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1
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Obara FK, Omwenga EO, Nzioki JM, Agasa LO. Factors influencing vaccination of dogs against rabies in South Mugirango Sub-County-Kisii County; Kenya. PLOS GLOBAL PUBLIC HEALTH 2025; 5:e0004194. [PMID: 40343963 PMCID: PMC12063882 DOI: 10.1371/journal.pgph.0004194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 03/23/2025] [Indexed: 05/11/2025]
Abstract
Rabies is a fatal zoonotic viral disease affecting all warm-blooded mammals, with approximately 99% of human cases resulting from bites by infected dogs. This study assessed the factors influencing dog vaccination against rabies in South Mugirango, Kisii County, Kenya, where the disease remains endemic and a major public health concern. A quantitative descriptive cross-sectional survey was conducted, utilizing structured questionnaires administered to 422 household heads. Additionally, 22 key informant interviews were carried out with officials from relevant government departments to gain deeper insights. This was a mixed method study involving both a cross sectional survey and qualitative data collection. Data were analyzed using appropriate statistical techniques to identify patterns and determine associations between socio-demographic factors and vaccination practices. Socio-demographic factors significantly associated with rabies awareness included marital status (p = 0.049), occupation (p = 0.029 for housewives), and the gender of the household breadwinner (p = 0.017 for males). Despite high awareness levels, 4.1% (17/422) of respondents had not vaccinated their dogs in the past year, and only 15.9% (67/422) reported recent vaccinations. Older individuals were 12% more likely to vaccinate their dogs per year of age (OR = 1.12, p = 0.002). Higher education (OR = 1.45, p = 0.010), income (OR = 1.20, p = 0.008), rabies awareness (OR = 2.30, p < 0.001), and access to veterinary services (OR = 1.75, p < 0.001) significantly improved adherence. Despite high awareness, dog vaccination rates in South Mugirango remain low, highlighting the need for targeted interventions. Expanding access to veterinary services, subsidizing vaccines, and prioritizing outreach to younger individuals, less-educated and female-headed households can improve vaccination adherence and reduce rabies transmission.
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Affiliation(s)
| | - Eric Omori Omwenga
- Department of Medical Microbiology and Parasitology, Kisii University, Kisii, Kenya
| | | | - Lameck Ondieki Agasa
- Department of Community Health and Behavioural Sciences, Kisii University, Kisii, Kenya
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2
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Zhang L, Sun S, Gong W, Thompson L, Cruz J, Dukpa K, Gonzales RM, Tu Z, He B, Liu Y, Tu C, Feng Y. Large-scale phylogenetic analysis reveals genetic diversity and geographic distribution of rabies virus in South-East and South Asia. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2023; 113:105472. [PMID: 37353186 DOI: 10.1016/j.meegid.2023.105472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/14/2023] [Accepted: 06/20/2023] [Indexed: 06/25/2023]
Abstract
South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis of rabies virus (RABV) has been conducted only at a country level; the results obtained from different countries are scattered and unequal, with a non-uniform system to name RABV genotypes. Therefore, it is difficult to undertake origin-tracking and compare inter-country RABV evolution and transmission. To avoid the confusion in understanding and to generate a panoramic picture of RABV genetic diversity, distribution, and transmission in SEA and SA, the present study conducted a systematic phylogenetic analysis by combining all sequences representing 2368 RABV strains submitted to GenBank by 14 rabies endemic SEA and SA countries. The results showed that RABVs circulating in two regions were classified into four major clades and many subclades: the Asia clade is circulating only in SEA, the Indian subcontinent, and Arctic-like clades only in SA, while the Cosmopolitan clade has been detected in both regions. The results also showed a wide range of hosts were infected by divergent RABV subclades, with dogs being the major transmission source. However, wildlife rabies was also found to be an important issue with 6 wild carnivore species identified as potential sources of spillover risk for sylvatic rabies to humans, domestic animals, and other wild animals. Current findings indicate that the two regions have separate virus clades circulating thus indicating the absence of cross-transmission between the regions. The study emphasizes the importance of phylogenetic analysis in the regions using uniform genotyping and naming systems for rabies surveillance, to coordinate actions of member countries to eliminate dog-mediated human rabies by 2030.
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Affiliation(s)
- Liang Zhang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China
| | - Sheng Sun
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China
| | - Wenjie Gong
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China; College of Animal Medicine, Jilin University, Changchun, Jilin Province, China
| | - Lesa Thompson
- World Organization for Animal Health Regional Representative for Asia and the Pacific, Tokyo, Japan
| | - Jeffrey Cruz
- Department of Agriculture Bureau of Animal Industry, Quezon, Philippines
| | - Kinzang Dukpa
- World Organization for Animal Health Regional Representative for Asia and the Pacific, Tokyo, Japan
| | | | - Zhongzhong Tu
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China
| | - Biao He
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China
| | - Yan Liu
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China
| | - Changchun Tu
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu Province, China.
| | - Ye Feng
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China; State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
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Liu Y, Mo X, Feng Y, Willoughby RE, Weng X, Wang Y, Li X, Gao J, Tian J, Peng J. Metagenomic next-generation sequencing for the etiological diagnosis of rabies virus in cerebrospinal fluid. Front Med (Lausanne) 2023; 10:982290. [PMID: 36844226 PMCID: PMC9947348 DOI: 10.3389/fmed.2023.982290] [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: 07/09/2022] [Accepted: 01/02/2023] [Indexed: 02/11/2023] Open
Abstract
Background Rabies is a highly fatal disease. Once symptoms develop, death usually occurs within days. Survivors were occasionally reported in the literatures. Ante-mortem diagnosis remains a challenge in most rabies endemic countries. A novel, accurate diagnostic assay is highly desirable. Methods We used metagenomic next-generation sequencing (mNGS) to examine the cerebrospinal fluid (CSF) samples of a 49-year-old patient with rabies and validated the results by TaqMan PCR and RT-PCR/Sanger sequencing. Results Metagenomic next-generation sequencing identified sequence reads uniquely aligned to the rabies virus (RABV). PCR confirmed the presence of the partial RABV N gene in the CSF. Phylogenetic analysis showed that the RABV grouped as an Asian clade, which is the most broadly distributed clade in China. Conclusion Metagenomic next-generation sequencing may be a useful screening tool for the etiological diagnosis of rabies, especially in the absence of timely rabies laboratory testing or in patients with no exposure history.
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Affiliation(s)
- Yong Liu
- Intensive Care Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Xichao Mo
- Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China
| | - Ye Feng
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China
| | - Rodney E. Willoughby
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, MI, United States
| | - Xing Weng
- Department of Infectious Disease, BGI-Shenzhen, Shenzhen, Guangdong, China
| | - Yuyang Wang
- Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin, China
| | - Xing Li
- Department of Infectious Disease, BGI-Shenzhen, Shenzhen, Guangdong, China
| | - Junling Gao
- Centre of Buddhists Studies, The University of Hong Kong, Hong Kong, Hong Kong SAR, China,Department of Medicine, LKS Medical Faculty, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Jinfei Tian
- Intensive Care Unit, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China,*Correspondence: Jie Peng,
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Pharande RR, Majee SB, Gaikwad SS, Moregoankar SD, Bannalikar A, Doiphode A, Gandge R, Dighe D, Ingle S, Mukherjee S. Evolutionary analysis of rabies virus using the partial Nucleoprotein and Glycoprotein gene in Mumbai region of India. J Gen Virol 2021; 102. [PMID: 33544071 DOI: 10.1099/jgv.0.001521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Nearly 1.7 million cases of dog bites are reported every year in India and many cases of animal rabies are left unattended and undiagnosed. Therefore, a mere diagnosis of rabies is not sufficient to understand the epidemiology and the spread of the rabies virus (RV) in animals. There is a paucity of information about the evolutionary dynamics of RV in dogs and its biodiversity patterns in India. In total, 50 dog-brain samples suspected of rabies were screened by the nucleoprotein- (N) and glycoprotein- (G) gene PCR. The N and G genes were subsequently sequenced to understand the molecular evolution in these genes. The phylogenetic analysis of the N gene revealed that six isolates in the Mumbai region belonged to a single Arctic lineage. Time-scaled phylogeny by Bayesian coalescent analysis of the partial N gene revealed that the time to the most recent common ancestor (TMRCA) for the sequences belonged to the cluster from 2006.68 with a highest posterior density of 95 % betweeen 2005-2008, which is assigned to Indian lineage I. Migration pattern revealed a strong Bayes factor between Mumbai to Delhi, Panji to Hyderabad, Delhi to Chennai, and Chennai to Chandigarh. Phylogenetic analysis of the G gene revealed that the RVs circulating in the Mumbai region are divided into three lineages. Time-scaled phylogeny by the Bayesian coalescent analysis method estimated that the TMRCA for sequences under study was from 1993 and Indian clusters was from 1962. In conclusion, the phylogenetic analysis of the N gene revealed that six isolates belonged to single Arctic lineages along with other Indian isolates and they were clustered into a single lineage but divided into three clades based on the G-gene sequences. The present study highlights and enhances the current molecular epidemiology and evolution of RV and revealed strong location bias and geographical clustering within Indian isolates on the basis of N and G genes.
