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Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) Ninth update, 24 April 2014 (ECDC/RRA, summary)

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  • Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) Ninth update, 24 April 2014 (ECDC/RRA, summary)

    [Source: European Centre for Disease Prevention and Control (ECDC), full PDF document: (LINK). Summary.]


    UPDATED RAPID RISK ASSESSMENT

    Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) Ninth update, 24 April 2014


    Main conclusions and options for action
    • The seventh update of the rapid risk assessment on 24 September 2013 provides options for actions on case finding, laboratory testing, reporting, contact tracing, infection control and travel advice. These options for actions remain valid and can be found in the annex.
    • In addition:
      • Visitors to and EU residents of the Arabian Peninsula should:
        • Follow general travel health precautions that lower the risk of infection in general, including illnesses such as influenza and traveller’s diarrhoea. This includes:
          • Wash hands often with soap and water. When hands are not visibly dirty, a hand rub can be used.
          • Adhere to good food-safety practices, such as avoiding undercooked meat and unpasteurised milk (especially from camels) or food prepared under unsanitary conditions, and properly washing fruits and vegetables before eating them.
          • Maintain good personal hygiene.
          • Avoid unnecessary contact with farm, domestic, and wild animals, especially camels.
          • Use appropriate precautions when in close contact with case-persons presenting with acute respiratory illness, diarrhoea or other potentially infectious diseases.

        • Consult their physician if suffering major medical conditions (e.g. chronic diseases such as diabetes, chronic lung or renal disease, immunodeficiency) that can increase the likelihood of illness including MERS-CoV infection, or contact with healthcare facilities during travel.

      • Returning travellers to EU/EEA Member States should:
        • If developing acute illness with severe respiratory symptoms or diarrhoea, advise the healthcare providers in advance of the possibility of exposure to Middle East respiratory syndrome coronavirus (MERS-CoV) on the Arabian Peninsula in order to ensure appropriate measures are taken and if needed, testing considered.
        • • Not travel if acutely ill with an infectious disease.

      • The international public health community and affected countries could:
        • Urgently provide support for an outbreak assessment to minimise the possibility of widespread human-to-human transmission in the community;
        • Encourage and support as urgent, studies to describe and determine modes and sources of transmission for MERS-CoV, in particular in the animal (/camel)-human interface, among primary cases of clusters and in the
          healthcare facilities. Epidemiological studies, such as cohort or case-control studies are well suited for such assessments.
        • Encourage and support as urgent, observational clinical studies to determine optimal management of patients in order to improve outcomes.
        • Ensure that appropriate serum samples (positive and negative controls) are available for international standardisation of serological tests.
        • Encourage serological surveys among close contacts of cases and in affected settings.
        • Ensure that adequate numbers of virus isolates are sequenced and submitted to publicly available databanks, such as GenBank throughout the evolving epidemic.
        • Improve timely and transparent risk communication practices in affected areas.

      • EU/EEA Member States could:
        • Review laboratory and healthcare preparedness for large clusters of MERS-CoV presenting in their healthcare systems;
        • Sensitise healthcare workers to the possibility of MERS-CoV presenting in EU hospitals;
        • Familiarise public health professionals, healthcare workers and risk communication experts with available guidance (see annex and seventh rapid risk assessment update).

    (…)
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  • #2
    Re: Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) Ninth update, 24 April 2014 (ECDC/RRA, summary)

    [Source: ECDC, full PDF document: (LINK). Continue from previous post.]

    (...)


    Source and date of request

    ECDC Internal Decision, 15 April 2014.


    Public health issue

    This ninth update of the rapid risk assessment of the MERS-CoV outbreak addresses the following public health question:
    • Has the risk to EU citizens from the transmission of MERS-CoV in the Middle East changed since the last update of the risk assessment of 6 November 2013, considering:
      • the updated epidemiological information
      • the recent findings of increased number of infections in healthcare workers (HCW) and suspicion of nosocomial transmission, and asymptomatic infections in close contacts
      • the updated scientific evidence on the virus and the animal reservoir (camels).


