【病毒外文文獻】2017 Public health risk and transmission route of Middle East respiratory syndrome (MERS)_ MERS coronavirus in dromedary

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Vol 9 3 pp 39 46 March 2017 DOI 10 5897 JVMAH2016 0519 Article Number 4038B5263030 ISSN 2141 2529 Copyright 2017 Author s retain the copyright of this article http www academicjournals org JVMAH Journal of Veterinary Medicine and Animal Health Review Public health risk and transmission route of Middle East respiratory syndrome MERS MERS coronavirus in dromedary camel Andualem Yimer and Sisay Fanta School of Veterinary Medicine Wollo University Dessie Ethiopia Received 26 August 2016 Accepted 28 November 2016 Middle East respiratory syndrome corona virus MERS CoV is a novel enzootic beta origin corona virus which was described in September 2012 for the first time According to the reports of different researchers the prevalence of MERS CoV antibodies during serological examination is very high in dromedary camels of Eastern Africa and the Arabian Peninsula However the infection in camel is mostly asymptomatic In contrast to the camel case the clinical signs and symptoms of MERS CoV infection in humans ranges from an asymptomatic or mild respiratory illness to severe pneumonia and multi organ failure with an overall mortality rate of about 35 Therefore the objective of this paper was to review the public health risk transmission routes of Middle East respiratory syndrome and to recommend the disease for further research The identification of MERS CoV RNA and viable virus from dromedary camels including samples with respiratory symptoms by different studies have been detected especially in isolation of identical strains of MERS CoV from epidemiologically linked humans and camels are the suggestive evidence for inter transmission of the virus primarily from camels to humans and its public health risks Though inter human spread within health care settings is responsible for the majority of reported MERS CoV human cases the virus is currently incapable of causing sustained human to human transmission pandemic occurrence Phylogenetic studies and viral sequencing results strongly suggest that MERS CoV originated from bat ancestors after evolutionary recombination process primarily in dromedary camels in Africa before its exportation to the Arabian Peninsula through the camel trading routes Currently there is no specific drug or vaccine available for treatment and prevention of infections due to MERS CoV in patients The important measures to control MERS CoV spread are strict regulation of camel movement regular herd screening and isolation of infected camels use of personal protective equipment by camel handlers and awareness creation on the public especially in African pastoralists where consumption of unpasteurized camel milk is common Therefore urgent global epidemiological studies are required especially in the poor camel rearing African countries to understand the transmission patterns and the human cases of MERS CoV and also for the proper implementation of the above mentioned control measures Key words Dromedary camel epidemiology MERS CoV public health respiratory syndrome INTRODUCTION Middle East respiratory syndrome coronavirus MERS CoV is a novel lineage C beta corona virus derived from bats which can cause acute viral respiratory disease in humans WHO 2014a and in camels also known 40 J Vet Med Anim Health as camel flu Richard 2015 Dromedary camels in the Middle East have high sero prevalence for MERS CoV and MERS CoV RNA has been consistently detected in these animals especially in settings such as camel abattoirs where camels from multiple origins are assembled but the exact source of infection in camels has not been identified More than 60 of the global population of dromedary camels is distributed in African countries and some of these countries are important camel exporters to the Arabian Peninsula Faye and Bonnet 2012 MERS CoV antibodies were also found with high prevalence in dromedary camels in these African countries with positive rates higher than 80 for the animals in Egypt Ethiopia Nigeria and Sudan and 30 to 54 in Tunisia Reusken et al 2014 According to WHO 2015c there were 1 618 laboratory confirmed cases of MERS reported with 579 human deaths and camels are believed to be involved in its spread to humans but its way of transmission is unclear Zumla et al 2015 This disease in human is zoonotic in origin although clusters of human to human transmission have been reported especially in health care or family settings WHO 2015a However this human zoonotic disease has so far been reported only from countries in the Middle East the reason for the absence of zoonotic disease report from Africa is unclear Chu et al 2014 and it should be of great concern to researchers In humans the virus is graver and opportunistic pathogen associated with the death rate of 40 from infection cases report It is yet to be established whether infections thought to have been acquired