peninsula. In Mozambique, outbreaks were reported in South; seroprevalence studies performed in livestock and water buffaloes were limited to central and south regions. We evaluated the seroprevalence of RVFPV among domestic ruminants and African buffaloes from 7 of 10 provinces of Mozambique, to understand the distribution of RVFPV and provide data for further RVF control programs. Materials and methods: A total of 1581 blood samples were collected in cattle, 1117 in goats, 85 in sheep and 69 in African buffaloes, between 2013 and 2014, and the obtained sera were analyzed by ELISA. Results and discussion: The overall seroprevalence of RVFPV domestic ruminants and African buffaloes was 25.6%. The highest was observed in cattle (37.3%) and African buffaloes (30.4%), which were higher than in previous studies within Mozambique. In south and central regions, the overall seroprevalences were higher (14.9%–62.4%) than in the north. Conclusion: This study showed the presence of anti-RVFPV antibodies in animals from all sampled provinces, suggesting that RVFPV is actively circulating among domestic ruminants and African buffaloes in Mozambique, therefore surveillance should be intensified. PMID:29321827

  7. Efficacy assessment of an MVA vectored Rift Valley Fever vaccine in lambs.

    PubMed

    Busquets, Núria; Lorenzo, Gema; López-Gil, Elena; Rivas, Raquel; Solanes, David; Galindo-Cardiel, Iván; Abad, F Xavier; Rodríguez, Fernando; Bensaid, Albert; Warimwe, George; Gilbert, Sarah C; Domingo, Mariano; Brun, Alejandro

    2014-08-01

    The present study has evaluated the protection conferred by a single subcutaneous dose of a modified vaccinia virus Ankara (MVA) vectored vaccine encoding the Rift Valley Fever virus (RVFV) glycoproteins Gn and Gc in lambs. Three groups of six to seven lambs were immunized as follows: one group received the vaccine (termed rMVA-GnGc), a second group received an MVA vector (vector control) and a third group received saline solution (non-vaccinated control). Fourteen days later, all animals were subcutaneously challenged with 10(5) TCID50 of the virulent RVFV isolate 56/74 and vaccine efficacy assessed using standard endpoints. Two lambs (one from the vaccine group and one from the vector control group) succumbed to RVFV challenge, showing characteristic liver lesions. Lambs from both the vector control and non-vaccinated groups were febrile from days 2 to 5 post challenge (pc) while those in the rMVA-GnGc group showed a single peak of pyrexia at day 3 pc. RVFV RNA was detected in both nasal and oral swabs from days 3 to 7 pc in some lambs from the vector control and non-vaccinated groups, but no viral shedding could be detected in the surviving lambs vaccinated with rMVA-GnGc. Together, the data suggest that a single dose of the rMVA-GnGc vaccine may be sufficient to reduce RVFV shedding and duration of viremia but does not provide sterile immunity nor protection from disease. Further optimization of this vaccine approach in lambs is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Emerging vector-borne diseases in dromedaries in Tunisia: West Nile, bluetongue, epizootic haemorrhagic disease and Rift Valley fever.

    PubMed

    Hassine, Thameur B; Amdouni, Jihane; Monaco, Federica; Savini, Giovanni; Sghaier, Soufien; Selimen, Imed B; Chandoul, Walid; Hamida, Khaled B; Hammami, Salah

    2017-03-31

    A total of 118 sera were collected during 2016 from two groups of dromedaries from Kebili and Medenine governorates in the south of Tunisia. The aim of this study was to provide the first serological investigation of four emerging vector-borne diseases in two groups of dromedaries in Tunisia. Sera were tested by ELISA and serum neutralisation test to identify West Nile virus (WNV), bluetongue virus (BTV), epizootic haemorrhagic disease virus (EHDV) and Rift Valley fever virus (RVFV). In the first group, the seroprevalence for BTV was 4.6%, while in the second group, it was 25.8% for WNV and 9.7% for BTV. Only serotype 1 was detected for BTV in the two groups. No evidence for circulation of RVF and EHD viruses was revealed. Results indicated that dromedaries can be infected with BTV and WNV, suggesting that this species might play a significant role in the epizootiology of these viral diseases in Tunisia and neighbouring countries.

  9. Prevalence and risk factors of Rift Valley fever in humans and animals from Kabale district in Southwestern Uganda, 2016

    PubMed Central

    de St. Maurice, Annabelle; Purpura, Lawrence; Ervin, Elizabeth; Balinandi, Stephen; Tumusiime, Alex; Kyondo, Jackson; Mulei, Sophia; Tusiime, Patrick; Lutwama, Julius; Klena, John D.; Brown, Shelley; Knust, Barbara; Rollin, Pierre E.; Nichol, Stuart T.

    2018-01-01

    Background Rift Valley fever (RVF) is a zoonotic disease caused by Rift Valley fever virus (RVFV) found in Africa and the Middle East. Outbreaks can cause extensive morbidity and mortality in humans and livestock. Following the diagnosis of two acute human RVF cases in Kabale district, Uganda, we conducted a serosurvey to estimate RVFV seroprevalence in humans and livestock and to identify associated risk factors. Methods Humans and animals at abattoirs and villages in Kabale district were sampled. Persons were interviewed about RVFV exposure risk factors. Human blood was tested for anti-RVFV IgM and IgG, and animal blood for anti-RVFV IgG. Principal findings 655 human and 1051 animal blood samples were collected. Anti-RVFV IgG was detected in 78 (12%) human samples; 3 human samples (0.5%) had detectable IgM only, and 7 (1%) had both IgM and IgG. Of the 10 IgM-positive persons, 2 samples were positive for RVFV by PCR, confirming recent infection. Odds of RVFV seropositivity were greater in participants who were butchers (odds ratio [OR] 5.1; 95% confidence interval [95% CI]: 1.7–15.1) and those who reported handling raw meat (OR 3.4; 95% CI 1.2–9.8). No persons under age 20 were RVFV seropositive. The overall animal seropositivity was 13%, with 27% of cattle, 7% of goats, and 4% of sheep seropositive. In a multivariate logistic regression, cattle species (OR 9.1; 95% CI 4.1–20.5), adult age (OR 3.0; 95% CI 1.6–5.6), and female sex (OR 2.1; 95%CI 1.0–4.3) were significantly associated with animal seropositivity. Individual human seropositivity was significantly associated with animal seropositivity by subcounty after adjusting for sex, age, and occupation (p < 0.05). Conclusions Although no RVF cases had been detected in Uganda from 1968 to March 2016, our study suggests that RVFV has been circulating undetected in both humans and animals living in and around Kabale district. RVFV seropositivity in humans was associated with occupation, suggesting that the

  10. 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.

  11. An Assessment of the Regional and National Socio-Economic Impacts of the 2007 Rift Valley Fever Outbreak in Kenya

    PubMed Central

    Rich, Karl M.; Wanyoike, Francis

    2010-01-01

    Although Rift Valley fever (RVF) has significant impacts on human health and livestock production, it can also induce significant (and often overlooked) economic losses among various stakeholders in the marketing chain. This work assesses and quantifies the multi-dimensional socio-economic impacts of the 2007 RVF outbreak in Kenya based on a rapid assessment of livestock value chains in the northeast part of the country and a national macroeconomic analysis. Although study results show negative impacts among producers in terms of food insecurity and reductions in income, we also found significant losses among other downstream actors in the value chain, including livestock traders, slaughterhouses, casual laborers, and butchers, as well as other, non-agricultural sectors. The study highlights the need for greater sensitivity and analyses that address the multitude of economic losses resulting from an animal disease to better inform policy and decision making during animal health emergencies. PMID:20682906

  12. An assessment of the regional and national socio-economic impacts of the 2007 Rift Valley fever outbreak in Kenya.

    PubMed

    Rich, Karl M; Wanyoike, Francis

    2010-08-01

    Although Rift Valley fever (RVF) has significant impacts on human health and livestock production, it can also induce significant (and often overlooked) economic losses among various stakeholders in the marketing chain. This work assesses and quantifies the multi-dimensional socio-economic impacts of the 2007 RVF outbreak in Kenya based on a rapid assessment of livestock value chains in the northeast part of the country and a national macroeconomic analysis. Although study results show negative impacts among producers in terms of food insecurity and reductions in income, we also found significant losses among other downstream actors in the value chain, including livestock traders, slaughterhouses, casual laborers, and butchers, as well as other, non-agricultural sectors. The study highlights the need for greater sensitivity and analyses that address the multitude of economic losses resulting from an animal disease to better inform policy and decision making during animal health emergencies.

  13. Anomalous High Rainfall and Soil Saturation as Combined Risk Indicator of Rift Valley Fever Outbreaks, South Africa, 2008-2011.

    PubMed

    Williams, Roy; Malherbe, Johan; Weepener, Harold; Majiwa, Phelix; Swanepoel, Robert

    2016-12-01

    Rift Valley fever (RVF), a zoonotic vectorborne viral disease, causes loss of life among humans and livestock and an adverse effect on the economy of affected countries. Vaccination is the most effective way to protect livestock; however, during protracted interepidemic periods, farmers discontinue vaccination, which leads to loss of herd immunity and heavy losses of livestock when subsequent outbreaks occur. Retrospective analysis of the 2008-2011 RVF epidemics in South Africa revealed a pattern of continuous and widespread seasonal rainfall causing substantial soil saturation followed by explicit rainfall events that flooded dambos (seasonally flooded depressions), triggering outbreaks of disease. Incorporation of rainfall and soil saturation data into a prediction model for major outbreaks of RVF resulted in the correctly identified risk in nearly 90% of instances at least 1 month before outbreaks occurred; all indications are that irrigation is of major importance in the remaining 10% of outbreaks.

  14. Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

    PubMed

    Ikegami, Tetsuro; Narayanan, Krishna; Won, Sungyong; Kamitani, Wataru; Peters, C J; Makino, Shinji

    2009-02-01

    Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibits the transcription of host mRNAs, including interferon-beta mRNA, and is a major virulence factor. The present study explored a novel function of the RVFV NSs protein by testing the replication of RVFV lacking the NSs gene in the presence of actinomycin D (ActD) or alpha-amanitin, both of which served as a surrogate of the host mRNA synthesis suppression function of the NSs. In the presence of the host-transcriptional inhibitors, the replication of RVFV lacking the NSs protein, but not that carrying NSs, induced double-stranded RNA-dependent protein kinase (PKR)-mediated eukaryotic initiation factor (eIF)2alpha phosphorylation, leading to the suppression of host and viral protein translation. RVFV NSs promoted post-transcriptional downregulation of PKR early in the course of the infection and suppressed the phosphorylated eIF2alpha accumulation. These data suggested that a combination of RVFV replication and NSs-induced host transcriptional suppression induces PKR-mediated eIF2alpha phosphorylation, while the NSs facilitates efficient viral translation by downregulating PKR and inhibiting PKR-mediated eIF2alpha phosphorylation. Thus, the two distinct functions of the NSs, i.e., the suppression of host transcription, including that of type I interferon mRNAs, and the downregulation of PKR, work together to prevent host innate antiviral functions, allowing efficient replication and survival of RVFV in infected mammalian hosts.

  15. A geographical information system-based multicriteria evaluation to map areas at risk for Rift Valley fever vector-borne transmission in Italy.

    PubMed

    Tran, A; Ippoliti, C; Balenghien, T; Conte, A; Gely, M; Calistri, P; Goffredo, M; Baldet, T; Chevalier, V

    2013-11-01

    Rift Valley fever (RVF) is a severe mosquito-borne disease that is caused by a Phlebovirus (Bunyaviridae) and affects domestic ruminants and humans. Recently, its distribution widened, threatening Europe. The probability of the introduction and large-scale spread of Rift Valley fever virus (RVFV) in Europe is low, but localized RVF outbreaks may occur in areas where populations of ruminants and potential vectors are present. In this study, we assumed the introduction of the virus into Italy and focused on the risk of vector-borne transmission of RVFV to three main European potential hosts (cattle, sheep and goats). Five main potential mosquito vectors belonging to the Culex and Aedes genera that are present in Italy were identified in a literature review. We first modelled the geographical distribution of these five species based on expert knowledge and using land cover as a proxy of mosquito presence. The mosquito distribution maps were compared with field mosquito collections from Italy to validate the model. Next, the risk of RVFV transmission was modelled using a multicriteria evaluation (MCE) approach, integrating expert knowledge and the results of a literature review on host sensitivity and vector competence, feeding behaviour and abundance. A sensitivity analysis was performed to assess the robustness of the results with respect to expert choices. The resulting maps include (i) five maps of the vector distribution, (ii) a map of suitable areas for vector-borne transmission of RVFV and (iii) a map of the risk of RVFV vector-borne transmission to sensitive hosts given a viral introduction. Good agreement was found between the modelled presence probability and the observed presence or absence of each vector species. The resulting RVF risk map highlighted strong spatial heterogeneity and could be used to target surveillance. In conclusion, the geographical information system (GIS)-based MCE served as a valuable framework and a flexible tool for mapping the

  16. A systematic review of Rift Valley Fever epidemiology 1931–2014

    PubMed Central

    Nanyingi, Mark O.; Munyua, Peninah; Kiama, Stephen G.; Muchemi, Gerald M.; Thumbi, Samuel M.; Bitek, Austine O.; Bett, Bernard; Muriithi, Reese M.; Njenga, M. Kariuki

    2015-01-01

    Background Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis that was first isolated and characterized in 1931 in Kenya. RVF outbreaks have resulted in significant losses through human illness and deaths, high livestock abortions and deaths. This report provides an overview on epidemiology of RVF including ecology, molecular diversity spatiotemporal analysis, and predictive risk modeling. Methodology Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched for relevant RVF publications in repositories of the World Health Organization Library and Information Networks for Knowledge (WHOLIS), U.S Centers for Disease Control and Prevention (CDC), and Food and Agricultural Organization (FAO). Detailed searches were performed in Google Scholar, SpringerLink, and PubMed databases and included conference proceedings and books published from 1931 up to 31st January 2015. Results and discussion A total of 84 studies were included in this review; majority (50%) reported on common human and animal risk factors that included consumption of animal products, contact with infected animals and residing in low altitude areas associated with favorable climatic and ecological conditions for vector emergence. A total of 14 (16%) of the publications described RVF progressive spatial and temporal distribution and the use of risk modeling for timely prediction of imminent outbreaks. Using distribution maps, we illustrated the gradual spread and geographical extent of disease; we also estimated the disease burden using aggregate human mortalities and cumulative outbreak periods for endemic regions. Conclusion This review outlines common risk factors for RVF infections over wider geographical areas; it also emphasizes the role of spatial models in predicting RVF enzootics. It, therefore, explains RVF epidemiological status that may be used for design of targeted surveillance and control programs in endemic

  17. Characterizing the effect of Bortezomib on Rift Valley Fever Virus multiplication.

    PubMed

    Keck, Forrest; Amaya, Moushimi; Kehn-Hall, Kylene; Roberts, Brian; Bailey, Charles; Narayanan, Aarthi

    2015-08-01

    Rift Valley Fever Virus (RVFV) belongs to the family Bunyaviridae and is a known cause of epizootics and epidemics in Africa and the Middle East. With no FDA approved therapeutics available to treat RVFV infection, understanding the interactions between the virus and the infected host is crucial to developing novel therapeutic strategies. Here, we investigated the requirement of the ubiquitin-proteasome system (UPS) for the establishment of a productive RVFV infection. It was previously shown that the UPS plays a central role in RVFV multiplication involving degradation of PKR and p62 subunit of TFIIH. Using the FDA-approved proteasome inhibitor Bortezomib, we observed robust inhibition of intracellular and extracellular viral loads. Bortezomib treatment did not affect the nuclear/cytoplasmic distribution of the non-structural S-segment protein (NSs); however, the ability of NSs to form nuclear filaments was abolished as a result of Bortezomib treatment. In silico ubiquitination prediction analysis predicted that known NSs interactors (SAP30, YY1, and mSin3A) have multiple putative ubiquitination sites, while NSs itself was not predicted to be ubiquitinated. Immunoprecipitation studies indicated a decrease in interaction between SAP30 - NSs, and mSin3A - NSs in the context of Bortezomib treatment. This decrease in association between SAP30 - NSs also correlated with a decrease in the ubiquitination status of SAP30 with Bortezomib treatment. Bortezomib treatment, however, resulted in increased ubiquitination of mSin3A, suggesting that Bortezomib dynamically affects the ubiquitination status of host proteins that interact with NSs. Finally, we observed that expression of interferon beta (IFN-β) was increased in Bortezomib treated cells which indicated that the cellular antiviral mechanism was revived as a result of treatment and may contribute to control of viral multiplication. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Seroepidemiological Study of Interepidemic Rift Valley Fever Virus Infection Among Persons with Intense Ruminant Exposure in Madagascar and Kenya.

    PubMed

    Gray, Gregory C; Anderson, Benjamin D; LaBeaud, A Desirée; Heraud, Jean-Michel; Fèvre, Eric M; Andriamandimby, Soa Fy; Cook, Elizabeth A J; Dahir, Saidi; de Glanville, William A; Heil, Gary L; Khan, Salah U; Muiruri, Samuel; Olive, Marie-Marie; Thomas, Lian F; Merrill, Hunter R; Merrill, Mary L M; Richt, Juergen A

    2015-12-01

    In this cross-sectional seroepidemiological study we sought to examine the evidence for circulation of Rift Valley fever virus (RVFV) among herders in Madagascar and Kenya. From July 2010 to June 2012, we enrolled 459 herders and 98 controls (without ruminant exposures) and studied their sera (immunoglobulin G [IgG] and IgM through enzyme-linked immunosorbent assay [ELISA] and plaque reduction neutralization test [PRNT] assays) for evidence of previous RVFV infection. Overall, 59 (12.9%) of 459 herders and 7 (7.1%) of the 98 controls were positive by the IgG ELISA assay. Of the 59 ELISA-positive herders, 23 (38.9%) were confirmed by the PRNT assay (21 from eastern Kenya). Two of the 21 PRNT-positive study subjects also had elevated IgM antibodies against RVFV suggesting recent infection. Multivariate modeling in this study revealed that being seminomadic (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 2.1-15.4) was most strongly associated with antibodies against RVFV. Although we cannot know when these infections occurred, it seems likely that some interepidemic RVFV infections are occurring among herders. As there are disincentives regarding reporting RVFV outbreaks in livestock or wildlife, it may be prudent to conduct periodic, limited, active seroepidemiological surveillance for RVFV infections in herders, especially in eastern Kenya. © The American Society of Tropical Medicine and Hygiene.

  19. Environmental change and Rift Valley fever in eastern Africa: projecting beyond HEALTHY FUTURES.

    PubMed

    Taylor, David; Hagenlocher, Michael; Jones, Anne E; Kienberger, Stefan; Leedale, Joseph; Morse, Andrew P

    2016-03-31

    Outbreaks of Rift Valley fever (RVF), a relatively recently emerged zoonosis endemic to large parts of sub-Saharan Africa that has the potential to spread beyond the continent, have profound health and socio-economic impacts, particularly in communities where resilience is already low. Here output from a new, dynamic disease model [the Liverpool RVF (LRVF) model], driven by downscaled, bias-corrected climate change data from an ensemble of global circulation models from the Inter-Sectoral Impact Model Intercomparison Project run according to two radiative forcing scenarios [representative concentration pathway (RCP)4.5 and RCP8.5], is combined with results of a spatial assessment of social vulnerability to the disease in eastern Africa. The combined approach allowed for analyses of spatial and temporal variations in the risk of RVF to the end of the current century. Results for both scenarios highlight the high-risk of future RVF outbreaks, including in parts of eastern Africa to date unaffected by the disease. The results also highlight the risk of spread from/to countries adjacent to the study area, and possibly farther afield, and the value of considering the geography of future projections of disease risk. Based on the results, there is a clear need to remain vigilant and to invest not only in surveillance and early warning systems, but also in addressing the socio-economic factors that underpin social vulnerability in order to mitigate, effectively, future impacts.

  20. Outbreak of Rift Valley fever affecting veterinarians and farmers in South Africa, 2008.

    PubMed

    Archer, Brett N; Weyer, Jacqueline; Paweska, Janusz; Nkosi, Deliwe; Leman, Patricia; Tint, Khin San; Blumberg, Lucille

    2011-04-01

    During 2008, Rift Valley fever (RVF) virus re-emerged in South Africa as focal outbreaks in several provinces. To investigate an outbreak affecting cattle farmers and farm workers, and the staff and students of a veterinary school, assess the prevalence of infection during the outbreak, document the clinical presentation of cases, and identify potential risk factors. We conducted a cross-sectional serological survey of exposed veterinarians and farmers, who were examined to determine the presence of current or recent illness. Blood specimens were collected for virus isolation, nucleic acid detection and serology. A subset was interviewed using a standardised questionnaire to obtain data on recent exposures and risk factors for infection. Of 53 participants potentially exposed to infected domestic ruminants, 15% had evidence of recent infection and 4% evidence of past exposure to the RVF virus. The prevalence of acute infection was 21% in veterinarians compared with 9% in farmers and farm workers. After a mean incubation period of 4.3 days, the most frequent symptoms experienced included myalgia (100%), headache (88%) and malaise (75%). No asymptomatic cases were identified. Transmission, by direct contact with infected animals was the major risk factor in these professional groups. Performing animal autopsies was significantly associated with acute infection (risk ratio 16.3, 95% confidence interval 2.3 - 114.2). Increased risks associated with veterinary practices highlight a need for the use of personal protective equipment, and identify veterinarians as a primary target group for future vaccination.

  1. Remote Sensing in a Changing Climate and Environment: the Rift Valley Fever Case

    NASA Astrophysics Data System (ADS)

    Tourre, Y. M.; Lacaux, J.-P.; Vignolles, C.; Lafaye, M.

    2012-07-01

    Climate and environment are changing rapidly whilst global population already reached 7 billions people. New public health challenges are posed by new and re-emerging diseases. Innovation is a must i.e., 1) using high resolution remote sensing, 2) re-invent health politics and trans-disciplinary management. The above are part of the 'TransCube Approach' i.e., Transition, Translation, and Transformation. The new concept of Tele-epidemiology includes such approach. A conceptual approach (CA) associated with Rift Valley Fever (RVF) epidemics in Senegal is presented. Ponds are detected using high-resolution SPOT-5 satellite images and radar data from space. Data on rainfall events obtained from the Tropical Rainfall Measuring Mission (NASA/JAXA) are combined with in-situ data. Localization of vulnerable and parked hosts (obtained from QuickBird satellite) is also used. The dynamic spatio-temporal distribution and aggressiveness of RVF mosquitoes, are based on total rainfall amounts, ponds' dynamics and entomological observations. Detailed risks maps (hazards + vulnerability) in real-time are expressed in percentages of parks where animals are potentially at risks. This CA which simply relies upon rainfall distribution from space, is meant to contribute to the implementation of the RVF early warning system (RVFews). It is meant to be applied to other diseases and elsewhere. This is particularly true in new places where new vectors have been rapidly adapting (such as Aedes albopictus) whilst viruses (such as West Nile and Chikungunya,) circulate from constantly moving reservoirs and increasing population.

  2. Rift Valley Fever Virus Structural and Nonstructural Proteins: Recombinant Protein Expression and Immunoreactivity Against Antisera from Sheep

    PubMed Central

    Faburay, Bonto; Wilson, William; McVey, D. Scott; Drolet, Barbara S.; Weingartl, Hana; Madden, Daniel; Young, Alan; Ma, Wenjun

    2013-01-01

    Abstract The Rift Valley fever virus (RVFV) encodes the structural proteins nucleoprotein (N), aminoterminal glycoprotein (Gn), carboxyterminal glycoprotein (Gc), and L protein, 78-kD, and the nonstructural proteins NSm and NSs. Using the baculovirus system, we expressed the full-length coding sequence of N, NSs, NSm, Gc, and the ectodomain of the coding sequence of the Gn glycoprotein derived from the virulent strain of RVFV ZH548. Western blot analysis using anti-His antibodies and monoclonal antibodies against Gn and N confirmed expression of the recombinant proteins, and in vitro biochemical analysis showed that the two glycoproteins, Gn and Gc, were expressed in glycosylated form. Immunoreactivity profiles of the recombinant proteins in western blot and in indirect enzyme-linked immunosorbent assay against a panel of antisera obtained from vaccinated or wild type (RVFV)-challenged sheep confirmed the results obtained with anti-His antibodies and demonstrated the suitability of the baculo-expressed antigens for diagnostic assays. In addition, these recombinant proteins could be valuable for the development of diagnostic methods that differentiate infected from vaccinated animals (DIVA). PMID:23962238

  3. Relationship of Climate, Geography, and Geology to the Incidence of Rift Valley Fever in Kenya during the 2006–2007 Outbreak

    PubMed Central

    Hightower, Allen; Kinkade, Carl; Nguku, Patrick M.; Anyangu, Amwayi; Mutonga, David; Omolo, Jared; Njenga, M. Kariuki; Feikin, Daniel R.; Schnabel, David; Ombok, Maurice; Breiman, Robert F.