    Previous rapid risk assessments

    ECDC has published nine previous Rapid Risk Assessments (1 initial and 8 updates) on Middle East respiratory syndrome coronavirus since the start of the outbreak. [1]


    Consulted experts

    ECDC (alphabetically):

    Kaja Kaasik-Aaslav, Cornelia Adlhoch, Sergio Brusin, Denis Coulombier, Niklas Danielson, Romit Jain, Josep Jansa, Daniel Palm, Pasi Penttinen, Diamantis Plachouras, Emmanuel Robesyn, Renι Snacken, Joanne Tay, Herve Zeller.

    External experts:

    Marion Koopmans, Netherlands; the World Health Organization (WHO) was consulted on this document. The views in this document do not necessarily represent the views of WHO


    Event background information

    As of 23 April 2014, 345 laboratory-confirmed cases of MERS-CoV have been reported to public health authorities worldwide, including 107 deaths. Seventy-two of the 345 cases have been healthcare workers. The following countries have reported MERS-CoV cases.

    [Reporting country – Cases – Deaths]
    • Saudi Arabia – 272 – 81
    • United Arab Emirates – 42 – 9
    • Qatar – 7 – 4
    • Jordan – 4 – 3
    • Oman – 2 – 2
    • Kuwait – 3 – 1
    • United Kingdom – 4 – 3
    • Germany – 2 – 1
    • France – 2 – 1
    • Italy – 1 – 0
    • Tunisia – 3 – 1
    • Malaysia – 1 – 1
    • Philippines – 1 – 0
    • Greece – 1 – 0
    • Total – 345 – 107

    Local person-to-person transmission has occurred outside of the Middle East in France, Tunisia and the UK after a primary case was imported. In France, the virus was transmitted from an imported case to a contact in a hospital before the infection was recognised. In Tunisia, transmission occurred to one close contact of a primary case. A second close contact who had accompanied the primary case in Saudi Arabia also developed confirmed infection but it is not clear when transmission occurred. In the UK, one imported case transmitted the virus to two family contacts.

    In November 2013, Spain reported two suspected imported case with exposure in Saudi Arabia, the first of whom triggered an update of the ECDC rapid risk assessment. The suspected cases imported to Spain could not be laboratory confirmed and were discarded. The cases have been deleted from the case count.

    (...)

    Recently the number of cases reported has increased substantially, leading to this updated rapid risk assessment. Between 13 and 23 April 2014, 108 cases have been reported by the respective Ministries of Health in the following countries: Saudi Arabia 83, United Arab Emirates (UAE) 23, one from Malaysia and one from Greece.

    (...)

    Most of the latest cases reported from the UAE are linked to a cluster in a hospital in Al Ain where 16 healthcare workers (including one case exposed in UAE and reported by the Philippines) have tested positive for MERS-CoV. All these cases are linked to a previously reported case, who died on 10 April 2014.

    Of the 23 cases in UAE, 10 had mild symptoms or were asymptomatic, two were reported to be in critical condition, one died, and there are no clinical details for the others. Only one of the healthcare workers is in critical condition and all the others are either asymptomatic or have mild symptoms. At least one case reported from UAE had travelled to Jeddah, Saudi Arabia. The average age of the latest cases in UAE is 41.

    Of the 83 cases reported in Saudi Arabia since 13 April 2014, 57 are from Jeddah (one additional case exposed in Jeddah has been reported by the UAE), 20 are from Riyadh, four are from Medina, and one each are from Najran and Tabuk. The case reported in Malaysia had recently performed Umrah in Saudi Arabia.

    The four cases in Medina are a family cluster with one death and three asymptomatic cases.

    The 20 cases in Riyadh are all in serious condition, hospitalised or having died. Two are healthcare workers linked to known cases whose clinical condition is described as stable. The average age of these cases is 62 years.

    The 57 cases reported from Jeddah are presenting an age distribution similar to the other groups. However, 13 (23%) are reported as healthcare workers, and, for the others, the occupation is not specified, but assumed not to be in the health sector. Six (46%) of the healthcare workers are asymptomatic, four (31%) are described as stable, two are critical and one is unknown. The average age of the healthcare workers is 41.