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Affiliation(s)
| | - Sharmila Badal Majee
- Department of Veterinary Microbiology, Mumbai Veterinary College, Parel, Mumbai-400012, India
| | - Satish S Gaikwad
- Animal Biotechnology Educational and Research Cell, COVAS, Parbhani, India
| | | | | | - Aakash Doiphode
- Department of Animal Genetics and Breeding, KNPCVS, Shirval, Pune, India
| | - Rajashri Gandge
- Department of Veterinary Microbiology, Mumbai Veterinary College, Mumbai, India
| | - Dhananjay Dighe
- Department of Preventive Medicine, Mumbai Veterinary College, Parel, Mumbai, India
| | - Sonal Ingle
- Animal Biotechnology, Mumbai Veterinary College, Mumbai
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Moulenat T, Petit C, Bosch Castells V, Houillon G. Purified Vero Cell Rabies Vaccine (PVRV, Verorab ®): A Systematic Review of Intradermal Use Between 1985 and 2019. Trop Med Infect Dis 2020; 5:E40. [PMID: 32156005 PMCID: PMC7157209 DOI: 10.3390/tropicalmed5010040] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/31/2020] [Accepted: 03/02/2020] [Indexed: 12/25/2022] Open
Abstract
The purified Vero cell rabies vaccine (PVRV; Verorab®, Sanofi Pasteur) has been used in rabies prevention since 1985. Evolving rabies vaccination trends, including shorter intradermal (ID) regimens with reduced volume, along with WHO recommendation for ID administration has driven recent ID PVRV regimen assessments. Thus, a consolidated review comparing immunogenicity of PVRV ID regimens during pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is timely and beneficial in identifying gaps in current research. A search of seven databases for studies published from 1985 to November 2019 identified 35 studies. PrEP was assessed in 10 studies (n = 926) with 1-3-site, 1-3-visit regimens of up to 3-months duration. Seroconversion (rabies virus neutralizing antibodies [RVNA] ≥ 0.5 IU/mL) rates of 90-100% were reported within weeks, irrespective of regimen, with robust booster responses at 1 year (100% seroconversion rates by day 14 post-booster). However, data are lacking for the current WHO-recommended, 2-site, 1-week ID PrEP regimen. PEP was assessed in 25 studies (n = 2136) across regimens of 1-week to 90-day duration. All ID PEP regimens assessed induced ≥ 99% seroconversion rates (except in HIV participants) by day 14-28. This review confirms ID PVRV suitability for rabies prophylaxis and highlights the heterogeneity of use in the field.
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Affiliation(s)
- Thomas Moulenat
- Université Claude Bernard Lyon 1, Institut des Sciences Pharmaceutiques et Biologiques (ISPB)—Faculté de Pharmacie de Lyon, 69008 Lyon, France;
| | - Céline Petit
- Sanofi Pasteur, 14 Espace Henry Vallée, 69007 Lyon, France; (C.P.); (V.B.C.)
| | | | - Guy Houillon
- Sanofi Pasteur, 14 Espace Henry Vallée, 69007 Lyon, France; (C.P.); (V.B.C.)
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Hsu AP, Tseng CH, Lu YT, Shih YH, Chou CH, Chen RS, Tsai KJ, Tu WJ, Cliquet F, Tsai HJ. Development of a quantitative real-time RT-PCR assay for detecting Taiwan ferret badger rabies virus in ear tissue of ferret badgers and mice. J Vet Med Sci 2018; 80:1012-1019. [PMID: 29709902 PMCID: PMC6021896 DOI: 10.1292/jvms.17-0539] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
In 2013, the first case of Taiwan ferret badger rabies virus (RABV-TWFB) infection was
reported in Formosan ferret badgers, and two genetic groups of the virus were
distinguished through phylogenetic analysis. To detect RABV-TWFB using a sensitive nucleic
acid-based method, a quantitative real-time reverse transcription polymerase chain
reaction targeting the conserved region of both genetic groups of RABV-TWFB was developed.
This method had a limit of detection (LOD) of 40 RNA copies/reaction and detected viral
RNA in brain and ear tissue specimens of infected and dead Formosan ferret badgers and
mice with 100% sensitivity and specificity. The mean viral RNA load detected in the ear
tissue specimens of ferret badgers ranged from 3.89 × 108 to 9.73 ×
108 RNA copies/g-organ, which was 111-fold to 2,220-fold lower than the
concentration detected in the brain specimens, but 2,000-fold to 5,000-fold higher than
the LOD of the assay. This highly sensitive technique does not require facilities or
instruments complying with strict biosafety criteria. Furthermore, it is efficient, safe,
and labor-saving as only ear specimens need be sampled. Therefore, it is a promising
technique for epidemiological screening of Taiwan ferret badger rabies.
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Affiliation(s)
- Ai-Ping Hsu
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.).,Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.)
| | - Chun-Hsien Tseng
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.)
| | - Yi-Ta Lu
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.)
| | - Yu-Hua Shih
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.).,Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.)
| | - Chung-Hsi Chou
- Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.).,Zoonoses Research Center, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.)
| | - Re-Shang Chen
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.).,Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.)
| | - Kuo-Jung Tsai
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.)
| | - Wen-Jane Tu
- Animal Health Research Institute, Council of Agriculture, No.376, Zhong zheng Rd., Tamsui Dist., New Taipei City 251, Taiwan (R.O.C.)
| | - Florence Cliquet
- Nancy OIE/WHO/EU Laboratory for Rabies and Wildlife, French Agency for Food, Environmental and Occupational Health &Safety, Technopole Agricole et Vétérinaire de Pixérécourt, Bâtiment H, CS 40009, 54220 MALZEVILLE, France
| | - Hsiang-Jung Tsai
- Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.).,Zoonoses Research Center, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 106, Taiwan (R.O.C.)
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7
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Zhang Y, Vrancken B, Feng Y, Dellicour S, Yang Q, Yang W, Zhang Y, Dong L, Pybus OG, Zhang H, Tian H. Cross-border spread, lineage displacement and evolutionary rate estimation of rabies virus in Yunnan Province, China. Virol J 2017; 14:102. [PMID: 28578663 PMCID: PMC5457581 DOI: 10.1186/s12985-017-0769-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2017] [Accepted: 05/25/2017] [Indexed: 12/12/2022] Open
Abstract
Background Rabies is an important but underestimated threat to public health, with most cases reported in Asia. Since 2000, a new epidemic wave of rabies has emerged in Yunnan Province, southwestern China, which borders three countries in Southeast Asia. Method We estimated gene-specific evolutionary rates for rabies virus using available data in GenBank, then used this information to calibrate the timescale of rabies virus (RABV) spread in Asia. We used 452 publicly available geo-referenced complete nucleoprotein (N) gene sequences, including 52 RABV sequences that were recently generated from samples collected in Yunnan between 2008 and 2012. Results The RABV N gene evolutionary rate was estimated to be 1.88 × 10−4 (1.37–2.41 × 10−4, 95% Bayesian credible interval, BCI) substitutions per site per year. Phylogenetic reconstructions show that the currently circulating RABV lineages in Yunnan result from at least seven independent introductions (95% BCI: 6–9 introductions) and represent each of the three main Asian RABV lineages, SEA-1, -2 and -3. We find that Yunnan is a sink location for the domestic spread of RABV and connects RABV epidemics in North China, South China, and Southeast Asia. Cross-border spread from southeast Asia (SEA) into South China, and intermixing of the North and South China epidemics is also well supported. The influx of RABV into Yunnan from SEA was not well-supported, likely due to the poor sampling of SEA RABV diversity. We found evidence for a lineage displacement of the Yunnan SEA-2 and -3 lineages by Yunnan SEA-1 strains, and considered whether this could be attributed to fitness differences. Conclusion Overall, our study contributes to a better understanding of the spread of RABV that could facilitate future rabies virus control and prevention efforts. Electronic supplementary material The online version of this article (doi:10.1186/s12985-017-0769-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yuzhen Zhang
- Yunnan Institute of Endemic Diseases Control and Prevention, Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, Dali, China
| | - Bram Vrancken
- Department of Microbiology and Immunology, Division of Clinical and Epidemiological Virology, Rega Institute, KU Leuven - University of Leuven, Leuven, Belgium
| | - Yun Feng
- Yunnan Institute of Endemic Diseases Control and Prevention, Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, Dali, China
| | - Simon Dellicour
- Department of Microbiology and Immunology, Division of Clinical and Epidemiological Virology, Rega Institute, KU Leuven - University of Leuven, Leuven, Belgium
| | - Qiqi Yang
- State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing, China
| | - Weihong Yang
- Yunnan Institute of Endemic Diseases Control and Prevention, Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, Dali, China
| | - Yunzhi Zhang
- Yunnan Institute of Endemic Diseases Control and Prevention, Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, Dali, China
| | - Lu Dong
- Ministry of Education Key Laboratory for Biodiversity and Ecological Engineering, College of Life Sciences, Beijing Normal University, Beijing, China
| | | | - Hailin Zhang
- Yunnan Institute of Endemic Diseases Control and Prevention, Yunnan Provincial Key Laboratory for Zoonosis Control and Prevention, Dali, China.
| | - Huaiyu Tian
- State Key Laboratory of Remote Sensing Science, College of Global Change and Earth System Science, Beijing Normal University, Beijing, China.
