The Pressing Need to Identify the Intermediate Hosts of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

In an ahead-of-print article in Virology Journal [1], Cui and associates report the results of a study of the molecular evolution of DPP4, a cell-surface receptor, across the mammalian phylogeny.  Their analyses showed that the dN/dS value on the bat lineage (0.96) was four times greater than the mammalian average leading to the conclusion that Middle East respiratory syndrome coronavirus (MERS-CoV) ultimately has a bat-origin.

From the article –

Our analysis therefore suggests that the evolutionary lineage leading to current MERS-CoV co-evolved with bat hosts for an extended time period, eventually jumping species boundaries to infect humans and perhaps through an intermediate host. As such, the emergence of MERS-CoV may parallel that of the related SARS-CoV. Although one bat species, Taphozous erforatus, in Saudi Arabia has been found to harbour a small RdRp (RNA-Dependent RNA Polymerase) fragment of MERS-CoV, a larger viral sampling of bats and other animals with close exposure to humans, including dromedary camels . . . are clearly needed to better understand the viral transmission route. . . .

While bats may ultimately be the host reservoir for this coronavirus, the distribution of human infections throughout the Arabian Peninsula, among individuals of both genders, and various ages and occupations, indicates that there is some other intermediate host infecting the index cases and other sporadic cases in the region. The sooner the intermediate host is identified, the more likely that these outbreaks of MERS-CoV can be contained.

[1] Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the origin and emergence of Middle East respiratory syndrome coronavirus

h/t bgw

MERS-CoV Clusters in Saudi Arabia

As previously noted, at least seven clusters of Middle East respiratory syndrome coronavirus (MERS-CoV) cases have occurred in the Kingdom of Saudi Arabia (KSA) [1]. An additional eighth cluster can be inferred from official reports for the city of Medina [2]. Besides Medina, 3 clusters have been reported from Riyadh, and one each from Al Hofuf, Mecca, Asir Province (Bisha?), and Hafar Al-Batin. 

Besides these clusters, in July, the World Health Organization (WHO) reported laboratory confirmation of a female healthcare worker from Hafar Al-Batin  who had contact with a previously confirmed case [3]. The only prior confirmed case from Hafar Al-Batin  was a 16-year-old male who was reported to have died in June [4]. This would constitute another cluster from Hafar Al-Batin.

Since August 1, the KSA  Ministry of Health has reported at least seven individuals from Riyadh who were in contact with previously confirmed cases. Because of the lack of case details it is not possible to ascertain how many clusters of MERS-CoV cases may have occurred since then in Riyadh or are occurring there at this time.

The table below presents information on the location and potential number of cases associated with MERS-CoV clusters in the KSA using cluster numbers assigned by the CDC [5]. The maps shows the general areas where these clusters occurred.

Location of MERS-CoV Clusters in Saudi Arabia

[1] MERS-CoV is a Threat to Healthcare Workers and Hospital Patients

[2] A MERS-CoV Cluster Outbreak in Medina, Saudi Arabia 

[3] Middle East respiratory syndrome coronavirus (MERS-CoV) - update 

[4] MOH: Two New Confirmed Cases of Coronavirus Recorded in Al-Ahsa and the Eastern Region and One Case Passed Away in Hafr Al-Batin 

[5] Middle East Respiratory Syndrome (MERS): Clusters under Investigation

MERS-CoV is a Threat to Healthcare Workers and Hospital Patients

Recently, the European Centre for Disease Prevention and Control (ECDC) produced a summary report on the status of the Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak for the 130+ cases that have been reported since March 2012 [1].

While epidemiological data about these cases are presented in this report, several aspects of the report need further elaboration and discussion. As discussed on a USA Center for Disease Control web page [2] and noted in the ECDC report,  human clusters are prevalent for this novel disease. At least 14 MERS-CoV clusters have been reported. Single clusters have been reported from several countries, France, Italy, Jordan, Tunisia, and the United Kingdom. And the Kingdom of Saudi Arabia, which has reported more than 100 MERS-CoV cases, has experienced at least seven cluster outbreaks in seven separate geographic areas.

The ECDC authors state

We identified 14 clusters of 2-34 cases, where the primary cases were identified or suspected. However, data quality on the clusters is weak. All of the known 14 primary cases in clusters were adult men (24-83 years old) who were most likely exposed on the Arabian Peninsula. Of 129 cases with available information on transmission, 33 (26 percent) were possible nosocomial transmissions, 15 of these cases were healthcare workers (HCW). 17 of the 23 cases reported as HCW were female.

Information on geographic clusters of cases can provide important insight for public health officials into the mode of transmission, the transmissibility of the novel pathogen, and the potential identification of the non-human reservoir of a pathogen. What is not mentioned by the ECDC authors is that about 50% of all reported MERS-CoV cases have occurred in a cluster as defined by the World Health Organization (WHO) [3]. What is also not mentioned by the ECDC authors is how the index cases in these clusters became infected. The non-human source of this coronavirus has yet to be identified.

Of greater concern is the fact that at least 33 cases may have resulted from nosocomial transmissions. Nosocomial infection is a result of pathogen transmission within a hospital or healthcare facility.  This means that these 30+ individuals, including healthcare workers, contracted MERS-CoV in a healthcare facility such as a hospital. They did not contract the disease from an intermediate animal source. Infections within a healthcare facility are associated with human-to-human transmission. 

Several reports indicate that at least nine of these nosocomial infections were hospital patients most likely with comorbidities.  However, more alarming is that a number of healthcare workers were also infected in the hospital or healthcare treatment facility. This means that the coronavirus is transmissible not just among elderly individuals with chronic diseases but also among healthy younger healthcare workers who should be aware of, and prepared for, the dangers of human-to-human transmission.

Discussion

 

The nature of the transmissibility of the MERS-CoV is not clear, but the fact that numerous clusters have been reported and that human-to-human transmission is occurring among both patients and healthcare workers in healthcare facilities is cause for serious concern and demonstrates a need for increased monitoring and surveillance for this novel disease.

 

 [1] Taking stock of the first 133 MERS coronavirus cases globally – Is the epidemic changing?

[2] Middle East Respiratory Syndrome (MERS): Clusters under Investigation

[3] Interim surveillance recommendations for human infection with Middle East respiratory syndrome coronavirus