Laboratory research in camel diseases, UAE: update on MERS-CoV Turkey – October 2017

Outline Camel in UAE MERS-CoV infection in dromedary camels Actions to face MERS-CoV infection Published research by UAE on MERS-CoV infection in camels 2014-2017 Un-answered research questions Ongoing research

I. Camels in UAE Camels play an effective role in the history of United Arab Emirates and considered a national wealth. Camels are raised in UAE for a variety of purposes, including racing and Beauty competitions and Investments in production of meat and milk

I. Camels in UAE Hosting the creation of CAMENENT ; the sub-regional network of laboratories, epidemiologists and husbandry specialists in camel in the Middle East.

II. MERS-CoV infection in dromedary camels Middle East respiratory syndrome (MERS) is a viral respiratory disease caused by a novel coronavirus (Middle East respiratory syndrome coronavirus, or MERS‐CoV) that was first identified in Saudi Arabia in 2012. In August 2013, Dromedary camels (Camelus dromedarius) were implicated as a possible source for human infection on the basis of the presence of MERS-CoV neutralizing antibodies Later, the presence of MERS-CoV antibodies in dromedaries has been reported in many countries including the United Arab Emirates The UAE ranks third, after Saudi Arabia and South Korea, for the number of Middle East Respiratory Syndrome infections among humans

II. MERS-CoV infection cont. Furthermore, MERS-CoV infection in dromedary camels was definitively proven by the detection of virus and virus sequences in respiratory specimens, feces, and milk collected from camels   Accumulating evidence points to dromedary camels, as an important reservoir of the virus

MERS-CoV livestock field surveys by country ‎(http://www.fao.org/ag/againfo/programmes/en/empres/mers/situation_update.html)‎ *Note: Positive findings in Spain refer to samples taken in the Canary Islands.

II. MERS-CoV infection cont. MERS-CoV only causes mild respiratory symptoms in camels and it is therefore, not easily recognized and difficult to diagnose clinically

III. Actions had taken to face MERS-CoV Raise the subject at national level Awareness campaign Screening for imported camels Researches

IV-Published research from UAE on MERS CoV infection in camels 2014-2017

Published research from UAE on MERS-CoV infection in camels 2014-2017 Reference Methodology Aim Center Alexandersen et al. Transbound Emerg Dis 2014 ELISA Antibodies detection in camels CVRL Meyer et al. Em.In.Dis 2014 Yusof et al., Virus Gene 2015 PCR Disease Prevalence in Abu Dhabi ADFCA Song et al., J.Clin.Microbiol. 2015 Test validation and comparison New test development Wernery et al., Em.In.Dis.2015 Case report/PCR Infection in camels Al Hammadi et al., Em.In.Dis. 2015 PCR/Sequencing/ phylogeny Human-camel interaction Wernery et al. Em. Microbe In. 2015 Virus isolation/ Virus detection in a camel calf Al-Muhairi et al., Virus Genes 2016 PCR/ Sequencing Epidemiology Lau et al., Em. Microbe In. 2016 Virus genotyping Li et al., PLOS One 2017 Next generation sequencing Virus genome detection

Example of a development-oriented joint research: Development and validation of a rapid immunochromatographic assay for detection of Middle East respiratory syndrome coronavirus antigen in dromedary camels. J Clin Microbiol. ‎2015 Apr;53(4):1178-82.. Song D, Ha G, Serhan W, Eltahir Y, Yusof M, Hashem F, Elsayed E, Marzoug B, Abdelazim A, Al Muhairi S.‎ new rapid immunochromatographic assay for the detection of  MERS-CoV) antigen dromedary camels relative sensitivity and specificity of 93.90% and 100%, respectively useful tool for the rapid diagnosis and epidemiological surveillance

Priority research on MERS-CoV Research is needed to understand: immunogenicity of MERS-CoV vaccines in dromedary camels genetic changes of MERS-CoV over the time molecular pathogenesis of MERS-CoV in dromedary camels epidemiology of MERS-CoV at the animal-human interface, what type of camel contact is associated with MERS-CoV infection in humans? Seasonality of MERS-CoV in the camel markets

Ongoing research in UAE to address some of these questions Genome Sequence Analysis of MERS-CoV in Human Clusters and Camels in UAE, (beginning 2013) Diversity of Middle East respiratory syndrome coronaviruses in 109 dromedary camels, Abu Dhabi, United Arab Emirates MERS-CoV- Animal-Human Interface Investigation in Camel Markets, Abu Dhabi, UAE

Major findings and Conclusions Phylogenetic analysis of partial sequences obtained from camels had 99.9% identity with corresponding sequence from the human complete genome previously reported of a farm owner, which provides further evidence for zoonosis. Major findings obtained from 129 camel MERS-CoV full genomes: Camel- and human- derived MERS-CoV Spike sequences both have amino acid variations throughout, however, no significant or unique amino acid changes present between human and camel MERS-CoV Spike proteins. High number of nucleotide changes within one week timeframe for 3 camels, could indicate reinfection from camels within the same area. Two new potential lineages were identified in Clade B within the phylogenetic tree with lineage switch ability of the virus.

Major findings and Conclusions 10 recombination events were detected. The junction between ORF1b and S was the most frequently identified location for the recombination breakpoints. The genetic diversity of MERS-CoVs and the frequency of recombination suggest the potential for emergence of new MERS-CoV variants.

شكراً Thank you Merci Gracias