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Chacko K, Parakadavathu RT, Al-Maslamani M, Nair AP, Chekura AP, Madhavan I. Diagnostic difficulties in human rabies: A case report and review of the literature. Qatar Med J 2017; 2016:15. [PMID: 28534007 PMCID: PMC5427514 DOI: 10.5339/qmj.2016.15] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 10/31/2016] [Indexed: 12/25/2022] Open
Abstract
Rabies is a zoonotic disease with the highest fatality rate of any infectious disease. The clinical features of rabies encephalopathy are highly nonspecific at the onset and clinicians from low endemic areas usually face difficulties in recognizing cases during the early stages. The need for establishing a rapid and accurate test to identify rabies during the ante-mortem period is important. However, in actual clinical practice, the latter may remain difficult for various reasons. In human rabies, positively identifying the antigen, antibody or genetic material by various diagnostic methods during the symptomatic period is affected by the unpredictable nature of viremia, levels of antibody immune response of the host, and the virulence of the infecting strain. Also, more advanced testing with greater sensitivity may not be readily available at all centers. Here we describe a case of a young male who was bitten by a rabid dog and developed progressive encephalopathy with a fatal outcome, with negative antibodies in the cerebrospinal fluid (CSF). A review of the literature on the clinical features, diagnostic tests, treatment and prevention of rabies is also presented.
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Affiliation(s)
- Kadavil Chacko
- Infectious Diseases Division, Hamad Medical Corporation, Doha, Qatar
| | | | - Muna Al-Maslamani
- Infectious Diseases Division, Hamad Medical Corporation, Doha, Qatar
| | - Arun P Nair
- Infectious Diseases Division, Hamad Medical Corporation, Doha, Qatar
| | | | - Indira Madhavan
- Department of Medicine, Government Medical College, Thrissur, Kerala, India
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9
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Johnson N, Cunningham AF. Interplay between rabies virus and the mammalian immune system. World J Clin Infect Dis 2015; 5:67-76. [DOI: 10.5495/wjcid.v5.i4.67] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 09/23/2015] [Accepted: 11/17/2015] [Indexed: 02/06/2023] Open
Abstract
Rabies is a disease caused following infection of the brain by the rabies virus (RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervous system (CNS). There appears to be little involvement of other organ systems and little detectable immune stimulation prior to infection of the CNS. This failure of the mammalian immune system to respond to rabies virus infection leads, in the overwhelming majority of cases, to death of the host. To some extent, this failure is likely due to the exclusive replication of RABV in neurons and the limited ability to generate, sufficiently rapidly, an anti-viral antibody response in situ. This is reflected in the ability of post-exposure vaccination, when given early after infection, to prevent disease. The lack of immune stimulation during RABV infection preceding neural invasion is the Achilles heel of the immune response. Whilst many viruses infect the brain, causing encephalitis and neuronal deficit, none are as consistently fatal to the host as RABV. This is in part due to prior replication of many viruses in peripheral, non-neural tissue by other viruses that allows timely activation of the immune response before the host is overwhelmed. Our current understanding of the correlates of protection for rabies suggests that it is the action of neutralising antibodies that prevent infection and control spread of RABV. Furthermore, it tells us that the induction of immunity can protect and understanding how and why this happens is critical to controlling infection. However, the paradigm of antibody development suggests that antigen presentation overwhelmingly occurs in lymphoid tissue (germinal and non-germinal centres) and these are external to the CNS. In addition, the blood-brain-barrier may provide a block to the delivery of immune effectors (antibodies/plasma B-cells) entering where they are needed. Alternatively, there may be insufficient antigen exposure after natural infection to mount an effective response or the virus actively suppresses immune function. To improve our ability to treat this fatal infection it is imperative to understand how immunity to RABV develops and functions so that parameters of protection are better defined.
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10
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Ross RS, Wolters B, Hoffmann B, Geue L, Viazov S, Grüner N, Roggendorf M, Müller T. Instructive even after a decade: Complete results of initial virological diagnostics and re-evaluation of molecular data in the German rabies virus "outbreak" caused by transplantations. Int J Med Microbiol 2015; 305:636-43. [PMID: 26384867 DOI: 10.1016/j.ijmm.2015.08.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
In 2005, six patients in Germany received solid organs and both corneas from a donor with an unrecognized rabies infection. Initial virological diagnostics with the machinery available at the two national reference laboratories could quickly clarify the situation. Rabies virus antigen was detected in the organ donor's brain. In two of the three recipients with neurological alterations, intra vitam diagnosis was achieved by conventional RT-PCRs. Comparison of the phylogenetic relatedness of the different viral isolates proved transmission from the donor and, consequently, also established the diagnosis for the third patient. As indicated by the titre of neutralizing antibodies, the liver transplant recipient was protected from the lethal infection due to a vaccination against rabies virus, which he had received more than 15 years ago. All samples from the recipients of the corneas were invariably negative. Re-evaluation of the molecular data by real-time PCR did not lead to an improvement of intra vitam diagnosis but provided intriguing insights regarding the relative amounts of rabies virus RNA in different body fluids and peripheral organs. In saliva and skin, they were 250-200,000 times lower than in the infected patient's brains. Furthermore, in saliva samples taken serially from the same patient fluctuations by a factor of 160-500 were recorded. These findings highlight the problems of intra vitam diagnosis of rabies virus infections and make understandable why the virus can escape from all diagnostic attempts. Finally, in this context one should recall an almost trivial fact: Simple and appropriate postexposure prophylaxis could not only have saved the young organ donor's life but would also have prevented the whole transplantation-associated rabies "outbreak" in Germany.
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Affiliation(s)
- R Stefan Ross
- Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany.
| | - Bernd Wolters
- Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany
| | - Bernd Hoffmann
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Diagnostic Virology, Südufer 10, D-17493 Greifswald-Insel Riems, Germany
| | - Lutz Geue
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Molecular Pathogenesis, Naumburger Str. 96 a, 07743 Jena, Germany
| | - Sergei Viazov
- Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany
| | - Nico Grüner
- Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany
| | - Michael Roggendorf
- Institute of Virology, National Consiliary Laboratory for Rabies, Essen University Hospital, University of Duisburg-Essen, Hufelandstr., D-45122 Essen, Germany
| | - Thomas Müller
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Molecular Virology and Cell Biology, WHO Collaborating Centre for Rabies Surveillance and Research, OIE and National Reference Laboratory for Rabies, Südufer 10, D-17493 Greifswald-Insel Riems, Germany
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Abstract
Rabies is one of the most deadly infectious diseases, with a case-fatality rate approaching 100%. The disease is established on all continents apart from Antarctica; most cases are reported in Africa and Asia, with thousands of deaths recorded annually. However, the estimated annual figure of almost 60,000 human rabies fatalities is probably an underestimate. Almost all cases of human rabies result from bites from infected dogs. Therefore, the most cost-effective approach to elimination of the global burden of human rabies is to control canine rabies rather than expansion of the availability of human prophylaxis. Mass vaccination campaigns with parenteral vaccines, and advances in oral vaccines for wildlife, have allowed the elimination of rabies in terrestrial carnivores in several countries worldwide. The subsequent reduction in cases of human rabies in such regions advocates the multidisciplinary One Health approach to rabies control through the mass vaccination of dogs and control of canine populations.
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Affiliation(s)
- Anthony R Fooks
- Animal Health and Veterinary Laboratories Agency (AHVLA, Weybridge), New Haw, Addlestone, UK; WHO Communicable Disease Surveillance and Response Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, Addlestone, Weybridge, UK; Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; National Consortium for Zoonosis Research, University of Liverpool, Leahurst, Neston, UK.
| | - Ashley C Banyard
- Animal Health and Veterinary Laboratories Agency (AHVLA, Weybridge), New Haw, Addlestone, UK; WHO Communicable Disease Surveillance and Response Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, Addlestone, Weybridge, UK
| | - Daniel L Horton
- Animal Health and Veterinary Laboratories Agency (AHVLA, Weybridge), New Haw, Addlestone, UK; WHO Communicable Disease Surveillance and Response Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, Addlestone, Weybridge, UK
| | - Nicholas Johnson
- Animal Health and Veterinary Laboratories Agency (AHVLA, Weybridge), New Haw, Addlestone, UK; WHO Communicable Disease Surveillance and Response Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, Addlestone, Weybridge, UK
| | - Lorraine M McElhinney
- Animal Health and Veterinary Laboratories Agency (AHVLA, Weybridge), New Haw, Addlestone, UK; WHO Communicable Disease Surveillance and Response Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, Addlestone, Weybridge, UK; National Consortium for Zoonosis Research, University of Liverpool, Leahurst, Neston, UK
| | - Alan C Jackson
- Departments of Internal Medicine (Neurology) and of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
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12
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Pathak S, Horton DL, Lucas S, Brown D, Quaderi S, Polhill S, Walker D, Nastouli E, Núñez A, Wise EL, Fooks AR, Brown M. Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report. Virol J 2014. [PMID: 24708671 DOI: 10.1186/174-422x-11-63] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management. CASE PRESENTATION A 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen. CONCLUSION Rapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are typical for the clinical course of rabies in humans. Management guided by the Milwaukee protocol is feasible within well-resourced intensive care units, but its role in improving outcome for canine-derived rabies remains theoretical.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Michael Brown
- Hospital for Tropical Diseases, Virology and Intensive Care Units, University College Hospitals NHS Foundation Trust, London, UK.
