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Afshar Moghaddam N, Yekanipour Z, Akbarzadeh S, Molavi Nia S, Abarghooi Kahaki F, Kalantar MH, Gholizadeh O. Recent advances in treatment and detection of Rift Valley fever virus: a comprehensive overview. Virus Genes 2025:10.1007/s11262-025-02164-0. [PMID: 40348846 DOI: 10.1007/s11262-025-02164-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 04/28/2025] [Indexed: 05/14/2025]
Abstract
Rift Valley fever virus (RVFV) is a newly discovered arboviral pathogen that infects humans and livestock. Numerous outbreaks have occurred in Africa and the Arab Peninsula. Epizootics of RVFV are sporadic and frequently associated with ongoing floods and excessive rainfall. This leads to the development of infected Aedes mosquitoes, which then amplify transmission by other mosquito species (like Anopheles and Culex genera). In animals, it typically results in high rates of death and abortion. In humans, Rift Valley fever (RVF) manifests as clinical symptoms that may vary in intensity from minor to severe. Common symptoms include retinitis, hepatitis, delayed onset encephalitis, and hemorrhagic illness. The possibilities for containing RVFV outbreaks are limited due to the lack of authorized human vaccinations and treatments. Although molecular detection techniques are available, they can only recognize viral nucleic acids during the short viremic phase. There are currently no specific treatments for RVFV infection. Ribavirin is one of the few therapies for viral hemorrhagic fevers, but severe adverse effects restrict its use. Significant studies have been done in recent years on using Nanotechnology to diagnose and treat viruses. This review summarizes the common and recent diagnostic and therapeutic approaches for RVFV, including nanoparticles, intravenous immunoglobulin (IVIG), stem cells, vaccines, and antibody-based therapies.
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Affiliation(s)
| | - Zahra Yekanipour
- Microbiology, Department of Microbiology, Marand Branch, Islamic Azad University, Marand, Iran
| | - Sama Akbarzadeh
- Institute of Graduate Studies in Health Sciences, Istanbul University, Istanbul, Türkiye
- Department of Biophysics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Sahar Molavi Nia
- Department of Medical Mycology, Faculty of Medical Sciences, Jundishapur University of Medical Sciences, Ahwaz, Iran
| | - Fatemeh Abarghooi Kahaki
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Zhao C, Hao M, Bian T, Zhao X, Chi X, Chen Z, Fu G, Zhu Z, Fang T, Yu C, Li J, Chen W. Screening of Neutralizing Antibodies Targeting Gc Protein of RVFV. Viruses 2025; 17:559. [PMID: 40285002 PMCID: PMC12031069 DOI: 10.3390/v17040559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/29/2025] Open
Abstract
Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that can cause substantial morbidity and mortality in livestock and humans, for which there are no currently available licensed human therapeutics or vaccines. Therefore, the development of safe and effective antivirals is both necessary and urgent. The Gc protein is the primary target of the neutralizing antibody response related to Rift Valley fever virus. Here, we report one Gc-specific neutralizing antibody (NA137) isolated from an alpaca and one bispecific antibody (E2-NA137), the protective efficacies of which we evaluated in A129 mice. In this prophylactic study, the survival rates of the NA137 and E2-NA137 groups were both 80%, and in the treatment study, the survival rates were 20% and 60%, respectively. Altogether, our results emphasize that NA137 and E2-NA137 provide a potential approach for treating RVFV either prophylactically or therapeutically.
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Affiliation(s)
- Chuanyi Zhao
- School of Medicine, Zhejiang University, Hangzhou 310058, China;
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Meng Hao
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Ting Bian
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Xiaofan Zhao
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Xiangyang Chi
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Zhengshan Chen
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Guangcheng Fu
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Zheng Zhu
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Ting Fang
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Changming Yu
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Jianmin Li
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
| | - Wei Chen
- School of Medicine, Zhejiang University, Hangzhou 310058, China;
- Laboratory of Advanced Biotechnology, Beijing Institute of Biotechnology, Beijing 100071, China; (M.H.); (T.B.); (X.Z.); (X.C.); (Z.C.); (G.F.); (Z.Z.); (T.F.); (C.Y.)
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Mwacalimba K, Kimeli P, Tiernan R, Mijten E, Miroshnychenko T, Poulsen Nautrup B. Diseases of Economic Importance in Feedlot Cattle in Sub-Saharan Africa: A Review with a Focus on Existing and Potential Options for Control. Animals (Basel) 2025; 15:97. [PMID: 39795040 PMCID: PMC11718847 DOI: 10.3390/ani15010097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/24/2024] [Accepted: 12/28/2024] [Indexed: 01/13/2025] Open
Abstract
A large number of livestock are found in sub-Saharan Africa (SSA), including 20-25% of the world's ruminants [...].
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Affiliation(s)
| | - Peter Kimeli
- Department of Clinical Studies, Faculty of Veterinary Medicine, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya;
| | | | - Erik Mijten
- Zoetis Belgium S.A., 1930 Zaventem, Belgium; (E.M.); (T.M.)
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Berguido FJ, Settypalli TBK, Mbuyi CGT, Bakhom MT, van Vuren PJ, Pawęska JT, Cattoli G, Grabherr R, Lamien CE. Development of a luminex-based assay for the detection of anti-capripoxvirus and rift valley fever virus antibodies in domestic ruminants. Virol J 2024; 21:335. [PMID: 39726039 PMCID: PMC11674245 DOI: 10.1186/s12985-024-02602-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/09/2024] [Indexed: 12/28/2024] Open
Abstract
The three members of the genus capripoxvirus (CaPV), lumpy skin disease virus (LSDV), sheeppox virus (SPPV), and goatpox virus (GTPV) have common hosts and areas of overlapping geographical distribution with Rift Valley fever virus (RVFV). Hence, to ensure more cost-effective disease surveillance we developed and evaluated a Luminex assay for the simultaneous detection of antibodies against CaPV and RVFV in domestic ruminants. In cattle, the assay had a sensitivity (Se) of 98.7% and a specificity (Sp) of 98.3% in detecting anti-LSDV antibodies; both diagnostic parameters were 100% for the detection of anti-RVFV antibodies in this species. In sheep and goats, Se and Sp were 100% for the detection of anti-SPPV and anti-GTPV antibodies while they were 100% and 98.9%, respectively for the detection of anti-RVFV antibody. The assay did not cross react with anti-parapoxvirus antibodies of cattle, sheep, and goats. This multiplex serological assay offers a practical tool for accurate detection and monitoring of the immunological status of domestic ruminant populations against veterinary and socio-economically important capripox- and phleboviral infections, thus has the potential to aid in the strategic application of vaccination programmes.
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Affiliation(s)
- Francisco J Berguido
- Animal Production and Health Laboratory, Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
- Institute of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse18, 1190, Vienna, Austria.
| | - Tirumala Bharani Kumar Settypalli
- Animal Production and Health Laboratory, Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | | | - Mame Thierno Bakhom
- Laboratoire National de L'Elevage et de Recherches Vétérinaires, Institut Sénégalais de Recherches Agricoles (ISRA), Dakar, Sénégal
| | - Petrus Jansen van Vuren
- Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, Johannesburg, 2131, South Africa
- Australian Centre for Disease Preparedness, Australian Animal Health Laboratory, CSIRO, Geelong, Australia
| | - Janusz T Pawęska
- Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham, Johannesburg, 2131, South Africa
| | - Giovanni Cattoli
- Animal Production and Health Laboratory, Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Reingard Grabherr
- Institute of Biotechnology, University of Natural Resources and Life Sciences (BOKU), Muthgasse18, 1190, Vienna, Austria
| | - Charles Euloge Lamien
- Animal Production and Health Laboratory, Joint FAO/IAEA Centre of Nuclear Techniques in Food and Agriculture, Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
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Onwongá AA, Oyola SO, Juma J, Konongoi S, Nyamota R, Mwangi R, Muli C, Dobi P, Bett BB, Ongus JR. Genome characterization of Rift Valley fever virus isolated from cattle, goats and sheep during interepidemic periods in Kenya. BMC Vet Res 2024; 20:376. [PMID: 39180076 PMCID: PMC11342565 DOI: 10.1186/s12917-024-04161-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2023] [Accepted: 06/26/2024] [Indexed: 08/26/2024] Open
Abstract
Rift Valley fever virus (RVFV) is a mosquito-borne RNA virus of the Phlebovirus genus in the phenuviridae family. Its genome is trisegmented with small (S), medium (M) and large (L) fragments. In nature, the virus exists as a single serotype that is responsible for outbreaks of Rift Valley fever (RVF), a zoonotic disease that often occurs in Africa and the Middle East. RVFV genomes are thought to undergo both recombination and reassortment and investigations of these events is important for monitoring the emergence of virulent strains and understanding the evolutionary characteristics of this virus. The aim of this study was to characterize the genomes of RVFV isolates from cattle, sheep, and goats collected during an interepidemic period in Kenya between June 2016 and November 2021. A total of 691 serum samples from cattle (n = 144), goats (n = 185) and sheep (n = 362) were analysed at the Central Veterinary Laboratories. The competitive IgM-capture ELISA, was used to screen the samples; 205 samples (29.67%) tested positive for RVFV. Of the 205 positive samples, 42 (20.5%) were from cattle, 57 (27.8%) from goats, and 106 (51.7%) from sheep. All the IgM-positive samples were further analyzed by qPCR, and 24 (11.71%) tested positive with Ct values ranging from 14.788 to 38.286. Two samples, 201808HABDVS from sheep and 201810CML3DVS from cattle, had Ct values of less than 20.0 and yielded whole genome sequences with 96.8 and 96.4 coverage, respectively. There was no statistically significant evidence of recombination in any of the three segments and also phylogenetic analysis showed no evidence of reassortment in the two isolated RVFV segments when compared with other isolates of different lineages from previous outbreaks whose genomes are deposited in the GenBank. No evidence of reassortment leaves room for other factors to be the most probable contributors of change in virulence, pathogenicity and emergence of highly virulent strains of the RVFV.
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Affiliation(s)
- Amos A Onwongá
- Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya.
- Department of Veterinary Services, Ministry of Agriculture Livestock and Fisheries, Nairobi, Kenya.
| | - Samuel O Oyola
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - John Juma
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | | | - Richard Nyamota
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - Reuben Mwangi
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - Collins Muli
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - Paul Dobi
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - Bernard B Bett
- International Livestock Research Institute (ILRI), Nairobi, Kenya
| | - Juliette R Ongus
- Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya
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Islam MR, Ahmed I, Urmi TJ. The pathogenicity and risk evaluation of Rift Valley virus to cause mysterious "Disease X": an update on recent evidences. Ann Med Surg (Lond) 2024; 86:1243-1246. [PMID: 38463056 PMCID: PMC10923333 DOI: 10.1097/ms9.0000000000001680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/24/2023] [Indexed: 03/12/2024] Open
Affiliation(s)
| | - Iftekhar Ahmed
- Department of Pharmacy, University of Asia Pacific, Farmgate, Dhaka, Bangladesh
| | - Taslima Jamal Urmi
- Department of Pharmacy, University of Asia Pacific, Farmgate, Dhaka, Bangladesh
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Bob NS, Dia M, Ndiaye O, Ba A, Prudhomme J, Diagne MM, Faye O, Faye O, Sall AA, Fall G. Detection and Diagnosis of Rift Valley Fever Virus. Methods Mol Biol 2024; 2824:35-65. [PMID: 39039405 DOI: 10.1007/978-1-0716-3926-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/24/2024]
Abstract
Rift Valley fever virus (RVFV) is a globally important mosquito-borne virus that can also be directly transmitted via aerosolization of body fluids from infected animals. RVFV outbreaks cause mass mortality of young livestock and abortions in animals. In most severe human cases, the disease can progress to hemorrhagic fever and encephalitis, leading to death. RVF has a significant economic impact due to the loss of livestock that is a great challenge for people who depend on animals for income and food. Several vaccines are available for animal use, but none are yet licensed for use in human populations. This situation emphasizes the need to have robust and efficient diagnostic methods that can be used for early case confirmation, assessment of seroprevalence, and virus surveillance as well as vaccine efficacy evaluation. Despite the existence of different diagnostic methods for RVFV, we still have untimely reporting or underreporting of cases, probably due to lack of appropriate surveillance systems or diagnostic tools in some endemic countries. Here, we describe different methods available for detection and diagnosis of RVFV.
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Affiliation(s)
- Ndeye Sakha Bob
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Moussa Dia
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Oumar Ndiaye
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Arame Ba
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Julie Prudhomme
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
- Pays de la Loire Regional Office, Santé Publique France, The French National Public Health Agency, Nantes, France
| | - Moussa Moise Diagne
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Oumar Faye
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Ousmane Faye
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Amadou Alpha Sall
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal
| | - Gamou Fall
- Virology Pole-WHO collaborating Center for Arbovirus and viral hemorrhagic fevers, Institut Pasteur de Dakar, Dakar, Senegal.