    2012-01-01

    We estimated Rift Valley fever (RVF) incidence as a function of geological, geographical, and climatological factors during the 2006–2007 RVF epidemic in Kenya. Location information was obtained for 214 of 340 (63%) confirmed and probable RVF cases that occurred during an outbreak from November 1, 2006 to February 28, 2007. Locations with subtypes of solonetz, calcisols, solonchaks, and planosols soil types were highly associated with RVF occurrence during the outbreak period. Increased rainfall and higher greenness measures before the outbreak were associated with increased risk. RVF was more likely to occur on plains, in densely bushed areas, at lower elevations, and in the Somalia acacia ecological zone. Cases occurred in three spatial temporal clusters that differed by the date of associated rainfall, soil type, and land usage. PMID:22302875

  4. Valley fever

    MedlinePlus

    ... get it by breathing in the fungus from soil. The infection starts in the lungs. It commonly ... during dust storms Avoiding activities that involve handling soil, such as gardening Take preventive medicines as prescribed ...

  5. The genetic basis for susceptibility to Rift Valley fever disease in MBT/Pas mice.

    PubMed

    Tokuda, S; Do Valle, T Z; Batista, L; Simon-Chazottes, D; Guillemot, L; Bouloy, M; Flamand, M; Montagutelli, X; Panthier, J-J

    2015-01-01

    The large variation in individual response to infection with Rift Valley fever virus (RVFV) suggests that host genetic determinants play a role in determining virus-induced disease outcomes. These genetic factors are still unknown. The systemic inoculation of mice with RVFV reproduces major pathological features of severe human disease, notably the hepatitis and encephalitis. A genome scan performed on 546 (BALB/c × MBT) F2 progeny identified three quantitative trait loci (QTLs), denoted Rvfs-1 to Rvfs-3, that were associated with disease susceptibility in MBT/Pas mice. Non-parametric interval-mapping revealed one significant and two suggestive linkages with survival time on chromosomes 2 (Rvfs-1), 5 (Rvfs-3) and 11 (Rvfs-2) with respective logarithm of odds (LOD) scores of 4.58, 2.95 and 2.99. The two-part model, combining survival time and survival/death, identified one significant linkage to Rvfs-2 and one suggestive linkage to Rvfs-1 with respective LOD scores of 5.12 and 4.55. Under a multiple model, with additive effects and sex as a covariate, the three QTLs explained 8.3% of the phenotypic variance. Sex had the strongest influence on susceptibility. The contribution of Rvfs-1, Rvfs-2 and Rvfs-3 to survival time of RVFV-infected mice was further confirmed in congenic mice.

  6. Four-segmented Rift Valley fever virus-based vaccines can be applied safely in ewes during pregnancy.

    PubMed

    Wichgers Schreur, Paul J; van Keulen, Lucien; Kant, Jet; Kortekaas, Jeroen

    2017-05-25

    Rift Valley fever virus (RVFV) causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. This mosquito-borne virus, belonging to the genus Phlebovirus of the family Bunyaviridae contains a tri-segmented negative-strand RNA genome. Previously, we developed four-segmented RVFV (RVFV-4s) variants by splitting the M-genome segment into two M-type segments each encoding one of the structural glycoproteins; Gn or Gc. Vaccination/challenge experiments with mice and lambs subsequently showed that RVFV-4s induces protective immunity against wild-type virus infection after a single administration. To demonstrate the unprecedented safety of RVFV-4s, we here report that the virus does not cause encephalitis after intranasal inoculation of mice. A study with pregnant ewes subsequently revealed that RVFV-4s does not cause viremia and does not cross the ovine placental barrier, as evidenced by the absence of teratogenic effects and virus in the blood and organs of the fetuses. Altogether, these results show that the RVFV-4s vaccine virus can be applied safely in pregnant ewes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Safety and immunogenecity of a live attenuated Rift Valley fever vaccine (CL13T) in camels.

    PubMed

    Daouam, S; Ghzal, F; Naouli, Y; Tadlaoui, K O; Ennaji, M M; Oura, C; El Harrak, M

    2016-07-26

    Rift Valley fever is an emerging zoonotic viral disease, enzootic and endemic in Africa and the Arabian Peninsula, which poses a significant threat to both human and animal health. The disease is most severe in ruminants causing abortions in pregnant animals, especially sheep animals and high mortality in young populations. High mortality rates and severe clinical manifestation have also been reported among camel populations in Africa, to attend however none of the currently available live vaccines against RVF have been tested for safety and efficacy in this species. In this study, the safety and efficacy (through a neutralizing antibody response) of the thermostable live attenuated RVF CL13T vaccine were evaluated in camels in two different preliminary experiments involving 16 camels, (that 12 camels and 4 pregnant camels). The study revealed that the CL13T vaccine was safe to use in camels and no abortions or teratogenic effects were observed. The single dose of the vaccine stimulated a strong and long-lasting neutralizing antibody response for up to 12 months. The presence of neutralization antibodies is likely to correlate with protection; however protection would need to be confirmed by challenge experiments using the virulent RVF virus.

  8. Has Rift Valley fever virus evolved with increasing severity in human populations in East Africa?

    PubMed

    Baba, Marycelin; Masiga, Daniel K; Sang, Rosemary; Villinger, Jandouwe

    2016-06-22

    Rift Valley fever (RVF) outbreaks have occurred across eastern Africa from 1912 to 2010 approximately every 4-15 years, most of which have not been accompanied by significant epidemics in human populations. However, human epidemics during RVF outbreaks in eastern Africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. We review the history of RVF outbreaks in eastern Africa to identify the epidemiological factors that could have influenced its increasing severity in humans. Diverse ecological factors influence outbreak frequency, whereas virus evolution has a greater impact on its virulence in hosts. Several factors could have influenced the lack of information on RVF in humans during earlier outbreaks, but the explosive nature of human RVF epidemics in recent years mirrors the evolutionary trend of the virus. Comparisons between isolates from different outbreaks have revealed an accumulation of genetic mutations and genomic reassortments that have diversified RVF virus genomes over several decades. The threat to humans posed by the diversified RVF virus strains increases the potential public health and socioeconomic impacts of future outbreaks. Understanding the shifting RVF epidemiology as determined by its evolution is key to developing new strategies for outbreak mitigation and prevention of future human RVF casualties.

  9. Modelling the effects of seasonality and socioeconomic impact on the transmission of Rift Valley fever virus

    USGS Publications Warehouse

    Xiao, Yanyu; Beier, John C.; Cantrell, Robert Stephen; Cosner, Chris; DeAngelis, Donald L.; Ruan, Shigui

    2015-01-01

    Rift Valley fever (RVF) is an important mosquito-borne viral zoonosis in Africa and the Middle East that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. Outbreaks of RVF are sporadic and associated with both seasonal and socioeconomic effects. Here we propose an almost periodic three-patch model to investigate the transmission dynamics of RVF virus (RVFV) among ruminants with spatial movements. Our findings indicate that, in Northeastern Africa, human activities, including those associated with the Eid al Adha feast, along with a combination of climatic factors such as rainfall level and hydrological variations, contribute to the transmission and dispersal of the disease pathogen. Moreover, sporadic outbreaks may occur when the two events occur together: 1) abundant livestock are recruited into areas at risk from RVF due to the demand for the religious festival and 2) abundant numbers of mosquitoes emerge. These two factors have been shown to have impacts on the severity of RVF outbreaks. Our numerical results present the transmission dynamics of the disease pathogen over both short and long periods of time, particularly during the festival time. Further, we investigate the impact on patterns of disease outbreaks in each patch brought by festival- and seasonal-driven factors, such as the number of livestock imported daily, the animal transportation speed from patch to patch, and the death rate induced by ceremonial sacrifices. In addition, our simulations show that when the time for festival preparation starts earlier than usual, the risk of massive disease outbreaks rises, particularly in patch 3 (the place where the religious ceremony will be held).

  10. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR.

    PubMed

    Kainulainen, Markus; Lau, Simone; Samuel, Charles E; Hornung, Veit; Weber, Friedemann

    2016-07-01

    Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we demonstrate that NSs

  11. NSs Virulence Factor of Rift Valley Fever Virus Engages the F-Box Proteins FBXW11 and β-TRCP1 To Degrade the Antiviral Protein Kinase PKR

    PubMed Central

    Kainulainen, Markus; Lau, Simone; Samuel, Charles E.; Hornung, Veit

    2016-01-01

    ABSTRACT Rift Valley fever virus (RVFV, family Bunyaviridae, genus Phlebovirus) is a relevant pathogen of both humans and livestock in Africa. The nonstructural protein NSs is a major virulence factor known to suppress the type I interferon (IFN) response by inhibiting host cell transcription and by proteasomal degradation of a major antiviral IFN effector, the translation-inhibiting protein kinase PKR. Here, we identified components of the modular SCF (Skp1, Cul1, F-box protein)-type E3 ubiquitin ligases as mediators of PKR destruction by NSs. Small interfering RNAs (siRNAs) against the conserved SCF subunit Skp1 protected PKR from NSs-mediated degradation. Consequently, RVFV replication was severely reduced in Skp1-depleted cells when PKR was present. SCF complexes have a variable F-box protein subunit that determines substrate specificity for ubiquitination. We performed an siRNA screen for all (about 70) human F-box proteins and found FBXW11 to be involved in PKR degradation. The partial stabilization of PKR by FBXW11 depletion upregulated PKR autophosphorylation and phosphorylation of the PKR substrate eIF2α and caused a shutoff of host cell protein synthesis in RVFV-infected cells. To maximally protect PKR from the action of NSs, knockdown of structurally and functionally related FBXW1 (also known as β-TRCP1), in addition to FBXW11 deletion, was necessary. Consequently, NSs was found to interact with both FBXW11 and β-TRCP1. Thus, NSs eliminates the antiviral kinase PKR by recruitment of SCF-type E3 ubiquitin ligases containing FBXW11 and β-TRCP1 as substrate recognition subunits. This antagonism of PKR by NSs is essential for efficient RVFV replication in mammalian cells. IMPORTANCE Rift Valley fever virus is a pathogen of humans and animals that has the potential to spread from Africa and the Arabian Peninsula to other regions. A major virulence mechanism is the proteasomal degradation of the antiviral kinase PKR by the viral protein NSs. Here, we

  12. Common Host-Derived Chemicals Increase Catches of Disease-Transmitting Mosquitoes and Can Improve Early Warning Systems for Rift Valley Fever Virus

    PubMed Central

    Tchouassi, David P.; Sang, Rosemary; Sole, Catherine L.; Bastos, Armanda D. S.; Teal, Peter E. A.; Borgemeister, Christian; Torto, Baldwyn

    2013-01-01

    Rift Valley fever (RVF), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-Saharan Africa. Surveillance to monitor mosquito populations during the inter-epidemic period (IEP) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. Using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decanal) common to RVF virus (RVFV) hosts including sheep, cow, donkey, goat and human serve as potent attractants for RVFV mosquito vectors. Furthermore, a blend formulated from the four aldehydes and combined with CO2-baited CDC trap without a light bulb doubled to tripled trap captures compared to control traps baited with CO2 alone. Our results reveal that (a) because of the commonality of the host chemical signature required for attraction, the host-vector interaction appears to favor the mosquito vector allowing it to find and opportunistically feed on a wide range of mammalian hosts of the disease, and (b) the sensitivity, specificity and superiority of this trapping system offers the potential for its wider use in surveillance programs for RVFV mosquito vectors especially during the IEP. PMID:23326620

  13. Rift Valley fever virus infection in African Buffalo (Syncerus caffer) herds in rural South Africa: Evidence of interepidemic transmission

    USGS Publications Warehouse

    LaBeaud, A.D.; Cross, P.C.; Getz, W.M.; Glinka, A.; King, C.H.

    2011-01-01

    Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000-2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001-2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk. Copyright ?? 2011 by The American Society of Tropical Medicine and Hygiene.

  14. Infection and Transmission of Rift Valley Fever Viruses Lacking the NSs and/or NSm Genes in Mosquitoes: Potential Role for NSm in Mosquito Infection

    PubMed Central

    Crabtree, Mary B.; Kent Crockett, Rebekah J.; Bird, Brian H.; Nichol, Stuart T.; Erickson, Bobbie Rae; Biggerstaff, Brad J.; Horiuchi, Kalanthe; Miller, Barry R.

    2012-01-01

    Background Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Methodology and Principal Findings Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. Conclusions/Significance In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes. PMID:22563517

  15. Infection and transmission of Rift Valley fever viruses lacking the NSs and/or NSm genes in mosquitoes: potential role for NSm in mosquito infection.

    PubMed

    Crabtree, Mary B; Kent Crockett, Rebekah J; Bird, Brian H; Nichol, Stuart T; Erickson, Bobbie Rae; Biggerstaff, Brad J; Horiuchi, Kalanthe; Miller, Barry R

    2012-01-01

    Rift Valley fever virus is an arthropod-borne human and animal pathogen responsible for large outbreaks of acute and febrile illness throughout Africa and the Arabian Peninsula. Reverse genetics technology has been used to develop deletion mutants of the virus that lack the NSs and/or NSm virulence genes and have been shown to be stable, immunogenic and protective against Rift Valley fever virus infection in animals. We assessed the potential for these deletion mutant viruses to infect and be transmitted by Aedes mosquitoes, which are the principal vectors for maintenance of the virus in nature and emergence of virus initiating disease outbreaks, and by Culex mosquitoes which are important amplification vectors. Aedes aegypti and Culex quinquefasciatus mosquitoes were fed bloodmeals containing the deletion mutant viruses. Two weeks post-exposure mosquitoes were assayed for infection, dissemination, and transmission. In Ae. aegypti, infection and transmission rates of the NSs deletion virus were similar to wild type virus while dissemination rates were significantly reduced. Infection and dissemination rates for the NSm deletion virus were lower compared to wild type. Virus lacking both NSs and NSm failed to infect Ae. aegypti. In Cx. quinquefasciatus, infection rates for viruses lacking NSm or both NSs and NSm were lower than for wild type virus. In both species, deletion of NSm or both NSs and NSm reduced the infection and transmission potential of the virus. Deletion of both NSs and NSm resulted in the highest level of attenuation of virus replication. Deletion of NSm alone was sufficient to nearly abolish infection in Aedes aegypti mosquitoes, indicating an important role for this protein. The double deleted viruses represent an ideal vaccine profile in terms of environmental containment due to lack of ability to efficiently infect and be transmitted by mosquitoes.

  16. Q fever in the Southern California desert: epidemiology, clinical presentation and treatment.

    PubMed

    Cone, Lawrence A; Curry, Noel; Shaver, Phillip; Brooks, David; DeForge, James; Potts, Barbara E

    2006-07-01

    Despite the absence of a natural reservoir for Q fever in the desert of Southern California, six cases have been identified during the past 32 years. During that period of time, two areas have been used by northern sheep ranchers from Idaho and Wyoming to import sheep to an area in the Coachella Valley through 1985. Thereafter, because of housing development, the sheep area was moved to Blythe along the Colorado River. All but two of these patients probably acquired infection by Coxiella burnetii by living or working in close proximity to these grazing areas but not directly involved with the sheep. The shift of infected patients from the Coachella Valley to Blythe (100 miles distant) seems to support that supposition. All patients with acute Q fever developed antibodies primarily to phase II antigen, whereas the only person with chronic Q fever developed phase I antibodies. All patients presented with granulomatous hepatitis. One also had a pulmonary infiltrate, and the single individual with chronic Q fever also had a mitral valve prosthesis, although echocardiography could not define endocarditis. All patients with acute infections responded to 3-5 weeks of therapy with doxycycline, whereas the patient with chronic disease failed 3 years of therapy with combination regimens. Further studies at the Eisenhower Medical Center on the prevalence of infection in Blythe, CA, and elsewhere are anticipated.

  17. Anomalous High Rainfall and Soil Saturation as Combined Risk Indicator of Rift Valley Fever Outbreaks, South Africa, 2008–2011

    PubMed Central

    Malherbe, Johan; Weepener, Harold; Majiwa, Phelix; Swanepoel, Robert

    2016-01-01

    Rift Valley fever (RVF), a zoonotic vectorborne viral disease, causes loss of life among humans and livestock and an adverse effect on the economy of affected countries. Vaccination is the most effective way to protect livestock; however, during protracted interepidemic periods, farmers discontinue vaccination, which leads to loss of herd immunity and heavy losses of livestock when subsequent outbreaks occur. Retrospective analysis of the 2008–2011 RVF epidemics in South Africa revealed a pattern of continuous and widespread seasonal rainfall causing substantial soil saturation followed by explicit rainfall events that flooded dambos (seasonally flooded depressions), triggering outbreaks of disease. Incorporation of rainfall and soil saturation data into a prediction model for major outbreaks of RVF resulted in the correctly identified risk in nearly 90% of instances at least 1 month before outbreaks occurred; all indications are that irrigation is of major importance in the remaining 10% of outbreaks. PMID:27403563

  18. Fever-like thermal conditions regulate the activation of maturing dendritic cells.

    PubMed

    Tournier, Jean-Nicolas; Hellmann, Anne Quesnel; Lesca, Gaëtan; Jouan, Alain; Drouet, Emmanuel; Mathieu, Jacques

    2003-04-01

    Fever is one of the most frequent clinical signs encountered in pathology, especially with respect to infectious diseases. It is currently thought that the role of fever on immunity is limited to activation of innate immunity; however, its relevance to activation of adaptive immunity remains unclear. Dendritic cells (DCs) that behave as sentinels of the immune system provide an important bridge between innate and adaptive immunity. To highlight the role of fever on adaptive immunity, we exposed murine bone marrow-derived lipopolysaccharide (LPS)- or live bacteria-maturing DCs over a 3-h period to 37 degrees C or to fever-like thermal conditions (39 degrees C or 40 degrees C). At these three temperatures, we measured the kinetics of cytokine production and the ability of DCs to induce an allogeneic mixed lymphocyte reaction. Our results show that short exposure of DCs to temperatures of 39 degrees C or 40 degrees C differentially increased the secretion of interleukin (IL)-12p70 and decreased the secretion of IL-10 and tumor necrosis factor alpha by maturing DCs. These fever-like conditions induced a regulation of cytokine production at the single-cell level. In addition, short-term exposed LPS-maturing DCs to 39 degrees C induced a stronger reaction with allogeneic CD4(+) T cells than maturing DCs incubated at 37 degrees C. These results provide evidence that temperature regulates cytokine secretion and DC functions, both of which are of particular importance in bacterial diseases.

  19. 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.

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

    PubMed

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

    2017-07-01

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

  1. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.

    PubMed

    Warimwe, George M; Lorenzo, Gema; Lopez-Gil, Elena; Reyes-Sandoval, Arturo; Cottingham, Matthew G; Spencer, Alexandra J; Collins, Katharine A; Dicks, Matthew D J; Milicic, Anita; Lall, Amar; Furze, Julie; Turner, Alison V; Hill, Adrian V S; Brun, Alejandro; Gilbert, Sarah C

    2013-12-05

    Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens. Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice. A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response. Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

  2. Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.

    PubMed

    Broce, Sean; Hensley, Lisa; Sato, Tomoharu; Lehrer-Graiwer, Joshua; Essrich, Christian; Edwards, Katie J; Pajda, Jacqueline; Davis, Christopher J; Bhadresh, Rami; Hurt, Clarence R; Freeman, Beverly; Lingappa, Vishwanath R; Kelleher, Colm A; Karpuj, Marcela V

    2016-05-14

    Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro-generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section.

  3. Coupling Vector-host Dynamics with Weather Geography and Mitigation Measures to Model Rift Valley Fever in Africa.

    PubMed

    McMahon, B H; Manore, C A; Hyman, J M; LaBute, M X; Fair, J M

    2014-01-01

    We present and characterize a multi-host epidemic model of Rift Valley fever (RVF) virus in East Africa with geographic spread on a network, rule-based mitigation measures, and mosquito infection and population dynamics. Susceptible populations are depleted by disease and vaccination and are replenished with the birth of new animals. We observe that the severity of the epidemics is strongly correlated with the duration of the rainy season and that even severe epidemics are abruptly terminated when the rain stops. Because naturally acquired herd immunity is established, total mortality across 25 years is relatively insensitive to many mitigation approaches. Strong reductions in cattle mortality are expected, however, with sufficient reduction in population densities of either vectors or susceptible (ie. unvaccinated) hosts. A better understanding of RVF epidemiology would result from serology surveys to quantify the importance of herd immunity in epidemic control, and sequencing of virus from representative animals to quantify the realative importance of transportation and local reservoirs in nucleating yearly epidemics. Our results suggest that an effective multi-layered mitigation strategy would include vector control, movement control, and vaccination of young animals yearly, even in the absence of expected rainfall.

  4. A Single Vaccination with an Improved Nonspreading Rift Valley Fever Virus Vaccine Provides Sterile Immunity in Lambs

    PubMed Central

    Oreshkova, Nadia; van Keulen, Lucien; Kant, Jet; Moormann, Rob J. M.; Kortekaas, Jeroen

    2013-01-01

    Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 106.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine. PMID:24167574

  5. Metal fume fever and polymer fume fever.

    PubMed

    Greenberg, Michael I; Vearrier, David

    2015-05-01

    Inhalational exposure to metal-containing fumes generated by welding and related processes may result in the development of the clinical syndrome known as "metal fume fever." Polymer fume fever is a separate and distinct but related disorder that has been associated with inhalational exposure to specific fluorinated polymer products, such as polytetrafluoroethylene or Teflon(®). We undertook a review of the peer-reviewed medical literature as it relates to these two disease entities in order to describe their epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, prevention, and prognosis. We performed a search of the PubMed ( www.pubmed.com ) and Ovid MEDLINE (ovidsp.tx.ovid.com) databases for keywords "metal fume fever," "polymer fume fever," and "fume fever," covering the period 1946 to September 2014, which resulted in a total of 141 citations. Limiting the search to articles published in the English language yielded 115 citations. These 115 articles were manually reviewed for relevance. In addition, the reference lists in each article retrieved were reviewed for additional relevant references. This left 48 relevant citations. Metal fume fever occurs most commonly as an occupational disease in individuals who perform welding and other metal-joining activities for a living. It is estimated that 1,500-2,500 cases of metal fume fever occur annually in the United States. Polymer fume fever was initially identified as an occupational disease but increased regulations have resulted in decreased incidence in the occupational setting. Overheating of Teflon(®)-coated cookware is one of the more common mechanisms for exposure. While the precise pathophysiology associated with the development of metal fume fever is yet to be elucidated, suggested pathophysiologic mechanisms include pro-inflammatory cytokine release, neutrophil activation, and oxygen radical formation. The pathophysiologic mechanism for polymer fume fever has not been definitively

  6. Seroprevalence of Alkhurma and other hemorrhagic fever viruses, Saudi Arabia.

    PubMed

    Memish, Ziad A; Albarrak, Ali; Almazroa, Mohammad A; Al-Omar, Ibrahim; Alhakeem, Rafat; Assiri, Abdullah; Fagbo, Shamsudeen; MacNeil, Adam; Rollin, Pierre E; Abdullah, Nageeb; Stephens, Gwen

    2011-12-01

    A 2009 deployment of military units from several Saudi Arabian provinces to Jazan Province, Saudi Arabia, enabled us to evaluate exposure to Alkhurma, Crimean-Congo, dengue, and Rift Valley hemorrhagic fever viruses. Seroprevalence to all viruses was low; however, Alkhurma virus seroprevalence was higher (1.3%) and less geographically restricted than previously thought.

  7. Has Rift Valley fever virus evolved with increasing severity in human populations in East Africa?

    PubMed Central

    Baba, Marycelin; Masiga, Daniel K; Sang, Rosemary; Villinger, Jandouwe

    2016-01-01

    Rift Valley fever (RVF) outbreaks have occurred across eastern Africa from 1912 to 2010 approximately every 4–15 years, most of which have not been accompanied by significant epidemics in human populations. However, human epidemics during RVF outbreaks in eastern Africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. We review the history of RVF outbreaks in eastern Africa to identify the epidemiological factors that could have influenced its increasing severity in humans. Diverse ecological factors influence outbreak frequency, whereas virus evolution has a greater impact on its virulence in hosts. Several factors could have influenced the lack of information on RVF in humans during earlier outbreaks, but the explosive nature of human RVF epidemics in recent years mirrors the evolutionary trend of the virus. Comparisons between isolates from different outbreaks have revealed an accumulation of genetic mutations and genomic reassortments that have diversified RVF virus genomes over several decades. The threat to humans posed by the diversified RVF virus strains increases the potential public health and socioeconomic impacts of future outbreaks. Understanding the shifting RVF epidemiology as determined by its evolution is key to developing new strategies for outbreak mitigation and prevention of future human RVF casualties. PMID:27329846

  8. Creation of a Recombinant Rift Valley Fever Virus with a Two-Segmented Genome ▿ †

    PubMed Central

    Brennan, Benjamin; Welch, Stephen R.; McLees, Angela; Elliott, Richard M.