from an animal origin produce a more severe outcome than those spread between humans WHO 2013a Therefore the objective of this paper was to review the public health risk transmission routes of Middle East respiratory syndrome and to recommend the disease for further research PUBLIC HEALTH RISK AND DESCRIPTIONS OF MERS CORONA VIRUS History and origin The first zoonotic introduction of a corona virus into the human population occurred by the severe acute respiratory syndrome corona virus SARS CoV in 2002 According to WHO 2003 SARS CoV causes a world pandemic outbreak with 8 400 recorded infection cases and 800 deaths similarly MERS CoV marks the second known zoonotic introduction of a highly pathogenic of evidence currently support this theory the very close phylogenetic similarity with the bat Beta corona viruses such as BtCoV HKU4 and BtCoV HKU5 van Boheemen et al 2012 closely related corona virus sequences have been recovered from bats in Africa Asia the Americas and Eurasia Therefore MERS CoV uses the evolutionary conserved dipeptidyl peptidase 4 DPP4 protein in Pipistrellus pipistrellus bats for cell entry Raj et al 2013 Middle East respiratory syndrome in human was first identified in 2012 in Saudi Arabia and more than 1000 infection cases of the disease have been reported in May 2015 and about 40 of those who were infected died due to the disease Zaki et al 2012 accordingly most cases have occurred in the Arabian Peninsula Zumla et al 2015 HCoV EMC 2012 is a strain of MERS CoV that is detected in the first infected person in London in 2012 which was found to have a 100 identical viral sequencing to the strain identified in Egypt from tomb bats Zaki et al 2012 this result is suggestive that bats are the primary origin of MERS CoV Etiology Middle East respiratory syndrome is caused by the newly identified MERS corona virus MERS CoV with single stranded RNA belonging to the genus beta corona virus which is distinct from SARS corona virus and the common cold corona virus Saey 2013 According to Eckerle et al 2014 MERS CoV uses the DPP4 CD26 receptor to gain entry and effectively replicate in camel cell lines and neutralizing antibodies for MERS CoV have been detected in dromedary camels from Africa and Middle East Milne Price et al 2014 Different studies suggested that the mean incubation period of the virus is 5 to 6 days it will take 13 to 14 days to show clinical illness in infected person and to subsequently spread to another person In progressively diseased patients death can occur within 11 to 13 days sometimes it will range from 5 to 27 days Chan et al 2014 Ki 2015 Pathogenesis and clinical sign The disease in human initially showed simple respiratory problem with mild fever chills muscle ache and respiratory stress shortness of breath Then it leads to severe pneumonia within 2 to 3 days after infection progressively after some period of time it will develop into severe acute respiratory syndrome SARS or acute corona virus probably originating from bats Three lines Corresponding author E mail anduyimer007 Author s agree that this article remain permanently open access under the terms of the Creative Commons Attribution License 4 0 International License respiratory distress syndrome ARDS In later cases MERS CoV causes clinical symptoms of upper and lower respiratory tract infections specific signs and symptoms including high grade fever non productive cough dyspnea headache myalgia nausea vomiting and diarrhea that may precede the respiratory symptoms Guery et al 2013 Finally death may occur in almost half of the cases especially in unmanaged patients more death rate will occur Abdullah et al 2013 Laboratory result on admission of patients indicates leukopenia lymphopenia thrombocytopenia and elevated lactate dehydrogenase levels Assiri et al 2013 MERS CoV can also cause severe pneumonia with acute respiratory distress syndrome ARDS requiring mechanical ventilation and intensive care admission Drosten et al 2013 Incontrast to the human cases camel showed minor clinical signs of the disease including of rhinorrhea and a mild increase in body temperature but no other clinical signs were observed Ahsa 2013 and the nasal discharge drained from both nostrils varied in character from serous to purulent Daniella et al 2014 Diagnosis The definitive diagnosis of cases of coronavirus infection basically rely on advanced diagnostic perceptions like the detection of unique sequences of viral RNA by real time reverse transcriptase polymerase chain reaction RTPCR and immunofluorescence because the disease has no pathognomonic clinical manifestation both in human and in camel WHO 2013b However antibodies against beta coronaviruses are identified to cross react within the other species of the genus due to their characteristic antigenic similarity Therefore immunofluorescence antibody tests effectively limit their use to confirmatory diagnosis of the disease Memish et al 2014 Throat swabs urine faeces and serum samples were collected from wild bats in Saudi Arabia