    Of the 44 non healthcare workers, seven (16%) are asymptomatic. The asymptomatic cases are thought to be contacts of hospitalised cases and on average are much younger, 24 years, compared to an average of 55 year in the symptomatic. Fourteen (32%) are reported in stable condition, 15 (34%) are critical, eight (18%) are dead, and for the remaining cases the clinical description is unclear.

    The average age of the cases not reported as healthcare workers is 50 years.

    The reporting process does not allow us to have a clear picture of the clustering of the cases although, from the media reports, it seems that there are clusters in at least two hospitals in Jeddah one of which is King Fahad Hospital. Currently, it is not possible to identify primary cases of the possible clusters with the information available.

    (...)

    On 18 April 2014, Greece reported its first case of MERS-CoV infection [2,3]. The case is a 69 year old male Greek citizen resident in Jeddah, Saudi Arabia. The patient arrived in Athens from Jeddah via Amman, Jordan, on 17 April 2014. He sought medical care on the same day for fever and diarrhoea at a large tertiary care centre. Laboratory testing of a throat swab at the national reference laboratory for influenza, Hellenic Pasteur Institute, confirmed the infection with MERS-CoV by polymerase chain reaction (PCR) for the Upstream E gene (screening test) and ORF-1A gene.

    The Hellenic Centre for Disease Control and Prevention has identified 73 close contacts in Greece, including potentially exposed healthcare workers. Twelve contacts of the patient during the two flights with Royal Jordanian Airlines from Jeddah via Amman to Athens on 17 April 2014 are being contacted for screening of symptoms and are being offered laboratory testing.


    Scientific developments

    Source and route of infection

    There is growing evidence that the dromedary camel is a host species for the MERS-CoV and that they play an important role in the transmission to humans.[4,5]

    The first evidence of dromedary camels being part of the transmission chain was the detection of high rates of antibodies against MERS-CoV in dromedary camels on the Arabian Peninsula [6,7]. Evidence of infection in camels precedes the first evidence of human infection [8]. Recently, viral RNA has been detected in different specimens from camels and the virus has been isolated from nasal and faecal samples.[8-11]

    The detection of MERS-CoV in dromedary camels imported from Sudan and Ethiopia for slaughter in Egypt [10], as well as serologic evidence of previous MERS-CoV infection in dromedaries in Nigeria, Ethiopia and Tunisia, suggest that the virus could be geographically widespread in the dromedary camel populations on the African continent, and that hitherto undetected transmission to humans may occur outside of the Arabian Peninsula [12].

    A recent study showed that when MERS-CoV is added to unpasteurised camel milk stored at 4 degrees centigrade, the virus remains infectious beyond 72 hours but that infectious viruses could not be found after pasteurisation [13].


    Virological characteristics

    In a prospective study of two camel herds in Saudi Arabia from November 2013 to February 2014, nasal, oral, or rectal swabs and blood samples were collected up to five times. The study showed that acute MERS-CoV infections diagnosed with PCR resulted in increased anti MERS-CoV titers.

    The infection of very young animals (<1 months) indicate that maternal antibodies may not fully protect very young animals from infection. There was no evidence of prolonged virus shedding or viremia among the tested animals [11].

    The full-genome sequences of the MERS coronaviruses retrieved from the dromedary camels in the above study were highly homologous to human isolates of clade B MERS-CoV [11,14].

    No gene sequences of MERS-CoV have been published from the cases reported in 2014 [15].


    Virological testing

    An external quality assessment was recently conducted by ENIVD (European network for viral imported diseases: www.enivd.de) for coronavirus detection focusing on MERS-CoV. The panel included 12 specimens. Preliminary results from 45 laboratories from 23 EU/EEA countries showed that:
    • There were no false positive test results
    • 100% of the laboratories detected the MERS-CoV samples for the two samples with the highest viral loads but only 73% of the laboratories correctly detected the specimen with a low viral load
    • Only 24% of the laboratories correctly identified the four other coronaviruses included in the panel. However 38% of the laboratories correctly identified three out of the four other coronaviruses included in this panel.