    2011-01-01

    Rift Valley fever virus (RVFV; family Bunyaviridae) is a clinically important, mosquito-borne pathogen of both livestock and humans, which is found mainly in sub-Saharan Africa and the Arabian Peninsula. RVFV has a trisegmented single-stranded RNA (ssRNA) genome. The L and M segments are negative sense and encode the L protein (viral polymerase) on the L segment and the virion glycoproteins Gn and Gc as well as two other proteins, NSm and 78K, on the M segment. The S segment uses an ambisense coding strategy to express the nucleocapsid protein, N, and the nonstructural protein, NSs. Both the NSs and NSm proteins are dispensable for virus growth in tissue culture. Using reverse genetics, we generated a recombinant virus, designated r2segMP12, containing a two-segmented genome in which the NSs coding sequence was replaced with that for the Gn and Gc precursor. Thus, r2segMP12 lacks an M segment, and although it was attenuated in comparison to the three-segmented parental virus in both mammalian and insect cell cultures, it was genetically stable over multiple passages. We further show that the virus can stably maintain an M-like RNA segment encoding the enhanced green fluorescent protein gene. The implications of these findings for RVFV genome packaging and the potential to develop multivalent live-attenuated vaccines are discussed. PMID:21795328

  9. Analysis of surveillance systems in place in European Mediterranean countries for West Nile virus (WNV) and Rift Valley fever (RVF).

    PubMed

    Cito, F; Narcisi, V; Danzetta, M L; Iannetti, S; Sabatino, D D; Bruno, R; Carvelli, A; Atzeni, M; Sauro, F; Calistri, P

    2013-11-01

    West Nile virus (WNV) and Rift Valley fever virus (RVFV) represent an important group of viral agents responsible for vector-borne zoonotic diseases constituting an emerging sanitary threat for the Mediterranean Basin and the neighbouring countries. WNV infection is present in several Mediterranean countries, whereas RVF has never been introduced into Europe, but it is considered a major threat for North African countries. Being vector-borne diseases, they cannot be prevented only through an animal trade control policy. Several approaches are used for the surveillance of WNV and RVFV. With the aim of assessing the surveillance systems in place in Mediterranean countries, two disease-specific questionnaires (WNV, RVFV) have been prepared and submitted to Public Health and Veterinary Authorities of six EU countries. This study presents the information gathered through the questionnaires and describes some critical points in the prevention and surveillance of these diseases as emerged by the answers received. © 2013 Blackwell Verlag GmbH.

  10. Rift valley Fever virus encephalitis is associated with an ineffective systemic immune response and activated T cell infiltration into the CNS in an immunocompetent mouse model.

    PubMed

    Dodd, Kimberly A; McElroy, Anita K; Jones, Tara L; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2014-06-01

    Rift Valley fever virus (RVFV) causes outbreaks of severe disease in livestock and humans throughout Africa and the Arabian Peninsula. In people, RVFV generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. One manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. In order to design targeted interventions, the basic pathogenesis of RVFV encephalitis must be better understood. To characterize the host immune responses and viral kinetics associated with fatal and nonfatal infections, mice were infected with an attenuated RVFV lacking NSs (ΔNSs) that causes lethal disease only when administered intranasally (IN). Following IN infection, C57BL/6 mice developed severe neurologic disease and succumbed 7-9 days post-infection. In contrast, inoculation of ΔNSs virus subcutaneously in the footpad (FP) resulted in a subclinical infection characterized by a robust immune response with rapid antibody production and strong T cell responses. IN-inoculated mice had delayed antibody responses and failed to clear virus from the periphery. Severe neurological signs and obtundation characterized end stage-disease in IN-inoculated mice, and within the CNS, the development of peak virus RNA loads coincided with strong proinflammatory responses and infiltration of activated T cells. Interestingly, depletion of T cells did not significantly alter survival, suggesting that neurologic disease is not a by-product of an aberrant immune response. Comparison of fatal (IN-inoculated) and nonfatal (FP-inoculated) ΔNSs RVFV infections in the mouse model highlighted the role of the host immune response in controlling viral replication and therefore determining clinical outcome. There was no evidence to suggest that neurologic disease is immune-mediated in RVFV infection. These results provide important insights for the future design of vaccines and therapeutic

  11. A 3-year serological and virological cattle follow-up in Madagascar highlands suggests a non-classical transmission route of Rift Valley fever virus.

    PubMed

    Nicolas, Gaëlle; Durand, Benoit; Rakotoarimanana, Tafika Tojofaniry; Lacote, Sandra; Chevalier, Véronique; Marianneau, Philippe

    2014-02-01

    Rift Valley fever virus (RVFV) is a mosquito-borne infection of livestock and human which causes a potentially severe disease. In 2008-2009, a RVF outbreak occurred in a temperate and mountainous area located on the highlands of Madagascar. A three-year cattle follow-up (2009-2011) was conducted in a pilot area of this highland. A seroprevalence rate of 28% was estimated in 2009 and a seroconversion rate of 7% in 2009-2010. A third cross-sectional survey showed a seroconversion rate of 14% in 2010-2011. In 2011 the longitudinal study suggested a RVFV circulation during the year. In this area where vectors density is low and cattle exchanges are linked to the virus local spread, we raise hypotheses that may explain the local persistence of the virus.

  12. Transmission Dynamics of Rift Valley Fever Virus: Effects of Live and Killed Vaccines on Epizootic Outbreaks and Enzootic Maintenance

    PubMed Central

    Chamchod, Farida; Cosner, Chris; Cantrell, R. Stephen; Beier, John C.; Ruan, Shigui

    2016-01-01

    Rift Valley fever virus (RVFV) is an arthropod-borne viral pathogen that causes significant morbidity and mortality in small ruminants throughout Africa and the Middle East. Due to the sporadic and explosive nature of RVF outbreaks, vaccination has proved challenging to reduce RVFV infection in the ruminant population. Currently, there are two available types of vaccines, live and killed, in endemic areas. In this study, two mathematical models have been developed to explore the impact of live and killed vaccines on the transmission dynamics of RVFV. We demonstrate in general that vaccination helps reduce the severity of RVF outbreaks and that less delay in implementation and more vaccination attempts and effective vaccines can reduce the outbreak magnitude and the endemic number of RVFV. However, an introduction of a number of ruminants vaccinated by live vaccines in RVFV-free areas may cause an outbreak and RVFV may become endemic if there is sustained use of live vaccines. Other factors that are the important determinants of RVF outbreaks include: unsustained vaccination programs, recruitment of susceptible ruminants, and the seasonal abundance of mosquitoes. PMID:26869999

  13. Low-dose ribavirin potentiates the antiviral activity of favipiravir against hemorrhagic fever viruses.

    PubMed

    Westover, Jonna B; Sefing, Eric J; Bailey, Kevin W; Van Wettere, Arnaud J; Jung, Kie-Hoon; Dagley, Ashley; Wandersee, Luci; Downs, Brittney; Smee, Donald F; Furuta, Yousuke; Bray, Mike; Gowen, Brian B

    2016-02-01

    Favipiravir is approved in Japan to treat novel or re-emerging influenza viruses, and is active against a broad spectrum of RNA viruses, including Ebola. Ribavirin is the only other licensed drug with activity against multiple RNA viruses. Recent studies show that ribavirin and favipiravir act synergistically to inhibit bunyavirus infections in cultured cells and laboratory mice, likely due to their different mechanisms of action. Convalescent immune globulin is the only approved treatment for Argentine hemorrhagic fever caused by the rodent-borne Junin arenavirus. We previously reported that favipiravir is highly effective in a number of small animal models of Argentine hemorrhagic fever. We now report that addition of low dose of ribavirin synergistically potentiates the activity of favipiravir against Junin virus infection of guinea pigs and another arenavirus, Pichinde virus infection of hamsters. This suggests that the efficacy of favipiravir against hemorrhagic fever viruses can be further enhanced through the addition of low-dose ribavirin. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Comprehensive Phylogenetic Reconstructions of Rift Valley Fever Virus: The 2010 Northern Mauritania Outbreak in the Camelus dromedarius Species

    PubMed Central

    Lo, Modou M.; Thiongane, Yaya; Diop, Mariame; Isselmou, Katia; Doumbia, Baba; Baba, Mohammed Ould; El Arbi, Ahmed S.; Lancelot, Renaud; Kane, Y.; Albina, Emmanuel; Cêtre-Sossah, Catherine

    2014-01-01

    Abstract Rift valley fever (RVF) is a mosquito-borne disease of domestic and wild ruminants caused by RVF virus (RVFV), a phlebovirus (Bunyaviridae). RVF is widespread in Sub-Saharan Africa. In September of 2010, an RVF outbreak occurred in northern Mauritania involving mass abortions in small ruminants and camels (Camelus dromedarius) and at least 63 human clinical cases, including 13 deaths. In camels, serological prevalence was 27.5–38.5% (95% confidence interval, n=279). For the first time, clinical signs other than abortions were reported in this species, including hemorrhagic septicemia and severe respiratory distress in animals. We assessed the presence of RVFV in camel sera sampled during this outbreak and generated whole-genome sequences of RVFV to determine the possible origin of this RVFV strain. Phylogenetic analyses suggested a shared ancestor between the Mauritania 2010 strain and strains from Zimbabwe (2269, 763, and 2373), Kenya (155_57 and 56IB8), South Africa (Kakamas, SA75 and SA51VanWyck), Uganda (Entebbe), and other strains linked to the 1987 outbreak of RVF in Mauritania (OS1, OS3, OS8, and OS9). PMID:25514121

  15. Comprehensive phylogenetic reconstructions of Rift Valley fever virus: the 2010 northern Mauritania outbreak in the Camelus dromedarius species.

    PubMed

    El Mamy, Ahmed B; Lo, Modou M; Thiongane, Yaya; Diop, Mariame; Isselmou, Katia; Doumbia, Baba; Baba, Mohammed Ould; El Arbi, Ahmed S; Lancelot, Renaud; Kane, Y; Albina, Emmanuel; Cêtre-Sossah, Catherine

    2014-12-01

    Rift valley fever (RVF) is a mosquito-borne disease of domestic and wild ruminants caused by RVF virus (RVFV), a phlebovirus (Bunyaviridae). RVF is widespread in Sub-Saharan Africa. In September of 2010, an RVF outbreak occurred in northern Mauritania involving mass abortions in small ruminants and camels (Camelus dromedarius) and at least 63 human clinical cases, including 13 deaths. In camels, serological prevalence was 27.5-38.5% (95% confidence interval, n=279). For the first time, clinical signs other than abortions were reported in this species, including hemorrhagic septicemia and severe respiratory distress in animals. We assessed the presence of RVFV in camel sera sampled during this outbreak and generated whole-genome sequences of RVFV to determine the possible origin of this RVFV strain. Phylogenetic analyses suggested a shared ancestor between the Mauritania 2010 strain and strains from Zimbabwe (2269, 763, and 2373), Kenya (155_57 and 56IB8), South Africa (Kakamas, SA75 and SA51VanWyck), Uganda (Entebbe), and other strains linked to the 1987 outbreak of RVF in Mauritania (OS1, OS3, OS8, and OS9).

  16. Activation of coagulation and endothelium with concurrent impairment of anticoagulant mechanisms in patients with typhoid fever.

    PubMed

    de Jong, Hanna K; Parry, Chris M; van der Vaart, Thomas W; Kager, Liesbeth M; van den Ende, Stannie J; Maude, Rapeephan R; Wijedoru, Lalith; Ghose, Aniruddha; Hassan, Mohammed U; Hossain, Mohammed A; Dondorp, Arjan M; Baker, Steve; Faiz, M Abul; Meijers, Joost C M; Wiersinga, W Joost

    2018-05-07

    Typhoid fever caused by Salmonella Typhi remains a major burden worldwide. Gastrointestinal bleeding can be seen in up to 10 percent of patients and may be fatal. The coagulopathy, which may be the driver of this severe complication in patients with typhoid fever, however is ill defined. The aim of this study was to evaluate the activation of coagulation, anticoagulation, and fibrinolysis in patients with acute typhoid fever. Parameters of coagulation and fibrinolysis were measured in 28 hospitalized patients with culture-confirmed or PCR-confirmed typhoid fever and compared to 38 age- and sex-matched healthy volunteers. Patients demonstrated activation of the coagulation system, as reflected by elevated in vitro thrombin generation and high plasma levels of fibrinogen, D-dimer and prothrombin fragment F1 + 2 in concert with consumption of coagulation factors resulting in a prolonged prothrombin-time and activated-partial-thromboplastin-time. Concurrently, the anticoagulant proteins, protein C and antithrombin, were significantly lower in comparison to healthy controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis and a marked activation of endothelial cells. The extent of coagulation activation was associated with the course of the disease, repeated testing during convalescence showed a return toward normal values. Activation of coagulation is an important clinical feature of typhoid fever and is associated with severity of disease. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression

    PubMed Central

    Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

    2016-01-01

    The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm’-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment. PMID:27231931

  18. Mutational Analysis of the Rift Valley Fever Virus Glycoprotein Precursor Proteins for Gn Protein Expression.

    PubMed

    Phoenix, Inaia; Lokugamage, Nandadeva; Nishiyama, Shoko; Ikegami, Tetsuro

    2016-05-24

    The Rift Valley fever virus (RVFV) M-segment encodes the 78 kD, NSm, Gn, and Gc proteins. The 1st AUG generates the 78 kD-Gc precursor, the 2nd AUG generates the NSm-Gn-Gc precursor, and the 3rd AUG makes the NSm'-Gn-Gc precursor. To understand biological changes due to abolishment of the precursors, we quantitatively measured Gn secretion using a reporter assay, in which a Gaussia luciferase (gLuc) protein is fused to the RVFV M-segment pre-Gn region. Using the reporter assay, the relative expression of Gn/gLuc fusion proteins was analyzed among various AUG mutants. The reporter assay showed efficient secretion of Gn/gLuc protein from the precursor made from the 2nd AUG, while the removal of the untranslated region upstream of the 2nd AUG (AUG2-M) increased the secretion of the Gn/gLuc protein. Subsequently, recombinant MP-12 strains encoding mutations in the pre-Gn region were rescued, and virological phenotypes were characterized. Recombinant MP-12 encoding the AUG2-M mutation replicated slightly less efficiently than the control, indicating that viral replication is further influenced by the biological processes occurring after Gn expression, rather than the Gn abundance. This study showed that, not only the abolishment of AUG, but also the truncation of viral UTR, affects the expression of Gn protein by the RVFV M-segment.

  19. Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain.

    PubMed

    Ly, Hoai J; Nishiyama, Shoko; Lokugamage, Nandadeva; Smith, Jennifer K; Zhang, Lihong; Perez, David; Juelich, Terry L; Freiberg, Alexander N; Ikegami, Tetsuro

    2017-12-04

    Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Development and characterization of a Rift Valley fever virus cell-cell fusion assay using alphavirus replicon vectors

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

    Filone, Claire Marie; Heise, Mark; Doms, Robert W.

    2006-12-20

    Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the Bunyaviridae family, is transmitted by mosquitoes and infects both humans and domestic animals, particularly cattle and sheep. Since primary RVFV strains must be handled in BSL-3+ or BSL-4 facilities, a RVFV cell-cell fusion assay will facilitate the investigation of RVFV glycoprotein function under BSL-2 conditions. As for other members of the Bunyaviridae family, RVFV glycoproteins are targeted to the Golgi, where the virus buds, and are not efficiently delivered to the cell surface. However, overexpression of RVFV glycoproteins using an alphavirus replicon vector resulted in the expressionmore » of the glycoproteins on the surface of multiple cell types. Brief treatment of RVFV glycoprotein expressing cells with mildly acidic media (pH 6.2 and below) resulted in rapid and efficient syncytia formation, which we quantified by {beta}-galactosidase {alpha}-complementation. Fusion was observed with several cell types, suggesting that the receptor(s) for RVFV is widely expressed or that this acid-dependent virus does not require a specific receptor to mediate cell-cell fusion. Fusion occurred over a broad temperature range, as expected for a virus with both mosquito and mammalian hosts. In contrast to cell fusion mediated by the VSV-G glycoprotein, RVFV glycoprotein-dependent cell fusion could be prevented by treating target cells with trypsin, indicating that one or more proteins (or protein-associated carbohydrate) on the host cell surface are needed to support membrane fusion. The cell-cell fusion assay reported here will make it possible to study the membrane fusion activity of RVFV glycoproteins in a high-throughput format and to screen small molecule inhibitors for the ability to block virus-specific membrane fusion.« less

  1. High-Throughput Screening Using a Whole-Cell Virus Replication Reporter Gene Assay to Identify Inhibitory Compounds against Rift Valley Fever Virus Infection.

    PubMed

    Islam, Md Koushikul; Baudin, Maria; Eriksson, Jonas; Öberg, Christopher; Habjan, Matthias; Weber, Friedemann; Överby, Anna K; Ahlm, Clas; Evander, Magnus

    2016-04-01

    Rift Valley fever virus (RVFV) is an emerging virus that causes serious illness in humans and livestock. There are no approved vaccines or treatments for humans. The purpose of the study was to identify inhibitory compounds of RVFV infection without any preconceived idea of the mechanism of action. A whole-cell-based high-throughput drug screening assay was developed to screen 28,437 small chemical compounds targeting RVFV infection. To accomplish both speed and robustness, a replication-competent NSs-deleted RVFV expressing a fluorescent reporter gene was developed. Inhibition of fluorescence intensity was quantified by spectrophotometry and related to virus infection in human lung epithelial cells (A549). Cell toxicity was assessed by the Resazurin cell viability assay. After primary screening, 641 compounds were identified that inhibited RVFV infection by ≥80%, with ≥50% cell viability at 50 µM concentration. These compounds were subjected to a second screening regarding dose-response profiles, and 63 compounds with ≥60% inhibition of RVFV infection at 3.12 µM compound concentration and ≥50% cell viability at 25 µM were considered hits. Of these, six compounds with high inhibitory activity were identified. In conclusion, the high-throughput assay could efficiently and safely identify several promising compounds that inhibited RVFV infection. © 2016 Society for Laboratory Automation and Screening.

  2. Rift Valley Fever: A survey of knowledge, attitudes, and practice of slaughterhouse workers and community members in Kabale District, Uganda

    PubMed Central

    Nyakarahuka, Luke; Purpura, Lawrence; Ervin, Elizabeth; Tumusiime, Alex; Balinandi, Stephen; Kyondo, Jackson; Mulei, Sophia; Tusiime, Patrick; Manning, Craig; Rollin, Pierre E.; Knust, Barbara; Shoemaker, Trevor

    2018-01-01

    Background Rift Valley Fever virus (RVF) is a zoonotic virus in the Phenuiviridae family. RVF outbreaks can cause significant morbidity and mortality in humans and animals. Following the diagnosis of two RVF cases in March 2016 in southern Kabale district, Uganda, we conducted a knowledge, attitudes and practice (KAP) survey to identify knowledge gaps and at-risk behaviors related to RVF. Methodology/Principal findings A multidisciplinary team interviewed 657 community members, including abattoir workers, in and around Kabale District, Uganda. Most participants (90%) had knowledge of RVF and most (77%) cited radio as their primary information source. Greater proportions of farmers (68%), herdsmen (79%) and butchers (88%) thought they were at risk of contracting RVF compared to persons in other occupations (60%, p<0.01). Participants most frequently identified bleeding as a symptom of RVF. Less than half of all participants reported fever, vomiting, and diarrhea as common RVF symptoms in either humans or animals. The level of knowledge about human RVF symptoms did not vary by occupation; however more farmers and butchers (36% and 51%, respectively) had knowledge of RVF symptoms in animals compared to those in other occupations (30%, p<0.01). The use of personal protective equipment (PPE) when handling animals varied by occupation, with 77% of butchers using some PPE and 12% of farmers using PPE. Although most butchers said that they used PPE, most used gumboots (73%) and aprons (60%) and less than 20% of butchers used gloves or eye protection when slaughtering. Conclusions Overall, knowledge, attitudes and practice regarding RVF in Kabale District Uganda could be improved through educational efforts targeting specific populations. PMID:29505579

  3. Vaccines for Viral Hemorrhagic Fevers – Progress and Shortcomings

    PubMed Central

    Falzarano, Darryl; Feldmann, Heinz

    2013-01-01

    With a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. In the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. The two exceptions to this are vaccines against Dengue virus and Rift Valley Fever virus, which recently have seen significant progress in putting forward new and improved vaccines, respectively. Experimental vaccines for filoviruses and Lassa virus do exist but are hindered by a lack of financial interest and only partially or ill-defined correlates/mechanisms of protection that could be assessed in clinical trials. PMID:23773330

  4. Virulence factor NSs of rift valley fever virus recruits the F-box protein FBXO3 to degrade subunit p62 of general transcription factor TFIIH.

    PubMed

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas; Weber, Friedemann

    2014-03-01

    The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity.

  5. Virulence Factor NSs of Rift Valley Fever Virus Recruits the F-Box Protein FBXO3 To Degrade Subunit p62 of General Transcription Factor TFIIH

    PubMed Central

    Kainulainen, Markus; Habjan, Matthias; Hubel, Philipp; Busch, Laura; Lau, Simone; Colinge, Jacques; Superti-Furga, Giulio; Pichlmair, Andreas

    2014-01-01

    ABSTRACT The nonstructural protein NSs is the main virulence factor of Rift Valley fever virus (RVFV; family Bunyaviridae, genus Phlebovirus), a serious pathogen of livestock and humans in Africa. RVFV NSs blocks transcriptional upregulation of antiviral type I interferons (IFN) and destroys the general transcription factor TFIIH subunit p62 via the ubiquitin/proteasome pathway. Here, we identified a subunit of E3 ubiquitin ligases, F-box protein FBXO3, as a host cell interactor of NSs. Small interfering RNA (siRNA)-mediated depletion of FBXO3 rescued p62 protein levels in RVFV-infected cells and elevated IFN transcription by 1 order of magnitude. NSs interacts with the full-length FBXO3 protein as well as with a truncated isoform that lacks the C-terminal acidic and poly(R)-rich domains. These isoforms are present in both the nucleus and the cytoplasm. NSs exclusively removes the nuclear pool of full-length FBXO3, likely due to consumption during the degradation process. F-box proteins form the variable substrate recognition subunit of the so-called SCF ubiquitin ligases, which also contain the constant components Skp1, cullin 1 (or cullin 7), and Rbx1. siRNA knockdown of Skp1 also protected p62 from degradation, suggesting involvement in NSs action. However, knockdown of cullin 1, cullin 7, or Rbx1 could not rescue p62 degradation by NSs. Our data show that the enzymatic removal of p62 via the host cell factor FBXO3 is a major mechanism of IFN suppression by RVFV. IMPORTANCE Rift Valley fever virus is a serious emerging pathogen of animals and humans. Its main virulence factor, NSs, enables unhindered virus replication by suppressing the antiviral innate immune system. We identified the E3 ubiquitin ligase FBXO3 as a novel host cell interactor of NSs. NSs recruits FBXO3 to destroy the general host cell transcription factor TFIIH-p62, resulting in suppression of the transcriptional upregulation of innate immunity. PMID:24403578

  6. CD8+ T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever

    PubMed Central

    de Matos, Andréia Manso; Carvalho, Karina Inacio; Rosa, Daniela Santoro; Villas-Boas, Lucy Santos; da Silva, Wanessa Cardoso; Rodrigues, Célia Luiza de Lima; Oliveira, Olímpia Massae Nakasone Peel Furtado; Levi, José Eduardo; Araújo, Evaldo Stanislau Affonso; Pannuti, Claudio Sergio; Luna, Expedito José Albuquerque; Kallas, Esper George

    2015-01-01

    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of São Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population. PMID:25675375

  7. Nonstructural NSs protein of rift valley fever virus interacts with pericentromeric DNA sequences of the host cell, inducing chromosome cohesion and segregation defects.

    PubMed

    Mansuroglu, Z; Josse, T; Gilleron, J; Billecocq, A; Leger, P; Bouloy, M; Bonnefoy, E

    2010-01-01

    Rift Valley fever virus (RVFV) is an emerging, highly pathogenic virus; RVFV infection can lead to encephalitis, retinitis, or fatal hepatitis associated with hemorrhagic fever in humans, as well as death, abortions, and fetal deformities in animals. RVFV nonstructural NSs protein, a major factor of the virulence, forms filamentous structures in the nuclei of infected cells. In order to further understand RVFV pathology, we investigated, by chromatin immunoprecipitation, immunofluorescence, fluorescence in situ hybridization, and confocal microscopy, the capacity of NSs to interact with the host genome. Our results demonstrate that even though cellular DNA is predominantly excluded from NSs filaments, NSs interacts with some specific DNA regions of the host genome such as clusters of pericentromeric gamma-satellite sequence. Targeting of these sequences by NSs was correlated with the induction of chromosome cohesion and segregation defects in RVFV-infected murine, as well as sheep cells. Using recombinant nonpathogenic virus rZHDeltaNSs210-230, expressing a NSs protein deleted of its region of interaction with cellular factor SAP30, we showed that the NSs-SAP30 interaction was essential for NSs to target pericentromeric sequences, as well as for induction of chromosome segregation defects. The effect of RVFV upon the inheritance of genetic information is discussed with respect to the pathology associated with fetal deformities and abortions, highlighting the main role played by cellular cofactor SAP30 on the establishment of NSs interactions with host DNA sequences and RVFV pathogenesis.