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Marzok M, Alkashif K, Kandeel M, Salem M, Sayed-Ahmed MZ, Selim A. Seroprevalence of Rift Valley Fever virus in one-humped camels (Camelus dromedaries) in Egypt. Trop Anim Health Prod 2023; 55:345. [PMID: 37789189 DOI: 10.1007/s11250-023-03765-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 09/12/2023] [Indexed: 10/05/2023]
Abstract
Rift Valley fever (RVF) is a mosquito-borne viral disease that affects a variety of domestic animals, including cattle, sheep, goats, and camels, and has zoonotic potential. Although the rift valley fever virus (RVFV) is usually asymptomatic in camels, it can induce abortion in some pregnant animals. In the current study, a serosurvey was carried out to investigate the prevalence of RVFV antibodies and related risk factors in camels from four Egyptian governorates. A total of 400 serum samples were examined for anti-RVFV antibodies using a competitive enzyme-linked immunosorbent assay (c-ELISA). The results revealed that the overall prevalence of RVF among examined camels was 21.5% and the disease was more prevalent in Kafr ElSheikh governorate in Nile Delta of Egypt. In addition, the age group of camels with more than 5 years (OR=4.49, 95%CI: 1.39-14.49), the female sex (OR=3.38, 95%CI: 1.51-7.58), the emaciated animals (OR=1.52, 95%CI: 0.86-2.66), the summer season's infection (OR=5.98, 95%CI: 1.79-19.93), the presence of mosquitoes (OR= 2.88, 95%CI: 1.39-5.95), and the absence of mosquitoes control (OR=3.97, 95%CI: 2.09-7.57) were identified as risk factors for RVFV infection. The results of this study support knowledge on the risk factors for RVFV infection and demonstrate that camels raising in Egypt have RVFV antibodies. Quarantine measures or vaccination program should be implemented to reduce the likelihood of RVFV introduction, dissemination among susceptible animals, and ultimately transmission to humans.
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Affiliation(s)
- Mohamed Marzok
- Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, 31982, Saudi Arabia.
- Department of Surgery, Faculty of Veterinary Medicine, Kafr El Sheikh University, Kafr El Sheikh, Egypt.
| | - Khalid Alkashif
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, 82722, Saudi Arabia
| | - Mahmoud Kandeel
- Department of Pharmacology, Faculty of Veterinary Medicine, Kafr elsheikh University, Kafrelsheikh, Egypt
- Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mohamed Salem
- Department of Clinical Pharmacy, College of Pharmacy, Jazan University, Jazan, 45142, Saudi Arabia
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Cairo, 12613, Egypt
| | - Mohamed Z Sayed-Ahmed
- Department of Internal Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt
- Department of Animal Medicine (Infectious Diseases), Faculty of Veterinary Medicine, Benha University, Toukh, 13736, Egypt
| | - Abdelfattah Selim
- Department of Animal Medicine (Infectious Diseases), Faculty of Veterinary Medicine, Benha University, Toukh, 13736, Egypt.
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Nair N, Osterhaus ADME, Rimmelzwaan GF, Prajeeth CK. Rift Valley Fever Virus-Infection, Pathogenesis and Host Immune Responses. Pathogens 2023; 12:1174. [PMID: 37764982 PMCID: PMC10535968 DOI: 10.3390/pathogens12091174] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/09/2023] [Accepted: 09/14/2023] [Indexed: 09/29/2023] Open
Abstract
Rift Valley Fever Virus is a mosquito-borne phlebovirus causing febrile or haemorrhagic illness in ruminants and humans. The virus can prevent the induction of the antiviral interferon response through its NSs proteins. Mutations in the NSs gene may allow the induction of innate proinflammatory immune responses and lead to attenuation of the virus. Upon infection, virus-specific antibodies and T cells are induced that may afford protection against subsequent infections. Thus, all arms of the adaptive immune system contribute to prevention of disease progression. These findings will aid the design of vaccines using the currently available platforms. Vaccine candidates have shown promise in safety and efficacy trials in susceptible animal species and these may contribute to the control of RVFV infections and prevention of disease progression in humans and ruminants.
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Rishi E, Thomas J, Fashina T, Kim L, Yeh S. Emerging Pathogenic Viral Infections of the Eye. Annu Rev Vis Sci 2023; 9:71-89. [PMID: 37018917 DOI: 10.1146/annurev-vision-100820-010504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
Global health security threats and the public health impact resulting from emerging infectious diseases including the ongoing COVID-19 pandemic and recent Ebola virus disease outbreaks continuously emphasize the need for a comprehensive approach to preparedness, management of disease outbreaks, and health sequelae associated with emergent pathogens. A spectrum of associated ophthalmic manifestations, along with the potential persistence of emerging viral pathogens in ocular tissues, highlight the importance of an ophthalmic approach to contributing to efforts in the response to public health emergencies from disease outbreaks. This article summarizes the ophthalmic and systemic findings, epidemiology, and therapeutics for emerging viral pathogens identified by the World Health Organization as high-priority pathogens with epidemic potential.
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Affiliation(s)
- Ekta Rishi
- Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA; , ,
| | | | - Tolulope Fashina
- Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA; , ,
| | - Lucas Kim
- Mercer University School of Medicine, Augusta, Georgia, USA;
| | - Steven Yeh
- Department of Ophthalmology and Visual Sciences, Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA; , ,
- Global Center for Health Security, University of Nebraska Medical Center, Omaha, Nebraska, USA
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Lapa D, Specchiarello E, Francalancia M, Girardi E, Maggi F, Garbuglia AR. Detection of Anti-Rift Valley Fever Virus Antibodies in Serum Samples of Patients with Suspected Arbovirus Infection. Microorganisms 2023; 11:2081. [PMID: 37630641 PMCID: PMC10460000 DOI: 10.3390/microorganisms11082081] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/11/2023] [Accepted: 08/12/2023] [Indexed: 08/27/2023] Open
Abstract
The definitive diagnosis of the Rift Valley fever virus (RVFV) requires a form of testing that is available only in reference laboratories. It includes indirect immunofluorescence assay (IFA), the serum neutralization assay (NA), and real-time PCR. Therefore, often, no attempts are made to detect it, even among travelers from endemic areas. In this study, the presence of anti-RVFV IgG and IgM was retrospectively screened in stored serum samples from people who were admitted with arbovirus symptoms at the National Institute for Infectious Diseases (INMI) L. Spallanzani, Rome, Italy. Overall, 80 residual serum samples were anonymized, and sub-aliquots were prepared and tested for anti-RVFV IgG and IgM. A serum neutralization assay was used as a confirmatory test. There was a positive result in eight out of 80 samples (10%) for anti-RVFV IgG, with titers ranging from 1:40 up to 1:1280. Three of eight (2.6%) samples were confirmed as seropositive through an in-house serum neutralization assay, with antibody titers ranging from 1:10 to 1:160. All samples resulted negative for anti-RVFV IgM and RVFV RNA when tested by IFA and real-time RT-PCR, respectively. Our data highlight that several RVFV infections can possibly escape routine virological diagnosis, which suggests RVFV testing should be set up in order to monitor virus prevalence.
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Affiliation(s)
- Daniele Lapa
- Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy; (E.S.); (M.F.); (F.M.); (A.R.G.)
| | - Eliana Specchiarello
- Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy; (E.S.); (M.F.); (F.M.); (A.R.G.)
| | - Massimo Francalancia
- Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy; (E.S.); (M.F.); (F.M.); (A.R.G.)
| | - Enrico Girardi
- Scientific Direction, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy;
| | - Fabrizio Maggi
- Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy; (E.S.); (M.F.); (F.M.); (A.R.G.)
| | - Anna Rosa Garbuglia
- Laboratory of Virology, National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), 00149 Rome, Italy; (E.S.); (M.F.); (F.M.); (A.R.G.)
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12
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Ayaz Kök S, Üstün S, Taşkent Sezgin H. Diagnosis of Ruminant Viral Diseases with Loop-Mediated Isothermal Amplification. Mol Biotechnol 2023; 65:1228-1241. [PMID: 36719638 PMCID: PMC9888337 DOI: 10.1007/s12033-023-00674-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/16/2023] [Indexed: 02/01/2023]
Abstract
Infectious diseases in livestock industry are major problems for animal health, food safety, and the economy. Zoonotic diseases from farm animals are significant threat to human population as well. These are notifiable diseases listed by the World Organization for Animal Health (OIE). Rapid diagnostic methods can help keep infectious diseases under control in herds. Loop-mediated isothermal amplification (LAMP) is a simple and rapid nucleic acid amplification method that is studied widely for detection of many infectious diseases in the field. LAMP allows biosensing of target DNA or RNA under isothermal conditions with high specificity in a short period of time. An untrained user can analyze results based on color change or turbidity. Here we review LAMP assays to diagnose OIE notifiable ruminant viral diseases in literature highlighting properties of LAMP method considering what is expected from an efficient, field usable diagnostic test.
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Affiliation(s)
- Sanem Ayaz Kök
- Biotechnology Interdisciplinary Program, İzmir Institute of Technology, Gülbahçe, Urla, İzmir, Turkey, 35430
- New Era Biotechnology, Teknopark İzmir, Gülbahçe, Urla, İzmir, Turkey, 35430
| | - Selcen Üstün
- Bioengineering Department, İzmir Institute of Technology, Gülbahçe, Urla, İzmir, Turkey, 35430
| | - Hümeyra Taşkent Sezgin
- Biotechnology Interdisciplinary Program, İzmir Institute of Technology, Gülbahçe, Urla, İzmir, Turkey, 35430.
- New Era Biotechnology, Teknopark İzmir, Gülbahçe, Urla, İzmir, Turkey, 35430.
- Bioengineering Department, İzmir Institute of Technology, Gülbahçe, Urla, İzmir, Turkey, 35430.
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13
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Perdiguero B, Pérez P, Marcos-Villar L, Albericio G, Astorgano D, Álvarez E, Sin L, Elena Gómez C, García-Arriaza J, Esteban M. Highly attenuated poxvirus-based vaccines against emerging viral diseases. J Mol Biol 2023:168173. [PMID: 37301278 DOI: 10.1016/j.jmb.2023.168173] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/04/2023] [Accepted: 06/05/2023] [Indexed: 06/12/2023]
Abstract
Although one member of the poxvirus family, variola virus, has caused one of the most devastating human infections worldwide, smallpox, the knowledge gained over the last 30 years on the molecular, virological and immunological mechanisms of these viruses has allowed the use of members of this family as vectors for the generation of recombinant vaccines against numerous pathogens. In this review, we cover different aspects of the history and biology of poxviruses with emphasis on their application as vaccines, from first- to fourth-generation, against smallpox, monkeypox, emerging viral diseases highlighted by the World Health Organization (COVID-19, Crimean-Congo haemorrhagic fever, Ebola and Marburg virus diseases, Lassa fever, Middle East respiratory syndrome and severe acute respiratory syndrome, Nipah and other henipaviral diseases, Rift Valley fever and Zika), as well as against one of the most concerning prevalent virus, the Human Immunodeficiency Virus, the causative agent of AcquiredImmunodeficiency Syndrome. We discuss the implications in human health of the 2022 monkeypox epidemic affecting many countries, and the rapid prophylactic and therapeutic measures adopted to control virus dissemination within the human population. We also describe the preclinical and clinical evaluation of the Modified Vaccinia virus Ankara and New York vaccinia virus poxviral strains expressing heterologous antigens from the viral diseases listed above. Finally, we report different approaches to improve the immunogenicity and efficacy of poxvirus-based vaccine candidates, such as deletion of immunomodulatory genes, insertion of host-range genes and enhanced transcription of foreign genes through modified viral promoters. Some future prospects are also highlighted.
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Affiliation(s)
- Beatriz Perdiguero
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Patricia Pérez
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.
| | - Laura Marcos-Villar
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Guillermo Albericio
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - David Astorgano
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain
| | - Enrique Álvarez
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Laura Sin
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Carmen Elena Gómez
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Juan García-Arriaza
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Mariano Esteban
- Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
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14
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Yadav M, Dahiya N, Sehrawat N. Mosquito gene targeted RNAi studies for vector control. Funct Integr Genomics 2023; 23:180. [PMID: 37227504 PMCID: PMC10211311 DOI: 10.1007/s10142-023-01072-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/26/2023]
Abstract
Vector-borne diseases are serious public health concern. Mosquito is one of the major vectors responsible for the transmission of a number of diseases like malaria, Zika, chikungunya, dengue, West Nile fever, Japanese encephalitis, St. Louis encephalitis, and yellow fever. Various strategies have been used for mosquito control, but the breeding potential of mosquitoes is such tremendous that most of the strategies failed to control the mosquito population. In 2020, outbreaks of dengue, yellow fever, and Japanese encephalitis have occurred worldwide. Continuous insecticide use resulted in strong resistance and disturbed the ecosystem. RNA interference is one of the strategies opted for mosquito control. There are a number of mosquito genes whose inhibition affected mosquito survival and reproduction. Such kind of genes could be used as bioinsecticides for vector control without disturbing the natural ecosystem. Several studies have targeted mosquito genes at different developmental stages by the RNAi mechanism and result in vector control. In the present review, we included RNAi studies conducted for vector control by targeting mosquito genes at different developmental stages using different delivery methods. The review could help the researcher to find out novel genes of mosquitoes for vector control.
