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Sultan S, Ahmed SAH, Abdelazeem MW, Hassan S. Molecular characterisation of rabies virus detected in livestock animals in the southern part of Egypt during 2018 and 2019. Acta Vet Hung 2021; 69:80-87. [PMID: 33764896 DOI: 10.1556/004.2021.00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 01/11/2021] [Indexed: 12/25/2022]
Abstract
Brain samples were collected from 33 animals of different species, including buffalo, cattle, dog, donkey, fox and wolf, that had been suspected to be infected by rabies virus (RABV) in different geographical regions of Aswan and Luxor governorates in Egypt. The samples were submitted for histopathological examination and the presence of the nucleic acid and antigens of RABV was tested by RT-PCR and indirect fluorescent antibody technique (IFAT), respectively. Sixteen samples were found positive by all the three examinations. Three samples were selected for further study from animals in which the highest virus loads were detected. The partial sequence of the RABV N gene was determined and analysed from the samples of a buffalo, a cow and a donkey. The viruses in the samples were found to share 95-98% and 95-97% nucleotide and amino acid sequence identities, respectively. In comparison to reference sequences, a few amino acid substitutions occurred in the N protein antigenic sites I and IV in the immunodominant epitopes of the viruses detected in the cow and the donkey but not in the one from the buffalo. The phylogenetic analysis revealed that the RABVs sequenced from the samples belonged to genotype 1, Africa-4 clade, and formed two distinct sub-clades within the Egyptian clade. These findings indicate the circulation of RABV among livestock animals in the southern part of Egypt and raise public health concerns. The amino acid changes detected in this work may contribute to the antigenic diversification of RABVs.
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Affiliation(s)
- Serageldeen Sultan
- 1Department of Microbiology, Virology Division, Faculty of Veterinary Medicine, South Valley University, 83523, Qena, Egypt
| | | | - Mohamed Wael Abdelazeem
- 3Department of Microbiology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt
| | - Sabry Hassan
- 4Department of Biology, College of Science, Taif University, Taif, Saudi Arabia
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Eze UU, Ngoepe EC, Anene BM, Ezeokonkwo RC, Nwosuh CI, Sabeta CT. Molecular Detection of Rabies Lyssaviruses from Dogs in Southeastern Nigeria: Evidence of TransboundaryTransmission of Rabies in West Africa. Viruses 2020; 12:v12020134. [PMID: 31979379 PMCID: PMC7077224 DOI: 10.3390/v12020134] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 09/20/2019] [Accepted: 09/24/2019] [Indexed: 12/25/2022] Open
Abstract
Despite being the first country to register confirmed cases of Mokola and Lagos bat lyssaviruses (two very distant lyssaviruses), knowledge gaps, particularly on the molecular epidemiology of lyssaviruses, still exist in Nigeria. A total of 278 specimens were collected from dogs in southeastern Nigeria between October 2015 and July 2016, and 23 (8.3%) of these tested positive for lyssaviruses with the direct fluorescent antibody test (DFA). The lyssaviruses were genetically characterized by amplifying the highly conserved nucleoprotein (N) gene of the rabies lyssaviruses (RABVs) of the viral genome. Phylogenetic analyses of the nucleotide sequences showed that all the RABV sequences in this study were of the Africa-2 lineage. Our results demonstrated that transboundary transmission of rabies lyssavirus is a key event, given that one of the RABV sequences (MN196576) clustered with rabies variants from neighboring Niger Republic. Furthermore, three RABVs from dogs from Anambra State clustered separately forming a novel and distinct group. Our results demonstrated that transboundary transmission of RABLVs is a key driver in the spread of rabies in West Africa. In order for the successful control of this zoonotic disease, a multinational stepwise surveillance and elimination of rabies in Africa by 2030 is probably the solution for regional elimination.
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Affiliation(s)
- Ukamaka U Eze
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Nigeria, Nsukka 410001, Nigeria;
- Correspondence:
| | - Ernest C Ngoepe
- Agricultural Research Council-Onderstepoort Veterinary Institute, OIE Rabies Reference Laboratory, Onderstepoort 0110, South Africa; (E.C.N.); (C.T.S.)
| | - Boniface M Anene
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Nigeria, Nsukka 410001, Nigeria;
| | - Romanus C Ezeokonkwo
- Department of Veterinary Parasitology and Entomology, Faculty of Veterinary Medicine, University of Nigeria, Nsukka 41001, Nigeria;
| | - Chika I Nwosuh
- National Veterinary Research Institute, Vom, Plateau State 930103, Nigeria;
| | - Claude T Sabeta
- Agricultural Research Council-Onderstepoort Veterinary Institute, OIE Rabies Reference Laboratory, Onderstepoort 0110, South Africa; (E.C.N.); (C.T.S.)
