Unanswered questions about the Middle East respiratory syndrome coronavirus (MERS-CoV)

BMC Research Notes

C Raina MacIntyre²  Lauren M Gardner¹ 

[1] NICTA, Sydney, NSW 2052, Australia;School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia

关键词: Epidemiology;    Emerging infectious disease;    MERS-CoV;   

Others  :  1132500
DOI  :  10.1186/1756-0500-7-358

 received in 2013-08-16, accepted in 2014-05-23,  发布年份 2014

【 摘 要 】

Background

The Middle East respiratory syndrome coronavirus (MERS-CoV) represents a current threat to the Arabian Peninsula, and potential pandemic disease. As of June 3, 2014, MERS CoV has reportedly infected 688 people and killed 282. We briefly summarize the state of the outbreak, and highlight unanswered questions and various explanations for the observed epidemiology.

Findings

The continuing but infrequent cases of MERS-CoV reported over the past two years have been puzzling and difficult to explain. The epidemiology of MERS-CoV, with many sporadic cases and a few hospital outbreaks, yet no sustained epidemic, suggests a low reproductive number. Furthermore, a clear source of infection to humans remains unknown. Also puzzling is the fact that MERS-CoV has been present in Saudi Arabia over several mass gatherings, including the 2012 and 2013 Hajj and Umrah pilgrimages, which predispose to epidemics, without an epidemic arising.

Conclusions

The observed epidemiology of MERS-CoV is quite distinct and does not clearly fit either a sporadic or epidemic pattern. Possible explanations of the unusual features of the epidemiology of MERS-CoV include sporadic ongoing infections from a non-human source; human to human transmission with a large proportion of undetected cases; or a combination of both. The virus has been identified in camels; however the mode of transmission of the virus to humans remains unknown, and many cases have no history of animal contact. In order to gain a better understanding of the epidemiology of MERS CoV, further investigation is warranted.