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Affiliation(s)
- Mahima Yadav
- Department of Genetics, Maharshi Dayanand University, Rohtak, Haryana India
| | - Nisha Dahiya
- Department of Genetics, Maharshi Dayanand University, Rohtak, Haryana India
| | - Neelam Sehrawat
- Department of Genetics, Maharshi Dayanand University, Rohtak, Haryana India
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15
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Bastard J, Durand GA, Parenton F, Hassani Y, Dommergues L, Paireau J, Hozé N, Ruello M, Grard G, Métras R, Noël H. Reconstructing Mayotte 2018-19 Rift Valley Fever outbreak in humans by combining serological and surveillance data. COMMUNICATIONS MEDICINE 2022; 2:163. [PMID: 36543938 PMCID: PMC9772320 DOI: 10.1038/s43856-022-00230-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Accepted: 12/12/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Rift Valley Fever (RVF) is a zoonosis that affects large parts of Africa and the Arabian Peninsula. RVF virus (RVFV) is transmitted to humans through contacts with infected animals, animal products, mosquito bites or aerosols. Its pathogenesis in humans ranges from asymptomatic forms to potentially deadly haemorrhagic fevers, and the true burden of human infections during outbreaks is generally unknown. METHODS We build a model fitted to both passive surveillance data and serological data collected throughout a RVF epidemic that occurred in Mayotte Island in 2018-2019. RESULTS We estimate that RVFV infected 10,797 (95% CrI 4,728-16,127) people aged ≥15 years old in Mayotte during the entire outbreak, among which only 1.2% (0.67%-2.2%) were reported to the syndromic surveillance system. RVFV IgG seroprevalence in people ≥15 years old was estimated to increase from 5.5% (3.6%-7.7%) before the outbreak to 12.9% (10.4%-16.3%) thereafter. CONCLUSIONS Our results suggest that a large part of RVFV infected people present subclinical forms of the disease and/or do not reach medical care that could lead to their detection by the surveillance system. This may threaten the implementation of exhaustive RVF surveillance and adequate control programs in affected countries.
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Affiliation(s)
- Jonathan Bastard
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France
| | - Guillaume André Durand
- grid.476258.aFrench Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France ,grid.5399.60000 0001 2176 4817Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Fanny Parenton
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France
| | - Youssouf Hassani
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France
| | | | - Juliette Paireau
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France ,Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Université Paris Cité, UMR2000, CNRS, Paris, France
| | - Nathanaël Hozé
- Mathematical Modelling of Infectious Diseases Unit, Institut Pasteur, Université Paris Cité, UMR2000, CNRS, Paris, France
| | - Marc Ruello
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France
| | - Gilda Grard
- grid.476258.aFrench Armed Forces Biomedical Research Institute, National Reference Laboratory for Arboviruses, Marseille, France ,grid.5399.60000 0001 2176 4817Unité des Virus Émergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207), Marseille, France
| | - Raphaëlle Métras
- Sorbonne Université, INSERM, Institut Pierre Louis d’Épidémiologie et de Santé Publique (IPLESP, UMRS 1136), Paris, France
| | - Harold Noël
- grid.493975.50000 0004 5948 8741Santé publique France, French national public health agency, F-94415 Saint-Maurice, France
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16
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Lean FZX, Johnson N. JMM Profile: Rift Valley fever: a zoonotic viral haemorrhagic disease. J Med Microbiol 2022; 72. [PMID: 36748539 DOI: 10.1099/jmm.0.001619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Rift Valley fever (RVF) is caused by infection with Rift Valley fever virus (RVFV), a mosquito-borne RNA virus that affects both humans and livestock species. Humans can also acquire infection from contact with infected animals and contaminated bodily fluid. Veterinary vaccines are available for use in livestock, but no vaccines have been approved for humans to date. The virus is currently endemic in most sub-Saharan regions of Africa but numerous incursions into Middle Eastern countries and islands in the Indian Ocean, such as Mayotte (an overseas Department of France), have occurred in the past decade. The risk of further geographical expansion is high and therefore additional investigation is warranted to better understand disease transmission and pathogenic mechanisms to develop threat mitigation strategies.
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Affiliation(s)
- Fabian Z X Lean
- Pathology and Animal Sciences Department, Animal and Plant Health Agency, Woodham Lane, Addlestone, KT15 3NB, UK
| | - Nicholas Johnson
- Vector Borne Diseases, Virology Department, Animal and Plant Health Agency, Woodham Lane, Addlestone, KT15 3NB, UK
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17
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Mechanistic models of Rift Valley fever virus transmission: A systematic review. PLoS Negl Trop Dis 2022; 16:e0010339. [PMID: 36399500 PMCID: PMC9718419 DOI: 10.1371/journal.pntd.0010339] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 12/02/2022] [Accepted: 10/31/2022] [Indexed: 11/19/2022] Open
Abstract
Rift Valley fever (RVF) is a zoonotic arbovirosis which has been reported across Africa including the northernmost edge, South West Indian Ocean islands, and the Arabian Peninsula. The virus is responsible for high abortion rates and mortality in young ruminants, with economic impacts in affected countries. To date, RVF epidemiological mechanisms are not fully understood, due to the multiplicity of implicated vertebrate hosts, vectors, and ecosystems. In this context, mathematical models are useful tools to develop our understanding of complex systems, and mechanistic models are particularly suited to data-scarce settings. Here, we performed a systematic review of mechanistic models studying RVF, to explore their diversity and their contribution to the understanding of this disease epidemiology. Researching Pubmed and Scopus databases (October 2021), we eventually selected 48 papers, presenting overall 49 different models with numerical application to RVF. We categorized models as theoretical, applied, or grey, depending on whether they represented a specific geographical context or not, and whether they relied on an extensive use of data. We discussed their contributions to the understanding of RVF epidemiology, and highlighted that theoretical and applied models are used differently yet meet common objectives. Through the examination of model features, we identified research questions left unexplored across scales, such as the role of animal mobility, as well as the relative contributions of host and vector species to transmission. Importantly, we noted a substantial lack of justification when choosing a functional form for the force of infection. Overall, we showed a great diversity in RVF models, leading to important progress in our comprehension of epidemiological mechanisms. To go further, data gaps must be filled, and modelers need to improve their code accessibility.
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18
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Domfe T, Njengele-Tetyana Z, Mhlanga N, Tetyana P, Skepu A, Ngila JC, Sikhwivhilu LM. Development of a Versatile Half-Strip Lateral Flow Assay toward the Detection of Rift Valley Fever Virus Antibodies. Diagnostics (Basel) 2022; 12:2664. [PMID: 36359507 PMCID: PMC9689200 DOI: 10.3390/diagnostics12112664] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/27/2022] [Accepted: 10/27/2022] [Indexed: 09/08/2024] Open
Abstract
Rift Valley fever (RVF) is a mosquito-borne zoonotic disease that is caused by the Rift Valley fever virus (RVFV); Bunyaviridae: Phlebovirus. RVF disease can affect several different species, including ruminants, camels and humans and thus present a dual threat to public health and livestock food production in endemic regions. In livestock, the RVFV infection is characterised by an acute hepatitis, abortion and high mortality rates in new-born animals. The current RVF diagnostic techniques have shown good sensitivity. However, they require extensive sample processing and complex instrumentation. Owing to speed, low cost, ease of use, and most importantly, the ability to diagnose diseases at sites where they are managed, lateral flow immunoassays (LFIA) are the most widely used point-of-care (POC) tools for disease diagnosis. In this study, a lateral flow assay (LFA) device that is able to detect antibodies against RVFV, with a minimum detectable concentration of 0.125 mg/mL, was successfully developed. The LFA also successfully detected RVFV antibodies in reference RVFV sera. Protein A (ProA), which has the ability to bind immunoglobulins from different species, was used in the detection probe, giving the developed RVFV LFA potential for multi-species diagnosis.
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Affiliation(s)
- Thulaganyo Domfe
- Department of Chemical Sciences, University of Johannesburg, Doornfontein, Johannesburg 2050, South Africa
| | - Zikhona Njengele-Tetyana
- Advanced Materials Division, DSI/Mintek NIC, Mintek, 200 Malibongwe Drive, Randburg 2194, South Africa
| | - Nikiwe Mhlanga
- Advanced Materials Division, DSI/Mintek NIC, Mintek, 200 Malibongwe Drive, Randburg 2194, South Africa
| | - Phumlani Tetyana
- Advanced Materials Division, DSI/Mintek NIC, Mintek, 200 Malibongwe Drive, Randburg 2194, South Africa
| | - Amanda Skepu
- Next Generation Health, Council for Scientific and Industrial Research, Meiring Naude Road, Brummeria, Pretoria 0001, South Africa
| | - Jane Catherine Ngila
- Department of Chemical Sciences, University of Johannesburg, Doornfontein, Johannesburg 2050, South Africa
- The African Academy of Science, 8 Miotoni Lane, Karen, Nairobi P.O. Box 24916-00502, Kenya
| | - Lucky Mashudu Sikhwivhilu
- Advanced Materials Division, DSI/Mintek NIC, Mintek, 200 Malibongwe Drive, Randburg 2194, South Africa
- Department of Chemistry, Faculty of Science, Engineering and Agriculture, Thohoyandou 0950, South Africa
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19
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Exotic viral hepatitis: A review on epidemiology, pathogenesis, and treatment. J Hepatol 2022; 77:1431-1443. [PMID: 35817222 DOI: 10.1016/j.jhep.2022.06.031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 06/14/2022] [Accepted: 06/19/2022] [Indexed: 12/04/2022]
Abstract
Certain "exotic" viruses are known to cause clinical diseases with potential liver involvement. These include viruses, beyond regular hepatotropic viruses (hepatitis A, -B(D), -C, -E, cytomegalovirus, Epstein-Barr virus), that can be found in (sub)tropical areas and can cause "exotic viral hepatitis". Transmission routes typically involve arthropods (Crimean Congo haemorrhagic fever, dengue, Rift Valley fever, yellow fever). However, some of these viruses are transmitted by the aerosolised excreta of rodents (Hantavirus, Lassa fever), or via direct contact or contact with bodily fluids (Ebola). Although some exotic viruses are associated with high fatality rates, such as Ebola for example, the clinical presentation of most exotic viruses can range from mild flu-like symptoms, in most cases, right through to being potentially fatal. A smaller percentage of people develop severe disease with haemorrhagic fever, possibly with (fulminant) hepatitis. Liver involvement is often caused by direct tropism for hepatocytes and Kupffer cells, resulting in virus-mediated and/or immune-mediated necrosis. In all exotic hepatitis viruses, PCR is the most sensitive diagnostic method. The determination of IgM/IgG antibodies is a reasonable alternative, but cross-reactivity can be a problem in the case of flaviviruses. Licenced vaccines are available for yellow fever and Ebola, and they are currently under development for dengue. Therapy for exotic viral hepatitis is predominantly supportive. To ensure that preventive measures can be introduced to control possible outbreaks, the timely detection of these viruses is very important.
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Jaleta MB, Tefera M, Negussie H, Mulatu T, Berhe T, Belete F, Yalew B, Gizaw O, Dabasa G, Abunna F, Regassa F, Amenu K, Leta S. Entomological survey of the potential vectors of Rift Valley fever virus and absence of detection of the virus genome from the vectors in various niches in the southern half of the Great Rift Valley of Ethiopia. Vet Med Sci 2022; 8:2716-2725. [DOI: 10.1002/vms3.941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Affiliation(s)
- Megarsa Bedasa Jaleta
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Mehari Tefera
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Haileleul Negussie
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | | | - Tsega Berhe
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Fasika Belete
- College of Veterinary Medicine and Agriculture Jimma University Jimma Ethiopia
| | - Bekele Yalew
- Animal Health Institute Entomology Unit Sebeta Ethiopia
| | - Oda Gizaw
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Golo Dabasa
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Fufa Abunna
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Fikru Regassa
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
- Ministry of Agriculture Livestock and Fishery Addis Ababa Ethiopia
| | - Kebede Amenu
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
| | - Samson Leta
- College of Veterinary Medicine and Agriculture Addis Ababa University Bishoftu Ethiopia
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21
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Selim A, Alsubki RA, Albohairy FM, Attia KA, Kimiko I. A survey of bluetongue infection in one-humped camels (Camelus Dromedarius); seroprevalence and risk factors analysis. BMC Vet Res 2022; 18:322. [PMID: 35996137 PMCID: PMC9394030 DOI: 10.1186/s12917-022-03421-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 08/05/2022] [Indexed: 11/14/2022] Open
Abstract
Bluetongue (BT) is an insect-borne, non-contagious viral disease which affects domestic ruminants including camels and is transmitted by Culicoides spp. Clinical symptoms of BT are typically seen in sheep, although subclinical BT infections are mostly seen in cattle, goats, and camelids. The goal of the present study was to evaluate the sero-prevalence of Bluetongue virus (BTV) in camels from some governorates in Egypt's southern and northern regions, as well as the infection's potential risk factors. During 2020-2021, a cross sectional study was conducted to screen presence of anti-BTV antibodies in 400 serum samples, which were collected randomly from camels, examined using competitive enzyme-linked immunosorbent assay (cELISA). The sera of 102 out of 400 camels tested positive for BTV, representing a frequency of 25.5%. Moreover, the odds of sero-positivity were higher among camels living in Aswan (OR = 5.33, 95%CI: 2.35-12.11), especially in females (OR = 2.63, 95%CI = 1.44-4.09) during summer season (OR = 2.40, 95%CI = 1.20-4.81). Furthermore, the probability of getting BTV infection increased when camels were exposed to the insect vectors (OR = 1.63, 95%CI = 0.87-3.09). The high prevalence of BTV in camels in several Egyptian regions highlights the need for more epidemiological investigations of BTV infection in other ruminant species in order to better control BT disease in these regions.