    In addition, results were also received from 47 laboratories worldwide including four laboratories in four affected countries in the Middle East. Data analyses for these results are still in process.


    ECDC threat assessment for the EU

    The number of human MERS-CoV cases reported from the Arabian Peninsula has increased rapidly in the past weeks. Specifically, two healthcare associated clusters in Jeddah and Abu Dhabi have been reported with large number of cases. Cases of MERS-CoV reported from the Philippines, Malaysia and Greece in the past week may be linked to these healthcare associated clusters.

    The cause of the rapid increase in cases is unknown. Possible scenarios include:
    • A. More sensitive case detection through more active case finding and contact tracing or changes in testing algorithms.
    • B. Increased zoonotic transmission with subsequent transmission in healthcare settings.
    • C. Breakdown in infection control measures or otherwise increased transmission in the local healthcare setting.
    • D. Change in the virus resulting in more effective human-to-human transmission, resulting in both nosocomial clusters, cases among travellers and increased numbers of asymptomatic community acquired cases.
    • E. False positive lab results.


    Scenario A: More sensitive case detection, improved surveillance

    To the best of our knowledge, the screening protocol in Saudi Arabia recommended testing of severe acute respiratory infections admitted to intensive care for MERS-CoV and testing of all close contacts of cases, including HCWs for the virus, however practices might differ at the facility level. These samples presumably have been tested according to WHO protocols with PCR of two target genes (e.g. upE specific and ORF-1a). Only cases confirmed by two tests have been reported to WHO.

    A recent change in the screening protocol, even if only at affected hospitals, such as testing of patients presenting with milder symptoms could explain the recent increase in reported cases and would indicate wider transmission of the virus in the community than previously estimated.

    ECDC does not have any evidence to suggest that screening practices have changed. A recent change of sensitivity in laboratory methods might also explain the recent increase of notified cases. During the past year, Saudi Arabia has rolled-out the PCR assays for MERS-CoV to at least five laboratories in the country, including Jeddah, but we are not aware of recent changes in laboratory assays used in Saudi Arabia for confirmation of cases.

    The limited information about current and past testing practices in Saudi Arabia does not allow conclusions to be made about the extent of changes in practices and its impact on the number of reported cases. However, the fact that the proportion of asymptomatic to symptomatic confirmed cases has remained stable during the increase in cases in April indicates that increased testing alone is unlikely to explain the increase, as increased testing of contacts is expected to increase the proportion of asymptomatic cases.

    If improved surveillance and/or more sensitive case detection are at the basis of the increase, it may indicate that many cases were missed in the past. If a majority of those were mild, the epidemiology would be quite different from what has previously been thought. On the one hand, the case-fatality would be lower, and on the other hand, human-to-human transmission might have been underestimated. In this scenario is it likely that more cases, but likely less severe ones, could be detected in the EU/EEA in the future.


    Scenario B: Increased zoonotic transmission

    Dromedary camels are a host species for MERS-CoV. Juvenile animals have higher virus load indicating a higher likelihood of transmission.

    Transmission could potentially occur via respiratory or faecal shedding, or other types of contact. Reinfection of animals appears to be possible and pre-existing antibodies are not completely protective. Therefore, a higher circulation can be assumed after the calving period in the winter months, when a larger number of animals is susceptible.

    Camel farming has progressively changed in Saudi Arabia in the last ten years with an increased number of farms near cities [16]. Intensive camel farming could be at the origin of an increased zoonotic risk, similar to what was observed in the Q-fever outbreak in the Netherlands, although the mode of transmission would be different [17].

    A good understanding of the epidemiology in camels, e.g. about seasonal calving periods and diarrheal outbreaks, is needed to fully assess the zoonotic risk. There currently remain many gaps in our knowledge on the epidemiology of coronavirus infections in dromedary camels, including the exact contact patterns with humans, both in the population in general and MERS-CoV cases. Though we know that MERS-CoV is widely circulating among the camel herds in the Arabian Peninsula, we do not know what triggers the apparent outbreak in humans and the absence of such outbreaks from other geographical regions where serological evidence exists for infection of dromedary camels.


