Hospital outbreak of Middle East respiratory syndrome coronavirus

Abstract

Background: In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections.

Methods: Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced.

Results: Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases).

Conclusions: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.

Figure 1. Epidemiologic Plot of Confirmed and Probable Cases of MERS-CoV Infection in Saudi Arabia, April 1–May 23, 2013

All confirmed and probable cases are shown, according to the location of the most probable transmission. One of the five family contacts (Patient M) who is included as having been exposed in Hospital A was also exposed through caring for the patient at home and may have acquired the infection either in the hospital or in the community.

Figure 2. Transmission Map of Outbreak of MERS-CoV Infection

All confirmed cases and the two probable cases linked to transmission events are shown. Putative transmissions are indicated, as well as the date of onset of illness and the settings. The letters within the symbols are the patient identifiers (see Fig. S2 in the Supplementary Appendix).

Figure 3. Estimates of the Incubation Period and Serial Interval of MERS-CoV Infection

The empirical cumulative density function of the observed cases (the fraction of all observations that fell below each observed value) (black lines) with respect to the incubation period (Panel A) and serial interval (the time between the onset of illness in a case patient and the onset of illness in a contact) (Panel B) is shown, with a plot of the cumulative distribution of log-normal distributions fit to the data indicated by thick yellow and blue lines, respectively. The 95% confidence intervals for the 5th, 50th, and 95th percentiles of these fitted distributions are indicated by the yellow and blue horizontal lines. Yellow and blue shading indicates cumulative distributions of log-normal distributions fit to bootstrapped samples of our observed data.

Figure 4. Phylogenetic Analysis of the Sequences of All Genes Identified in Four Patients Infected with MERS-CoV

Panel A shows single-nucleotide differences (vertical colored bars) between the England2 genome and the four Al-Hasa genomes as well as the four additional full genomes available; gray indicates a gap in the query sequence, orange a change to A, crimson a change to T, blue a change to G, and purple a change to C. The reference genomes we used were from a Jordanian patient in April 2012 (Gen-Bank accession number, KC776174), EMC/2012 from a Saudi Arabian patient in July 2012 (JX869059), England/Qatar/2012 from a London Qatari patient in September 2012 (KC667074), England2 from a patient who had traveled to Pakistan and Saudi Arabia in February 2013, and the Munich/AbuDhabi sequence from a patient from the United Arab Emirates in March 2013. Panel B shows an unrooted maximum-likelihood phylogeny inferred under a generalized-time-reversal (GTR)+Gamma substitution model that compares the five previously identified Middle East respiratory syndrome (MERS) genomes with the four Al-Hasa genomes. Bootstrap values are shown for the highly supported nodes. Panel C shows a time-resolved maximum clade credibility tree for the five previously identified genomes and the four Al-Hasa MERS coronavirus genomes. Posterior probability values are shown for nodes with posterior support greater than 0.5. Findings are consistent with previously published estimates.