  8. The Dominant-Negative Inhibition of Double-Stranded RNA-Dependent Protein Kinase PKR Increases the Efficacy of Rift Valley Fever Virus MP-12 Vaccine

    PubMed Central

    Lihoradova, Olga; Kalveram, Birte; Indran, Sabarish V.; Lokugamage, Nandadeva; Juelich, Terry L.; Hill, Terence E.; Tseng, Chien-Te K.; Gong, Bin; Fukushi, Shuetsu; Morikawa, Shigeru; Freiberg, Alexander N.

    2012-01-01

    Rift Valley fever virus (RVFV), belonging to the genus Phlebovirus, family Bunyaviridae, is endemic to sub-Saharan Africa and causes a high rate of abortion in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. MP-12 is the only RVFV strain excluded from the select-agent rule and handled at a biosafety level 2 (BSL2) laboratory. MP-12 encodes a functional major virulence factor, the NSs protein, which contributes to its residual virulence in pregnant ewes. We found that 100% of mice subcutaneously vaccinated with recombinant MP-12 (rMP12)-murine PKRN167 (mPKRN167), which encodes a dominant-negative form of mouse double-stranded RNA (dsRNA)-dependent protein kinase (PKR) in place of NSs, were protected from wild-type (wt) RVFV challenge, while 72% of mice vaccinated with MP-12 were protected after challenge. rMP12-mPKRN167 induced alpha interferon (IFN-α) in sera, accumulated RVFV antigens in dendritic cells at the local draining lymph nodes, and developed high levels of neutralizing antibodies, while parental MP-12 induced neither IFN-α nor viral-antigen accumulation at the draining lymph node yet induced a high level of neutralizing antibodies. The present study suggests that the expression of a dominant-negative PKR increases the immunogenicity and efficacy of live-attenuated RVFV vaccine, which will lead to rational design of safe and highly immunogenic RVFV vaccines for livestock and humans. PMID:22573861

  9. Comparison of Rift Valley fever virus replication in North American livestock and wildlife cell lines.

    PubMed

    Gaudreault, Natasha N; Indran, Sabarish V; Bryant, P K; Richt, Juergen A; Wilson, William C

    2015-01-01

    Rift Valley fever virus (RVFV) causes disease outbreaks across Africa and the Arabian Peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. The possibility of RVFV spreading to the United States or other countries worldwide is of significant concern to animal and public health, livestock production, and trade. The mechanism for persistence of RVFV during inter-epidemic periods may be through mosquito transovarial transmission and/or by means of a wildlife reservoir. Field investigations in endemic areas and previous in vivo studies have demonstrated that RVFV can infect a wide range of animals, including indigenous wild ruminants of Africa. Yet no predominant wildlife reservoir has been identified, and gaps in our knowledge of RVFV permissive hosts still remain. In North America, domestic goats, sheep, and cattle are susceptible hosts for RVFV and several competent vectors exist. Wild ruminants such as deer might serve as a virus reservoir and given their abundance, wide distribution, and overlap with livestock farms and human populated areas could represent an important risk factor. The objective of this study was to assess a variety of cell lines derived from North American livestock and wildlife for susceptibility and permissiveness to RVFV. Results of this study suggest that RVFV could potentially replicate in native deer species such as white-tailed deer, and possibly a wide range of non-ruminant animals. This work serves to guide and support future animal model studies and risk model assessment regarding this high-consequence zoonotic pathogen.

  10. Using reverse genetics to manipulate the NSs gene of the Rift Valley fever virus MP-12 strain to improve vaccine safety and efficacy.

    PubMed

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Ikegami, Tetsuro

    2011-11-01

    Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain as well as wild-type RVFV strains, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level. IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs), which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a screening method to identify

  11. 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.

  12. Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge.

    PubMed

    Gowen, Brian B; Bailey, Kevin W; Scharton, Dionna; Vest, Zachery; Westover, Jonna B; Skirpstunas, Ramona; Ikegami, Tetsuro

    2013-05-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20-30 min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24 h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Geomorphological characteristics of increased landslide activity in the Gudbrandsdalen valley, Norway

    NASA Astrophysics Data System (ADS)

    Heyerdahl, Håkon; Høydal, Øyvind

    2016-04-01

    The Gudbrandsdalen valley in Eastern Norway lies in a region where annual precipitation is generally low (down to 300 mm/year). The landslide activity has consequently historically been low, although the lower part of the valley sides generally is draped with thick layers of Quaternary deposits, primarily of glacial or glaciofluvial origin. The perception of natural hazards in the valley was previously primarily connected to flooding in the main river in the valley bottom during early summer, due to large discharges resulting from snowmelt in the mountainous regions west and east of the valley. However, several high-intensity events have changed the image of the region. Starting with a localized, but intense, landslide event in the Northern part of the valley in year 2008, two larger events covering almost the entire valley occurred in the years 2011 and 2013. A high number of landslides was triggered in all these events, including many flash floods and debris flows/debris slides in small and steep tributary rivers along the valley slopes. Landslide triggering covers different release mechanisms: In 2008, landslides were triggered without precipitation in not-frozen soil deposits without snow cover in the lower part of the valley. Groundwater flow through the permeable bedrock ("Otta schist") resulting from snow-melt in the elevated mountainous areas caused landslide triggering due to positive pore-water pressures forming at the bedrock surface below soil deposits, or at depressions in the terrain. Subsequent rainfall resulted in even more landslides being released. In later events (years 2011 and 2013) many landslides were caused by surface water taking new paths downslope, often due to man-made changes in existing waterways (typically poorly planned drainage solutions or new roads). Relatively small discharges in slopes with unconsolidated and easily erodible glacial deposits (typically lateral moraine) in many cases lead to small initial slides that down

  14. Single-Molecule FISH Reveals Non-selective Packaging of Rift Valley Fever Virus Genome Segments

    PubMed Central

    Wichgers Schreur, Paul J.; Kortekaas, Jeroen

    2016-01-01

    The bunyavirus genome comprises a small (S), medium (M), and large (L) RNA segment of negative polarity. Although genome segmentation confers evolutionary advantages by enabling genome reassortment events with related viruses, genome segmentation also complicates genome replication and packaging. Accumulating evidence suggests that genomes of viruses with eight or more genome segments are incorporated into virions by highly selective processes. Remarkably, little is known about the genome packaging process of the tri-segmented bunyaviruses. Here, we evaluated, by single-molecule RNA fluorescence in situ hybridization (FISH), the intracellular spatio-temporal distribution and replication kinetics of the Rift Valley fever virus (RVFV) genome and determined the segment composition of mature virions. The results reveal that the RVFV genome segments start to replicate near the site of infection before spreading and replicating throughout the cytoplasm followed by translocation to the virion assembly site at the Golgi network. Despite the average intracellular S, M and L genome segments approached a 1:1:1 ratio, major differences in genome segment ratios were observed among cells. We also observed a significant amount of cells lacking evidence of M-segment replication. Analysis of two-segmented replicons and four-segmented viruses subsequently confirmed the previous notion that Golgi recruitment is mediated by the Gn glycoprotein. The absence of colocalization of the different segments in the cytoplasm and the successful rescue of a tri-segmented variant with a codon shuffled M-segment suggested that inter-segment interactions are unlikely to drive the copackaging of the different segments into a single virion. The latter was confirmed by direct visualization of RNPs inside mature virions which showed that the majority of virions lack one or more genome segments. Altogether, this study suggests that RVFV genome packaging is a non-selective process. PMID:27548280

  15. Prevalence of Rift Valley fever infection in ruminants in Madagascar after the 2008 outbreak.

    PubMed

    Jeanmaire, Elisabeth Marie; Rabenarivahiny, René; Biarmann, Marcellin; Rabibisoa, Lalao; Ravaomanana, Fleurette; Randriamparany, Tantely; Andriamandimby, Soa Fy; Diaw, Cécile Squarzoni; Fenozara, Peter; de La Rocque, Stéphane; Reynes, Jean-Marc

    2011-04-01

    A Rift Valley fever (RVF) outbreak occurred in Madagascar from January to May 2008. The objectives of this study were (1) to assess the current and past circulation of RVF virus (RVFV) in livestock in Madagascar and (2) to evaluate the extent and magnitude of the 2008 RVF outbreak in livestock. The results of a country-wide serosurvey conducted in August 2008 on small and large ruminants are reported here. The study included 3437 cattle and 989 small ruminants (227 sheep and 762 goats) sampled in 30 of the 111 Malagasy districts, selected to be representative of the different ecozones and livestock density areas. Sera of animals were tested for the detection of immunoglobulins M (IgM) and G (IgG) against RVFV using commercial enzyme-linked immunosorbent assays kits. Recent infections (presence of IgM against RVFV) were detected in only 9 cattle (0.3% [0.1-0.4]) and 33 small ruminant (3.3% [2.2-4.5]) samples. Past infections (presence of IgG and absence of IgM against RVFV) were detected in 887 cattle (25.8% [24.3-27.3]) and 244 small ruminant (24.7% [22.0-27.4]) samples. Past infections were detected in all sampled sites. All ecozones were affected. In the southern and northwestern areas, the prevalence of cattle showing evidence of past infection with RVFV increased with the age of the animals. Our results suggest that there has been country-wide circulation of RVFV in 2008 in Madagascar, including in parts of the country where no clinical illness, either in animals or in humans, was reported. The data also suggest that the southern and northwestern areas may be endemic for RVFV, and that the virus may spread when ecological conditions are favorable for its amplification.

  16. Phylogeographic Reconstructions of a Rift Valley Fever Virus Strain Reveals Transboundary Animal Movements from Eastern Continental Africa to the Union of the Comoros.

    PubMed

    Maquart, M; Pascalis, H; Abdouroihamane, S; Roger, M; Abdourahime, F; Cardinale, E; Cêtre-Sossah, C

    2016-04-01

    Major explosive outbreaks of Rift Valley fever (RVF), an arthropod borne zoonotic disease, occur in humans and animals with significant mortality and economic impact across continental Africa and the Indian Ocean region (Madagascar, the Comoros archipelago). Recently, sporadic human cases have been reported in Mayotte and Grande Comore, two islands belonging to the Comoros archipelago. To identify the hypothetical source of virus introduction in an inter-epidemic or a post-epidemic period, a longitudinal survey of livestock was set up in Comorian ruminant populations, known to be susceptible hosts. The phylogeographic genomic analysis has shown that RVF virus (RVFV) detected in a zebu collected in Anjouan in August 2011 seems to be related to the last known epidemic of RVF which occurred in East Africa and Madagascar (2007-2009). This result highlights the fact that RVFV is maintained within local livestock populations and transboundary animal movements from eastern continental Africa to Indian Ocean islands likely result in RVFV crossover. © 2014 Blackwell Verlag GmbH.

  17. A novel indirect ELISA based on glycoprotein Gn for the detection of IgG antibodies against Rift Valley fever virus in small ruminants.

    PubMed

    Jäckel, S; Eiden, M; Balkema-Buschmann, A; Ziller, M; van Vuren, P Jansen; Paweska, J T; Groschup, M H

    2013-10-01

    Rift Valley fever virus (RVFV) is an emerging zoonotic pathogen that causes high morbidity and mortality in humans and livestock. In this paper, we describe the cloning, expression and purification of RVFV glycoprotein Gn and its application as a diagnostic antigen in an indirect ELISA for the specific detection of RVF IgG antibodies in sheep and goats. The performance of this Gn based ELISA is validated using a panel of almost 2000 field samples from sheep and goats from Mozambique, Senegal, Uganda and Yemen. All serum samples were also tested by virus neutralization test (VNT), the gold standard method for RVFV serological testing. Compared to the VNT results the Gn based ELISA proved to have an excellent sensitivity (94.56%) and specificity (95.57%). Apart from establishing this new diagnostic assay, these results also demonstrate a close correlation between the presence of RVFV Gn and neutralizing antibodies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. TRAINING PROGRAM FOR NURSING STAFF REGARDING VIRAL HEMORRHAGIC FEVERS IN A MILITARY HOSPITAL.

    PubMed

    El-Bahnasawy, Mamdouh M; Megahed, Laila Abdel-Mawla; Saleh, Halla Ahmed Abdullah; Abdelfattah, Magda Abdelhamid; Morsy, Tosson Aly

    2015-08-01

    Viral hemorrhagic fevers (VHFs) refer to a group of illnesses caused by several distinct families of viruses. In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome (multisystem in that multiple organ systems in the bpdy are affected). Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is impaired. These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is it rarely life-threatening. While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease. The selected disaster diseases for this study included: 1-Crimean-Congo hemorrhagic Fever, 2-Dengue Fever, 3-Ebola Fever, 4-Hem-orrhagic Fever with renal syndrome (HFRS), 5-Hantavirus Pulmonary Syndrome, 6-Lassa Fever, 7-Marburg Fever, 8-Rift Valley Fever and 9-Yellow Fever. The educational training program was given over ten sessions to a group of Staff Nurses. The results showed that the program succeeded in enhancing nurse' knowledge, awareness, responsibility, and obligations toward patients with the Viral Hemorrhagic Fevers The results showed a significant impact of training sessions illuminated in the follow-up test on the knowledge score of nurses in all types of diseases except for the Congo hemorrhagic fever, while, statistical significance varied in some diseases in the study when it comes to the comparison between pretest and post-test. All results confirmed on the positive impact of the training program in enhancing the knowledge of nurses toward VHFs patients and their relevant. There was a significant positive impact of the training sessions on changing the attitude of nurses toward patients with VHFs. This result was confirmed on the collective level since the total scores on tests revealed significant positive impact of the study on changing the attitude of nurses toward relevant patients. The relationship

  19. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence

    PubMed Central

    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R.; Kehn-Hall, Kylene; Omichinski, James G.

    2015-01-01

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH. PMID:25918396

  20. A ΩXaV motif in the Rift Valley fever virus NSs protein is essential for degrading p62, forming nuclear filaments and virulence.

    PubMed

    Cyr, Normand; de la Fuente, Cynthia; Lecoq, Lauriane; Guendel, Irene; Chabot, Philippe R; Kehn-Hall, Kylene; Omichinski, James G

    2015-05-12

    Rift Valley fever virus (RVFV) is a single-stranded RNA virus capable of inducing fatal hemorrhagic fever in humans. A key component of RVFV virulence is its ability to form nuclear filaments through interactions between the viral nonstructural protein NSs and the host general transcription factor TFIIH. Here, we identify an interaction between a ΩXaV motif in NSs and the p62 subunit of TFIIH. This motif in NSs is similar to ΩXaV motifs found in nucleotide excision repair (NER) factors and transcription factors known to interact with p62. Structural and biophysical studies demonstrate that NSs binds to p62 in a similar manner as these other factors. Functional studies in RVFV-infected cells show that the ΩXaV motif is required for both nuclear filament formation and degradation of p62. Consistent with the fact that the RVFV can be distinguished from other Bunyaviridae-family viruses due to its ability to form nuclear filaments in infected cells, the motif is absent in the NSs proteins of other Bunyaviridae-family viruses. Taken together, our studies demonstrate that p62 binding to NSs through the ΩXaV motif is essential for degrading p62, forming nuclear filaments and enhancing RVFV virulence. In addition, these results show how the RVFV incorporates a simple motif into the NSs protein that enables it to functionally mimic host cell proteins that bind the p62 subunit of TFIIH.

  1. Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses.

    PubMed

    Chang, Jinhong; Warren, Travis K; Zhao, Xuesen; Gill, Tina; Guo, Fang; Wang, Lijuan; Comunale, Mary Ann; Du, Yanming; Alonzi, Dominic S; Yu, Wenquan; Ye, Hong; Liu, Fei; Guo, Ju-Tao; Mehta, Anand; Cuconati, Andrea; Butters, Terry D; Bavari, Sina; Xu, Xiaodong; Block, Timothy M

    2013-06-01

    Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure-activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Tri-phasic fever in dengue fever.

    PubMed

    D, Pradeepa H; Rao, Sathish B; B, Ganaraj; Bhat, Gopalakrishna; M, Chakrapani

    2018-04-01

    Dengue fever is an acute febrile illness with a duration of 2-12 days. Our observational study observed the 24-h continuous tympanic temperature pattern of 15 patients with dengue fever and compared this with 26 others with fever due to a non-dengue aetiology. A tri-phasic fever pattern was seen among two-thirds of dengue fever patients, but in only one with an inflammatory disease. One-third of dengue fever patients exhibited a single peak temperature. Continuous temperature monitoring and temperature pattern analysis in clinical settings can aid in the early differentiation of dengue fever from non-dengue aetiology.

  3. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    PubMed Central

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

  4. Structure of the Rift Valley fever virus nucleocapsid protein reveals another architecture for RNA encapsidation

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

    Raymond, Donald D.; Piper, Mary E.; Gerrard, Sonja R.

    2010-07-13

    Rift Valley fever virus (RVFV) is a negative-sense RNA virus (genus Phlebovirus, family Bunyaviridae) that infects livestock and humans and is endemic to sub-Saharan Africa. Like all negative-sense viruses, the segmented RNA genome of RVFV is encapsidated by a nucleocapsid protein (N). The 1.93-{angstrom} crystal structure of RVFV N and electron micrographs of ribonucleoprotein (RNP) reveal an encapsidated genome of substantially different organization than in other negative-sense RNA virus families. The RNP polymer, viewed in electron micrographs of both virus RNP and RNP reconstituted from purified N with a defined RNA, has an extended structure without helical symmetry. N-RNA speciesmore » of {approx}100-kDa apparent molecular weight and heterogeneous composition were obtained by exhaustive ribonuclease treatment of virus RNP, by recombinant expression of N, and by reconstitution from purified N and an RNA oligomer. RNA-free N, obtained by denaturation and refolding, has a novel all-helical fold that is compact and well ordered at both the N and C termini. Unlike N of other negative-sense RNA viruses, RVFV N has no positively charged surface cleft for RNA binding and no protruding termini or loops to stabilize a defined N-RNA oligomer or RNP helix. A potential protein interaction site was identified in a conserved hydrophobic pocket. The nonhelical appearance of phlebovirus RNP, the heterogeneous {approx}100-kDa N-RNA multimer, and the N fold differ substantially from the RNP and N of other negative-sense RNA virus families and provide valuable insights into the structure of the encapsidated phlebovirus genome.« less

  5. San Diego Gas and Electric Company Imperial Valley geothermal activities

    NASA Technical Reports Server (NTRS)

    Hinrichs, T. C.

    1974-01-01

    San Diego Gas and Electric and its wholly owned subsidiary New Albion Resources Co. have been affiliated with Magma Power Company, Magma Energy Inc. and Chevron Oil Company for the last 2-1/2 years in carrying out geothermal research and development in the private lands of the Imperial Valley. The steps undertaken in the program are reviewed and the sequence that must be considered by companies considering geothermal research and development is emphasized. Activities at the south end of the Salton Sea and in the Heber area of Imperial Valley are leading toward development of demonstration facilities within the near future. The current status of the project is reported.

  6. Ecological distribution and population dynamics of Rift Valley fever virus mosquito vectors (Diptera, Culicidae) in Senegal.

    PubMed

    Biteye, Biram; Fall, Assane G; Ciss, Mamadou; Seck, Momar T; Apolloni, Andrea; Fall, Moussa; Tran, Annelise; Gimonneau, Geoffrey

    2018-01-09

    Many zoonotic infectious diseases have emerged and re-emerged over the last two decades. There has been a significant increase in vector-borne diseases due to climate variations that lead to environmental changes favoring the development and adaptation of vectors. This study was carried out to improve knowledge of the ecology of mosquito vectors involved in the transmission of Rift Valley fever virus (RVFV) in Senegal. An entomological survey was conducted in three Senegalese agro-systems, Senegal River Delta (SRD), Senegal River Valley (SRV) and Ferlo, during the rainy season (July to November) of 2014 and 2015. Mosquitoes were trapped using CDC light traps set at ten sites for two consecutive nights during each month of the rainy season, for a total of 200 night-traps. Ecological indices were calculated to characterize the different populations of RVFV mosquito vectors. Generalized linear models with mixed effects were used to assess the influence of climatic conditions on the abundance of RVFV mosquito vectors. A total of 355,408 mosquitoes belonging to 7 genera and 35 species were captured in 200 night-traps. RVFV vectors represented 89.02% of the total, broken down as follows: Ae. vexans arabiensis (31.29%), Cx. poicilipes (0.6%), Cx. tritaeniorhynchus (33.09%) and Ma. uniformis (24.04%). Comparison of meteorological indices (rainfall, temperature, relative humidity), abundances and species diversity indicated that there were no significant differences between SRD and SRV (P = 0.36) while Ferlo showed significant differences with both (P < 0.001). Mosquito collection increased significantly with temperature for Ae. vexans arabiensis (P < 0.001), Cx. tritaeniorhynchus (P = 0.04) and Ma. uniformis (P = 0.01), while Cx. poicilipes decreased (P = 0.003). Relative humidity was positively and significantly associated with the abundances of Ae. vexans arabiensis (P < 0.001), Cx. poicilipes (P = 0.01) and Cx. tritaeniorhynchus (P

  7. Wetlands, wild Bovidae species richness and sheep density delineate risk of Rift Valley fever outbreaks in the African continent and Arabian Peninsula

    PubMed Central

    Willem de Smalen, Allard; Mor, Siobhan M.

    2017-01-01

    Rift Valley fever (RVF) is an emerging, vector-borne viral zoonosis that has significantly impacted public health, livestock health and production, and food security over the last three decades across large regions of the African continent and the Arabian Peninsula. The potential for expansion of RVF outbreaks within and beyond the range of previous occurrence is unknown. Despite many large national and international epidemics, the landscape epidemiology of RVF remains obscure, particularly with respect to the ecological roles of wildlife reservoirs and surface water features. The current investigation modeled RVF risk throughout Africa and the Arabian Peninsula as a function of a suite of biotic and abiotic landscape features using machine learning methods. Intermittent wetland, wild Bovidae species richness and sheep density were associated with increased landscape suitability to RVF outbreaks. These results suggest the role of wildlife hosts and distinct hydrogeographic landscapes in RVF virus circulation and subsequent outbreaks may be underestimated. These results await validation by studies employing a deeper, field-based interrogation of potential wildlife hosts within high risk taxa. PMID:28742814

  8. Rift Valley fever in a zone potentially occupied by Aedes vexans in Senegal: dynamics and risk mapping

    NASA Astrophysics Data System (ADS)

    Tourre, Y. M.; Vignolles, C.; Lacaux, J.-P.; Bigeard, G.; Ndione, J.-A.; Lafaye, M.

    2009-09-01

    This paper presents an analysis of the interaction between the various variables associated with Rift Valley fever (RVF) such as the mosquito vector, available hosts and rainfall distribution. To that end, the varying zones potentially occupied by mosquitoes (ZPOM), rainfall events and pond dynamics, and the associated exposure of hosts to the RVF virus by Aedes vexans, were analyzed in the Barkedji area of the Ferlo, Senegal, during the 2003 rainy season. Ponds were identified by remote sensing using a high-resolution SPOT-5 satellite image. Additional data on ponds and rainfall events from the Tropical Rainfall Measuring Mission were combined with in-situ entomological and limnimetric measurements, and the localization of vulnerable ruminant hosts (data derived from QuickBird satellite). Since "Ae. vexans productive events” are dependent on the timing of rainfall for their embryogenesis (six days without rain are necessary to trigger hatching), the dynamic spatio-temporal distribution of Ae. vexans density was based on the total rainfall amount and pond dynamics. Detailed ZPOM mapping was obtained on a daily basis and combined with aggressiveness temporal profiles. Risks zones, i.e. zones where hazards and vulnerability are combined, are expressed by the percentages of parks where animals are potentially exposed to mosquito bites. This new approach, simply relying upon rainfall distribution evaluated from space, is meant to contribute to the implementation of a new, operational early warning system for RVF based on environmental risks linked to climatic and environmental conditions.