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13
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Pathak S, Horton DL, Lucas S, Brown D, Quaderi S, Polhill S, Walker D, Nastouli E, Núñez A, Wise EL, Fooks AR, Brown M. Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report. Virol J 2014; 11:63. [PMID: 24708671 PMCID: PMC3977668 DOI: 10.1186/1743-422x-11-63] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 03/24/2014] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Human rabies infection continues to be a significant public health burden globally, and is occasionally imported to high income settings where the Milwaukee Protocol for intensive care management has recently been employed, with limited success in improving survival. Access to molecular diagnostics, pre- and post-mortem, and documentation of pathophysiological responses while using the Milwaukee protocol, can add useful insights for the future of rabies management. CASE PRESENTATION A 58-year-old British Asian woman was referred to a regional general hospital in the UK with hydrophobia, anxiety and confusion nine weeks after receiving a dog bite in North West India. Nuchal skin biopsy, saliva, and a skin biopsy from the site of the dog bite wound, taken on the day of admission, all demonstrated the presence of rabies virus RNA. Within 48 hours sequence analysis of viral RNA confirmed the diagnosis and demonstrated that the virus was a strain closely related to canine rabies viruses circulating in South Asia. Her condition deteriorated rapidly with increased agitation and autonomic dysfunction. She was heavily sedated and intubated on the day after admission, treated according to a modified Milwaukee protocol, and remained stable until she developed heart block and profound acidosis and died on the eighth day. Analysis of autopsy samples showed a complete absence of rabies neutralizing antibody in cerebrospinal fluid and serum, and corresponding high levels of virus antigen and nucleic acid in brain and cerebrospinal fluid. Quantitative PCR showed virus was also distributed widely in peripheral tissues despite mild or undetectable histopathological changes. Vagus nerve branches in the heart showed neuritis, a probable Negri body but no demonstrable rabies antigen. CONCLUSION Rapid molecular diagnosis and strain typing is helpful in the management of human rabies infection. Post-mortem findings such as vagal neuritis highlight clinically important effects on the cardiovascular system which are typical for the clinical course of rabies in humans. Management guided by the Milwaukee protocol is feasible within well-resourced intensive care units, but its role in improving outcome for canine-derived rabies remains theoretical.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Michael Brown
- Hospital for Tropical Diseases, Virology and Intensive Care Units, University College Hospitals NHS Foundation Trust, London, UK.
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14
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Murthy JMK, Dastur FD, Khadilkar SV, Kochar DK. Rabies, tetanus, leprosy, and malaria. HANDBOOK OF CLINICAL NEUROLOGY 2014; 121:1501-20. [PMID: 24365433 DOI: 10.1016/b978-0-7020-4088-7.00101-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The developing world is still endemic to rabies, tetanus, leprosy, and malaria. Globally more than 55000 people die of rabies each year, about 95% in Asia and Africa. Annually, more than 10 million people, mostly in Asia, receive postexposure vaccination against the disease. World Health Organization estimated tetanus-related deaths at 163000 in 2004 worldwide. Globally, the annual detection of new cases of leprosy continues to decline and the global case detection declined by 3.54% during 2008 compared to 2007. Malaria is endemic in most countries, except the US, Canada, Europe, and Russia. Malaria accounts for 1.5-2.7 million deaths annually. Much of the disease burden related to these four infections is preventable.
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Affiliation(s)
- J M K Murthy
- Continental Institute of Neurosciences & Rehabilitation, Continental Hospitals, IT & Financial District, Gachibowli, Hyderabad, India.
| | - Faram D Dastur
- Department of Medicine, P.D. Hinduja National Hospital, Mumbai, India
| | - Satish V Khadilkar
- Department of Neurology, Grant Medical College and Sir J.J. Group of Hospitals and Bombay Hospital Institute of Medical Sciences, Mumbai, India
| | - Dhanpat K Kochar
- Medical Research, Rajasthan University of Health Sciences, Jaipur, India
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15
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Han MG, Jung Sang R, Jeong YE, Ju YR, Cho JE, Park JS. Epidemiologic features of animal bite cases occurring in rabies-endemic areas of Korea, 2005 to 2009. Osong Public Health Res Perspect 2013; 3:14-8. [PMID: 24159481 PMCID: PMC3738676 DOI: 10.1016/j.phrp.2012.01.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Revised: 12/15/2011] [Accepted: 01/05/2012] [Indexed: 10/31/2022] Open
Abstract
OBJECTIVES Human rabies is a reemerging infectious disease in Korea. There was no human rabies case for 14 years until the disease had reoccurred in 1999. To prevent occurrence of human rabies, surveillance for animal bite patients in rabies endemic areas in Korea was conducted since 2005 as a part of a human rabies control program. The animal bite cases were analyzed to determine whether patients were treated according to the post-exposure prophylaxis (PEP) guideline of the Korea Centers for Disease Control and Prevention. METHODS Information of animal bite cases that occurred from 2005 to 2009 in rabies high-risk regions were collected by cooperation with Regional Public Health Centers in 18 cities/districts of rabies endemic areas. RESULTS A total of 2458 animal bite cases were reported. Dogs accounted for 86% of animal bites and 67% of the animals were not vaccinated against rabies virus. For PEP, among rabies-vaccinated animals, 92.7% were observed for clinical signs and 1.4% underwent necropsy. Among unvaccinated animals, 72.7% were observed for clinical signs and 4.1% underwent necropsy. The remaining animals were not available for examination. Of the animal bite patients, 32.5% received PEP and 51.6% were treated by first aid or by washing the wound. CONCLUSIONS Given that no human rabies cases were reported since 2005 and animal rabies was continuously reported in endemic areas of Korea, the human rabies control program implemented in 2005 appears to have a significant role in the prevention and control of human rabies.
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Affiliation(s)
- Myung Guk Han
- Division of Arboviruses, Korea National Institute of Health, Osong, Korea
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16
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Guo Z, Tao X, Yin C, Han N, Yu J, Li H, Liu H, Fang W, Adams J, Wang J, Liang G, Tang Q, Rayner S. National borders effectively halt the spread of rabies: the current rabies epidemic in China is dislocated from cases in neighboring countries. PLoS Negl Trop Dis 2013; 7:e2039. [PMID: 23383359 PMCID: PMC3561166 DOI: 10.1371/journal.pntd.0002039] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Accepted: 12/14/2012] [Indexed: 12/25/2022] Open
Abstract
China has seen a massive resurgence of rabies cases in the last 15 years with more than 25,000 human fatalities. Initial cases were reported in the southwest but are now reported in almost every province. There have been several phylogenetic investigations into the origin and spread of the virus within China but few reports investigating the impact of the epidemic on neighboring countries. We therefore collected nucleoprotein sequences from China and South East Asia and investigated their phylogenetic and phylogeographic relationship. Our results indicate that within South East Asia, isolates mainly cluster according to their geographic origin. We found evidence of sporadic exchange of strains between neighboring countries, but it appears that the major strain responsible for the current Chinese epidemic has not been exported. This suggests that national geographical boundaries and border controls are effective at halting the spread of rabies from China into adjacent regions. We further investigated the geographic structure of Chinese sequences and found that the current epidemic is dominated by variant strains that were likely present at low levels in previous domestic epidemics. We also identified epidemiological linkages between high incidence provinces consistent with observations based on surveillance data from human rabies cases.
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Affiliation(s)
- Zhenyang Guo
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - Xiaoyan Tao
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Cuiping Yin
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Na Han
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - Jinning Yu
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Hao Li
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Haizhou Liu
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - Wei Fang
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - James Adams
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - Jun Wang
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
| | - Guodong Liang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Qing Tang
- State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
- * E-mail: (QT); (SR)
| | - Simon Rayner
- State Key Laboratory for Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China
- * E-mail: (QT); (SR)
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17
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Reaves EJ, Salmón-Mulanovich G, Guevara C, Kochel TJ, Steinbach TJ, Bentzel DE, Montgomery JM. Susceptibility and lack of evidence for a viremic state of rabies in the night owl monkey, Aotus nancymaae. Virol J 2012; 9:95. [PMID: 22612895 PMCID: PMC3522049 DOI: 10.1186/1743-422x-9-95] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Accepted: 04/24/2012] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Rabies causes an acute fatal encephalomyelitis in most mammals following infection with rhabdovirus of the genus Lyssavirus. Little is known about rabies virus infection in species of New World non-human Primates (NHP). To investigate the suitability of the owl monkey Aotus nancymaae asissue sections examined were unremarkable for inflammation or other histologic signs of rabies a viable animal model for rabies virus candidate vaccine testing, we used clinical presentation, serology, viral isolation, and PCR to evaluate the incubation period, immunity, and pathogenesis of infected animals. We tested the hypothesis that no viremic state exists for rabies virus. METHODS Eight monkeys divided into two equal groups were inoculated intramuscularly either in the neck or footpad with 105 pfu of rabies virus (Pasteur/V-13R) and observed for >130 days. Oral and blood samples were collected and analyzed. RESULTS Two monkeys inoculated in the neck displayed classic paralytic rabies. The mean incubation period was 11.5 days. The average maximum IgG response (antibody titer >0.200 O.D.) was achieved at day 10.0 and 62.3 in the clinical rabies and non-clinical rabies cases, respectively (p = 0.0429). No difference in IgM or IgG time to seroconversion or average maximum IgM level was observed between neck versus footpad inoculation groups. No viremia or viral shedding was detected by PCR or viral isolation during the observation period, including within the two symptomatic animals three days after disease onset. Tissue sections examined were unremarkable for inflammation or other histologic signs of rabies within the asymptomatic animal. Similarly none of the brain sections exhibited immunoreactivity for rabies virus antibody. DISCUSSION This study demonstrates there is no difference in time to immune response between inoculation sites and distance to the brain; however, immune response tends to be more rapid in cases of clinically apparent disease and prolonged in cases infected at sites further from the brain. CONCLUSIONS Our findings support the hypothesis that a viremic state for rabies does not exist in the New World Monkey, Aotus nancymaae, and it appears that this species may be refractory to infection. The species does provide a suitable model to assess post infection immune responses. Additional studies that address the limitations of sample size, length of observation, and lack of measurable infection should be conducted.