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Affiliation(s)
- Abdelfattah Selim
- Department of Animal Medicine (Infectious Diseases), Faculty of Veterinary Medicine, Benha University, Toukh, 13736, Egypt.
| | - Roua A Alsubki
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, , P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Fatima M Albohairy
- Department of Clinical Laboratory Science, College of Applied Medical Sciences, King Saud University, , P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Kotb A Attia
- Department of Biochemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia
| | - Itoh Kimiko
- Institute of Science and Technology, Niigata University, Ikarashi-2, Nishi-ku, Niigata, 950-2181, Japan
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22
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Fine mapping of the antigenic epitopes of the Gc protein of Guertu virus. PLoS One 2022; 17:e0271878. [PMID: 35881569 PMCID: PMC9321374 DOI: 10.1371/journal.pone.0271878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 07/08/2022] [Indexed: 11/19/2022] Open
Abstract
Guertu virus (GTV), a newly discovered member of the genus Banyangvirus in the family Phenuiviridae, poses a potential health threat to humans and animals. The viral glycoprotein (GP) binds to host cell receptors to induce a neutralizing immune response in the host. Therefore, identification of the B-cell epitopes (BCEs) in the immunodominant region of the GTV Gc protein is important for the elucidation of the virus–host cell interactions and the development of GTV epitope assays and vaccines. In this study, an improved overlapping biosynthetic peptide method and rabbit anti-GTV Gc polyclonal antibodies were used for fine mapping of the minimal motifs of linear BCEs of the GTV Gc protein. Thirteen BCE motifs were identified from eleven positive 16mer-peptides, namely EGc1 (19KVCATTGRA27), EGc2 (58KKINLKCKK66), EGc3 (68SSYYVPDA75), EGc4 (75ARSRCTSVRR84), EGc5 (79CTSVRRCRWA88), EGc6 (90DCQSGCPS97), EGc7 (96PSHFTSNS103), EGc8 (115AGLGFSG121), EGc9 (148ENPHGVI154), EGc10 (179KVFHPMS185), EGc11 (230QAGMGVVG237), EGc12 (303RSHDSQGKIS312), and EGc13 (430DIPRFV435). Of these, 7 could be recognized by GTV IgG-positive sheep sera. Three-dimensional structural analysis revealed that all 13 BCEs were present on the surface of the Gc protein. Sequence alignment of the 13 BCEs against homologous proteins from 10 closely related strains of severe fever with thrombocytopenia syndrome virus from different geographical regions revealed that the amino acid sequences of EGc4, EGc5, EGc8, EGc11, and EGc12 were highly conserved, with 100% similarity. The remaining 8 epitopes (EGc1, EGc2, EGc3, EGc6, EGc7, EGc9, EGc10, and EGc13) showed high sequence similarity in the range of 71.43%–87.50%. These 13 BCEs of the GTV Gc protein provide a molecular foundation for future studies of the immunological properties of GTV glycoproteins and the development of GTV multi-epitope assays and vaccines.
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Fang Y, Khater EIM, Xue JB, Ghallab EHS, Li YY, Jiang TG, Li SZ. Epidemiology of Mosquito-Borne Viruses in Egypt: A Systematic Review. Viruses 2022; 14:v14071577. [PMID: 35891557 PMCID: PMC9322113 DOI: 10.3390/v14071577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/12/2022] [Accepted: 07/18/2022] [Indexed: 12/21/2022] Open
Abstract
There are at least five common mosquito-borne viruses (MBVs) recorded in Egypt, including dengue virus (DENV), Rift Valley fever virus (RVFV), West Nile virus (WNV), Chikungunya virus, and Sindbis virus. Unexpected outbreaks caused by MBVs reflect the deficiencies of the MBV surveillance system in Egypt. This systematic review characterized the epidemiology of MBV prevalence in Egypt. Human, animal, and vector prevalence studies on MBVs in Egypt were retrieved from Web of Science, PubMed, and Bing Scholar, and 33 eligible studies were included for further analyses. The monophyletic characterization of the RVFV and WNV strains found in Egypt, which spans about half a century, suggests that both RVFV and WNV are widely transmitted in this nation. Moreover, the seropositive rates of DENV and WNV in hosts were on the rise in recent years, and spillover events of DENV and WNV to other countries from Egypt have been recorded. The common drawback for surveillance of MBVs in Egypt is the lack of seroprevalence studies on MBVs, especially in this century. It is necessary to evaluate endemic transmission risk, establish an early warning system for MBVs, and develop a sound joint system for medical care and public health for managing MBVs in Egypt.
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Affiliation(s)
- Yuan Fang
- NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China; (Y.F.); (J.-B.X.); (Y.-Y.L.)
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
| | - Emad I. M. Khater
- Department of Entomology, Faculty of Science, Ain Shams University, Abbasiah, Cairo 11566, Egypt; (E.I.M.K.); (E.H.S.G.)
| | - Jing-Bo Xue
- NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China; (Y.F.); (J.-B.X.); (Y.-Y.L.)
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
| | - Enas H. S. Ghallab
- Department of Entomology, Faculty of Science, Ain Shams University, Abbasiah, Cairo 11566, Egypt; (E.I.M.K.); (E.H.S.G.)
| | - Yuan-Yuan Li
- NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China; (Y.F.); (J.-B.X.); (Y.-Y.L.)
| | - Tian-Ge Jiang
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
| | - Shi-Zhu Li
- NHC Key Laboratory of Parasite and Vector Biology, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai 200025, China; (Y.F.); (J.-B.X.); (Y.-Y.L.)
- School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
- Correspondence:
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Islam K, Carlsson M, Enquist PA, Qian W, Marttila M, Strand M, Ahlm C, Evander M. Structural Modifications and Biological Evaluations of Rift Valley Fever Virus Inhibitors Identified from Chemical Library Screening. ACS OMEGA 2022; 7:6854-6868. [PMID: 35252679 PMCID: PMC8892858 DOI: 10.1021/acsomega.1c06513] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 02/04/2022] [Indexed: 06/14/2023]
Abstract
The Rift Valley fever virus (RVFV) is an emerging high-priority pathogen endemic in Africa with pandemic potential. There is no specific treatment or approved antiviral drugs for the RVFV. We previously developed a cell-based high-throughput assay to screen small molecules targeting the RVFV and identified a potential effective antiviral compound (1-N-(2-(biphenyl-4-yloxy)ethyl)propane-1,3-diamine) as a lead compound. Here, we investigated how structural modifications of the lead compound affected the biological properties and the antiviral effect against the RVFV. We found that the length of the 2-(3-aminopropylamino)ethyl chain of the compound was important for the compound to retain its antiviral activity. The antiviral activity was similar when the 2-(3-aminopropylamino)ethyl chain was replaced with a butyl piperazine chain. However, we could improve the cytotoxicity profile of the lead compound by changing the phenyl piperazine linker from the para-position (compound 9a) to the meta-position (compound 13a). Results from time-of-addition studies suggested that compound 13a might be active during virus post-entry and/or the replication phase of the virus life cycle and seemed to affect the K+ channel. The modifications improved the properties of our lead compound, and our data suggest that 13a is a promising candidate to evaluate further as a therapeutic agent for RVFV infection.
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Affiliation(s)
- Koushikul Islam
- Department
of Clinical Microbiology, Umeå University, Umeå 901 85, Sweden
| | - Marcus Carlsson
- Department
of Chemistry, Umeå University, Umeå 901 87, Sweden
| | | | - Weixing Qian
- Department
of Chemistry, Umeå University, Umeå 901 87, Sweden
| | - Marko Marttila
- Department
of Clinical Microbiology, Umeå University, Umeå 901 85, Sweden
| | - Mårten Strand
- Department
of Clinical Microbiology, Umeå University, Umeå 901 85, Sweden
| | - Clas Ahlm
- Department
of Clinical Microbiology, Umeå University, Umeå 901 85, Sweden
| | - Magnus Evander
- Department
of Clinical Microbiology, Umeå University, Umeå 901 85, Sweden
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Anywaine Z, Lule SA, Hansen C, Warimwe G, Elliott A. Clinical manifestations of Rift Valley fever in humans: Systematic review and meta-analysis. PLoS Negl Trop Dis 2022; 16:e0010233. [PMID: 35333856 PMCID: PMC8986116 DOI: 10.1371/journal.pntd.0010233] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 04/06/2022] [Accepted: 02/03/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The clinical signs and symptoms in humans are non-specific and case definitions vary. We reviewed and analysed the clinical manifestations of RVF in humans. METHODS In this systematic review and meta-analysis we searched on different dates, the Embase (from 1947 to 13th October 2019), Medline (1946 to 14th October 2019), Global Health (1910 to 15th October 2019), and Web of Science (1970 to 15th October 2019) databases. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animal studies, studies among asymptomatic volunteers, and single case reports for which a proportion could not be estimated, were excluded. Quality assessment was done using a modified Hoy and Brooks et al tool, data was extracted, and pooled frequency estimates calculated using random effects meta-analysis. RESULTS Of the 3765 articles retrieved, less than 1% (32 articles) were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including the general febrile, renal, gastrointestinal, hepatic, haemorrhagic, visual, neurological, cardio-pulmonary, and obstetric syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91; [26 studies, 1286 patients]), renal failure (41%; 23-59; [4, 327]), nausea (38%; 12-67; [6, 325]), jaundice (26%; 16-36; [15, 393]), haemorrhagic disease (26%; 17-36; [16, 277]), partial blindness (24%; 7-45; [11, 225]), encephalitis (21%; 11-33; [4, 327]), cough (4%; 0-17; [4, 11]), and miscarriage (54%) respectively. Death occurred in 21% (95% CI 14-29; [16 studies, 328 patients]) of cases, most of whom were hospitalised. DISCUSSION This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreak control, increase public awareness about RVF, and subsequently inform 'one-health' policies. This study provides a pooled estimate of the proportion of RVF clinical manifestations alongside a narrative description of clinical syndromes. However, most studies reviewed were case series with small sample sizes and enrolled mostly in-patients and out-patients, and captured symptoms either sparsely or using broad category terms.
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Affiliation(s)
- Zacchaeus Anywaine
- Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- * E-mail:
| | - Swaib Abubaker Lule
- Institute for Global Health, University College London, London, United Kingdom
| | - Christian Hansen
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- MRC International Statistics & Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - George Warimwe
- Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom
- KEMRI WellcomeTrust Research Programme, Kilifi, Kenya
| | - Alison Elliott
- Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
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Bracci N, de la Fuente C, Saleem S, Pinkham C, Narayanan A, García-Sastre A, Balaraman V, Richt JA, Wilson W, Kehn-Hall K. Rift Valley fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley fever virus production. Virology 2022; 567:65-76. [PMID: 35032865 PMCID: PMC8877469 DOI: 10.1016/j.virol.2021.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/15/2021] [Accepted: 12/31/2021] [Indexed: 02/03/2023]
Abstract
Rift Valley fever virus (RVFV) is an arbovirus that was first reported in the Rift Valley of Kenya which causes significant disease in humans and livestock. RVFV is a tri-segmented, negative-sense RNA virus consisting of a L, M, and S segments with the M segment encoding the glycoproteins Gn and Gc. Host factors that interact with Gn are largely unknown. To this end, two viruses containing an epitope tag (V5) on the Gn protein in position 105 or 229 (V5Gn105 and V5Gn229) were generated using the RVFV MP-12 vaccine strain as a backbone. The V5-tag insertion minimally impacted Gn functionality as measured by replication kinetics, Gn localization, and antibody neutralization assays. A proteomics-based approach was used to identify novel Gn-binding host proteins, including the E3 ubiquitin-protein ligase, UBR4. Depletion of UBR4 resulted in a significant decrease in RVFV titers and a reduction in viral RNA production.