  9. New assay of protective activity of Rocky Mountain spotted fever vaccines.

    PubMed Central

    Anacker, R L; Smith, R F; Mann, R E; Hamilton, M A

    1976-01-01

    Areas under the fever curves of guinea pigs inoculated with Rocky Mountain spotted fever vaccine over a restricted dose range and infected with a standardized dose of Rickettsia rickettsii varied linearly with log10 dose of vaccine. A calculator was programmed to plot fever curves and calculate the vaccine dose that reduced the fever of infected animals by 50%. PMID:823177

  10. Genetic Evidence for an Interferon-Antagonistic Function of Rift Valley Fever Virus Nonstructural Protein NSs

    PubMed Central

    Bouloy, Michèle; Janzen, Christian; Vialat, Pierre; Khun, Huot; Pavlovic, Jovan; Huerre, Michel; Haller, Otto

    2001-01-01

    Rift Valley fever virus (RVFV), a phlebovirus of the family Bunyaviridae, is a major public health threat in Egypt and sub-Saharan Africa. The viral and host cellular factors that contribute to RVFV virulence and pathogenicity are still poorly understood. All pathogenic RVFV strains direct the synthesis of a nonstructural phosphoprotein (NSs) that is encoded by the smallest (S) segment of the tripartite genome and has an undefined accessory function. In this report, we show that MP12 and clone 13, two attenuated RVFV strains with mutations in the NSs gene, were highly virulent in IFNAR−/− mice lacking the alpha/beta interferon (IFN-α/β) receptor but remained attenuated in IFN-γ receptor-deficient mice. Both attenuated strains proved to be excellent inducers of early IFN-α/β production. In contrast, the virulent strain ZH548 failed to induce detectable amounts of IFN-α/β and replicated extensively in both IFN-competent and IFN-deficient mice. Clone 13 has a defective NSs gene with a large in-frame deletion. This defect in the NSs gene results in expression of a truncated protein which is rapidly degraded. To investigate whether the presence of the wild-type NSs gene correlated with inhibition of IFN-α/β production, we infected susceptible IFNAR−/− mice with S gene reassortant viruses. When the S segment of ZH548 was replaced by that of clone 13, the resulting reassortants became strong IFN inducers. When the defective S segment of clone 13 was exchanged with the wild-type S segment of ZH548, the reassortant virus lost the capacity to stimulate IFN-α/β production. These results demonstrate that the ability of RVFV to inhibit IFN-α/β production correlates with viral virulence and suggest that the accessory protein NSs is an IFN antagonist. PMID:11152510

  11. Rift Valley Fever Virus Circulating among Ruminants, Mosquitoes and Humans in the Central African Republic.

    PubMed

    Nakouné, Emmanuel; Kamgang, Basile; Berthet, Nicolas; Manirakiza, Alexandre; Kazanji, Mirdad

    2016-10-01

    Rift Valley fever virus (RVFV) causes a viral zoonosis, with discontinuous epizootics and sporadic epidemics, essentially in East Africa. Infection with this virus causes severe illness and abortion in sheep, goats, and cattle as well as other domestic animals. Humans can also be exposed through close contact with infectious tissues or by bites from infected mosquitoes, primarily of the Aedes and Culex genuses. Although the cycle of RVFV infection in savannah regions is well documented, its distribution in forest areas in central Africa has been poorly investigated. To evaluate current circulation of RVFV among livestock and humans living in the Central African Republic (CAR), blood samples were collected from sheep, cattle, and goats and from people at risk, such as stock breeders and workers in slaughterhouses and livestock markets. The samples were tested for anti-RVFV immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies. We also sequenced the complete genomes of two local strains, one isolated in 1969 from mosquitoes and one isolated in 1985 from humans living in forested areas. The 1271 animals sampled comprised 727 cattle, 325 sheep, and 219 goats at three sites. The overall seroprevalence of anti-RVFV IgM antibodies was 1.9% and that of IgG antibodies was 8.6%. IgM antibodies were found only during the rainy season, but the frequency of IgG antibodies did not differ significantly by season. No evidence of recent RVFV infection was found in 335 people considered at risk; however, 16.7% had evidence of past infection. Comparison of the nucleotide sequences of the strains isolated in the CAR with those isolated in other African countries showed that they belonged to the East/Central African cluster. This study confirms current circulation of RVFV in CAR. Further studies are needed to determine the potential vectors involved and the virus reservoirs.

  12. Identifying landscape features associated with Rift Valley fever virus transmission, Ferlo region, Senegal, using very high spatial resolution satellite imagery.

    PubMed

    Soti, Valérie; Chevalier, Véronique; Maura, Jonathan; Bégué, Agnès; Lelong, Camille; Lancelot, Renaud; Thiongane, Yaya; Tran, Annelise

    2013-03-01

    Dynamics of most of vector-borne diseases are strongly linked to global and local environmental changes. Landscape changes are indicators of human activities or natural processes that are likely to modify the ecology of the diseases. Here, a landscape approach developed at a local scale is proposed for extracting mosquito favourable biotopes, and for testing ecological parameters when identifying risk areas of Rift Valley fever (RVF) transmission. The study was carried out around Barkedji village, Ferlo region, Senegal. In order to test whether pond characteristics may influence the density and the dispersal behaviour of RVF vectors, and thus the spatial variation in RVFV transmission, we used a very high spatial resolution remote sensing image (2.4 m resolution) provided by the Quickbird sensor to produce a detailed land-cover map of the study area. Based on knowledge of vector and disease ecology, seven landscape attributes were defined at the pond level and computed from the land-cover map. Then, the relationships between landscape attributes and RVF serologic incidence rates in small ruminants were analyzed through a beta-binomial regression. Finally, the best statistical model according to the Akaike Information Criterion corrected for small samples (AICC), was used to map areas at risk for RVF. Among the derived landscape variables, the vegetation density index (VDI) computed within a 500 m buffer around ponds was positively correlated with serologic incidence (p<0.001), suggesting that the risk of RVF transmission was higher in the vicinity of ponds surrounded by a dense vegetation cover. The final risk map of RVF transmission displays a heterogeneous spatial distribution, corroborating previous findings from the same area. Our results highlight the potential of very high spatial resolution remote sensing data for identifying environmental risk factors and mapping RVF risk areas at a local scale.

  13. Identifying landscape features associated with Rift Valley fever virus transmission, Ferlo region, Senegal, using very high spatial resolution satellite imagery

    PubMed Central

    2013-01-01

    Introduction Dynamics of most of vector-borne diseases are strongly linked to global and local environmental changes. Landscape changes are indicators of human activities or natural processes that are likely to modify the ecology of the diseases. Here, a landscape approach developed at a local scale is proposed for extracting mosquito favourable biotopes, and for testing ecological parameters when identifying risk areas of Rift Valley fever (RVF) transmission. The study was carried out around Barkedji village, Ferlo region, Senegal. Methods In order to test whether pond characteristics may influence the density and the dispersal behaviour of RVF vectors, and thus the spatial variation in RVFV transmission, we used a very high spatial resolution remote sensing image (2.4 m resolution) provided by the Quickbird sensor to produce a detailed land-cover map of the study area. Based on knowledge of vector and disease ecology, seven landscape attributes were defined at the pond level and computed from the land-cover map. Then, the relationships between landscape attributes and RVF serologic incidence rates in small ruminants were analyzed through a beta-binomial regression. Finally, the best statistical model according to the Akaike Information Criterion corrected for small samples (AICC), was used to map areas at risk for RVF. Results Among the derived landscape variables, the vegetation density index (VDI) computed within a 500 m buffer around ponds was positively correlated with serologic incidence (p<0.001), suggesting that the risk of RVF transmission was higher in the vicinity of ponds surrounded by a dense vegetation cover. The final risk map of RVF transmission displays a heterogeneous spatial distribution, corroborating previous findings from the same area. Conclusions Our results highlight the potential of very high spatial resolution remote sensing data for identifying environmental risk factors and mapping RVF risk areas at a local scale. PMID:23452759

  14. Dengue fever

    MedlinePlus

    Clothing, mosquito repellent, and netting can help reduce the risk for mosquito bites that can spread dengue fever and other infections. Limit outdoor activity during mosquito season, especially when they ...

  15. Co-housing of Rift Valley Fever Virus Infected Lambs with Immunocompetent or Immunosuppressed Lambs Does Not Result in Virus Transmission

    PubMed Central

    Wichgers Schreur, Paul J.; van Keulen, Lucien; Kant, Jet; Oreshkova, Nadia; Moormann, Rob J. M.; Kortekaas, Jeroen

    2016-01-01

    Rift Valley fever virus (RVFV) is transmitted among susceptible animals by mosquito vectors. Although the virus can be isolated from nasal and oral swabs of infected animals and is known to be highly infectious when administered experimentally via oral or respiratory route, horizontal transmission of the virus is only sporadically reported in literature. We considered that immunosuppression resulting from stressful conditions in the field may increase the susceptibility to horizontally transmitted RVFV. Additionally, we reasoned that horizontal transmission may induce immune responses that could affect the susceptibility of contact-exposed animals to subsequent infection via mosquito vectors. To address these two hypotheses, viremic lambs were brought into contact with sentinel lambs. One group of sentinel lambs was treated with the immunosuppressive synthetic glucocorticosteroid dexamethasone and monitored for signs of disease and presence of virus in the blood and target organs. Another group of contact-exposed sentinel lambs remained untreated for three weeks and was subsequently challenged with RVFV. We found that none of the dexamethasone-treated contact-exposed lambs developed detectable viremia, antibody responses or significant increases in cytokine mRNA levels. Susceptibility of immunocompetent lambs to RVFV infection was not influenced by previous contact-exposure. Our results are discussed in light of previous findings. PMID:27014211

  16. [Microbiological surveillance: viral hemorrhagic fever in Central African Republic: current serological data in man].

    PubMed

    Nakounné, E; Selekon, B; Morvan, J

    2000-01-01

    An investigation was conducted between 1994 and 1997 in forested areas of the Central African Republic (CAR) to determine the seroprevalence of IgG antibodies against several haemorrhagic fever viruses present in the region. Sera were obtained from 1762 individuals in two groups (Pygmy and Bantu locuted populations) living in 4 forested areas in the south of the country. Sera were tested for IgG antibodies against Ebola, Marburg, Rift Valley fever (RVF), Yellow fever (YF) and Hantaviruses by enzyme immunoassay (EIA), and against Lassa virus by immunofluorescent assay. The prevalence of IgG antibodies was 5.9% for Ebola, 2% for Marburg, 6.9% pour RVF, 6.5% for YF, 2% for Hantaan. No antibodies were detected against Lassa, Seoul, Puumala and Thottapalayam viruses. No IgM antibodies were detected against RVF and YF viruses. The distribution of antibodies appears to be related to tropical rain forest areas. This study indicates that several haemorrhagic fever viruses are endemic in forested areas of the CAR and could emerge due to environmental modification.

  17. The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks

    PubMed Central

    Hassan, Osama Ahmed; Affognon, Hippolyte; Rocklöv, Joacim; Mburu, Peter; Sang, Rosemary; Ahlm, Clas; Evander, Magnus

    2017-01-01

    Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants’ food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased. PMID:28207905

  18. The One Health approach to identify knowledge, attitudes and practices that affect community involvement in the control of Rift Valley fever outbreaks.

    PubMed

    Hassan, Osama Ahmed; Affognon, Hippolyte; Rocklöv, Joacim; Mburu, Peter; Sang, Rosemary; Ahlm, Clas; Evander, Magnus

    2017-02-01

    Rift Valley fever (RVF) is a viral mosquito-borne disease with the potential for global expansion, causes hemorrhagic fever, and has a high case fatality rate in young animals and in humans. Using a cross-sectional community-based study design, we investigated the knowledge, attitudes and practices of people living in small village in Sudan with respect to RVF outbreaks. A special One Health questionnaire was developed to compile data from 235 heads of household concerning their knowledge, attitudes, and practices with regard to controlling RVF. Although the 2007 RVF outbreak in Sudan had negatively affected the participants' food availability and livestock income, the participants did not fully understand how to identify RVF symptoms and risk factors for both humans and livestock. For example, the participants mistakenly believed that avoiding livestock that had suffered spontaneous abortions was the least important risk factor for RVF. Although the majority noticed an increase in mosquito population during the 2007 RVF outbreak, few used impregnated bed nets as preventive measures. The community was reluctant to notify the authorities about RVF suspicion in livestock, a sentinel for human RVF infection. Almost all the respondents stressed that they would not receive any compensation for their dead livestock if they notified the authorities. In addition, the participants believed that controlling RVF outbreaks was mainly the responsibility of human health authorities rather than veterinary authorities. The majority of the participants were aware that RVF could spread from one region to another within the country. Participants received most their information about RVF from social networks and the mass media, rather than the health system or veterinarians. Because the perceived role of the community in controlling RVF was fragmented, the probability of RVF spread increased.

  19. A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep.

    PubMed

    Faburay, Bonto; Lebedev, Maxim; McVey, D Scott; Wilson, William; Morozov, Igor; Young, Alan; Richt, Juergen A

    2014-10-01

    Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.

  20. Computational prediction and biochemical characterization of novel RNA aptamers to Rift Valley fever virus nucleocapsid protein.

    PubMed

    Ellenbecker, Mary; St Goddard, Jeremy; Sundet, Alec; Lanchy, Jean-Marc; Raiford, Douglas; Lodmell, J Stephen

    2015-10-01

    Rift Valley fever virus (RVFV) is a potent human and livestock pathogen endemic to sub-Saharan Africa and the Arabian Peninsula that has potential to spread to other parts of the world. Although there is no proven effective and safe treatment for RVFV infections, a potential therapeutic target is the virally encoded nucleocapsid protein (N). During the course of infection, N binds to viral RNA, and perturbation of this interaction can inhibit viral replication. To gain insight into how N recognizes viral RNA specifically, we designed an algorithm that uses a distance matrix and multidimensional scaling to compare the predicted secondary structures of known N-binding RNAs, or aptamers, that were isolated and characterized in previous in vitro evolution experiment. These aptamers did not exhibit overt sequence or predicted structure similarity, so we employed bioinformatic methods to propose novel aptamers based on analysis and clustering of secondary structures. We screened and scored the predicted secondary structures of novel randomly generated RNA sequences in silico and selected several of these putative N-binding RNAs whose secondary structures were similar to those of known N-binding RNAs. We found that overall the in silico generated RNA sequences bound well to N in vitro. Furthermore, introduction of these RNAs into cells prior to infection with RVFV inhibited viral replication in cell culture. This proof of concept study demonstrates how the predictive power of bioinformatics and the empirical power of biochemistry can be jointly harnessed to discover, synthesize, and test new RNA sequences that bind tightly to RVFV N protein. The approach would be easily generalizable to other applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. A Glycoprotein Subunit Vaccine Elicits a Strong Rift Valley Fever Virus Neutralizing Antibody Response in Sheep

    PubMed Central

    Lebedev, Maxim; McVey, D. Scott; Wilson, William; Morozov, Igor; Young, Alan

    2014-01-01

    Abstract Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species. PMID:25325319

  2. Dengue and Dengue Hemorrhagic Fever

    PubMed Central

    Gubler, Duane J.

    1998-01-01

    Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever. PMID:9665979

  3. TerraSAR-X high-resolution radar remote sensing: an operational warning system for Rift Valley fever risk.

    PubMed

    Vignolles, Cécile; Tourre, Yves M; Mora, Oscar; Imanache, Laurent; Lafaye, Murielle

    2010-11-01

    In the vicinity of the Barkedji village (in the Ferlo region of Senegal), the abundance and aggressiveness of the vector mosquitoes for Rift Valley fever (RVF) are strongly linked to rainfall events and associated ponds dynamics. Initially, these results were obtained from spectral analysis of high-resolution (~10 m) Spot-5 images, but, as a part of the French AdaptFVR project, identification of the free water dynamics within ponds was made with the new high-resolution (down to 3-meter pixels), Synthetic Aperture Radar satellite (TerraSAR-X) produced by Infoterra GmbH, Friedrichshafen/Potsdam, Germany. During summer 2008, within a 30 x 50 km radar image, it was found that identified free water fell well within the footprints of ponds localized by optical data (i.e. Spot-5 images), which increased the confidence in this new and complementary remote sensing technique. Moreover, by using near real-time rainfall data from the Tropical Rainfall Measuring Mission (TRMM), NASA/JAXA joint mission, the filling-up and flushing-out rates of the ponds can be accurately determined. The latter allows for a precise, spatio-temporal mapping of the zones potentially occupied by mosquitoes capable of revealing the variability of pond surfaces. The risk for RVF infection of gathered bovines and small ruminants (~1 park/km(2)) can thus be assessed. This new operational approach (which is independent of weather conditions) is an important development in the mapping of risk components (i.e. hazards plus vulnerability) related to RVF transmission during the summer monsoon, thus contributing to a RVF early warning system.

  4. Rift valley fever virus nonstructural protein NSs promotes viral RNA replication and transcription in a minigenome system.

    PubMed

    Ikegami, Tetsuro; Peters, C J; Makino, Shinji

    2005-05-01

    Rift Valley fever virus (RVFV), which belongs to the genus Phlebovirus, family Bunyaviridae, has a tripartite negative-strand genome (S, M, and L segments) and is an important mosquito-borne pathogen for domestic animals and humans. We established an RVFV T7 RNA polymerase-driven minigenome system in which T7 RNA polymerase from an expression plasmid drove expression of RNA transcripts for viral proteins and minigenome RNA transcripts carrying a reporter gene between both termini of the M RNA segment in 293T cells. Like other viruses of the Bunyaviridae family, replication and transcription of the RVFV minigenome required expression of viral N and L proteins. Unexpectedly, the coexpression of an RVFV nonstructural protein, NSs, with N and L proteins resulted in a significant enhancement of minigenome RNA replication. Coexpression of NSs protein with N and L proteins also enhanced minigenome mRNA transcription in the cells expressing viral-sense minigenome RNA transcripts. NSs protein expression increased the RNA replication of minigenomes that originated from S and L RNA segments. Enhancement of minigenome RNA synthesis by NSs protein occurred in cells lacking alpha/beta interferon (IFN-alpha/beta) genes, indicating that the effect of NSs protein on minigenome RNA replication was unrelated to a putative NSs protein-induced inhibition of IFN-alpha/beta production. Our finding that RVFV NSs protein augmented minigenome RNA synthesis was in sharp contrast to reports that Bunyamwera virus (genus Bunyavirus) NSs protein inhibits viral minigenome RNA synthesis, suggesting that RVFV NSs protein and Bunyamwera virus NSs protein have distinctly different biological roles in viral RNA synthesis.

  5. Advanced Development of Antiviral Prophylactics and Therapeutics (ADAPT) - Research Area 10

    DTIC Science & Technology

    2014-11-17

    various Prosetta compounds against Rift Valley Fever Virus (RVFV), Lassa virus (LASV) and Marburg virus (MARV), respectively. Activity is demonstrated as...USAMRIID for in vitro efficacy testing against various hemorrhagic fever viruses, including Ebola (EBOV), Marburg (MARV), Lassa (LASV), Rift Valley...unless so designated by other documentation. 14. ABSTRACT The pmpose of the proposed work is to continue the promising anti-hemonhagic fever vims (HFV

  6. Evaluation of the Efficacy, Potential for Vector Transmission, and Duration of Immunity of MP-12, an Attenuated Rift Valley Fever Virus Vaccine Candidate, in Sheep

    PubMed Central

    Bennett, Kristine E.; Drolet, Barbara S.; Lindsay, Robbin; Mecham, James O.; Reeves, Will K.; Weingartl, Hana M.; Wilson, William C.

    2015-01-01

    Rift Valley fever virus (RVFV) causes serious disease in ruminants and humans in Africa. In North America, there are susceptible ruminant hosts and competent mosquito vectors, yet there are no fully licensed animal vaccines for this arthropod-borne virus, should it be introduced. Studies in sheep and cattle have found the attenuated strain of RVFV, MP-12, to be both safe and efficacious based on early testing, and a 2-year conditional license for use in U.S. livestock has been issued. The purpose of this study was to further determine the vaccine's potential to infect mosquitoes, the duration of humoral immunity to 24 months postvaccination, and the ability to prevent disease and viremia from a virulent challenge. Vaccination experiments conducted in sheep found no evidence of a potential for vector transmission to 4 North American mosquito species. Neutralizing antibodies were elicited, with titers of >1:40 still present at 24 months postvaccination. Vaccinates were protected from clinical signs and detectable viremia after challenge with virulent virus, while control sheep had fever and high-titered viremia extending for 5 days. Antibodies to three viral proteins (nucleocapsid N, the N-terminal half of glycoprotein GN, and the nonstructural protein from the short segment NSs) were also detected to 24 months using competitive enzyme-linked immunosorbent assays. This study demonstrates that the MP-12 vaccine given as a single dose in sheep generates protective immunity to a virulent challenge with antibody duration of at least 2 years, with no evidence of a risk for vector transmission. PMID:26041042

  7. An equine herpesvirus type 1 (EHV-1) vector expressing Rift Valley fever virus (RVFV) Gn and Gc induces neutralizing antibodies in sheep.

    PubMed

    Said, Abdelrahman; Elmanzalawy, Mona; Ma, Guanggang; Damiani, Armando Mario; Osterrieder, Nikolaus

    2017-08-14

    Rift Valley fever virus (RVFV) is an arthropod-borne bunyavirus that can cause serious and fatal disease in humans and animals. RVFV is a negative-sense RNA virus of the Phlebovirus genus in the Bunyaviridae family. The main envelope RVFV glycoproteins, Gn and Gc, are encoded on the M segment of RVFV and known inducers of protective immunity. In an attempt to develop a safe and efficacious RVF vaccine, we constructed and tested a vectored equine herpesvirus type 1 (EHV-1) vaccine that expresses RVFV Gn and Gc. The Gn and Gc genes were custom-synthesized after codon optimization and inserted into EHV-1 strain RacH genome. The rH_Gn-Gc recombinant virus grew in cultured cells with kinetics that were comparable to those of the parental virus and stably expressed Gn and Gc. Upon immunization of sheep, the natural host, neutralizing antibodies against RVFV were elicited by rH_Gn-Gc and protective titers reached to 1:320 at day 49 post immunization but not by parental EHV-1, indicating that EHV-1 is a promising vector alternative in the development of a safe marker RVFV vaccine.

  8. Mechanisms of fever production and lysis: lessons from experimental LPS fever.

    PubMed

    Roth, Joachim; Blatteis, Clark M

    2014-10-01

    Fever is a cardinal symptom of infectious or inflammatory insults, but it can also arise from noninfectious causes. The fever-inducing agent that has been used most frequently in experimental studies designed to characterize the physiological, immunological and neuroendocrine processes and to identify the neuronal circuits that underlie the manifestation of the febrile response is lipopolysaccharide (LPS). Our knowledge of the mechanisms of fever production and lysis is largely based on this model. Fever is usually initiated in the periphery of the challenged host by the immediate activation of the innate immune system by LPS, specifically of the complement (C) cascade and Toll-like receptors. The first results in the immediate generation of the C component C5a and the subsequent rapid production of prostaglandin E2 (PGE2). The second, occurring after some delay, induces the further production of PGE2 by induction of its synthesizing enzymes and transcription and translation of proinflammatory cytokines. The Kupffer cells (Kc) of the liver seem to be essential for these initial processes. The subsequent transfer of the pyrogenic message from the periphery to the brain is achieved by neuronal and humoral mechanisms. These pathways subserve the genesis of early (neuronal signals) and late (humoral signals) phases of the characteristically biphasic febrile response to LPS. During the course of fever, counterinflammatory factors, "endogenous antipyretics," are elaborated peripherally and centrally to limit fever in strength and duration. The multiple interacting pro- and antipyretic signals and their mechanistic effects that underlie endotoxic fever are the subjects of this review.

  9. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus

    PubMed Central

    Das, Sanchita; Rundell, Mark S.; Mirza, Aashiq H.; Pingle, Maneesh R.; Shigyo, Kristi; Garrison, Aura R.; Paragas, Jason; Smith, Scott K.; Olson, Victoria A.; Larone, Davise H.; Spitzer, Eric D.; Barany, Francis; Golightly, Linnie M.

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus). PMID:26381398

  10. A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.

    PubMed

    Das, Sanchita; Rundell, Mark S; Mirza, Aashiq H; Pingle, Maneesh R; Shigyo, Kristi; Garrison, Aura R; Paragas, Jason; Smith, Scott K; Olson, Victoria A; Larone, Davise H; Spitzer, Eric D; Barany, Francis; Golightly, Linnie M

    2015-01-01

    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in the essentially non-immune world population. Early detection of the causative agents, and the ability to distinguish them from other pathogens, is essential to contain outbreaks, implement proper control measures, and prevent morbidity and mortality. We have developed a multiplex detection assay that uses several species-specific PCR primers to generate amplicons from multiple pathogens; these are then targeted in a ligase detection reaction (LDR). The resultant fluorescently-labeled ligation products are detected on a universal array enabling simultaneous identification of the pathogens. The assay was evaluated on 32 different isolates associated with VHF (ebolavirus, marburgvirus, Crimean Congo hemorrhagic fever virus, Lassa fever virus, Rift Valley fever virus, Dengue virus, and Yellow fever virus) as well as variola virus and vaccinia virus (the agent of smallpox and its vaccine strain, respectively). The assay was able to detect all viruses tested, including 8 sequences representative of different variola virus strains from the CDC repository. It does not cross react with other emerging zoonoses such as monkeypox virus or cowpox virus, or six flaviviruses tested (St. Louis encephalitis virus, Murray Valley encephalitis virus, Powassan virus, Tick-borne encephalitis virus, West Nile virus and Japanese encephalitis virus).

  11. Ecology and Epidemiology of Crimean-Congo Hemorrhagic Fever Virus Transmission in the Republic of Senegal.

    DTIC Science & Technology

    1992-07-01

    that simultaneously circulate in the region were investigated. Most notably, studies of Rift Valley fever ( RVF ) virus transmission in southern Mauritania...and Senegal were undertaken: we documented antibody prevalance in domestic animals during the 1987 outbreak, a decline in RVF virus transmission...following that epidemic, and human risk factors for RVF and associated mosquito vectors in Senegal. - 1 - FOREWORD Citations of commercial organizations

  12. Enhanced surveillance for Rift Valley Fever in livestock during El Niño rains and threat of RVF outbreak, Kenya, 2015-2016.