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Affiliation(s)
- Erik J Reaves
- Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru
| | | | - Carolina Guevara
- Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru
| | - Tadeusz J Kochel
- Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru
| | - Thomas J Steinbach
- Walter Reed Army Institute of Research, 503 Robert Grant Av, Silver Spring, MD, 20910-7500, USA
| | - David E Bentzel
- Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru
| | - Joel M Montgomery
- Naval Medical Research Unit No. 6, Av. Venezuela cdra. 36 s/n, Callao 2, Peru
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Wu X, Smith TG, Rupprecht CE. From brain passage to cell adaptation: the road of human rabies vaccine development. Expert Rev Vaccines 2012; 10:1597-608. [PMID: 22043958 DOI: 10.1586/erv.11.140] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.
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Affiliation(s)
- Xianfu Wu
- Centers for Disease Control and Prevention, Rabies Program/PRB/DHCPP/NCEZID, 1600 Clifton Road, Atlanta, GA 30333, USA.
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19
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Gautret P, Parola P. Rabies vaccination for international travelers. Vaccine 2011; 30:126-33. [PMID: 22085557 DOI: 10.1016/j.vaccine.2011.11.007] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Revised: 10/21/2011] [Accepted: 11/01/2011] [Indexed: 12/15/2022]
Abstract
Rabies prevention in travelers is a controversial issue. According to experts, the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveler, the rabies endemicity and access to appropriate medical care in the country of destination. However, no detailed information is available regarding the last two determinants in many regions. Twenty-two cases of rabies were reported in tourists, expatriates and migrant travelers over the last decade, including three cases following short-term travel of no more than two weeks. Studies on rabies post-exposure prophylaxis (PEP) in travelers show that overall, 0.4% (range 0.01-2.3%) of travelers have experienced an at-risk bite per month of stay in a rabies-endemic country, while 31% of expatriates and 12% of tourists were vaccinated against rabies before traveling. The main reason cited by travelers for not being vaccinated is the cost of the vaccine. The majority of patients who sustained a high risk injury was not vaccinated against rabies before traveling and were not properly treated abroad. From available studies, the following risk factors for injuries sustained from potentially rabid animals may be identified: traveling to South-East Asia, India or North Africa, young age, and traveling for tourism. The duration of travel does not appear to be a risk factor. It should be noted that "at-risk activities" have not been addressed in these studies. Detailed rabies distribution maps and information on the availability of rabies biologics are urgently needed in order to identify those travelers who need pre-travel vaccination. Meanwhile, cost-minimization of rabies pre-exposure vaccination may be achieved in several ways, notably by using the intra-dermal method of vaccination.
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Affiliation(s)
- Philippe Gautret
- Institut Hospitalo-Universitaire en Maladies Infectieuses et Tropicales, Hôpital Nord, AP-HM, Marseille, France.
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20
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Malerczyk C, Detora L, Gniel D. Imported human rabies cases in europe, the United States, and Japan, 1990 to 2010. J Travel Med 2011; 18:402-7. [PMID: 22017716 DOI: 10.1111/j.1708-8305.2011.00557.x] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Faizee N, Hailat NQ, Ababneh MMK, Hananeh WM, Muhaidat A. Pathological, Immunological and Molecular Diagnosis of Rabies in Clinically Suspected Animals of Different Species Using Four Detection Techniques in Jordan. Transbound Emerg Dis 2011; 59:154-64. [DOI: 10.1111/j.1865-1682.2011.01255.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Abstract
BACKGROUND In 2009, 58.6 million UK residents traveled abroad. Of these, 49.5 million (84.5%) visits were to Europe and North America and 9.1 million (15.5%) were to other parts of the world. Rabies is widely distributed and continues to be a major public health issue in many developing countries. The UK is free of rabies in carnivore host species, although cases of rabies in bats have been reported. This study examined the rabies postexposure prophylaxis (PEP) service from 2000 to July 2009 at the Liverpool School of Tropical Medicine. METHODS Medical records of patients who attended the clinic for rabies PEP were reviewed. RESULTS During the study period, 139 patients were treated for possible rabies exposure. The mean age was 35 years. Thailand and Turkey each accounted for 31 (22.3%) cases. Sixty-nine (49.6%) of those seen were due to dog bites. Most injuries involved a lower limb (n = 67, 48.2%) or hands (n = 26, 18.7%). Eighty-six (61.9%) cases had initiated rabies PEP overseas, but only 3 of the 78 (3.8%) meeting UK criteria for rabies immunoglobulin (RIG) received it while overseas. Only an additional 11 patients received RIG on return to the UK; most were seen more than 7 days after initiation of PEP. The median time from exposure to receiving rabies PEP was 1 day (range: 0-1,720). Only 14 (10.1%) had received preexposure rabies vaccination. CONCLUSIONS The majority of travelers seeking PEP at this clinic initiated treatment overseas. Most had not received RIG abroad, when it would have been appropriate. Initiation of appropriate treatment is often delayed and is a concern to those without preexposure rabies immunization. In view of the scarcity of RIG, travelers need to be aware of the risks, consider preexposure immunization, and present early for PEP.
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Affiliation(s)
- Limin Wijaya
- Department of Infectious Disease,Singapore Clinical Group, Singapore General Hospital, Outram Road, Singapore.
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Harkess G, Fooks AR. Lyssaviruses: special emphasis on rabies virus and other members of the lyssavirus genus. Methods Mol Biol 2011; 665:279-307. [PMID: 21116807 DOI: 10.1007/978-1-60761-817-1_16] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Rabies is routinely diagnosed based on the clinical description and history of exposure in a rabies-endemic country. A negative diagnostic test for rabies virus or a related lyssavirus does not exclude the clinical diagnosis. Diagnostic tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. Often, only a sample from a single time point is investigated reducing the overall sensitivity of any diagnosis. With the advent of molecular biology, tests have been developed that are rapid, robust, and sensitive in support of the rapid detection and strain identification of rabies virus from clinical specimens. These molecular tests complement conventional tests in rabies diagnosis, particularly for human cases, for which an early laboratory diagnosis is critical and may decrease the number of unnecessary contacts with the patient, reduce the requirement for invasive and costly interventions, and enable the appropriate medical treatment regimen to be administered for the patient. The barrier to success is in transferring the technology for the latest techniques in rabies diagnosis to rabies-endemic countries. These barriers are not insurmountable and in liaison with international organisations, especially OIE, FAO, and WHO, these diagnostic tests will be validated for rabies diagnosis and surveillance, and implemented in modern and well-equipped diagnostic laboratories throughout the world.
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Affiliation(s)
- Graeme Harkess
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency, New Haw, Surrey, UK
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24
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Wacharapluesadee S, Hemachudha T. Ante- and post-mortem diagnosis of rabies using nucleic acid-amplification tests. Expert Rev Mol Diagn 2010; 10:207-18. [PMID: 20214539 DOI: 10.1586/erm.09.85] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Sensitivity, specificity and short turn-around time nucleic acid-amplification tests (NATs) have been steadily improving. NATs have been employed in the diagnosis of rabies to distinct different strains, as well as to identify new lyssaviruses. NATs have advantages over traditional methods, such as the direct fluorescence antibody test. They can be applied to fluid samples and brain tissue that is substantially decomposed. NATs can be used as an alternative method for confirmation or exclusion of the diagnosis in a suspected rabies patient. Real-time PCR methods are more favored than conventional reverse-transcription PCR methods by several laboratories. Second-round PCR, either nested or heminested, has been used for ante-mortem diagnosis to detect low levels of RNA. This review the details obstacles in making a diagnosis, how to properly utilize NATs (sample preparation, nucleic amplification techniques, amplification targets and primer design); and interprets the results obtained in recent studies.
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Affiliation(s)
- Supaporn Wacharapluesadee
- WHO Collaborating Centre for Research and Training on Viral Zoonoses, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand, 10330.
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Comparative analysis of rabies virus reverse transcription-PCR and virus isolation using samples from a patient infected with rabies virus. J Clin Microbiol 2010; 48:2960-2. [PMID: 20554825 DOI: 10.1128/jcm.00728-10] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Definite and rapid diagnosis of rabies is required for individual case management as well as for public health. For the first time, a direct comparison of virus isolation with quantitative real-time reverse transcription (RT)-PCR on human rabies samples was conducted. RT-PCR was found to be more sensitive than virus isolation.
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Banyard AC, Hartley M, Fooks AR. Reassessing the risk from rabies: a continuing threat to the UK? Virus Res 2010; 152:79-84. [PMID: 20558215 PMCID: PMC7126864 DOI: 10.1016/j.virusres.2010.06.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2010] [Revised: 06/07/2010] [Accepted: 06/08/2010] [Indexed: 12/25/2022]
Abstract
The threat of re-introduction of rabies virus into the United Kingdom exists on several levels. Firstly, importation of live animals into the UK continues to challenge the regulations in place to ensure that the virus does not enter the country. Secondly, the indigenous bat population is known to carry a virus genetically related to rabies virus, the European bat lyssavirus (EBLV). Molecular characterization of this virus has further characterized it as being EBLV type 2, genetically distinct from a similar virus that has caused several human deaths across Europe. Finally, a lack of awareness of the threat of rabies and related viruses to travelers visiting endemic areas also constitutes a re-introduction threat to the UK population. This review will address the most recent cases of lyssavirus infection, in both humans and animals, either contracted within the UK or from abroad. We highlight the current diagnostic necessity for testing indigenous and foreign cases and comment on current UK government policy in light of a European call to harmonise rabies legislation across Europe.
