Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility

Abstract

SummaryBackgroundThe novel Middle East respiratory syndrome coronavirus (MERS-CoV) had, as of Aug 8, 2013, caused 111 virologically confirmed or probable human cases of infection worldwide. We analysed epidemiological and genetic data to assess the extent of human infection, the performance of case detection, and the transmission potential of MERS-CoV with and without control measures.MethodsWe assembled a comprehensive database of all confirmed and probable cases from public sources and estimated the incubation period and generation time from case cluster data. Using data of numbers of visitors to the Middle East and their duration of stay, we estimated the number of symptomatic cases in the Middle East. We did independent analyses, looking at the growth in incident clusters, the growth in viral population, the reproduction number of cluster index cases, and cluster sizes to characterise the dynamical properties of the epidemic and the transmission scenario.FindingsThe estimated number of symptomatic cases up to Aug 8, 2013, is 940 (95% CI 290–2200), indicating that at least 62% of human symptomatic cases have not been detected. We find that the case-fatality ratio of primary cases detected via routine surveillance (74%; 95% CI 49–91) is biased upwards because of detection bias; the case-fatality ratio of secondary cases was 20% (7–42). Detection of milder cases (or clinical management) seemed to have improved in recent months. Analysis of human clusters indicated that chains of transmission were not self-sustaining when infection control was implemented, but that R in the absence of controls was in the range 0·8–1·3. Three independent data sources provide evidence that R cannot be much above 1, with an upper bound of 1·2–1·5.InterpretationBy showing that a slowly growing epidemic is underway either in human beings or in an animal reservoir, quantification of uncertainty in transmissibility estimates, and provision of the first estimates of the scale of the epidemic and extent of case detection biases, we provide valuable information for more informed risk assessment.FundingMedical Research Council, Bill & Melinda Gates Foundation, EU FP7, and National Institute of General Medical Sciences.

Assessing the risk of observing multiple generations of Middle East respiratory syndrome (MERS) cases given an imported case

“…The risk of involving tertiary, quaternary and quinary cases was also calculated ( Figure 2B). Although our study only relied upon importation events consisting of a small number of clusters, the estimated R 0 was broadly consistent with published estimates that analysed larger cluster datasets mainly observed in Middle East countries [3][4][5] and was smaller than estimates derived from the early phase of hospitalassociated outbreaks [13]. Considering that countries at risk of importation (i.e.…”

“…Firstly, our exercise regarded each observed importation event as a random draw governed by the proposed probability model. Indeed, this assumption is unavoidable for fitting a branching process model to the data [3,4]. While the assumption may be common among modelling studies, it did not allow us to account for the variable type and effectiveness of interventions, especially at later generations of cases in each cluster.…”

“…generation 3 counting from the index case as generation 0) have been reported in South Korea [2]. Although the inter-human transmission potential of MERS is considered to be too low to cause large-scale epidemics [3][4][5], high variability and heterogeneity in the transmission potential have been underscored [6]. As MERS continues to spread globally, it is vital that risk assessment involves an evaluation of the potential outcomes following MERS importation events [7].…”

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“…In addition, Gierer et al, did not detect MERS-CoV neutralizing antibodies in any of the 268 samples tested that were obtained from persons from the Eastern province of Saudi Arabia 74 . Using independent data sources, different investigators demonstrated that R, the basic reproduction number representing the number of secondary cases per index case in a fully susceptible population, cannot be much above 1, with an upper bound of 1.2 -1.5 69,75 .…”

Middle East Respiratory Syndrome (MERS): The Emerging Zoonoses

“…The MERS has also been transmitted to other countries through travelers infected in Arabian Peninsula and neighboring countries. Human-to-human transmission has been observed to a limited extent in households and healthcare workers (Cauchemez et al, 2014).…”