including the area where the first MERS CoV patient had reported and worked this study result indicate that 227of the samples was found positive for nucleotide fragment of the RNA dependent RNA polymerase region of MERS CoV genome from the examined different 1003 samples this result suggest that bats are the evolutionary origin of the virus for camel and human infections Memish et al 2013 EPIDEMIOLOGY OF THE DISEASE Distribution According to WHO 2014b official report 707 infected patients were identified in 21 countries from three Yimer and Sisay 41 continents of the world From those detected human cases 252 patients have died due to MERS CoV indicating the case fatality rate of the disease to be about 35 Drosten et al 2013 The infection so far has been acquired either directly through a probable zoonotic source or as a result of human to human transmission through close contacts Hijawi et al 2012 An unexplained observation has shown the seasonal variation in the number of reported cases with a peak occurrence from April to June of each year The number of cases reported during April 2014 alone was alarming because it was greater than the cumulative number of cases reported since the outbreak began 2014 The possible justification for the seasonal variation of camel case reports may be that it coincides with camel breeding season and younger camels seem to be more often infected than older camels in the herds Holmes et al 2014 Human cases have also been reported in Kuwait Yemen Oman Iran Lebanon Tunisia Algeria Bangladesh Malaysia even in non camel rearing countries like France Italy Germany the Netherlands United Kingdom Greece Italy and United States WHO 2014c which is suggestive of the presence of other probable intermediate hosts in addition to camel Furthermore sero positive camels for MERS CoV antibodies were identified in Egypt Kenya Nigeria Tunisia and Ethiopia Figure 1 suggesting that there may be MERS CoV human cases that are undetected in Africa Reusken et al 2014 Species affected reservoirs and route of transmission The disease due to MERS Cov is thought to be zoonotic because of its close genetic similarity to bat corona viruses Karesh et al 2012 Identical strains with human MERS Cov have been isolated from camels in Egypt Qatar and Saudi Arabia and MERS CoV antibodies have also been detected in camels of Africa and the Middle East Memish et al 2014 According to Reusken et al 2013 camels are thought to be a source of human infection this is because genetic sequence similarities have been determined between human and camel corona viruses Memish et al 2014 Transmission from dromedary camels to humans has been shown with RT PCR and viral genome sequence analysis molecular detection and phylogenetic analysis have been also performed to investigate transmission Azhar et al 2014 Other animals such as goats cows sheep buffalo pigs and wild birds have been tested for MERS CoV antibodies but no positive findings have been reported these investigation results provide evidence that camels are a primary probable source of the MERS CoV zoonotic infection for humans Reusken et al 2013 Bats are known natural reservoirs for several 42 J Vet Med Anim Health Figure 1 Distribution of human MERS CoV cases and prevalence of MERS CoV based on serological and RNA detection in dromedary camels Source Taylor and Francis 2016 emerging viral infections in humans including rabies Nipah virus Hendra virus and Ebola virus Han et al 2015 Due to their extremely diverse species with a long evolutionary history bats have co evolved with a variety of viruses and due to their lack of B cell mediated immune responses which allows them to carry viruses without showing overt clinical signs of viral infections Dobson 2005 Karesh et al 2012 As a result of their low metabolic rate and suppressed immune response during bats hibernation time there is delayed viral clearance which make them the potential reservoirs for different viruses George et al 2011 Generally species affected by Middle East respiratory syndrome and used as source of infection are Homo sapiens human camels and bats Augustina et al 2013 MERS CoV is a zoonotic virus that is transmitted from animals to humans WHO 2015b The route of transmission from animal to human is not fully understood Zumla and Memish 2014 but researchers hypothesize that camels are a likely reservoir host for MERS CoV Figure 2 and most likely camels are the animal which is source of infection for humans Saad and Said 2011 In some areas of the Arabian Peninsula the consumption of unpasteurized milk is common and in some cultural practices of the region camel milk and urine are consumed for their believed medicinal effects Saad and Said 2011 Researchers have proved that MERS CoV in milk can survive for prolonged periods van Doremalen et al 2014 Contact with a MERS CoV infected animal such as a dromedary or its bodily fluids may be responsible for zoonotic transmission to humans but investigations continue to better clarify this question Aburizaiza