- Department of Veterinary Tropical Diseases, University of Pretoria, Onderstepoort 0110, South Africa
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Vagheshwari DH, Bhanderi BB, Mathakiya RA, Jhala MK. Sequencing and sequence analysis of partial nucleoprotein (N) gene and phylogenetic analysis of rabies virus field isolates from Gujarat state, India. Virusdisease 2018; 28:320-327. [PMID: 29291220 DOI: 10.1007/s13337-017-0387-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 06/20/2017] [Indexed: 11/28/2022] Open
Abstract
The present study was undertaken with an aim of characterization of rabies virus (genus Lyssavirus of the family Rhabdoviridae under the order Mononegavirales) by sequencing of partial nucleoprotein (N) gene of rabies virus and phylogenetic analysis to know the genotype and lineage of rabies virus present in Gujarat state of India. A total of 32 samples (18 brain samples and 14 saliva samples) were aseptically collected from live and dead animals (viz. dog, buffalo, cow, goat, donkey and hyena) for rabies virus detection. Out of 32 samples, 24 samples were found positive by Reverse Transcriptase Polymerase Chain Reactions and from these 24 positive samples, 20 samples were selected for sequencing having good concentration of gene product. ClustalW alignment of nucleotide sequences and amino acid sequences of field rabies isolates revealed 95.20-100 and 97.95-100% similarity among themselves, respectively. Multiple sequence alignment of field rabies isolates and reference vaccine strains [Pasteur strain and Challenge Virus Strain (CVS)] indicated single nucleotide mutations at total 91 positions and amino acid mutations at total 17 different positions. Phylogenetic analysis of N gene sequences using our 20 field rabies isolates and 21 other reported isolates in Genbank resulted in 3 phylogenetic clusters. All the field rabies isolates showed same genetic lineage among themselves and with other earlier reported Indian rabies isolates placing them in Arctic like lineage of Genotype 1 Rabies virus. However, they were at genetic distance with reference Pasteur and CVS strains, which grouped in different phylogenetic cluster.
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Affiliation(s)
- Dhaval H Vagheshwari
- Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, Gujarat 388001 India
| | - Bharat B Bhanderi
- Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, Gujarat 388001 India
| | - Rafyuddin A Mathakiya
- Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, Gujarat 388001 India
| | - Mayurdhvaj K Jhala
- Department of Veterinary Microbiology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, Gujarat 388001 India
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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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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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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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Simani S, Fayaz A, Rahimi P, Eslami N, Howeizi N, Biglari P. Six fatal cases of classical rabies virus without biting incidents, Iran 1990-2010. J Clin Virol 2012; 54:251-4. [PMID: 22554714 DOI: 10.1016/j.jcv.2012.03.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2011] [Revised: 03/07/2012] [Accepted: 03/28/2012] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rabies is an endemic fatal zoonotic disease, commonly transmitted to humans through contact (bites and scratches) with infected animals. OBJECTIVES During the years 1990-2010, six patients with the clinical symptoms of rabies (fever, tinnitus, buzzing, delirium and hydrophobia), with no history of a bite, were diagnosed by physicians in Iran. To obtain laboratory confirmation of rabies infection, different clinical specimens from each patient were sent to the World Health Organisation (WHO) Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran. The first case was a 39-year-old male veterinary technician who entered his uncovered scratched hand into the mouth of a rabid bovine and became infected. Two years later, a herd of sheep being tended by a shepherd and his two sons were attacked by a rabid wolf. All three individuals were infected when they applied burnt thorny wool to the sheep's wounds as a bandage. Their hands were scratched and then infected through contact with the remaining saliva of the rabid wolf on the sheep's wounds. In 1994, two other human cases occurred through corneal transplantation from the same donor who had died with the clinical signs of food poisoning (according to his hospital record), which probably was a misdiagnosis of rabies infection. STUDY DESIGN This is a case series study that describes human rabies cases without biting incidents. According to the WHO recommendation, human rabies cases are notifiable, therefore, in Iran, a rabies surveillance system has been established to follow these cases. During the last decade, six patients with no 'history of a bite' were hospitalised with growing symptoms of rabies. The data were collected from each patient by the physicians and transferred to the Ministry of Health and Medical Education of Iran, and to the WHO Collaborating Center for Reference and Research on Rabies, Pasteur Institute of Iran as the only testing laboratory. Thus, they came to the attention of the surveillance system. Ante-mortem diagnosis was performed on saliva, cerebrospinal fluid and blood samples that were collected from the first patient by the physicians. Fresh brain specimens from all patients were kept in a mixture of 50% glycerol in phosphate-buffered saline and transported on ice to the WHO Collaborating Center for Reference and Research on Rabies. RESULTS For the first patient, rabies virus was investigated in saliva using the rapid tissue cell inoculation test (RTCIT) and the mouse inoculation test (MIT). Anti-rabies antibodies in this patient's serum and cerebrospinal fluid (CSF) were examined using the mouse neutralisation test (MNT). Fresh brain specimens from all patients were examined using the fluorescence antibody test (FAT) as recommended by the WHO laboratory manual in rabies as the post-mortem diagnostic test for rabies. Rabies infection was confirmed in all of the deceased patients. Anti-rabies antibodies were identified only in one patient's serum specimen. Testing also showed that the rabies virus isolated was the classic rabies virus (serotype 1), which is widespread in Iran. CONCLUSIONS Prevention and control of this fatal disease require a sensitive surveillance system to follow 'suspected' animal and human rabies cases thoroughly through the improved reporting system, which contains the history of exposure, clinical examinations, symptoms and laboratory results. This study describes some notable human rabies infections and their transmission modes to prevent occupational accidents.