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Affiliation(s)
- Nicole Bracci
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University,National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University
| | - Cynthia de la Fuente
- The National Institutes of Health, National Institute of Allergy and Infectious Diseases, DEA,National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University
| | - Sahar Saleem
- National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University
| | - Chelsea Pinkham
- National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University
| | - Aarthi Narayanan
- National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University
| | | | - Velmurugan Balaraman
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University
| | - Juergen A. Richt
- Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University
| | - William Wilson
- National Bio and Agro-Defense Facility, Agricultural Research Service, USDA
| | - Kylene Kehn-Hall
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University,National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University,Center for Zoonotic and Arthropod-borne Pathogens, Virginia Polytechnic Institute and State University,Corresponding Author: Kylene Kehn-Hall, Ph.D., Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Integrated Life Sciences Building, 1981 Kraft Drive, Blacksburg, VA 24060 USA,
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27
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Mahmoud AS, Sawesi OK, El-Waer OR, Bennour EM. Rift valley fever in Africa with the emerging interest in Libya. INTERNATIONAL JOURNAL OF ONE HEALTH 2021. [DOI: 10.14202/ijoh.2021.237-245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Rift valley fever (RVF) is an acute vector-borne viral zoonotic disease of domestic and wild ruminants. The RVF virus (RVFV) belonging to the Phlebovirus genus of the Bunyaviridae family causes this disease. Studies have shown that mosquitoes are the vectors that transmit RVFV. Specifically, Aedes and Culex mosquito species are among the many vectors of this virus, which affects not only sheep, goats, buffalo, cattle, and camels but also human beings. Since the 30s of the last century, RVF struck Africa, and to a lesser extent, Asian continents, with subsequent episodes of epizootic, epidemic, and sporadic outbreaks. These outbreaks, therefore, resulted in the cumulative loss of thousands of human lives, thereby disrupting the livestock market or only those with seropositive cases. After that outbreak episode, RVF was not reported in Libya until January 13, 2020, where it was reported for the 1st time in a flock of sheep and goats in the southern region of the country. Although insufficient evidence to support RVF clinical cases among the confirmed seropositive animals exists, neither human cases nor death were reported in Libya. Yet, the overtime expansion of RVF kinetics in the Libyan neighborhoods, in addition to the instability and security vacuum experienced in the country, lack of outbreak preparedness, and the availability of suitable climatic and disease vector factors, makes this country a possible future scene candidate for RVF expansion. Urgently, strengthening veterinary services (VS) and laboratory diagnostic capacities, including improvement of monitoring and surveillance activity programs, should be implemented in areas at risk (where imported animals crossing borders from Libyan neighborhoods and competent vectors are found) at national, sub-national, and regional levels. The Libyan government should also implement a tripartite framework (one health approach) among the veterinary public health, public health authority, and environmental sanitation sectors to implement RVF surveillance protocols, along with an active partnership with competent international bodies (OIE, FAO, and WHO). Therefore, this review comprises the most updated data regarding the epidemiological situation of RVF infections and its socioeconomic impacts on African and Asian continents, and also emphasize the emerging interest of RVF in Libya.
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Affiliation(s)
- Abdusalam S. Mahmoud
- Department of Preventive Medicine, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya
| | - Osama K. Sawesi
- Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya
| | - Osama R. El-Waer
- Department of Microbiology and Parasitology, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya
| | - Emad M. Bennour
- Department of Internal Medicine, Faculty of Veterinary Medicine, University of Tripoli, Tripoli, Libya
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28
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Adamu AM, Allam L, Sackey AKB, Nma AB, Mshelbwala PP, Mambula-Machunga S, Idoko SI, Adikwu AA, Nafarnda WD, Garba BS, Owolodun OA, Dzikwi AA, Balogun EO, Simon YA. Risk factors for Rift Valley fever virus seropositivity in one-humped camels ( Camelus dromedarius) and pastoralist knowledge and practices in Northern Nigeria. One Health 2021; 13:100340. [PMID: 34820498 PMCID: PMC8600062 DOI: 10.1016/j.onehlt.2021.100340] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 10/16/2021] [Accepted: 10/17/2021] [Indexed: 12/21/2022] Open
Abstract
Rift Valley fever (RVF) is a complex emerging arboviral hemorrhagic disease that causes significant illness in animals and humans. Camel trade across the land borders between Nigeria and the Niger Republic occurs frequently and poses a significant risk for RVF transmission to pastoralists and traders. We carried a cross-sectional study between November 2016 and April 2017 in two northern States (Katsina and Jigawa) known for camel trade in Nigeria to investigate the seroprevalence and potential risk factors for RVFV occurrence. We collected 720 sera and administered questionnaire to pastoralists. We used the competitive enzyme-linked immunosorbent assay (c-ELISA) to determine the previous exposure to RVFV infection. We retrieved environmental information from public data sources that might explain RVFV seropositivity at the LGA level. To asses potential risk factors,we categorized LGAs with RVFV as "1" and those without a case" 0". We fitted a logistic model to the data and estimated odds ratios and 95% confidence intervals. An overall 19.9% prevalence was reported among camel herd-the highest seropositivity (33.3%) was recorded in SuleTankarkar LGA. In the multivariable model, only rain-fed croplands was significantly associated with RVFV antibodies occurrence p = 0.048 (OR = 0.87, 95% CI: 0.76-0.99). Only a minority of the respondents, 19.3% (n = 17/88), knew that RVF is zoonotic. Separation of healthy animals from the infected animals was carried out by 53.4% (47/88) pastoralists while 59.1% (52/88) pastoralists still use ethnoveterinary practices to control or mitigate disease outbreaks. Our study demonstrates the presence of RVFV antibodies among camel in Nigeria and the associated risk factors. These findings highlight the need for enhancing surveillance and control efforts and the public health education of camel pastoralists. Further investigation to unravel the zoonotic transmission potential to pastoralists and other animal species is pertinent.
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Affiliation(s)
- Andrew Musa Adamu
- Department of Veterinary Public Health and Preventive Medicine, University of Abuja, Nigeria.,Department of Veterinary Medicine, Ahmadu Bello University Zaria, Nigeria
| | - Lushakyaa Allam
- Veterinary Teaching Hospital, Ahmadu Bello University, Zaria, Nigeria
| | - Anthony K B Sackey
- Department of Veterinary Medicine, Ahmadu Bello University Zaria, Nigeria
| | - Alhaji Bida Nma
- Department of Veterinary Public Health and Preventive Medicine, University of Abuja, Nigeria
| | - Philip Paul Mshelbwala
- UQ Spatial Epidemiology Laboratory, School of Veterinary Science, The University of Queensland, Australia
| | | | | | - Alex Adikwu Adikwu
- Department of Veterinary Public Health and Preventive Medicine, University of Agriculture, Makurdi, Benue State, Nigeria
| | - Wesley Daniel Nafarnda
- Department of Veterinary Public Health and Preventive Medicine, University of Abuja, Nigeria
| | | | | | - Asabe Adamu Dzikwi
- Department of Veterinary Public Health and Preventive Medicine, University of Jos, Nigeria
| | | | - Yila Ayo Simon
- Center for Blood Research and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.,National Centers for Animal Disease Research, Lethbridge Laboratory, Science Branch, Canadian Food Inspection Agency, Government of Canada, Lethbridge, Alberta, Canada
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29
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Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage. Viruses 2021; 13:v13112265. [PMID: 34835071 PMCID: PMC8625252 DOI: 10.3390/v13112265] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/08/2021] [Accepted: 11/10/2021] [Indexed: 02/05/2023] Open
Abstract
The mosquito-borne Rift Valley fever (RVF) is a prioritised disease that has been listed by the World Health Organization for urgent research and development of counteraction. Rift Valley fever virus (RVFV) can cause a cytopathogenic effect in the infected cell and induce hyperimmune responses that contribute to pathogenesis. In livestock, the consequences of RVFV infection vary from mild symptoms to abortion. In humans, 1–3% of patients with RVFV infection develop severe disease, manifested as, for example, haemorrhagic fever, encephalitis or blindness. RVFV infection has also been associated with miscarriage in humans. During pregnancy, there should be a balance between pro-inflammatory and anti-inflammatory mediators to create a protective environment for the placenta and foetus. Many viruses are capable of penetrating that protective environment and infecting the foetal–maternal unit, possibly via the trophoblasts in the placenta, with potentially severe consequences. Whether it is the viral infection per se, the immune response, or both that contribute to the pathogenesis of miscarriage remains unknown. To investigate how RVFV could contribute to pathogenesis during pregnancy, we infected two human trophoblast cell lines, A3 and Jar, representing normal and transformed human villous trophoblasts, respectively. They were infected with two RVFV variants (wild-type RVFV and RVFV with a deleted NSs protein), and the infection kinetics and 15 different cytokines were analysed. The trophoblast cell lines were infected by both RVFV variants and infection caused upregulation of messenger RNA (mRNA) expression for interferon (IFN) types I–III and inflammatory cytokines, combined with cell line-specific mRNA expression of transforming growth factor (TGF)-β1 and interleukin (IL)-10. When comparing the two RVFV variants, we found that infection with RVFV lacking NSs function caused a hyper-IFN response and inflammatory response, while the wild-type RVFV suppressed the IFN I and inflammatory response. The induction of certain cytokines by RVFV infection could potentially lead to teratogenic effects that disrupt foetal and placental developmental pathways, leading to birth defects and other pregnancy complications, such as miscarriage.
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30
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Pawęska JT, Jansen van Vuren P, Msimang V, Lô MM, Thiongane Y, Mulumba-Mfumu LK, Mansoor A, Fafetine JM, Magona JW, Boussini H, Bażanow B, Wilson WC, Pepin M, Unger H, Viljoen G. Large-Scale International Validation of an Indirect ELISA Based on Recombinant Nucleocapsid Protein of Rift Valley Fever Virus for the Detection of IgG Antibody in Domestic Ruminants. Viruses 2021; 13:1651. [PMID: 34452515 PMCID: PMC8402881 DOI: 10.3390/v13081651] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Revised: 08/06/2021] [Accepted: 08/13/2021] [Indexed: 12/21/2022] Open
Abstract
Diagnostic performance of an indirect enzyme-linked immunosorbent assay (I-ELISA) based on a recombinant nucleocapsid protein (rNP) of the Rift Valley fever virus (RVFV) was validated for the detection of the IgG antibody in sheep (n = 3367), goat (n = 2632), and cattle (n = 3819) sera. Validation data sets were dichotomized according to the results of a virus neutralization test in sera obtained from RVF-endemic (Burkina Faso, Democratic Republic of Congo, Mozambique, Senegal, Uganda, and Yemen) and RVF-free countries (France, Poland, and the USA). Cut-off values were defined using the two-graph receiver operating characteristic analysis. Estimates of the diagnostic specificity of the RVFV rNP I-ELISA in animals from RVF-endemic countries ranged from 98.6% (cattle) to 99.5% (sheep) while in those originating from RVF-free countries, they ranged from 97.7% (sheep) to 98.1% (goats). Estimates of the diagnostic sensitivity in ruminants from RVF-endemic countries ranged from 90.7% (cattle) to 100% (goats). The results of this large-scale international validation study demonstrate the high diagnostic accuracy of the RVFV rNP I-ELISA. Standard incubation and inactivation procedures evaluated did not have an adverse effect on the detectable levels of the anti-RVFV IgG in ruminant sera and thus, together with recombinant antigen-based I-ELISA, provide a simple, safe, and robust diagnostic platform that can be automated and carried out outside expensive bio-containment facilities. These advantages are particularly important for less-resourced countries where there is a need to accelerate and improve RVF surveillance and research on epidemiology as well as to advance disease control measures.
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Affiliation(s)
- Janusz T. Pawęska
- Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa;
- Centre for Viral Zoonoses, Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
- Faculty of Health Sciences, School of Pathology, University of Witwatersrand, Johannesburg 2050, South Africa
| | - Petrus Jansen van Vuren
- Australian Centre for Disease Preparedness, CSIRO Health & Biosecurity, Geelong, VIC 3220, Australia;
| | - Veerle Msimang
- Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Sandringham 2131, South Africa;
| | - Modu Moustapha Lô
- Laboratoire National de l’Elevage et de Recherches Vétérinaires, Route de Front de Terre, Dakar Hann 2057, BP, Senegal; (M.M.L.); (Y.T.)
| | - Yaya Thiongane
- Laboratoire National de l’Elevage et de Recherches Vétérinaires, Route de Front de Terre, Dakar Hann 2057, BP, Senegal; (M.M.L.); (Y.T.)
| | - Leopold K. Mulumba-Mfumu
- Ministry of Agriculture, Democratic Republic of Congo, Kinshasa 7948, Democratic Republic of the Congo;
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Kinshasa, P.O. Box 127, Kinshasa XI, Democratic Republic of the Congo
| | - Alqadasi Mansoor
- Central Veterinary Laboratory, General Directorate of Animal Health & Veterinary Quarantine, Ministry of Agriculture and Irrigation, Sana’a 31220, Yemen;
- Food and Agriculture Organization Office, Sana’a 31220, Yemen
| | - José M. Fafetine
- Veterinary Faculty, Eduardo Mondlane University, Maputo 1103, Mozambique;
| | - Joseph W. Magona
- National Livestock Resources Research Institute, Tororo P.O. Box 96, Uganda;
- Food and Agriculture Organization, Gaborone P.O. Box 54, Botswana
| | - Hiver Boussini
- Direction Generale Des Services Veterinaires, Ministère des Ressources Animales, Ouagadougou 09 BP 907, Burkina Faso;
- African Union Interafrican Bureau for Animal Resources, Nairobi P.O. Box 30786-00100, Kenya
| | - Barbara Bażanow
- Department of Pathology, Faculty of Veterinary Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland;
| | - William C. Wilson
- United States Department of Agriculture, Agricultural Research Service, Foreign Arthropod Borne Animal Diseases Research Unit, National Bio- and Agro-Defense Facility, Manhattan, KS 66502, USA;
| | - Michel Pepin
- Agence Française de Sécurité Sanitaire des Aliments, F-69364 Lyon, France;
- VetAgro Sup, Campus Vétérinaire de Lyon, F-69364 Lyon, France
| | - Hermann Unger
- Joint FAO/IAEA Centre for Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, 1400 Vienna, Austria; (H.U.); (G.V.)
| | - Gerrit Viljoen
- Joint FAO/IAEA Centre for Nuclear Techniques in Food and Agriculture, International Atomic Energy Agency, 1400 Vienna, Austria; (H.U.); (G.V.)