    PubMed

    Oyas, Harry; Holmstrom, Lindsey; Kemunto, Naomi P; Muturi, Matthew; Mwatondo, Athman; Osoro, Eric; Bitek, Austine; Bett, Bernard; Githinji, Jane W; Thumbi, Samuel M; Widdowson, Marc-Alain; Munyua, Peninah M; Njenga, M Kariuki

    2018-04-01

    In mid-2015, the United States' Pandemic Prediction and Forecasting Science and Technical Working Group of the National Science and Technology Council, Food and Agriculture Organization Emergency Prevention Systems, and Kenya Meteorological Department issued an alert predicting a high possibility of El-Niño rainfall and Rift Valley Fever (RVF) epidemic in Eastern Africa. In response to the alert, the Kenya Directorate of Veterinary Services (KDVS) carried out an enhanced syndromic surveillance system between November 2015 and February 2016, targeting 22 RVF high-risk counties in the country as identified previously through risk mapping. The surveillance collected data on RVF-associated syndromes in cattle, sheep, goats, and camels from >1100 farmers through 66 surveillance officers. During the 14-week surveillance period, the KDVS received 10,958 reports from participating farmers and surveillance officers, of which 362 (3.3%) had at least one syndrome. The reported syndromes included 196 (54.1%) deaths in young livestock, 133 (36.7%) abortions, and 33 (9.1%) hemorrhagic diseases, with most occurring in November and December, the period of heaviest rainfall. Of the 69 herds that met the suspect RVF herd definition (abortion in flooded area), 24 (34.8%) were defined as probable (abortions, mortalities in the young ones, and/or hemorrhagic signs) but none were confirmed. This surveillance activity served as an early warning system that could detect RVF disease in animals before spillover to humans. It was also an excellent pilot for designing and implementing syndromic surveillance in animals in the country, which is now being rolled out using a mobile phone-based data reporting technology as part of the global health security system.

  13. Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers.

    PubMed

    Gale, Trevor V; Horton, Timothy M; Grant, Donald S; Garry, Robert F

    2017-09-01

    Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients.

  14. Metabolomics analyses identify platelet activating factors and heme breakdown products as Lassa fever biomarkers

    PubMed Central

    Gale, Trevor V.; Horton, Timothy M.; Grant, Donald S.

    2017-01-01

    Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level. Effects of LASV infection on pathways mediating blood coagulation, and lipid, amino acid, nucleic acid metabolism are manifest in changes in the levels of numerous metabolites in the circulation. Several compounds, including platelet activating factor (PAF), PAF-like molecules and products of heme breakdown emerged as candidates that may prove useful in diagnostic assays to inform better care of Lassa fever patients. PMID:28922385

  15. 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.

  16. Single-Dose Intranasal Treatment with DEF201 (Adenovirus Vectored Consensus Interferon) Prevents Lethal Disease Due to Rift Valley Fever Virus Challenge

    PubMed Central

    Gowen, Brian B.; Ennis, Jane; Bailey, Kevin W.; Vest, Zachary; Scharton, Dionna; Sefing, Eric J.; Turner, Jeffrey D.

    2014-01-01

    Rift Valley fever virus (RVFV) causes severe disease in humans and ungulates. The virus can be transmitted by mosquitoes, direct contact with infected tissues or fluids, or aerosol, making it a significant biological threat for which there is no approved vaccine or therapeutic. Herein we describe the evaluation of DEF201, an adenovirus-vectored interferon alpha which addresses the limitations of recombinant interferon alpha protein (cost, short half-life), as a pre- and post-exposure treatment in a lethal hamster RVFV challenge model. DEF201 was delivered intranasally to stimulate mucosal immunity and effectively bypass any pre-existing immunity to the vector. Complete protection against RVFV infection was observed from a single dose of DEF201 administered one or seven days prior to challenge while all control animals succumbed within three days of infection. Efficacy of treatment administered two weeks prior to challenge was limited. Post‑exposure, DEF201 was able to confer significant protection when dosed at 30 min or 6 h, but not at 24 h post-RVFV challenge. Protection was associated with reductions in serum and tissue viral loads. Our findings suggest that DEF201 may be a useful countermeasure against RVFV infection and further demonstrates its broad-spectrum capacity to stimulate single dose protective immunity. PMID:24662673

  17. Diagnosis and Chemotherapy of Human Trypanosomiasis and Vector Ecology of Rift Valley Fever and Congo-Crimean Hemorrhagic Fever in Kenya

    DTIC Science & Technology

    1991-11-06

    CONGO-CRIMEAN HEMORRHAGIC FEVER IN KENYA PRINCIPAL INVESTIGATOR: J. K. Omuse, Ph.D. CONTRACTING ORGANIZATION : Kenya Trypanosomiasis Research Institute P.O...Distribution unlimited 4. PERFORMING ORGANIZATION REPORT NUMBER(S) S. MONITORING ORGANIZATION REPORT NUMBER(S) Go. NAME OF PERFORMING ORGANIZATION 6b...OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATION Kenya Trypanosomiasis (I akabe) Research Institute I 6r. ADDRESS (Cit,, State, and ZIP Cod#) 7b

  18. Evidence for Circulation of the Rift Valley Fever Virus among Livestock in the Union of Comoros

    PubMed Central

    Soulé, Miradje; Faharoudine, Abdourahime; Foray, Coralie; Olive, Marie-Marie; Maquart, Marianne; Soulaimane, Abdouroihamane; Madi Kassim, Ahmed; Cêtre-Sossah, Catherine; Cardinale, Eric

    2014-01-01

    Rift Valley fever virus (RVFV) is an arthropod-borne phlebovirus reported to be circulating in most parts of Africa. Since 2009, RVFV has been suspected of continuously circulating in the Union of Comoros. To estimate the incidence of RVFV antibody acquisition in the Comorian ruminant population, 191 young goats and cattle were selected in six distinct zones and sampled periodically from April 2010 to August 2011. We found an estimated incidence of RVFV antibody acquisition of 17.5% (95% confidence interval (CI): [8.9–26.1]) with a significant difference between islands (8.2% in Grande Comore, 72.3% in Moheli and 5.8% in Anjouan). Simultaneously, a longitudinal entomological survey was conducted and ruminant trade-related information was collected. No RVFV RNA was detected out of the 1,568 blood-sucking caught insects, including three potential vectors of RVFV mosquito species. Our trade survey suggests that there is a continuous flow of live animals from eastern Africa to the Union of Comoros and movements of ruminants between the three Comoro islands. Finally, a cross-sectional study was performed in August 2011 at the end of the follow-up. We found an estimated RVFV antibody prevalence of 19.3% (95% CI: [15.6%–23.0%]). Our findings suggest a complex RVFV epidemiological cycle in the Union of Comoros with probable inter-islands differences in RVFV circulation patterns. Moheli, and potentially Anjouan, appear to be acting as endemic reservoir of infection whereas RVFV persistence in Grande Comore could be correlated with trade in live animals with the eastern coast of Africa. More data are needed to estimate the real impact of the disease on human health and on the national economy. PMID:25078616

  19. Attenuation and efficacy of live-attenuated Rift Valley fever virus vaccine candidates in non-human primates.

    PubMed

    Smith, Darci R; Johnston, Sara C; Piper, Ashley; Botto, Miriam; Donnelly, Ginger; Shamblin, Joshua; Albariño, César G; Hensley, Lisa E; Schmaljohn, Connie; Nichol, Stuart T; Bird, Brian H

    2018-05-09

    Rift Valley fever virus (RVFV) is an important mosquito-borne veterinary and human pathogen that has caused large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Currently, no licensed vaccine or therapeutics exists to treat this potentially deadly disease. The explosive nature of RVFV outbreaks and the severe consequences of its accidental or intentional introduction into RVFV-free areas provide the impetus for the development of novel vaccine candidates for use in both livestock and humans. Rationally designed vaccine candidates using reverse genetics have been used to develop deletion mutants of two known RVFV virulence factors, the NSs and NSm genes. These recombinant viruses were demonstrated to be protective and immunogenic in rats, mice, and sheep, without producing clinical illness in these animals. Here, we expand upon those findings and evaluate the single deletion mutant (ΔNSs rRVFV) and double deletion mutant (ΔNSs-ΔNSm rRVFV) vaccine candidates in the common marmoset (Callithrix jacchus), a non-human primate (NHP) model resembling severe human RVF disease. We demonstrate that both the ΔNSs and ΔNSs-ΔNSm rRVFV vaccine candidates were found to be safe and immunogenic in the current study. The vaccinated animals received a single dose of vaccine that led to the development of a robust antibody response. No vaccine-induced adverse reactions, signs of clinical illness or infectious virus were detected in the vaccinated marmosets. All vaccinated animals that were subsequently challenged with RVFV were protected against viremia and liver disease. In summary, our results provide the basis for further development of the ΔNSs and ΔNSs-ΔNSm rRVFV as safe and effective human RVFV vaccines for this significant public health threat.

  20. The Epidemiology of Rift Valley Fever in Mayotte: Insights and Perspectives from 11 Years of Data

    PubMed Central

    Métras, Raphaëlle; Cavalerie, Lisa; Dommergues, Laure; Mérot, Philippe; Edmunds, W. John; Keeling, Matt J.; Cêtre-Sossah, Catherine; Cardinale, Eric

    2016-01-01

    Rift Valley fever (RVF) is a zoonotic arboviral disease that is a threat to human health, animal health and production, mainly in Sub-Saharan Africa. RVF virus dynamics have been poorly studied due to data scarcity. On the island of Mayotte in the Indian Ocean, off the Southeastern African coast, RVF has been present since at least 2004. Several retrospective and prospective serological surveys in livestock have been conducted over eleven years (2004–15). These data are collated and presented here. Temporal patterns of seroprevalence were plotted against time, as well as age-stratified seroprevalence. Results suggest that RVF was already present in 2004–07. An epidemic occurred between 2008 and 2010, with IgG and IgM peak annual prevalences of 36% in 2008–09 (N = 142, n = 51, 95% CI [17–55]) and 41% (N = 96, n = 39, 95% CI [25–56]), respectively. The virus seems to be circulating at a low level since 2011, causing few new infections. In 2015, about 95% of the livestock population was susceptible (IgG annual prevalence was 6% (N = 584, n = 29, 95% CI [3–10])). Monthly rainfall varied a lot (2–540mm), whilst average temperature remained high with little variation (about 25–30°C). This large dataset collected on an insular territory for more than 10 years, suggesting a past epidemic and a current inter-epidemic period, represents a unique opportunity to study RVF dynamics. Further data collection and modelling work may be used to test different scenarios of animal imports and rainfall pattern that could explain the observed epidemiological pattern and estimate the likelihood of a potential re-emergence. PMID:27331402

  1. Epidemiologic and Environmental Risk Factors of Rift Valley Fever in Southern Africa from 2008 to 2011.

    PubMed

    Glancey, Margaret M; Anyamba, Assaf; Linthicum, Kenneth J

    2015-08-01

    Rift Valley fever (RVF) outbreaks have been associated with periods of widespread and above-normal rainfall over several months. Knowledge on the environmental factors influencing disease transmission dynamics has provided the basis for developing models to predict RVF outbreaks in Africa. From 2008 to 2011, South Africa experienced the worst wave of RVF outbreaks in almost 40 years. We investigated rainfall-associated environmental factors in southern Africa preceding these outbreaks. RVF epizootic records obtained from the World Animal Health Information Database (WAHID), documenting livestock species affected, location, and time, were analyzed. Environmental variables including rainfall and satellite-derived normalized difference vegetation index (NDVI) data were collected and assessed in outbreak regions to understand the underlying drivers of the outbreaks. The predominant domestic vertebrate species affected in 2008 and 2009 were cattle, when outbreaks were concentrated in the eastern provinces of South Africa. In 2010 and 2011, outbreaks occurred in the interior and southern provinces affecting over 16,000 sheep. The highest number of cases occurred between January and April but epidemics occurred in different regions every year, moving from the northeast of South Africa toward the southwest with each progressing year. The outbreaks showed a pattern of increased rainfall preceding epizootics ranging from 9 to 152 days; however, NDVI and rainfall were less correlated with the start of the outbreaks than has been observed in eastern Africa. Analyses of the multiyear RVF outbreaks of 2008 to 2011 in South Africa indicated that rainfall, NDVI, and other environmental and geographical factors, such as land use, drainage, and topography, play a role in disease emergence. Current and future investigations into these factors will be able to contribute to improving spatial accuracy of models to map risk areas, allowing adequate time for preparation and prevention

  2. Reconstruction of Rift Valley fever transmission dynamics in Madagascar: estimation of force of infection from seroprevalence surveys using Bayesian modelling

    PubMed Central

    Olive, Marie-Marie; Grosbois, Vladimir; Tran, Annelise; Nomenjanahary, Lalaina Arivony; Rakotoarinoro, Mihaja; Andriamandimby, Soa-Fy; Rogier, Christophe; Heraud, Jean-Michel; Chevalier, Veronique

    2017-01-01

    The force of infection (FOI) is one of the key parameters describing the dynamics of transmission of vector-borne diseases. Following the occurrence of two major outbreaks of Rift Valley fever (RVF) in Madagascar in 1990–91 and 2008–09, recent studies suggest that the pattern of RVF virus (RVFV) transmission differed among the four main eco-regions (East, Highlands, North-West and South-West). Using Bayesian hierarchical models fitted to serological data from cattle of known age collected during two surveys (2008 and 2014), we estimated RVF FOI and described its variations over time and space in Madagascar. We show that the patterns of RVFV transmission strongly differed among the eco-regions. In the North-West and Highlands regions, these patterns were synchronous with a high intensity in mid-2007/mid-2008. In the East and South-West, the peaks of transmission were later, between mid-2008 and mid-2010. In the warm and humid northwestern eco-region favorable to mosquito populations, RVFV is probably transmitted all year-long at low-level during inter-epizootic period allowing its maintenance and being regularly introduced in the Highlands through ruminant trade. The RVF surveillance of animals of the northwestern region could be used as an early warning indicator of an increased risk of RVF outbreak in Madagascar. PMID:28051125

  3. Climate impacts on environmental risks evaluated from space: a conceptual approach to the case of Rift Valley Fever in Senegal.

    PubMed

    Tourre, Yves M; Lacaux, Jean-Pierre; Vignolles, Cécile; Lafaye, Murielle

    2009-11-11

    Climate and environment vary across many spatio-temporal scales, including the concept of climate change, which impact on ecosystems, vector-borne diseases and public health worldwide. To develop a conceptual approach by mapping climatic and environmental conditions from space and studying their linkages with Rift Valley Fever (RVF) epidemics in Senegal. Ponds in which mosquitoes could thrive were identified from remote sensing using high-resolution SPOT-5 satellite images. Additional data on pond dynamics and rainfall events (obtained from the Tropical Rainfall Measuring Mission) were combined with hydrological in-situ data. Localisation of vulnerable hosts such as penned cattle (from QuickBird satellite) were also used. Dynamic spatio-temporal distribution of Aedes vexans density (one of the main RVF vectors) is based on the total rainfall amount and ponds' dynamics. While Zones Potentially Occupied by Mosquitoes are mapped, detailed risk areas, i.e. zones where hazards and vulnerability occur, are expressed in percentages of areas where cattle are potentially exposed to mosquitoes' bites. This new conceptual approach, using precise remote-sensing techniques, simply relies upon rainfall distribution also evaluated from space. It is meant to contribute to the implementation of operational early warning systems for RVF based on both natural and anthropogenic climatic and environmental changes. In a climate change context, this approach could also be applied to other vector-borne diseases and places worldwide.

  4. Ecological niche modeling and land cover risk areas for rift valley fever vector, culex tritaeniorhynchus giles in Jazan, Saudi Arabia.

    PubMed

    Sallam, Mohamed F; Al Ahmed, Azzam M; Abdel-Dayem, Mahmoud S; Abdullah, Mohamed A R

    2013-01-01

    The mosquito, Culex tritaeniorhynchus Giles is a prevalent and confirmed Rift Valley Fever virus (RVFV) vector. This vector, in association with Aedimorphus arabiensis (Patton), was responsible for causing the outbreak of 2000 in Jazan Province, Saudi Arabia. Larval occurrence records and a total of 19 bioclimatic and three topographic layers imported from Worldclim Database were used to predict the larval suitable breeding habitats for this vector in Jazan Province using ArcGIS ver.10 and MaxEnt modeling program. Also, a supervised land cover classification from SPOT5 imagery was developed to assess the land cover distribution within the suitable predicted habitats. Eleven bioclimatic and slope attributes were found to be the significant predictors for this larval suitable breeding habitat. Precipitation and temperature were strong predictors of mosquito distribution. Among six land cover classes, the linear regression model (LM) indicated wet muddy substrate is significantly associated with high-very high suitable predicted habitats (R(2) = 73.7%, P<0.05). Also, LM indicated that total dissolved salts (TDS) was a significant contributor (R(2) = 23.9%, P<0.01) in determining mosquito larval abundance. This model is a first step in understanding the spatial distribution of Cx. tritaeniorhynchus and consequently the risk of RVFV in Saudi Arabia and to assist in planning effective mosquito surveillance and control programs by public health personnel and researchers.

  5. Generation and characterization of a recombinant Rift Valley fever virus expressing a V5 epitope-tagged RNA-dependent RNA polymerase.

    PubMed

    Brennan, Benjamin; Li, Ping; Elliott, Richard M

    2011-12-01

    The viral RNA-dependent RNA polymerase (RdRp; L protein) of Rift Valley fever virus (RVFV; family Bunyaviridae) is a 238 kDa protein that is crucial for the life cycle of the virus, as it catalyses both transcription of viral mRNAs and replication of the tripartite genome. Despite its importance, little is known about the intracellular distribution of the polymerase or its other roles during infection, primarily because of lack of specific antibodies that recognize L protein. To begin to address these questions we investigated whether the RVFV (MP12 strain) polymerase could tolerate insertion of the V5 epitope, as has been previously demonstrated for the Bunyamwera virus L protein. Insertion of the 14 aa epitope into the polymerase sequence at aa 1852 resulted in a polymerase that retained functionality in a minigenome assay, and we were able to rescue recombinant viruses that expressed the modified L protein by reverse genetics. The L protein could be detected in infected cells by Western blotting with anti-V5 antibodies. Examination of recombinant virus-infected cells by immunofluorescence revealed a punctate perinuclear or cytoplasmic distribution of the polymerase that co-localized with the nucleocapsid protein. The generation of RVFV expressing a tagged RdRp will allow detailed examination of the role of the viral polymerase in the virus life cycle.

  6. Reconstruction of Rift Valley fever transmission dynamics in Madagascar: estimation of force of infection from seroprevalence surveys using Bayesian modelling.

    PubMed

    Olive, Marie-Marie; Grosbois, Vladimir; Tran, Annelise; Nomenjanahary, Lalaina Arivony; Rakotoarinoro, Mihaja; Andriamandimby, Soa-Fy; Rogier, Christophe; Heraud, Jean-Michel; Chevalier, Veronique

    2017-01-04

    The force of infection (FOI) is one of the key parameters describing the dynamics of transmission of vector-borne diseases. Following the occurrence of two major outbreaks of Rift Valley fever (RVF) in Madagascar in 1990-91 and 2008-09, recent studies suggest that the pattern of RVF virus (RVFV) transmission differed among the four main eco-regions (East, Highlands, North-West and South-West). Using Bayesian hierarchical models fitted to serological data from cattle of known age collected during two surveys (2008 and 2014), we estimated RVF FOI and described its variations over time and space in Madagascar. We show that the patterns of RVFV transmission strongly differed among the eco-regions. In the North-West and Highlands regions, these patterns were synchronous with a high intensity in mid-2007/mid-2008. In the East and South-West, the peaks of transmission were later, between mid-2008 and mid-2010. In the warm and humid northwestern eco-region favorable to mosquito populations, RVFV is probably transmitted all year-long at low-level during inter-epizootic period allowing its maintenance and being regularly introduced in the Highlands through ruminant trade. The RVF surveillance of animals of the northwestern region could be used as an early warning indicator of an increased risk of RVF outbreak in Madagascar.

  7. Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever

    PubMed Central

    Roe, Chandler C.; Hepp, Crystal M.; Teixeira, Marcus; Driebe, Elizabeth M.; Schupp, James M.; Gade, Lalitha; Waddell, Victor; Komatsu, Kenneth; Arathoon, Eduardo; Logemann, Heidi; Thompson, George R.; Chiller, Tom; Keim, Paul; Litvintseva, Anastasia P.

    2016-01-01

    ABSTRACT Coccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region. PMID:27118594

  8. Serological evidence of Rift Valley fever virus circulation in sheep and goats in Zambézia Province, Mozambique.

    PubMed

    Fafetine, José; Neves, Luis; Thompson, Peter N; Paweska, Janusz T; Rutten, Victor P M G; Coetzer, J A W

    2013-01-01

    Rift Valley fever (RVF) is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats), 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV) antibodies in a virus neutralization test (VN) and in an IgG enzyme-linked immunosorbent assay (ELISA). In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001) using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats) failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province.

  9. 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 ...

  10. Isolated fever induced by mesalamine treatment.

    PubMed

    Slim, Rita; Amara, Joseph; Nasnas, Roy; Honein, Khalil; Jaoude, Joseph Bou; Yaghi, Cesar; Daniel, Fady; Sayegh, Raymond

    2013-02-21

    Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology.

  11. Dengue Fever

    MedlinePlus

    ... Staying Safe Videos for Educators Search English Español Dengue Fever KidsHealth / For Parents / Dengue Fever What's in ... Print en español Fiebre del dengue What Is Dengue Fever? Dengue (DEN-gee) fever is a tropical ...

  12. Fever

    PubMed Central

    Conti, Bruno

    2010-01-01

    Measurement of body temperature remains one of the most common ways to assess health. An increase in temperature above what is considered to be a normal value is inevitably regarded as a sure sign of disease and referred to with one simple word: fever. In this review, we summarize how research on fever allowed the identification of the exogenous and endogenous molecules and pathways mediating the fever response. We also show how temperature elevation is common to different pathologies and how the molecular components of the fever-generation pathway represent drug targets for antipyretics, such as acetylsalicylic acid, the first “blockbuster drug”. We also show how fever research provided new insights into temperature and energy homeostasis, and into treatment of infection and inflammation. PMID:20305990

  13. Estimating sources of Valley Fever pathogen propagation in southern Arizona: A remote sensing approach

    NASA Astrophysics Data System (ADS)

    Pianalto, Frederick S.

    Coccidioidomycosis (Valley Fever) is an environmentally-mediated respiratory disease caused by the inhalation of airborne spores from the fungi Coccidioides spp. The fungi reside in arid and semi-arid soils of the Americas. The disease has increased epidemically in Arizona and other areas within the last two decades. Despite this increase, the ecology of the fungi remains obscure, and environmental antecedents of the disease are largely unstudied. Two sources of soil disturbance, hypothesized to affect soil ecology and initiate spore dissemination, are investigated. Nocturnal desert rodents interact substantially with the soil substrate. Rodents are hypothesized to act as a reservoir of coccidioidomycosis, a mediator of soil properties, and a disseminator of fungal spores. Rodent distributions are poorly mapped for the study area. We build automated multi-linear regression models and decision tree models for ten rodent species using rodent trapping data from the Organ Pipe Cactus National Monument (ORPI) in southwest Arizona with a combination of surface temperature, a vegetation index and its texture, and a suite of topographic rasters. Surface temperature, derived from Landsat TM thermal images, is the most widely selected predictive variable in both automated methods. Construction-related soil disturbance (e.g. road construction, trenching, land stripping, and earthmoving) is a significant source of fugitive dust, which decreases air quality and may carry soil pathogens. Annual differencing of Landsat Thematic Mapper (TM) mid-infrared images is used to create change images, and thresholded change areas are associated with coordinates of local dust inspections. The output metric identifies source areas of soil disturbance, and it estimates the annual amount of dust-producing surface area for eastern Pima County spanning 1994 through 2009. Spatially explicit construction-related soil disturbance and rodent abundance data are compared with coccidioidomycosis

  14. Transmission of Rift Valley fever virus from European-breed lambs to Culex pipiens mosquitoes.

    PubMed

    Vloet, Rianka P M; Vogels, Chantal B F; Koenraadt, Constantianus J M; Pijlman, Gorben P; Eiden, Martin; Gonzales, Jose L; van Keulen, Lucien J M; Wichgers Schreur, Paul J; Kortekaas, Jeroen

    2017-12-01

    Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus of the genus Phlebovirus that is highly pathogenic to ruminants and humans. The disease is currently confined to Africa and the Arabian Peninsula, but globalization and climate change may facilitate introductions of the virus into currently unaffected areas via infected animals or mosquitoes. The consequences of such an introduction will depend on environmental factors, the availability of susceptible ruminants and the capacity of local mosquitoes to transmit the virus. We have previously demonstrated that lambs native to the Netherlands are highly susceptible to RVFV and we here report the vector competence of Culex (Cx.) pipiens, the most abundant and widespread mosquito species in the country. Vector competence was first determined after artificial blood feeding of laboratory-reared mosquitoes using the attenuated Clone 13 strain. Subsequently, experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs were performed. Finally, the transmission of RVFV from viremic lambs to mosquitoes was studied. Artificial feeding experiments using Clone 13 demonstrated that indigenous, laboratory-reared Cx. pipiens mosquitoes are susceptible to RVFV and that the virus can be transmitted via their saliva. Experiments with wild-type RVFV and mosquitoes hatched from field-collected eggs confirmed the vector competence of Cx. pipiens mosquitoes from the Netherlands. To subsequently investigate transmission of the virus under more natural conditions, mosquitoes were allowed to feed on RVFV-infected lambs during the viremic period. We found that RVFV is efficiently transmitted from lambs to mosquitoes, although transmission was restricted to peak viremia. Interestingly, in the mosquito-exposed skin samples, replication of RVFV was detected in previously unrecognized target cells. We here report the vector competence of Cx. pipiens mosquitoes from the Netherlands for RVFV. Both laboratory

  15. Spatial-temporal analysis of the of the risk of Rift Valley Fever in Kenya

    NASA Astrophysics Data System (ADS)

    Bett, B.; Omolo, A.; Hansen, F.; Notenbaert, A.; Kemp, S.