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Affiliation(s)
- Ashley C Banyard
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency, Weybridge, Addlestone, Surrey, UK.
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Jain S, Parwar VR. Rabies: Post exposure prophylaxis for the health care workers. Indian J Pediatr 2009; 76:1276-7. [PMID: 20108064 DOI: 10.1007/s12098-009-0325-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Fooks AR, Johnson N, Freuling CM, Wakeley PR, Banyard AC, McElhinney LM, Marston DA, Dastjerdi A, Wright E, Weiss RA, Müller T. Emerging technologies for the detection of rabies virus: challenges and hopes in the 21st century. PLoS Negl Trop Dis 2009; 3:e530. [PMID: 19787037 PMCID: PMC2745658 DOI: 10.1371/journal.pntd.0000530] [Citation(s) in RCA: 78] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis.
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Affiliation(s)
- Anthony R. Fooks
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Nicholas Johnson
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Conrad M. Freuling
- Friedrich-Loeffler-Institute, Federal Research Institute of Animal Health, Wusterhausen, Germany
| | - Philip R. Wakeley
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Ashley C. Banyard
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Lorraine M. McElhinney
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Denise A. Marston
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Akbar Dastjerdi
- Rabies and Wildlife Zoonoses Group, Veterinary Laboratories Agency (VLA, Weybridge), WHO Collaborating Centre for the Characterisation of Rabies and Rabies-related Viruses, New Haw, Addlestone, United Kingdom
| | - Edward Wright
- Division of Infection and Immunity, University College London, London, United Kingdom
| | - Robin A. Weiss
- Division of Infection and Immunity, University College London, London, United Kingdom
| | - Thomas Müller
- Friedrich-Loeffler-Institute, Federal Research Institute of Animal Health, Wusterhausen, Germany
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Gurrala R, Dastjerdi A, Johnson N, Nunez-Garcia J, Grierson S, Steinbach F, Banks M. Development of a DNA microarray for simultaneous detection and genotyping of lyssaviruses. Virus Res 2009; 144:202-8. [DOI: 10.1016/j.virusres.2009.04.028] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2009] [Revised: 04/28/2009] [Accepted: 04/30/2009] [Indexed: 12/25/2022]
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Nadin-Davis SA, Sheen M, Wandeler AI. Development of real-time reverse transcriptase polymerase chain reaction methods for human rabies diagnosis. J Med Virol 2009; 81:1484-97. [PMID: 19551825 DOI: 10.1002/jmv.21547] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
To improve timely ante-mortem human rabies diagnosis, methods to detect viral RNA by TaqMan-based quantitative reverse transcriptase polymerase chain reactions (qRT-PCRs) have been developed. Three sets of two primers and one internal dual-labeled probe for each primer set that target distinct conserved regions of the rabies virus N gene were designed and evaluated. Using a collection of 203 isolates representative of the world-wide diversity of rabies virus, all three primers/probe sets were shown to detect a wide range of rabies virus strains with very few detection failures; the RABVD1 set in particular was the most broadly reactive. These qRT-PCR assays were shown to be quantitative over a wide range of viral titer and were 100-1,000 times more sensitive than nested RT-PCR; however, both the standard and real-time PCR methods yielded concordant results when used to test a collection of archived human suspect samples. The qRT-PCR assay was employed to monitor virus load in the saliva of a rabies virus-infected patient undergoing the Milwaukee treatment protocol. However in this case it would appear that reduction of the viral load in the patient's saliva over time did not appear to correlate well with clearance of viral components from the brain.
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Dacheux L, Reynes J, Buchy P, Sivuth O, Diop B, Rousset D, Rathat C, Jolly N, Dufourcq J, Nareth C, Diop S, Iehlé C, Rajerison R, Sadorge C, Bourhy H. A Reliable Diagnosis of Human Rabies Based on Analysis of Skin Biopsy Specimens. Clin Infect Dis 2008; 47:1410-7. [DOI: 10.1086/592969] [Citation(s) in RCA: 130] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
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Gautret P, Shaw M, Gazin P, Soula G, Delmont J, Parola P, Soavi MJ, Brouqui P, Matchett DE, Torresi J. Rabies postexposure prophylaxis in returned injured travelers from France, Australia, and New Zealand: a retrospective study. J Travel Med 2008; 15:25-30. [PMID: 18217866 DOI: 10.1111/j.1708-8305.2007.00164.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND There is little published information available describing rabies pre- and postexposure prophylaxis (PEP) in tourists returning to their home country and seeking care for animal-associated injuries, especially those associated with a rabies risk. METHOD We analyzed 261 travelers seeking care on returning to their home country following an animal-related injury acquired abroad. Information on individual cases of rabies (PEP) including preexposure status, type of contact with a potentially rabid animal, type of animal, and the nature of rabies PEP was collected by retrospectively analyzing records from May 1997 to May 2005. RESULTS The majority of injuries were acquired in South-east Asia and North Africa. Only 6.8% of injured patients were previously vaccinated against rabies, while 75.4% of the cohort experienced a severe injurious contact with animals (World Health Organization category III). Of travelers who sustained a high-risk injury, only 24% received both vaccination and rabies immune globulin,(RIG) while 76% received vaccination only. Of the travelers who did not receive RIG, 43% had received a first dose of vaccine more than 7 days after return and before presenting to a clinic in their home country. CONCLUSIONS This study highlights important deficiencies in rabies PEP for travelers who acquire high-risk, animal-associated injuries in rabies-endemic countries, with the majority not receiving adequate PEP or experiencing a substantial delay before receiving rabies vaccination.
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Affiliation(s)
- Philippe Gautret
- Service des Maladies Infectieuses et Tropicales, Hôpital Nord, Marseille, France.
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Madhusudana SN, Sukumaran SM. Antemortem diagnosis and prevention of human rabies. Ann Indian Acad Neurol 2008; 11:3-12. [PMID: 19966972 PMCID: PMC2781142 DOI: 10.4103/0972-2327.40219] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2008] [Revised: 02/17/2008] [Accepted: 02/24/2008] [Indexed: 12/25/2022] Open
Abstract
Human rabies still continues to be a significant health problem in India and other developing countries where dogs are the major vectors of transmission. Rabies in humans can present in two clinical forms, i.e., furious and paralytic. While diagnosis of furious rabies can be made based on the typical symptoms and signs, paralytic rabies poses a diagnostic dilemma to the neurologists who may encounter these cases in their practice. Although there are certain clinical features that distinguish this disease from other forms of Guillain-Barre syndromes, confirmation of diagnosis may require laboratory assistance. Conventional techniques such as antigen detection, antibody assays and virus isolation have limited success. The recently introduced molecular techniques show more promise in confirming the cases of paralytic rabies. There has not been much success in the treatment of confirmed rabies cases and recovery from rabies is extremely rare. Therefore, preventive measures of this dreaded disease after an exposure become extremely important. The present article reviews the current status of human rabies with regard to antemortem diagnosis, disease management and post-exposure prophylaxis.
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Affiliation(s)
- Shampur Narayana Madhusudana
- Department of Neurovirology, Human Brain Tissue Repository, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore - 560 029, India
| | - Suja Moorlyath Sukumaran
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore - 560 029, India
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Use of a molecular epidemiological database to track human rabies case histories in South Africa. Epidemiol Infect 2007; 136:1270-6. [PMID: 17961278 DOI: 10.1017/s0950268807009582] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
The KwaZulu Natal and Eastern Cape provinces of South Africa have experienced a serious dog rabies epidemic over the past three decades. Towards a better understanding of this epidemic, we have previously analysed nucleotide sequences of 142 rabies virus specimens that were obtained from these regions during 2003-2004 and provided a molecular description of the geographical distribution of rabies viral variants in the affected provinces. Here, as an extension, we studied five human cases that occurred during 2002-2003 and demonstrated the use of the sequence database in tracking unknown human rabies case histories. We were able to identify the geographical origin of viruses responsible for each human infection and in one case obtained evidence that suggested a non-bite transmission of rabies virus from an infected dog to a child. We argue for the value of this information in surveillance and epidemiological study and in the follow-up and management of potential exposures.
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Tamashiro H, Matibag GC, Ditangco RA, Kanda K, Ohbayashi Y. Revisiting rabies in Japan: Is there cause for alarm? Travel Med Infect Dis 2007; 5:263-75. [PMID: 17870631 DOI: 10.1016/j.tmaid.2007.06.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2007] [Revised: 06/08/2007] [Accepted: 06/12/2007] [Indexed: 12/25/2022]
Abstract
Since 1957 Japan has successfully eradicated human and animal rabies through registration, confinement and compulsory vaccination of family dogs, and elimination of stray dogs. However, in November 2006, two cases of human rabies infections were reported in the country. These patients were bitten by dogs during travel in the Philippines, and did not receive pre- and post-exposure prophylaxes. With the mounting numbers of Japanese travelers every year, the risk of infection increases especially to those who visit regions where the disease is endemic. In this paper, we shall discuss the two recent human deaths from rabies, review the current situation and control measures in Japan and surrounding countries where the disease is prevalent, summarize precautionary measures for travelers, and suggest public health strategies to prevent the re-introduction of rabies in the country.