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31
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Gortázar C, Barroso P, Nova R, Cáceres G. The role of wildlife in the epidemiology and control of Foot-and-mouth-disease And Similar Transboundary (FAST) animal diseases: A review. Transbound Emerg Dis 2021; 69:2462-2473. [PMID: 34268873 DOI: 10.1111/tbed.14235] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 06/28/2021] [Accepted: 07/10/2021] [Indexed: 12/19/2022]
Abstract
Transboundary Animal Diseases (TADs) are notifiable diseases which are highly transmissible and have the potential for rapid spread regardless of national borders. Many TADs are shared between domestic animals and wildlife, with the potential to affect both livestock sector and wildlife conservation and eventually, public health in the case of zoonosis. The European Commission for the Control of Foot-and-Mouth Disease (EuFMD), a commission of the Food and Agriculture Organization of the United Nations (FAO), has grouped six TADs as 'Foot-and-mouth disease (FMD) And Similar Transboundary animal diseases' (FAST diseases). FAST diseases are ruminant infections caused by viruses, for which vaccination is a control option. The EuFMD hold-FAST strategy aims primarily at addressing the threat represented by FAST diseases for Europe. Prevention and control of FAST diseases might benefit from assessing the role of wildlife. We reviewed the role of wildlife as indicators, victims, bridge hosts or maintenance hosts for the six TADs included in the EuFMD hold-FAST strategy: FMD, peste des petits ruminants, lumpy skin disease, sheep and goatpox, Rift Valley fever and bovine ephemeral fever. We observed that wildlife can act as indicator species. In addition, they are occasionally victims of disease outbreaks, and they are often relevant for disease management as either bridge or maintenance hosts. Wildlife deserves to become a key component of future integrated surveillance and disease control strategies in an ever-changing world. It is advisable to increase our knowledge on wildlife roles in relevant TADs to improve our preparedness in case of an outbreak in previously disease-free regions, where wildlife may be significant for disease surveillance and control.
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Affiliation(s)
- Christian Gortázar
- Grupo Sanidad y Biotecnología (SaBio), Instituto de Investigación en Recursos Cinegéticos (IREC; CSIC-UCLM-JCCM), Ciudad Real, Spain
| | - Patricia Barroso
- Grupo Sanidad y Biotecnología (SaBio), Instituto de Investigación en Recursos Cinegéticos (IREC; CSIC-UCLM-JCCM), Ciudad Real, Spain
| | - Rodrigo Nova
- School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, Leicestershire, UK
| | - Germán Cáceres
- European Commission for the Control of Foot-and-Mouth Disease, Rome, Italy
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Castillo-León J, Trebbien R, Castillo JJ, Svendsen WE. Commercially available rapid diagnostic tests for the detection of high priority pathogens: status and challenges. Analyst 2021; 146:3750-3776. [PMID: 34060546 DOI: 10.1039/d0an02286a] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The ongoing COVID-19 pandemic has shown the importance of having analytical devices that allow a simple, fast, and robust detection of pathogens which cause epidemics and pandemics. The information these devices can collect is crucial for health authorities to make effective decisions to contain the disease's advance. The World Health Organization published a list of primary pathogens that have raised concern as potential causes of future pandemics. Unfortunately, there are no rapid diagnostic tests commercially available and approved by the regulatory bodies to detect most of the pathogens listed by the WHO. This report describes these pathogens, the available detection methods, and highlights areas where more attention is needed to produce rapid diagnostic tests for future pandemic surveillance.
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Affiliation(s)
- Jaime Castillo-León
- Bioengineering Department, Technical University of Denmark, Ørsteds Plads, DK-2800 Kgs. Lyngby, Denmark.
| | - Ramona Trebbien
- Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen, Denmark
| | - John J Castillo
- Escuela de Química, Universidad Industrial de Santander, Bucaramanga, Colombia
| | - Winnie E Svendsen
- Bioengineering Department, Technical University of Denmark, Ørsteds Plads, DK-2800 Kgs. Lyngby, Denmark.
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Detection of Rift Valley Fever Virus RNA in Formalin-Fixed Mosquitoes by In Situ Hybridization (RNAscope ®). Viruses 2021; 13:v13061079. [PMID: 34198809 PMCID: PMC8227582 DOI: 10.3390/v13061079] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/29/2021] [Accepted: 06/02/2021] [Indexed: 12/15/2022] Open
Abstract
Rift Valley fever virus (RVFV) causes a zoonotic mosquito-borne haemorrhagic disease that emerges to produce rapid large-scale outbreaks in livestock within sub-Saharan Africa. A range of mosquito species in Africa have been shown to transmit RVFV, and recent studies have assessed whether temperate mosquito species are also capable of transmission. In order to support vector competence studies, the ability to visualize virus localization in mosquito cells and tissue would enhance the understanding of the infection process within the mosquito body. Here, the application of in situ hybridization utilizing RNAscope® to detect RVFV infection within the mosquito species, Culex pipiens, derived from the United Kingdom was demonstrated. Extensive RVFV replication was detected in many tissues of the mosquito with the notable exception of the interior of ovarian follicles.
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Rift Valley fever virus detection in susceptible hosts with special emphasis in insects. Sci Rep 2021; 11:9822. [PMID: 33972596 PMCID: PMC8110843 DOI: 10.1038/s41598-021-89226-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 04/15/2021] [Indexed: 11/09/2022] Open
Abstract
Rift Valley fever phlebovirus (RVFV, Phenuiviridae) is an emerging arbovirus that can cause potentially fatal disease in many host species including ruminants and humans. Thus, tools to detect this pathogen within tissue samples from routine diagnostic investigations or for research purposes are of major interest. This study compares the immunohistological usefulness of several mono- and polyclonal antibodies against RVFV epitopes in tissue samples derived from natural hosts of epidemiologic importance (sheep), potentially virus transmitting insect species (Culex quinquefasciatus, Aedes aegypti) as well as scientific infection models (mouse, Drosophila melanogaster, C6/36 cell pellet). While the nucleoprotein was the epitope most prominently detected in mammal and mosquito tissue samples, fruit fly tissues showed expression of glycoproteins only. Antibodies against non-structural proteins exhibited single cell reactions in salivary glands of mosquitoes and the C6/36 cell pellet. However, as single antibodies exhibited a cross reactivity of varying degree in non-infected specimens, a careful interpretation of positive reactions and consideration of adequate controls remains of critical importance. The results suggest that primary antibodies directed against viral nucleoproteins and glycoproteins can facilitate RVFV detection in mammals and insects, respectively, and therefore will allow RVFV detection for diagnostic and research purposes.
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Isolation and Identification of a Novel Phlebovirus, Hedi Virus, from Sandflies Collected in China. Viruses 2021; 13:v13050772. [PMID: 33925561 PMCID: PMC8145316 DOI: 10.3390/v13050772] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 04/20/2021] [Accepted: 04/25/2021] [Indexed: 02/06/2023] Open
Abstract
We report the isolation of a newly recognized phlebovirus, Hedi virus (HEDV), from Phlebotomus chinensis sandflies collected in Shanxi Province, China. The virus’ RNA is comprised of three segments. The greatest amino acid sequence similarity of the three gene segments between this virus and previously recognized phleboviruses is 40.85–63.52%, and the RNA-dependent RNA polymerase (RdRp) amino acid sequence has the greatest similarity (63.52%) to the Rift Valley fever virus (RVFV) ZH-548 strain. Phylogenetic analysis of the amino acid sequence of the virus RdRp indicated that HEDV is close to RVFV and distinct from other phleboviruses, forming its own evolutionary branch. We conclude that it is necessary to increase the monitoring of phleboviruses carried by sandflies in China.
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Fakour S, Naserabadi S, Ahmadi E. A serological and hematological study on Rift valley fever and associated risk factors in aborted sheep at Kurdistan province in west of Iran. Comp Immunol Microbiol Infect Dis 2021; 75:101620. [PMID: 33609990 DOI: 10.1016/j.cimid.2021.101620] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 01/29/2021] [Accepted: 02/04/2021] [Indexed: 10/22/2022]
Abstract
Rift Valley fever (RVF) is a disease caused by RVF virus (RVFV) which can cause infections in a range of wild and domestic ruminants as well as in humans and characterized by an increased incidence of abortion in ruminants. This study aims to survey the seroprevalence and risk factors of this zoonose among aborted sheep in Kurdistan province, the west of Iran. 182 blood samples were collected from aborted sheep during the past one month under age groups <1, ≥1-3, >3-5 year in four seasons in two groups of border and non-border cities of Kurdistan province. The presence of RVFV-specific Antibodies was investigated by using competitive ELISA. Indirect immunofluorescence assay (IIFA) was used to confirm positive samples, after separation of serum, as well as blood samples were analyzed for description of hematological parameters. Of a total sheep sampled 1.65 % (n = 3) were positive for RVFV antibodies in both test. The results of IIFA were correlated with the ELISA results. All of the positive samples showed leucopenia and had significant relation with seroprevalence of RVF (P < 0.05). The seroprevalence of RVF in the border cities were significantly higher than other group (P < 0.05) Age of sheep and season had no significant effect on prevalence of RVF (P > 0.05). Results obtained in this study indicated the presence of low-level RVFV circulation among the sheep of Kurdistan Province in Iran, so it is necessary to carry out further studies in other areas of Iran. Doing an epidemiologically study aimed at isolating RVFV in the ruminants of Kurdistan province is recommended. The risk factor of bordering with Iran's western neighbor (Iraq) requires seriously control of the exchange of animals and the relevant products between the two countries.
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Affiliation(s)
- Shahin Fakour
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Sanandaj Branch Islamic Azad University, Sanandaj, Iran.
| | - Salahedin Naserabadi
- Department of Clinical Sciences, Faculty of Veterinary Medicine, Sanandaj Branch Islamic Azad University, Sanandaj, Iran
| | - Elham Ahmadi
- Department of Microbiology, Faculty of Veterinary Medicine, Sanandaj Branch Islamic Azad University, Sanandaj, Iran
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Mahmoud HYAH, Ali AO. Epidemiology and serological detection of Rift Valley Fever disease in farm animals in southern Egypt. ACTA ACUST UNITED AC 2021; 88:e1-e5. [PMID: 33567844 PMCID: PMC7876994 DOI: 10.4102/ojvr.v88i1.1877] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 09/25/2020] [Indexed: 12/25/2022]
Abstract
In this study, the serological surveillance of Rift Valley Fever virus (RVFV) in southern Egypt was carried out for 460 serum samples collected from domestic animals (unvaccinated), including cattle, sheep, goat, camel and donkey reared in three different provinces (Qena, Luxor and Aswan). Enzyme linked immunosorbent assay (ELISA) was used to detect RVFV antibodies. The results showed that 97 out of 460 animals were positive by using blocking ELISA. The percentage of RVFV infection in cattle, sheep, goat, camel and donkey was 5.55%, 65.21%, 14.44%, 20.65% and 0%, respectively. Geographical distribution and breeding system were taken into consideration for RVFV infection in these animals. The most prevalent type of infection was identified in intensive breeding farms systems (27.63%), and then in individual breeding systems (11.68%). Qena had a higher infection rate of RVFV (23.55%), in comparison to Aswan and Luxor (20.65% and 14.14%, respectively). Marked seroprevalence recorded in this study indicates a high incidence of infection in sheep (65.21%) and camel (20.65%); this necessitates the application of more effective strategies to control these types of infections in Egypt. This study provides a concise picture about the RVFV disease in southern Egypt. We need more similar studies targeted to clarify the reliable epidemiological status of RVFV disease in southern Egypt and other localities.
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Affiliation(s)
- Hassan Y A H Mahmoud
- Department of Animal Medicine, Division of Infectious Disease, Faculty of Veterinary Medicine, South Valley University, Qena.
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Abstract
Rift Valley fever (RVF) is a zoonotic, vector-borne infectious disease of ruminants and camels transmitted mainly by the Aedes and Culex mosquito species. Contact with the blood or organs of infected animals may infect humans. Its etiological factor is the Rift Valley fever virus (RVFV) of the Phlebovirus genus and Bunyaviridae family. Sheep and goats are most susceptible to infection and newborns and young individuals endure the most severe disease course. High abortion rates and infant mortality are typical for RVF; its clinical signs are high fever, lymphadenitis, nasal and ocular secretions and vomiting. Conventional diagnosis is done by the detection of specific IgM or IgG antibodies and RVFV nucleic acids and by virus isolation. Inactivated and live-attenuated vaccines obtained from virulent RVFV isolates are available for livestock. RVF is endemic in sub-Saharan Africa and the Arabian Peninsula, but in the last two decades, it was also reported in other African regions. Seropositive animals were detected in Turkey, Tunisia and Libya. The wide distribution of competent vectors in non-endemic areas coupled with global climate change threaten to spread RVF transboundarily. The EFSA considers the movement of infected animals and vectors to be other plausible pathways of RVF introduction into Europe. A very low risk both of introduction of the virus through an infected animal or vector and of establishment of the virus, and a moderate risk of its transmission through these means was estimated for Poland. The risk of these specific modes of disease introduction into Europe is rated as very low, but surveillance and response capabilities and cooperation with the proximal endemic regions are recommended.
