A genomic analysis of 32 Middle East respiratory syndrome coronavirus (MERS-CoV) isolates from Saudi Arabia has revealed little evidence that the virus is evolving to become more contagious in humans, according to a new report by Saudi, British, and US researchers.
The team analyzed isolates from MERS cases that were confirmed in Sauda Arabia from May through September of 2013. They identified four different MERS-CoV clades or families, but three of those no longer seem to be contributing to cases, says the report, published in mBio.
The findings also suggest that the pace of human MERS cases gradually increased until April 2013 but has declined since then, the researchers say.
The number of publicly reported MERS cases has ebbed in recent months. A World Health Organization (WHO) chart shows that the monthly tally of cases peaked last year at about 35 in August and then hovered around 10 to 12 the rest of the year. A case list maintained by the FluTrackers infectious disease message board shows six cases so far this year.
In-depth genetic analysis
The research team sequenced the genomes of all 32 isolates and completed at least 99% of the sequence for 20 of those, with partial sequencing of the rest. They compared these 32 viruses with 33 previously sequenced isolates to map their phylogenetic relationships.
The researchers identified four clades with at least four cases each (Hafr-Al-Batin_1, Buraidah_1, Al-Hasa, and Riyadh_3) and six sporadic cases that didn't fit in any of the clades.
In mapping the clades, the team found that the Al-Hasa clade was confined to that region of eastern Saudi Arabia, but each of the other three included cases in several locations. "The geographical dispersion of MERS-CoV lineages suggests a mobile infection source, either as human-to-human or nonhuman-to-human infection or via transported animal product," they wrote.
The persistence of each clade was assessed by checking the dates of the first and last recognized isolates belonging to it. This revealed that the durations ranged from 62 to 147 days, with an average of 98 days. Three of the clades appeared to have faded out of circulation by the end of the observation period, the team said.
"This pattern of clade disappearance may be due to the increased MERS surveillance and patient isolation that was implemented during the course of the outbreak, combined with [a basic reproduction number] of less than 1, but it could also reflect undiagnosed asymptomatic spread," the report states. The basic reproduction number is the number of new cases caused by one case occurring in a susceptible population.
The authors applied mathematical modeling to the phylogenetic findings to estimate the trend in the incidence of human infections. The results indicated that the incidence increased gradually until about April 2013 and has declined since then, "reflecting the apparent disappearance of multiple lineages."
In other steps, the team used the genetic data to estimate how rapidly the virus is evolving, in number of mutations per genome site per year. This led to the conclusion that the most recent common ancestor for the isolates from 42 sporadic cases existed in March 2012—about the time the first known MERS cases occurred in Jordan (though they were not identified as such until late in 2012).
The investigators identified just one genomic site, on the gene for the virus's spike protein, that shows signs of evolving in response to pressure from human hosts, indicating "only limited evidence of adaptation to human transmission in the form of positively selected amino acids in MERS-CoV lineages."
"MERS-CoV adaptation toward higher rates of sustained human-to-human transmission appears not to have occurred yet," the report states.
The authors conclude that the rapid identification of MERS cases and isolation of patients may control transmission of the virus so long as its transmissibility doesn't change. "Full control of the MERS epidemic requires identification of the source of infections to prevent the initiation of the observed human-to-human transmission chains," they add.
Camels' possible role
They also briefly discuss the evidence that camels may be a source of the virus in humans, including the finding that pieces of MERS-CoV sequences from a camel in Qatar were related to sequences from viruses isolated from two patients in contact with the camel. Experts say the camel connection has not yet been conclusively demonstrated.
In that regard, the authors write, "The strongest argument for a persistent animal reservoir may be that the occurrence of MERS-CoV infections in multiple sites in Saudi Arabia, as well as in Jordan, Qatar, and United Arab Emirates (Dubai and Abu Dhabi), is unlikely to be sustained by the observed limited human-to-human MERS-CoV transmission, and thus, a more widespread population of MERS-CoV in animals could exist."
They add that the pattern of MERS-CoV lineages they found is not consistent with a uniform pattern of MERS-CoV evolution across the Arabian peninsula, but "is more consistent with the movement of infected livestock or animal products."
See also:
Jan 20 WHO report with chart of MERS cases by month
FluTrackers list of hospitalized MERS cases