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Affiliation(s)
- Hiko Tamashiro
- Department of Global Health and Epidemiology, Division of Preventive Medicine, Graduate School of Medicine Hokkaido University, Kita-15 Nishi-7, Kita-ku, Sapporo 060-8638 Japan.
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Gautret P, Schwartz E, Shaw M, Soula G, Gazin P, Delmont J, Parola P, Soavi MJ, Matchett E, Brown G, Torresi J. Animal-associated injuries and related diseases among returned travellers: A review of the GeoSentinel Surveillance Network. Vaccine 2007; 25:2656-63. [PMID: 17234310 DOI: 10.1016/j.vaccine.2006.12.034] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2006] [Revised: 11/06/2006] [Accepted: 12/05/2006] [Indexed: 12/25/2022]
Abstract
BACKGROUND Increased travel to exotic destinations around the world is escalating the risk of exposure to animal-associated injuries with a risk of acquiring rabies. METHODS We have examined data reported to GeoSentinel Surveillance Network to highlight characteristics of animal-associated injuries in travellers. RESULTS A total of 320 cases were reported from 1998 to 2005. Travellers were predominantly tourists from developed countries with median travel duration of 23 days. A pre-travel encounter was recorded in 45.0% of the cases. A significantly greater proportion of patients with animal-related injuries were female compared to other travel associated diagnosis (54.7% versus 47.4%) and were most likely patients aged <15 years (6.2% versus 2.6%). The proportionate morbidity for sustaining an animal bite was higher among travellers visiting Southeast Asia (3.9%) and the rest of Asia (2.2%) compared to Australia-New Zealand (1.9%), Africa (1.0%), Latin America (0.8%), North America (0.9%) and Europe (1.2%). Seventy-five percent of cases occurred in countries endemic for rabies. Dogs were involved in 51.3% of cases, monkeys in 21.2%, cats in 8.2%, bats in 0.7% and humans in 0.7%. The higher likelihood for animal-related injuries among female travellers was dependant on the animal species involved, with monkeys accounting for the majority of injuries. In contrast, males were more likely to be injured by dogs. Only 66.1% of all patients reported with animal-related injury received rabies post-exposure prophylaxis. CONCLUSIONS This data shows that animal-associated injuries are not uncommon among returned travellers presenting to GeoSentinel sites. The highest proportion of injuries was recorded in travellers to Asia, mostly in regions, which are endemic for rabies, and this had led to a requirement for PEP.
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Affiliation(s)
- Philippe Gautret
- Service des Maladies Infectieuses et Tropicales, AP-HM, Hôpital Nord, 13015 Marseille, Cedex 05, France.
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Solomon T, Ooi MH, Mallewa M. Chapter 10 Viral infections of lower motor neurons. HANDBOOK OF CLINICAL NEUROLOGY 2007; 82:179-206. [PMID: 18808895 DOI: 10.1016/s0072-9752(07)80013-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Affiliation(s)
- Tom Solomon
- Viral CNS Infections Group, Divisions of Neurological Sciences and Medical Biology, and School of Tropical Medicine, University of Liverpool, Liverpool, UK
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Nadin-Davis SA, Turner G, Paul JPV, Madhusudana SN, Wandeler AI. Emergence of Arctic-like rabies lineage in India. Emerg Infect Dis 2007; 13:111-6. [PMID: 17370523 PMCID: PMC2725804 DOI: 10.3201/eid1301.060702] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
A collection of 37 rabies-infected samples, 10 human saliva and 27 animal brain, were recovered during 2001-2004 from the cities of Bangalore and Hyderabad in southern India and from Kasauli, a mountainous region in Himachal Pradesh, northern India. Phylogenetic analysis of partial N gene nucleotide sequences of these 37 specimens and 1 archival specimen identified 2 groups, divided according to their geographic (north or south) origins. Comparison of selected Indian viruses with representative rabies viruses recovered worldwide showed a close association of all Indian isolates with the circumpolar Arctic rabies lineage distributed throughout northern latitudes of North America and Europe and other viruses recovered from several Asian countries.
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Affiliation(s)
- Rajaraman Durai
- Academic Department of Surgery, Royal London Hospital, London E1 1BB
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Nagarajan T, Mohanasubramanian B, Seshagiri EV, Nagendrakumar SB, Saseendranath MR, Satyanarayana ML, Thiagarajan D, Rangarajan PN, Srinivasan VA. Molecular epidemiology of rabies virus isolates in India. J Clin Microbiol 2006; 44:3218-24. [PMID: 16954251 PMCID: PMC1594703 DOI: 10.1128/jcm.00801-06] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
In India, rabies is enzootic and is a serious public health and economic problem. India has a large population of stray dogs which, together with a lack of effective control strategies, might have led to the persistence of rabies virus (RV) in the canine population. Our objective was to study the molecular epidemiology of RV isolates in India based on nucleotide sequence analysis of 29 RV isolates originating from different species of animals in four states. Here we have analyzed two sets of sequence data based upon a 132-nucleotide region of the cytoplasmic domain (CD) of the G gene (G-CD) and a 549-nucleotide region (Psi-L) that combines the noncoding G-L intergenic region (Psi) and a fragment of the polymerase gene (L). Phylogenetic analysis revealed that the RV isolates belong to genotype 1 and that they were related geographically but were not related according to host species. Five different genetic clusters distributed among three geographical regions were identified. Comparison of the deduced amino acid sequences of G-CD between RV isolates revealed three amino acid changes (amino acid 462G [aa462G], aa465H, and aa468K) that distinguished the Indian RVs from RV isolates in other parts of the world. Analysis of the data indicated that the dog rabies virus variants are the major circulating viruses in India that transmit the disease to other domestic animals and humans as well.
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Affiliation(s)
- T Nagarajan
- Indian Immunologicals Limited, Gachibowli, Hyderabad 500 032, India
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Vázquez-Morón S, Avellón A, Echevarría JE. RT-PCR for detection of all seven genotypes of Lyssavirus genus. J Virol Methods 2006; 135:281-7. [PMID: 16713633 DOI: 10.1016/j.jviromet.2006.03.008] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2005] [Revised: 03/15/2006] [Accepted: 03/20/2006] [Indexed: 10/24/2022]
Abstract
The Lyssavirus genus includes seven species or genotypes named 1-7. Rabies genotypes correlate with geographical distribution and specific hosts. Co-circulation of different lyssaviruses, imported cases, and the presence of unknown viruses, such as Aravan, Khujand, Irkut and West Caucasian Bat Virus, make it necessary to use generic methods able to detect all lyssaviruses. Primer sequences were chosen from conserved regions in all genotypes in order to optimise a generic RT-PCR. Serial dilutions of 12 RNA extracts from all seven Lyssavirus genotypes were examined to compare the sensitivity of the RT-PCR standardised in this study with a published RT-PCR optimised for EBLV1 detection and capable of amplifying RNA from all seven lyssaviruses. All seven genotypes were detected by both RT-PCRs, however, the sensitivity was higher with the new version of the test. Twenty samples submitted for rabies diagnosis were tested by the new RT-PCR. Eight out of 20 samples from six dogs, one horse and one bat were found positive, in agreement with immunofluorescence results. Seven samples from terrestrial mammals were genotype 1 and one from a bat was genotype 5. In conclusion, this method can be used to complement immunofluorescence for the diagnosis of rabies, enabling the detection of unexpected lyssaviruses during rabies surveillance.
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Affiliation(s)
- S Vázquez-Morón
- Instituto de Salud Carlos III, Centro Nacional de Microbiología, Servicio de Microbiología Diagnóstica, Aislamiento y Detección de Virus, Ctra. Majadahonda-Pozuelo Km2, 28220 Majadahonda, Madrid, Spain.
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Nagaraj T, Vasanth JP, Desai A, Kamat A, Madhusudana SN, Ravi V. Ante mortem diagnosis of human rabies using saliva samples: comparison of real time and conventional RT-PCR techniques. J Clin Virol 2006; 36:17-23. [PMID: 16504574 DOI: 10.1016/j.jcv.2006.01.009] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2005] [Revised: 01/03/2006] [Accepted: 01/09/2006] [Indexed: 12/25/2022]
Abstract
BACKGROUND Rabies is an enzootic and fatal disease and is still a major problem in developing countries. Ante mortem diagnosis in human cases is necessary for medical management of the patient and to ensure appropriate post-exposure treatment of contacts. Both conventional RT-PCR and Real time PCR (TaqMan) have been described for the detection of rabies virus RNA from saliva and tissue respectively, however to date, there have been no studies comparing conventional and real time PCR assays for detection of rabies virus nucleic acid using saliva samples for ante mortem diagnosis. OBJECTIVES In this study, we evaluated the utility of conventional RT-PCR and SYBR Green I Real time PCR in the ante mortem diagnosis of rabies using saliva samples. STUDY DESIGN Saliva samples collected from twenty-four patients presenting with typical clinical manifestations of rabies were tested in the two assays. RESULTS Amongst the 24 samples tested, 21 samples (87.5%) were positive by either of the two molecular methods. Of these 21, rabies virus RNA was detected in 6/21 in the conventional RT-PCR assay while SYBR Green I Real time PCR could detect RNA in 18/21 samples. CONCLUSION Real time PCR assay was more sensitive than conventional RT-PCR assay (sensitivity 75% versus 37%, p=0.0189). This study highlights the utility of molecular diagnostic tests in establishing ante mortem diagnosis of rabies using saliva samples within a few hours.