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Mahmoud HY, Ali AO. Epidemiology and serological detection of Rift Valley Fever disease in farm animals in southern Egypt. Onderstepoort J Vet Res 2020. [DOI: 10.4102/ojvr.v87i1.1877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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40
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Núñez AI, Esteve-Codina A, Gómez-Garrido J, Brustolin M, Talavera S, Berdugo M, Dabad M, Alioto T, Bensaid A, Busquets N. Alteration in the Culex pipiens transcriptome reveals diverse mechanisms of the mosquito immune system implicated upon Rift Valley fever phlebovirus exposure. PLoS Negl Trop Dis 2020; 14:e0008870. [PMID: 33301456 PMCID: PMC7755283 DOI: 10.1371/journal.pntd.0008870] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 12/22/2020] [Accepted: 10/10/2020] [Indexed: 01/02/2023] Open
Abstract
Rift Valley fever phlebovirus (RVFV) causes an emerging zoonotic disease and is mainly transmitted by Culex and Aedes mosquitoes. While Aedes aegypti-dengue virus (DENV) is the most studied model, less is known about the genes involved in infection-responses in other mosquito-arboviruses pairing. The main objective was to investigate the molecular responses of Cx. pipiens to RVFV exposure focusing mainly on genes implicated in innate immune responses. Mosquitoes were fed with blood spiked with RVFV. The fully-engorged females were pooled at 3 different time points: 2 hours post-exposure (hpe), 3- and 14-days post-exposure (dpe). Pools of mosquitoes fed with non-infected blood were also collected for comparisons. Total RNA from each mosquito pool was subjected to RNA-seq analysis and a de novo transcriptome was constructed. A total of 451 differentially expressed genes (DEG) were identified. Most of the transcriptomic alterations were found at an early infection stage after RVFV exposure. Forty-eight DEG related to immune infection-response were characterized. Most of them were related with the RNAi system, Toll and IMD pathways, ubiquitination pathway and apoptosis. Our findings provide for the first time a comprehensive view on Cx. pipiens-RVFV interactions at the molecular level. The early depletion of RNAi pathway genes at the onset of the RVFV infection would allow viral replication in mosquitoes. While genes from the Toll and IMD immune pathways were altered in response to RVFV none of the DEG were related to the JAK/STAT pathway. The fact that most of the DEG involved in the Ubiquitin-proteasome pathway (UPP) or apoptosis were found at an early stage of infection would suggest that apoptosis plays a regulatory role in infected Cx. pipiens midguts. This study provides a number of target genes that could be used to identify new molecular targets for vector control.
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Affiliation(s)
- Ana I. Núñez
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Anna Esteve-Codina
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain
| | - Jèssica Gómez-Garrido
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain
| | - Marco Brustolin
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
- Department of Entomology, The Pennsylvania State University, University Park, Pennsylvania, United States of America
| | - Sandra Talavera
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Miguel Berdugo
- Instituto de Biología Evolutiva, Universitat Pompeu i Fabra-CSIC, Dr. Aigüader 88, Barcelona, Spain
| | - Marc Dabad
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain
| | - Tyler Alioto
- CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain
- Universitat Pompeu i Fabra (UPF), Barcelona, Catalonia, Spain
| | - Albert Bensaid
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
| | - Núria Busquets
- IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain
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Han Q, Zhang S, Liu D, Yan F, Wang H, Huang P, Bi J, Jin H, Feng N, Cao Z, Gao Y, Chi H, Yang S, Zhao Y, Xia X. Development of a Visible Reverse Transcription-Loop-Mediated Isothermal Amplification Assay for the Detection of Rift Valley Fever Virus. Front Microbiol 2020; 11:590732. [PMID: 33281787 PMCID: PMC7691480 DOI: 10.3389/fmicb.2020.590732] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/28/2020] [Indexed: 12/14/2022] Open
Abstract
Rift Valley fever (RVF) is a severe infectious disease, which can through mosquito bites, direct contact and aerosol transmission infect sheep, goats, people, camels, cattle, buffaloes, and so on. In this paper, a conserved region of the S RNA segment of Rift Valley fever virus (RVFV) ZH501 strain was used as target sequence. The RVFV RT-LAMP-VF assay was successfully established combined reverse transcription-loop-mediated isothermal amplification with a vertical flow visualization strip. The detection limit is up to 1.94 × 100 copies/μl of synthesized RVFV-RNA. RNA extracted from cell culture of an inactivated RVFV-BJ01 strain was also used as templates, and the detection limit is 1.83 × 103 copies/μl. In addition, there was no cross-reactivity with other viruses that can cause similar fever symptoms. The RVFV-LAMP-VF assay exhibited very high levels of diagnostic sensitivity, which had 100-fold more sensitive than RVFV real-time RT-PCR assay. Accordingly, the RVFV RT-LAMP-VF assay developed in this study is suitable for the rapid and sensitive diagnosis of RVFV without specialized equipment and can rapidly complete detection within 60 min, and the results are visible by vertical flow visualization strip within 5 min.
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Affiliation(s)
- Qiuxue Han
- Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China
| | - Shengnan Zhang
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China
| | - Dongping Liu
- The Nanjing Unicorn Academy of Innovation, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Nanjing, China
| | - Feihu Yan
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
| | - Hualei Wang
- College of Veterinary Medicine, Jilin University, Changchun, China
| | - Pei Huang
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Animal Science and Technology College, Jilin Agricultural University, Changchun, China
| | - Jinhao Bi
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Animal Science and Technology College, Jilin Agricultural University, Changchun, China
| | - Hongli Jin
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,College of Veterinary Medicine, Jilin University, Changchun, China
| | - Na Feng
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China
| | - Zengguo Cao
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yuwei Gao
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
| | - Hang Chi
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
| | - Songtao Yang
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
| | - Yongkun Zhao
- Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
| | - Xianzhu Xia
- Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical College (PUMC), Beijing, China.,Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, China.,Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou University, Yangzhou, China
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Pérez-Ramírez E, Cano-Gómez C, Llorente F, Adzic B, Al Ameer M, Djadjovski I, El Hage J, El Mellouli F, Goletic T, Hovsepyan H, Karayel-Hacioglu I, Maksimovic Zoric J, Mejri S, Sadaoui H, Salem SH, Sherifi K, Toklikishvili N, Vodica A, Monaco F, Brun A, Jiménez-Clavero MÁ, Fernández-Pinero J. External quality assessment of Rift Valley fever diagnosis in 17 veterinary laboratories of the Mediterranean and Black Sea regions. PLoS One 2020; 15:e0239478. [PMID: 32986725 PMCID: PMC7521712 DOI: 10.1371/journal.pone.0239478] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 09/07/2020] [Indexed: 11/17/2022] Open
Abstract
Rift Valley fever (RVF) is an arboviral zoonosis that primarily affects ruminants but can also cause illness in humans. The increasing impact of RVF in Africa and Middle East and the risk of expansion to other areas such as Europe, where competent mosquitos are already established, require the implementation of efficient surveillance programs in animal populations. For that, it is pivotal to regularly assess the performance of existing diagnostic tests and to evaluate the capacity of veterinary labs of endemic and non-endemic countries to detect the infection in an accurate and timely manner. In this context, the animal virology network of the MediLabSecure project organized between October 2016 and March 2017 an external quality assessment (EQA) to evaluate the RVF diagnostic capacities of beneficiary veterinary labs. This EQA was conceived as the last step of a training curriculum that included 2 diagnostic workshops that were organized by INIA-CISA (Spain) in 2015 and 2016. Seventeen veterinary diagnostic labs from 17 countries in the Mediterranean and Black Sea regions participated in this EQA. The exercise consisted of two panels of samples for molecular and serological detection of the virus. The laboratories were also provided with positive controls and all the kits and reagents necessary to perform the recommended diagnostic techniques. All the labs were able to apply the different protocols and to provide the results on time. The performance was good in the molecular panel with 70.6% of participants reporting 100% correct results, and excellent in the serological panel with 100% correct results reported by 94.1% of the labs. This EQA provided a good overview of the RVFV diagnostic capacities of the involved labs and demonstrated that most of them were able to correctly identify the virus genome and antibodies in different animal samples.
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Affiliation(s)
- Elisa Pérez-Ramírez
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain
| | - Cristina Cano-Gómez
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain
| | - Francisco Llorente
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain
| | - Bojan Adzic
- Diagnostic Veterinary Laboratory, Podgorica, Montenegro
| | - Maisa Al Ameer
- Animal Wealth Laboratory Sector, Ministry of Agriculture, Amman, Jordan
| | - Igor Djadjovski
- Faculty of Veterinary Medicine, Ss. Cyril and Methodius University, Skopje, Republic of North Macedonia
| | - Jeanne El Hage
- Animal Health Laboratory, Lebanese Agricultural Research Institute, Fanar, Lebanon
| | - Fatiha El Mellouli
- Casablanca Regional Research and Analysis Laboratory of National Office of Sanitary Safety and Food Products (ONSSA), Nouaceur, Casablanca, Morocco
| | - Teufik Goletic
- Veterinary Faculty, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
| | - Hermine Hovsepyan
- Republican Veterinary-Sanitary and Phytosanitary Center of Laboratory Services SNCO, Yerevan, Armenia
| | - Ilke Karayel-Hacioglu
- Virology Department, Faculty of Veterinary Medicine, Ankara University, Ankara, Turkey
| | - Jelena Maksimovic Zoric
- Virology Department, Scientific Institute of Veterinary Medicine of Serbia, Belgrade, Serbia
| | - Selma Mejri
- Virology Department, Institute of Veterinary Research of Tunisia, Tunis, Tunisia
| | - Hassiba Sadaoui
- Laboratoire Central Vétérinaire d'Alger, Institut National de la Médecine Vétérinaire, Algiers, Algeria
| | | | - Kurtesh Sherifi
- Department of Veterinary Medicine, Faculty of Agriculture and Veterinary Sciences, University of Prishtina, "Hasan Pristhina", Kosovo
| | - Natela Toklikishvili
- Laboratory of Virology and Molecular Biology, LEPL State Laboratory of Agriculture (SLA), Tbilisi, Georgia
| | - Ani Vodica
- Department of Animal Health, Food Safety and Veterinary Institute, Tirana, Albania
| | - Federica Monaco
- Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise "G. Caporale", Teramo, Italy
| | - Alejandro Brun
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain
| | - Miguel Ángel Jiménez-Clavero
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain.,CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Jovita Fernández-Pinero
- Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA-CISA), Valdeolmos, Spain
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43
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Otręba M, Kośmider L, Rzepecka-Stojko A. Antiviral activity of chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine towards RNA-viruses. A review. Eur J Pharmacol 2020; 887:173553. [PMID: 32949606 PMCID: PMC7493736 DOI: 10.1016/j.ejphar.2020.173553] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Revised: 08/31/2020] [Accepted: 09/11/2020] [Indexed: 01/11/2023]
Abstract
In 2020 the whole world focused on antivirus drugs towards SARS-CoV-2. Most of the researchers focused on drugs used in other viral infections or malaria. We have not seen such mobilization towards one topic in this century. The whole situation makes clear that progress needs to be made in antiviral drug development. The first step to do it is to characterize the potential antiviral activity of new or already existed drugs on the market. Phenothiazines are antipsychotic agents used previously as antiseptics, anthelminthics, and antimalarials. Up to date, they are tested for a number of other disorders including the broad spectrum of viruses. The goal of this paper was to summarize the current literature on activity toward RNA-viruses of such drugs like chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine. We identified 49 papers, where the use of the phenothiazines for 23 viruses from different families were tested. Chlorpromazine, fluphenazine, perphenazine, prochlorperazine, and thioridazine possess anti-viral activity towards different types of viruses. These drugs inhibit clathrin-dependent endocytosis, cell-cell fusion, infection, replication of the virus, decrease viral invasion as well as suppress entry into the host cells. Additionally, since the drugs display activity at nontoxic concentrations they have therapeutic potential for some viruses, still, further research on animal and human subjects are needed in this field to verify cell base research.
Phenothiazines possess antiviral activity towards RNA viruses. An antiviral activity can be achieved below toxic serum concentration. Phenothiazines are characterized by multidirectional points of action.
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Affiliation(s)
- Michał Otręba
- Department of Drug Technology, Medical University of Silesia, Katowice Faculty of Pharmaceutical Sciences in Sosnowiec, Jednosci 8, 41-200, Sosnowiec, Poland.
| | - Leon Kośmider
- Department of General and Inorganic Chemistry, Medical University of Silesia, Katowice Faculty of Pharmaceutical Sciences in Sosnowiec, Jagiellonska 4, 41-200, Sosnowiec, Poland
| | - Anna Rzepecka-Stojko
- Department of Drug Technology, Medical University of Silesia, Katowice Faculty of Pharmaceutical Sciences in Sosnowiec, Jednosci 8, 41-200, Sosnowiec, Poland
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44
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Calvo-Pinilla E, Marín-López A, Moreno S, Lorenzo G, Utrilla-Trigo S, Jiménez-Cabello L, Benavides J, Nogales A, Blasco R, Brun A, Ortego J. A protective bivalent vaccine against Rift Valley fever and bluetongue. NPJ Vaccines 2020; 5:70. [PMID: 32793399 PMCID: PMC7393076 DOI: 10.1038/s41541-020-00218-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 07/06/2020] [Indexed: 11/09/2022] Open
Abstract
Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR(-/-) mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.