    2012-04-01

    Historical data on Rift Valley Fever (RVF) outbreaks in Kenya covering the period 1951 - 2010 were analyzed using a logistic regression model to identify factors associated with RVF occurrence. The analysis used a division, an administrative unit below a district, as the unit of analysis. The infection status of each division was defined on a monthly time scale and used as a dependent variable. Predictors investigated include: monthly precipitation (minimum, maximum and total), normalized difference vegetation index, altitude, agro-ecological zone, presence of game, livestock and human population densities, the number of times a division has had an outbreak before and time interval in months between successive outbreaks (used as a proxy for immunity). Both univariable and multivariable analyses were conducted. The models used incorporated an auto-regressive correlation matrix to account for clustering of observations in time, while dummy variables were fitted in the multivariable model to account for spatial relatedness/topology between divisions. This last procedure was followed because it is expected that the risk of RVF occurring in a given division increases when its immediate neighbor gets infected. Functional relationships between the continuous and the outcome variables were assessed to ensure that the linearity assumption was met. Deviance and leverage residuals were also generated from the final model and used for evaluating the goodness of fit of the model. Descriptive analyzes indicate that a total of 91 divisions in 42 districts (of the original 69 districts in place by 1999) reported RVF outbreaks at least once over the period. The mean interval between outbreaks was determined to be about 43 months. Factors that were positively associated with RVF occurrence include increased precipitation, high outbreak interval and the number of times a division has been infected or reported an outbreak. The model will be validated and used for developing an RVF

  16. Doxycycline-induced drug fever: a case report.

    PubMed

    Yuan, Hai-Ling; Lu, Ning-Wei; Xie, Hua; Zheng, Yuan-Yuan; Wang, Qiu-Hong

    2016-01-01

    Drug fever is a febrile reaction induced by a drug without additional clinical symptoms. This adverse reaction is not rare but under diagnosed and under reported. Doxycycline is a tetracycline compound with broad-spectrum antibiotic activity. Drug fever induced by doxycycline is rarely reported. In this study, we describe a patient in whom doxycycline induced drug fever after 17 days of therapy for brucellosis.

  17. Enhanced surveillance for Rift Valley Fever in livestock during El Niño rains and threat of RVF outbreak, Kenya, 2015-2016

    PubMed Central

    Kemunto, Naomi P.; Muturi, Matthew; Mwatondo, Athman; Osoro, Eric; Bitek, Austine; Bett, Bernard; Githinji, Jane W.; Thumbi, Samuel M.; Widdowson, Marc-Alain; Munyua, Peninah M.

    2018-01-01

    Background In mid-2015, the United States’ Pandemic Prediction and Forecasting Science and Technical Working Group of the National Science and Technology Council, Food and Agriculture Organization Emergency Prevention Systems, and Kenya Meteorological Department issued an alert predicting a high possibility of El-Niño rainfall and Rift Valley Fever (RVF) epidemic in Eastern Africa. Methodology/Principal findings In response to the alert, the Kenya Directorate of Veterinary Services (KDVS) carried out an enhanced syndromic surveillance system between November 2015 and February 2016, targeting 22 RVF high-risk counties in the country as identified previously through risk mapping. The surveillance collected data on RVF-associated syndromes in cattle, sheep, goats, and camels from >1100 farmers through 66 surveillance officers. During the 14-week surveillance period, the KDVS received 10,958 reports from participating farmers and surveillance officers, of which 362 (3.3%) had at least one syndrome. The reported syndromes included 196 (54.1%) deaths in young livestock, 133 (36.7%) abortions, and 33 (9.1%) hemorrhagic diseases, with most occurring in November and December, the period of heaviest rainfall. Of the 69 herds that met the suspect RVF herd definition (abortion in flooded area), 24 (34.8%) were defined as probable (abortions, mortalities in the young ones, and/or hemorrhagic signs) but none were confirmed. Conclusion/Significance This surveillance activity served as an early warning system that could detect RVF disease in animals before spillover to humans. It was also an excellent pilot for designing and implementing syndromic surveillance in animals in the country, which is now being rolled out using a mobile phone-based data reporting technology as part of the global health security system. PMID:29698487

  18. Fever: Its History, Cause, and Function

    PubMed Central

    Atkins, Elisha

    1982-01-01

    Concepts of fever from Hippocrates to the present are briefly outlined and compared with current ideas of the pathogenesis of fever. Evidence is presented that endogenous pyrogen, the hormone that elevates body temperature, is identical with lymphocyte-activating factor, a monokine that stimulates lymphocyte proliferation and function. It now appears that inflammation and fever are closely interrelated phenomena that are modulated by a single hormone and that have been selected by evolution to protect the host against infection. PMID:6758374

  19. Grizzly Valley fault system, Sierra Valley, CA

    USGS Publications Warehouse

    Gold, Ryan; Stephenson, William; Odum, Jack; Briggs, Rich; Crone, Anthony; Angster, Steve

    2012-01-01

    The Grizzly Valley fault system (GVFS) strikes northwestward across Sierra Valley, California and is part of a network of active, dextral strike-slip faults in the northern Walker Lane (Figure 1). To investigate Quaternary motion across the GVFS, we analyzed high-resolution (0.25 m) airborne LiDAR data (Figure 2) in combination with six, high-resolution, P-wave, seismic-reflection profiles [Gold and others, 2012]. The 0.5- to 2.0-km-long seismic-reflection profiles were sited orthogonal to suspected tectonic lineaments identified from previous mapping and our analysis of airborne LiDAR data. To image the upper 400–700 m of subsurface stratigraphy of Sierra Valley (Figure 3), we used a 230-kg accelerated weight drop source. Geophone spacing ranged from 2 to 5 m and shots were co-located with the geophones. The profiles reveal a highly reflective, deformed basal marker that we interpret to be the top of Tertiary volcanic rocks, overlain by a 120- to 300-m-thick suite of subhorizontal reflectors we interpret as Plio-Pleistocene lacustrine deposits. Three profiles image the principle active trace of the GVFS, which is a steeply dipping fault zone that offsets the volcanic rocks and the basin fill (Figures 4 & 5).

  20. Isolated fever induced by mesalamine treatment

    PubMed Central

    Slim, Rita; Amara, Joseph; Nasnas, Roy; Honein, Khalil; Jaoude, Joseph Bou; Yaghi, Cesar; Daniel, Fady; Sayegh, Raymond

    2013-01-01

    Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology. PMID:23467507

  1. Neurogenic Fever.

    PubMed

    Meier, Kevin; Lee, Kiwon

    2017-02-01

    Fever is a relatively common occurrence among patients in the intensive care setting. Although the most obvious and concerning etiology is sepsis, drug reactions, venous thromboembolism, and postsurgical fevers are all on the differential diagnosis. There is abundant evidence that fever is detrimental in acute neurologic injury. Worse outcomes are reported in acute stroke, subarachnoid hemorrhage, and traumatic brain injury. In addition to the various etiologies of fever in the intensive care setting, neurologic illness is a risk factor for neurogenic fevers. This primarily occurs in subarachnoid hemorrhage and traumatic brain injury, with hypothalamic injury being the proposed mechanism. Paroxysmal sympathetic hyperactivity is another source of hyperthermia commonly seen in the population with traumatic brain injury. This review focuses on the detrimental effects of fever on the neurologically injured as well as the risk factors and diagnosis of neurogenic fever.

  2. Development and Assessment of a Geographic Knowledge-Based Model for Mapping Suitable Areas for Rift Valley Fever Transmission in Eastern Africa

    PubMed Central

    Tran, Annelise; Trevennec, Carlène; Lutwama, Julius; Sserugga, Joseph; Gély, Marie; Pittiglio, Claudia; Pinto, Julio; Chevalier, Véronique

    2016-01-01

    Rift Valley fever (RVF), a mosquito-borne disease affecting ruminants and humans, is one of the most important viral zoonoses in Africa. The objective of the present study was to develop a geographic knowledge-based method to map the areas suitable for RVF amplification and RVF spread in four East African countries, namely, Kenya, Tanzania, Uganda and Ethiopia, and to assess the predictive accuracy of the model using livestock outbreak data from Kenya and Tanzania. Risk factors and their relative importance regarding RVF amplification and spread were identified from a literature review. A numerical weight was calculated for each risk factor using an analytical hierarchy process. The corresponding geographic data were collected, standardized and combined based on a weighted linear combination to produce maps of the suitability for RVF transmission. The accuracy of the resulting maps was assessed using RVF outbreak locations in livestock reported in Kenya and Tanzania between 1998 and 2012 and the ROC curve analysis. Our results confirmed the capacity of the geographic information system-based multi-criteria evaluation method to synthesize available scientific knowledge and to accurately map (AUC = 0.786; 95% CI [0.730–0.842]) the spatial heterogeneity of RVF suitability in East Africa. This approach provides users with a straightforward and easy update of the maps according to data availability or the further development of scientific knowledge. PMID:27631374

  3. Spatial Heterogeneity of Habitat Suitability for Rift Valley Fever Occurrence in Tanzania: An Ecological Niche Modelling Approach

    PubMed Central

    Sindato, Calvin; Stevens, Kim B.; Karimuribo, Esron D.; Mboera, Leonard E. G.; Paweska, Janusz T.; Pfeiffer, Dirk U.

    2016-01-01

    Background Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Materials and Methods Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Principal Findings Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). Conclusion/Significance The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with

  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. Climate impacts on environmental risks evaluated from space: a conceptual approach to the case of Rift Valley Fever in Senegal

    PubMed Central

    Tourre, Yves M.; Lacaux, Jean-Pierre; Vignolles, Cécile; Lafaye, Murielle

    2009-01-01

    Background Climate and environment vary across many spatio-temporal scales, including the concept of climate change, which impact on ecosystems, vector-borne diseases and public health worldwide. Objectives To develop a conceptual approach by mapping climatic and environmental conditions from space and studying their linkages with Rift Valley Fever (RVF) epidemics in Senegal. Design Ponds in which mosquitoes could thrive were identified from remote sensing using high-resolution SPOT-5 satellite images. Additional data on pond dynamics and rainfall events (obtained from the Tropical Rainfall Measuring Mission) were combined with hydrological in-situ data. Localisation of vulnerable hosts such as penned cattle (from QuickBird satellite) were also used. Results Dynamic spatio-temporal distribution of Aedes vexans density (one of the main RVF vectors) is based on the total rainfall amount and ponds’ dynamics. While Zones Potentially Occupied by Mosquitoes are mapped, detailed risk areas, i.e. zones where hazards and vulnerability occur, are expressed in percentages of areas where cattle are potentially exposed to mosquitoes’ bites. Conclusions This new conceptual approach, using precise remote-sensing techniques, simply relies upon rainfall distribution also evaluated from space. It is meant to contribute to the implementation of operational early warning systems for RVF based on both natural and anthropogenic climatic and environmental changes. In a climate change context, this approach could also be applied to other vector-borne diseases and places worldwide. PMID:20052381

  6. Inactivation of infectious virus and serological detection of virus antigen in Rift Valley fever virus-exposed mosquitoes fixed with paraformaldehyde.

    PubMed

    Kading, Rebekah; Crabtree, Mary; Miller, Barry

    2013-04-01

    Formaldehyde is routinely used to fix tissues in preparation for pathology studies, however concerns remain that treatment of tissues with cellular fixatives may not entirely inactivate infectious virus particles. This concern is of particular regulatory importance for research involving viruses that are classified as select agents such as Rift Valley fever virus (RVFV). Therefore, the specific aims of this study were to (1) assay RVFV-exposed Aedes aegypti mosquitoes fixed in 4% paraformaldehyde for the presence of infectious RVFV particles at various time points following infection and (2) demonstrate the utility of immunofluorescence assay (IFA) for the detection of RVFV antigen in various tissues of paraformaldehyde-fixed mosquitoes. Mosquitoes were administered an infectious blood meal containing one of two strains of RVFV, harvested at various time points following infection, intrathoracically inoculated with 4% paraformaldehyde, and fixed overnight at 4°C. The infection status of a subset of mosquitoes was verified by IFA on leg tissues prior to fixation, and infectivity of RVFV in fixed mosquito carcasses was determined by Vero cell plaque assay. Paraformaldehyde-fixed mosquitoes harvested 14 days post infection were also paraffin-embedded and sectioned for detection of RVFV antigen to particular tissues by IFA. None of the RVFV-exposed mosquitoes tested by Vero cell plaque assay contained infectious RVFV after fixation. Furthermore, incubation of mosquito sections with trypsin prior to antibody staining is recommended for optimal visualization of RVFV antigen in infected mosquito tissues by IFA. Published by Elsevier B.V.

  7. Serological Evidence of Rift Valley Fever Virus Circulation in Sheep and Goats in Zambézia Province, Mozambique

    PubMed Central

    Fafetine, José; Neves, Luis; Thompson, Peter N.; Paweska, Janusz T.; Rutten, Victor P. M. G.; Coetzer, J. A. W.

    2013-01-01

    Rift Valley fever (RVF) is endemic in most parts of Africa and has also been reported to occur in the Arabian Peninsula. It is responsible for significant morbidity and mortality, particularly in livestock, but also in humans. During the last two decades several outbreaks of RVF have been reported in countries in Southern Africa. In contrast to other countries, no clinical disease has been reported in Mozambique during this period. In a serological study conducted in 2007 in five districts of Zambézia Province, Mozambique, of a total of 654 small ruminants sampled (277 sheep and 377 goats), 35.8% of sheep sera and 21.2% of goat sera were positive for RVF virus (RVFV) antibodies in a virus neutralization test (VN) and in an IgG enzyme-linked immunosorbent assay (ELISA). In 2010, a cross-sectional survey was conducted in 313 sheep and 449 goats in two districts of the same province. This study revealed an overall seropositivity rate of 9.2% in sheep and 11.6% in goat and an increased likelihood of being seropositive in older animals (OR = 7.3; p<0.001) using an IgG ELISA. 29 out of 240 animals assessed for RVF specific IgM by ELISA were positive, suggesting recent exposure to RVFV. However, a longitudinal study carried out between September 2010 and April 2011 in a cohort of 125 of these animals (74 sheep and 51 goats) failed to demonstrate seroconversion. The results of the study indicate that RVFV circulates sub-clinically in domestic small ruminants in Zambézia Province. PMID:23469300

  8. Evaluation of dengue fever reports during an epidemic, Colombia.

    PubMed

    Romero-Vega, Liliana; Pacheco, Oscar; de la Hoz-Restrepo, Fernando; Díaz-Quijano, Fredi Alexander

    2014-12-01

    OBJECTIVE To assess the validity of dengue fever reports and how they relate to the definition of case and severity. METHODS Diagnostic test assessment was conducted using cross-sectional sampling from a universe of 13,873 patients treated during the fifth epidemiological period in health institutions from 11 Colombian departments in 2013. The test under analyses was the reporting to the National Public Health Surveillance System, and the reference standard was the review of histories identified by active institutional search. We reviewed all histories of patients diagnosed with dengue fever, as well as a random sample of patients with febrile syndromes. The specificity and sensitivity of reports were estimated for this purpose, considering the inverse of the probability of being selected for weighting. The concordance between reporting and the findings of the active institutional search was calculated using Kappa statistics. RESULTS We included 4,359 febrile patients, and 31.7% were classified as compatible with dengue fever (17 with severe dengue fever; 461 with dengue fever and warning signs; 904 with dengue fever and no warning signs). The global sensitivity of reports was 13.2% (95%CI 10.9;15.4) and specificity was 98.4% (95%CI 97.9;98.9). Sensitivity varied according to severity: 12.1% (95%CI 9.3;14.8) for patients presenting dengue fever with no warning signs; 14.5% (95%CI 10.6;18.4) for those presenting dengue fever with warning signs, and 40.0% (95%CI 9.6;70.4) for those with severe dengue fever. Concordance between reporting and the findings of the active institutional search resulted in a Kappa of 10.1%. CONCLUSIONS Low concordance was observed between reporting and the review of clinical histories, which was associated with the low reporting of dengue fever compatible cases, especially milder cases.

  9. Sorafenib Impedes Rift Valley Fever Virus Egress by Inhibiting Valosin-Containing Protein Function in the Cellular Secretory Pathway.

    PubMed

    Brahms, Ashwini; Mudhasani, Rajini; Pinkham, Chelsea; Kota, Krishna; Nasar, Farooq; Zamani, Rouzbeh; Bavari, Sina; Kehn-Hall, Kylene

    2017-11-01

    There is an urgent need for therapeutic development to combat infections caused by Rift Valley fever virus (RVFV), which causes devastating disease in both humans and animals. In an effort to repurpose drugs for RVFV treatment, our previous studies screened a library of FDA-approved drugs. The most promising candidate identified was the hepatocellular and renal cell carcinoma drug sorafenib. Mechanism-of-action studies indicated that sorafenib targeted a late stage in virus infection and caused a buildup of virions within cells. In addition, small interfering RNA (siRNA) knockdown studies suggested that nonclassical targets of sorafenib are important for the propagation of RVFV. Here we extend our previous findings to identify the mechanism by which sorafenib inhibits the release of RVFV virions from the cell. Confocal microscopy imaging revealed that glycoprotein Gn colocalizes and accumulates within the endoplasmic reticulum (ER) and the transport of Gn from the Golgi complex to the host cell membrane is reduced. Transmission electron microscopy demonstrated that sorafenib caused virions to be present inside large vacuoles inside the cells. p97/valosin-containing protein (VCP), which is involved in membrane remodeling in the secretory pathway and a known target of sorafenib, was found to be important for RVFV egress. Knockdown of VCP resulted in decreased RVFV replication, reduced Gn Golgi complex localization, and increased Gn ER accumulation. The intracellular accumulation of RVFV virions was also observed in cells transfected with siRNA targeting VCP. Collectively, these data indicate that sorafenib causes a disruption in viral egress by targeting VCP and the secretory pathway, resulting in a buildup of virions within dilated ER vesicles. IMPORTANCE In humans, symptoms of RVFV infection mainly include a self-limiting febrile illness. However, in some cases, infected individuals can also experience hemorrhagic fever, neurological disorders, liver failure, and

  10. 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.

  11. Rescue of infectious rift valley fever virus entirely from cDNA, analysis of virus lacking the NSs gene, and expression of a foreign gene.

    PubMed

    Ikegami, Tetsuro; Won, Sungyong; Peters, C J; Makino, Shinji

    2006-03-01

    Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) has a tripartite negative-strand genome, causes a mosquito-borne disease that is endemic in sub-Saharan African countries and that also causes large epidemics among humans and livestock. Furthermore, it is a bioterrorist threat and poses a risk for introduction to other areas. In spite of its danger, neither veterinary nor human vaccines are available. We established a T7 RNA polymerase-driven reverse genetics system to rescue infectious clones of RVFV MP-12 strain entirely from cDNA, the first for any phlebovirus. Expression of viral structural proteins from the protein expression plasmids was not required for virus rescue, whereas NSs protein expression abolished virus rescue. Mutants of MP-12 partially or completely lacking the NSs open reading frame were viable. These NSs deletion mutants replicated efficiently in Vero and 293 cells, but not in MRC-5 cells. In the latter cell line, accumulation of beta interferon mRNA occurred after infection by these NSs deletion mutants, but not after infection by MP-12. The NSs deletion mutants formed larger plaques than MP-12 did in Vero E6 cells and failed to shut off host protein synthesis in Vero cells. An MP-12 mutant carrying a luciferase gene in place of the NSs gene replicated as efficiently as MP-12 did, produced enzymatically active luciferase during replication, and stably retained the luciferase gene after 10 virus passages, representing the first demonstration of foreign gene expression in any bunyavirus. This reverse genetics system can be used to study the molecular virology of RVFV, assess current vaccine candidates, produce new vaccines, and incorporate marker genes into animal vaccines.

  12. Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain.

    PubMed

    Rummel, Christoph; Sachot, Christelle; Poole, Stephen; Luheshi, Giamal N

    2006-11-01

    Interleukin (IL)-6 is an important humoral mediator of fever following infection and inflammation and satisfies a number of criteria for a circulating pyrogen. However, evidence supporting such a role is diminished by the moderate or even absent ability of the recombinant protein to induce fever and activate the cyclooxygenase-2 (COX-2) pathway in the brain, a prerequisite step in the initiation and maintenance of fever. In the present study, we investigated the role of endogenous circulating IL-6 in a rodent model of localized inflammation, by neutralizing its action using a specific antiserum (IL-6AS). Rats were injected with LPS (100 microg/kg) or saline into a preformed air pouch in combination with an intraperitoneal injection of either normal sheep serum or IL-6AS (1.8 ml/rat). LPS induced a febrile response, which was accompanied by a significant rise in plasma IL-6 and nuclear STAT3 translocation in endothelial cells throughout the brain 2 h after treatment, including areas surrounding the sensory circumventricular organs and the median preoptic area (MnPO), important regions in mediating fever. These responses were abolished in the presence of the IL-6AS, which also significantly inhibited the LPS-induced upregulation of mRNA expression or immunoreactivity (IR) of the inducible form of COX, the rate-limiting enzyme for PGE2-synthesis. Interestingly, nuclear signal transducer and activator of transcription (STAT)3-positive cells colocalized with COX-2-IR, signifying that IL-6-activated cells are directly involved in PGE2 production. These observations suggest that IL-6 is an important circulating pyrogen that activates the COX-2-pathway in cerebral microvasculature, most likely through a STAT3-dependent pathway.

  13. A Retrospective Analysis of Sera Collected by the Hemorrhagic Fever Commission during the Korean Conflict

    DTIC Science & Technology

    1990-05-01

    of leptospirosis ; no diagnosis could be made for the other 14. virus-specific pooled mouse monoclonal antibodies or control fluids: Seropositive...day 7 of disease. Further, 1184 Concise Communications JID 1990:162 INovember) 100,00o - tion of a single case of leptospirosis , the etiology of the...prototype Hantaan tibodies to Rift Valley fever virus in ovine and bovine sera. Am JVet Res 1987:48:1138-1141virus as the causative agent of hemorrhagic

  14. Structure of the active rift zone and margins of the northern Imperial Valley from Salton Seismic Imaging Project (SSIP) data

    NASA Astrophysics Data System (ADS)

    Livers, A.; Han, L.; Delph, J. R.; White-Gaynor, A. L.; Petit, R.; Hole, J. A.; Stock, J. M.; Fuis, G. S.

    2012-12-01

    First-arrival refraction data were used to create a seismic velocity model of the upper crust across the actively rifting northern Imperial Valley and its margins. The densely sampled seismic refraction data were acquired by the Salton Seismic Imaging Project (SSIP) , which is investigating rift processes in the northern-most rift segment of the Gulf of California extensional province and earthquake hazards at the southern end of the San Andreas Fault system. A 95-km long seismic line was acquired across the northern Imperial Valley, through the Salton Sea geothermal field, parallel to the five Salton Butte volcanoes and perpendicular to the Brawley Seismic Zone and major strike-slip faults. Nineteen explosive shots were recorded with 100 m seismometer spacing across the valley and with 300-500 m spacing into the adjacent ranges. First-arrival travel times were picked from shot gathers along this line and a seismic velocity model was produced using tomographic inversion. Sedimentary basement and seismic basement in the valley are interpreted to be sediment metamorphosed by the very high heat flow. The velocity model shows that this basement to the west of the Brawley Seismic Zone is at ~4-km depth. The basement shallows to ~2-km depth in the active geothermal field and Salton Buttes volcanic field which locally coincide with the Brawley Seismic Zone. At the eastern edge of the geothermal field, the basement drops off again to ~3.5-km depth. The eastern edge of the valley appears to be fault bounded by the along-strike extension of the Sand Hills Fault, an inactive strike-slip fault. The seismic velocities to the east of the fault correspond to metamorphic rock of the Chocolate Mountains, different from the metamorphosed basement in the valley. The western edge of the valley appears to be fault bounded by the active Superstition Hills Fault. To the west of the valley, >4-km deep valley basement extends to the active Superstition Hills Fault. Basement then shallows

  15. A Patient with Dengue Fever Presenting with Rhabdomyolysis.

    PubMed

    Nakamura, Masayuki; Ikeda, Shuntaro; Nagahara, Hiroyuki; Hitsumoto, Tatsurou; Matsui, Shogo; Kadota, Hisaki; Shimizu, Hideaki; Ohshima, Kiyotaka; Yakushiji, Naoki; Hamada, Mareomi

    2015-01-01

    A 16-year-old boy stayed in Tokyo near Yoyogi Park for extracurricular high school activities. After returning home, he experienced an episode of fever and visited our emergency outpatient unit. He initially exhibited symptoms of leukopenia, thrombocytopenia and concomitant rhabdomyolysis and after admission simultaneously developed a biphasic fever and systemic erythema. Based on the results of reverse transcription polymerase chain reaction testing, he was finally diagnosed with dengue fever. After an absence of 70 years, dengue fever has reemerged as a domestic infection. Awareness of this trend led to our diagnosis.