    Assessment of risk for the EU

    Our assessment of the risk is limited by gaps in our knowledge about the animal-human interface with camels and the epidemiology of the infection in animals and humans. Serological studies and case-control studies are needed to estimate risk factors for infection and risk factors for severe disease. This would allow better targeting of preventive measures and advice to EU citizens.

    In the absence of further information, a risk for individual EU citizens travelling or residing in the Arabian Peninsula and especially Saudi Arabia, to be infected through direct or indirect camel contact exists. The magnitude of that risk is difficult to quantify in the absence of evidence.


    Scenario C: Increased nosocomial transmission because of ineffective infection control measures

    The reports of hospital associated clusters of MERS-CoV infections provide further evidence for the risk of nosocomial transmission and question the effectiveness of the precautionary measures used in the affected healthcare facilities. A full evaluation of the precautionary measures applied at the healthcare facilities involved in the outbreak would be useful to assess the effectiveness of hospital hygiene measures and possibly provide much needed information on the mode of transmission. If no important gaps were identified at the respective hospitals, it could indicate an increased risk for human-to-human transmission. The latter could be indicative of an important change in the risk for further spread of the outbreak.


    Assessment of risk for EU

    More detailed information regarding the events of healthcare-associated MERS-CoV infection would allow better assessment of the risk for spread of the disease through various modes of transmission. With the information currently available, strict adherence to standard precautions (including hand hygiene) and additional contact and airborne transmission precautions remain the recommended infection prevention and control measures for any suspected case or case under investigation of MERS-CoV.


    Scenario D: More effective human-to-human transmission

    Most asymptomatic or mild cases tend to be younger and do not have pre-existing illnesses. In recent clusters, secondary cases tend to be milder than previously reported.

    The increased number of cases reported could be a result of more effective human-to-human transmission, even if the main source of infection is still zoonotic as indicated by the fact that cases are still associated with stay in the Arabian Peninsula. If the case-finding procedures are not more sensitive than before, the fact that more asymptomatic infections have been reported, more close contacts infected, and that there is more nosocomial transmission, could indicate more effective transmission. However, the absence of more detailed information about transmission risks, does not allow us to draw more significant conclusions.


    Assessment of risk for EU

    More detailed information is needed about the risk factors at the basis of the recent increase of cases to assess the risk of human-to-human transmission. Current epidemiology still relates the majority of the cases to the Arabian Peninsula, and thus the risk of sustainable human-to-human transmission in Europe is very low.


    Scenario E: Laboratory artefact

    Laboratories performing PCR assays need to ensure that samples do not get cross-contaminated. A rapid scale-up of laboratory capacity for MERS-CoV in local laboratories in response to the outbreak might compromise stringent quality standards, increasing the possibility of cross-contamination. ECDC is not aware of the regional laboratory capability, laboratory standards or recent scale-up activities and it is therefore difficult to assess the likelihood of this scenario.


    Assessment of risk for EU

    If laboratory contamination is shown to explain the reported cases even partially, this would decrease the current risk to populations in the affected area as well to European citizens to levels before April 2014. Considering the recent outbreaks have occurred simultaneously in three different cities in two countries, it is unlikely that laboratory contamination would be the only explanation of the evolving outbreak.


    Conclusions

    The first confirmed case in Greece increased to five the number of EU countries that have reported confirmed cases of MERS-CoV infection: France, Germany, Greece, Italy and the UK. Given the current epidemiology on the Arabian Peninsula, it is likely that more cases will be imported and detected in EU Member States. Further vigilance in assessing patients with travel history to the affected region is warranted.

    The quality of verified information on the recent events in Saudi Arabia and United Arab Emirates is insufficient to draw firm conclusions on the risks posed by the outbreaks. It is not clear what role nosocomial transmission is playing in these clusters or whether wider community transmission is taking place.

