Community case clusters of Middle East respiratory syndrome coronavirus in Hafr Al-Batin, Kingdom of Saudi Arabia: a descriptive genomic study

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first described in September 2012 and to date 86 deaths from a total of 206 cases of MERS-CoV infection have been reported to the WHO. Camels have been implicated as the reservoir of MERS-CoV, but the exact source and mode of transmission for most patients remain unknown. During a 3 month period, June to August 2013, there were 12 positive MERS-CoV cases reported from the Hafr Al-Batin region district in the north east region of the Kingdom of Saudi Arabia. In addition to the different regional camel festivals in neighboring countries, Hafr Al-Batin has the biggest camel market in the entire Kingdom and hosts an annual camel festival. Thus, we conducted a detailed epidemiological, clinical and genomic study to ascertain common exposure and transmission patterns of all cases of MERS-CoV reported from Hafr Al-Batin. Analysis of previously reported genetic data indicated that at least two of the infected contacts could not have been directly infected from the index patient and alternate source should be considered. While camels appear as the likely source, other sources have not been ruled out. More detailed case control studies with detailed case histories, epidemiological information and genomic analysis are being conducted to delineate the missing pieces in the transmission dynamics of MERS-CoV outbreak.

Keywords: Clusters; Community; Coronavirus; Genome; MERS-CoV; Middle East; Phylogeny; Virus transmission.

Figure 1

(A) The epidemiologically defined transmission pathway of the two MERS-CoV clusters. Markers for each MERS case were placed by sample date (x-axis) and colored dark grey for fatal outcome or green for non-fatal outcome. Patient numbers are indicated within each marker. The age and gender of each case are indicated, and epidemiologically-possible contacts of Patients 1, 3 and 8 are marked by arrows. (B) Determination of genetically plausible transmission for the Hafr Al-Batin Cluster 2. Time of sample collection is indicated on the x-axis. Colored markers indicate the MERS case with the following code. Blue: MERS-CoV sequence was available for that case, grey: no sequence was available, orange: no sequence was available but the ancestral reconstructed sequence for the clade was used. Green arrows indicate statistically plausible transmission between the pair (with no direction implied), red arrows indicate that transmission between the pair is not supported statistically. Statistical tests of transmission were performed as previously described.

Figure 2

Statistically possible transmission pairs between MERS cases infected with the Hafr-Al-Batin_1 clade of MERS-CoV. All MERS cases known to be infected with the Hafr-Al-Batin_1 clade of MERS-CoV were plotted by sample date (x-axis) and color-coded by Hafr-Al-Batin_1 subclade as previously described . Upper panel: All statistically supported transmission pairs are marked by arcs. Lower panel: Only potential transmission pairs whose collection dates differ by 21 days or less are marked by arcs. See Methods section for additional details.