et al 2014 Transmission of MERS CoV from human to human occurs similarly to other corona viruses It is believed that it is transmitted by contact with the respiratory secretions of an infected individual that are aerosolized by coughing or sneezing WHO 2015a Many of those infected with MERS CoV were associated with healthcare settings such as hospitals but the virus does not have a chance to pass easily from human to human if there is not direct close contact with the infected individual Oboho et al 2014 Group at risk Studies on MERS CoV genetic sequences from humans and camels in Egypt Oman Qatar and Saudi Arabia point out a close similarity between the virus identified in camels and that detected in human in the same geographic area These and other studies also have found MERS CoV antibodies in camels in Africa and the Middle East and also preliminary results from an ongoing investigation in Qatar show that people working closely with camels e g farm workers slaughterhouse workers and veterinarians Yimer and Sisay 43 Figure 2 Reported Infection sources and transmission routes of MERS CoV between bats camels and human Source Taylor and Francis 2016 may be at higher risk of MERS CoV infection than people who do not have regular close contacts with camels and also health care workers WHO 2014d MERS coronavirus in dromedary camel According to Informer East Africa 2016 many outbreak cases of MERS in camels of Kenya is reported and more than 500 camels died due to the disease An investigation using real time polymerase chain reaction RT PCR identified MERS CoV prevalence rate of 3 6 in apparently healthy camels in a slaughterhouse of Egypt Other research report also indicate that 92 of examined sera collected from camels were reactive to MERS CoV antibodies and the camels that tested positive were all imported from either Sudan or Ethiopia Chu et al 2014 Studies conducted from 2010 to 2013 in which incidence of MERS was examined in 310 dromedary camels indicate high titers of neutralizing antibodies to MERS CoV in the collected serum sample of these animals Hemida et al 2013 A further investigation was conducted on sequenced MERS CoV on nasal swabs of dromedary camels in Saudi Arabia result indicate that MERS CoV in camels had sequenced exact similarity with previously sequenced human isolates Briese et al 2014 The prevalence of MERS CoV antibodies is significantly higher in older camels when compared with those aged two years or less Alagaili et al 2014 which indicates MERS CoV have been found circulating in dromedary camels for more than 20 years in camel rearing in middle east and African countries Corman et al 2014 In addition to the high total prevalence of MERS CoV serum antibody in dromedary camels from Kenya and other African countries 14 28 of MERS CoV sero prevalence in dromedary camels from the Canary Islands were also reported by Hemida et al 2014 this result also included three positive camels that were imported from Morocco to the Canary Islands even though there is no current report from Morocco on the disease In contrast to the Middle East and African camel infection prevalence report currently there is no published report on MERS CoV antibodies detection in dromedary camels from Australia Canada the United States of America Germany the Netherlands or Japan which will be a research question for researchers indicating that further global epidemiological study on the disease is mandatory The investigated high sero prevalence of MERS CoV in dromedary camel of Africa and the Middle East Table 1 suggests that animal movement has facilitated the transmission and circulation of MERS CoV Briese et al 2014 Which is also suggestive of the risk of emerging new outbreak in those countries currently free from MERS CoV 44 J Vet Med Anim Health Table 1 Sero prevalence of MERS CoV antibodies in dromedary camel in different countries reporting the disease Country Number of camel tested Prevalence Year Saudi Arabia 9 100 2013 UAE 8 100 2015 Oman 50 100 2015 Jordan 11 100 2013 Qatar 105 97 2014 Egypt 110 98 2 2013 Tunisia 158 54 2009 Ethiopia 31 93 2010 2011 Nigeria 358 94 2010 2014 Somalia 86 83 7 1983 1984 Sudan 60 86 7 1984 Kenya 774 29 5 1992 2013 Canary Island 105 14 3 2013 Source Taylor and Francis 2016 Prevention and control Understanding the route of transmission of MERS CoV and its pattern of transmission is important for proper implementation control and prevention of the disease Currently as mentioned above the pattern of the disease transmission will dictate the methods for prevention Figure 2 The WHO advises people at risk of MERS CoV infection to avoid contact with camels to practice good hand hygiene and to avoid drinking raw milk or eating contaminated food unless it is properly washed peeled or cooked WHO 2014a Since most of the cases occur in the health care setting it is thoughtful that all health care workers practice appropriate infection control measures when taking care of patients with suspected or confirmed MERS CoV WHO 2014b Curr