    However, unless these recent detections are due to laboratory contaminations, the epidemiological evidence from Saudi Arabia and UAE seems to suggest increased circulation of the virus or increased case detection among humans.
    More cases have recently been reported in individuals travelling out of the region, which might indicate increased transmissibility of the virus and perhaps longer human transmission chains than have been seen in the past.
    An apparent increase in the size of nosocomial clusters also supports this hypothesis.

    Camels are a host species for this virus and it is likely that at least some of the primary cases in clusters have been infected through direct or indirect camel contact. Dromedary camels could be the direct or indirect source of human MERS-CoV infection. Full-genome sequences of MERS-CoV with very high homology have been retrieved from nasal specimens from dromedary camels with respiratory symptoms. However, many of the cases detected or treated outside of the Arabian Peninsula could have been healthcare acquired.

    Gene sequences from the recent human cases have not been submitted to GENBANK or other publicly available databases, therefore it is impossible to verify whether significant mutations have appeared.

    Extensive contact tracing efforts on board flights, on which cases have travelled, have thus far not shown evidence of transmission to other passengers.

    No case control-studies or other epidemiological studies have been done to determine exposures and host factors related to increased risk of infection for primary cases in clusters. The World Health Organization has provided the affected countries in the region with a study protocol and questionnaire.

    Important gaps remain in appropriate treatment protocols and effectiveness of available antiviral medications. Observational clinical studies are urgently needed to improve the existing knowledge base in these areas.

    This event has had a serious public health impact in the region and has the potential to spread and have a wider geographic impact, if the virus is transmitting among humans.

    This unusual and unexpected disease has already been detected outside of the Middle East in Asia, Africa, Europe. More details and analysis of the evolving events in UAE and Saudi Arabia are urgently needed to further define the risks posed by this event.

    (...)


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    Comment


    • #3
      Re: Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) Ninth update, 24 April 2014 (ECDC/RRA, summary)

      [Source: ECDC, full PDF document: (LINK). Continue from the above post.]


      (...)


      Options for action

      The seventh update of the rapid risk assessment on 24 September 2013 provides options for actions on case finding, laboratory testing, reporting, contact tracing, infection control and travel advice [18]. These options for actions remain valid and can be found in the annex.

      In addition:
      • Visitors to and EU residents of the Arabian Peninsula should:
        • Follow general travel health precautions that lower the risk of infection in general, including illnesses such as influenza and traveller’s diarrhoea. This includes:
          • Wash hands often with soap and water. When hands are not visibly dirty, a hand rub can be used.
          • Adhere to good food-safety practices, such as avoiding undercooked meat and unpasteurised milk (especially from camels) or food prepared under unsanitary conditions, and properly washing fruits and vegetables before eating the.
          • Maintain good personal hygiene.
          • Avoid unnecessary contact with farm, domestic, and wild animals, especially camels.
          • Use appropriate precautions when in close contact with case-persons presenting with acute respiratory illness, diarrhoea or other potentially infectious diseases.

        • Consult their physician if suffering major medical conditions (e.g. chronic diseases such as diabetes, chronic lung or renal disease, immunodeficiency) that can increase the likelihood of illness including MERS-CoV infection, or contact with healthcare facilities during travel.

      • Returning travellers to EU/EEA Member States should:
        • If developing acute illness with severe respiratory symptoms or diarrhoea, advise the healthcare providers in advance of the possibility of exposure to MERS-CoV on the Arabian Peninsula, in order to ensure appropriate measures are taken and if needed, testing considered.
        • Not travel if acutely ill with an infectious disease.

      • The international public health community and affected countries could:
        • Urgently provide support for an outbreak assessment to minimise the possibility of widespread human-to-human transmission in the community.
        • Encourage and support as urgent, studies to describe and determine modes and sources of transmission for MERS-CoV, in particular in the animal (/camel)-human interface, among primary cases of clusters and in the healthcare facilities.
        • Epidemiological studies, such as cohort or case-control studies are well suited for such assessments.
        • Encourage and support as urgent, observational clinical studies to determine optimal management of patients in order to improve outcomes.
        • Ensure that appropriate serum samples (positive and negative controls) are available for international standardisation of serological tests.
        • Encourage serological surveys among close contacts of cases and in affected settings.
        • Ensure that adequate numbers of virus isolates are sequenced and submitted to publicly available databanks, such as GenBank throughout the evolving epidemic.
        • Improve timely and transparent risk communication practices in affected areas.