  16. Rat bite fever without fever.

    PubMed

    Stehle, P; Dubuis, O; So, A; Dudler, J

    2003-09-01

    Rat bite fever is a rarely reported acute febrile bacterial illness caused by Streptobacillus moniliformis or Spirillum minus following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.

  17. Dengue fever (image)

    MedlinePlus

    Dengue fever, or West Nile fever, is a mild viral illness transmitted by mosquitoes which causes fever, ... second exposure to the virus can result in Dengue hemorrhagic fever, a life-threatening illness.

  18. Rat-bite fever

    MedlinePlus

    Streptobacillary fever; Streptobacillosis; Haverhill fever; Epidemic arthritic erythema; Spirillary fever; Sodoku ... Rat-bite fever can be caused by either of 2 different bacteria, Streptobacillus moniliformis or Spirillum minus. Both of these are ...

  19. Neutropenic Fever.

    PubMed

    White, Lindsey; Ybarra, Michael

    2017-12-01

    Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Development and evaluation of loop-mediated isothermal amplification assay for detection of Crimean Congo hemorrhagic fever virus in Sudan.

    PubMed

    Osman, Hana A M; Eltom, Kamal H; Musa, Nasreen O; Bilal, Nasreldin M; Elbashir, Mustafa I; Aradaib, Imadeldin E

    2013-06-01

    Crimean-Congo hemorrhagic fever (CCHF) virus (CCHFV) activity has been detected in Kordufan region of the Sudan in 2008 with high case-fatality rates in villages and rural hospitals in the region. Therefore, in the present study, a reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay was developed and compared to nested RT-PCR for rapid detection of CCHFV targeting the small (S) RNA segment. A set of RT-LAMP primers, designed from a highly conserved region of the S segment of the viral genome, was employed to identify all the Sudanese CCHFV strains. The sensitivity studies indicated that the RT-LAMP detected 10fg of CCHFV RNA as determined by naked eye turbidity read out, which is more likely the way it would be read in a resource-poor setting. This level of sensitivity is good enough to detect most acute cases. Using agarose gel electrophoresis, the RT-LAMP assay detected as little as 0.1fg of viral RNA (equivalent to 50 viral particle). There was 100% agreement between results of the RT-LAMP and the nested PCR when testing 10-fold serial dilution of CCHFV RNA. The specificity studies indicated that there was no cross-reactivity with other related hemorrhagic fever viruses circulating in Sudan including, Rift Valley fever virus (RVFV), Dengue fever virus, and yellow fever virus. The RT-LAMP was performed under isothermal conditions at 63°C and no special apparatus was needed, which rendered the assay more economical and practical than real-time PCR in such developing countries, like Sudan. In addition, the RT-LAMP provides a valuable tool for rapid detection and differentiation of CCHFV during an outbreak of the disease in remote areas and in rural hospitals with resource-poor settings. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Hemorrhagic Fever with Renal Syndrome (Korean Hemorrhagic Fever).

    DTIC Science & Technology

    1986-07-23

    fever , chills, nausea, headache and muscle ache in July 1985. One day after admission he developed petechial haemorrhage over his body and limbs and in...ftOA179 565 NENORNAGIC FEVER WI TH RENAL SYNDOMNE (KOREAN HEMORRHAIC FEVER )(U) KOREN UNIV SEOUL COLL OF MEDICINE N N LEE 23 JUL " DAD7-94-G-4616...34,, , " S , S S .S =. 5 5 . S S S * B M Lfl IC) uIeuCc FVM WITH RENAL SYNDR~OME (KOREAN EMORRHAGIC FEVER ) ANNUAL AND FINAL REPORT S HO WANG LIZB N.D. 5

  2. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

    PubMed Central

    Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary; Kota, Krishna P.; Whitehouse, Chris A.; Bavari, Sina

    2016-01-01

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection. PMID

  3. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase.

    PubMed

    Mudhasani, Rajini; Tran, Julie P; Retterer, Cary; Kota, Krishna P; Whitehouse, Chris A; Bavari, Sina

    2016-02-01

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.

  4. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

    DOE PAGES

    Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary; ...

    2016-02-02

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through anmore » alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.« less

  5. Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase

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

    Mudhasani, Rajini; Tran, Julie P.; Retterer, Cary

    Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)FBXW11 E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through anmore » alternate binding site to the SCFFBXW11 E3 ligase. We further show that disrupting the assembly of the SCFFBXW11-NSs E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCFFBXW11-NSs E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the βTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of βTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCFFBXW11 complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection.« less

  6. Further studies on the role of prostaglandin in fever

    PubMed Central

    Dey, P. K.; Feldberg, W.; Gupta, K. P.; Milton, A. S.; Wendlandt, Sabine

    1974-01-01

    1. Experiments were carried out in unanaesthetized cats to find out if a prostaglandin is the mediator (a) for the long lasting fever which often follows injections of phsyiological salt solutions into the cerebral ventricles or into the cisterna magna, as well as their perfusions through the cerebral ventricles, and (b) for the sodium fever which occurs during a perfusion of the cerebral ventricles with calcium-free artificial c.s.f. A fever mediated by prostaglandin should be accompanied by an increase of prostaglandin activity in cisternal c.s.f., and be abolished or prevented by antipyretics like paracetamol or indomethacin which inhibit prostaglandin synthesis. Both criteria were applied. 2. The fever which follows injections or perfusions of physiological salt solutions appears to be mediated by a prostaglandin of the E series, probably E2 (PGE2) because it was accompanied by increased prostaglandin E-like activity in the c.s.f. and abolished by paracetamol and indomethacin. During the first few days after pre-treatment of the cats with intramuscular chloramphenicol the injections were rarely followed by fever. 3. The fever which occurs during a perfusion with calcium-free artificial c.s.f. appears not to be mediated by prostaglandin, because it was not associated with increased prostaglandin activity in the cisternal effluent, and not prevented by paracetamol or indomethacin, although these antipyretics usually attenuated the fever. 4. A perfusion of the cerebral ventricles with artificial c.s.f. containing calcium in an abnormally high concentration (6·25 mM) brought down fever produced by PGE1, or PGE2, or bacterial pyrogen. PMID:4215879

  7. The Long Valley Caldera GIS database

    USGS Publications Warehouse

    Battaglia, Maurizio; Williams, M.J.; Venezky, D.Y.; Hill, D.P.; Langbein, J.O.; Farrar, C.D.; Howle, J.F.; Sneed, M.; Segall, P.

    2003-01-01

    This database provides an overview of the studies being conducted by the Long Valley Observatory in eastern California from 1975 to 2001. The database includes geologic, monitoring, and topographic datasets related to Long Valley caldera. The CD-ROM contains a scan of the original geologic map of the Long Valley region by R. Bailey. Real-time data of the current activity of the caldera (including earthquakes, ground deformation and the release of volcanic gas), information about volcanic hazards and the USGS response plan are available online at the Long Valley observatory web page (http://lvo.wr.usgs.gov). If you have any comments or questions about this database, please contact the Scientist in Charge of the Long Valley observatory.

  8. [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.

  9. Knowledge, Attitudes and Practices (KAP) on Rift Valley Fever among Pastoralist Communities of Ijara District, North Eastern Kenya

    PubMed Central

    Abdi, Ismail H.; Affognon, Hippolyte D.; Wanjoya, Anthony K.; Onyango-Ouma, Washington; Sang, Rosemary

    2015-01-01

    Outbreaks of Rift Valley fever (RVF), a mosquito-borne viral zoonosis, have previously been associated with unusually heavy rainfall and extensive flooding. The disease is a serious public health problem in Africa and the Middle East, and is a potential global health threat. In Kenya, outbreaks of the disease have disproportionately affected impoverished pastoralist communities. This study sought to assess the knowledge, attitudes and practices (KAP) regarding RVF among the pastoralists of North Eastern Kenya, and to establish the determinants of KAP on RVF. A cross-sectional study involving 392 pastoralists living in Ijara district (Masalani and Ijara wards) was carried out using an interview questionnaire. All respondents interviewed (100%) had heard about RVF disease. They recognized that the disease is dangerous (99%), and had a positive attitude towards vaccination of animals (77%). However, few respondents knew that abortion (11%) and high mortality of young animals (10%) were key signs of RVF in animals. Very few (4%) use any form of protection when handling sick animals to avoid infection. Significant factors associated with knowledge were being in a household with a history of RVF infection (OR = 1.262, 95% CI = 1.099–1.447), having more livestock (OR = 1.285, 95% CI = 1.175–1.404) and the place of residence, Masalani (OR = 0.526, 95% CI = 0.480–0.576). Overall knowledge score on RVF was found to be a significant predictor of good preventive practice of the disease (OR = 1.073, 95% CI = 1.047–1.101). Despite the positive attitude that pastoralist communities have towards the prevention of RVF, there exist gaps in knowledge and good practices on the disease. Therefore there is need for public health education to address these gaps, and to identify and facilitate the removal of barriers to behavioural change related to the prevention of RVF. PMID:26566218

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

    PubMed

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

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that primarily affects ruminants but also has the capacity to infect humans. To determine the abundance and distribution of mosquito vectors in relation to their potential role in the virus transmission and maintenance in disease epidemic areas of Ngorongoro district in northern Tanzania. A cross-sectional entomological investigation was carried out before the suspected RVF outbreak in October 2012. Mosquitoes were sampled both outdoors and indoors using the Centre for Disease Control (CDC) light traps and Mosquito Magnets baited with attractants. Outdoor traps were placed in proximity with breeding sites and under canopy in banana plantations close to the sleeping places of animals. A total of 1,823 mosquitoes were collected, of which 87% (N=1,588) were Culex pipiens complex, 12% (N=226) Aedes aegypti, and 0.5% (N=9) Anopheles species. About two-thirds (67%; N=1,095) of C. pipiens complex and nearly 100% (N=225) of A. aegypti were trapped outdoors using Mosquito Magnets. All Anopheles species were trapped indoors using CDC light traps. There were variations in abundance of C. pipiens complex and A. aegypti among different ecological and vegetation habitats. Over three quarters (78%) of C. pipiens complex and most (85%) of the A. aegypti were trapped in banana and maize farms. Both C. pipiens complex and A. aegypti were more abundant in proximity with cattle and in semi-arid thorn bushes and lower Afro-montane. The highest number of mosquitoes was recorded in villages that were most affected during the RVF epidemic of 2007. Of the tested 150 pools of C. pipiens complex and 45 pools of A. aegypti, none was infected with RVF virus. These results provide insights into unique habitat characterisation relating to mosquito abundances and distribution in RVF epidemic-prone areas of Ngorongoro district in northern Tanzania.

  11. First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region

    PubMed Central

    Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment—EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently

  12. Rift Valley fever MP-12 vaccine Phase 2 clinical trial: Safety, immunogenicity, and genetic characterization of virus isolates.

    PubMed

    Pittman, Phillip R; Norris, Sarah L; Brown, Elizabeth S; Ranadive, Manmohan V; Schibly, Barbara A; Bettinger, George E; Lokugamage, Nandadeva; Korman, Lawrence; Morrill, John C; Peters, Clarence J

    2016-01-20

    An outbreak or deliberate release of Rift Valley fever (RVF) virus could have serious public health and socioeconomic consequences. A safe RVF vaccine capable of eliciting long-lasting immunity after a single injection is urgently needed. The live attenuated RVF MP-12 vaccine candidate has shown promise in Phase 1 clinical trials; no evidence of reversion to virulence has been identified in numerous animal studies. The objective of this Phase 2 clinical trial was to (a) further examine the safety and immunogenicity of RVF MP-12 in RVF virus-naïve humans and (b) characterize isolates of RVF MP-12 virus recovered from the blood of vaccinated subjects to evaluate the genetic stability of MP-12 attenuation. We found that RVF MP-12 was well tolerated, causing mostly mild reactions that resolved without sequelae. Of 19 subjects, 18 (95%) and 19 (100%) achieved, respectively, 80% and 50% plaque reduction neutralization titers (PRNT80 and PRNT50)≥1:20 by postvaccination day 28. All 18 PRNT80 responders maintained PRNT80 and PRNT50≥1:40 until at least postvaccination month 12. Viremia was undetectable in the plasma of any subject by direct plaque assay techniques. However, 5 of 19 vaccinees were positive for MP-12 isolates in plasma by blind passage of plasma on Vero cells. Vaccine virus was also recovered from buffy coat material from one of those vaccinees and from one additional vaccinee. Through RNA sequencing of MP-12 isolates, we found no reversions of amino acids to those of the parent virulent virus (strain ZH548). Five years after a single dose of RVF MP-12 vaccine, 8 of 9 vaccinees (89%) maintained a PRNT80≥1:20. These findings support the continued development of RVF MP-12 as a countermeasure against RVF virus in humans. Published by Elsevier Ltd.

  13. First External Quality Assessment of Molecular and Serological Detection of Rift Valley Fever in the Western Mediterranean Region.

    PubMed

    Monaco, Federica; Cosseddu, Gian Mario; Doumbia, Baba; Madani, Hafsa; El Mellouli, Fatiha; Jiménez-Clavero, Miguel Angel; Sghaier, Soufien; Marianneau, Philippe; Cetre-Sossah, Catherine; Polci, Andrea; Lacote, Sandra; Lakhdar, Magtouf; Fernandez-Pinero, Jovita; Sari Nassim, Chabane; Pinoni, Chiara; Capobianco Dondona, Andrea; Gallardo, Carmina; Bouzid, Taoufiq; Conte, Annamaria; Bortone, Grazia; Savini, Giovanni; Petrini, Antonio; Puech, Lilian

    2015-01-01

    Rift Valley fever (RVF) is a mosquito-borne viral zoonosis which affects humans and a wide range of domestic and wild ruminants. The large spread of RVF in Africa and its potential to emerge beyond its geographic range requires the development of surveillance strategies to promptly detect the disease outbreaks in order to implement efficient control measures, which could prevent the widespread of the virus to humans. The Animal Health Mediterranean Network (REMESA) linking some Northern African countries as Algeria, Egypt, Libya, Mauritania, Morocco, Tunisia with Southern European ones as France, Italy, Portugal and Spain aims at improving the animal health in the Western Mediterranean Region since 2009. In this context, a first assessment of the diagnostic capacities of the laboratories involved in the RVF surveillance was performed. The first proficiency testing (external quality assessment--EQA) for the detection of the viral genome and antibodies of RVF virus (RVFV) was carried out from October 2013 to February 2014. Ten laboratories participated from 6 different countries (4 from North Africa and 2 from Europe). Six laboratories participated in the ring trial for both viral RNA and antibodies detection methods, while four laboratories participated exclusively in the antibodies detection ring trial. For the EQA targeting the viral RNA detection methods 5 out of 6 laboratories reported 100% of correct results. One laboratory misidentified 2 positive samples as negative and 3 positive samples as doubtful indicating a need for corrective actions. For the EQA targeting IgG and IgM antibodies methods 9 out of the 10 laboratories reported 100% of correct results, whilst one laboratory reported all correct results except one false-positive. These two ring trials provide evidence that most of the participating laboratories are capable to detect RVF antibodies and viral RNA thus recognizing RVF infection in affected ruminants with the diagnostic methods currently

  14. The role of endothelial activation in dengue hemorrhagic fever and hantavirus pulmonary syndrome.

    PubMed

    Spiropoulou, Christina F; Srikiatkhachorn, Anon

    2013-08-15

    The loss of the endothelium barrier and vascular leakage play a central role in the pathogenesis of hemorrhagic fever viruses. This can be caused either directly by the viral infection and damage of the vascular endothelium, or indirectly by a dysregulated immune response resulting in an excessive activation of the endothelium. This article briefly reviews our knowledge of the importance of the disruption of the vascular endothelial barrier in two severe disease syndromes, dengue hemorrhagic fever and hantavirus pulmonary syndrome. Both viruses cause changes in vascular permeability without damaging the endothelium. Here we focus on our understanding of the virus interaction with the endothelium, the role of the endothelium in the induced pathogenesis, and the possible mechanisms by which each virus causes vascular leakage. Understanding the dynamics between viral infection and the dysregulation of the endothelial cell barrier will help us to define potential therapeutic targets for reducing disease severity.

  15. The Pinjaur dun (intermontane longitudinal valley) and associated active mountain fronts, NW Himalaya: Tectonic geomorphology and morphotectonic evolution

    NASA Astrophysics Data System (ADS)

    Singh, Vimal; Tandon, S. K.

    2008-12-01

    The Himalayan orogenic belt, formed as a result of collision tectonic processes, shows abundant evidence of neotectonic activity, active tectonics, and the occurrence of historical earthquakes. Its frontal deformation zone is characterized, in some segments, by intermontane longitudinal valleys (duns). Such frontal segments of the Himalaya are marked by the occurrence of multiple mountain fronts. In one such segment of the foothills of the NW Himalaya, the Pinjaur dun is developed and marked by three mountain fronts: MF1A and MF1B associated with the southernmost Himalayan Frontal Thrust (HFT), MF2 associated with the Sirsa fault, and MF3 associated with the Barsar thrust along the southern margin of the relatively higher main part of the sub-Himalaya. Geomorphic responses to the tectonic activity of these and related structural features have been analyzed through the use of geomorphic indices, drainage density, stream longitudinal profiles, drainage anomalies, and hypsometric analysis. Also, fault and fold growth and their expression on landform development was studied using a combination of surface profiles and field observations. The values of valley floor width to height ratio ( Vf) for valleys associated with MF1 ranged between 0.07 and 0.74, and for valleys associated with MF2 ranged from 1.02-5.12. Vf for the four major valleys associated with MF1B ranged from 1.1-1.7. The asymmetry factor for 26 drainage basins related to MF1A indicate these have developed under the influence of a transverse structure. These results taken together with those obtained from the Hack profiles and SL index values, hypsometry, drainage density, and drainage anomalies suggest that the faults associated with the mountain fronts and related structures are active. Active tectonics and neotectonic activity have led to the formation of four surfaces in the Pinjaur dun. In addition, an important drainage divide separating the Sirsa and Jhajara drainage networks also developed in the

  16. Present and Future of Dengue Fever in Nepal: Mapping Climatic Suitability by Ecological Niche Model

    PubMed Central

    Cao, Chunxiang; Xu, Min; Pandit, Shreejana

    2018-01-01

    Both the number of cases of dengue fever and the areas of outbreaks within Nepal have increased significantly in recent years. Further expansion and range shift is expected in the future due to global climate change and other associated factors. However, due to limited spatially-explicit research in Nepal, there is poor understanding about the present spatial distribution patterns of dengue risk areas and the potential range shift due to future climate change. In this context, it is crucial to assess and map dengue fever risk areas in Nepal. Here, we used reported dengue cases and a set of bioclimatic variables on the MaxEnt ecological niche modeling approach to model the climatic niche and map present and future (2050s and 2070s) climatically suitable areas under different representative concentration pathways (RCP2.6, RCP6.0 and RCP8.5). Simulation-based estimates suggest that climatically suitable areas for dengue fever are presently distributed throughout the lowland Tarai from east to west and in river valleys at lower elevations. Under the different climate change scenarios, these areas will be slightly shifted towards higher elevation with varied magnitude and spatial patterns. Population exposed to climatically suitable areas of dengue fever in Nepal is anticipated to further increase in both 2050s and 2070s on all the assumed emission scenarios. These findings could be instrumental to plan and execute the strategic interventions for controlling dengue fever in Nepal. PMID:29360797

  17. Protection against Rift Valley fever virus infection in mice upon administration of interferon-inducing RNA transcripts from the FMDV genome.

    PubMed

    Lorenzo, Gema; Rodríguez-Pulido, Miguel; López-Gil, Elena; Sobrino, Francisco; Borrego, Belén; Sáiz, Margarita; Brun, Alejandro

    2014-09-01

    In this work we have addressed the effect of synthetic, non-infectious, RNA transcripts, mimicking structural domains of the non-coding regions (NCRs) of the foot-and-mouth disease virus (FMDV) genome on the infection of mice with Rift Valley fever virus (RVFV). Groups of 5 mice were inoculated intraperitoneally (i.p.) with 200 μg of synthetic RNA resembling the 5'-terminal S region, the internal ribosome entry site (IRES) or the 3'-NCR of the FMDV genome. RNA inoculation was performed 24h before (-24 h), 24 h after (+24 h) or simultaneously to the challenge with a lethal dose of RVFV. Administration of the IRES RNA afforded higher survival rates than administration of S or 3'NCR transcripts either at -24h or +24h after challenge. In contrast, when RNA inoculation and viral challenge were performed simultaneously, all mice survived in both IRES- and 3'NCR-inoculated groups, with an 80% survival in mice receiving the S RNA. Among survivors, a complete correlation between significant anti-RVFV circulating antibody titers and resistance to a second lethal challenge with the virus was observed, supporting a limited viral replication in the RNA-inoculated animals upon the first challenge. All three RNA transcripts were able to induce the production of systemic antiviral and pro-inflammatory cytokines. These data show that triggering of intracellular pathogen sensing pathways constitutes a promising approach towards development of novel RVF preventive or therapeutic strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. The first serological evidence for Rift Valley fever infection in the camel, goitered gazelle and Anatolian water buffaloes in Turkey.

    PubMed

    Gür, Sibel; Kale, Mehmet; Erol, Nural; Yapici, Orhan; Mamak, Nuri; Yavru, Sibel

    2017-10-01

    Rift valley fever (RVF), a vector-borne zoonotic disease, is caused by a phlebovirus (family Bunyaviridae). The virus was initially characterized approximately 80 years ago in Kenya and disseminated to many countries in the continental Africa, Saudi Arabia, and Yemen. The infection has not been reported in Turkey. In this study, blood serum samples collected from camel (Camelus dromedairus), goitered gazelle (Gazella subgutturosa subgutturosa), and buffaloes (Bubalus bubalis linneaus) from 2000 to 2006 were investigated for RVF using C-ELISA. Camel samples (n = 72) were obtained from private small enterprises in Aydın province in theAegean region. Gazella samples (82) were taken from the biggest captive gazelle herd in Şanlıurfa province in the southeast Anatolia. Buffalo samples were collected mostly from small private family type farms in Afyon (168), Amasya (80), Samsun (69), Ankara (35), Sivas (21), Tokat (19), Konya (10), and Elazığ (8) provinces in the central, north, west, and east Anatolia. All of the gazella samples were negative; whereas, one of the 71 camel samples (1.3%) was positive for RVF-specific antibodies. Buffalos from Sivas, Tokat, Konya, and Elazığ provinces were negative. However, 35 of the 410 samples (8.5%) from rural areas in the following four provinces were positive: Amasya (12/80, 15%), Ankara (5/35, 14.2%), Samsun (8/69, 11.5%), and Afyon (10/168, 5.9%). To our knowledge, this is the first report of presence of RVF infection in Turkey.

  19. Landslide activity as a threat to infrastructure in river valleys - An example from outer Western Carpathians (Poland)

    NASA Astrophysics Data System (ADS)

    Łuszczyńska, Katarzyna; Wistuba, Małgorzata; Malik, Ireneusz

    2017-11-01

    Intensive development of the area of Polish Carpathians increases the scale of landslide risk. Thus detecting landslide hazards and risks became important issue for spatial planning in the area. We applied dendrochronological methods and GIS analysis for better understanding of landslide activity and related hazards in the test area (3,75 km2): Salomonka valley and nearby slopes in the Beskid Żywiecki Mts., Outer Western Carpathians, southern Poland. We applied eccentricity index of radial growth of trees to date past landslide events. Dendrochronological results allowed us to determine the mean frequency of landsliding at each sampling point which were next interpolated into a map of landslide hazard. In total we took samples at 46 points. In each point we sampled 3 coniferous trees. Landslide hazard map shows a medium (23 sampling points) and low (20 sampling points) level of landslide activity for most of the area. The highest level of activity was recorded for the largest landslide. Results of the dendrochronological study suggest that all landslides reaching downslope to Salomonka valley floor are active. LiDAR-based analysis of relief shows that there is an active coupling between those landslides and river channel. Thus channel damming and formation of an episodic lake are probable. The hazard of flooding valley floor upstream of active landslides should be included in the local spatial planning system and crisis management system.

  20. 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.