【 授权许可】

   
2014 Gardner and MacIntyre; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA: Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012, 367(19):1814-1820.
• [2]Global Alert and Response: Novel coronavirus infections. http://www.who.int/csr/don/archive/disease/coronavirus_infections/en/ webcite
• [3]Anderson RM, Fraser C, Ghani AC, Donnelly CA, Riley S, Ferguson NM, Leung GM, Lam T, Hedley AJ: Epidemiology, transmission dynamics and control of SARS: the 2002–2003 epidemic. Philos Trans R Soc Lond Ser B Biol Sci 2004, 359(1447):1091-1105.
• [4]Meyer B, Müller MA, Corman VM, Reusken CBEM, Ritz D, Godeke GJ: Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg Infect Dis 2014, 20(4):552-559.
• [5]Cotten M, Watson SJ, Zumla AI, Makhdoom HQ, Palser AL, Ong SH: Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus. MBio 2014, 5(1):e01062-01013.
• [6]Preliminary 2012 World Airport Traffic and Rankings http://www.aci.aero/ webcite
• [7]Khan K, Sears J, Wei Hu V, Brownstein JS, Hay S, Kossowsky D, Eckhardt R, Chim T, Berry I, Bogoch I, Cetron M: Potential for the international spread of middle East respiratory syndrome in association with mass gatherings in saudi arabia. PLOS Currents Outbreaks 2013. Edition 1
• [8]The WHO MERS-CoV Research Group: State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERSCoV) in Humans. PLOS Current Outbreaks 2013. Edition 1
• [9]Memish Z, Al-Tawfiq J, Makhdoom H, Al-Rabeeah A, Assiri A, Alhakeem R, Alrabiah F, Al Hajjar S, Albarrak A, Flemban H, Balkhy H, Barry M, Alhassan S, Alsubaie S, Zumla A: Screening for Middle East Respiratory Syndrome Coronavirus Infection in Hospital patients and their Health care Worker and Family Contacts: a prospective descriptive study. Clin Microbiol Infect 2014, 20(5):469-474.
• [10]Drosten C, Seilmaier M, Corman VM, Hartmann W, Scheible G, Sack S, Guggemos W, Kallies R, Muth D, Junglen S, Müller MA, Haas W, Guberina H, Röhnisch T, Schmid-Wendtner M, Aldabbagh S, Dittmer U, Gold H, Graf P, Bonin F, Rambaut A, Wendtner C-M: Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet Infect Dis 2013, 13(9):745-751.
• [11]The Health Protection Agency (HPA) UK Novel Coronavirus Investigation Team: Evidence of person-to-person transmission within a family cluster of novel coronavirus infections, United Kingdom. Euro Surveill 2013.
• [12]Wallinga J, Teunis P: Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures. Am J Epidemiol 2004, 160(6):509-516.
• [13]Buchholz U, Müller , Marcel A, Nitsche , Andreas , Sanewski A, Wevering N, Bauer-Balci T, Bonin F, Drosten , Christian , Schweiger , Brunhilde , Wolff , Thorsten : Contact investigation of a case of human novel coronavirus infection treated in a German hospital. Euro surveill 2013.
• [14]Pebody R, Chand MA, Thomas HL, Green HK, Boddington NL, Carvalho C, Brown CS, Anderson SR, Rooney C, Crawley-Boevey E: The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012. Euro Surveill 2012., 17(40)
• [15]Aburizaiza A, Mattes FM, Azhar EI, Hassan AM, Memish ZA, Muth D, Meyer B, Lattwein E, Müller M, Drosten C: Investigation of anti‒MERS‒Coronavirus antibodies in blood donors and abattoir workers in Jeddah and Makkah, Kingdom of Saudi Arabia, Fall 2012. J Infect Dis 2013.
• [16]Lu G, Liu D: SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases. Protein Cell 2012, 3(11):803-805.
• [17]Ithete N, Stoffberg S, Corman V, Al E: Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis 2013., 19(10)
• [18]Cotten M, Lam T, Watson S, Palser A, Petrova V, Grant P, Oliver G, Pybus AR, Yi G, Deenan P, Paul K, Eleni N, Comments to Author: Full-genome deep sequencing and phylogenetic analysis of novel human betacoronavirus. Emerg Infect Dis 2013, 19(5):736-42B.
• [19]Annan A, Baldwin H, Corman V, Klose S, Owusu M, Nkrumah E, Al E: Human betacoronavirus 2c EMC/2012–related viruses in bats, Ghana and Europe. Emerg Infect Dis 2013, 19(3):456-9.
• [20]Reusken C, Haagmans BL, Muller MA, Gutierrez C, Godeke GJ, Meyer B: Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis 2013, 13(10):859-866.
• [21]Perera R, Wang P, Gomaa M, El-Shesheny R, Kandeil A, Bagato O, Siu L, Shehata M, Kayed A, Moatasim Y, Li M, Poon L, Guan Y, Webby R, Ali M, Peiris J, Kayali G: Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt. Euro Surveill 2013, 18:36.
• [22]Reusken C, Messadi L, Feyisa A, Ularamu H, Godeke G-J, Danmarwa A, Dawo F, Jemli M, Melaku S, Shamaki D, Woma Y, Wungak Y, Gebremedhin EZ, Zutt I, Bosch B-J, Haagmans BL, Koopmans MPG: Geographic distribution of MERS coronavirus among dromedary camels, Africa. Emerg Infect Dis 2014., 20(8)
• [23]Reusken C, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S: 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.
• [24]Chu D, Poon LLM, Gomaa MM, Shehata MM, Perera RAPM, Zeid DA, El Rifay AS, Siu LY, Guan Y, Webby RJ, Ali MA, Peiris M, Kayali G: MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis 2014, 20(6):1049-53.