      • EU/EEA Member States could:
        • Review laboratory and healthcare preparedness for large clusters of MERS-CoV presenting in their healthcare systems.
        • Sensitise healthcare workers to the possibility of MERS-CoV presenting in EU hospitals.
        • Familiarise public health professionals, healthcare workers and risk communication experts with available guidance (see annex and 7th RRA update).


      References
      1. European Centre for Disease Prevention and Control. Rapid Risk Assessment and updates on MERS-CoV. Available from: http://ecdc.europa.eu/en/healthtopics/coronavirus-infections/Pages/publications.aspx
      2. Sprenger M; Coulombier D. Middle East Respiratory Syndrome coronavirus - two years into the epidemic Euro Surveill. 2014;19(16):pii=20783.
      3. Tsiodras S BA, Mentis A, Iliopoulos D, Dedoukou X, Papamavrou G, Karadima S et al.. A case of imported Middle East Respiratory Syndrome coronavirus infection and public health response, Greece, April 2014. Euro Surveill. 2014;19(16):pii=20782.
      4. Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M, et al. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill. 2013;18(50):20659.
      5. Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S, et al. Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. Euro Surveill. 2013;18(50):20662.
      6. Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O, et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill [Internet]. 2013; 2013;18(36):pii=20574. Available from: Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20574
      7. Reusken CB, Haagmans BL, Muller MA, Gutierrez C, Godeke GJ, Meyer B, et al. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis. 2013 Aug 8.
      8. Memish ZA CM, Meyer B, Watson SJ, Alsahafi AJ, Al Rabeeah AA, et al. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. June 2014.
      9. Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, de Wit E, et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio. 2014;5(2):e00884-14.
      10. Chu DKW PL, Gomaa MM, Shehata MM, Perera RAPM, Zeid DA, et al. MERS Coronaviruses in Dromedary Camels, Egypt. Emerg Infect Dis. 2014 Jun.
      11. Hemida MG CD, Poon LLM,. Perera RAPM, Alhammadi MA, Ng H-Y, et al. MERS coronavirus in dromedary camel herd, Saudi Arabia. . Infect Dis. 2014 July.
      12. Reusken CBEM ML, Feyisa A, Ularamu H, Godeke G-J, Danmarwa A, et al. Geographic distribution of MERS coronavirus among dromedary camels, Africa. Emerg Infect Dis
      13. van Doremalen N BT, Munster VJ. Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions 2013 [cited 2013 20 September]. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20590.
      14. Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL, Ong SH, et al. Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. MBio. 2014;5(1).
      15. The National Center for Biotechnology Information (NCBI), BLAST tree view. Available from: http://www.ncbi.nlm.nih.gov/blast/treeview/treeView.cgi?request=page&blastRID=NCMS8DB6014&que ryID=gb|KF192507.1|&entrezLim=&ex=&exl=&exh=&ns=10 0&screenWidth=1229&screenHeight=983.
      16. H. R. Abdallah BF. Typology of camel farming system in Saudi Arabia. Emirates Journal of Food and Agriculture. 2013;25(4).
      17. Dijkstra F, van der Hoek W, Wijers N, Schimmer B, Rietveld A, Wijkmans CJ, et al. The 2007-2010 Q fever epidemic in The Netherlands: characteristics of notified acute Q fever patients and the association with dairy goat farming. FEMS immunology and medical microbiology. 2012 Feb;64(1):3-12.
      18. European Centre for Disease Prevention and Control. Severe respiratory disease associated with Middle East respiratory syndrome coronavirus (MERS-CoV) - Seventh update, 24 September 2013. Available from: http://ecdc.europa.eu/en/publications/Publications/RRA_MERS-CoV_7th_update.pdf.

      (…)


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