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Affiliation(s)
- Eva Calvo-Pinilla
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Alejandro Marín-López
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain.,Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT USA
| | - Sandra Moreno
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Gema Lorenzo
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Sergio Utrilla-Trigo
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Luis Jiménez-Cabello
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Julio Benavides
- Instituto de Ganadería de Montaña (CSIC-Universidad de León), León, Spain
| | - Aitor Nogales
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Rafael Blasco
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Departamento de Biotecnología, Madrid, Spain
| | - Alejandro Brun
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
| | - Javier Ortego
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Centro de Investigación en Sanidad Animal (INIA-CISA), Madrid, Spain
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45
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Wichgers Schreur PJ, Oreshkova N, van Keulen L, Kant J, van de Water S, Soós P, Dehon Y, Kollár A, Pénzes Z, Kortekaas J. Safety and efficacy of four-segmented Rift Valley fever virus in young sheep, goats and cattle. NPJ Vaccines 2020; 5:65. [PMID: 32728479 PMCID: PMC7382487 DOI: 10.1038/s41541-020-00212-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/02/2020] [Indexed: 01/02/2023] Open
Abstract
Rift Valley fever virus (RVFV) is a mosquito-borne bunyavirus that causes severe and recurrent outbreaks on the African continent and the Arabian Peninsula and continues to expand its habitat. RVFV induces severe disease in newborns and abortion in pregnant ruminants. The viral genome consists of a small (S), medium (M) and large (L) RNA segment of negative polarity. The M segment encodes a glycoprotein precursor protein that is co-translationally cleaved into the two structural glycoproteins Gn and Gc, which are involved in receptor attachment and cell entry. We previously constructed a four-segmented RVFV (RVFV-4s) by splitting the M genome segment into two M-type segments encoding either Gn or Gc. RVFV-4s replicates efficiently in cell culture but was shown to be completely avirulent in mice, lambs and pregnant ewes. Here, we show that a RVFV-4s candidate vaccine for veterinary use (vRVFV-4s) does not disseminate in vaccinated animals, is not shed or spread to the environment and does not revert to virulence. Furthermore, a single vaccination of lambs, goat kids and calves was shown to induce protective immunity against a homologous challenge. Finally, the vaccine was shown to provide full protection against a genetically distinct RVFV strain. Altogether, we demonstrate that vRVFV-4s optimally combines efficacy with safety, holding great promise as a next-generation RVF vaccine.
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Affiliation(s)
- Paul J Wichgers Schreur
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands.,BunyaVax B.V., Lelystad, The Netherlands
| | - Nadia Oreshkova
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands
| | - Lucien van Keulen
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands
| | - Jet Kant
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands
| | - Sandra van de Water
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands
| | - Pál Soós
- Ceva Animal Health, Ceva-Phylaxia, Budapest, Hungary
| | - Yves Dehon
- Ceva Animal Health, Ceva-Phylaxia, Budapest, Hungary
| | - Anna Kollár
- Ceva Animal Health, Ceva-Phylaxia, Budapest, Hungary
| | - Zoltán Pénzes
- Ceva Animal Health, Ceva-Phylaxia, Budapest, Hungary
| | - Jeroen Kortekaas
- Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands.,BunyaVax B.V., Lelystad, The Netherlands.,Laboratory of Virology, Wageningen University and Research, Wageningen, The Netherlands
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46
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Tong C, Javelle E, Grard G, Dia A, Lacrosse C, Fourié T, Gravier P, Watier-Grillot S, Lancelot R, Letourneur F, Comby F, Grau M, Cassou L, Meynard JB, Briolant S, Leparc-Goffart I, Pommier de Santi V. Tracking Rift Valley fever: From Mali to Europe and other countries, 2016. ACTA ACUST UNITED AC 2020; 24. [PMID: 30808441 PMCID: PMC6446957 DOI: 10.2807/1560-7917.es.2019.24.8.1800213] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.
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Affiliation(s)
- Christelle Tong
- French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | | | - Gilda Grard
- Unité des Virus Émergents (UVE), Aix-Marseille Université - IRD 190 - Inserm 1207 - IHU Méditerranée Infection, Marseille, France.,French Armed Forces Biomedical Research Institute (IRBA), National Reference Centre for Arboviruses, Marseille, France
| | - Aissata Dia
- French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Constance Lacrosse
- French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Toscane Fourié
- Unité des Virus Émergents (UVE), Aix-Marseille Université - IRD 190 - Inserm 1207 - IHU Méditerranée Infection, Marseille, France.,French Armed Forces Biomedical Research Institute (IRBA), National Reference Centre for Arboviruses, Marseille, France
| | - Patrick Gravier
- Unité des Virus Émergents (UVE), Aix-Marseille Université - IRD 190 - Inserm 1207 - IHU Méditerranée Infection, Marseille, France.,French Armed Forces Biomedical Research Institute (IRBA), National Reference Centre for Arboviruses, Marseille, France
| | | | - Renaud Lancelot
- UMR ASTRE, Univ. Montpellier, CIRAD, INRA, Montpellier, France.,International Centre of Agricultural Research for Development (CIRAD), Animals, Health, Territories, Risks and Ecosystems Unit (ASTRE), Montpellier, France
| | | | - Frédéric Comby
- French Military Health Service, 10th Medical Unit, Laudun, France
| | - Martin Grau
- French Military Health Service, 18th Medical Unit, Fréjus, France
| | - Lionel Cassou
- French Military Health Service, 11th Medical Unit, Toulouse, France
| | - Jean-Baptiste Meynard
- French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
| | - Sébastien Briolant
- UMR VITROME, Aix-Marseille Université, IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Marseille, France.,French Armed Forces Biomedical Research Institute (IRBA), Marseille, France
| | - Isabelle Leparc-Goffart
- Unité des Virus Émergents (UVE), Aix-Marseille Université - IRD 190 - Inserm 1207 - IHU Méditerranée Infection, Marseille, France.,French Armed Forces Biomedical Research Institute (IRBA), National Reference Centre for Arboviruses, Marseille, France
| | - Vincent Pommier de Santi
- UMR VITROME, Aix-Marseille Université, IRD, AP-HM, SSA, VITROME, IHU-Méditerranée Infection, Marseille, France.,French Armed Forces Centre for Epidemiology and Public Health (CESPA), Marseille, France
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47
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Kroeker AL, Babiuk S, Pickering BS, Richt JA, Wilson WC. Livestock Challenge Models of Rift Valley Fever for Agricultural Vaccine Testing. Front Vet Sci 2020; 7:238. [PMID: 32528981 PMCID: PMC7266933 DOI: 10.3389/fvets.2020.00238] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 04/07/2020] [Indexed: 11/13/2022] Open
Abstract
Since the discovery of Rift Valley Fever virus (RVFV) in Kenya in 1930, the virus has become widespread throughout most of Africa and is characterized by sporadic outbreaks. A mosquito-borne pathogen, RVFV is poised to move beyond the African continent and the Middle East and emerge in Europe and Asia. There is a risk that RVFV could also appear in the Americas, similar to the West Nile virus. In light of this potential threat, multiple studies have been undertaken to establish international surveillance programs and diagnostic tools, develop models of transmission dynamics and risk factors for infection, and to develop a variety of vaccines as countermeasures. Furthermore, considerable efforts to establish reliable challenge models of Rift Valley fever virus have been made and platforms for testing potential vaccines and therapeutics in target species have been established. This review emphasizes the progress and insights from a North American perspective to establish challenge models in target livestock such as cattle, sheep, and goats in comparisons to other researchers' reports. A brief summary of the potential role of wildlife, such as buffalo and white-tailed deer as reservoir species will also be discussed.
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Affiliation(s)
- Andrea Louise Kroeker
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB, Canada
| | - Shawn Babiuk
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB, Canada.,Department of Immunology, University of Manitoba, Winnipeg, MB, Canada
| | - Bradley S Pickering
- Canadian Food Inspection Agency, National Centre for Foreign Animal Disease, Winnipeg, MB, Canada.,Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada
| | - Juergen A Richt
- Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), Manhattan, KS, United States
| | - William C Wilson
- USDA, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Manhattan, KS, United States
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48
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Grossi-Soyster EN, LaBeaud AD. Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks. Trop Med Infect Dis 2020; 5:tropicalmed5020089. [PMID: 32498264 PMCID: PMC7345646 DOI: 10.3390/tropicalmed5020089] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/22/2020] [Accepted: 05/28/2020] [Indexed: 12/02/2022] Open
Abstract
Rift Valley fever virus (RVFV) is a zoonotic phlebovirus of the Phenuiviridae family with great opportunity for emergence in previously unaffected regions, despite its current geographical limits. Outbreaks of RVFV often infect humans or domesticated animals, such as livestock, concurrently and occur sporadically, ranging from localized outbreaks in villages to multi-country events that spread rapidly. The true burden of Rift Valley fever (RVF) is not well defined due to underreporting, misdiagnosis caused by the broad spectrum of disease presentation, and minimal access for rapid and accurate laboratory confirmation. Severe symptoms may include hemorrhagic fever, loss of vision, psychological impairment or disturbances, and organ failure. Those living in endemic areas and travelers should be aware of the potential for exposure to ongoing outbreaks or interepidemic transmission, and engage in behaviors to minimize exposure risks, as vaccinations in humans are currently unavailable and animal vaccinations are not used routinely or ubiquitously. The lack of vaccines approved for use in humans is concerning, as RVFV has proven to be highly pathogenic in naïve populations, causing severe disease in a large percent of confirmed cases, which could have considerable impact on human health.
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49
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Mrzljak A, Novak R, Pandak N, Tabain I, Franusic L, Barbic L, Bogdanic M, Savic V, Mikulic D, Pavicic-Saric J, Stevanovic V, Vilibic-Cavlek T. Emerging and neglected zoonoses in transplant population. World J Transplant 2020; 10:47-63. [PMID: 32257849 PMCID: PMC7109593 DOI: 10.5500/wjt.v10.i3.47] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 03/15/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023] Open
Abstract
Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative.
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Affiliation(s)
- Anna Mrzljak
- Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Rafaela Novak
- School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Nenad Pandak
- Depatment of Medicine, The Royal Hospital Muscat, Muscat 111, Oman
| | - Irena Tabain
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | | | - Ljubo Barbic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Maja Bogdanic
- Department of Virology, Croatian Institute of Public Health, Zagreb 10000, Croatia
| | - Vladimir Savic
- Poultry Center, Croatian Veterinary Institute, Zagreb 10000, Croatia
| | - Danko Mikulic
- Department of Abdominal and Transplant Surgery, Merkur University Hospital, Zagreb 10000, Croatia
| | - Jadranka Pavicic-Saric
- Department of Anesthesiology and Intensive Medicine, Merkur University Hospital, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Vladimir Stevanovic
- Department of Microbiology and Infectious Diseases with Clinic, Faculty of Veterinary Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Tatjana Vilibic-Cavlek
- Department of Virology, Croatian Institute of Public Health; School of Medicine, University of Zagreb, Zagreb 10000, Croatia
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50
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Iannetta M, Di Caro A, Nicastri E, Vairo F, Masanja H, Kobinger G, Mirazimi A, Ntoumi F, Zumla A, Ippolito G. Viral Hemorrhagic Fevers Other than Ebola and Lassa. Infect Dis Clin North Am 2020; 33:977-1002. [PMID: 31668201 DOI: 10.1016/j.idc.2019.08.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Viral hemorrhagic fevers represent a group of diseases caused by enveloped RNA viruses. The epidemiology is broadly variable, ranging from geographically localized to more diffuse infections. Viral hemorrhagic fevers are classified as category A bioweapon agents by the Centers for Disease Control and Prevention. Viral hemorrhagic fevers are severe febrile illnesses with hemorrhagic phenomena. Laboratory diagnosis takes place in highly specialized reference laboratories. Treatment is essentially supportive. In this article, we focus the attention on yellow fever and viral hemorrhagic fevers other than Ebola and Lassa virus diseases that have been described elsewhere in this issue.
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Affiliation(s)
- Marco Iannetta
- National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense 292, Rome 00149, Italy
| | - Antonino Di Caro
- National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense 292, Rome 00149, Italy
| | - Emanuele Nicastri
- National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense 292, Rome 00149, Italy
| | - Francesco Vairo
- National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense 292, Rome 00149, Italy
| | - Honorati Masanja
- Ifakara Health Institute, Ifakara Health Research and Development Centre, Kiko Avenue, Plot N 463, Mikocheni, Dar es Salaam, Tanzania
| | - Gary Kobinger
- Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, Université Laval, 2325 Rue de l'Université, Quebec City, Quebec G1V 0A6, Canada
| | - Ali Mirazimi
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels Alle 8 Plan 7, Stockholm 14183, Sweden
| | - Francine Ntoumi
- Université Marien NGouabi, Fondation Congolaise pour la Recherche Médicale (FCRM), Villa D6, Campus OMS//AFRO Djoué, Brazzaville, Congo; Institute for Tropical Medicine, University of Tübingen, Germany
| | - Alimuddin Zumla
- Center for Clinical Microbiology, University College London, Royal Free Campus 2nd Floor, Rowland Hill Street, London NW3 2PF, United Kingdom
| | - Giuseppe Ippolito
- National Institute for Infectious Diseases, Lazzaro Spallanzani, IRCCS, Via Portuense 292, Rome 00149, Italy.
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