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US & Dutch Confusion Linked to Withheld MERS Sequences
Recombinomics Commentary 17:00
May 30, 2014

Exchange of information between the US Centers for Disease Control and Prevention and Dutch experts did not reveal any clues about mutual exposure of the Dutch and US cases. The current, limited scientific information does not support any conclusion on the meaning of this genetic resemblance,

The above comments from the recent paper on the two Dutch pilgrims who were MERS confirmed, describes efforts between investigators in The Netherlands and United States to explain the close relationship between sequences from the two Dutch pilgrims (70M and 73F) and the Riyadh health care worker (HCW) who was confirmed in Munster, Indiana, with onward transmission to a colleague in Cook County, Illinois (likely Chicago) based on positive serological data on two assays (ELISA and IFA) which have been defined by the CDC as lab confirmation of a prior MERS infection (CDC retraction not withstanding). 

Like the cluster in the United States, the cluster in the Netherlands appears to have been acquired via casual contact (45 minutes in the waiting room of a Medina hospital).

The sequence identity between the three PCR confirmed cases originating in Riyadh (
Indiana/USA-1_Saudi Arabia_2014) and Medina raises concerns that a novel sub-clade is responsible for the explosion of MERS cases in these two cities.  However, US and Dutch investigators were unable to draw conclusions from the match because sequences from these two cities have been withheld.

Although the Drostin lab, which appears to have exclusive access to samples from the cases in the Kingdom of Saudi Arabia (KSA), has indicated sequence data from areas outside of Jeddah and Mecca have been transmitted to WHO, the failure to make these sequences public has led to comments such as those cited above from the recent paper on the Netherlands cluster.

The presence of a novel sub-clade in Medina could have significant impact on pilgrims traveling to Mecca and Medina while performing Umrah, which will increase significantly during Ramadan, which begins in less than a month.

The Droston lab has released six nearly complete sequences from a sub-clade which is circulating in Jeddah and Mecca (
(C7149 and C7770 from hospital A collected on April 3 and 7, respectively, as well as C7569 from hospital B collected on April 5, followed by Jeddah sequences C8826 and C9055 collected on April 12 and April 14 from hospital A and C, respectively, as well as Mecca (C9355) collected on April 15).  This sub-clade was also found in a Jeddah HCW who traveled to Orlando, Florida (Florida/USA-2_Saudi Arabia_2014), as well as a Jeddah resident (69M) who developed symptoms after visiting his wife in a Jeddah hospital who was diagnosed with Dengue Fever.  When he developed symptoms, he was diagnosed with Typhoid Fever, but after travel to Athens, Greece he was diagnosed with MERS and sequencing of the S and N genes revealed a close similarity with the Jeddah sub-clade.

The presence of this sub-clade in Mecca raises additional Umrah/Ramadan concerns since most pilgrims who fly to KSA pass through Jeddah, Mecca, and Medina.  The hospital linked to the Jeddah export to Orlando, Florida has not been disclosed.  However, the export to Greece appears to have originated from the Al-Jedaani Hospitals, which has recently been cited in media reports as a hospital that has seen a dramatic drop in ER visits due to fears of nosocomial transmission.  It is unlikely that this hospital is hospital B or C, linked to Droston sequences (and hospital A is almost certainly King Fahd, which was force to temporarily close its ER in April due to the number of MERS cases, which included HCWs), because the direct has claimed there are no MERS infected patients or HCWs in his hospital system. 

Thus, although the MERS explosion in Jeddah has been attributed to poor infection control, the presence of the same sub-clade in four Jeddah hospitals as well as a Mecca hospital suggests this sub-clade is widespread and not limited to a limited number of nosocomial outbreaks.

The widespread presence of the Jeddah/Mecca sub-clade in Jeddah and possibly Mecca, as well as the detection of the Medina/Riyadh sub-clade in exports to the Netherlands and United States, which are associated with transmission via casual contact, the withholding of the Medina and Riyadh sequences continues to increase pandemic concerns.

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