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Affiliation(s)
- T Nagaraj
- Department of Neurovirology, National Institute of Mental Health and Neurosciences, Bangalore 560029, India
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Solomon T, Marston D, Mallewa M, Felton T, Shaw S, McElhinney LM, Das K, Mansfield K, Wainwright J, Kwong GNM, Fooks AR. Paralytic rabies after a two week holiday in India. BMJ 2005; 331:501-3. [PMID: 16141158 PMCID: PMC1199033 DOI: 10.1136/bmj.331.7515.501] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Tom Solomon
- Viral CNS Infections Group, Division of Neurological Science, University of Liverpool, Walton Centre for Neurology and Neurosurgery, Liverpool L9 7LJ.
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Wakeley PR, Johnson N, McElhinney LM, Marston D, Sawyer J, Fooks AR. Development of a real-time, TaqMan reverse transcription-PCR assay for detection and differentiation of lyssavirus genotypes 1, 5, and 6. J Clin Microbiol 2005; 43:2786-92. [PMID: 15956398 PMCID: PMC1151886 DOI: 10.1128/jcm.43.6.2786-2792.2005] [Citation(s) in RCA: 105] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Several reverse transcription-PCR (RT-PCR) methods have been reported for the detection of rabies and rabies-related viruses. These methods invariably involve multiple transfers of nucleic acids between different tubes, with the risk of contamination leading to the production of false-positive results. Here we describe a single, closed-tube, nonnested RT-PCR with TaqMan technology that distinguishes between classical rabies virus (genotype 1) and European bat lyssaviruses 1 and 2 (genotypes 5 and 6) in real time. The TaqMan assay is rapid, sensitive, and specific and allows for the genotyping of unknown isolates concomitant with the RT-PCR. The assay can be applied quantitatively and the use of an internal control enables the quality of the isolated template to be assessed. Despite sequence heterogeneity in the N gene between the different genotypes, a universal forward and reverse primer set has been designed, allowing for the simplification of previously described assays. We propose that within a geographically constrained area, this assay will be a useful tool for the detection and differentiation of members of the Lyssavirus genus.
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Affiliation(s)
- P R Wakeley
- World Health Organization Collaborating Centre for the Characterization of Rabies and Rabies-Related Viruses, Department of Virology, Veterinary Laboratories Agency, Addlestone, United Kingdom.
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Peigue-Lafeuille H, Bourhy H, Abiteboul D, Astoul J, Cliquet F, Goudal M, Lerasle S, Mailles A, Montagne MC, Morer I, Rotivel Y, Floret D. [Human rabies in France in 2004: update and management]. Med Mal Infect 2005; 34:551-60. [PMID: 15603930 DOI: 10.1016/j.medmal.2004.07.031] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2004] [Accepted: 07/23/2004] [Indexed: 11/26/2022]
Abstract
Twenty people died of rabies in France between 1970 and 2003 (compared to 55,000 yearly worldwide), 80% on returning from Africa. Dogs were the contaminating animals in 90% of the cases and children were the most common victims. The last instance of rabies in a native French animal was reported in 1998. However the illegal importation of animals still poses a risk. The disease is transmitted by saliva, even before the appearance of clinical symptoms, through a bite, scratch, or licks of mucous membranes or broken skin. Person-to-person transmission has only been observed in cases of grafts (cornea). The mean incubation time of 1 to 3 months is long enough to allow passive immunization and vaccination. After its onset, the disease presents as encephalitis or a paralytic syndrome the outcome of which is always fatal. Clinical diagnosis may be difficult in the early stages of the disease. If rabies is suspected, the National Reference Centre is responsible for the sampling and proper transportation of these samples so as to ensure assessment results within 5 days. If stringent hygiene rules are complied to, there is no risk of contamination for those in close contact. Vaccination, which is performed in official rabies centers, is only performed after a diagnosis based on laboratory evidence, and solely for exposed persons or those for whom a reliable history cannot be established (children under 6 years). Prevention is based on information. People traveling abroad, particularly to Africa, are warned not to approach unknown animals (especially dogs) nor to try to import them, and are advised to comply with vaccinal recommendations for travelers, particularly for toddlers.
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Affiliation(s)
- H Peigue-Lafeuille
- Service de virologie, faculté de médecine, 28, place Henri-Dunant, 63001 Clermont-Ferrand cedex, France.
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Woldehiwet Z. Clinical laboratory advances in the detection of rabies virus. Clin Chim Acta 2005; 351:49-63. [PMID: 15563871 DOI: 10.1016/j.cccn.2004.09.018] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2004] [Revised: 09/20/2004] [Accepted: 09/23/2004] [Indexed: 11/18/2022]
Abstract
Rabies is one of the most feared zoonotic diseases in the world. All warm-blooded animals are susceptible to infection by the virus, but the main vectors of human infection are dogs and cats. Development of rabies can be prevented by postexposure vaccination, and with a few exceptions, the exact time and source of human infection is usually known. However, the effective use of postexposure vaccination depends on the rapid and accurate detection of rabies virus in specimens obtained from the source of human infection. This paper provides an overview on developments on laboratory methods for the early detection of rabies virus. In most laboratories, the fluorescent antibody test (FAT) is used as the most important primary test, with the rabies tissue culture infection test (RTCIT) or the mouse inoculation test (MIT) being used as confirmatory backup procedures. However, other methods for the detection of antigens, such as rapid rabies-specific enzyme-linked immunosorbent assay (rapid-ELISA) and the detection of viral nucleic acids by reverse transcription polymerase chain reaction (RT-PCR) are increasingly being used for diagnosis and, in combination with nucleotide sequencing, for epidemiological investigations.
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Affiliation(s)
- Zerai Woldehiwet
- University of Liverpool, Department of Veterinary Pathology, Veterinary Teaching Hospital, Leahurst, Neston Wirral CH64 7TE, UK.
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Fooks AR, McElhinney LM, Pounder DJ, Finnegan CJ, Mansfield K, Johnson N, Brookes SM, Parsons G, White K, McIntyre PG, Nathwani D. Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Virol 2003; 71:281-9. [PMID: 12938204 DOI: 10.1002/jmv.10481] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.
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Affiliation(s)
- Anthony R Fooks
- Rabies Research and Diagnostic Group, Veterinary Laboratories Agency (Weybridge) [WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses], Surrey, United Kingdom.
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Fooks AR, Johnson N, Brookes SM, Parsons G, McElhinney LM. Risk factors associated with travel to rabies endemic countries. J Appl Microbiol 2003; 94 Suppl:31S-36S. [PMID: 12675934 DOI: 10.1046/j.1365-2672.94.s1.4.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Increased travel to exotic destinations around the world is escalating the risk that an emerging virus may be imported into the UK. Rabies should be considered in the differential diagnosis of any encephalitic illness presenting in an appropriate epidemiological context. Molecular diagnostic tests that can rapidly discriminate rabies from other suspected infections will influence the use of anti-rabies prophylaxis for potential contacts with the victim. In 2001, the UK had two confirmed human rabies cases, imported from the Philippines and Nigeria, respectively. In case one, hemi-nested reverse transcriptase polymerase chain reaction (hn-RT-PCR) and automated sequencing confirmed the presence of rabies virus (RABV) within both the saliva and skin specimens within 36 h of sample submission. Subsequent phylogenetic analysis using a partial sequence of the nucleoprotein (N-) gene segment demonstrated that the virus was closely related to that of canine variants currently circulating in the Philippines. In the second case, the fluorescent antibody test and reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the diagnosis on post-mortem tissue. Phylogenetic analysis of two genomic segments of this isolate confirmed that it was a classical RABV (genotype 1) of the Africa 2 subgroup. These cases have highlighted the capability of molecular diagnostic tests for the rapid identification and subsequent genotyping of RABV to host and geographical location. In the first instance, rabies diagnosis often rests on clinical and epidemiological grounds. Negative tests, even late in the illness, do not exclude the diagnosis as these tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. For this reason, rapid molecular detection and virus typing will be essential in considering the appropriate medical treatment regimen for a patient. In addition, an early diagnosis may decrease the number of unnecessary contacts with the patient and reduce the requirement for invasive and costly interventions. Rabies should form part of a differential diagnosis for any patient presenting with a history of travel to a rabies endemic country and displaying an undiagnosed encephalopathy.
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Affiliation(s)
- A R Fooks
- Rabies Research and Diagnostic Group [WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses], Veterinary Laboratories Agency (Weybridge), Surrey, UK.
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Nathwani D, McIntyre PG, White K, Shearer AJ, Reynolds N, Walker D, Orange GV, Fooks AR. Fatal human rabies caused by European bat Lyssavirus type 2a infection in Scotland. Clin Infect Dis 2003; 37:598-601. [PMID: 12905146 DOI: 10.1086/376641] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2003] [Accepted: 03/31/2003] [Indexed: 11/03/2022] Open
Abstract
We wish to report the first recorded case of indigenous human rabies caused by a bat bite in the United Kingdom in 100 years. This instructive case report highlights a number of key lessons: first, bites from insectivorous bats indiginous to the United Kingdom can cause rabies in humans; second, rabies immunization is essential for bat-handlers, and postexposure treatment for rabies is essential for patients bitten by bats; third, patients able to give a history who present with acute flaccid paralysis and/or presumptive viral encephalitis should be asked if they have been bitten by bats, irrespective of travel history, or this history should be obtained from family or friends; fourth, antemortem diagnosis of bat rabies (EBLV type 2a infection) in humans is possible using RT-PCR.
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Affiliation(s)
- D Nathwani
- Department of Infectious Diseases, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.
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