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Affiliation(s)
- Susan Simani
- WHO Collaborating Center for Reference and Research on Rabies, Institute Pasteur, 12 Farvardin Ave., Enghelab Square, Tehran, Iran
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Meynard JB, Flamand C, Dupuy C, Mahamat A, Eltges F, Queuche F, Renner J, Fontanella JM, Hommel D, Dussart P, Grangier C, Djossou F, Dacheux L, Goudal M, Berger F, Ardillon V, Krieger N, Bourhy H, Spiegel A. First human rabies case in French Guiana, 2008: epidemiological investigation and control. PLoS Negl Trop Dis 2012; 6:e1537. [PMID: 22363830 PMCID: PMC3283561 DOI: 10.1371/journal.pntd.0001537] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2011] [Accepted: 01/03/2012] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Until 2008, human rabies had never been reported in French Guiana. On 28 May 2008, the French National Reference Center for Rabies (Institut Pasteur, Paris) confirmed the rabies diagnosis, based on hemi-nested polymerase chain reaction on skin biopsy and saliva specimens from a Guianan, who had never travelled overseas and died in Cayenne after presenting clinically typical meningoencephalitis. METHODOLOGY/PRINCIPAL FINDINGS Molecular typing of the virus identified a Lyssavirus (Rabies virus species), closely related to those circulating in hematophagous bats (mainly Desmodus rotundus) in Latin America. A multidisciplinary Crisis Unit was activated. Its objectives were to implement an epidemiological investigation and a veterinary survey, to provide control measures and establish a communications program. The origin of the contamination was not formally established, but was probably linked to a bat bite based on the virus type isolated. After confirming exposure of 90 persons, they were vaccinated against rabies: 42 from the case's entourage and 48 healthcare workers. To handle that emergence and the local population's increased demand to be vaccinated, a specific communications program was established using several media: television, newspaper, radio. CONCLUSION/SIGNIFICANCE This episode, occurring in the context of a Department far from continental France, strongly affected the local population, healthcare workers and authorities, and the management team faced intense pressure. This observation confirms that the risk of contracting rabies in French Guiana is real, with consequences for population educational program, control measures, medical diagnosis and post-exposure prophylaxis.
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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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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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Abstract
Rabies virus (RABV) is enzootic throughout Africa, with the domestic dog (Canis familiaris) being the principal vector. Dog rabies is estimated to cause 24,000 human deaths per year in Africa, however, this estimate is still considered to be conservative. Two sub-Saharan African RABV lineages have been detected in West Africa. Lineage 2 is present throughout West Africa, whereas Africa 1a dominates in northern and eastern Africa, but has been detected in Nigeria and Gabon, and Africa 1b was previously absent from West Africa. We confirmed the presence of RABV in a cohort of 76 brain samples obtained from rabid animals in Ghana collected over an eighteen-month period (2007-2009). Phylogenetic analysis of the sequences obtained confirmed all viruses to be RABV, belonging to lineages previously detected in sub-Saharan Africa. However, unlike earlier reported studies that suggested a single lineage (Africa 2) circulates in West Africa, we identified viruses belonging to the Africa 2 lineage and both Africa 1 (a and b) sub-lineages. Phylogeographic Bayesian Markov chain Monte Carlo analysis of a 405 bp fragment of the RABV nucleoprotein gene from the 76 new sequences derived from Ghanaian animals suggest that within the Africa 2 lineage three clades co-circulate with their origins in other West African countries. Africa 1a is probably a western extension of a clade circulating in central Africa and the Africa 1b virus a probable recent introduction from eastern Africa. We also developed and tested a novel reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of RABV in African laboratories. This RT-LAMP was shown to detect both Africa 1 and 2 viruses, including its adaptation to a lateral flow device format for product visualization. These data suggest that RABV epidemiology is more complex than previously thought in West Africa and that there have been repeated introductions of RABV into Ghana. This analysis highlights the potential problems of individual developing nations implementing rabies control programmes in the absence of a regional programme.