• [25]Woo P, Lau SKP, Wernery U, Wong EYM, Tsang AKL, Johnson B: Novel betacoronavirus in dromedaries of the Middle East. Emerg Infect Dis 2014, 20(4):560-572.
• [26]Hemida M, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M: Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill 2013, 18(50):20659.
• [27]Alagaili A, Briese T, Mishra N, Kapoor V, Sameroff SC, De Wit E: Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio 2014, 5(2):e00884-00814.
• [28]Alexandersen S, Kobinger GP, Soule G, Wernery U: Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis 2014, 61(2):105-108.
• [29]Haagmans B, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R: Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis 2014, 14(2):140-145.
• [30]Hemida M, Chu DKW, Poon LLM, Perera RAPM, Alhammadi MA, Ng H-Y: MERS coronavirus in dromedary camel herd, Saudi Arabia. Emerg Infect Dis 2014., 20(7)
• [31]Briesea T, Mishraa , Nischay , Jaina , Komal , Zalmoutb , Iyad S, Jabadoc , Omar J, Kareshd , William B, Daszakd , Peter , Mohammedb , Osama B, Alagailib , Abdulaziz , Lipkina W, Ian : Middle East respiratory syndrome coronavirus quasispecies that include homologues of human isolates revealed through whole-genome analysis and virus cultured from dromedary camels in Saudi Arabia. MBio 2014, 5(2):e01146-01114.
• [32]Memish ZA, Cotten , Matthew , Meyer , Benjamin , Watson , Simon J, Alsahafi , Abdullah J, Al R, Abdullah A, Victor Max C, Andrea S, Makhdoom HQ, Abdullah A, Malaki Al M, Souhaib A, BerendJan B, Martin B, Müller MA, Paul K, Christian D: Human Infection With MERS Coronavirus After Exposure to Infected Camels. Emerg Infect Dis 2014, 20:6.
• [33]Breban R, Riou J, Fontanet A: Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk. Lancet 2013, 382(9893):694-699.
• [34]Cauchemez S, Van Kerkhove MD, Riley S, Donnelly CA, Fraser C, Ferguson NM: Transmission scenarios for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and how to tell them apart. Euro Surveill 2013, 18:24.
• [35]Memish Z, Zumla AI, Al-Hakeem RF, Al-Rabeeah AA, Stephens GM: Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med 2013, 368:2487-2494.
• [36]Omrani A, Matin MA, Haddad Q, Al-Makhli D, Memish ZA, Albarrak AM: A family cluster of Middle East Respiratory Syndrome Coronavirus infections related to a likely unrecognized asymptomatic or mild case. Int J Infect Dis 2013, 17(9):e668-e672.
• [37]Assiri A, McGeer , Allison P, Trish M, Price , Connie S, Al R, Abdullah A, Cummings , Derek AT, Alabdullatif , Zaki , Assad M, Almulhim A, Makhdoom H, Madani H, Alhakeem R, Al-Tawfiq JA, Cotten M, Watson SJ, Kellam P, Zumla AI, Memish ZA: Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus. N Engl J Med 2013, 369(5):407-416.
• [38]Cotten M, Watson , Simon J, Kellam , Paul , Al-Rabeeah , Abdullah A, Makhdoom , Hatem Q, Assiri , Abdullah , Al-Tawfiq , Jaffar A, Alhakeem RF, Hossam M, AlRabiah FA, Sami Al H, Al-nassir WN, Ali A, Hesham F, Balkhy HH, Sarah A, Palser A, Gall A, Bashford-Rogers R, Rambaut A, Zumla A, Memish Z: Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 2013, 382(9909):1993-2002.
• [39]Memish ZA, Cotten , Matthew , Watson , Simon J, Kellam P, Zumla A, Alhakeem , Rafat F, Assiri , Abdullah , Al R, Abdullah A, Al-Tawfiq , Jaffar A: Community Case Clusters of Middle East Respiratory Syndrome Coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: A Descriptive Genomic study. Int J Infect Dis 2014, 23:63-68.
• [40]Memish Z, Rabeeah A: Health conditions for travellers to Saudi Arabia for the Umra and Hajj pilgrimage to Mecca: requirements for 2012 (1433). J Infect Public Health 2012, 5(2):113-115.
• [41]Memish Z, Assiri A, Almasri M, Alhakeem R, Turkestani A, Al Rabeeah A, Al-Tawfiq J, Alzahrani A, Azhar E, Makhdoom H, Hajomar W, Alshingiti A, Yezli S: Prevalence of MERS-CoV nasal carriage and compliance with the Saudi health recommendations among pilgrims attending the 2013 Hajj. J Infect Dis 2014.
• [42]Gautret P, Charrel R, Benkouiten S, Belhouchat K, Nougairede A, Drali T, Salez N, Memish ZA, al Masri M, Lagier J-C, Million M, Raoult D, Brouqui P, Parola P: Lack of MERS coronavirus but prevalence of influenza virus in French pilgrims after 2013 Hajj [letter]. Emerg Infect Dis [Internet] 2014, 20(4):728-30.
• [43]Rashid HAM, Heron L, Haworth E, Booy R, Memish ZA: Has Hajj-associated MERSCoV transmission occurred? The case for effective post-Hajj surveillance for infection. Clin Microbiol Infect 2013, 20(4):271-6.
• [44]Gautret P, Charrel R, Belhouchat K, Drali T, Benkouiten S, Nougairede A, Zandotti C, Memish ZA, Al Masri M, Gaillard C: Lack of nasal carriage of novel corona virus (HCoV‒EMC) in French Hajj pilgrims returning from the Hajj 2012, despite a high rate of respiratory symptoms. Clin Microbiol Infect 2013, 19(7):E315-E317.
• [45]Cauchemez S, Fraser C, Van Kerkhove MD, Donnelly CA, Riley S, Rambaut A, Enouf V, van der Werf S, Ferguson NM: Middle East respiratory syndrome coronavirus: quantifi cation of the extent of the epidemic, surveillance biases, and transmissibility. The Lancet 2013, 14(1):50-56.