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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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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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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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15
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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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16
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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: 78] [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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17
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Mallewa M, Fooks AR, Banda D, Chikungwa P, Mankhambo L, Molyneux E, Molyneux ME, Solomon T. Rabies encephalitis in malaria-endemic area, Malawi, Africa. Emerg Infect Dis 2007; 13:136-9. [PMID: 17370529 PMCID: PMC2725806 DOI: 10.3201/eid1301.060810] [Citation(s) in RCA: 139] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
In a malaria-endemic area of Africa, rabies was an important cause of fatal central nervous system infection, responsible for 14 (10.5%) of 133 cases. Four patients had unusual clinical manifestations, and rabies was only diagnosed postmortem. Three (11.5%) of 26 fatal cases originally attributed to cerebral malaria were due to rabies.
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Affiliation(s)
- Macpherson Mallewa
- University of Liverpool, Liverpool, United Kingdom
- College of Medicine, Blantyre, Malawi
| | - Anthony R. Fooks
- Veterinary Laboratories Agency (Weybridge) WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses, Surrey, United Kingdom
| | | | | | | | | | | | - Tom Solomon
- University of Liverpool, Liverpool, United Kingdom
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18
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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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19
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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: 37] [Impact Index Per Article: 1.9] [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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20
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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: 106] [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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21
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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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22
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Johnson N, McElhinney LM, Ali YH, Saeed IK, Fooks AR. Molecular epidemiology of canid rabies in Sudan: evidence for a common origin of rabies with Ethiopia. Virus Res 2004; 104:201-5. [PMID: 15246657 DOI: 10.1016/j.virusres.2004.04.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2003] [Revised: 04/01/2004] [Accepted: 04/01/2004] [Indexed: 11/29/2022]
Abstract
Rabies is an endemic zoonosis in Sudan with the principal reservoir species being the domestic dog. A panel of rabies virus isolates from dogs in Sudan have been used to establish a molecular phylogeny based on a partial sequence of the viral nucleoprotein. These isolates were then compared to those from countries bordering Sudan in north-east Africa. The Sudanese viruses form a tight cluster of isolates with a single outlier. When compared to other African viruses, the Sudanese isolates cluster most closely with isolates from Ethiopia to the East suggesting a common origin for rabies in both countries which supports historical records of the movement of rabies into Sudan. The Sudanese group of viruses belong to the Africa 1a group of viruses that are present throughout much of north Africa.
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Affiliation(s)
- N Johnson
- Rabies Research and Diagnostic Group, WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses, Veterinary Laboratories Agency, Weybridge, Woodham Lane, Addlestone, Surrey KT15 3NB, UK
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23
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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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24
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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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25
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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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Smith J, McElhinney L, Parsons G, Brink N, Doherty T, Agranoff D, Miranda ME, Fooks AR. Case report: rapid ante-mortem diagnosis of a human case of rabies imported into the UK from the Philippines. J Med Virol 2003; 69:150-5. [PMID: 12436491 DOI: 10.1002/jmv.10253] [Citation(s) in RCA: 57] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The United Kingdom is free from rabies, with the last human death from indigenous rabies recorded in 1902. However, between 1946 and 2000, 20 deaths were reported in the United Kingdom in people who were bitten and infected while abroad in rabies endemic areas. The rapid diagnosis of suspected human rabies cases influences the use of anti-rabies post-exposure prophylaxis for potential contacts with the victim. In addition, the occurrence of a human rabies case requires urgent investigation to support patient management policies. In May 2001, a case of human rabies imported into the United Kingdom from the Philippines was identified. A 55-year-old man was admitted to University College Hospital, London, with clinical symptoms and a history consistent with exposure to rabies. Saliva, cerebrospinal fluid), and skin biopsies (from the wound site and nape of the neck) were submitted for conventional ante-mortem diagnostic techniques. Established diagnostic techniques, including the fluorescent antibody test (FAT), mouse inoculation test, (MIT) and the rabies tissue culture inoculation test (RTCIT), failed to detect the virus. In contrast, hemi-nested reverse transcription-polymerase chain reaction (RT-PCR), followed by automated sequencing confirmed the presence of classical rabies virus (genotype 1) in both the saliva and skin specimens within 36 hr of sample submission. Subsequent phylogenetic analysis demonstrated that this isolate was closely related to that of canine variants currently circulating in the Philippines.
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Affiliation(s)
- Jemma Smith
- Rabies Research and Diagnostic Group, WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses, Veterinary Laboratories Agency (Weybridge), Surrey, United Kingdom
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